Clinical Paediatric Dietetics 2020

Clinical Paediatric Dietetics
0004760602.INDD 1 6/12/2020 11:14:11 AM

Clinical Paediatric Dietetics
EDITED BY
Vanessa Shaw, MBE, MA, PG Dip Dietetics, RD, FBDA

Honorary Associate Professor of Paediatric Dietetics
University of Plymouth
Plymouth, UK
Fifth Edition
0004760602.INDD 3 6/12/2020 11:14:13 AM

This edition first published 2020
© 2020 John Wiley & Sons Ltd
Edition History
Wiley‐Blackwell (4e, 2014)
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means,
electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material
from this title is available at http://www.wiley.com/go/permissions.
The right of Vanessa Shaw to be identified as the author of the editorial material in this work has been asserted in accordance with law.
Registered Office(s)
John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK
Editorial Office
9600 Garsington Road, Oxford, OX4 2DQ, UK
For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.
Wiley also publishes its books in a variety of electronic formats and by print‐on‐demand. Some content that appears in standard print versions of
this book may not be available in other formats.
Limit of Liability/Disclaimer of Warranty

The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should
not be relied upon as recommending or promoting scientific method, diagnosis, or treatment by physicians for any particular patient. In view
of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of
medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for
each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and
precautions. While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with
respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any
implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written
sales materials or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation
and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization,
website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged
in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a
specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when
this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages,
including but not limited to special, incidental, consequential, or other damages.
Library of Congress Cataloging‐in‐Publication Data
Names: Shaw, Vanessa, editor.
Title: Clinical paediatric dietetics / edited by Vanessa Shaw.
Description: Fifth edition. | Hoboken, NJ : Wiley-Blackwell, 2020. |
Includes bibliographical references.
Identifiers: LCCN 2020001244 (print) | LCCN 2020001245 (ebook) | ISBN
9781119467298 (cloth) | ISBN 9781119467199 (adobe pdf) | ISBN
9781119467281 (epub)
Subjects: MESH: Diet Therapy | Child
Classification: LCC RJ53.D53 (print) | LCC RJ53.D53 (ebook) | NLM WS 366
| DDC 615.8/54083–dc23
LC record available at https://lccn.loc.gov/2020001244
LC ebook record available at https://lccn.loc.gov/2020001245
Cover Design: Wiley

Cover Images: © David Crunelle/EyeEm/Getty Images, BDA logo courtesy of the British Dietetic Association
Set in 9.5/11.5pt Palatino by SPi Global, Pondicherry, India
Printed and bound by CPI Group (UK) Ltd, Croydon, CR0 4YY
10 9 8 7 6 5 4 3 2 1
0004760602.INDD 4 6/12/2020 11:14:13 AM

Contents
List of Contributors vii 11 Endocrinology 189

Preface x S. Francesca Annan and Sarah Price
Acknowledgements xi
About the Companion Website xii 12 Cystic Fibrosis 216
Carolyn Patchell and Katie Stead
1 Principles of Paediatric Dietetics: Nutritional 13 Kidney Diseases 238

Assessment, Dietary Requirements and Feed Leila Qizalbash, Shelley Cleghorn and Louise McAlister
Supplementation 1
Vanessa Shaw and Helen McCarthy 14 Congenital Heart Disease 287
David Hopkins and Luise Marino
2 Healthy Eating 18
Judy More 15 Food Hypersensitivity 315
Rosan Meyer and Carina Venter
3 Provision of Nutrition in a Hospital Setting 43
Julie Royle 16 Prevention of Food Allergy 339
Kate Grimshaw
4 Enteral Nutrition 52
Tracey Johnson 17 Ketogenic Diets 344
Julia Ackrill, Vanessa Appleyard
5 Parenteral Nutrition 64 and Victoria Whiteley
Joanne Louise Price
18 Childhood Cancers and Immunodeficiency
6 Nutrition in Critically Ill Children 80 Syndromes 371
Rosan Meyer and Luise Marino Evelyn Ward and James Evans
7 Preterm Infants 96 19 Eating Disorders 393

Karen King and Lynne Radbone Graeme O’Connor and Dasha Nicholls
8 Gastroenterology 113 20 Autism 405

Sarah Macdonald and Joanne Louise Price Zoe Connor
9 Surgery in the Gastrointestinal Tract 149 21 Feeding Children with Neurodisabilities 419

Danielle Petersen and Tracey Johnson Jennifer Douglas
10 The Liver and Pancreas 166 22 Epidermolysis Bullosa and Rare Skin Disorders 438

Sara Mancell Natalie Yerlett
ftoc.indd 5 6/4/2020 10:27:17 PM

vi Contents
23 Burns 456 28 Disorders of Amino Acid Metabolism, Organic

Helen McCarthy and Jacqueline Lowdon Acidaemias and Urea Cycle Disorders 513
Marjorie Dixon, Anita MacDonald and Fiona J. White
24 Faltering Weight 464
Lisa Cooke and Julie Lanigan 29 Disorders of Carbohydrate Metabolism 599
Anita MacDonald, Marjorie Dixon and Fiona J. White
25 Obesity in Childhood 472
Laura Stewart and Chris Smith 30 Disorders of Mitochondrial Fatty Acid Oxidation
and Lipid Metabolism 640
26 Eating for Children from Minority Marjorie Dixon, Rachel Skeath and Fiona J. White
Ethnic Groups 486
Eulalee Green 31 Emergency Regimens for Inherited Metabolic
Disorders 673
27 Inherited Metabolic Disorders: Introduction Marjorie Dixon
and Rare Disorders 502
Fiona J. White Index 681
ftoc.indd 6 6/4/2020 10:27:17 PM

List of Contributors
Julia Ackrill BSc, RD Jennifer Douglas BSc, BPhEd, PG Dip Dietetics, NZRD
Specialist Paediatric Dietitian Formerly Specialist Paediatric Dietitian
Birmingham Women’s and Children’s Hospital NHS Mile End Hospital
Foundation Trust London E1 4DG
Steelhouse Lane, Birmingham B4 6NH and
Currently Dietitian, Jumpstart Nutrition
S. Francesca Annan BSc, MSc, RD, FBDA
George St, Dunedin 9016, New Zealand
Clinical Specialist Paediatric/Adolescent Diabetes Dietitian
University College London Hospital James Evans BSc, MRes, RD
Euston Road, London NW1 2PG Highly Specialist Paediatric Dietitian – Bone Marrow
Vanessa Appleyard BSc, PG Dip Nutrition and Dietetics, RD Transplantation and Immunology
Senior Specialist Paediatric Dietitian Great Ormond Street Hospital for Children NHS
Birmingham Women’s and Children’s Hospital NHS Foundation Trust
Foundation Trust Great Ormond Street, London WC1N 3JH
Steelhouse Lane, Birmingham B4 6NH
Eulalee Green BSc, MSc, RD
Shelley Cleghorn BSc, RD Dietitian and Public Health Nutritionist
Team Leader and Clinical Lead Dietitian – Nephrology eulalee@familynutritioncoach.com
Great Ormond Street Hospital for Children NHS
Foundation Trust Kate Grimshaw PhD, RD
Great Ormond Street, London WC1N 3JH Operational Manager and Highly Specialist Allergy
Dietitian
Zoe Connor MSc, RD
Salford Royal NHS Foundation Trust
Assistant Professor (Senior Lecturer) in Dietetics
Stott Lane, Salford M6 8HD
School of Nursing, Midwifery and Health, Faculty of
Health and Life Sciences David Hopkins BSc, MSc, RD
Coventry University, Coventry CV1 5FB Advanced Paediatric Dietitian
and Yeovil District Hospital
Freelance Paediatric Dietitian Higher Kingston, Yeovil BA21 4AT
www.zoeconnor.co.uk
Lisa Cooke BSc, MA, RD Tracey Johnson BSc, RD
Head of Paediatric Dietetics, Nutrition and Speech and Senior Specialist Paediatric Dietitian
Language Therapy Birmingham Women’s and Children’s Hospital NHS
Bristol Royal Hospital for Children Foundation Trust
Upper Maudlin Street, Bristol BS2 8BJ Steelhouse Lane, Birmingham B4 6NH
Marjorie Dixon BSc, RD Karen King BSc, RD

Clinical Lead Dietitian – Metabolic Medicine Advanced Neonatal Dietitian
Great Ormond Street Hospital for Children NHS Cambridge University Hospitals
Foundation Trust NHS Foundation Trust
Great Ormond Street, London WC1N 3JH Hills Road, Cambridge CB2 0QQ
fbetw.indd 7 6/12/2020 11:20:41 AM

viii List of Contributors
Julie Lanigan BSc, PhD, RD Dasha Nicholls FRCPsych, MD (Res), FAED

Principal Research Fellow Reader in Child Psychiatry and Honorary Consultant
Childhood Nutrition Research Child and Adolescent Psychiatrist
UCL Great Ormond Street Institute of Child Health The Centre for Psychiatry, Imperial College,
Guilford Street, London WC1N 1EH Du Cane Road, London W12 0NN
Jacqueline Lowdon BSc, MSc, PGCE (FE), RD Graeme O’Connor PhD, RD
Clinical Specialist Dietitian Research Lead for Dietetics and Honorary Research
Leeds Children’s Hospital Associate
Leeds General Infirmary, Leeds LS1 3EX Great Ormond Street Hospital for Children NHS
Anita MacDonald BSc, PhD, RD Foundation Trust
Consultant Dietitian in Inherited Metabolic Disorders Great Ormond Street, London WC1N 3JH
Birmingham Women’s and Children’s Hospital NHS Carolyn Patchell BSc, RD
Foundation Trust Head of Nutrition and Dietetics and CF Specialist Dietitian
Steelhouse Lane, Birmingham B4 6NH Birmingham Women’s and Children’s Hospital NHS
and Foundation Trust
Honorary Professor of Paediatric Dietetics Steelhouse Lane, Birmingham B4 6NH
Derriford Road, Plymouth PL6 8BH Danielle Petersen BSc, MSc, RD
Freelance Paediatric Dietitian
Sarah Macdonald BSc, RD
www.childrensnutritionpractice.co.uk
Team Leader and Clinical Lead – Intestinal Rehabilitation
and Nutrition Joanne Louise Price BSc, RD
Great Ormond Street Hospital for Children NHS Paediatric Dietitian
Foundation Trust Royal Manchester Children’s Hospital
Great Ormond Street, London WC1N 3JH Manchester University NHS Foundation Trust
Sara Mancell BSc, BA, MRes, RD Oxford Road, Manchester M13 9WL
Lead Children’s Dietitian Sarah Price BSc, RD
King’s College Hospital NHS Foundation Trust Paediatric Dietitian Specialised in Congenital
Denmark Hill, London SE5 9RS Hyperinsulinism and Neonatal Nutrition
Luise Marino BSc, PG Dip Dietetics, MMed Sci Nutr, PhD Royal Manchester Children’s Hospital
Clinical Academic Paediatric Dietitian Manchester University NHS Foundation Trust
Southampton Children’s Hospital Oxford Road, Manchester M13 9WL
University Hospital Southampton NHS Leila Qizalbash BSc, PG Dip Practice Education
Foundation Trust (UHS) Lead Dietitian in Paediatric Nephrolgy
Tremona Road, Southampton SO16 6YD Great Northern Children’s Hospital
Louise McAlister BSc, RD Queen Victoria Road, Newcastle Upon Tyne NE1 4LP
Highly Specialist Paediatric Dietitian – Nephrology
Lynne Radbone BSc, RD
Principal Paediatric Dietitian/East of England Neonatal
Foundation Trust
Operational Delivery Network Dietitian
Great Ormond Street, London WC1N 3JH
Cambridge University Hospitals NHS Foundation Trust
Helen McCarthy PhD BSc (Hons), PgCHEP(UK) Hills Road, Cambridge CB2 0QQ
RD (UK), APD (Aus)
Julie Royle BSc, PG Dip Dietetics
Senior Lecturer (Dietetics and Nutrition)
Former Clinical Specialist Dietitian (Renal) and Team
College of Health and Biomedicine
Leader
Victoria University, Melbourne, VIC 8001
Royal Manchester Children’s Hospital
Rosan Meyer B Dietetics, MNutr, PhD, RD Manchester University NHS Foundation Trust
Paediatric Research Dietitian Oxford Road, Manchester M13 9WL
Honorary Senior Lecturer and Visiting Professor MSc
Vanessa Shaw MBE, MA, PG Dip Dietetics, RD, FBDA
Deglutology, KU Leuven
Honorary Associate Professor of Paediatric Dietetics
Department of Paediatrics, Imperial College, Praed
Street, London W2 1NY
Derriford Road, Plymouth PL6 8BH
Judy More BSc, RD, RNutr
Rachel Skeath BSc, MSc, MRes, RD
Freelance Paediatric Dietitian
Clinical Lead Dietitian – Metabolic Medicine
London
and
Foundation Trust
Director, Child‐nutrition.co.uk Ltd
www.child‐nutrition.co.uk
fbetw.indd 8 6/12/2020 11:20:41 AM

List of Contributors ix
Chris Smith BSc, RD Fiona J. White BSc, RD

Senior Paediatric Dietitian Lead Specialist Metabolic Dietitian
Royal Alexandra Children’s Hospital Royal Manchester Children’s Hospital
Eastern Road, Brighton BN2 5BE Manchester University NHS Foundation Trust
Oxford Road, Manchester M13 9WL
Katie Stead BSc, RD
Specialist Paediatric Dietitian Victoria Whiteley BSc, RD
Birmingham Women’s and Children’s Hospital Trainee Advanced Clinical Practitioner in Ketogenic
NHS Foundation Trust Therapies
Steelhouse Lane, Birmingham B4 6NH Royal Manchester Children’s Hospital
Manchester University NHS Foundation Trust
Laura Stewart PhD, RD
Oxford Road, Manchester M13 9WL
Lead Consultant, AppleTree Healthy Lifestyle
and
Consultancy, Perth, UK
School of Health and Society, University of Salford,
Carina Venter PhD, RD Salford M6 6PU
Associate Professor of Pediatrics, Section of Allergy &
Natalie Yerlett BSc, ARCS, PG Dip Dietetics, RD
Immunology
Advanced Practitioner EB and Rare Dermatology
University of Colorado Denver School of Medicine and
Dietitian
Children’s Hospital Colorado
Anschutz Medical Campus
Foundation Trust
13123 East 16th Avenue, Box B518
Aurora, CO 80045
Evelyn Ward BSc, MSc, RD
Children’s Clinical Dietetic Manager
The Leeds Children’s Hospital
Leeds LS1 3EX
fbetw.indd 9 6/12/2020 11:20:41 AM

Preface
The continuing aim of this fifth edition of Clinical Paediatric adolescence is described and underpins many clinical
Dietetics is to provide a very practical approach to the dietary interventions. The trend for children to be discharge from
management of children with a wide range of disorders that hospital for continuing care at home makes this text a valu-
benefit from dietary therapy. Interventions range from nutri- able resource for both acute and community‐based health-
tional support to the diet being the major or sole treatment care professionals.
for particular disorders. The text is relevant for professional There has been an expansion of the range of disorders,
dietitians, dietetic students and their tutors, paediatricians, treatments, guidelines and recommendations described in
paediatric nurses and members of the community health many chapters, e.g. diabetes technology, the wider use of the
team caring for children who require therapeutic diets. The ketogenic diet, renal tubular disorders, refeeding syndrome
importance of nutritional support and dietary management and the use of blended diets in enteral nutrition, new guide-
in many paediatric conditions is increasingly recognised and lines for parenteral nutrition, irritable bowel syndrome and
is reflected in new text for this edition. rare skin disorders – in addition to a thorough review of all
The authors are drawn from practising paediatric dieti- the topics in the fourth edition. With much information pre-
tians, with additional contributions from academic research sented in tabular form and with worked examples and case
dietitians and a psychiatrist. The need for evidence‐based studies, the manual is easy to use.
practice demands a thorough review of scientific and medi- The most recent information and data on dietetic products
cal literature to support clinical practice, wherever possible, has been used in the preparation of this edition, but no guar-
and this has been undertaken by the authors. Where the evi- antee can be given for validity or availability at the time of
dence base is lacking, expert clinical opinion is given. While going to press.
the practice described is largely UK focused, the principles Of particular note, the new Commission Delegated
can be applied in other areas. Regulation (EU) 2016/128 on food for special medical pur-
The major part of the text concentrates on nutritional poses (FSMP) has come into force, with the rules for infant
requirements of sick infants, children and young people formulas applying from 22 February 2020. Hence, there may
in the clinical setting. Normal dietary constituents are be slight changes in some of the dilutions and compositions
used alongside special dietetic products to provide a pre- of formulas shown in the text.
scription that will control progression and symptoms of
disease while maintaining the growth potential of the indi- Vanessa Shaw
vidual. Healthy eating throughout infancy, childhood and May 2020
0004760604.INDD 10 6/12/2020 11:16:11 AM

Acknowledgements
I would like to thank a number of dietitians who wrote for Ketogenic Diets: Georgiana Fitzsimmons and Marian Sewell
the fourth edition of this book whose work contributed to Immunodeficiency Syndromes: Natalie Yerlett
the following chapters: Feeding Children with Neurodisabilities: Leanne Huxham
Epidermolysis Bullosa: Melanie Sklar and Lesley Haynes
Provision of Nutrition in the Hospital Setting: Ruth Watling
Faltering Growth: Zofia Smith
Preterm Infants: Caroline King and Kate Tavener
Inherited Metabolic Disorders: Nicol Clayton, Janine
The Liver and Pancreas: Jason Beyers
Gallagher, Pat Portnoi, Jacky Stafford
Endocrinology: Alison Johnstone and Jacqueline Lowdon
Kidney Diseases: Julie Royle
0004760605.INDD 11 5/22/2020 11:33:14 PM

About the Companion Website
The book is accompanied by a website:
www.wiley.com/go/shaw/paediatricdietetics-5e
The website features:
• Figures in PowerPoint format.

• Tables in PDF format.
• References, further reading, guidelines, support groups and other useful links.
0004760605.INDD 12 5/22/2020 11:33:15 PM

1
Principles of Paediatric Dietetics: Nutritional
Assessment, Dietary Requirements and Feed
Supplementation
Vanessa Shaw and Helen McCarthy
Introduction protein–energy undernutrition [1]. Despite the recommenda-

tions from benchmark standards and national and international
This text provides a practical approach to the dietary man- guidelines that screening for nutrition risk be an integral com-
agement of a range of paediatric disorders. The principles ponent of clinical care for all [2–5], the development of nutrition
outlined in this chapter are relevant to all infants, children screening tools for use with children has lagged behind work in
and young people and provide the basis for many of the the adult world. However, internationally, a number of child‐
therapies described later in the text. Chapter 2 describes specific nutrition screening tools have been developed includ-
healthy eating throughout childhood and adolescence to ing the Nutrition Risk Score (Paris tool), the Subjective Global
support normal growth and development and may inform Nutrition Assessment (SGNA), StrongKids and the Paediatric
dietetic interventions; special considerations for children Nutrition Screening Tool (PNST) [6–9]. Each of these has
from minority ethnic groups are addressed in Chapter 26. strengths and limitations in terms of validity and reliability of
The remaining text focuses on nutritional requirements and the tool, the time taken to complete and the level of skill required
management in the clinical setting, illustrating how normal by individuals applying the tool.
dietary constituents are used alongside special dietetic prod- Two child‐specific tools have been developed in the UK: the
ucts to allow for the continued growth of the child while Screening Tool for the Assessment of Malnutrition in
controlling the progression and symptoms of disease. Paediatrics (STAMP) and the Paediatric Yorkhill Malnutrition
Score (PYMS) [10, 11]. Both of these tools have been evaluated
in practice and comprise a number of elements that are scored
Assessment of nutritional status to give a final risk score (Table 1.1). The reliability of each of
Assessment and monitoring of nutritional status should be these tools has been published, along with a number of other
included in any dietary regimen, audit procedure or research studies evaluating their use in a variety of clinical settings and
project where a modified diet has a role. Although the terms conditions [12–14]. The main limitation of these evaluation
are used interchangeably in the literature, nutrition screen- studies is that they rely on the dietetic assessment of nutri-
ing is a simple and rapid means of identifying individuals at tional status as the ‘gold standard’, and the findings of studies
nutritional risk, which can be undertaken by a range of comparing the tools to date have been equivocal. A large mul-
healthcare professionals, whereas nutrition assessment is a ticentre Europe‐wide study under the auspices of the
more detailed and lengthy means for nutrition experts, i.e. European Society for Paediatric Gastroenterology, Hepatology
dietitians, to quantify nutritional status. and Nutrition (ESPGHAN) has evaluated STAMP, PYMS and
StrongKids in 14 centres across 12 countries. The results found
only modest agreement between the three tools in identifying
Nutrition screening children at high malnutrition risk, with PYMS and STAMP
classifying more children in this category than StrongKids.
While nutrition screening tools can be used to identify all aspects The authors concluded that there was still much work needed
of malnutrition (excess, deficiency or imbalance in macro‐ in this area and that none of the three tools evaluated could be
and micronutrients), they are generally used to identify recommended for routine clinical practice [15–17].
Clinical Paediatric Dietetics, Fifth Edition. Edited by Vanessa Shaw.

© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/shaw/paediatricdietetics-5e
2 Principles of Paediatric Dietetics: Nutritional Assessment, Dietary Requirements and Feed Supplementation
Table 1.1 Child‐specific screening tools developed and evaluated Table 1.2 Recommendations for routine measurements for healthy
in the UK. infants and children.
STAMP PYMS Head

Weight Length/height circumference
Criteria utilised Diagnosis Diagnosis
Dietary intake Dietary intake Birth Birth Birth or neonatal
Anthropometrics: Weight loss period
weight and height Anthropometrics: BMI In the first week of life as
centile part of overall
Scored High/medium/ High/medium/low risk assessment of feeding
low risk 8 weeks 6−8 weeks if 6−8 weeks
Criterion validity birthweight <2.5 kg
or if other cause
Agreement with 54% 46%
for concern
full nutritional
assessment* 12 weeks
Positive 55% 47% 16 weeks
predictive value† 1 year
Negative 95% 95%
Additional weights if No other routine No other routine
predictive value††
there are concerns: not measurement of measurement of
Training 30 minutes 60 minutes more frequently than length/height head
Used by Any trained Registered nurses once a month for infants circumference
healthcare <6 months; once every 2
professional months from 6 to 12
months; once every 3
STAMP, Screening Tool for the Assessment of Malnutrition in Paediatrics; months over 1 year
PYMS, Paediatric Yorkhill Malnutrition Score; BMI, body mass index. School entry School entry
*Children identified as being at nutritional risk by tool and full nutritional
assessment. Source: Adapted from Hall [18] and NICE PH11 [19].
†
The proportion of children identified as at risk by the tool who are
actually at risk.
††
The proportion of children identified as not at risk by the tool who are infants should be weighed naked and children wearing just
actually not at risk. a dry nappy or pants; however, this is often not possible or
appropriate. In these situations, it is important to record if
the infant is weighed wearing a clean dry nappy and the
Nutritional assessment amount and type of clothing worn by older children. A
higher degree of accuracy is required for the assessment of
Nutritional assessment comprises anthropometric, clinical sick children than for routine measurements in the commu-
and dietary assessment, all of which should be used to pro- nity. Frequent weight monitoring is important for the sick
vide as full a picture of the nutritional status of the individ- infant or child, and local policies for weighing and measur-
ual as possible; no one method will give an overall picture of ing hospitalised infants and children should be in place.
nutritional status. Within these areas there are several assess- Recommendations for the routine measurement of healthy
ment techniques, some of which should be used routinely in infants where there are no concerns about growth are given
all centres, while others are better suited to specialist clinical in Table 1.2 [18]. If there are concerns about weight gain that
areas or research. This chapter provides a brief overview of is too slow or too rapid, measurement of weight should be
the common techniques and sources of further information. carried out more frequently.
Anthropometry Height
Measurement of weight and height (or length) is critical as Height or length measurement requires a stadiometer or
the basis for calculating dietary requirements as well as length board. Measurement of length using a tape measure
monitoring the effects of dietary intervention. It is important is too inaccurate to be of use for longitudinal monitoring of
that all measurements are taken using standardised tech- growth, although an approximate length may be useful as a
niques and calibrated equipment. Ideally staff taking meas- single measure. Under the age of 2 years, supine length is
urements should receive some training on how to do this measured; standing height is usually measured over this age
accurately. There are a variety of online resources to support or whenever the child can stand straight and unsupported.
training in anthropometric measurement of children. When the method of measurement changes from length to
height, there is likely to be a drop in stature; this is accounted
for in the UK‐WHO growth charts (p. 3). Measurement of
Weight length is difficult and requires careful positioning of the
Measurement of weight is an easy and routine procedure infant; positioning of the child is also important when meas-
that should be done using a calibrated digital scale. Ideally uring standing height. It is recommended to have two
Assessment of Nutritional Status 3
observers involved in measuring an infant or young child. It MUAC are less likely to be affected by oedema than body
is good practice for sick infants to be measured monthly and weight; they can also provide a useful method of assessing
older children at clinic appointments or on admission to hos- changes in children with solid tumours and liver disease. There
pital. Healthy infants should have a length measurement at are age‐related standards for infants and children [23, 24].
birth, but further routine stature checks are not recom- Measurement of waist circumference and the index of waist to
mended until the preschool check [18]. Whenever there are height can be helpful in the identification and monitoring of
concerns about growth or weight gain, a height measure- overweight and obesity [25–27]. Research has shown links with
ment should be made more often. dyslipidaemias, insulin resistance and blood pressure, although
the evidence for benefit using waist circumference centiles over
BMI centiles is limited [27, 28].
Proxy measurements for length/height
When monitoring interventions, particularly those
In some cases it is difficult to obtain length or height meas-
addressing undernutrition, it is important to determine if
urements, e.g. in very sick or preterm infants and in older
changes in weight are due to increases in fat mass or lean
children with scoliosis. A number of proxy measurements
muscle mass. In order to fully differentiate between lean and
can be used, which are useful to monitor whether longitudi-
fat, measurement of skinfold thickness (SFT) can be used.
nal growth is progressing in an individual, but there are no
While this can be unpleasant for young children and is not
recognised centile charts as yet, and indices such as body
used as a routine anthropometric measurement in general
mass index (BMI) cannot be calculated. In younger adults
clinical practice, it is used in some specialist areas and can
arm span is approximately equivalent to height, but body
provide valuable data when taken by an experienced and
proportions depend upon age, and while there is some evi-
practised observer. The equipment and technique are identi-
dence that there is a correlation in older children and adoles-
cal to those used in adults, and the measurement is subject to
cents, this measurement may be of limited usefulness in
the same high rates of inter‐observer and intra‐observer error.
children. Ulna length has been demonstrated to act as a good
Reference data for infants and children are available [24], and
proxy for stature in adults although evidence in children is
arm muscle and arm fat area can be calculated. Full details on
limited [20]. Measurements of lower leg length or knee−heel
skinfold measurements and their interpretation have been
length have been used and are a useful proxy for growth
published elsewhere [23, 29].
[21]. Total leg length is rarely measured outside specialist
Modern technologies can provide information on body
growth clinics and is calculated as the difference between
composition. Bioelectric impedance analysis is easily
measured sitting height and standing height. A number of
undertaken in a clinical setting using foot‐to‐foot or hand‐to‐
other measures have been used in children with cerebral
foot techniques. However, while studies have reported
palsy as a proxy for height (p. 424), but numbers are too
validity of this method of determining body composition in
small for reference standards to be established [22]. Formulas
healthy populations of young children, validity in sick chil-
for calculating stature in children from proxy measurements
dren and infants has yet to be fully established but may have
are available [23]. It should always be remembered that
a role in monitoring change if used on admission to hospital
when using a proxy for length or height measurements, mul-
[30–32]. More invasive technologies for assessing body com-
tiple sources of error are present, from the techniques and
position include dual‐energy X‐ray absorptiometry and air
equipment used to obtain the measurement to calculation
displacement plethysmography. These tend to be restricted
errors in estimation of length/height.
to research assessments of body composition, and further
information can be found elsewhere [23].
Head circumference
Head circumference is generally considered a useful meas-
urement in children under the age of 2 years. After this age Interpreting anthropometric measurements
head growth slows and is a less useful indicator of somatic Anthropometric measurements alone confer limited infor-
growth. A number of genetic and acquired conditions, such mation on growth, nutritional status and health and require
as cerebral palsy, will affect head growth, and measurement the use of growth reference data and conversion to indices
of head circumference will not be a useful indicator of nutri- for interpretation. One of the greatest challenges, however, is
tional status in these conditions. Head circumference is meas- the compliance with weighing and measuring infants and
ured using a narrow, flexible, non‐stretch tape. Accuracy is children, particularly when hospitalised [33, 34]. Staff train-
dependent on the skill of the observer, and, as such, training ing on measurement techniques and the importance of
and practice in this technique is a requirement. obtaining these should be reinforced regularly within all
healthcare settings.
Supplementary measurements
Growth charts
While the measurement of weight and length or height forms
the basis of routine anthropometric assessment, there are a Measurements should be regularly plotted on a relevant growth
number of supplementary measurements, which can be used. chart. In the UK the growth charts are the UK‐WHO growth
These include the proxy measurements for stature already chart 0−4 years and the UK growth chart 2−18 years [35].
mentioned and mid‐upper arm circumference (MUAC). This They are based on WHO 2006 data between the ages of 2 weeks
is a useful measurement in children under the age of 5 years, as and 4 years (from the WHO multicentre longitudinal study of
MUAC increases fairly rapidly up until this age. Increases in optimal growth in breastfed singleton births from six countries
across the world [36]) and UK 1990 data for preterm infants, for sex. BMI is now routinely used to identify and monitor over-
birthweights and for children over 4 years of age. They show weight and obesity in children, on an individual and popula-
nine centiles from the 0.4th to the 99.6th. Length data are used tion basis, in the clinical and research environments [39]. There
up to 2 years of age and standing height from age 2 onwards. are limitations, however, to the use of BMI in children:
The centile lines shift down slightly at the 2 years of age junc-
• It is not recommended in children <2 years of age as dur-
ture to reflect that standing height is less than the measured
ing this period BMI changes rapidly and weight gain
length. Every child in the UK is issued with a growth centile
rather than BMI has been shown to be more indicative of
chart as part of the personal child health record that is held by
future overweight and obesity [40]
parents and completed by healthcare professionals whenever
• In chronic undernutrition there is stunting as well as low
the child is weighed or measured.
weight for age, and thus undernutrition may be masked
Accuracy is crucial when plotting growth charts and,
by using BMI
therefore, training is essential as a number of different pro-
• Although BMI is a relative index of weight to height, it
fessionals may be plotting on a single chart and errors could
does not provide information about body composition;
result in the misdiagnosis or non‐identification of nutritional
it cannot be used to distinguish between fat mass and
and growth problems. When assessing a child in relation to
lean mass
the growth charts, a number of factors need to be accounted
for, including gestational age at birth and parental height. Paediatric BMI charts have been developed and can be
The growth charts give clear guidance on correction for pre- used to indicate how heavy a child is relevant to its height
maturity and the estimation of the child’s adult height. and age [41]. The UK growth charts have a quick reference
It can be difficult to assess progress or decide upon targets guide to estimate BMI centile on the basis of the child’s
where a measurement falls outside the nine centile lines weight and height centiles. More detailed BMI charts show-
(<0.4th centile or >99.6th centile). The Neonatal and Infant ing +3, +3.33, +3.66, +4 SD lines above the 99.6th centile and
Close Monitoring growth chart [35] shows −3, −4 and −5 −4, −5 SD below the 0.4th centile are available from Harlow
standard deviation (SD) lines to allow assessment of very Healthcare [38].
small infants up to the age of 2 years. ‘Thrive lines’ have also
been developed to aid interpretation of infants with either
Anthropometric indices and the classification
slow or rapid weight gain. The 5% thrive lines define the
of nutrition status
slowest rate of normal weight velocity in healthy infants. If
an infant is growing at a rate parallel to or slower than a 5% The World Health Organization (WHO) and research publi-
thrive line, weight gain is abnormally slow. The 95% thrive cations frequently report SD score or z‐score for length/
lines define the most rapid rate of normal weight gain in height, weight and BMI. This involves converting the meas-
healthy infants, and weight gain that parallels or is faster urement or index into a finite proportion of a reference or
than the 95% thrive line is abnormally rapid [36]. There is standard measurement, the calculation giving a numerical
also a Child and Puberty Close Monitoring Chart 2–20 years, score indicating how far away from the 50th centile for age
which is a modification of the UK growth chart 2−18 years, the child’s measurements/index falls. For the UK growth
designed to monitor unusually short, thin or overweight charts, each centile space equates to 0.67 SD; therefore, a
children. Puberty phase specific thresholds allow assess- child on the 2nd centile will have a z‐score of −2 SD, and a
ment of small children with late onset puberty and tall chil- child on the 98th centile will have a z‐score of +2 SD; a meas-
dren with early onset puberty [35]. urement that falls exactly on the 50th centile will have a z‐
There are a range of resources available to support train- score of 0 SD. Calculation of z‐scores by hand is extremely
ing on the plotting and interpretation of growth charts on laborious, but computer software is available that will e nable
the Royal College of Paediatrics and Child Health (RCPCH) calculation of z‐scores from height, weight, BMI, sex and age
website [35]. data [38]. The z‐score can also be used when comparing
Some medical conditions have a significant effect on groups of children when a comparison of the measurements
growth, and where sufficient data exist, separate growth themselves would not be useful.
charts have been developed. Charts for Down syndrome The WHO defines moderate malnutrition and obesity in
were jointly published by the Down Syndrome Medical children in terms of z‐score for weight as −2 SD and +2 SD,
Interest Group and the RCPCH in 2011 [37]. Charts for a respectively [36].
number of other conditions including Williams syndrome, The calculations of height for age, height age and weight
sickle cell and Turner syndrome are available from Harlow for height are useful when assessing nutritional status ini-
Healthcare [38]. tially or when monitoring progress in children who are short
for their chronological age. Table 1.3 shows examples of cal-
culations for these indices. The Waterlow classification [42]
Body mass index
may be of use when assessing children in the UK with severe
A BMI measurement can be calculated from weight and height faltering growth. An adaptation of the classification is shown
measurements: BMI = weight (kg)/height (m2). This provides in Table 1.4. Calculation of height age is necessary when
an indication of relative fatness or thinness. In children the determining nutrient requirements for children who are
amount and distribution of body fat is dependent on age and much smaller (or larger) than their chronological age.
Table 1.3 Height for age, height age and weight for height. Table 1.5 Physical signs of nutritional problems.
Worked example: 6‐year‐old girl with cerebral palsy referred with Assessment Clinical sign Possible nutrient(s)
severe feeding problems
Hair Thin, sparse Protein and
Visit 1 Decimal age = 6.2 years Colour energy, zinc,
change – ‘flag sign’ copper
Height = 93 cm (<0.4th centile)
Easily plucked
Weight = 10 kg (<0.4th centile)
Skin Dry, flaky Essential fatty
50th centile for height for a girl aged 6.2 Rough, ‘sandpaper’ acids
years = 117 cm texture B vitamins
93 Petechiae, bruising Vitamin A
Height for age = 117 = 79.5% height for age
Vitamin C
Height age is the age at which 93 cm
(measured height) falls on 50th centile = 2.7 Eyes Pale conjunctiva Iron
years Xerosis Vitamin A
Keratomalacia
50th centile for weight for 2.7 years = 14 kg
10 Lips Angular stomatitis B vitamins
Weight for height = = 71% weight for height Cheilosis
14
Visit 2 Decimal age = 6.8 years Tongue Colour changes B vitamins

(after intervention) Height = 95.5 cm (<0.4th centile) Teeth Mottling of enamel Fluorosis (excess
Weight = 12 kg (<0.4th centile) fluoride)
50th centile for height for a girl aged 6.8 Gums Spongy, bleed easily Vitamin C
years = 121 cm Face Thyroid enlargement Iodine
95.5
Height for age = = 79% height for age Nails Spoon shape, Iron, zinc, copper
121
Height age = 3.1 years koilonychia
50th centile for weight for age 3.1 Subcutaneous tissue Oedema Protein, sodium
years = 14.5 kg Overhydration
12 Depleted Energy
Weight for height = = 82.7% weight for subcutaneous fat
height 14 .5
Muscles Wasting Protein, energy,
Conclusions: The girl has shown catch‐up weight gain. Weight for height zinc
has increased from 71% to 83%. She has continued to grow in height, Bones Craniotabes Vitamin D
but has not had any catch‐up height. Her height continues to be about Parietal and frontal
79% of that expected for her chronological age. bossing
Epiphyseal
enlargement
Beading of ribs
Table 1.4 Classification of malnutrition.
Chronic malnutrition
Acute malnutrition (wasting) (stunting ± wasting) stage in the development of a deficiency disease, and the
absence of clinical signs should not be taken as indicating
Weight for height Height for age that a deficiency is not present.
80%−90% standard – grade 1 90%−95% standard – grade 1 Typical physical signs associated with poor nutrition,
70%−80% standard – grade 2 85%−90% standard – grade 2 which have been described in children in Western countries,
are summarised in Table 1.5. Physical signs represent very
<70% standard – grade 3 <80% standard – grade 3
general changes and may not be due to nutrient deficiencies
Source: Adapted from Waterlow [42]. alone. Other indications such as poor weight gain and/or
low dietary intake are needed in order to reinforce s uspicions,
and biochemical and haematological tests should be carried
Clinical assessment out to confirm the diagnosis. These include the analysis of
levels of nutrients or nutrient‐dependent metabolites in body
Clinical assessment of the child involves a medical history fluids or tissues or measuring functional impairment of a
and a physical examination. The medical history will i dentify nutrient‐dependent metabolic process. The most commonly
medical, social or environmental factors that may be risk used tissue for investigation is the blood. Whole blood,
factors for the development of nutritional problems. Such plasma, serum or blood cells can be used, depending on the
factors may include parental knowledge and finance availa- test. Tests may be static, e.g. levels of zinc in plasma, or
ble for food purchase, underlying disease, treatments, inves- may be functional, e.g. the measurement of the activity of
tigations and medications. Clinical signs of poor nutrition, glutathione peroxidase, a selenium‐dependent enzyme, as a
revealed in the physical examination, only appear at a late measure of selenium status.
Although an objective measurement is obtained from a blood • Contamination from exogenous materials such as equip-
test, there are a number of factors that can affect the validity of ment or endogenous sources such as sweat or interstitial
such biochemical or haematological investigations: fluid is important for nutrients such as trace elements,
and care must be taken to choose the correct sampling
• Age‐specific normal ranges need to be established for the procedure
individual centre unless the laboratory participates in a
regional or national quality control scheme A summary of some biochemical and haematological
• Recent food intake and time of sampling can affect levels, measurements is given in Table 1.6.
and it may be necessary to take a fasting blood sample Urine is often used for investigations in adults, but
for some nutrients many tests require the collection of a 24 hour urine s ample,
• Physiological processes such as infection, disease or and this is difficult in babies and children. The usefulness
drugs may alter normal levels of a single urine sample for nutritional tests is limited and
Table 1.6 Biochemical and haematological tests.
Nutrient Test Normal values in children Comments
Biochemical tests
Protein Total plasma protein 55−80 g/L Low levels reflect long‐term not acute
Albumin 30−45 g/L depletion
Caeruloplasmin 0.18−0.46 g/L Low levels indicate acute protein
Retinol‐binding protein 2.6−7.6 g/L depletion but are acute phase proteins,
which increase during infection
Thiamin Erythrocyte transketolase 1−1.15 High activity coefficient (>1.15)
activity coefficient indicates thiamin deficiency
Vitamin B12 Plasma B12 value 263−1336 pmol/L Low levels indicate deficiency
Riboflavin Erythrocyte glutathione 1.0−1.3 High activity coefficient (>1.3)
reductase activity coefficient indicates riboflavin deficiency
Vitamin C Plasma ascorbate level 8.8−124 μmol/L Low levels indicate deficiency
Vitamin A Plasma retinol level 0.54−1.56 μmol/L Low level indicates deficiency
Vitamin D Plasma 25‐hydroxy‐ 30−110 nmol/L Low level indicates deficiency
colecalciferol level
Vitamin E Plasma tocopherol level α‐Tocopherol Low levels indicate deficiency
10.9−28.1 μmol/L
Copper Plasma level 70−140 μmol/L Low levels indicate deficiency
Selenium Plasma level 0.76−1.07 μmol/L Low levels indicate deficiency
Glutathione peroxidase activity >1.77 μmol/L Low levels indicate deficiency
Zinc Plasma level 10−18 μmol/L Low levels indicate deficiency
Haematology tests
Folic acid Plasma folate 7−48 nmol/L Low levels indicate deficiency
Red cell folate 429−1749 nmol/L Low levels indicate deficiency
Haemoglobin Whole blood 104−140 g/L Levels <110 g/L indicate iron
deficiency
Red cell distribution width Whole blood <16% High values indicate iron deficiency
Mean corpuscular volume Whole blood 70−86 fL Small volume (microcytosis) indicates
iron deficiency
Large volume (macrocytosis) indicates
folate or B12 deficiency
Mean cell haemoglobin Whole blood 22.7−29.6 pg Low values indicate iron deficiency
Percentage hypochromic Whole blood <2.5% High values (>2.5%) indicate iron
cells deficiency
Zinc protoporphyrin Red cell 32−102 μmol/mol haem High levels indicate iron deficiency
Ferritin Plasma level 5−70 μg/L Low levels indicate depletion of iron
stores. Ferritin is an acute phase
protein and increases during infection
needs to be compared with a standard metabolite, usually For most clinical purposes an oral history from the usual
creatinine. However, creatinine excretion itself is age‐ caregivers (or from the child if appropriate) will provide
dependent, and this needs to be taken into consideration. sufficient information on which to base recommendations.
Stool samples can be useful in determining reasons for In addition to assessing the range and quantity of foods
malabsorption if suspected. Hair and nails have been used eaten, it is also useful to assess whether the texture and
to assess trace element and heavy metal status in popula- presentation of food is appropriate for the age and develop-
tions, but a number of environmental and physiological mental level of the child. Estimation of food intake is
factors affect levels, and these tissues are not routinely particularly difficult in infants, as it is not possible to assess
used in the UK. Tissues that store certain nutrients, such as accurately the amount of food wasted through, for exam-
the liver and bone, also provide useful materials for ple, spitting or drooling. Similar difficulties occur in chil-
investigation, but sampling is too invasive for routine
dren with physical feeding difficulties and dysphagia.
clinical use. Observation of feeding can be particularly useful in these
A more detailed overview of clinical assessment can be situations. Recorded intake can often be utilised at annual
found elsewhere [24]. assessments of children with chronic conditions, in the
identification of food‐related symptoms (allergies and
intolerances) or in the assessment of diet‐related doses of
Dietary intake medications such as pancreatic enzymes or insulin. A range
of tools are available to assist with the assessment of dietary
For children over the age of 2 years, food intake is assessed intake including pictorial portion size guides, computerised
in the same way as for adults: using a recall diet history; a dietary analysis p rogrammes and texture descriptors [44].
quantitative food diary or food record chart at home or on The adequacy of dietary intake is assessed in relation to
the ward, recorded over a number of days; a weighed the dietary reference values (DRV).
food intake over a number of days; or a food frequency The assessment of milk intake for breastfed infants is dif-
questionnaire. These methods are not mutually exclusive, ficult, and only very general estimations can be made.
and combinations are often used to provide the greatest Historically infants have been test weighed before and after
depth of information. There are benefits and limitations to a breastfeed to allow the amount of milk consumed to be
each of these methods, and these are summarised in estimated. This required the use of very accurate scales
Table 1.7 [24, 43]. (±1–2 g) and included all feeds over a 24 hour period as the
volume consumed varied throughout the day. Test weighing
should be avoided if at all possible as it is disturbing for the
Table 1.7 Strengths and limitations of dietary assessment methodologies infant, engenders anxiety in the mother and is likely to com-
for individuals. promise breastfeeding. Studies have shown that the volume
of breastmilk consumed is approximately 770 mL at 5 weeks
Method Strength Limitation and 870 mL at 11 weeks of age [45]. In general an intake of
850 mL is assumed for infants who are fully breastfed and
24 hour recall Quick and easy Relies on memory
Low respondent burden May not be over the age of 6 weeks. Estimation of nutritional intake in a
representative of breastfed infant is further complicated by the varying com-
usual intake position of breastmilk [46].
Estimated food Assesses actual usual Respondents must
diary intake be literate
Ability to estimate Expected growth in childhood
portion size
Longer time frames The 50th centile birthweight for infants in the UK is 3.5 kg for
increase respondent boys and 3.3 kg for girls [47]. Most babies lose weight after
burden
birth while full feeding is gradually established during the
Weighed food Accurate assessment of High respondent first week of life (p. 19). They begin to gain weight between
diary actual intake burden
3 and 5 days of age, with the majority regaining their birth-
Respondents must
be literate and
weight by the 10th−14th day of life. The National Institute
motivated for Health and Care Excellence (NICE) recommends that
Setting may not be babies are weighed at birth and in the first week of life as
conducive to part of the overall assessment of their feeding. Thereafter,
weighing (e.g. babies should be weighed at 8, 12 and 16 weeks and again at
eating out) 1 year of age [19].
Food frequency Quick Ability to quantify The average weight gain during the first year of life, using
questionnaire Low respondent burden intakes is poor the 50th centile for age of the UK‐WHO growth charts [35], is
Can identify food
shown in Table 1.8. The increase in length during the first
consumption patterns:
high/medium/low year of life is 24−25 cm. It is important to remember that the
first 12 weeks of life see the most rapid postnatal growth. If
Source: Gibson [23]. length and weight measurements are static for just 2 weeks
Table 1.8 Average weight gain throughout the first year of life. revised in the SACN 2011 report [49] in the light of advance-
ments in the methodology to measure total energy expendi-
Boys (g/week) Girls (g/week) ture. This report gives a detailed account of the evidence that
First 3 months 240 210 SACN used when updating the EAR for energy for infants,
children, adolescents and adults in the UK. This has coin-
Second 3 months 130 120
cided with other revisions of energy requirements by the
Third 3 months 80 75 Food and Agriculture Organization of the United Nations,
Fourth 3 months 65 60 World Health Organization and United Nations University
(FAO/WHO/UNU) and the Institute of Medicine (IoM) in
the USA.
during this period, there will be a fall of one centile; if static The revised EAR for energy has decreased for infants and
for 4 weeks, there will be a fall of two centiles. Growth rate children under 10 years of age and slightly increased for
slows as the baby gets older. older children and adults. The revised EAR for energy for
During the second year, the toddler following the 50th infants and children is shown in Tables 1.10 and 1.11.
centile gains 2.5−2.6 kg in weight and a further 11−12 cm It must be emphasised that these values are for assessing
in length. Average weight gain continues at a rate of approxi- the energy requirements of large groups of people and are
mately 2−3 kg/year. Height gain in the second year is 10 cm, not requirements for healthy or sick individuals. Also, when
steadily declining to 7 cm down to 5 cm/year until the estimating requirements for the individual sick child, it is
growth spurt at puberty. Puberty in boys usually starts important to calculate energy and nutrient intakes based on
between the ages of 9 and 14 years. Onset of puberty before actual body weight and not expected body weight. The latter
9 years of age is considered precocious, while puberty is will lead to a proposed intake that is inappropriately high for
delayed if there are no signs by 14 years. For girls, puberty the child who has an abnormally low body weight. In some
usually begins between 8 and 13 years, with the onset of instances it may be more appropriate to consider the child’s
puberty before 8 years considered to be precocious and height age rather than chronological age when comparing
puberty not present by 13 years considered to be delayed. intakes with the DRV as this is a more realistic measure of the
child’s body size and, hence, nutrient requirement.
In order to make the revised EAR for energy more usable
Dietary reference values in clinical practice, it is suggested that the data given in
Tables 1.10 and 1.11 are condensed and summarised
The 1991 Department of Health report on DRV [48] provides (Table 1.12).
information and figures for requirements for a comprehen- The estimated requirements for children with specific dis-
sive range of nutrients and energy. The Scientific Advisory orders are given in the relevant chapters. It is important to
Committee on Nutrition (SACN) revised the requirements remember that requirements are not necessarily increased
for energy in 2011 [49]. The requirements are termed dietary during illness. Factors to consider when estimating require-
reference values and are for normal healthy populations of ments for the individual are as follows: nutritional status
infants fed with artificial formulas and for older infants, prior to onset of the disease; whether the disorder is acute or
children and adults consuming food. The 1991 DRV were not chronic; is mobility affected; are there any impacts on nor-
set for breastfed babies as it was considered that human mal feeding such as dysphagia or reduced appetite; are there
milk provides the necessary amounts of nutrients when increased gastrointestinal losses such as vomiting and diar-
fed on demand. In some cases the DRV for infants aged up to rhoea; consider any urinary losses; is there an inability to
3 months who are formula fed are in excess of those that metabolise dietary constituents.
would be expected to derive from breastmilk; this is because A guide to increased oral and enteral (feeding by tube into
of the different bioavailability of some nutrients from breast- the gut) requirements is given in Table 1.13.
milk and artificial formulas.
It is important to remember that these are recommenda-
tions for groups, not for individuals; however, they can be Fluid requirements
used as a basis for estimating suitable intakes for the indi-
vidual, using the reference nutrient intake (RNI) for protein
Preterm and low birthweight infants
and other nutrients. This level of intake should satisfy the
requirements of 97.5% of healthy individuals in a population
Chapter 7 gives a full account of the special requirements of
group. A summary of the 1991 DRV for energy, protein,
these babies.
sodium, potassium, vitamin C, calcium and iron is given in
Table 1.9. The DRV for other nutrients may be found in the
full report. There has been a further revision for vitamin D The newborn infant over 2.5 kg birthweight
requirements [50].
The DRV for energy is expressed as the estimated average Breastfeeding is the most appropriate method of feeding the
requirement (EAR); about half of a population will need more normal infant [51] and may be suitable for sick infants with
energy than the EAR and half less. Energy requirements were a variety of clinical conditions. Demand breastfeeding will
Fluid Requirements 9
Table 1.9 Selected dietary reference values, 1991.
RNI per day
Weight* Energy (EAR) per day Protein Sodium Potassium Vitamin C Calcium Iron
Age kg MJ kJ/kg kcal kcal/kg g g/kg mmol mmol/kg mmol mmol/kg mg mmol mg
Males
0–3 months 5.9 2.28 480–420 545 115–100 12.5 2.1 9 1.5 20 3.4 25 13.1 1.7
4–6 7.7 2.89 400 690 95 12.7 1.6 12 1.6 22 2.8 25 13.1 4.3
7–9 8.9 3.44 400 825 95 13.7 1.5 14 1.6 18 2.0 25 13.1 7.8
10–12 9.8 3.85 400 920 95 14.9 1.5 15 1.5 18 1.8 25 13.1 7.8
1–3 years 12.6 5.15 400 1230 95 14.5 1.1 22 1.7 20 1.6 30 8.8 6.9
4–6 17.8 7.16 380 1715 90 19.7 1.1 30 1.7 28 1.6 30 11.3 6.1
7–10 28.3 8.24 – 1970 – 28.3 – 50 – 50 – 30 13.8 8.7
11–14 43.1 9.27 – 2220 – 42.1 – 70 – 80 – 35 25.0 11.3
15–18 64.5 11.51 – 2755 – 55.2 – 70 – 90 – 40 25.0 11.3
Females
0–3 months 5.9 2.16 480–420 515 115–100 12.5 2.1 9 1.5 20 3.4 25 13.1 1.7
4–6 7.7 2.69 400 645 95 12.7 1.6 12 1.6 22 2.8 25 13.1 4.3
7–9 8.9 3.20 400 765 95 13.7 1.5 14 1.6 18 2.0 25 13.1 7.8
10–12 9.8 3.61 400 865 95 14.9 1.5 15 1.5 18 1.8 25 13.1 7.8
1–3 years 12.6 4.86 400 1165 95 14.5 1.1 22 1.7 20 1.6 30 8.8 6.9
4–6 17.8 6.46 380 1545 90 19.7 1.1 30 1.7 28 1.6 30 11.3 6.1
7–10 28.3 7.28 – 1740 – 28.3 – 50 – 50 – 30 13.8 8.7
11–14 43.8 7.92 – 1845 – 42.1 – 70 – 80 – 35 20.0 14.8
15–18 55.5 8.83 – 2110 – 45.4 – 70 – 90 – 40 20.0 14.8
EAR, estimated average requirement; RNI, reference nutrient intake.

*Standard weights for age ranges [48].
Source: Department of Health [48]. Reprinted with permission of The Stationery Office.
Table 1.10 Estimated average requirement (EAR) for energy for infants, 2011.
Breastfed Breastmilk substitute fed Mixed feeding or unknown
Age kcal (MJ) kcal (MJ) kcal (MJ) kcal (MJ) kcal (MJ) kcal (MJ)
(months) per kg/day per day per kg/day per day per kg/day per day
Boys
1–2 96 (0.4) 526 (2.2) 120 (0.5) 598 (2.5) 120 (0.5) 574 (2.4)
3–4 96 (0.4) 574 (2.4) 96 (0.4) 622 (2.6) 96 (0.4) 598 (2.5)
5–6 72 (0.3) 598 (2.5) 96 (0.4) 646 (2.7) 72 (0.3) 622 (2.6)
7–12 72 (0.3) 694 (2.9) 72 (0.3) 742 (3.1) 72 (0.3) 718 (3.0)
Girls
1–2 96 (0.4) 478 120 (0.5) 550 (2.3) 120 (0.5) 502 (2.1)
3–4 96 (0.4) 526 96 (0.4) 598 (2.5) 96 (0.40) 550 (2.3)
5–6 72 (0.3) 550 96 (0.4) 622 (2.6) 72 (0.3) 574 (2.4)
7–12 72 (0.3) 646 72 (0.3) 670 (2.8) 72 (0.3) 646 (2.7)
Source: Scientific Advisory Committee on Nutrition [49].

Table 1.11 Estimated average requirement (EAR) for energy Most babies will need 150−200 mL/kg/day of infant
for children, 2011. f ormula by the end of the first week until they are 6 months
old, although this will vary for the individual baby [53].
EAR (kcal (MJ) per day)*
Bottle‐fed babies should be allowed to feed on demand
Age (years) Boys Girls and not be encouraged to ‘finish the bottle’. A suggested
way to feed these babies is to offer on the first day approxi-
1 765 (3.2) 717 (3.0) mately one seventh of requirements, say, 20–30 mL/kg,
2 1004 (4.2) 932 (3.9) divided into eight feeds and fed every 2−3 hours. The
3 1171 (4.9) 1076 (4.5) volume offered should be gradually increased over the fol-
lowing days to appetite so that newborn babies gradually
4 1386 (5.8) 1291 (5.4)
increase their intake from about 20–30 mL/kg on the first
5 1482 (6.2) 1362 (5.7) day of life to around 150–200 mL/kg by 7−14 days. Of
6 1577 (6.6) 1482 (6.2) course, more should be offered if the baby is hungry and
7 1649 (6.9) 1530 (6.4) demands more. Breastfed infants will regulate their own
8 1745 (7.3) 1625 (6.8)
intake of milk.
9 1840 (7.7) 1721 (7.2)
10 2032 (8.5) 1936 (8.1) Fluid requirements after the first few weeks
11 2127 (8.9) 2023 (8.5)
12 2247 (9.4) 2103 (8.8) Healthy formula‐fed infants should be allowed to feed on
demand, although parents often wish to get them into a
13 2414 (10.1) 2223 (9.3)
‘routine’. Many infants will take their feeds 4 hourly, five to
14 2629 (11.0) 2342 (9.8) six bottles per day at around 4−6 weeks of age, although
15 2820 (11.8) 2390 (10.0) many will continue to demand feeds more frequently. The
16 2964 (12.4) 2414 (10.1) infant may start to sleep longer through the night and drop a
17 3083 (12.9) 2462 (10.3) feed. A fluid intake of around 150 mL/kg should be main-
tained to provide adequate fluids, energy and nutrients.
18 3155 (13.2) 2462 (10.3)
Infants should not normally be given more than 1200 mL of
*Calculated with the median physical activity ratio. feed per 24 hours as this may induce vomiting and, in the
Source: Scientific Advisory Committee on Nutrition [49]. long term, will lead to an inappropriately high energy intake.
Sick infants may need smaller, more frequent feeds than the
healthy baby and, according to their clinical condition, may
have increased or decreased fluid requirements. Breastfed
automatically ensure that the healthy infant gets the right infants will continue to regulate their own intake of milk and
volume of milk and, hence, nutrients. The suck−swallow− feeding pattern.
breathe sequence that allows the newborn infant to feed After the age of 6 months, a follow‐on milk may be used
orally is usually well developed by 35−37 weeks of gesta- (Table 1.14). These milks are higher in protein, iron and some
tion. If the infant is too ill or too immature to suckle, the other minerals and vitamins than formulas designed to be
mother may express her breastmilk; expressed breastmilk given from birth and may be useful for infants with a poor
(EBM) may be modified to suit the sick infant’s require- intake of solids or who are fluid restricted. There is no need
ments. If EBM is unavailable or inappropriate to feed in to change the feed from an infant formula to a follow‐on
certain circumstances (p. 20), infant milk formulas must be milk if a baby is feeding well and growing normally.
used, preferably whey-based. Common brands of infant ‘Growing up’ milks (or young child formulas) are also on
formulas available in the UK are given in Table 1.14. the market. Designed for children aged 1–3 years, they are
A systematic review of the volumes of breastmilk and not recommended for routine use, but they may increase the
infant formula taken in early infancy [52] has revealed that intake of iron, vitamin D and n‐3 polyunsaturated acids that
formula‐fed infants have a higher intake than breastfed may be in poor supply in the toddler diet [54].
babies (Table 1.15). While there was variation in the amount
of breastmilk taken in the first few days of life, on average
demand breastfed babies took only 21.5 ± 4.2 mL on day 1, Fluid requirements in older infants and children
whereas formula‐fed babies took 170 ± 55.8 mL on day 1. By
day 14, the bottle‐fed babies were still taking a greater Once solids are introduced around the age of 6 months, the
volume: 761.8 ± 18 mL vs. 673.6 ± 29 mL in the breastfed infant’s appetite for milk will lessen. Breastmilk and infant
babies. Not only did the bottle‐fed babies take a larger vol- formulas fed at 150 mL/kg provide 130 mL water/kg. The
ume, but they also had a more energy‐dense milk: fluid requirements for older infants aged 7–12 months
67 kcal/100 mL vs. 53.6 ± 2.5 kcal/100 mL for colostrum decrease to 120 mL/kg, assuming that some water is
(days 1−5) and 57.7 ± 4.2 kcal/100 mL for transitional milk obtained from solid foods (Table 1.16). At 1 year, the healthy
(days 6−14). child’s thirst will largely determine how much fluid is
Fluid Requirements 11
Table 1.12 Guide to energy requirements in clinical practice.
Boys Girls
Energy (EAR) Energy (EAR)* Energy (EAR) Energy (EAR)*

Age (kcal/day) Weight† (kcal/kg/day) (kcal/day) Weight† (kcal/kg/day)
1−2 months 5.0 96−120 4.7 96−120

3−4 6.7 96 6.1 96
5−6 7.7 72−96 7.0 72−96
7−12 9.0 72 8.3 72
1 years 770 9.6 80 720 9.0 80
2 1000 12.2 82 930 11.5 81
3 1170 14.4 82 1080 13.9 78
4 1390 16.3 85 1290 16.0 81
5 1480 18.6 80 1360 18.2 75
6 1560 21.0 74 1480 21.0 70
7 1650 23.0 71 1530 23.0 67
8 1750 26.0 67 1630 26.0 63
9 1840 29.0 63 1720 29.0 59
10 2030 31.5 64 1940 32.0 61
11 2130 34.5 62 2020 35.9 56
12 2250 38.0 59 2100 40.0 53
13 2410 43.0 56 2220 46.0 48
14 2630 49.0 54 2340 51.0 46
15 2820 55.5 51 2390 53.0 45
16 2970 60.2 49 2410 55.3 44
17 3080 64.0 48 2460 57.0 43
18 3160 66.2 48 2460 57.2 43
1 kcal = 4.18 kJ.
* Depending on method of feeding for infants (Table 1.10).
†
Median weight from the UK‐WHO growth chart 0−4 years and the UK growth chart 2−18 years [35].
Table 1.13 Guide to increased oral and enteral requirements.
Infants 0–1 year* Children
Energy High: 130−150 kcal (545−630 kJ)/kg/day High: 120% EAR†

Very high: 150−180 kcal (630−750 kJ)/kg/day Very high: 150% EAR
Protein High: 3−4.5 g/kg/day High: 2 g/kg/day*
Very high: maximum of 6 g/kg/day It should be recognised that children may
easily eat more than this amount
Sodium High: 3.0 mmol/kg/day
Very high: 4.5 mmol/kg/day
A concentration >7.7 mmol Na+/100 mL of
infant formula will have an emetic effect
Potassium High: 3.0 mmol/kg/day
Very high: 4.5 mmol/kg/day
* Based on actual weight, not expected weight.

†
May be better to base on height age rather than chronological age in very small children.
Table 1.14 Infant milk formulas and follow‐on milks. Table 1.17 Daily water requirements for infants and children.
Whey‐based infant Casein‐based EFSA 2010* [56] IoM 2005† [57]

formula infant formula Follow‐on milks* Dietary reference Dietary reference
Age values intakes
Aptamil 1 First Infant Aptamil Hungry Aptamil 2†
Milk† (Danone) 0−6 months 100−190 mL/kg 700 mL
Cow & Gate 1 First Infant Cow & Gate Cow & Gate 2 6−12 800−1000 mL 800 mL
Milk (Cow & Gate) Hungrier Baby
12−24 1100−1200 mL
HiPP Combiotic First HiPP Combiotic HiPP Combiotic 2
1−3 years 1300 mL (900 mL
Infant Milk (HiPP UK) Hungry Infant
from drinks)
Holle 1 (Holle) Holle 2
2−3 1300 mL
Kendamil 1 (Kendal Kendamil 2
4−8 1600 mL 1700 mL (1200 mL
Nutricare)
from drinks)
SMA PRO 1 First Infant SMA Extra Hungry SMA PRO 2**
9−13 (boys) 2100 mL 2400 mL (1800 mL
Milk** (SMA Nutrition)
from drinks)
*Suitable from 6 months. 9−13 (girls) 1900 mL 2100 mL (1600 mL
†
Also available in Aptamil Profutura range containing long chain from drinks)
polyunsaturated acids and oligosaccharides. 14−18 (boys) 2500 mL (adult) 3300 mL
**Also available in SMA Advanced range containing oligosaccharides.
14−18 (girls) 2000 mL (adult) 2300 mL
Table 1.15 Volume of milk taken in the first 2 weeks of life. *Includes water from beverages and food.
†
Includes water from beverages, food and drinking water.
Day of life Breastmilk (mL) Infant formula (mL)
designed to calculate fluid requirements for parenteral nutri-
1 21.5 ± 4.2 170.5 ± 55.8
tion and is based on the child’s weight, using an average
2 100.3 ± 21.8 265.0 ± 67.7 requirement of 100 mL water for each 100 kcal (420 kJ) of
7 495.3 ± 33.4 576 ± 29 energy metabolised. If less energy is required, then less
14 673.6 ± 29 761.8 ± 18 water will be needed. If nutritional requirements are met
from a smaller volume of feed, then any extra fluid needed
Source: Hester et al. [52]. https://www.ncbi.nlm.nih.gov/pmc/articles/ (e.g. if the child is losing more than usual fluid through
PMC3463945/. Licensed under CC BY. breathing, sweating, vomiting, diarrhoea and passing dilute
urine) may simply be given as water.
Table 1.16 Water content of foods.
Body weight Estimated fluid requirement
Food Percentage water content 11−20 kg 100 mL/kg for the first 10 kg +
50 mL/kg for the next 10 kg
Fruits and vegetables 80−85
>20 kg 100 mL/kg for the first 10 kg +
Yoghurt and milk puddings 70−80 50 mL/kg for the next 10 kg +
Rice and pasta 65−80 25 mL/kg thereafter
Fish 70−80 Worked example for a child weighing 22 kg
Eggs 65−80 100 mL/kg for =1000 mL
the first 10 kg
Meat 45−65
+50 mL/kg for =500 mL
Cheese 40−50 the next 10 kg
Bread 30−45 +25 mL/kg for =50 mL
the final 2 kg
Source: Adapted from Grandjean and Campbell [55].
Total =1550 mL = 70 mL/kg
Overweight children will need less fluid than the

taken. There are some published fluid requirements for
c alculated volume as their actual body weight is higher than
healthy populations (Table 1.17). These are all based on
normal. It would be reasonable to estimate their weight for
observations of water intakes and urine osmolality, not
these calculations as the value on the centile that matches
hydration status.
their height centile, e.g.
If all a child’s nutrition comes from feed and there is no
significant contribution to fluid intake from foods, then fluid • 7‐year‐old boy with a weight of 35 kg = 99.6th
requirements may be estimated using an adaptation of the centile: fluid requirement using above formula =

Holliday−Segar formula [58]. This formula was originally (1000 + 500 + 375) = 1875 mL
Supplementing Feeds for Infants with Faltering Growth or who are Fluid Restricted 13
• He is 122 cm tall = 50th centile Concentrating infant formulas

• Base fluid requirement initially on a body weight of
23 kg = 50th centile: fluid requirement using above Normally infant formula powders, whether whey‐ and
formula = (1000 + 500 + 75) = 1575 mL casein‐based milk formulas or special therapeutic formulas,
• Monitor fluid status and adjust accordingly. More water should be diluted according to the manufacturers’ instruc-
may be required, but not necessarily more feed tions as this provides the correct balance of energy, protein
For underweight children it is important to calculate their and nutrients when fed at the appropriate volume. However,
fluid requirement based on their actual weight, not their there are occasions when, to achieve a feed that is more
expected weight for age or height, but as this is lower than dense in energy, protein and other nutrients, it is necessary
normal, they will need increased energy and protein density to concentrate the formula. Most normal infant milk formu-
in their feed to achieve catch‐up growth. las in the UK are made up at a dilution of around 13% (13 g
powder per 100 mL water). By making up the infant formula
at a dilution of 15% (15 g powder per 100 mL water), more
Supplementing feeds for infants with faltering nutrition can be given in a given volume of feed, e.g. energy
growth or who are fluid restricted content may be increased from 67 kcal (280 kJ) per 100 mL to
77 kcal (325 kJ) per 100 mL and protein content from
Supplements may be used to fortify standard infant for- 1.3 g/100 mL to 1.5 g/100 mL. Infant formulas may be con-
mulas and special therapeutic formulas to achieve the nec- centrated further if tolerated. Similarly, special therapeutic
essary increase in energy, protein and other nutrients formulas that are usually made up at a dilution of, say, 15%
required by some infants. EBM can also be fortified using a may be concentrated to 17% (17 g powder per 100 mL water)
standard infant formula powder in term babies (Table 1.18) or further if tolerated. This concentrating of feeds should
or a breastmilk fortifier in preterm infants (p. 104). Care only be performed as a therapeutic procedure and is not
needs to be taken not to present an osmotic load of more usual practice. The consequence of concentrating feeds is to
than 500 mOsm/kg H2O to the normal functioning gut; increase the osmolality. Steele et al. have shown a linear rela-
otherwise an osmotic diarrhoea will result. If the infant has tionship between feed concentration and osmolality so that
malabsorption, an upper limit of 400 mOsm/kg H2O may the osmolality of a concentrated feed can be reliably calcu-
be necessary. Infants who are fluid restricted will need to lated from the manufacturer’s data for normal dilution,
meet their nutritional requirements in a lower volume of rather than necessitating the feed to be measured by osmom-
feed than usual, and the following feed manipulations can etry in the laboratory [60]. Table 1.18 shows an example of an
be used for these babies. infant formula concentrated to 15% and 17%.
Table 1.18 Examples of energy‐ and nutrient‐dense formulas for infants (per 100 mL).
Osmolality
(mOsm/kg
Energy (kcal) kJ Protein (g) CHO (g) Fat (g) Na (mmol) K (mmol) H2O) PE ratio
13.1% SMA PRO 1 67 280 1.3 7.1 3.6 1.0 1.6 296 7.8
(normal concentration)
15% SMA PRO 1 77 320 1.5 8.1 4.1 1.1 1.8 339* 7.8
17% SMA PRO 1 87 365 1.7 9.2 4.7 1.3 2.1 384* 7.8
EBM† + 3% Cow & Gate 1 84 350 1.6 8.8 4.8 0.9 1.9 – 7.6
17% Cow & Gate 100 420 1.6 12.0 5.0 0.9 2.3 – 6.4
1 + Maxijul to 12%
CHO + Calogen to 5% fat
Ready‐to‐feed formulas
SMA High Energy 99 415 2.6 10.0 5.4 1.2 2.6 377 10.5
(SMA Nutrition)
Similac High Energy 100 420 2.6 10.1 5.4 1.1 2.3 333 10.4
(Abbott)
Infatrini (Nutricia) 101 420 2.6 10.3 5.4 1.6 2.4 360 10.3
PE, protein–energy ratio; EBM, expressed breastmilk.

The Scientific Advisory Committee on Nutrition used an energy density for breastmilk of 0.67 kcal/g (2.8 kJ/g) rather than 0.69 kcal/g (2.9 kJ/g) in the
revised Dietary Reference Values for Energy, 2011 [49].
*Calculated value.
†
Holland et al. [59].
The protein–energy (PE) ratio of the feed should ideally be formulas. They are suitable for use from birth and are
kept within the range 7.2%−12% for infants (i.e. 7.2%−12% designed for infants who have increased nutritional
energy from protein). For accelerated weight gain or catch‐ requirements or who are fluid restricted. They obviate the
up growth [61]: need for carers to make up normal infant milk formulas at
concentrations other than the usual one scoop of powder
• Weight gain of 10 g/kg/day requires 126 kcal (530 kJ)/
to 30 mL water.
kg/day, 2.8 g protein/kg/day, 8.9% PE
• Weight gain of 20 g/kg/day requires 167 kcal (700 kJ)/
kg/day, 4.8 g protein/kg/day, 11.5% PE Energy and protein modules
• Optimal PE for catch‐up height is not determined, but is
likely to be 11%−12% There may be therapeutic circumstances when energy and/
In some clinical situations it is not possible to preserve this or protein supplements need to be added to normal infant
protein–energy ratio as carbohydrate and fat sources alone milk formulas or special therapeutic formulas rather than
may be added to a feed to control deranged blood biochem- increasing the concentration of the base feed. Sometimes a
istry, for example. In these situations it is important to ensure ready‐to‐feed formula does not meet the needs of the indi-
that the infant is receiving at least the RNI for protein. vidual child, and energy and protein modules may need to
If infants are to be discharged home on a concentrated be added. Energy and protein modules and their use are
feed, the recipe may be translated into scoop measures for described below.
ease of use. This will mean that more scoops of milk powder
will be added to a given volume of water than recom-
mended by the manufacturer. As this is contrary to normal Carbohydrate
practice, the reasons for this deviation should be carefully
Carbohydrate provides 4 kcal/g (16 kJ/g). It is preferable
explained to the parents and communicated to primary
to add carbohydrate to a feed in the form of glucose poly-
healthcare staff.
mer, rather than using monosaccharides or disaccharides,
because it exerts a lesser osmotic effect on the gut. Hence,
Nutrient‐dense ready‐to‐feed formulas a larger amount can be used per given volume of feed.
Glucose polymers (Table 1.19) should be added in 1%
Nutrient‐dense ready‐to‐feed formulas are available for increments each 24 hours, i.e. 1 g/100 mL feed per 24
hospital use and in the community (Table 1.18). They are hours. This will allow the concentration at which the
nutritionally complete formulas containing more energy, infant becomes intolerant (i.e. has loose stools) of the
protein and nutrients per 100 mL than standard infant extra carbohydrate to be identified. Tolerance depends on
Table 1.19 Energy modules.
Per 100 g Ingredients* Energy (kcal)* kJ Na (mmol) K (mmol) PO4 (mmol)
Glucose polymer powders

Caloreen (Nestle) Maltodextrin 385 1610 <1.8 <0.3 0
Maxijul Super Soluble (SHS) Dried glucose syrup 380 1590 <0.9 0.12 0.16
Polycal** (Nutricia) Maltodextrin 384 1605 0.1 Trace 0
Vitajoule (Vitaflo) Dried glucose syrup 380 1590 <0.9 0 0
Fat emulsions % fat as MCT
Calogen† (Nutricia) Canola oil, sunflower oil 450 1880 0.3 0.12 0
Liquigen (Nutricia) Palm kernel and/or coconut oil 450 1880 2.2 <0.01 96
Combined fat and carbohydrate powdered module
Duocal Super Soluble Hydrolysed cornstarch, corn oil, 492 2055 <0.9 <0.1 35
(Nutricia) coconut oil, palm kernel oil
MCT, medium chain triglycerides.

*As quoted by manufacturers.
**Not suitable for children <1 year.
†
Unflavoured.
Supplementing Feeds for Infants with Faltering Growth or who are Fluid Restricted 15
the age of the infant and the maturity and absorptive There is a combined carbohydrate and fat module using
capacity of the gut. The addition of 2% (2 g/100 mL) both long and medium chain fats (Table 1.19). Again this
glucose polymer (Super Soluble Maxijul) to infant formu- must be introduced to feeds in 1% increments to determine
las has been shown to increase the feed osmolality by the child’s tolerance of the product. The addition of 2% of a
31.2 mOsm/kg H2O [58]. combined fat and glucose polymer powder (Duocal Super
As a guideline the following percentage concentrations of Soluble) to infant formulas increases the feed osmolality by
carbohydrate (g total carbohydrate per 100 mL feed) may be 23.0 mOsm/kg H2O [58].
tolerated if glucose polymer is introduced slowly: A schedule for the addition of energy modules to infant
formulas is given in Table 1.20.
• 10%−12% carbohydrate concentration in infants under 6
months (i.e. 7 g from formula, 3−5 g added)
• 12%−15% in infants aged 6 months to 1 year Protein
• 15%−20% in toddlers aged 1−2 years Protein may be added to feeds in the form of whole protein,
• 20%−30% in older children peptides or amino acids (Table 1.21). Protein supplementa-
If glucose or fructose needs to be added to a feed where tion is rarely required without an accompanying increase in
there is an intolerance of glucose polymer, an upper limit of energy consumption.
tolerance may be reached at a total carbohydrate concentra-
tion of 7%−8% in infants and young children, so much less
energy will be provided from the feed.
Table 1.20 Schedule for the addition of energy modules to infant
Fat formulas.
Fat provides 9 kcal/g (37 kJ/g). Long chain fat emulsions Additional Energy
are favoured over medium chain fat emulsions because CHO/fat per added per
they have a lower osmotic effect on the gut and provide a Day Energy source added 100 mL feed 100 mL (kcal) (kJ)
source of essential fatty acids. Medium chain fats are
used where there is malabsorption of long chain fat 1 1% glucose polymer 1 g CHO 4 17
(Table 1.19). 2 2% glucose polymer 2 g CHO 8 33
Fat emulsions should be added to feeds in 1% increments 3 3% glucose polymer 3 g CHO 12 50
each 24 hours, providing an increase of 0.5 g fat per 100 mL 4 3% glucose polymer 3 g CHO 17 69
per 24 hours. Infants will tolerate a total fat concentration of + 1% fat emulsion 0.5 g fat
5%−6% (i.e. 5−6 g fat per 100 mL feed) if the gut is function-
5 3% glucose polymer 3 g CHO 21 88
ing normally. The addition of 2% long chain fat emulsion + 2% fat emulsion 1 g fat
(Calogen) to infant formulas has been shown to increase the
feed osmolality by only 0.7 mOsm/kg H2O [58]. Children + 2% fat emulsion 1 g fat
over 1 year of age will tolerate more fat, although concentra-
tions above 7% may induce a feeling of nausea and cause
+ 2% fat emulsion 1 g fat
vomiting. Medium chain fat will not be tolerated at such
high concentrations and may be the cause of abdominal
+ 3% fat emulsion 1 5 g fat
cramps and osmotic diarrhoea if they are not introduced
slowly to the feed. CHO, carbohydrate.
Table 1.21 Protein modules (powders).
Energy
Per 100 g Type of protein (kcal) kJ Protein (g) CHO (g) Fat (g) Na (mmol) K (mmol) Ca (mmol) PO4 (mmol)
Protifar (Nutricia) Whole milk 368 1540 87.2 1.2 1.6 4.8 3.6 33.8 22.6
protein
Hydrolysed Whey Protein/ 348 1455 49.8 37.2 0 19.8 16.2 9.0 3.5
Maltodextrin (Nutricia)
Complete amino acid mix (Nutricia) 328 1370 82 0 0 0 0 0 0
Table 1.22 Vitamin supplements.
Abidec
Healthy Start Children’s Multivitamin Drops* DaliVit Drops (Boston Ketovite (Essential
Vitamin Drops (NHS) (Omega Pharma Ltd) Healthcare Ltd) Pharmaceuticals Ltd)
5 drops for all infants 0.3 mL < 1 year 0.3 mL < 1 year

from 4 weeks to 4 years† 0.6 mL > 1 year** 0.6 mL > 1 year** 5 mL liquid + 3 tablets
Thiamin (B1) mg − 0.4 1 3.0

Riboflavin (B2) mg − 0.8 0.4 3.0
Pyridoxine (B6) mg – 0.8 0.5 1.0
Nicotinamide mg – 8 5 9.9
Pantothenate mg − − − 3.5
Ascorbic acid (C) mg 20 40 50 50
Alpha‐tocopherol (E) mg − − − 15
Inositol mg − − − 150
Biotin μg − − − 510
Folic acid μg − − − 750
Acetomenaphthone (K) μg − − − 1500
Vitamin A μg 200 400 1500 750
Vitamin D μg 7.5 (D3) 10 (D2) 10 (D2) 10 (D2)
Choline chloride mg − − − 150
Cyanocobalamin (B12) μg − − − 12.5
†
Children who are having 500 mL or more of formula a day do not need Healthy Start vitamins.
*Contains peanut oil.
**Values relate to 0.6 mL dose.
Protein modules are added to feeds to provide a specific be different, and these are fully described in the dietary man-
amount of protein per kilogram actual body weight of the agement of each clinical condition.
child. It is rarely necessary to give intakes >6 g protein/kg; if The prescribable vitamin and mineral supplements that
intakes do approach this value, blood urea levels should be are most often used in paediatrics are given in Tables 1.22
monitored twice weekly to avoid the danger of uraemia and 1.23.
developing. Modules should be added in small increments
as they can very quickly and inappropriately increase the
child’s intake of protein. The osmotic effect of whole protein Prescribing products for paediatric practice
products will be less than that of peptides and peptides less
than the effect of amino acids. Special therapeutic formulas, supplements and special
dietary foods can be prescribed for specific conditions.
The Advisory Committee on Borderline Substances
Vitamins and minerals recommends suitable products that can be prescribed for
use in the community and defines their indications.
Vitamin and mineral requirements for populations of normal Prescriptions from the general practitioner should
children are provided by the DRV [48]. Where no RNI is set, be endorsed ‘ACBS’ to indicate that the prescription
safe levels are given. The RNI for the main vitamins and min- complies with recommendations. A list of prescribable
erals are shown in Table 1.9. As a quick assessment of nutri- items for paediatric use appears in the British National
tional adequacy in the well child, when there is sufficient Formulary for Children under the borderline substances
energy, protein, calcium, iron and vitamin C in the diet, it appendix and is available on line at bnfc.nice.org.uk [62].
will probably be sufficient in other nutrients. In disease Dietetic products are categorised as enteral feeds (non‐
states, requirements for certain vitamins and minerals will disease specific), n
utritional supplements (non‐disease
Prescribing Products for Paediatric Practice 17
Table 1.23 Vitamin and mineral supplements, daily dose.
Paediatric Seravit Forceval FruitiVits Soluble

Unflavoured Forceval Soluble Soluble Adult** Orange flavoured Phlexy‐Vits Powder
powder (Nutricia) Junior (Alliance) (Alliance) powder (Vitaflo) (Nutricia)
14 g 0–6 months

17 g 6−12 months
25 g* 1−7 years 1 effervescent 1 effervescent 6 g sachet 3−10
35 g 7–14 years tablet >6 years tablet >12 years years 7 g sachet >11 years
Energy kcal (kJ) 75 (315) 8.7 (37.5) 7.5 (32.6) 2 (10) 0.2 (1)
CHO g 18.8 0.86 0.34 0.5 0.04
Protein g 0 0 0 0 0.2
Fat g 0 0 0 0 0
Sodium mg <5 Tr Tr 4.7 8.8
Potassium mg <8 96 4 4.0 <1.4
Calcium mg 643 — 120 804 1000
Phosphorus mg 429 — 105 502 775
Magnesium mg 89 56 56 201 300
Iron mg 17.3 5 12 10 15.1
Zinc mg 11.5 5 15 10 11.1
Copper mg 1.2 1 2 1 1.5
Iodine μg 83 75 140 169 150
Manganese mg 1.2 0.35 3 1.5 1.5
Molybdenum μg 88 50 250 68 70
Selenium μg 34 25 50 41 75
Chromium μg 34 50 200 41 30
Vitamin A μg 1050 375 750 500 800
Vitamin D μg 14 5 10 15 10
Vitamin E mg 5.4 5 10 9.3 9
Vitamin K μg 41.5 25 0 60 70
Vitamin C mg 100 25 60 40 50
Thiamin mg 0.8 1.2 1.2 1.2 1.2
Riboflavin mg 1.1 1 1.6 1.4 1.4
Niacin mg 8.8 7,5 18 15 20
Pyridoxine mg 0.9 1 2 1.7 1.6
Pantothenic acid mg 4.3 2 4 4.7 5
Vitamin B12 μg 2.2 2 3 2.8 5
Folate μg 76 100 400 240 700
Biotin μg 54 50 100 112 150
Choline mg 88 0 0 250 0
CHO, carbohydrate.
* 25 g dose.
** Also available as Forceval Capsule Adult. Same composition except for Energy 0, CHO 0, Calcium 108 mg, Phosphorus 83 mg, Magnesium 30 mg,
Sodium 0 and Potassium 4 mg. Not for children <12 years.
specific), specialised formulas, feed supplements, feed

additives, nutritional supplements for metabolic diseases References, further reading, guidelines, support groups
and foods for special diets. Children under the age of 16 and other useful links are on the companion website:
years in the UK are exempt from prescription charges. www.wiley.com/go/shaw/paediatricdietetics-5e
2
Judy More
Healthy Eating
Introduction Table 2.1 Guideline daily amounts of sodium and salt.
Infants, toddlers and schoolchildren need to satisfy their Daily recommended

Reference nutrient maximum intake [5]
energy and nutrient requirements for normal growth, devel-
intake [2]
opment and activity through eating a varied and balanced Age Sodium (g/day) Sodium (g/day) Salt (g/day)
diet based on five food groups, along with a daily vitamin D
supplement. Energy and nutrient requirements for healthy 0–12 0.21–0.35 0.4 1
UK children vary with age and are found in the following months
documents: 1–3 years 0.5 0.8 2
4–6 years 0.7 1.2 3
• estimated average requirements (EAR) for energy: rec-
7–10 years 1.2 2.0 5
ommendations from the Scientific Advisory Committee
on Nutrition (SACN) 2011 [1] 11+ years 1.6 2.4 6
• reference nutrient intakes (RNI) and lower reference
nutrient intakes (LRNI) for macro‐ and micronutrients:
• Healthy Child Programmes [6, 7]
the Department of Health’s Report on Dietary Reference
• widening children’s exposure to fruit and vegetables
Values (DRV) 1991 [2]
through the School Fruit and Vegetable Scheme [8]
• safe intakes (SI) and revised RNI for vitamin D: SACN
• voluntary guidelines on food to be served to children in
Report on Vitamin D and Health 2016 [3]
early years settings [9]
• fibre: SACN Report on Carbohydrates and Health 2015 [4]
• School Food Standards, but these are non‐statutory and
In addition, SACN’s 2003 Report on Salt and Health pub- not monitored. In England they apply to all maintained
lished set population goals for salt and sodium consumption schools and academies that were founded before 2010
for various age groups of babies and children [5] in order to and after June 2014 [10]
tackle the longer‐term problems of hypertension and cardio- • the Childhood Obesity Strategy [11]
vascular disease found in the adult population (Table 2.1).
These are not intended for individual intakes, and at only 50% Infants (0–12 months)
above the RNI for sodium, they would be difficult to achieve
in practice, despite a reduction of approximately 15% of the Infants are exclusively milk fed from birth until complemen-
salt content in some commercial foods over the last few years. tary feeding is introduced alongside milk feeding between 4
UK government policies promote healthy eating for and 6 months (further details on the age for complementary
infants and children through a number of initiatives: feeding are given on p. 25). Breastmilk is the optimal milk
feed throughout the first year of life, and the only nutrition-
• promoting breastfeeding ally adequate alternatives are formula milks made according
• broadening the nutritional support for low‐income fami- to EU regulations: infant formula from birth and from 6
lies through the Sure Start and Healthy Start schemes months either infant formula or follow‐on milk.

Infants (0–12 Months) 19
Breastmilk demand breastfeeding, mothers may need to feed every 2–3

hours or 8–12 times a day. Once lactation has become fully
It is the best option as it protects the infant against certain established, the time between feeds usually increases although
illnesses that formula milks cannot. Breastmilk: some infants continue to prefer smaller more frequent feeds.
• contains thousands of distinct bioactive molecules that
protect against infection and inflammation and contrib- Breastmilk composition
ute to immune maturation, organ development and
healthy microbial colonisation [12]. It has its own micro- The volume of milk produced depends on the glandular
biome and oligosaccharides that feed both the breastmilk tissue content in each breast and varies between a wom-
and infant gut bacteria an’s two breasts and between women [17]. Breastmilk
• is a dynamic fluid that changes in composition from composition varies considerably between women and
colostrum, produced in the first few days, to transitional depends on [18]:
milk – a mixture of colostrum and mature milk – and
• beginning or end of feeding; energy and fat content
finally to mature milk from about 2 to 3 weeks of age [12]
increase during each feed
• composition also varies with each mother and during
• duration of lactation
each feed and at different feeds over the day [13]
• time of day
Colostrum is high in proteins, especially immunoglobu- • diet and body composition of the mother
lins, which confer maternal immunity against infection. It is • maternal genes
low in fat and energy and its provision is under hormonal • possibly infant factors such as sex
control and will not be influenced by frequent suckling.
The average energy composition of mature breastmilk
Newborn babies generally take very small volumes infre-
was estimated to be 69 kcal (289 kJ)/100 mL, but a recent sys-
quently over the first few days (21.5 ± 4.2 mL on day 1)
tematic review of data from 1088 samples of mature breast-
(Table 2.2) [15]. At the same time, it is normal for infants to
milk showed an energy content of 65.2 ± 1.1 kcal/100 mL
have a net weight loss, which is mostly fluid, of up to around
(273 ± 4.6 kJ/100 mL) [14] (Table 2.3). At the beginning of the
10% of their birthweight.
feed, the milk is low in fat and higher in lactose and satisfies
From about day 2–3 post‐partum, the composition of breast-
the infant’s thirst; as the feed progresses, the fat and energy
milk changes to transitional milk, which has a higher water
content increases and the high fat milk towards the end of a
content. This change usually coincides with the infant demand-
feed is more satisfying. Mothers should, therefore, be encour-
ing higher volumes of milk more frequently (Table 2.2). Most
aged to let their infant drink as much as desired from the
mothers experience discomfort in their breasts due to this sud-
first breast before offering the second breast; this way the
den increase in the volume of milk produced. They need to be
infant gets the higher energy milk at the end of feeding at
advised to expect the temporary discomfort and reassured that
each breast. Less milk (or none at all) may be taken from the
it will only last about 24 hours as the volume produced adjusts
second breast offered. The first breast offered should be
to the amount demanded by the infant.
alternated at each feed so that both breasts receive equal
Some women experience a delay in this change to transi-
stimulation and drainage. Young infants may need to be
tional milk, and this includes mothers who have [16]:
woken by cuddling them upright and changing their nappy
• poorly controlled diabetes after finishing at the first breast before being offered the sec-
• had a stressful or traumatic delivery ond breast.
• had a caesarean section Some infants demand feeds frequently, while others take
larger volumes less frequently, but the total daily fat intake is
The delay can create anxiety and these mothers need an
not affected by the frequency of feeding nor whether one or
explanation of why there is a delay in providing a larger vol-
both breasts are suckled at each feed [17].
ume of transitional milk and reassurance that establishing
breastfeeding to satisfy their infant’s needs is still possible.
From this time onwards, the volume of transitional and Benefits of breastfeeding
later mature breastmilk is produced in response to the infant’s
suckling and the removal of milk from the breast during feed- Breastfeeding is associated with health benefits for both the
ing or expressing the milk [16]. During the early weeks of infant and mother [19, 20].
Table 2.2 Average volumes (mL/day) of breastmilk consumed compared with formula milk intakes [14].
Day 1 Day 2 Day 3 Day 4 Day 5 Day 7 14 + days
Breastfeeding 21.5 ± 4.2 100.3 ± 21.8 285.3 ± 40.1 383.8 ± 17.4 457.2 ± 20.9 495.3 ± 33.4 673.6 ± 29

Infant formula 170.5 ± 55.8 265 ± 67.7 410 ± 26 493 ± 32 566 ± 30 576 ± 29 761.8 ± 18
Source: Licensed under CC BY 3.0.

20 Healthy Eating
Table 2.3 Comparison of average energy and macronutrient composition of breastmilk compared with formula milks [14].
Energy (kcal/100 mL) Protein (g/100 mL) Fat (g/100 mL) Carbohydrate (g/100 mL)
Colostrum 53.6 ± 2.5 2.5 ± 0.2 2.2 ± 0.2 5.6 ± 0.6

1–5 days
Transitional breastmilk 57.7 ± 4.2 1.7 ± 0.1 3.0 ± 0.1 5.9 ± 0.4
3–14 days
Mature breastmilk 65.2 ± 1.1 1.3 ± 0.1 3.8 ± 0.1 6.7 ± 0.2
from about 14 days
Infant formula 67 1.3 3.4 7.4
(average various UK brands)
Source: Licensed under CC BY 3.0.
For the infant: then be brought quickly and firmly to the breast aiming to
get a good mouthful of breast tissue.
• reduced incidence of non‐specific gastroenteritis and
Once attached to the breast, there should be more areola
lower severe respiratory infections
visible above the baby’s top lip than the lower lip; the lower
• reduced risk of otitis media
lip should be turned out and the tongue under the mother’s
• fewer visits to the doctor in the first 2 years of life
nipple; the chin can be indented into the breast and the nose
For the mother: must be free for breathing.
If the baby is unable to suckle at birth, the mother can
• delay in return to menstruation allowing maternal iron
express her milk. Expressing 8–12 times a day will be neces-
stores to replenish following pregnancy and childbirth
sary to establish a good milk supply, and considerable prac-
• reduced risk of breast and ovarian cancer
tical and emotional support is important for these mothers.
• lower risk of postnatal depression
Provided there is no restriction on how much an infant can
The contraindications to breastfeeding are as follows: breastfeed (i.e. demand feeding is practised), no extra water
is needed, even in very hot weather, as the infant will simply
• The baby has classical galactosaemia, a long chain fatty
feed more frequently to obtain more fluid when thirsty.
acid oxidation defect or glucose–galactose malabsorption
Health professionals can support and promote breastfeed-
• The mother is taking certain medications, is receiving
ing through policy development, through the provision of
radiotherapy or chemotherapy, is a drug abuser or takes
environments conducive to breastfeeding and by having the
excessive alcohol
knowledge and skills to give consistent practical advice and
• HIV‐positive status of the mother as HIV transmission
support to breastfeeding mothers. Factors that improve rates
from mother to infant can occur via breastmilk; however,
of breastfeeding include:
in developing countries, where formula feeding may
greatly increase the risk of gastrointestinal infections and
• early contact between mother and baby. Healthy infants should
mortality, exclusive breastfeeding is preferable
be placed and remain in direct skin‐to‐skin contact with
mother immediately after delivery until the first feeding is
Supporting and maintaining breastfeeding accomplished [22]. The World Health Organization (WHO)
recommends putting the baby to the breast within an hour
Breastfeeding is not an entirely instinctive process and most after birth to assist in developing the suckling reflex, which
new mothers need support and advice. At least 95% of is particularly strong for a short while after delivery [23].
women are able to produce sufficient milk, and, therefore, • extra support by trained professionals with special skills in
less than 5% of women will have primary lactation insuffi- breastfeeding to help with good positioning and technique
ciency [21]. Good positioning and attachment are essential [24]. A good understanding of the physiology of lactation
for successful breastfeeding. Infants should be held so that: is essential for all who are involved in the care of breast-
feeding mothers and can be achieved with training. The
• they are close to mum; the angle of the breast will deter-
UNICEF UK Baby Friendly Initiative has developed an
mine which position is best for the baby to effectively
accreditation system for assessing higher education insti-
milk the breast
tutions in the UK based on the training they provide to
• the baby’s back, shoulders and neck are supported,
midwives and health visitors on breastfeeding.
allowing the head to easily tilt backwards
• WHO/UNICEF Baby Friendly status of the maternity unit
• their ear, shoulder and hip are in a line; this will ensure
where the baby is born. The WHO/UNICEF Baby Friendly
the neck is not twisted while they are feeding
Initiative provides a framework for the implementation
When the baby is positioned correctly, their nose should of best infant feeding practice in maternity units and is
be brought to the nipple; this will stimulate the rooting reflex represented by the Ten Steps to Successful Breastfeeding
and the baby will give a nice wide gape. The baby should (Table 2.4), revised by WHO in 2018. Accredited units
Table 2.4 The 10 steps to successful breastfeeding [25]. Table 2.5 Summary of UNICEF UK Achieving Sustainability standard [28].
Critical management procedures Theme

1a. Comply fully with the International Code of Marketing of
Breast‐milk Substitutes and relevant World Health Assembly Leadership • A named Baby Friendly lead/team with sufficient
resolutions. knowledge, skills and hours to meet objectives
1b. Have a written infant feeding policy that is routinely • A mechanism for the Baby Friendly lead/team to
communicated to staff and parents. remain up to date with education and skills
1c. Establish ongoing monitoring and data‐management systems. • A Baby Friendly Guardian with sufficient seniority
2. Ensure that staff have sufficient knowledge, competence and skills and engagement in post
to support breastfeeding. • Leadership structures support proportionate
responsibility and accountability
Key clinical practices • Relevant managers educated to support the
3. Discuss the importance and management of breastfeeding with maintenance of the standards
pregnant women and their families.
Culture • Support for ongoing staff learning
4. Facilitate immediate and uninterrupted skin‐to‐skin contact and
• Mechanisms in place to support a positive culture
support mothers to initiate breastfeeding as soon as possible after
(e.g. staff recognition schemes), mechanisms for staff
birth.
to feedback concerns, systems to enable parents’
5. Support mothers to initiate and maintain breastfeeding and
and families’ feedback to be heard and acted upon
manage common difficulties.
6. Do not provide breastfed newborns any food or fluids other than Monitoring • Baby Friendly audits carried out regularly according
breast milk, unless medically indicated. to service needs
7. Enable mothers and their infants to remain together and to practise • All relevant data available and accessed
rooming‐in 24 hours a day. • Data analysed effectively and collectively to give an
8. Support mothers to recognize and respond to their infants’ cues for overall picture
feeding. • Action plans developed in response to findings
9. Counsel mothers on the use and risks of feeding bottles, teats and • Relevant data routinely reported to the leadership team
pacifiers. • Relevant data routinely reported to UNICEF UK
10. Coordinate discharge so that parents and their infants have timely Progression • Service demonstrates innovation and progress
access to ongoing support and care. • Evidence to demonstrate that outcomes have improved
• Needs of babies, their mothers and families are met
Source: Reproduced with permission of WHO. through effective integrated working
that have successfully implemented all 10 steps have

• embarrassment. Some mothers are embarrassed to breast-
increased breastfeeding rates.
feed in public places and even within the home for some,
• local peer support groups that are particularly effective [26].
particularly those in lower socioeconomic groups [29].
Intensive interventions from community peer support,
Many women find that the attitude of other people to
with at least five planned contacts, have a greater effect on
breastfeeding in public, coupled with the frequent lack of
breastfeeding continuation than lower intensity interven-
facilities to feed in private, make prolonged excursions
tions [27]. In the UK, the large nationally organised groups
outside the home difficult.
that provide peer support and training for counsellors are:
• jealousy and lack of support from other family members.
◦◦ Association of Breastfeeding Mothers
Husbands, relatives and siblings may resent the exclu-
◦◦ Breastfeeding Network
sive role of the mother in breastfeeding. Involving every-
◦◦ La Leche League
one in all other aspects of caring for the infant can help
◦◦ Multiple Births Foundation
alleviate this problem.
◦◦ National Childbirth Trust
• incompatibility with work. Women in the UK are entitled to 12
• Family support and encouragement
months’ maternity leave (9 months of this paid). However,
• Supportive communities where breastfeeding is seen as
many return to work within 12 months, and unless there
the norm and facilities are available for women to
are suitable facilities for childcare or expressing breastmilk,
breastfeed
continuing with full breastfeeding can be difficult. Partial
Both England and Scotland have legislated against dis-
breastfeeding, e.g. in the mornings and evenings, is often
crimination towards mothers feeding infants in public
possible on return to work and can be encouraged.
places. The UNICEF UK Baby Friendly Initiative has devel-
oped standards to guide healthcare professionals through
Problems and difficulties with breastfeeding
their staged Baby Friendly accreditation programme for
maternity, neonatal, health visiting and children’s centre ser- Some common problems with breastfeeding and sugges-
vices [28]. The elements of the Achieving Sustainability tions for their management are given in Table 2.6.
standard are given in Table 2.5.
Perceived barriers to breastfeeding may include: Supplementary milk feeds
• too much demand on the mother’s time. Family members can Breastfeeding may be supplemented with additional milk
provide invaluable support by helping with other chil- feeds if the baby cannot get enough milk from the breast for
dren or taking over household duties. normal growth or if the mother chooses to do this. The extra
22 Healthy Eating
Table 2.6 Common breastfeeding problems and suggestions for their management.
Concern Background Action
Perceived inadequate supply Crying in a baby does not always signal a Check the baby is feeding for as long as she/he wishes on both
A common reason cited by demand for food. It may be because the baby breasts. More frequent breastfeeds may help establish a better
mothers and may be due to is uncomfortable, needs a nappy change or is supply or suit a mother who produces low volumes of breastmilk.
persistent crying or fussing of overtired or just bored and lonely. A breastfed Check mother’s diet and fluid intake are adequate and that she is
infants that are not baby having an adequate intake will: getting enough rest. Check medications.
necessarily signs of hunger If available, a trained professional can observe the baby feeding and
• Be alert and responsive and have a healthy advise on how to ensure the baby is effectively transferring
appearance breastmilk
• Have 6+ feeds in 24 hours during the day
and night
• Have 6+ wet nappies daily
• Have 2+ yellow stools daily
Sore nipples Some tenderness is normal, but breastfeeding Treatment from a general practitioner (GP) is necessary to resolve
should not be painful. Pain is usually due to thrush in both the mother and infant. Heat treatment and feeding in
poor attachment and positioning. However, in a warm room may help in Raynaud’s syndrome
some cases, it may be due to thrush (Candida
albicans). In rare cases it may be due to
Raynaud’s syndrome, where nipples become
blanched due to poor blood supply
Cracked nipples Usually due to poor attachment With improved attachment and positioning, nipples will begin to heal
Engorgement Usually due to poor drainage of the breast as a Hand expressing before the feed can make it easier for the infant to
Oedema caused when the consequence of poor positioning and suck efficiently. Advice may include:
breast is full of milk and the attachment and can occur when feeds are
• Use of warm compresses or taking a warm shower before feeding
blood and lymph flows are missed
• Frequent breastfeeding (every 1–2 hours) and encouraging the
slow and seep into breast
tissue infant to suckle from both breasts
• Applying an ice pack to breast and underarm after feeding until
swelling decreases can also be helpful
• Seek expert advice if the problem persists
Mastitis Usually a result of engorgement or poor Advise rest, frequent breastfeeds and that the mother should drink
Swollen, inflamed or infected drainage of the breast, so it is important not to plenty of fluids. Antibiotics may be needed
area in breast stop breastfeeding
Baby has poor weight gain Less emphasis is now placed on frequently Check the weight chart carefully and reassure the mother if
weighing healthy infants as small variations in possible. Check position and feeding technique. Check the number
weight centiles can cause considerable of feeds being offered and if necessary advise an increase to
parental stress. Weight gain is not expected to stimulate breastmilk production. If top‐up formula feeding is
be regular: necessary in the first couple of weeks, advise the mother to give the
bottle at the end of each breastfeed to encourage stimulation of
• Infants often cross centiles in the first 6–8 breastmilk with the goal of fully resuming breastfeeding. After the
weeks to adjust for the intrauterine
infant is about 2 weeks old, advise the mother to give one bottle of
environment formula per day and continue breastfeeding at the other feeds.
• Thereafter variations of up to 1 centile space Refer to the GP for assessment if growth is faltering by falling
are normal through 2 centile spaces after 8 weeks of age
Tongue tie If severe can limit the infant’s ability to suckle Refer for an assessment. Surgery resolves the problem
effectively
milk can be expressed breastmilk (EBM), infant formula or, if to a reduction in the breastmilk demanded by the infant and
available, pasteurised human donor milk. consequently diminishing breastmilk production.
A supplementary feed can be given in a bottle, by cup or via • The infant can be given a bottle of formula milk at one
a nursing supplementor. Infants suck against a lower pressure feed per day and continue to breastfeed only at the other
when sucking from a bottle teat compared with sucking from feeds. Some mothers successfully maintain breastfeeding
the nipple [30], and some will prefer to suck against this lower for longer by doing this [31].
pressure, which requires less effort, if bottle feeding is offered.
There is little evidence on the best way to combine breast-
Expressing breastmilk
feeding and bottle feeding if a top‐up of EBM or formula
milk is needed. There are two ways to do this: Once breastmilk supply is established, it can be expressed
using one of three methods:
• Mothers can feed from both breasts to stimulate breastmilk
production and then offer a bottle feed if the baby still seems • by hand
hungry. This may be best in the newborn period when • using a hand pump
breastfeeding is being established. However later, it can lead • using an electric pump
The National Institute for Health and Care Excellence Table 2.7 Recommended intakes from the five food groups for lactating
(NICE) recommends that all mothers be taught to hand mothers.
express their milk [32]. EBM can be given to the baby via a
Food group Recommended daily intake
bottle, cup or spoon although not all babies are happy to
accept an occasional feed in this way. Bottles, containers for Bread, rice, Base each meal and some snacks on these foods.
storage and other utensils must be sterilised until the infant potatoes and Use wholegrain varieties as often as possible
is 1 year of age. EBM should be labelled and stored correctly pasta and other
to minimise the risk of infection. The Department of Health starchy foods
recommends that EBM is stored: Fruit and Include one or more of these at each meal and aim
vegetables for at least 5 portions per day
• in the refrigerator for up to 5 days if parents are confi- Milk, cheese 2–3 portions of milk, cheese and yoghurt. Use low
dent that the fridge remains at 4 °C or lower. It should be and yoghurt fat varieties if weight needs to be managed
stored at the back of the fridge where it is colder. A Meat, fish, eggs, 2–3 portions. Two servings of fish per week are
domestic fridge that is opened frequently may not main- beans and nuts recommended, one of which should be oily fish
tain a low enough temperature; it is preferable to freeze Butter, oils and Limit these to small quantities in food preparation.
EBM if it is not going to be used within 48 hours fat spreads For those trying to lose weight, limit them ½ to 2
• in the freezer compartment of a fridge for up to 2 weeks small portions per day
• in a domestic freezer at −18 °C for up to 6 months Sugary foods Avoid for those trying to lose weight and limit to
small amounts for others
Frozen EBM should be thawed in a fridge and then used
Fluid intake To satisfy thirst, but at least 6–8 drinks per day
within 24 hours. It must not be reheated in a microwave
(1½–2 L). Include a drink with each breastfeed. Fluids
oven because of the risk of ‘hotspots’ occurring and causing include water, tea, coffee, milk, soup, fruit juices,
burns [33]. Standing the bottle in warm water is a suitable squashes and fizzy drinks. More drinks may be
way of reheating milk if necessary; some babies will drink it needed in hot weather and after physical activity
cold from the fridge. Vitamin 10 μg vitamin D
supplement
Nutrition for lactating mothers

does not need to be avoided, but some mothers find large
The nutritional quality of breastmilk is only affected if the
amounts of caffeine unsettle their baby.
mother is undernourished. To support lactation higher
Breastmilk is believed to be flavoured by foods eaten by
requirements for energy, fluid, thiamin, riboflavin, niacin,
the mother and may influence the infant’s response to tastes
vitamin B12, folate, vitamins C, A and D, calcium, phospho-
when complementary foods are introduced [35]. There are
rus, magnesium, zinc, copper and selenium are set [2]. The
reports that highly spiced or strong tasting foods can unset-
increased energy requirement is usually met through uti-
tle some infants.
lising the adipose stores deposited during pregnancy.
Infants may become sensitised to antigens in breastmilk,
Eating a balance of the five food groups (Table 2.7) will
e.g. cow’s milk protein, eggs or nuts. If the infant reacts to
meet the increased nutrient requirements with the excep-
the presence of these antigens in breastmilk, the mother
tion of vitamin D, where a daily supplement of 10 μg is
needs to avoid these foods. If dairy products are avoided,
recommended [3].
she will need advice on dietary adequacy, which may need
Vegan mothers need to plan their diets carefully and may
to include a calcium and iodine supplement.
need additional supplements of calcium, riboflavin, iodine,
iron and vitamins A, B12 and D.
Formula milk feeding
Foods to be limited or avoided
In contrast to the variation in breastmilk, the composition of
To ensure a good intake of omega‐3 long chain polyunsatu- infant and follow‐on formulas is uniform, complying with
rated fatty acids (LCP), mothers should be encouraged to EU regulations, and does not provide the antibodies that
include fish in the diet, but oily fish and tuna should be breastmilk does. These regulations are based on expert
limited to no more than two servings per week; marlin, advice from the European Food Safety Authority and also
swordfish and shark should be avoided [34]. implement the 1981 WHO International Code of Marketing
Alcohol and caffeine both readily pass into breastmilk and of Breastmilk Substitutes as appropriate to the EU.
high intakes of either should be avoided during lactation. Recent research suggests that current infant formulas
The highest level of alcohol in milk will occur between 30 may contain too high an energy level for normal growth.
and 90 minutes after ingesting alcohol; mothers should not The energy content of breastmilk may be lower than cur-
ingest alcohol for about 2 hours before breastfeeding and rent accepted estimations, and the higher energy density of
should keep alcohol intake to a minimum, e.g. 1–2 units once infant formulas may account for the different growth pat-
or twice per week. Regular or binge drinking should be terns seen between breastfed and formula‐fed infants
avoided. Caffeine in tea, coffee, chocolate and energy drinks (Table 2.3).
24 Healthy Eating
Table 1.14 lists the infant formulas available in the UK. The • the feed must be cooled (by holding the sealed bottle
whey‐dominant formulas (whey–casein ratio of 60 : 40) have a under cold running water) and the temperature tested
protein ratio that is similar to that found in mature breastmilk; before giving to the baby
those with a lower whey–casein ratio (20 : 80) are more similar • bottles should be made up freshly for each feed
to the protein ratio found in cow’s milk. The energy and nutri- • any leftover milk at the end of the feed should be thrown
ent contents are similar in both types of feed, although the away
casein‐dominant formulas are marketed as more suitable for • parents who require a feed for later are advised to keep
hungry babies; this is simply because the curd formed by the water they have just boiled in a sealed flask and make up
higher casein level slows gastric emptying. fresh formula milk when needed
Formula‐fed babies should be demand fed just as breastfed
If parents choose not to follow this advice and make up
babies are and offered adequate feed to satisfy their hunger and
feeds for up to 24 hours in advance, the bottles of formula
growth needs. They should be allowed to stop feeding when
should be cooled quickly and stored in a fridge at <5 °C.
they signal they have had enough and not coerced to finish
These feeds can be warmed just before use by standing the
every bottle. An average total daily intake is around 150 mL/kg
bottle in a container of hot water. Microwave ovens must not
body weight/day up to about 4 months of age, although it var-
be used as the milk is not uniformly heated and hotspots in
ies with each baby. The number of feeds per day and the vol-
the milk could burn the baby’s mouth [33]. Feeds should be
ume taken at each feed will vary as with breastfeeding.
made up using boiled water and sterile bottles or cups until
1 year of age because of the potential for bacterial growth.
Follow‐on milks This is enhanced if bottles, teats and cups are not cleaned
properly.
These milks (Table 1.14) are only recommended from 6 In the case where a baby is prescribed a multi‐ingredient
months of age as they may have higher levels of protein, feed, the dietitian may deem it safer, from the point of view
minerals and some vitamins than the infant formulas of accuracy of feed reconstitution, for the parent to make up
designed for feeding from birth. Some mothers choose to use 24 hours’ worth of feeds at one time. It is incumbent on the
them, but it is not generally necessary. They can be used to dietitian to give advice about scrupulous hygiene, rapid
give additional nutrients to infants who are slow to accept cooling and safe storage at <5 °C if feeds are to be made up in
complementary feeding. advance. Any remaining milk not consumed after 1 hour of
feeding should be discarded.
Making up infant formula from powder
Bottle feeding
Tap water or bottled waters that comply with EU standards
for tap water [36] may be used for making up infant formula. Feeding position
Up to 200 mg/L sodium is allowed in tap water, which will
Bottle‐fed babies should be held in a supportive, semi‐
add 0.9 mmol sodium/100 mL feed. This extra sodium will
upright position, which encourages eye contact and bonding
not matter for most infants and powdered feeds on sale in
with the caregiver. The bottle should be angled so that the
the UK will still comply with the EU Directive’s acceptable
teat is always full of milk, thus minimising the amount of air
sodium content if made up with water containing this level
consumed. It is usual to ‘wind’ bottle‐fed babies halfway
of sodium. Bottled mineral waters may contain excess
through and after a feed.
amounts of sodium or other electrolytes and should not be
used for making up infant formula. Just as tap water must be
boiled before being used for reconstituting formula feeds, so Feeding equipment
must any bottled water. Carbonated fizzy water is not suit- Various types of bottles are available, some with air release
able for making up formula feeds. devices to reduce colic. The several different types of teats
Infant formula powder is not sterile and may contain available have varying flow rates according to the size and
microorganisms such as salmonella and Enterobacter sakazakii number of holes, and they also vary in size and shape.
(now known as Cronobacter sakazakii). Neonates, particularly
those who are preterm, of low birthweight or immunocom-
Problems preparing feeds
promised, are most at risk. To minimise the risk of gastroen-
teritis from these bacteria: Lucas et al. [37] measured the energy content of infant formulas
made up by a group of bottle feeding mothers and found the
• feeds should be made up using boiled water >70 °C (that
energy content ranged from 41 to 91 kcal (171–380 kJ)/100 mL,
has been left to cool in the kettle for no more than half an
whereas the manufacturer’s intended energy content was
hour)
68 kcal (284 kJ)/100 mL. One third of feeds contained less than
• this water is measured into a sterile bottle and the appro-
50 kcal (210 kJ)/100 mL and around half the feeds over 80 kcal
priate number of scoops of powder added (1 level
(335 kJ)/l00 mL. These discrepancies may arise from:
unpacked scoop of powder per 30 mL/1 fluid ounce water)
• the bottle should then be sealed with a sterilised cap and • compression of the powder in the scoop or by using
shaken to mix the powder heaped scoops
• miscounting the number of scoops Complementary feeding

• adding an extra scoop mistakenly believing it will be
more satisfying or nourishing for the baby The introduction of solid foods alongside milk feeds is needed
Overconcentration feeds may lead to hypernatraemia to provide a more energy and nutrient‐dense diet at the time
with consequent dehydration and possible severe brain when a milk only diet becomes inadequate to support con-
damage or death or to hypercalcaemia and hyperphospha- tinuing growth and development. The critical nutrient is iron
taemia. Much of this potential danger has been reduced fol- as it is low in breastmilk, and during the first 4–6 months of
lowing compositional changes to modern infant formulas life, infants rely on the iron derived from delayed cord clamp-
and the redesign of packaging to improve standards of ing at birth and iron stores laid down during foetal life. Recent
hygiene and accuracy of mixing. The use of ready‐to‐feed evidence indicates that the timing of introduction of highly
(RTF) liquid formulas ensures the correct concentration is allergenic food during complementary feeding plays a role in
always given. the prevention of food allergy in infants (p. 340).
Overdilution of feeds may lead to excessive volumes being
ingested in order to meet energy needs, and this can cause A time of learning new skills
vomiting and hyponatraemia. Faltering growth and malnu- During complementary feeding, infants must learn new
trition may ensue because the capacity of the young infant’s feeding skills, and they do this as their physical coordination
stomach cannot cope with the much larger volumes of feed develops and by being given the opportunity to try, and to
required to meet nutritional requirements. practise, managing food in their mouths and swallowing it.
As complementary feeding progresses with a varied diet,
Additional fluids infants will learn to like and accept the new different tastes
Formula‐fed infants may become thirsty between feeds in and food textures they are offered.
very hot weather, and additional drinks of cooled boiled
water can be given so long as these do not interfere with the When to begin
required intake of formula. Fruit juices and baby juices are not
The ideal age to begin is individual as infants grow and
recommended; formula milks contain adequate vitamin C.
develop at different rates. Evidence suggests beginning before
Infants with fever, diarrhoea or vomiting can dehydrate
3 months of age increases the risk of respiratory infections [45]
quickly and need additional fluids, and possibly electrolytes,
and waiting until after 6 months increases the risk of nutrient
to replace losses.
deficiencies, of iron in particular [46–48]. There is no evidence
of harm in beginning complementary feeding between 4 and
Sleeping through the night 6 months of age. Policies and population recommendations
vary and have changed over the last two decades. Current
When infants begin to sleep through the night is related to recommendations are to begin complementary feeding:
the hormonally driven development of their circadian
• at 6 months (WHO Global Feeding Strategy 2003) based
rhythm and is not related to their energy or nutritional
on the afforded protection against gastroenteritis and
intake. The earliest that any infant will begin sleeping
mortality in developing countries. They also recommend
through the night is 6–8 weeks [38].
that each country interpret the age at which to begin
complementary feeding depending on the health needs
Poor appetite regulation and inappropriate of their own populations [49]
• between 4 and 6 months (WHO recommendations for
weight gain
Europe 2003) [50]
• between 4 and 6 months (ESPGHAN 2017) for
A small number of infants have genetically inherited poor
European countries where the risk of death due to
appetite regulation and may demand too little or too much
gastroenteritis is very low. The European Society

milk to support optimal growth patterns. After 8 weeks of
for Paediatric Gastroen te
rology, Hepatology and
age, consistent rising across the weight‐for‐age centiles indi-
Nutrition (ESPGHAN) recommends beginning com-
cates an infant has an excess milk intake and this is a risk
plementary feeding between 4 and 6 months of age as
factor for childhood obesity [39–41]. This can occur with
this will cause no harm to infants and may provide
breastfed infants, but more commonly occurs with bottle
benefits in terms of improved iron status [51]
feeding [42] because the bottle teat can be held or forced into
• around 6 months, but not before 4 months (SACN
an infant’s mouth even when the infant has consumed
2018) [20]
enough milk and is signalling satiation. Infants who are bot-
• around 6 months, but not before 4 months (British
tle fed in early infancy are more likely to empty the bottle or
Dietetic Association 2016) [52]
cup in late infancy than those who are fed directly at the
breast [43]. A recent study has shown that 3‐month‐old These are population recommendations and most stipu-
infants taking high volumes of formula milk were at greater late that each infant should be considered individually due
risk of higher body weight and overweight at 12 months than to the considerable range of growth rates and physical devel-
breastfed infants or those with lower formula intakes [44]. opment between 4 and 6 months of age in term infants.
26 Healthy Eating
UK studies have shown that mothers of larger male infants who had been randomised to begin complementary feeding
introduce complementary feeding at an earlier age than at 6 months of age [58].
mothers of smaller and female infants [53]. The last UK
Infant Feeding Survey (IFS) (2010) reported [54]: Foods to offer
• 30% of infants began complementary feeding before 4 As infants learn new skills, they will progress through the
months developmental stages of complementary feeding as they are
• 75% were having solid food by 5 months given the opportunities to learn [59]. Some progress faster
• 94% by 6 months than others and will begin to take more energy from food
• 5% after 6 months and cut down their milk intake more quickly that those
whose skills develop more slowly and who will remain more
The Diet and Nutrition Survey of Infants and Young milk dependent for longer. Table 2.8 gives a rough guide of
Children (2011) reported [55]: the pattern of complementary feeding.
• 42% of infants receiving solid food by 4 months Complementary feeding usually begins with 1–2 tea-
• similar figures to the IFS at 5 and 6 months spoons of a smooth mashed or puréed food being offered
once a day. The addition of solids to bottles of milk is not
The Scottish Maternal and Infant Survey in 2017 advised in the UK; however, this is accepted practice in some
reported [56]: other European countries.
• 3% of infants began complementary feeding before 4 The food given at the first attempts may come back out as
months the infant pushes their tongue forward, as they do when
• 54% before 6 months sucking from the nipple or teat. With practice infants will
realise that the food stays in the mouth when the tongue
Parents should therefore be encouraged to consider their moves backwards. As the infant learns to manage and swal-
infant’s signs of readiness for complementary feeding and low solid food effectively and begins to take a larger quan-
begin when they perceive their infant is ready physically tity, a second meal and then a third meal can be introduced.
and nutritionally. Signs of readiness include: Once three meals are established, a variety of foods from the
• able to sit with support and control the head to reduce four main food groups should be included to provide a
the risk of choking range of nutrients. Table 2.11 shows the food groups and rec-
• putting toys and other objects in the mouth ommended number of daily servings.
• chewing fists
Energy and nutrient density
• watching others intently when they are eating
• seeming hungry between milk feeds or demanding feeds Meals should be nutrient dense and contain iron‐rich foods
more often even though larger milk feeds have been [20, 62] from the beginning of complementary feeding. The
offered best food sources of iron are meat, oily fish, pulses, eggs and
nut butters. Meat and oily fish provide the haem form of
These developmental signs are generally seen between 4
iron, which is easily absorbed. Pulses, eggs and nuts contain
and 6 months, and from this age, infants learn to accept new
the non‐haem form of iron, and absorption is less efficient,
tastes and textures relatively quickly [57].
but can be improved by combining them with a high vitamin
Sleep patterns also change around this time and infants
C food.
are more likely to wake when in a light sleep mode. Waking
Savoury courses for infants should ideally contain (by
during the night after beginning to sleep through the night
volume):
has not been considered an indication to begin solids, but the
EAT (Enquiring About Tolerance) study found that parents • ⅓ high iron foods: meat/fish/eggs/nut butter/pulses
who had been randomised to begin complementary feeding (lentils, hummus, starchy beans)
from 3 to 4 months reported that their infants slept for • ⅓ starchy foods: potato/rice/pasta/bread
slightly longer and woke less frequently than the parents • ⅓ vegetables
Table 2.8 Pattern of complementary feeding.
Stage Age guide Number of milk feeds/day Number of meals/day Variety of foods
1 4–6 months 5−4 1–2 From 1 to 3 food groups (Table 2.11)

(17–26 weeks) Vitamin D supplement
2 6–9 months 4–3 3 3 different meals from 4 nutritious food groups
1–2 courses per meal
Vitamin D supplement
3 9–12 months 3–2 3 3 different meals from 4 nutritious food groups
Discontinue early morning feed so 2 courses per meal
that more food is eaten at breakfast Vitamin D supplement
This will meet the WHO recommendation that comple- choking in infants and children can be accessed at www.resus.
mentary foods are energy and nutrient dense providing org.uk/resuscitation‐guidelines/paediatric‐basic‐life‐support
about 80–120 kcal (335–500 kJ)/100 g food [62].
Second courses based on fruit and/or yoghurt/custard/ Gagging: a reflex closing off the throat and pushing the tongue to the
milk pudding can be given to replace the milk feed at one and front of the mouth
then two meals as the infant takes more food and two courses Choking: a piece of food partially or completely blocking the airway,
are offered at each mealtime. The amount of breastmilk or affecting breathing
infant formula consumed by the infant will gradually reduce
to about 500–600 mL/day towards the end of the first year.
Low nutrient foods high in fat and sugar do not have a place Research surveys using parental questionnaires in the UK
in complementary feeding. report that:
Ingredients to avoid are:
• 12% of infants were given finger foods at 4–5 months and
• salt and added free sugars, although a small amount of 40% by 6 months of age [67]
sugar can be added to make tart or sour fruits palatable • 43% of infants were eating toast before 6 months of age
• honey, which should not be given before 12 months as and 27% biscuits [68]
there is a small risk of infant botulism
Infants progress in different ways and some develop a
Although recommended in the past, there is no evidence preference for self‐feeding finger foods while others for
to support delaying any foods before 6 months to reduce the spoon feeding. Therefore, it is best that each infant has the
incidence of allergy. Evidence and policies now indicate that opportunity to learn and acquire both skills. Giving infants
highly allergenic foods can be introduced from the begin- their own spoon during spoon feeding encourages inde-
ning of complementary feeding [20]. Advice differs for pendence and an opportunity to learn to coordinate transfer-
infants at high risk of food allergy (p. 343). ring food from spoon to mouth. Including infants in family
meals allows them to learn by copying those eating around
Learning to like new tastes them. There is inadequate research on outcomes for health-
The majority of infants will try a wide variety of tastes and care professionals to recommend only giving finger foods
textures and they learn to like the foods they are offered [63]. with no spoon feeding [69].
The frequency with which they are offered a food, rather Table 2.9 shows the developmental stages of complemen-
than the amount they eat, determines how quickly they will tary feeding.
learn to like it. By the end of their first year, infants should be
eating family foods, and the more variety they have been Responsive feeding
offered by around 12 months, the wider the range of foods Responsive feeding allows each infant to decide how much
they will be familiar with and accept before food neophobia solid food is eaten and how much milk is drunk. There are
begins in their second year (p. 32). no set food or milk feed portion sizes for infants (under 12
months of age) because infants develop their feeding skills at
Learning to manage new textures different ages and grow at different rates. Most infants will
After beginning with smooth foods, to develop confidence,
offering thicker textures, lumps and soft finger foods Table 2.9 Developmental stages of complementary feeding.
allows infants to progress their skills [64]. Some need a lot
Age New food textures
of practice with new textures before they master eating Stage guide Skills to learn to introduce
them and are ready to move on. Others may manage soft
finger foods and thicker textures from the beginning of 1 4–6 • Taking food from a spoon Smooth purées
complementary feeding. The gag reflex makes it safe for months • Moving food from the front Mashed foods
(17–26 of the mouth to the back for
infants to try finger foods and lumps that they cannot at
weeks) swallowing
first process. Lumps or pieces of food that are too big to be • Managing thicker purées
swallowed are gagged and cleared from the back of the and mashed food
tongue to the front of the mouth and either spat out or
2 6–9 • Moving lumps around the Mashed food with
reprocessed to the sides of the mouth [65, 66]. Soft finger months mouth soft lumps
foods early in complementary feeding offer infants the • Chewing lumps Soft finger foods
opportunity to: • Self‐feeding using hands Water in a lidded
and fingers beaker or cup
• touch and play with food • Sipping from a cup
• learn to visually recognise foods and to associate them
3 9–12 • Chewing minced and Firmer finger
with their smell and taste months chopped food foods
• develop their self‐feeding skills • Self‐feeding attempts with a Minced and
spoon chopped family
Although gagging is a normal part of learning feeding skills,
foods
choking, which is not common, is not. Guidelines on treating
28 Healthy Eating
continue to accurately regulate their energy intake and will Fluids

drink the volume of milk they need depending on how much
Once food textures have progressed to thick mash and finger
energy they have ingested through food.
foods, water should be offered from a cup or beaker with
Parents may need support to recognise their infant’s hun-
meals. This water does not have to be boiled for babies over
ger and satiation signals. Coercing or force feeding an infant
6 months old, but can be freshly drawn tap water or bottled
to eat or drink more when they have indicated they have had
water given from a clean cup.
enough is counterproductive to enjoyable mealtimes and to
Infants should never be left alone with cups or bottles of
developing a positive attitude to food. Excess energy intake
water or other fluids as they may choke.
through force feeding leads to excess weight gain. Hunger
The following are unsuitable fluids:
cues are given in Table 2.10.
Infants clearly signal to parents that they no longer want
• All sweet drinks including fruit juices and baby juices are
food or milk. They do this when tired from practising a new
acidic, even when diluted, and contain free sugars; con-
feeding skill or later when their hunger and thirst are satis-
sequently they can cause dental erosion. Infants do not
fied. Signals indicating physical tiredness or hunger satia-
need fruit juices or baby fruit juices as:
tion include:
◦◦ both breastmilk and infant formula contain adequate
• turning their head away from the spoon vitamin C
• keeping their mouth shut ◦◦ fruit and vegetables are introduced from the begin-
• blocking their mouth with their hand or pushing away ning of complementary feeding
the spoon or food ◦◦ if a parent chooses to use fruit juices, they should
• holding food in their mouth be well diluted and served only at mealtimes in a
• crying cup or beaker, never a bottle; not be given at, or
after, bedtime as during sleep saliva that buffers
Older infants will:
acid levels is not produced in the mouth; drinking
• throw food times should be kept short
• signal ‘no’ in response to unwanted food given to them • Tea and coffee as they contain caffeine and the tannins and
• vomit polyphenols present inhibit iron absorption
Commercial baby foods

Vitamin D supplementation
The energy density and composition of home‐made foods for
infants varies widely [71] as does the taste and texture. By
SACN recommends an SI of 8.5–10 μg vitamin D each day
contrast commercial weaning foods are more uniform in their
from birth irrespective of feeding method. Vitamin D levels
texture and must conform to EU Directives, which govern
in breastmilk are low, and although infant formula is forti-
their composition [72]. However, energy density varies and is
fied with vitamin D to higher levels, a supplement is still
often below WHO recommendations, particularly those com-
required.
prising vegetables only. The regulations governing pesticide
Infants whose mothers entered the pregnancy with low
residues in all commercial baby foods are very strict, but most
vitamin D levels and who did not take a vitamin D supple-
commercial baby foods purchased are now organic, which
ment during pregnancy are likely to be born with low levels
allow no pesticides to be used in their culture and prepara-
of vitamin D and poor stores [73]. Exclusively breastfed
tion. Organic food regulations prohibit iron fortification, and
infants born with low stores of vitamin D are at risk as the
consequently organic savoury baby foods are lower in iron
vitamin D content of breastmilk is normally low. It is lower
content than non‐organic iron‐fortified savoury baby foods.
still in the milk of mothers who are vitamin D deficient [74].
The level of vitamin D in formula milk appears to be inade-
quate for an infant born with very low stores; formula‐fed
Table 2.10 Hunger cues.
infants have been diagnosed with hypocalcaemic seizures,
Approximate age Hunger cues cardiomyopathy and rickets [75].
Public Health England (PHE) recommendations for
4–6 months • Cries or fusses vitamin D supplements (Table 2.21) advise that infants drink-
• Smiles, gazes at caregiver or coos during ing 500 mL formula milk/day do not need a supplement.
feeding to indicate wanting more
However, the European Society for Paediatric Endocrinology
• Moves head towards spoon or tries to swipe
food towards mouth
recommends a supplement of 10 μg of vitamin D per day for
all infants from birth to 12 months of age, independent of
5–11 months • Reaches for food
their mode of feeding, to prevent nutritional rickets [77]. The
• Points to food
• Gets excited when food is presented European tolerable upper intake level (UL) for infants under
six months of age of 25 μg/day and 35μg/day for infants
10–12 months • Expresses desire for specific food with words
or sounds aged 6–12 months is unlikely to be reached.
Vitamin drops are best given from a spoon or syringe, not
Source: Adapted from the USDA Infant Nutrition and Feeding Guide [70]. added to bottles, to ensure the full dose is taken.
Preschool Children 1–4 Years 29
Preschool children 1–4 years can change to semi‐skimmed milk if they are eating well and
growing normally, but this is not necessary and the extra vita-
Basing the diets of toddlers and preschool children on a com- min A in whole milk will support their immune system.
bination of foods from the food groups in Table 2.11, along Growing up and toddler milks marketed for this age
with a vitamin D supplement, will provide nutritional ade- group are enriched with more iron, zinc and vitamin D than
quacy. Although the PHE Eatwell Guide (Figure 2.1) is not is provided in cow’s milk. They can provide a nutritional
designed for children under 5 years of age, children in this safety net for toddlers who are not eating well, but a cheaper
age group do grow satisfactorily on the same percentage option is to give the toddler a vitamin and mineral supple-
energy contributions from the macronutrients as discussed ment. These milks are lower in certain nutrients than cow’s
below for school‐age children. However, under 5s are grow- milk: calcium, phosphorus, iodine and riboflavin.
ing rapidly and need a nutrient‐rich diet. Their diet differs Substitute drinks for milk such as drinks based on soya,
from that of the infant or that of older children and adults in cereals, nuts or coconut do not have the same nutrient profile
having: as mammalian milks and are not suitable for children as a
milk substitute unless they are fortified with calcium, ribo-
• less milk than the infant diet
flavin, iodine and vitamin A. If unfortified versions are used,
• a meal pattern of three meals with two to three planned
a supplement of those key nutrients should be given.
nutritious snacks per day, as these children may only
take small quantities of food at any one time
Meat, fish, eggs, nuts and pulses
Two courses at each meal, a savoury course followed by a
Many toddlers do not like the texture of chewy meat and
fruit‐ or milk‐based second course, ensure a wider variety of
prefer soft tender cuts of meat products made from minced
foods and nutrients will be offered and consumed. Parents
meat such as sausages, burgers and meatballs. As long as
should be encouraged to think of the second course as a sec-
these foods are made from good quality ingredients with a
ond opportunity to offer energy and nutrients and should
high lean meat and low salt content, they will make a valu-
not offer it only as a reward for finishing the savoury course.
able contribution to a healthy diet. Chicken, which often
has a softer texture than red meat, is popular with this
The food groups age group.
Fish should be offered twice a week and one portion
Bread, rice, potatoes, pasta and other starchy foods should be oily (p. 41). Most toddlers enjoy fish when served
as fish fingers, fish cakes or fish and potato pie.
A mixture of some white and some wholegrain varieties can Dhal, lentils, chickpea flour in bhajis and starchy beans are
be offered as the fibre load from only wholegrain cereals commonly used by ethnic cultures and pulses can be used in
may be too high for some toddlers. Excess fibre can fill up soups and stews. Baked beans are popular and hummus and
the stomach and reduce food intake, thereby restricting nut butters can be used as spreads. Finely ground nuts can
energy and nutrient intake. Phytates in fibre reduce the be added to muesli or used in cakes, biscuits and puddings.
absorption of certain nutrients, and excess fibre may exacer-
bate loose stools in some toddlers.
Butter, oils and fat spreads
Fruit and vegetables Only small amounts should be used in food preparation.
Fruit and vegetables should be offered at each meal and some Foods high in sugar
snacks. Toddlers may be averse to the bitter taste of some veg-
etables and may eat a limited variety. This should not be a These high energy foods add flavour and enjoyment to
cause for concern as this age should be seen as a time for learn- meals. Limiting sugary foods to the amounts below will
ing to like fruits and vegetables and parents should encourage retain an average intake of around the SACN recommended
their preschool children to eat these foods by setting an exam- maximum of 5% of energy from free sugars [4]:
ple and eating and enjoying these foods themselves. • one serving per day of a nutritious sweet food such as
cake, biscuits, pudding, cereal bar
Milk, cheese and yoghurt • one serving per day of sweet spread such as jam or honey
• one serving per week of sweet drink or confectionery
Milk intake should reduce from 12 months of age. Three
servings of milk, yoghurt and cheese per day will ensure cal- An excess of butter, oils and fat spreads and/or foods high
cium, riboflavin and iodine requirements are met. An excess in sugar will increase the likelihood of obesity, which is ris-
of milk in the diet usually means less iron‐rich foods are ing in this age group.
eaten and iron deficiency and anaemia are associated with
toddler diets where there is 400 mL milk or more drunk daily
[79, 80]. This is often toddlers drinking large bottles of milk Drinks
during the day and/or night.
Toddlers up to 2 years of age should have whole (full‐fat) The use of bottles for drinks should be discontinued around
milk for the extra vitamin A it contains. After 2 years toddlers 12 months as sucking on a bottle of milk can become a
30 Healthy Eating
Table 2.11 Food groups and recommended number of daily servings.
Recommendations
Infants Toddlers and preschoolers Schoolchildren

Food group Foods included Main nutrients supplied 6–12 months [60] 1–4 years 5–18 years
1. Bread, rice, Bread, chapatti, breakfast cereals, Carbohydrate 3–4 servings a day Serve at each meal and some 4 servings per day
potatoes, pasta rice, couscous, pasta, millet, B vitamins snacks Serve at each meal and
and other potatoes, yam and foods made with Fibre one snack
starchy foods flour such as pizza bases, buns and Some iron, zinc and calcium
pancakes
2. Fruit and Fresh, frozen, tinned and dried Vitamin C 3–4 servings a day Offer at each meal and some Aim for 5 servings a day
vegetables fruits and vegetables. Also pure fruit Phytochemicals snacks and aim for about
juices Fibre 5 small servings a day
Carotenes
3. Milk, cheese Breastmilk, infant formulas, follow‐ Calcium Demand feeds of 3 servings a day 3 servings a day
and yoghurt on milks, cow’s milk, yoghurts, Protein breastmilk or infant
cheese, custard and milk puddings Iodine formula as main drink
Riboflavin (about 500–600 mL/day)
Vitamin A in full‐fat milk Some yoghurt and cheese
Cow’s milk in food
4. Meat, fish, Meat, fish, eggs, pulses, dhal, nuts, Iron 1–2 servings a day 2 servings a day 2 servings a day
eggs, nuts and seeds Protein 2–3 for vegetarians 3 for vegetarians 3 for vegetarians
pulses Zinc Fish should be offered twice Fish should be offered
Magnesium per week and oily fish at least twice per week and oily
B vitamins once per week* fish at least once per
Vitamin A week*
Omega‐3 fatty acids: EPA
and DHA from oily fish
5. Oils, butter Cream, butter, fat spreads, cooking Vitamin E Not required In food preparation In food preparation
and fat spreads and salad oils, mayonnaise Omega‐3 fatty acids
High sugar Puddings, biscuits, cakes, Not required Pudding, cakes or biscuits Pudding, cakes or
foods and jam, honey, syrups, chocolate, once per day biscuits once per day
savoury snacks confectionery, sweet drinks, fruit Jam, honey or syrups once Jam, honey or syrups
juices, crisps and other high fat per day once per day
savoury snacks Chocolate, confectionery, Chocolate, confectionery,
sweet drinks, fruit juices, sweet drinks, fruit juices,
crisps and other high fat crisps and other high fat
snacks snacks
one item once per week one item once per week
Fluid Drinks Water Milk feeds 6–8 drinks per day and more 6–8 drinks per day and
Fluoride in areas with Water with meals in hot weather or after extra more in hot weather or
fluoridated tap water physical activity after extra physical activity
Vitamin Vitamin D Vitamin D Vitamin D
supplements Folic acid for adolescent
girls who could become
pregnant
EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid.

Serving sizes of food and drinks will increase as children grow. Examples of average portion sizes for different ages are shown in Tables 2.12 and 2.14.
*
See p. 41.
Preschool Children 1–4 Years 31
Check the label on

Eatwell Guide
packaged foods Use the Eatwell Guide to help you get a balance of healthier and more sustainable food
Each serving contains It shows how much of what you eat overall should come from each food group
6–8
Fat Saturates Sugars Salt
Energy
Choos a day
5g 1.3g 34g 0.9g
day
1046kJ
e who
very
250kcal
legr
es e
LOW LOW HIGH MED
ain
12.5% 7% 6.5% 38% 15%
et abl Po t a or h
eg t oes igh Water, lower fat
of an adult’s reference intake
dv , br er
Typical values (as sold) per 100 g: 697 kJ/ 167 kcal an ead fib milk, sugar-free
uit , ri re
Choose foods lower f fr ce
,p
ve
rsi
drinks including
yo
s
in fat, salt and sugars t b le a
st a o ns
tea and coffee
rie ge
ta an w all count
va ve d
ot Limit fruit juice
ith
d
a
of
and/or smoothies
an
les
he
ns
r
to a total of
sa
it
st
rtio
u
Fr
ar
150 mL a day
dd
po
ch
ed
yc
t5
fat,
arb
leas
salt
ohy
Eat at
d rat e
and su
s
gar
Be s
an e Oil and spreads
Ea s, p at iv
ulse lt er n
so t more s , fi s
h, e g and
a
and Choose unsaturated oils
u
red ced beans
r g s, mea Dairy r fat and use in small amounts
and fish and p
t and ot her p ro t eins
ose lowe ptions
proc per we ulses, 2 portions of sustainably Cho ro
suga
esse
d mea
ek, one
of which is oily. Eat less lower
Eat less often and t
in small amounts
Per day 2000 kcal 2500 kcal = ALL FOOD + ALL DRINKS
Source: Public Health England in association with the Welsh government, Food Standards Scotland and the Food Standards Agency in Northern Ireland © Crown copyright 2016
Figure 2.1 Eatwell Guide [78].
comfort habit that is hard to break. Children who drink eat a balanced diet, other nutrient supplements are not
sweet drinks from bottles have a higher risk of dental caries required; however, some nutrients are ‘at risk’ in the
[61]. Water and milk are preferred drinks and should be preschool diet in addition to vitamin D, namely, iron and
given in a cup, beaker or glass. Six to eight drinks of about vitamin A (p. 38). Children who are particularly fussy eaters
100–120 mL can be offered throughout the day, with meals and exclude whole food groups may need additional
and snacks. More may be needed in very hot weather or after supplements.
a lot of physical activity. Drinks containing artificial sweet-
eners should be kept to a minimum and be well diluted.
Guidance documents on food served in early
years settings
Portion sizes
The following guidelines are not mandatory and are not
The under 5s eat more on some days and less on other days; monitored by local authorities:
hence set portion sizes are not useful for them. The mid-
points of the portion size ranges in Table 2.12 meet the RNI • England: The Voluntary Food and Drink Guidelines for
for nutrients and average energy requirement for children Early Years Settings. https://app.croneri.co.uk/feature‐
aged 1–4 years when combined according to the specified articles/voluntary‐food‐and‐drink‐guidelines‐early‐
number of daily servings [81]. They can be used both to reas- years‐settings
sure parents of young children who eat small amounts and • Scotland: Setting the Table: Nutritional guidance and
to limit overeating, particularly of high sugar foods. food standards for early years childcare providers in
Scotland. http://www.healthscotland.com/documents/
30341.aspx
Vitamin and mineral supplementation
• Wales: Food and nutrition for childcare settings. https://
A supplement of vitamin D is recommended for children up gov.wales/food‐and‐nutrition‐childcare‐settings‐full‐
to at least the age of 5 years [3]. For preschool children who guidance
32 Healthy Eating
Table 2.12 Portion size ranges for children aged 1–4 years.
Food group Foods Range of portion sizes
Bread, rice, potatoes, pasta and other starchy Bread 1

∕2–1 medium slice
foods Mashed potato 1–4 tbsp
• 5 servings per day Pasta (cooked) 2–5 tbsp
Rice 2–5 tbsp
Fruit and vegetables Apple/pear/peach 1
∕4–1∕2 medium fruit
• 3 servings fruit and 3 servings of vegetables Broccoli/cauliflower 1–4 small florets or 1∕2–2 tbsp
per day Clementine/tangerine/mandarin 1
∕2–1 fruit
Sweet corn 1
∕2–2 tbsp
Milk, cheese and yoghurt Cow’s milk 100–120 mL or 3–4 fluid oz
• 3 servings per day Grated cheese 2–4 tbsp
Yoghurt 1 average pot or 125 mL
Meat, fish, eggs, nuts and pulses Baked beans in tomato sauce 2–4 tbsp
• 2 servings per day Chicken drumsticks 1
∕2–1 drumstick
Peanut butter 1
∕2–1 tbsp
Scrambled egg 2–4 tbsp
Tinned fish 1
∕2–11∕2 tbsp
Butter, oils and fat spreads Butter Thinly spread or 1 tsp
• 2 servings per day Oil
Foods high in sugar/savoury snacks Fruit crumble (e.g. apple or rhubarb) 2–4 tbsp
• 1 serving per day of cake, biscuit, pudding Ice cream 2–3 heaped tbsp
or starchy snack Plain biscuits 1–2 biscuits
• 1 serving per day of sauces or sweet/ Honey/jam 1 tsp
savoury spreads Sugar 1
∕2–1 tsp
• 1 serving per week of confectionery, Crisps 4–6 crisps
savoury snacks and sweet drinks
tbsp, tablespoon (15 mL); tsp, teaspoon (5 mL).

Source: Adapted from More and Emmett [81]. Reproduced with permission of John Wiley & Sons.
• Northern Ireland: Nutrition matters for the early years: months, then they will enter their second year with a wider
Guidance for feeding under fives in the childcare setting. range of foods they recognise, like and readily accept [82].
https://www.publichealth.hscni.net/publications/
nutrition‐matters‐early‐years‐guidance‐feeding‐under‐ Disgust and contamination fears
fives‐childcare‐setting
Between 3 and 5 years, young children may develop disgust
fears and stop eating foods they may have previously
Nursery milk enjoyed [83]. They will refuse a food on sight if it resembles
something they find disgusting, e.g. they may find spaghetti
Children under 5 years are entitled to 1∕3 pint (189 mL) milk per in sauce suddenly looks like worms. Contamination fears
day if they attend a nursery or are with a registered childmin- occur around the same time; if a disliked food is put on a
der for more than 2 hours per day (www.nurserymilk.co.uk). plate next to a liked food, the toddler may refuse both foods.
Learning to like new foods

Developmental changes in preschool children
The neophobic response dissipates slowly throughout the
How easily parents manage to feed their young children rest of childhood and adolescence [84, 85]. Toddlers and
depends to some extent on parental knowledge and parent- young children can be helped to pass through this stage by
ing skills. At the same time developmental changes in tod- eating in social groups, as they learn by copying adults and
dlers affect how they respond to food and meals. other children. It is, therefore, important that families eat
together as often as possible and that toddlers are praised
Neophobia when they eat well. Toddlers may also learn to eat new foods
when eating with other children at nursery or with friends.
During their second year, toddlers develop a neophobic
Some toddlers need to be offered a new food more than 10
response to food, which means they become wary of trying
times before they accept it as a liked food [82, 86].
new foods. The origin of this may be a survival mechanism
Some toddlers have more problems than others and there
to prevent the mobile toddler from poisoning themselves.
are two main reasons for this in healthy individuals:
This neophobic response usually peaks around 18 months
and is more evident in some toddlers than others. If toddlers • Some become very rigid about the foods they will eat.
are being offered a wide variety of foods by around 12 They tend to be more emotional and more stubborn about
Schoolchildren (5–18 Years) 33
what they will or will not do. They do not copy other chil- Table 2.13 Voucher entitlement for infants and children through
dren and so will not copy other people’s eating behaviour. Healthy Start.
• Others may be more sensory sensitive and have extreme
Number of vouchers valued at
reactions to touch, taste and smell. They may be orally
£3.10/week*
hypersensitive and have problems with different tex-
tures of food – they may have taken longer to progress Term infants up to 12 months 2
from smooth to lumpy food and onto more difficult tex- Preterm infants up to 12 months 2
tures during complementary feeding. They may worry after EDD
about getting their hands and face dirty and find it diffi- Children 1–4 years 1
cult to handle food and feed themselves.
EDD, estimated date of delivery.
Avoidant restrictive food intake disorder (ARFID) is the * Voucher value as defined in 2020.
diagnosis given where there are nutritional or growth con-
cerns with a restrictive eating pattern [87]. Toddlers who
experience faltering growth need to be referred to specialists 4 years in these families are also entitled to free vitamin
who can assess and advise. drops containing vitamins A, C and D. Details of entitlement
and how to access the scheme can be found on the Healthy
Start website (www.healthystart.nhs.uk).
Exacerbating food refusal
Parental anxiety when toddlers only eat a limited variety of Sure Start children’s centres
foods can exacerbate the problem, especially if parents try to
coerce or force‐feed the child with food they are wary of or Sure Start is a government‐led initiative aimed at giving
dislike. Until 4–5 years of age, young children’s appetites are every child aged 0–4 years the best possible start in life; it
determined mainly by their energy and growth needs. They offers a broad range of services focusing on family health,
eat well at sometimes and less so at other times, and those early years care, education and improved well‐being pro-
who are not gaining excess weight should be allowed to grammes. Services include advice on healthcare and child
decide the quantity they eat themselves. development, play schemes, parenting classes, family out-
Some parents expect their toddlers to eat more than they reach support and adult education and advice. One aim is to
need and coerce or force‐feed when the toddler is signalling help overcome the barriers to feeding young children a
they have had enough food. As mealtimes develop into a healthy diet, and dietitians have been involved in:
battle ground between toddler and parent, the toddler can • training Sure Start workers, community food assistants and
lose their appetite just by becoming anxious as the mealtime playworkers about weaning and healthy eating messages
approaches. Toddlers may use the following signals to indi- • developing food policies with parents and staff
cate that they have had enough food: • developing resources with parents
• saying ‘no’ • education sessions for parents on cooking, shopping and
• keeping their mouth shut when food is offered weaning. Cook and eat sessions are popular, and devel-
• turning their head away from food being offered oping literacy skills has become part of some shopping
• pushing away a spoon, bowl or plate containing food and cooking sessions
• holding food in their mouth and refusing to swallow it • holiday play schemes
• spitting food out repeatedly • clinical input and home visits
• crying, shouting or screaming Recently many schemes have closed, but operating
• gagging, retching or vomiting schemes and activities can be accessed on the Sure Start web-
• trying to escape from the meal by climbing out of their site (www.gov.uk/find‐sure‐start‐childrens‐centre).
chair or highchair
From around 5 years of age, children learn to modify their Schoolchildren (5–18 years)
eating according to social rules and will learn to finish what
is on their plate or eat when others are eating even if they are From around the age of 5 years, the principles of healthy eat-
not hungry, and they will also begin to comfort eat. ing that are recommended for the adult population apply.
Guidance on macronutrient intakes is [2]:
• at least 50% of energy from total carbohydrates
Social support for preschool children in low‐income • a maximum of 5% of energy from free sugars [4]
families • a maximum of 35% of energy from fat
• a maximum of 11% of energy from saturated fat
Healthy Start • about 15% energy from protein
Families who qualify for this scheme are those in receipt of In order to satisfy the nutrient requirements of children, the
certain benefits. Under the scheme they are entitled to vouch- recommendations need to be more specific than those given
ers that can be exchanged for cow’s milk, fresh fruit and by PHE for the general population (Figure 2.1). Table 2.14 is
vegetables and infant formula (Table 2.13). Children up to based on recommendations from the Paediatric Specialist
34 Healthy Eating
Group of the British Dietetic Association, which meet the RNI instead of meat and fish. At least three servings are needed
for each age group when providing the EAR for energy. each day to provide an adequate iron intake as the bioavail-
ability of iron from eggs and plant sources is much lower
than that of haem iron found in meat and oily fish. Good
Vegetarian and vegan diets sources of omega‐3 fatty acids such as walnuts, linseeds and
walnut and rapeseed oils need to be recommended.
A well‐planned vegetarian diet based around the same food Vegan diets are unlikely to provide adequate nutrients
groups shown in Table 2.11 can be nutritionally adequate. for optimal growth and development. Replacing milk,
Of the group 4 foods eggs, nuts and pulses will be eaten cheese and yoghurt with substitute drinks based on pulses
Table 2.14 Portion size ranges and food group servings per day for school‐age children.
15–18 years
Food groups 4–6 years 7–10 years 11–14 years Girls Boys
Bread, rice, potatoes, pasta and Bread 36–72 g 54–108 g 72–144 g 72–144 g 108–180 g
other starchy foods – medium slices 1–2 1½–3 2–4 2–4 3–5
• 4 servings per day Potato 70–100 g 90–150 g 120–180 g 120–180 g 170–190 g
Pasta (cooked) 70–100 g 90–150 g 120–180 g 120–180 g 180–220 g
Rice (cooked) 65–95 g 90–150 g 120–180 g 120–180 g 170–200 g
Dry breakfast cereal 18–32 g 25–45 g 30–50 g 30–50 g 45–55 g
Weetabix 1–2 1½–2½ 2–3½ 2–3½ 3–5
Porridge, cooked 100–160 g 120–180 g 175–275 g 175–275 g 240–360 g
Fruit and vegetables Apple/pear/orange 1 small 1 medium 1 medium 1 large 1 large
• 3 servings of fruit and 3 Banana 1 medium 1 medium 1 large 1 large 1 large
servings of vegetables per day Berries/grapes 45–75 g 55–85 g 60–100 g 80–100 g 80–100 g
Kiwi/plums/apricots 1 fruit 1–2 fruits 2 fruits 2–3 fruits 2–3 fruits
Vegetables 30–40 g 45–60 g 60–80 g 80 g 80 g
Milk, cheese and yoghurt Milk 120–140 mL 140–180 mL 190–210 mL 190–210 mL 230–250 mL
• 3 servings per day Yoghurt/lassi 125 g 130–150 g 140–160 g 140–160 g 160–240 g
Cheese/paneer 20–30 g 25–38 g 30–45 g 30–45 g 35–50 g
Custard 70–110 g 90–150 g 100–160 g 100–160 g 110–210 g
Rice pudding 60–120 g 800–160 g 120–180 g 120–180 g 135–180 g
Meat, fish, eggs, nuts and pulses Meat 35–55 g 45–75 g 60–100 g 60–100 g 70–110 g
• 2 servings per day Fish 35–50 g 45–75 g 70–110 g 70–110 g 75–125 g
• 2 portions fish/week – one of Fishcakes/fingers 35–55 g 50–70 g 65–105 g 65–105 g 110–130 g
oily fish Eggs 1 medium 1 large 1–2 eggs 1–2 eggs 2 eggs
Nut butter 22–27 g 30–35 g 40–50 g 40–50 g 60–70 g
Nuts/Bombay mix 25–35 g 30–40 g 40–50 g 40–50 g 45–55 g
Baked beans 55–95 g 75–115 g 90–150 g 90–150 g 110–170 g
Pulses/beans (cooked) 35–65 g 60–120 g 70–130 g 75–125 g 105–175 g
Butter, oils and fat spreads Butter/fat spread 1½ tsp 2 tsp 3 tsp 3 tsp 4 tsp
• 2 servings per day Oil 1 tsp 2 tsp 1 tbsp 1 tbsp 1 tbsp
Mayonnaise ½ tbsp ½–1 tbsp 1 tbsp 1 tbsp 1‐1½ tbsp
Double cream 1 tbsp 2 tbsp 2–3 tbsp 2–3 tbsp 2–3 tbsp
Cake, biscuit, pudding Biscuits 1–2 2–3 3–4 3–4 3–4
• 1 serving per day Cake/croissant 25–35 g 40–50 g 50–70 g 50–70 g 80–100 g
Fruit‐based pudding 30–60 g 45–80 g 60–100 g 60–100 g 90–120 g
Ice cream 50–70 g 65–85 g 75–95 g 75–95 g 80–110 g
Sauces and sweet/savoury Jam/honey/syrup 1–2 tsp 2 tsp 2 tsp 2 tsp 3 tsp
spreads Gravy 1½–2 tbsp 2 tbsp 3 tbsp 3 tbsp 4 tbsp
• 2 servings per day Tomato or curry sauce 2–2½ tbsp 2½–3½ tbsp 3–4 tbsp 3–4 tbsp 4–5 tbsp
Ketchup/savoury sauce 1 tbsp 1½ tbsp 2 tbsp 2 tbsp 2–3 tbsp
1 serving per week of either Fruit juices/sweet 120–140 mL 150–200 mL 200–250 mL 200–250 mL 250–330 mL
sweet drinks, confectionery or drinks
savoury snacks Sweets 25 g 35 g 40 g 40 g 45 g
Chocolate/Indian 25 g 35 g 40 g 40 g 45 g
sweets
Crisps/other packet ½ small 1 small 1 small 1 small 1 packet
snacks packet (25 g) packet (25 g) packet (25 g) packet (25 g) (37.5 g)

Schoolchildren (5–18 Years) 35
such as soy, nuts, coconut and cereals will not provide chil- • onion and vegetable bhajis
dren with the amounts of calcium, riboflavin, zinc, vitamin
Suitable healthy drinks for meal and snack times include:
A and iodine found in dairy products. Micronutrient
supplementation providing the RNI for iron, iodine, ribo- • water
flavin, calcium, phosphorus and vitamins A, B12 and D is • milk (plain or flavoured)
required to prevent malnutrition. • vegetable juices
Vegan children are unlikely to achieve their full adult • no added sugar (sugar‐free) squashes
height potential even with micronutrient supplements as
epidemiological studies show milk and meat in diets are
Emotional changes in adolescents
associated with increased height [88, 89]. It is hypothesised
that milk and meat proteins along with zinc, iodine and
During adolescence teenagers develop their own autonomy,
other hormonal factors exert positive effects on the growth
rejecting their parents’ values and developing their own.
plate of growing children [90, 91].
Values around food and meals are no exception to this, and
many teenagers change their eating habits so that they are
Neophobia different from the rest of their family [85]. Their choices often
include commercial and low nutrient snack foods. Hill [85]
During childhood many children remain neophobic, preferring suggested adolescents may:
to eat foods they are familiar with. They must be motivated to
• eat more and more food outside the home and conveni-
taste new foods. Work in this field continues to show that the
ence may be influential in choices made
number of times children are exposed to food increases the like-
• eat according to personal ideology such as the use of veg-
lihood they will try the food and then learn to like it [92].
etarian or vegan diets
• begin slimming or weight control (whether justified or
Adolescent growth spurt not)
• choose less healthy foods as an act of parental defiance
The adolescent growth spurt lasts approximately 2 years and and peer solidarity
takes place, on average, around 12 years of age for girls and • consume certain foods or brands due to peer group
14 years for boys, but can be 2 years earlier or later. The peak pressure
height velocity can be up to 13 cm/year for boys and 10 cm/ • follow specific diets to enhance sporting prowess
year for girls [93]. Growth rate then declines until full height
Understanding why adolescents choose the foods they do
is reached. During this time adolescents’ energy require-
is crucial when developing health education programmes
ments will be noticeably higher and appetite may be larger.
for this age group.
Extra snacks often make up this increase in food intake, but
their snacks are often low nutrient, high fat and high sugar
foods, rather than snacks from combinations of the five food Nutritional initiatives in schools
groups, which would enhance their nutrient intakes.
Food and drinks consumed at school can make a large con-
tribution to a child’s nutrient intake.
Good choices for snacks and drinks
These snacks are suitable for all children from 1 year of age, School food standards
not just for adolescents:
These vary slightly across the four countries in the UK,
• fresh fruit (dried fruit can be cariogenic when eaten as a and it is up to the Board of Governors for each school
snack so it is not advised) to ensure they are followed as there is no statutory
• vegetable sticks, e.g. carrot, cucumber, pepper, baby corn monitoring.
and dips based on yoghurt, cream cheese or pulses such England has food‐based standards (www.legislation.gov.
as hummus uk/uksi/2014/1603/pdfs/uksi_20141603_en.pdf).
• wholegrain breakfast cereals with milk They apply to:
• cheese cubes and crackers or chapatti
• local authority maintained nursery, primary, secondary,
• unsalted nuts
boarding and special schools
• sandwiches, filled rolls and pitta breads
• Pupil Referral Units
• French toast or toast with a range of spreads, used sparingly
• academies that opened prior to 2010 and academies and
• slices of pizza with a plain dough base that has not been
free schools entering into a funding agreement from
fried
June 2014
• yoghurt and fromage frais
• non‐maintained special schools
• crumpets, scones, currant buns, teacakes, Scotch pan-
cakes and fruit muffins Practical guidance is given on the School Food Plan web-
• home‐made plain popcorn site (www.schoolfoodplan.com). From September 2014,
• cakes containing nuts or dried fruit or vegetables, e.g. every child in reception, year 1 and year 2 in state‐funded
fruit cake and carrot cake schools, is entitled to a free school lunch.
36 Healthy Eating
Wales has food‐based standards (http://learning.gov. Table 2.15 Suggestions for packed lunchboxes.
wales/docs/learningwales/publications/160226‐healthy‐
eating‐maintained‐schools‐en‐v2.pdf). Food group Suitable foods
Scotland has nutrient‐ and food‐based standards (www. Bread, rice, potatoes, This should be the base of the lunch:
gov.scot/publications/healthy‐eating‐schools‐guide‐ pasta and other starchy
implementing‐nutritional‐requirements‐food‐drink‐ • Breads, rolls, wraps and pittas can be filled
foods
or used for sandwiches
schools‐9780755958306).
• Crispbread or bread sticks
Northern Ireland has food‐based standards (www. • Pasta, rice or cooked potatoes as the base
education‐ni.gov.uk/sites/default/files/publications/de/ for a salad or soup
de1‐09‐125640‐nutritional‐standards‐for‐school‐lunches‐a‐ • Buns, scones, tea breads
guide‐for‐implementation‐3‐2.pdf). Fruit and vegetables • Sliced in sandwiches
• Combined in a salad
The National Fruit and Veg Scheme • Sticks of raw vegetables (celery, carrots,
cucumber) or small tomatoes as finger
All 4‐ to 6‐year‐old children in fully state‐funded infant, pri- foods or crunchy alternative to crisps
mary and special schools are entitled to a free piece of fruit • Pieces of fruit or small packets of dried fruit
or vegetable each school day (www.nhs.uk/live‐well/eat‐ Milk, cheese and • Cheese is a popular sandwich filling
well/school‐fruit‐and‐vegetable‐scheme). yoghurt • Cubes or triangles of cheese as finger foods
• Pots of yoghurts, fromage frais or rice
Subsidised school milk pudding are popular desserts
• Cartons of milk or flavoured milk as the drink
This is available for primary schoolchildren. In England schools
Meat, fish, eggs, nuts • Cold meats or flaked fish can be included
choose whether they wish to offer it, but in Wales children up to and pulses in sandwiches or salads
7 years of age are entitled to 1∕3 pint (189 mL) milk free per day • Chicken drumsticks
(www.gov.uk/guidance/eligibility‐for‐the‐school‐ • Hard‐boiled eggs
milk‐subsidy‐scheme‐milk‐consumed‐from‐1‐august‐2017). • Falafels or vegetable bhajis
• Sausages, ham and salamis are processed
meats and should be limited
School breakfasts
Combined food group • Slices of quiche or pizza
Many schools have begun offering breakfasts, and anecdotal foods • Soups
claims have been made that school attendance, behaviour Foods high in sugar • Small cakes, plain biscuits, pancakes or
and performance have improved as a result. However, a sys- muffins
tematic review found that although a school breakfast is bet-
ter than no breakfast, this only makes a difference in children
who are malnourished. Furthermore they found that any
improved academic performance may be due in part to the or teenager who could become pregnant. Since most teenage
increased school attendance that a school breakfast encour- pregnancies are unplanned, a diet rich in folate should be
ages, rather than the food itself [94]. Children say they enjoy recommended to all teenage girls.
the social side of school breakfasts.
Pregnancy
Packed lunches
Many children bring a packed lunch rather than have school Pregnancy during the teenage years places extra nutritional
meals that they dislike, or that their parents either cannot needs on girls who may not have finished growing them-
afford or of which they disapprove. Packed lunches can be of selves and who will not have attained their peak bone mass.
poor nutritional content; a survey of primary school lunch- Nutrient requirements have not been specified for these
boxes showed that only 1% met all the food‐based standards young mothers, but a healthy balanced diet with folic acid
for school meals [95]: 85% contained a sandwich; 82% con- and vitamin D supplementation would be a minimum
tained confectionery and/or crisps; 54% contained fruit; 19% requirement. For those eating poorly a multivitamin and
contained vegetables. mineral supplement (not containing retinol) could be recom-
A government leaflet on suggestions for healthy lunch- mended. Under the Healthy Start scheme, all pregnant girls
boxes is available at www.healthylunch.org.uk/government. under 18 years old are entitled to benefits regardless of their
Suggestions for packed lunchboxes are given in Table 2.15. A financial circumstances [96].
small ice pack or a frozen drink will keep a closed lunchbox
cool for a few hours.
Nutritional needs of adolescents training as athletes
Teenage girls of childbearing age Meeting the higher energy needs for adolescents undertak-
ing sports training is essential and may require specialist
All women of childbearing age should have a nutritious diet input from a registered sports dietitian. Energy requirements
with adequate folate content. The Department of Health rec- should be calculated to support the training programme
ommends a supplement of 400 μg folic acid for any woman using basal metabolic rate and physical activity level and
Current Challenges in Paediatric Nutrition in the UK 37
adding in 60–100 kcal (250–420 kJ)/day to allow for extra 50%, 35% and 15% of energy, respectively, but those of free
growth [2]. Monthly height measurement can be used to sugars and saturated fat are higher than recommended
assess when the pubertal growth spurt is taking place. It is (Table 2.17) and intakes of fibre are lower than recommenda-
essential to meet all micronutrient requirements as sports tions (Table 2.18).
training can have a negative effect on the immune system Foods eaten on the way to and from school make a signifi-
[97]. Adolescents in sports training should eat a high carbo- cant contribution to schoolchildren’s nutrition, particularly
hydrate snack or meal, containing some protein, within an intakes of free sugars and saturated fats. A survey produced by
hour of finishing training to ensure good glycogen stores a large international school caterer reported that in 2005 [98]:
within muscles (as should any other athlete).
• £519 million was spent by schoolchildren on their way to
and from school
Current challenges in paediatric nutrition • Main purchases were sweets, crisps and savoury snacks,
in the UK chocolate, canned fizzy drinks, chewing gum, other soft
drinks, cigarettes, bottled water, chips and ice cream
Persistently high rates of obesity in UK children remain the
greatest challenge and are discussed in Chapter 25. Other
specific nutritional problems are discussed in other chapters: Micronutrient intakes are not met in all populations
faltering weight (Chapter 24), constipation and diarrhoea of children
(Chapter 8) and food allergy (Chapter 15).
Despite the initiatives and guidelines for healthy eating Preschool children
outlined above, several other paediatric nutritional chal-
The 2018 NDNS indicates that the mean intake of the 1½–3
lenges persist in the UK.
years population is above the RNI for all nutrients except iron
and vitamin D. Less than 50% of this population met the RNI
Breastfeeding rates during infancy are low for iron and the mean intake of vitamin D was 34% RNI. More
than 3% of this population did not meet the LRNI for iron, vita-
The last UK IFS in 2010 reported that 81% of mothers initiate min A and zinc [76] (Table 2.19). However, zinc deficiency
breastfeeding soon after birth; however, exclusive breast- would not be seen in this population if the UK LRNI and RNI
feeding declines rapidly with only 46% mothers doing so at were not set higher than in other countries, e.g. the RNI for zinc
the end of the first week, 23% at 6 weeks and 1% at 6 months is 3 mg/day in the USA compared with 5 mg/day in the UK.
[54] (Table 2.16). Similar figures were reported in the Scottish
Maternal and Infant Nutrition Survey in 2017 [56]. This Schoolchildren
decline is often due to lack of support to address common
problems and difficulties and a mother’s perception of an The food intakes of primary schoolchildren are fairly closely
inadequate breastmilk supply for her infant. NICE recom- controlled by their parents and the 2018 NDNS showed that
mends that when mothers leave a maternity unit, they the ‘at‐risk’ nutrients for primary‐age schoolchildren (4–10
should be given contact details of breastfeeding counsellors years of age) are vitamins A and D, iodine and zinc. In stark
and information on local peer support groups [32]. contrast older children (11–18 years), who are making more
of their own food choices, have low average intakes for most
micronutrients (Table 2.19).
Free sugar, saturated fat and fibre intakes in all age
Implications of poor teenage diets on future risk
groups of children do not meet recommendations
of osteoporosis
Figures from the 2018 National Diet and Nutrition Survey Even after the growth spurt, calcification of bones continues
(NDNS) [76] show that children’s current intakes of carbohy- as peak bone mass is not reached until the early to late 20s. It
drates, total fat and protein are close to the guidelines of is later for males than females [99]. A vitamin D supplement
Table 2.16 Incidence and prevalence of breastfeeding in the UK [54].
% of infants in the UK being

% of infants in the UK receiving some breastmilk exclusively breastfed
Age of infants 1995 2000 2005 2010 2005 2010
At birth 66 69 76 81 76 81
1 week 56 55 63 69 45 46
6 weeks 42 42 48 55 21 23
4 months 27 28 34 42 7 12
6 months 21 21 25 34 <1 1
9 months 14 13 18 23 – –
38 Healthy Eating
Table 2.17 Macronutrient intakes of children, National Diet Preventable dietary iron deficiency remains prevalent
and Nutrition Survey [76].
in 1‐ to 5‐year‐olds and adolescent girls
Macronutrient intakes as % energy [76]
Iron deficiency is associated with frequent infections, poor
Age group Free Total Saturated weight gain, developmental delay and behaviour disorders.
(years) Carbohydrates sugars fat Fat It is usually of dietary origin. Table 2.20 shows the low hae-
moglobin and ferritin levels of population groups from the
1½–3 50.5 11.3 34.4 14.5
2018 NDNS.
4–10 51.6 13.5 33.4 13
11–18 50.3 14.1 33.7 12.4 Preschool children
Recommendation 50 <5 35 <10
Iron deficiency is more common in 1‐ to 5‐years‐olds than
[2]
those over 5 years and is seen more in socially disadvan-
Source: Food Standards Agency and Public Health England 2018. taged groups and in immigrant populations.
Depletion of iron stores in the second half of infancy
occurs when the iron content of the weaning diet is poor
Table 2.18 Fibre recommendations and current intakes in children,
National Diet and Nutrition Survey [76]. [47], even though deficiency may not be evident until
after 12 months of age. The early introduction of cow’s
Age group Recommendations Age group Average intakes milk as a main drink before 12 months of age is a risk fac-
(years) (g/day) [4] (years) (g/day) [76] tor [102]. Availability and choice of commercial baby
foods may contribute to an iron‐deficient weaning diet
2–5 15 1½–3 10.3
for Muslim families; there is a range of halal meat‐based
5–11 20 4–11 14 baby foods in the UK, but many families only buy or have
11–16 25 11–18 15.3 access to low iron vegetable‐only‐based savoury varieties
16–18 30 and desserts.
Overdependence on milk (consuming in excess of
Source: Food Standards Agency and Public Health England 2018. 400 mL/day) in toddlers and preschool children, where
it replaces iron‐rich foods, is another common cause [79,
Table 2.19 Percentage of population groups with nutrient intakes 80, 103].
from food and supplements below the LRNI, National Diet and Nutrition
Survey [76].
Schoolchildren
Age groups In older children deficiency occurs most commonly in teen-
age girls who have begun menstruating and have high iron
11∕2–3 years 4–10 years 11–18 years
requirements and in children who are vegetarian or vegan or
Nutrient Boys and girls Boys Girls Boys Girls
who do not eat a balanced diet.
Vitamin A 15 13 11 19 24 Prevention of iron deficiency

Riboflavin 1 0 1 13 26 Dietary advice should emphasise:
Folate 1 0 1 2 15
• the importance of regularly consuming iron‐rich foods:
Iron 10 0 3 12 54 meat, oily fish, eggs, nuts, pulses, iron‐fortified breakfast
Calcium 1 2 1 11 22 cereals and dried fruit
Magnesium 0 0 1 27 50 • liver and liver products are a very rich source of iron, but
Potassium 0 0 0 18 38
because they contain very high levels of vitamin A, they
should be limited to one serving per week
Iodine 3 6 4 14 27
Selenium 0 1 1 26 45
Zinc 5 9 14 18 27 Table 2.20 Percentage of population groups with low haemoglobin
and/or ferritin levels, National Diet and Nutrition Survey [76].
LRNI, lower reference nutrient intake.
Source: Food Standards Agency and Public Health England 2018. 1½–3 years 4–10 years 11–18 years
Age Boys and girls Boys Girls Boys Girls

and three servings of milk, cheese or yoghurt daily will
ensure that calcium and phosphorus requirements are being Low haemoglobin levels 5 1 4 1 9
met to ensure bone deposition, but a balanced diet providing Low ferritin levels 31 9 9 2 24
a wider range of nutrients is now considered necessary for Low haemoglobin and – 2 0 1 9
optimal peak bone mass [100]. Calcium from dietary cow’s low ferritin levels
milk is more effective than calcium supplements in prevent-
ing osteoporosis in older women [101]. Source: Food Standards Agency and Public Health England 2018.
Current Challenges in Paediatric Nutrition in the UK 39
• haem iron in meat and fish is absorbed much more effi- • 125 cases of nutritional rickets over 2 years (March 2015
ciently than non‐haem iron from eggs, nuts, pulses, cere- to March 2017)
als, fruit and vegetables. Simultaneous consumption of • the majority were of black and South Asian origin and
fruits and vegetables rich in vitamin C will enhance non‐ more boys than girls were affected
haem iron absorption. This is a particularly important • 78% were not taking vitamin D supplements because
measure in vegetarian children parents had not been informed by healthcare practition-
• iron uptake can be maximised by including foods rich in ers to give them
vitamin C and avoiding drinking tea, which hampers • radiological abnormalities included bowed legs and
absorption at mealtimes swollen wrists
• co‐morbidities included:
◦◦ delayed gross motor development in 26%
Preventable dental caries and tooth extractions are ◦◦ fractures in 10%
common in all ages of children due to high sugar ◦◦ hypocalcaemic seizures in 8%
intakes and poor oral hygiene ◦◦ dilated cardiomyopathy in four cases, of whom two
died
Children, particularly the under 5s, are more susceptible to Epidemiological studies [109] report associations between
dental caries than adults although the incidence of caries in low vitamin D levels and higher rates of inflammatory and
children in the UK decreased following the introduction of autoimmune diseases and other chronic diseases in children
fluoride toothpaste in the 1970s. However, the current high including:
and frequent consumption of sugary foods and sugary acidic • type 1 and type 2 diabetes
drinks contributes to: • upper respiratory tract infections
• 23.3% of 5‐year‐olds in 2017 having at least one decayed, • wheeze, including asthma
missing or filled tooth. The average was 3–4 teeth • infectious diseases
affected. The incidence ranged from 13.6% in children Food sources of vitamin D are few in UK diets:
from the least deprived backgrounds to 33.7% from the
most deprived backgrounds [104] • Oily fish is the only significant food source
• the NHS spending £50.5 million on hospital‐based tooth • Eggs and meat provide very small amounts
extractions for 0‐ to 19‐year‐olds in 2015–2016 • Breastmilk provides extremely small amounts and varies
depending on the mother’s own vitamin D status
The incidence of dental disease is lower in children who
Some foods in the UK are fortified with small amounts of
brush their teeth twice a day with fluoridated toothpaste and
vitamin D:
those over the age of 1 year limiting sugary and acidic food
and drinks to four eating episodes per day, e.g. three meals • margarine, but not necessarily all fat spreads
and one snack [105]. PHE recommendations on delivering • evaporated milk
better oral health include the following [106]: • infant, follow‐on and toddler formula milks
• tooth brushing should begin in infancy from the time the • some brands of breakfast cereals and yoghurts
first tooth erupts Some countries, e.g. Finland, the USA and Canada, fortify
• teeth should be brushed twice daily with fluoridated a wider variety of foods with vitamin D such as fresh cow’s
toothpaste, once in the morning and last thing at night milk, dairy products and fruit juices.
• use a smear of paste containing at least 1000 ppm of fluo- The 2018 NDNS [76] reports that very few children con-
ride up to the age of 3 years sumed the recommended SI or RNI for vitamin D through
• use a pea‐sized amount of at least 1000 ppm of fluoride food alone (Table 2.21) and very few took the recommended
paste between 3 and 6 years supplements to ensure nutritional requirements are met
• use a pea‐sized amount of 1350–1500 ppm of fluoride (Table 2.22). Blood results from the NDNS indicate defi-
paste from the age of 7 years ciency is highest in January to March when:
• 19% of children aged 4–10 years
Vitamin D supplements are not routinely given to all • 37% of children aged 11–18 years
children to prevent deficiency had blood vitamin D concentrations below 25 nmol/L, the
threshold indicating risk of deficiency.
When body stores are low and cutaneous synthesis and die- Over‐the‐counter supplements containing only vitamin
tary sources of vitamin D are limited, vitamin D deficiency D are widely available, and most multivitamin supple-
can develop in rapidly growing infants, toddlers and adoles- ments for infants, children and pregnant and breastfeeding
cents. The number of infants and children with preventable women include vitamin D. The Healthy Start vitamins are
rickets, hypocalcaemic seizures or cardiomyopathy resulting the most cost‐effective supplement, but they are only
from extremely low levels of vitamin D has been rising in available in some NHS clinics. Although NICE recom-
developed countries [107]. British paediatricians recently mends that local authorities provide them free of charge
reported the following [108]: to beneficiaries of the Healthy Start scheme and sell them
40 Healthy Eating
Table 2.21 Mean daily vitamin D intakes (μg/day) in children in the • season – the critical wavelength in daylight only
UK [76]. reaches the UK between April and September; it is
absorbed by the atmosphere during autumn and win-
Age groups
ter months
11∕2–3 years 4–10 years 11–18 years • latitude – less vitamin D is made in the north of the UK
than in the south where more of the UVB rays are
Source of vitamin D Boys and girls Boys Girls Boys Girls present
• weather – on a cloudy day less vitamin D is made than
Food only 2 2.1 1.9 2.3 1.9
on a bright sunny day
Food and supplements 2.9 2.5 2.8 2.5 4.6 • pollution in the air – reduces the critical UV light waves
• time of day – more vitamin D is synthesised when sun-
Source: Food Standards Agency and Public Health England 2018.
light is most intense in the middle of the day compared
with early morning and late afternoon
• skin type – darker skins require more time in the sun to
Table 2.22 Public Health England recommendations for vitamin D produce the same amount of vitamin D so children with
supplementation [110] and European tolerable upper intake levels pigmented skins are at higher risk of deficiency
for infants, mothers and children. • lifestyles:
◦◦ time spent outside in April to September
European tolerable ◦◦ amount of bare skin exposure when outside; cutane-
Recommended daily upper intake levels
Population group supplement per day
ous synthesis is extremely limited when most skin is
covered as dictated by fashion or religious and cul-
Breastfed and formula‐ 8.5–10 μg 25/35 μg* tural traditions
fed infants from birth • use of sunscreen – it blocks cutaneous synthesis
Formula‐fed infants who 8.5–10 μg 25/35 μg*
are drinking less than
500 mL formula milk Conflicting advice on the use of sunscreen
Breastfed preterm A vitamin supplement Concern over the balance between having sufficient sun
infants that includes vitamin D exposure to produce vitamin D and overexposure leading to
is usually prescribed burning of the skin and an increased risk of skin cancer has
Preschool children 10 μg 50 μg led to confusion in public health messages. To provide uni-
1–4 years fied, evidence‐based advice on the subject, a consensus state-
Children 5–10 years 10 μg during autumn 50 μg ment on vitamin D was agreed in 2010 by several
and winter organisations with an interest in this area [112]:
Children 11–17 years 10 μg during autumn 100 μg
and winter The time required to make sufficient vitamin D varies
Pregnant and 10 μg 100 μg according to a number of environmental, physical and per-
breastfeeding women sonal factors, but is typically short and less than the amount
of time needed for skin to redden and burn. Enjoying the
* 25 μg for infants under 6 months, 35μg for infants 6–12 months. sun safely, while taking care not to burn, can help to provide
the benefits of vitamin D without unduly raising the risk of
skin cancer. Vitamin D supplements and specific foods can
help to maintain sufficient levels of vitamin D, particularly
to other clients, not all do this. There is no harm in school- in people at risk of deficiency. However, there is still a lot of
children taking a daily 10 μg supplement all year round as uncertainty around what levels qualify as ‘optimal’ or
the European UL (shown in Table 2.22) will not be ‘sufficient’.
exceeded.
Cutaneous synthesis can be the major source of vitamin D
for some children, but only occurs in the UK when outside Inappropriate dieting leading to poor
with some bare skin exposed to daylight in the summer nutritional intakes
months. Synthesis is regulated and shuts off when a particu-
lar plateau is reached so excessive amounts are not synthe- Girls as young as 9 years old, and some younger, indicate
sised [111]. Vitamin D is stored in the body when cutaneous body dissatisfaction and a desire to be thinner. Similar‐aged
synthesis and dietary intakes exceed daily requirements and boys aspire for a more muscled body, but overweight boys
these stores can be used during the winter months, although and girls both desire weight loss and are unhappy with their
stored levels may not last all winter. body shape [113, 114]. Hill suggested this body dissatisfac-
The ideal time to spend outside each day to ensure ade- tion was a result of picking up on parental attitudes to weight
quate vitamin D levels is not defined as cutaneous synthesis and shape and the idealisation of thinness promoted in the
varies depending on: media and peer behaviour [85].
Controversial Issues Around Nutrients and Foods 41
Food safety Controversial issues around nutrients and foods

Good food hygiene and storage is extremely important for
Omega‐3 fatty acids and learning skills
young children, particularly infants and children under 5
years. To offset any risks of bacterial food poisoning, meat,
Optimum brain functioning and sight are dependent on an
fish, shellfish and eggs should be well cooked right through.
adequate intake of the omega‐3 LCP, eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA), during foetal
Dioxin levels in oily fish growth and early infancy [121]. They are present in breast-
milk and are added to all whey‐dominant and casein‐domi-
Varying levels of dioxins accumulate in the fatty tissues of nant infant formulas (Table 1.14). Whether their presence in
oily fish, and to limit their intake, the Food Standards Agency food or supplements for older infants and children influ-
recommends that boys have a maximum of four portions of ences brain function, behaviour or the risk of atopy remains
oily fish per week. A maximum limit of two portions is set controversial.
for girls to reduce the amounts they will have accumulated A weekly serve of oily fish will ensure an adequate intake
in their tissues as they enter their childbearing years [115]. of omega‐3 LCP. Walnuts and linseeds as well as rapeseed,
walnut, linseed and soya oils are good sources of the omega‐3
essential fatty acid, α‐linolenic acid. Current research has not
Mercury levels in large fish shown that children with adequate dietary intake of omega‐3
fats will benefit from extra supplements. However, omega‐3
Large fish (marlin, swordfish and shark) live for many years supplements and foods that have been enriched with omega‐3
and can accumulate high levels of mercury in their flesh. fats are now subject to high level marketing following limited
PHE recommends that pregnant women, babies and young and controversial evidence of children’s reading, learning
children under 5 years do not eat these fish [115]. skills and behaviour improving with supplementation [122].
High vitamin A levels in liver

Food advertising
Although liver is a very good source of several nutrients,
particularly some ‘at‐risk’ nutrients discussed above, e.g.
Media messages about food are targeted at children through:
iron and zinc, it contains very high levels of vitamin A.
SACN has recommended that no one should increase their • television, radio, Internet and social media
consumption of liver beyond one portion per week [116]. advertisements
• in store displays
• child‐friendly packaging including familiar cartoon
Organic foods
characters on the packaging
• stealth marketing techniques such as embedding prod-
Many parents choose to buy organic food for their infants
ucts in the programme content in films, online and in
and children despite the extra expense; the majority of com-
video games
mercially prepared baby foods sold are now organic. Parents
do this to avoid the possible detrimental effects that pesti- The majority of foods advertised are high fat, high sugar
cide residues found in foods from non‐organic sources may and low fibre foods [123]. Packet snack foods are also high in
have on the developing organs and systems. This remains a salt. These advertisements often feature messages implying
controversial issue as food safety bodies in the UK and that these low nutrient foods are desirable or beneficial.
Europe only allow pesticides at levels that are judged not to These implications may confuse children and their parents
be harmful in commercial foods for infants and young chil- about what makes a particular food a healthy choice.
dren (0–3 years). However, advocates of organic food point Marketing experts know that toddlers and children have
out that there may be toxic effects of ingesting combinations considerable purchasing influence and successfully negoti-
of several different chemicals that may have been harmless ate purchases through ‘nag factor’ or ‘pester power’.
when tested individually. Many of these chemicals are new, Requests are often made for brand‐name products and food
having only been synthesised in the last few decades, so accounts for over half of total requests, with parents honour-
their potential cumulative effects are unknown. Recent pub- ing these 50% of the time [124]. The most requested item is
lications support this view and the advantage of an absence breakfast cereal, followed by snacks, drinks and toys.
of antibiotics in organic food [117]. Children younger than 8 years are especially vulnerable to
Studies have been published linking pesticide or synthetic these marketing strategies because they lack the cognitive
chemical exposure in children with an increased incidence of skills to understand the persuasive intent of television and
cancer [118] and impaired cognitive function [119]. In utero online advertisements [125]. Older children exposed to
exposure of the foetus to these chemicals may be the most advertising choose advertised food products significantly
damaging [120]. more often than those who are not exposed [124].
42 Healthy Eating
Several studies point towards the contribution of food comparable and, therefore, do not affect infants’ and chil-
marketing to the rising levels of childhood obesity [126]. In dren’s nutritional intakes. Many parents choose not to give
Australia and Canada, industry self‐regulation initiatives to GM food to their children, but they may not always be
restrict low nutrient food advertising to children have not aware of the extent to which GM ingredients are used in
shown any success [127, 128]. processed foods.
Genetic modification
The long‐term effects of genetic modification (GM) are as References, further reading, guidelines, support groups
yet unknown and remain controversial. The nutritional and other useful links are on the companion website:
contents of GM and non‐GM foods sold in the UK are www.wiley.com/go/shaw/paediatricdietetics-5e
3
Julie Royle
Provision of Nutrition in a Hospital Setting
Introduction of children having moderate or severe malnutrition on

admission, with a deterioration to 32% on discharge [6]. In
Legally binding hospital food standards were set by the chronic childhood diseases the contribution of frequent and
government within the National Health Service (NHS)
extended admissions combined with the impact of treatment
Standard Contract in 2014 to highlight the importance of may have a negative effect on nutritional intake and conse-
nutrition and hospital food [1]. All NHS hospitals should quently on nutritional status. In Pichler’s study the most
develop and maintain a food and drink strategy. This should nutritionally vulnerable patients were those less than 2 years
include the nutrition and hydration needs of all patients, of age, those who had been an inpatient for more than 1
healthier eating for the whole hospital community and sus- month and those who had multiple medical problems [6].
tainable procurement of food and catering services. The use of a nutrition screening tool should, in theory, provide
The provision of adequate and appropriate nutrition for a simple and rapid means of determining those at risk and those
infants, children and young people in hospital poses a signifi- who have specific dietary requirements. From this information a
cant challenge. The diverse needs of the paediatric inpatient nutritional care pathway for each individual patient can be
population with respect to age, developmental stage, ethnic- determined, implemented and monitored. There are a number
ity and religious beliefs need to be considered. Additionally, of paediatric nutrition screening tools available; these are at var-
the provision of nutrition incorporates the requirements of ying stages of validation [7–9]. There is as yet no universally
the nutritionally well, the nutritionally vulnerable and those accepted paediatric nutrition screening tool for the assessment
requiring therapeutic diets. Dietitians will be primarily of paediatric inpatients, and recent work indicates variable cor-
involved with the latter two groups. Recognising that the pro- relation with anthropometric assessment when comparing two
vision of nutritional care is multidisciplinary [2], dietitians of the tools and a need for further validation [10].
must also act in an expert advisory capacity to those involved Meticulous anthropometry identifies those who are under‐
with the provision of food to the nutritionally well. or overnourished, but may not detect those at risk of devel-
oping malnutrition. For screening to be of benefit, it must
identify those at greater risk of malnutrition and be linked to
Nutrition care planning appropriate ensuing monitoring and intervention [11]. The
implementation of nutrition support teams has been pro-
In the Western world, the prevalence of acute undernutrition posed to improve malnutrition diagnosis and nutritional
in paediatric inpatients is reported to be between 6% and care in paediatric inpatients [12].
14% [3] with acute malnutrition being highly prevalent in In summary, individual nutrition care planning is a pre-
children with an underlying disease. A nationwide study of requisite to optimum nutritional provision. This needs to be
all newly admitted children in Dutch hospitals over 3 con- undertaken in such a way that there is confidence that it can
secutive days showed a prevalence of malnutrition in 19% of identify the significant numbers who are already malnour-
children [4]. For a child with mild illness (grade 1 clinical ished, those who are at risk of becoming so and those with
conditions), nutritional status can deteriorate over the course specific requirements, while avoiding unnecessary screening
of a hospital admission [5]. In a study in the tertiary care of those who are nutritionally well and undergoing a
setting, the incidence of malnutrition was higher, with 27% relatively short length of hospital stay.

44 Provision of Nutrition in a Hospital Setting
Condition‐specific assessment tools, such as the one devel- Table 3.1 Nutrient provision guidelines.
oped for children and young people with cancer (p. 375),
may be a more appropriate future strategy to identify Snacks and
Breakfast Lunch Supper drinks
nutritional risk among paediatric inpatients [13]. Further
information about nutrition screening tools may be found in Energy % EAR 20 30 30 20
Chapter 1, p. 1. Protein % RNI 20 30 30 20
Salt % SACN 20 30 30 20
Nutritionally well inpatients recommendations
Provision of nutrition to nutritionally well inpatients should EAR, estimated average requirement; RNI, reference nutrient intake;
SACN, Scientific Advisory Committee on Nutrition.
consider:
• the age and developmental stage of the patient including
the level of support needed to eat and drink improve food and drink provision across the NHS for a
• religious and cultural beliefs healthier food experience where everyone needs to ‘eat for
• the need to provide adequate food and fluid, together good health’ [1]. The food and drinks available for nutrition-
with choice of both, to meet standard nutritional require- ally well children and young people should be designed to
ments of a healthy balanced diet meet their nutritional requirements and allow them to eat a
• food provided should be familiar, appetising and avail- healthy well‐balanced diet of familiar foods.
able to accommodate the feeding pattern of the child; a Good eating habits can be encouraged by a well‐planned
hospital admission may provide the opportunity to hospital menu and by the availability of healthy snacks,
promote aspects of healthier eating to families including fresh fruit and drinks, including water. The Eatwell
Guide (p. 31) can be used to inform menu planning to include
the right proportions of the five food groups for children over
Nutritionally well infants 2 years of age. The focus of nutritional provision from hospital
food should be on achievement of an adequate energy intake
Paediatric inpatient facilities should endeavour to support [15]. An average day’s intake from breakfast, two main meals,
mothers in breastfeeding their infants unless there is a clini- two to three snacks and milk (or a suitable alternative), should
cal reason to discontinue breastfeeding. Support should meet the estimated average requirement (EAR) for energy.
include facilities for mothers to feed in comfort, respecting The UK Department of Health Dietary Reference Values
their privacy and dignity; support, facilities and equipment [16] and Scientific Advisory Committee on Nutrition Dietary
for mothers to express breastmilk; and safe and hygienic Reference Values for Energy [17] can be used as guidelines for
storage of expressed breastmilk (EBM). Evidence is emerg- nutritional requirements. The Eating Well for 5‐11 Year Olds
ing that breastfeeding can be sustained even in infants guidelines [18] can be extrapolated to the design of hospital
requiring significant surgical intervention [14]. menus; the nutrient provision guidelines that should be
For those infants who are not breastfed and not requiring worked towards are shown in Table 3.1 [15]. The high salt con-
a specialised infant formula, ready‐to‐feed (RTF) infant tent of hospital meals is well recognised, and caterers should
milks should be available. RTF milks minimise the potential be advised to adhere to age‐specific recommendations [19].
infection risks that can result from reconstituting powdered For children, the following nutrients require special
infant milks at ward level and also ensure a constant compo- attention:
sition. The availability of a variety of both whey‐ and casein‐ Calcium: 350–500 mL milk should be available to all children
dominant milks will accommodate the personal preference and young adults; full‐fat milk for the under 2‐year‐olds
of the family. Casein‐dominant RTF formulas are less readily and semi‐skimmed for those older
available in UK hospitals, and parents can be reassured that Vitamin C: 150 mL fruit juice for all and provision of fresh
their infants’ nutritional needs will be adequately met using fruit and vegetables
the appropriate volume of a whey‐based infant milk. Iron: inclusion of red meat dishes, iron‐fortified breakfast
For infants 6 months of age and older, age‐appropriate cereals, green leafy vegetables and pulses
commercial weaning foods must be part of the catering pro- Vitamin D: provision of adequate vitamin D in the diet can be
vision. Weaning foods should include first weaning foods a challenge; supplementation may be required in long‐
such as baby rice, pureed fruits and pureed vegetables as stay patients or those at specific risk of deficiency
well as weaning foods with lumps.
A wide variety of portion sizes need to be provided to
ensure that protein and energy requirements are met across
Nutritionally well children and young people the age ranges (Table 3.2). Food should be served in a man-
ner and in an environment that encourages eating. Crockery
Food standards for NHS hospitals were recommended by and cutlery appropriate to the age ranges are required. Menu
the government in the Hospital Food Standards Panel choices should meet the needs of vegetarians and those with
Report, 2014 [1]. The panel identified required standards to specific cultural or religious beliefs (Chapter 26).
The Nutritionally Vulnerable and those Requiring Therapeutic Diets 45
Table 3.2 Food portion sizes for age.
1–2 years 3–5 years 10+ years 12+ years
Meal pattern 3 small meals and 3 snacks 3 meals, 2–3 snacks or 3 meals, 1–2 snacks or 3 meals and 2–3 snacks
plus milk milk drinks milk drinks
Protein sources, 20–40 g or 2–4 tablespoons 50–80 g or 4–8 90–120 g or 9–10 120 g or 10 tablespoons
e.g. meat, fish, or 1 small item, e.g. fish or tablespoons or 1–3 items tablespoons or 1–3 items or 2–3 items
eggs, pulses chicken goujon, egg depending on size, e.g. 2 depending on size
fish fingers, 1 egg
Dairy 20 g cheese, 1 small pot 20–30 g cheese, 2 small 30–40 g cheese, 1 50–60 g cheese, 1–2
yoghurt, 1 cup milk, 5–8 or 1 standard pot yoghurt, standard pot yoghurt, 1 standard pots yoghurt, 1
tablespoons custard 1 glass milk, 8–10 glass milk, bowl of large glass milk, bowl of
tablespoons custard custard custard
Bread and other 1
∕2–1 slice or 1∕2–1 item, e.g. 1 slice or 1 item, 6–8 2 slices or 2 items, 10–15 2–3 slices or items, 10–20
carbohydrates crumpet, bagel, 3–5 tablespoons pasta or rice, tablespoons pasta or rice, tablespoons pasta or rice
tablespoons pasta or rice, 2–3 tablespoons potato, 3–4 tablespoons potato, or 4–6 tablespoons
1–2 tablespoons potato, 3–5 6–8 tablespoons breakfast bowl of breakfast cereal potato, bowl of breakfast
tablespoons breakfast cereal cereal or 1–2 Weetabix or 2 Weetabix cereal or 2–3 Weetabix
Fruit and vegetables 5 a day 5 a day 5 a day 5 a day
portion sizes to
increase with age
1 tablespoon = 15 g.
The nutritionally vulnerable and those requiring address this issue, the World Health Organization (WHO)
therapeutic diets issued guidelines for the safe preparation, storage and han-
dling of powdered infant formula (PIF) [24] in 2007. In a hos-
For nutritionally vulnerable children and young people, the pital environment local guidelines need to be produced for
relative proportions of the food groups in The Eatwell Guide making large volumes of feeds on a daily basis.
will not be appropriate, and a greater reliance on energy‐ Powdered feeds must be prepared in a specific location away
dense foods and snacks is needed [15]. from the bedside with adequate space and equipment [25]. The
Patients in this group will require some or all of the fol- area for the preparation of specialised feeds must ensure the
lowing during the course of a hospital admission: preparation and delivery of safe feeds using an aseptic tech-
nique [26] as well as minimising airborne contamination (as
• adapted infant milks and specialised formulas
from open windows, vents). A room that is routinely used for a
• enteral feeds
function necessitating similar requirements for cleanliness and
• parenteral nutrition (Chapter 5)
equipment can provide an acceptable work area.
• nutrient‐dense meals
Where there is a high demand for specialised feeds, as in
• therapeutic diets
paediatric hospitals, a separate room for the preparation and
handling of powdered feeds is recommended. This is desig-
nated the Special Feed Unit (SFU) [20].
Adapted infant milks and specialised formulas
Infants and children requiring specialised formulas should Guidelines for the preparation of adapted infant
receive the appropriate RTF product, where available, as milks and specialised formulas
these are commercially sterile in preference to powdered
products [20]. In the absence of RTF products, many infants In the UK there are no mandatory standards for feed prepa-
and children are prescribed individualised feeds or adapted ration areas in hospital settings. Feed preparation must com-
infant milks requiring the use of a powdered formula and/ ply with the requirements of the Food Safety and Hygiene
or supplement. Powdered feed products are not sterile; they (England) Regulations 2013 [27]; this provides for the
can be intrinsically contaminated with pathogens [21]. enforcement of certain provisions of Regulation 178/2002
Powdered feeds are a food source and once reconstituted and for the food hygiene legislation. The Paediatric Specialist
become a medium for bacterial proliferation. This concern Group of the British Dietetic Association has produced best
was heightened after the increase in the notification of seri- practice guidelines, and, in conjunction with the comprehen-
ous cases and outbreaks of disease caused by Cronobacter sive guidelines from the American Dietetic Association,
spp. [22]. This problem is especially serious in vulnerable these documents provide essential reference standards for
infants, i.e. those who are preterm, low birthweight, immu- safe, effective and efficient feed making units [20, 26], which
nocompromised or in the first 2 months of life [23]. To are summarised below.
Structural design of feed making areas permit ease of cleaning and coved junctions between
floors, walls and ceilings to prevent collection of dust
The area or unit should be physically isolated from direct patient
and dirt. Light‐coloured sheen finish to reflect light and
care with access restricted to authorised personnel to minimise
increase illumination.
the risk of cross infection and tampering of feeds. It should be
• doors in the production area: self‐closing with glass obser-
designed to be easily cleaned, prevent the entrance and harbour-
vation panel.
ing of vermin and pests and operated to the highest standards of
• windows: sealed to prevent opening.
hygiene. Ideally there should be three separate areas:
• mechanical ventilation to provide a clean air supply: with tem-
• storage area: situated adjacent to the feed preparation perature (and preferably humidity) control to give opti-
area, where bulk goods are delivered, unpacked and mum working environment and control bacterial and
stored. It should be large enough to accommodate ade- dust contamination. Steam‐producing equipment such as
quate storage racks that are constructed and sited to per- dishwashers and pasteurisers should be fitted with a can-
mit segregation of commodities, stock rotation and opy and exhaust fan system to draw off steam and fumes.
effective cleaning. Items must be stored on racks or • lighting level: to allow staff to work cleanly and safely
shelves above floor level. The temperature should be without eye strain and to expose dirt and dust. Light fix-
ambient without large shifts in temperature and be tures flush with wall or ceiling.
checked daily. Where the storage is integrated within the • wash hand basins: one provided in each utility and prepa-
preparation area, the above criteria continue to apply. ration area. Hot and cold water with foot‐ or elbow‐oper-
There must be a designated area for feed storage and a ated taps. Hand soap and sanitiser as per local policies
separate area for cleaning equipment. and single‐use disposable towels or a hot air hand dryer.
• feed preparation area: contains a stainless steel work sur- • water supply: of potable quality from a rising main. The
face, a handwash sink with hand‐free taps, antibacterial Department of Health has not advised against the use of
handwash and drying facilities, storage for utensils and tap water in the preparation of feeds. Tap water should
current feeds being used and refrigerators for holding be provided from a fixed device such as a gas or electric
the prepared feeds. Utensils and currently used feed water boiler to dispense water >80 °C. If sterile water is
products should be stored in closed cupboard(s). used, it must be heated to >80 °C if it is used in the prepa-
Depending on the procedures required by the individual ration of powdered formulas.
healthcare facility, optional equipment used in the prepa-
ration room may include a pasteuriser, blast chiller and
Equipment
freezer. There should be provision for water for feed
preparation to meet national and institutional standards. All equipment and utensils used within the preparation
Adequate electric outlets with sufficient power should room should be made of stainless steel or other non‐
be provided for the equipment within the room and be absorbent material. They must be easily cleaned and
compliant with local standards. Electric outlets for the decontaminated and withstand temperatures of a commer-
refrigerators and freezers should be backed by emer- cial dishwasher. Strong and persistent biofilms can form on
gency generators in cases of power failure. Lights within surfaces such as steel, plastic, silicone and latex [28]. Proper
the unit should be enclosed and allow adequate illumi- cleaning and decontamination of the equipment used in feed
nation for accurate feed production. Clean air should be preparation is essential to avoid Cronobacter spp. biofilms
supplied through the ventilation system. Floors, walls contaminating subsequent feeds if not removed.
and ceilings should be of a material that can be easily
maintained clean. The unit must be cleaned daily and
deep cleaned on a weekly basis. All waste bins must be Large Equipment
covered, foot operated and emptied daily. • Large equipment such as shelving, tables and refrigera-
• utility area for equipment washing and administrative work: tors should be castor mounted with wheel brakes to
this can be a designated area within the preparation allow easy access for cleaning. Surfaces should be smooth
room or in larger units situated in a separate area. In the and impervious to allow easy cleaning and disinfection.
former, the processes of preparation and clean‐up must • Refrigerators that operate at a temperature between 1
be separated by time and space. Small equipment can be and 4 °C; the temperature should be monitored and
cleaned in a dishwasher or sterilised in an autoclave. recorded twice daily. Commercial refrigerators are rec-
When a dishwasher with an 82 °C final rinse cycle is ommended in an SFU.
used, a single sink for pre‐rinsing is sufficient [26]. If bot- • Blast chillers to allow rapid cooling of all feeds to <4 °C
tles are reused, a two‐ or three‐compartment sink with within 15 minutes of preparation. This is advised in
bottle‐washing brushes and a rinse nozzle is suggested. larger units as it is the most efficient way of cooling feeds.
• If maternal expressed breastmilk (MEBM) is stored and
Recommendations for the construction of feed units are as fortified in the feed preparation room, a freezer that holds
follows: the milk at −20 °C is needed. A commercial‐grade freezer
with external thermometer and alarm systems is recom-
• walls, floors and ceilings: hardwearing, impervious and mended [26]. Both the refrigerator and freezer should be
free from cracks and open joints. Smooth surfaces to self‐defrosting and have shelves that are easy to clean.
The Nutritionally Vulnerable and those Requiring Therapeutic Diets 47
• Pasteurisation equipment with a range of cycles for pow- Training should cover personal hygiene, prevention of bac-
dered feeds and MEBM (see Feed preparation) together terial and foreign matter contamination, preparation proce-
with a means of data logging for monitoring and record- dures and basic knowledge of the feed composition and
ing pasteurisation cycles. clinical indication.
• Thermal disinfection of equipment is desirable in a small Suitable protective uniforms and footwear are required.
unit and essential in a large centralised SFU. This is a During feed preparation a disposable plastic apron and a
two‐stage process achieved with a dishwasher adapted disposable hat completely covering the hair should be worn.
for an initial wash of bottles and equipment plus a high
temperature rinse that holds a temperature of >80–85 °C
Feed preparation
for 2 minutes. This ensures a surface temperature of 80 °C
for at least 15 seconds, which is an effective disinfectant.
There are three key components of safe feed preparation.
A drying cycle is useful [29].
These are appropriate ingredients, safe and accurate prepa-
• A feed delivery trolley either insulated or with ice packs
ration and limitation of microbial growth:
to ensure feeds remain at <4 °C during delivery to the
wards. • All ingredients received into a feed making area should
be of the required standards and specification. Goods
received should be checked and stock rotated according
Small Equipment to date. Opened tins or packets, e.g. from the patient’s
• Mixing and measuring equipment including jugs, meas-
home, should not be accepted into the feed making area.
ures, cutlery and whisks should be made from plastic or
If pasteurised cow’s milk is used, e.g. to reconstitute
stainless steel. They must be easily decontaminated and
powdered oral nutritional supplements, it should be
withstand a high temperature wash.
stocked according to its dated shelf life; if opened any
• Weighing equipment must be easy to clean or easy to use
unused milk should be discarded at the end of the work-
and of the appropriate accuracy for the task.
ing day. MEBM will require an agreed procedure for stor-
• Feed bottles are available in glass, polycarbonate or plas-
age and use. Any feed containing MEBM must be made
tic polythene in 50–240 mL sizes. Bottles and teats are for
up at the end of formula preparation after work surfaces
single‐use only unless they can be sterilised or decontam-
have been cleaned and fresh equipment used [20].
inated adequately [20]. Glass is a hazardous material
• Details of each feed to be prepared should be in a clearly
prone to cracking and chipping; polycarbonate shrinks if
written or printed form including the patient’s name,
autoclaved at temperatures >119 °C and the bottles
date of birth and hospital number, the weight or volume
become scratched or crazed with repeated use. Reusable
of each feed ingredient, the total fluid volume and the
bottles require washing, sanitising by heat or chemical
number and volume of each feed required. All ingredi-
means; sealing discs or caps require the same treatment.
ents should be weighed or measured accurately. Prepared
Disposable sterile polythene bottles reduce the workload
feeds should be decanted into the appropriate number
in the unit. The decision to use disposable or reusable bot-
and size of bottles and each bottle labelled. The label
tles necessitates a detailed cost–benefit analysis for each
must include details of the patient’s name, ward, feed
establishment plus a risk analysis of possible contamina-
type, preparation, date and preferably advice to refriger-
tion from inadequately cleaned bottles. Single‐use enteral
ate and discard after 24 hours.
feeding containers will be required for larger volumes of
• Limitation of microbial growth is critical to safe feed pro-
prepared or decanted RTF formulas.
vision. The UK Department of Health and the WHO rec-
ommend reconstituting PIF with previously boiled tap
Staffing water cooled to ≥70 °C for all infants (≤12 months) [20,
24]. This fresh water should come from the cold water
Feed provision is usually required every day of the year. The tap. In practice this equates to boiling 1 L of water and
number of employees will depend on the volume of work allowing it to cool for 30 minutes in a covered container.
within each facility. A sufficient number of trained staff This evidence has been used as best practice to make up
should be available to provide 7‐day cover for the SFU, formulas for special medical purposes within the SFU in
accounting for planned and unplanned leave [20]. In large the UK. Risk assessment modelling found that reconsti-
units the operational management for staff and feed prepa- tuting PIF with ≥70 °C water resulted in a >100 000‐fold
ration is usually the responsibility of the dietitian. In small reduction in risk [30]. Such made‐up feeds must be stored
areas attached to a ward, the supervision and management in the refrigerator for no longer than 24 hours from the
may be the responsibility of the nursing staff with the dieti- time of reconstitution.
tian acting in an advisory capacity. Productivity measures • For compositional reasons, several formulas for special
for SFU staff have not been published to date. medical purposes cannot be reconstituted with water at
The manager of the unit must ensure that staff are ade- ≥70 °C. These include feeds with a high fat content for
quately trained in all aspects of food safety as it relates to use in a ketogenic diet, feeds containing probiotics
feed preparation in line with the Food Safety and Hygiene and pre‐thickened feeds. For these products a local
Regulations 2013 [30]. All staff preparing feeds should main- risk assessment needs to be undertaken, and a strict
tain food hygiene qualifications in line with local policy. preparation technique put in place [20].
• The aseptic technique must be followed in the prepara- and sealed; this is costly and time consuming. In addition
tion of all feeds in healthcare settings to control the water condensation forms and remains in feeding bottles,
microbiological quality of the feed. Prior to feed prepa- where it can induce bacterial activity.
ration, work surfaces must be cleaned with a food‐ Thermal disinfection in a dishwasher is the practical pre-
grade antibacterial sanitising solution. During feed ferred option. This requires less time and the inclusion of a
preparation, there should be no admittance of allied drying cycle will ensure that all equipment is dry and ready
staff to the feed preparation room and no other for storage. To achieve thermal disinfection the water in the
activities taking place. The aseptic technique combines dishwasher should reach a minimum temperature of >80–
hand decontamination with the no touch technique to 85 °C for 2 minutes [29].
exclude contact contamination from personnel, work Chemical disinfection, e.g. hypochlorite, reduces levels of
surfaces, equipment and environment. Each healthcare harmful bacteria to acceptable levels and is satisfactory for
facility should have written guidelines for the aseptic small (non‐metallic) equipment provided recommendations
technique [20]. are followed.
• Pasteurisation can limit microbial growth. There is an
absence of evidence supporting or disputing the pasteur-
isation of specialised feeds and modified enteral feeds.
Quality assurance
Some of the larger children’s hospitals in the UK have
The primary infection prevention and control aim for feed
adopted the pasteurisation of feeds for at‐risk groups as
preparation is to prevent any infant or child from ingesting
best practice. These include preterm infants, low birth-
microorganisms that can result in illness. Each establishment
weight infants, neonates (infants <28 days of age), immu-
must have in place hazard analysis and critical control point
nocompromised children and those on powdered jejunal
(HACCP) guidelines for the preparation of powdered feeds
feeds. For these groups the feeds are heated to a tempera-
and special feeds. These should address factors that influence
ture of 67 °C for 4 minutes and rapidly cooled to a safe
and discourage microbial growth relating to the cleanliness of
temperature. Pasteurisers must be data logged to ensure
equipment, the use of the aseptic technique, storage tempera-
that correct temperatures are reached [20].
tures and the handling at ward level [31]. There is no epide-
There is evidence to support the pasteurisation of
miological evidence to support routine microbiological
donor breastmilk [20]; human milk is heated to 62.5 °C for
sampling of prepared feeds in healthcare facilities. Routine
30 minutes and is rapidly cooled to a safe temperature.
culturing is unlikely to detect intermittent contamination due
• Blast chilling is an effective method of limiting microbial
to breaches in the preparation technique, but may be helpful in
growth in prepared feeds by cooling rapidly to <4 °C
establishing trends and in evaluating root cause analysis [26].
within 15 minutes [20]. Following preparation and blast
Individual or multiple cases of infection with suspected
chilling feeds should be refrigerated at <4 °C until deliv-
food‐borne illness from potentially contaminated feeds must
ery to the wards. In small units blast chilling or pasteuri-
be investigated and managed in line with local policies.
sation may not be feasible, but systems must be in place
All premises specifically designated for feed preparation
for rapid cooling and refrigeration of prepared feeds.
in hospitals must be inspected annually (or as deemed
appropriate) by an environmental health officer.
Delivery
Procedures and documentation
Transporting reconstituted feeds can increase the risk of bac-
terial proliferation. Local guidelines must be produced for Clear written procedures and local guidelines are required
the safe transportation of prepared feeds. Equipment that for each phase of feed preparation. This includes guidelines
prevents contamination of feeds and maintains a safe tem- from personal hygiene to procedures for ordering supplies,
perature should be used to deliver feeds. If transport takes feed reconstitution and aseptic technique, instructions for
more than 30 minutes, it is recommended that feeds are pasteurisation and blast chilling, cleaning and disinfection,
transported under refrigerated conditions [24]. A cool box risk management, equipment maintenance and breakdown
with ice packs or chilled trolley is suitable transportation. procedures.
Cleaning procedures Enteral feeds
Sterilisation of small equipment (the destruction of all micro- Older children and young people at risk of malnutrition as a
organisms and their spores) is not attainable in an SFU. result of underlying disease are often dependent on nutri-
Sanitation or disinfection of small equipment can be achieved tion support in hospital and will frequently require enteral
by autoclaving, by a dishwasher or by chemical means. tube feeding. The increase in the range of sterile RTF prod-
Autoclaving, although effective, has a number of disad- ucts has reduced the need to prepare powdered enteral
vantages: equipment first has to be washed, dried, packed feeds. A few remain as powdered products, and these should
Preparation of Food for Neutropenic Patients 49
be prepared to the same standards as described for adapted as gluten‐free and low protein products should be avail-
infant milks and specialised formulas. able, and those working in the area should be familiar
Care must be taken at ward level to ensure that all prepared with the use of these products.
feeds are stored in refrigerators at <4 °C. The hanging time • Appropriate equipment for preparation of small quantities
for feeds that are administered continuously is debatable. of food must be available for the diet cooks. An industrial
The UK National Institute for Health and Care Excellence liquidiser, small pots and pans and accurate scales are all
(NICE) recommends that (non‐sterile) reconstituted feeds essential items. Freezer space is also required, as it is use-
should hang for no more than 4 hours. These are best prac- ful to keep frozen portions of special items, e.g. vegetable
tice guidelines for the prevention of healthcare‐associated casserole for low protein diets; minimal fat snacks; and
infections in the community; the guidelines can be adapted milk‐, egg‐, wheat‐ and soya‐free baked goods.
for local use in the hospital setting [32]. Sterile RTF enteral • A suitable plating system for diets must be used. Where
formulas may be hung for 24 hours if the administration sys- a bulk catering system is operated, individual contain-
tem (feed reservoir and giving set) is closed. ers, clearly labelled with relevant dietary details, are suit-
able for diet meals. If a plated system is in use, the
individual diet meals should be clearly labelled with the
Food for those at nutritional risk or requiring patient’s name and relevant dietary details.
therapeutic diets • The dietitian should always provide the diet cooks with
clear written and verbal instructions for each individual
Good food and good food services for children and young
diet being prepared. The written information should
adults are vital and are recognised by the Children’s National
include the patient’s name, age and ward, the diet
Service Framework [33]. Children on therapeutic diets espe-
required and specific instructions regarding the compo-
cially need to have the right food, at the right time, in an envi-
sition of the diet.
ronment that will encourage them to eat [34]. In contrast to
• A diet manual within the diet preparation area should
food provision in adult hospitals where menu coding is
include instructions regarding commonly requested
designed to allow patients with specific dietary requirements
modified diets and appropriate recipes. It is also useful
to choose from the main catering menu, it is preferable in large
to include details of any patients on unusual diets if they
children’s units to have a designated diet kitchen or diet bay.
are likely to be admitted. This manual should be regu-
This is supported by the need for attention to detail where food
larly updated.
items often have to be weighed very accurately; preparation of
• To ensure consistency and accuracy and a high quality
prescribed dietary food products, which demands special
product, the provision of modified diets should be moni-
cooking skills to get a good result; and prevention of cross‐con-
tored regularly. The following should all be considered:
tamination of food allergens. The exception to this is for those
the quality, freshness and suitability of the provisions,
with higher than normal requirements for protein and energy
the storage methods, the preparation of raw ingredients
where ordinary food from the main menu can be fortified or
and the presentation to the patient.
the provision of extra food at snacks or mealtimes may be suf-
ficient. Consistent use of standard recipes and ingredients in
food preparation in the main catering kitchen may render
some items from the main menu suitable for therapeutic diets. Preparation of food for neutropenic patients
Patient groups can provide helpful collaboration in attempts
Children undergoing bone marrow or haematopoietic stem
to improve the food on offer to some of the most nutritionally
cell transplantation have periods of severe immunosuppres-
at‐risk groups in hospitals [33]. For some groups of children,
sion and neutropenia. Opportunistic infection is a significant
specific initiatives have improved their food intake [13].
cause of morbidity and mortality in immunocompromised
Staff involved in the preparation of therapeutic diets must
patients. Bacterial translocation from the gastrointestinal tract
be aware of the need for accuracy, appropriate portion size
can cause significant infection and, in theory, can be decreased
for age, consistency of nutrient content and variety. For those
by reducing the potential sources of bacteria and other patho-
on a therapeutic diet, the food provided in hospital is taken
gens from food. This has been referred to as a low microbial,
as an example of what must be continued at home and must,
clean or sterile diet depending on the degree of restriction.
therefore, be accurate and appetising. It is advisable that
The evidence on the effectiveness of low microbial diets is
staff employed to prepare special modified diets have as a
extremely limited [35, 36]. In the absence of larger well‐
minimum qualification City and Guilds 706/2. In‐service
controlled studies, some have advocated the use of food safety
training of diet cooks by the dietitian is good practice to
guidelines for neutropenic patients [37]. The need to minimise
ensure that staff are kept up to date with changes to dietary
risk from food‐borne infection must, of course, be balanced
treatment. The following points must be considered when
with the need to support nutritional status in this vulnerable
providing a therapeutic diet service:
group, with the avoidance of unnecessary restrictions that
• The dietitian should specify to the caterer the standards may impact adversely on nutritional intake.
of quality and suitability of provisions for use in the diet Current consensus suggests the use of a low microbial
preparation area. Stocks of specific dietary products such diet that avoids the use of raw or lightly cooked foods,
Table 3.3 Suggested foods for a low microbial diet.
Foods to avoid Alternatives
Meats
Raw or undercooked meat and poultry Well‐cooked meat and poultry
Smoked or cured meats Vacuum‐packed cold meats such as turkey or ham
Tinned meats
Pâté Pasteurised pâté or paste in tins or jars
The Foods to avoid column will need to be realigned.
Fish
Raw, smoked or lightly cooked fish Well‐cooked fish
Eggs
Raw or soft‐cooked eggs such as home‐made mayonnaise, Hard‐boiled eggs, shop‐bought mayonnaise, mousses, sauces or
mousses, sauces or meringues meringues
Other products made with pasteurised eggs
Milk and milk products
All unpasteurised dairy products Any pasteurised milk, soya milk, Jersey milk, UHT milk and cheese
Blue‐veined cheese, e.g. stilton products
Soft ripened cheeses, e.g. brie, camembert, goat’s cheese, Vacuum‐packed pasteurised and hard cheeses such as cheddar and edam
paneer Processed cheese
Probiotics; live, active or bio products such as live yoghurts, Pasteurised plain or fruit yoghurts
probiotic supplements or drinks
Soft ice cream Commercial ice cream individually wrapped portions
Vegetables
Unpeeled vegetables including salad items Good quality vegetables that are well cooked or peeled
Damaged or overripe vegetables UHT or long‐life vegetable juices sold in cartons or jars
Unpasteurised or freshly squeezed vegetable juices or smoothies Pasteurised smoothies
Fruit
Unpeeled fruit Good quality fruit that is well cooked or peeled
Raw dried fruit such as dates or raisins and products containing UHT or long‐life fruit juices sold in cartons or jars
these such as muesli Pasteurised smoothies
Damaged or overripe fruit Tinned fruit or cooked dried fruit such as in cake, flapjacks or cereal bars
Unpasteurised or freshly squeezed fruit juices or smoothies
Herbs and condiments
Uncooked herbs, spices and pepper
Drinks
Non‐drinking water, bottled mineral or spring water, water from Cooled boiled water
wells, coolers or drinking fountains Sterilised water
Nuts
All nuts
Honey
Unpasteurised or ‘farm fresh’ honey and honeycomb Pasteurised or heat‐treated honey
Miscellaneous
Food items from ‘pick and mix’ or ‘buffet’ counters Packets should be individually wrapped or portioned on the ward only
Deli counter
Preparation of Food for Neutropenic Patients 51
reheated foods and foods known to contain higher levels of Table 3.4 High risk foods.
potential pathogens such as soft cheeses, unpasteurised Raw and undercooked meat, fish or eggs
products, nuts and buffet or deli counter foods. Practice Soft and blue‐veined cheeses
varies, but a summary of common foods to avoid is given in Pâté
Table 3.3 [38]. Live and bio yoghurts
In addition strict food hygiene practices must be used Take‐away foods
in the storage, preparation and service of food to Reheated food
Soft whip ice cream
n eutropenic patients requiring low microbial diets,

Deli and buffet foods
including:
• ensuring that all preparation surfaces and equipment are After discharge neutrophil counts will have recovered, but
clean and avoidance of wooden chopping boards and there remains a risk and a small number of high risk foods
spoons should be avoided, usually for 3–6 months. These foods are
• thorough handwashing outlined in Table 3.4 and food hygiene advice should be
• use of protective clothing for preparation and service emphasised [38].
of food
• cooking methods to ensure a core temperature of 70 °C in
References, further reading, guidelines, support groups
the final product
and other useful links are on the companion website:
• an agreed minimum delay between the food being
cooked and eaten
4
Tracey Johnson
Enteral Nutrition
Introduction Choice of feeds

Enteral nutrition is the method of supplying nutrients to Infants under 12 months
the gastrointestinal tract. Although enteral nutrition is
the term often used to describe nasogastric, gastrostomy Many infants requiring tube feeding may be given the same
and jejunal feeding, guidelines from the European feed they would otherwise be taking orally. Children who
Society for Parenteral and Enteral Nutrition (ESPEN) are breastfed may be able to continue breastmilk, and there
suggest it should also include supplementary nutrition are physiological and psychological advantages to this.
taken orally [1]. Mother’s expressed breastmilk (EBM) may be given to her
Enteral feeding is the preferred method of providing own baby or pasteurised donor breastmilk may be available.
nutrition support to children who have a functioning gastro- The principal benefits of using breastmilk are the presence of
intestinal tract, with parenteral nutrition reserved for chil- immunoglobulins, antimicrobial factors and lipase activity.
dren with severely compromised gut function. It is safer and In addition, there is a psychological benefit to the mother if
easier to administer than parenteral nutrition both in hospi- she is able to contribute to the care of her sick child by pro-
tal and at home and can be adapted to meet the individual viding breastmilk. These benefits may be outweighed by the
requirements of infants and children of all ages. possible poorer energy density of EBM, particularly if the
Some children receive their full nutritional requirements foremilk is used, which is lower in fat than the hindmilk. If
via a nasogastric, gastrostomy or jejunal tube, whereas oth- the infant fails to gain weight on breastmilk alone, intake can
ers require nutrition support to supplement poor oral intake be supplemented with a commercial human milk fortifier in
or to meet increased nutritional requirements. Enteral feed- preterm infants (p. 104) or with standard or high energy for-
ing may be short term, but for many children it can be a mulas (p. 14).
long‐term or even lifelong method of feeding. As a result Currently there are no national guidelines for whether
regimens need to be adaptable to ensure each child receives mother’s EBM to be fed to her own baby needs to be pas-
the essential nutrients they require for normal growth and teurised and individual hospitals and units have developed
development. their own local protocols, largely influenced by the cleanli-
Tube feeding children requires the expert input of a paedi- ness of the collection and handling techniques of the EBM.
atric dietitian who, along with a specialist multidisciplinary Pasteurisation destroys some of the nutritional, antimicro-
team, has the knowledge to use feeds and feeding equip- bial, probiotic, hormonal and enzymic properties [2–4] of
ment appropriate for the individual requirements and clini- EBM, so non‐pasteurisation is recommended. The evidence
cal condition of the patient. Indications for enteral feeding for the transmission of infection via EBM is limited, but
are given in Table 4.1. there are clear guidelines from the National Institute for

Choice of Feeds 53
Table 4.1 Indications for enteral feeding. retains an appropriate protein–energy ratio similar to the
commercial nutrient‐dense formulas (p. 13).
Indication Example Standard infant formulas are based on cow’s milk protein,
Inability to suck or Prematurity lactose and long chain fat. Infants with impaired gut func-
swallow Neurological impairment and tion who do not tolerate whole protein feeds frequently ben-
degenerative disorders efit from the use of hydrolysed protein or amino acid‐based
Trauma and burns feeds. Such feeds are hypoallergenic and are free of cow’s
Tumours milk protein and lactose. Many of these formulas also have a
Critically ill child requiring ventilation
proportion of the fat content as medium chain triglycerides,
Anorexia associated Cystic fibrosis which can be beneficial where there is fat malabsorption, e.g.
with chronic illness Malignancy liver disease and short bowel syndrome (p. 141). If the specific
Inflammatory bowel disease
requirements of an infant cannot be met by a commercial
Liver disease
Chronic kidney disease infant formula, it is possible to formulate a feed from sepa-
Congenital heart disease rate ingredients. These modular feeds allow a choice of pro-
Inherited metabolic disorders tein, fat and carbohydrate and give the flexibility to meet the
Increased requirements Cystic fibrosis needs of individual patients. However, they are expensive
Congenital heart disease and time consuming to prepare, and there is a greater risk of
Malabsorption syndromes (e.g. short bacterial contamination and mistakes being made during
bowel syndrome, liver disease) their preparation. It will take several days to establish a child
Trauma on a full‐strength modular feed (p. 147). Consequently, mod-
Severe burns
ular feeds should only be used if a complete feed is unsuita-
Congenital anomalies Tracheo‐oesophageal fistula ble and, in the hospital setting, should ideally be prepared in
Oesophageal atresia a dedicated special feed preparation area (p. 45).
Orofacial malformations
Primary disease Crohn’s disease
management Severe gastro‐oesophageal reflux Children aged 1–12 years (8–45 kg body weight)
Short bowel syndrome
Glycogen storage disease
Very long chain fatty acid disorders Specialist paediatric feeds are available for children 1–12
years of age or who weigh 8–45 kg. Children have differing
Refusal to eat Anorexia nervosa
Feeding aversion nutritional requirements according to their age, and conse-
quently specifically designed feeds for these age groups are
recommended to ensure provision of appropriate levels of
protein, micronutrients and electrolytes to optimise growth.
Health and Care Excellence (NICE) for the processing of Although nutritional profiles of paediatric feeds are designed
donor breastmilk, and pasteurisation is recommended to to meet the specific requirements of children, it is still impor-
protect against pathological bacterial contamination [5]. In tant to assess requirements and intakes for the individual.
2017 the Paediatric Specialist Group of the British Dietetic All feeds are categorised as Foods for Special Medical
Association (BDA) published best practice guidelines for the Purposes (FSMPs) and must comply with the EU Regulation
handling of EBM (p. 45), available from www.bda.uk.com/ (EU) 2016/128 [8], which came into effect in February 2019.
uploads/assets/a230ba75-c66a-4157-8ff6a6ca9f2eb971/201 The Regulation maintains the rules of the previous Directive
9sfuguidelines.pdf. 1999/21/EC, which lays down essential requirements on the
Standard infant formulas are suitable for enteral feeding composition of FSMPs and gives guidance for their minimum
from birth to 12 months of age for those children with nor- and maximum levels of vitamins and minerals, but has some
mal gut function and normal nutritional requirements. They additional labelling requirements and a prohibition on making
provide an energy density of 65–70 kcal (270–290 kJ)/100 mL nutrition and health claims. FSMPs intended for infants must
and meet the European Community Infant Formula now obey all rules on labelling, presentation, advertising and
Regulations [6]. An updated Regulation (EU) 2016/127 was marketing that are applicable to standard infant formulas for
adopted on 25 September 2015 and will start to apply on 22 healthy infants and must abide by the same rules on pesticides
February 2020. Follow‐on milks may also be used after 6 that apply to infant formulas and follow‐on milks.
months of age if their composition is thought to be more ben- Standard paediatric enteral feeds are based on cow’s
eficial to the child. Many infants requiring enteral feeding milk protein, but are lactose‐free, and provide three levels
will have increased nutritional requirements. Nutrient‐dense of energy density: 100 kcal (420 kJ)/100 mL, 120 kcal
infant formulas such as SMA High Energy, Infatrini and (500 kJ)/100 mL and 150 kcal (630 kJ)/100 mL. A lower
Similac High Energy are commercially available and have energy feed, 75 kcal (315 kJ)/100 mL, is also available. A
been shown to promote better growth than standard formu- range of oral nutritional supplements are available, specifi-
las with added energy supplements (glucose polymer pow- cally developed for children who may benefit from a
ders and fat emulsions) [7]. Concentrating standard infant smaller volume of feed (e.g. Fortini Compact, PaediaSure
formulas achieves a feed that is more nutrient dense and Compact) (Table 12.5). These have an energy density of
54 Enteral Nutrition
Table 4.2 Paediatric enteral feeds.
Per 100 mL
Age/weight Energy kcal (kJ) Protein (g) Fibre (g)
Nutrini Low Energy Multi Fibre (Nutricia) 1–6 years (8–20 kg) 75 (315) 2.0 0.7
Nutrini (Nutricia) 1–6 years (8–20 kg) 100 (420) 2.7 –
Nutrini Multi Fibre (Nutricia) 1–6 years (8–20 kg) 100 (420) 2.7 0.8
PaediaSure (Abbott) 1–10 years (8–30 kg) 101 (424) 2.8 –
PaediaSure Fibre (Abbott) 1–10 years (8–30 kg) 101 (424) 2.9 0.73
Frebini Original (Fresenius) 1–10 years (8–30 kg) 100 (420) 2.5 –
Frebini Original Fibre (Fresenius) 1–10 years (8–30 kg) 100 (420) 2.5 0.75
Isosource Junior Mix (Nestle) 1–10 years (8–30kg) 120 (500) 3.6 1.0
Nutrini Energy (Nutricia) 1–6 years (8–20 kg) 150 (630) 4.0 –
Nutrini Energy Multi Fibre (Nutricia) 1–6 years (8–20 kg) 150 (630) 4.0 0.8
PaediaSure Plus (Abbott) 1–10 years (8–30 kg) 151 (632) 4.2 –
PaediaSure Plus Fibre (Abbott) 1–10 years (8–30 kg) 151 (632) 4.2 1.1
Frebini Energy (Fresenius) 1–10 years (8–30 kg) 150 (630) 3.75 –
Frebini Energy Fibre (Fresenius) 1–10 years (8–30 kg) 150 (630) 3.75 1.13
Tentrini (Nutricia) 7–12 years (21–45 kg) 100 (420) 3.3 –
Tentrini Multi Fibre (Nutricia) 7–12 years (21–45 kg) 100 (420) 3.3 1.1
Tentrini Energy (Nutricia) 7–12 years (21–45 kg) 150 (630) 4.9 –
Tentrini Energy Multi Fibre (Nutricia) 7–12 years (21–45 kg) 150 (630) 4.8 1.1
240 kcal (1010 kJ)/100 mL and can also be used for nasogas- children, even if they are over 12 years of age, as they may
tric or gastrostomy feeding if there is intolerance to high provide an excessively high amount of protein. Intakes of
volume feeds or a fluid restriction. copper, chromium, molybdenum and vitamins E, C, B6 and
Most product ranges are formulated either with or with- B12 will also be high. Adult peptide‐based and amino acid‐
out added fibre. Those with fibre contain a mix of soluble based feeds can be used for children with impaired gut func-
and insoluble fibre. Constipation is common in exclusively tion, and it is also necessary in special circumstances to
tube‐fed children, particularly those with neurological employ the flexibility of a modular feed.
impairment [9]. A normal diet contains fibre, and, with an The choice of feeds for children according to their energy
improved knowledge of the role of dietary fibre, it is now requirements and gut function is given in Table 4.3.
common practice for children to receive a fibre‐containing
feed as the standard. Fibre and its fermentation products Learning points: choice of feeds
(short chain fatty acids) impact on intestinal physiology and
can prevent both constipation and diarrhoea [10–13]. The choice of feed depends on a number of factors:
Children with neurological impairment form the largest sin-
gle diagnostic group who have long‐term enteral feeding at • age of child
home [14]. This group of children frequently has low energy • weight of child
expenditure, and, if a standard feed is provided in the neces- • gastrointestinal function
sary volume to meet recommendations for protein and micro- • dietary restrictions and specific nutrient requirements
nutrients, they may show excessive weight gain. The nutritional • route of administration
needs of this group of children are discussed in Chapter 21. • prescribability and cost
The range of paediatric enteral feeds available for children
is outlined in Table 4.2.
For children with abnormal gut function, as for infants, Feed thickeners
feeds based on hydrolysed protein and amino acids are
available (Tables 8.15 and 8.16), and it is also sometimes nec- Feed thickeners are recommended by NICE as an early
essary to use a modular feed (Table 8.25). intervention to manage gastro‐oesophageal reflux (GOR) in
formula‐fed infants [15]. With or without the concurrent
Children over 12 years (>45 kg body weight) use of anti‐reflux medication, feed thickeners can help to
reduce vomiting and minimise the risk of aspiration. Feed
The requirements of children over 12 years of age may still thickeners can also be added to enteral feeds that would
be met by a paediatric feed designed for 7‐ to 12‐year‐olds; otherwise separate out when left to stand (e.g. some modu-
individual assessment is necessary. Standard adult feeds lar feeds).
may also be used and are available with energy densities of There is a wide range of commercial products that are
1 kcal (4 kJ)/mL and 1.5 kcal (6 kJ)/mL, with and without suitable for thickening enteral feeds (Table 21.2). Thickened
fibre. Some adult feeds have a protein content of 6 g/100 mL feeds may be difficult to give as a bolus via a fine bore
or more, so care should be taken when using such feeds for nasogastric tube, and pump feeding may be necessary. It is
Routes of Feed Administration 55
Table 4.3 Choice of feeds for enteral feeding according to energy requirements and gut function.
Normal gut function Impaired gut function
Infants Normal energy requirements

Breastmilk or standard/preterm infant formula Hydrolysed protein formula, e.g. Aptamil Pepti‐Junior
(Aptamil), Nutramigen LGG 1 and 2 (Mead Johnson)
Amino acid infant formula, e.g. Neocate LCP, Neocate
Syneo (Nutricia), Nutramigen PURAMINO (Mead Johnson)
Modular feed
High energy requirements
Breastmilk + BMF Infatrini Peptisorb (Nutricia)
Breastmilk + standard/preterm infant formula
Concentrated infant formula
Nutrient-dense infant formula, e.g. Infatrini (Nutricia),
SMA Pro High Energy (SMA), Similac High Energy (Abbott)
1–6 years Normal energy requirements
(8–20/30 kg) Standard paediatric enteral feed, e.g. Nutrini (Nutricia), Hydrolysed protein formula, e.g. Nutrini Peptisorb
PaediaSure (Abbott) (Nutricia), Peptamen Junior (Nestle)
± fibre Amino acid formula, e.g. Neocate Junior (Nutricia)
High energy requirements Modular feed
High energy paediatric enteral feed, e.g. Nutrini Energy Nutrini Peptisorb Energy (Nutricia)
(Nutricia), PaediaSure Plus (Abbott) Peptamen Junior Advance (Nestle)
± fibre
Low energy requirements
Low energy paediatric feed, e.g. Nutrini Low Energy Multi
Fibre (Nutricia)
6–12 years Normal energy requirements
(20–45 kg) Standard paediatric enteral feed, e.g. Tentrini (Nutricia), Hydrolysed protein formula, e.g. Peptamen Junior (Nestle)
PaediaSure (Abbott) Amino acid formula, e.g. Neocate Junior (Nutricia), E028
± fibre Extra (Nutricia)
Modular feed
High energy requirements
High energy paediatric enteral feed, e.g. Tentrini Energy Peptamen Junior Advance (Nestle)
(Nutricia), PaediaSure Plus (Abbott)
± fibre
12+ years Normal energy requirements*
(>45 kg) Standard adult enteral feed, e.g. Nutrison Standard Hydrolysed protein formula, e.g. Peptamen (Nestle),
(Nutricia), Osmolite (Abbott) Nutrison Peptisorb (Nutricia)
± fibre Amino acid feed, e.g. E028 Extra (Nutricia)
Modular feed
High energy requirements*
High energy adult enteral feed, e.g. Nutrison Energy Perative (Abbott), Vital (Abbott), Peptamen AF (Nestle)
(Nutricia), Ensure Plus (Abbott)
± fibre
BMF, breastmilk fortifier.

*Paediatric feed designed for 6–12 years old may be suitable.
also important to consider the energy contribution of some clear explanation of the procedure can help older children,
of the thickening agents. The thickeners based on modified and play therapy with the use of dolls, mannequins [17] and
starch given at a concentration of 3 g/100 mL may result in picture books has been shown to alleviate anxieties in the
an increased energy content of more than 10%. younger age group. Older children, particularly teenagers,
are naturally sensitive about their body image, and they may
Routes of feed administration be reluctant to start nasogastric feeding. Some children suc-
cessfully pass their own nasogastric tube at night and remove
Nasogastric feeding their tube in the daytime, which can be a successful way of
administering supplementary feeds without the embarrass-
Nasogastric is the most common route for enteral feeding, ment of a permanent nasogastric tube in situ.
and unless prolonged enteral nutrition is anticipated, it would Nasogastric feeding is a lifeline for many children, but it is
usually be the route of choice. However, passing a nasogastric not without its complications. Some of the more serious
tube can be distressing for both parents and children, and complications are related to dislodgement, poor placement
careful preparation is beneficial [16]. Frank discussions and a and migration of tubes. Training is required to pass a
nasogastric tube. Measures need to be in place to test place- performed by open surgery and are completed with a shorter
ment [18], and methods include measurement to predict anaesthetic time with fewer complications than an open sur-
tube insertion length [19]. gically placed gastrostomy tube. A systematic review of
Following a number of deaths, the National Patient Safety insertion techniques suggests that a laparoscopic approach is
Agency published a report suggesting that conventional associated with decreased patient morbidity when compared
methods to check tube placement were inaccurate. The com- with an endoscopic gastrostomy insertion approach [23].
mon method to aspirate the tube and test with blue litmus Ultimately, the technique chosen for gastrostomy tube place-
paper is not sensitive enough to distinguish between gastric ment will depend on individual patient’s clinical condition
and bronchial secretions; auscultation of air or observation of and surgical expertise.
gastric contents is also considered ineffective. Radiology and After about 3 months, once the tract is formed, a child can
testing of gastric aspirate with pH paper are the only accept- be fitted with a gastrostomy button that sits almost flush
able methods of confirming nasogastric tube position [20]. against the skin. This is far more discreet than the tubing asso-
Some feeds based on hydrolysed protein have been shown ciated with a conventional gastrostomy catheter and is a pop-
to have a pH < 4. There is a potential risk that a tube would ular choice, particularly with teenagers. Primary placement
test acidic if misplaced due to the feed pH rather than gastric of gastrostomy buttons for feeding tubes is also practised [24].
contents. This has led some health professionals avoiding This less common intervention often leads to some minor
the use of such feeds in children. post‐operative problems, including gastrostomy site leakage.
Long‐term nasogastric feeding in some children can cause Gastrostomy tubes and buttons require less frequent changes
inflammation and irritation to the skin where the nasogastric than nasogastric tubes. A device secured by a deflatable balloon
tube is secured to the face. Use of Duoderm or Granuflex is easier to change than one secured by an internal bumper bar
placed onto the skin can improve this. Another common prob- or disc. If a tube is inadvertently removed, it should be replaced
lem, particularly with fine bore tubes, is tube blockage. This within 6–8 hours or the tract will start to close.
may result from using the tube to administer drugs, the use of The main complications of gastrostomy feeding are wound
viscous formulas and inadequate flushing of the tube. Regular infection, leakage and excessive granulation tissue around
flushing of tubes can help to prevent this problem, and the use the exit site. Leakage of acidic gastric content can cause
of carbonated liquids can clear and prevent the build‐up of severe inflammation and skin irritation, and patients and
feed within the lumen of the tube. It may sometimes be neces- parents should be taught about skin care. Infection may
sary to replace the tube for one with a larger lumen. require treatment with topical or systemic antibiotics. There
are no evidence‐based guidelines on the use of prophylactic
antibiotics for the insertion of PEG or other gastrostomies in
children, but adult studies, including a Cochrane review,
Gastrostomy feeding
suggest a single dose of broad‐spectrum antibiotics before
PEG insertion reduces peristomal infections [25–27].
Gastrostomy is a widely used route of feeding when longer‐
Feeding can be recommenced soon after endoscopic or
term enteral nutrition is indicated [21]. Gastrostomy feeding
laparoscopic gastrostomy insertion. Early feeding is well tol-
is generally well accepted by children as it is more com
erated and reduces length of hospital stay, and resumption
fortable, obviates the need for frequent tube changes and is
of full feeding within 24 hours is safe [28, 29].
cosmetically more acceptable. Indications are not solely for
long‐term feeding; in certain situations gastrostomy feeding
is the first route of choice. This includes children with con- Feeding into the jejunum
genital abnormalities such as tracheo‐oesophageal fistula
and oesophageal atresia and children with oesophageal Indications for feeding into the jejunum include:
injuries (e.g. following the ingestion of caustic chemicals). It
has been suggested that a contraindication for gastrostomy • congenital gastrointestinal anomalies
is severe GOR. This can be exacerbated with the introduction • gastric dysmotility
of a gastrostomy tube [22], and gastrostomy placement in • severe vomiting resulting in faltering growth
such children is generally done in combination with a fun- • children at risk of aspiration
doplication (p. 152).
Placement of a nasojejunal tube and maintaining the posi-
The procedures used to place gastrostomies have signifi-
tion of the tube can be difficult. There are a number of meth-
cantly evolved over the past decades, and a device can be
ods of placement that include ‘blind’ bedside insertion,
inserted by four different methods:
weighted tubes, fluoroscopic or endoscopic placement and
• surgically, using the Stamm or open technique the use of prokinetic agents such as erythromycin [30]. The
• using the percutaneous endoscopic approach (PEG) position of the tube can be checked using pH paper. The tube
• using interventional radiology (RIG) can spontaneously re‐site into the stomach or can be inad-
• or by laparoscopic surgery vertently pulled back; weighted tubes do not seem to be of
much value in preventing this [31]. For longer‐term feeding
PEG, RIG and laparoscopic gastrostomy tube placement a surgical jejunostomy tube or a gastrojejunal tube is usually
are minimally invasive compared with a gastrostomy a more successful route for delivering nutrition support.
Methods of Feed Administration 57
When children are fed directly into the jejunum, feed Orogastric feeding
enters the intestine distal to the site of release of pancre-
atic enzymes and bile. Whole protein feeds are often tol- Orogastric feeding is principally used for feeding neonates
erated, but if malabsorption occurs, a trial period of where nasal access is not feasible or where breathing would
feeding a hydrolysed protein feed is recommended. The be compromised. The tube is passed via the mouth into the
stomach normally acts as a reservoir for food or feed, reg- stomach. If all feeds are given via the orogastric tube, it can
ulating the amount that is delivered into the small intes- be taped in place, but if the infant is taking some breast or
tine. Feed given as a bolus directly into the small intestine bottle feeds, the tube can be passed as required and removed
can cause abdominal pain, diarrhoea and dumping syn- between feeds.
drome (p. 155), resulting from rapid delivery of a hyper-
osmolar feed into the jejunum. Feeds delivered into the
jejunum should, therefore, always be given slowly by Gastrostomy coupled with oesophagostomy
continuous infusion.
Complications can include bacterial overgrowth, malab- Following surgery in infants born with tracheo‐oesophageal
sorption, bowel perforation and tube blockage. Stomach acid fistula or oesophageal atresia, it is not always possible to join
offers an antimicrobial effect that is bypassed in children the upper and lower ends of the oesophagus in continuity. If
receiving jejunal feeds. Like nasogastric and gastrostomy a surgical reconnection is delayed to a later date, the child
tubes, jejunostomy tubes need regular flushing to maintain will receive nutrition via a gastrostomy tube but is encour-
patency, and it is recommended that sterile water be used. aged to feed orally to learn normal feeding skills. Any feed
A gastrostomy device with jejunal tube (PEG‐J or G‐J tube) or food that is taken orally is collected at an oesophagostomy
may be used if access to the stomach and jejunum is required. site and is commonly referred to as a ‘sham feed’ (p. 151).
These devices can be useful in children with delayed gastric
emptying or those at risk of aspiration. Feed can be adminis-
Methods of feed administration
tered via the transgastric jejunal tube, and the gastrostomy
port can be used for aspiration, decompression or adminis- Enteral feeds can be given continuously via an enteral feed-
tration of medicines. ing pump, or as boluses, or a combination of both. A regimen
The routes of enteral feeding are shown in Figure 4.1. The should be chosen to meet the individual requirements of the
advantages and disadvantages of the routes of feed adminis- child, and in most cases it can be tailored to the most practi-
tration are given in Table 4.4. cal method of feeding to cause minimum disruption to the
child’s lifestyle and that of their family. Certain situations
will dictate a preferred feeding regimen, but a flexible
approach should be taken wherever possible. This enables
the child to maintain usual day‐to‐day activities and for the
Nasogastric
family to experience minimal disruption to their routines.
Nasoduodenal
Nasojejunal
Flexibility is especially important in children with a need for
long‐term tube feeding who, as time passes, will need a feed
Oesophagostomy
that is appropriate to their age and changing nutritional
Orogastric requirements and a regimen that is adaptable as they grow
and develop.
Continuous feeding
Generally children will tolerate a slow continuous infusion

of feed better than bolus feeds, and this method is sometimes
chosen when enteral feeding is first started. Potentially there
are fewer problems with intolerance when small feed vol-
Gastrostomy umes are infused continuously and there is a smaller time
commitment for ward staff and for parents/caregivers at
home. Mobility is affected but is minimised by the use of
portable feeding pumps, particularly for children who are
on continuous feeding for longer than 12 hours. These port-
able pumps can be carried by older children as backpacks
Jejunostomy and for infants can be carried by their parents/caregivers or
attached to a pram or pushchair. Children under 6 years are
often too small to carry a heavy backpack, yet cannot be kept
still for long periods of continuous feeding. In these children
Figure 4.1 Routes of enteral feeding. the extra hours of feeding can sometimes be achieved during
Table 4.4 Advantages and disadvantages of various routes of feed administration.
Nasogastric feeds Gastrostomy feeds Jejunostomy feeds
Advantages Advantages Advantages

• No surgical procedure required • PEG and RIG tubes can be inserted • No possibility of aspiration
• Placement can be easily taught with a short anaesthetic • No nightly insertion of tube
• Non‐invasive • No nightly insertion of tube and
non‐visible
Disadvantages Disadvantages Disadvantages

• Nausea • Nausea • Nausea
• Dislodgement of tube with • Vomiting associated with coughing • Tube blockage
coughing/vomiting and reflux • Feeling of satiety
• Vomiting associated with • Local infection • Placed under general anaesthesia
coughing/reflux • Leakage around the exit site • Increased risk of nutrient malabsorption
• Feeling of satiety causing granuloma formation • Leakage around the exit site causing
• Difficulty in inserting tube • Possibility of aspiration granuloma formation
• Irritation to the nose and throat • Tube blockage • Local infection
• Possibility of aspiration • Tube dislodgement
• Visible • Micronutrient malabsorption
PEG, percutaneous endoscopic gastrostomy; RIG, radiologically inserted gastrostomy.

Source: Reprinted with permission of Anita MacDonald.
daytime sleeps and when they are occupied with quieter Intermittent bolus feeding
activities such as watching television and tablets.
There are situations where continuous feeding is essen- Bolus tube feeding is successfully used in many children who
tial. As previously discussed, feeds given through a naso- require enteral feeding both in hospital and at home. Intermittent
jejunal tube or a feeding jejunostomy should always be boluses given 3–4 hourly throughout the day via the nasogas-
delivered by continuous infusion. Severe GOR can be man- tric or gastrostomy tube mimic a physiologically normal feed-
aged with a slow continuous infusion of feed as an adjunct ing pattern, providing cyclical surges of gastrointestinal
to anti‐reflux medication and positioning. Infants and chil- hormones that will have a trophic effect on the intestinal mucosa
dren with malabsorption will also benefit from a continu- [32]. It is more time consuming than continuous feeding, but is
ous infusion of feed. This will slow transit time and may the preferred method for many families with children requiring
improve symptoms of diarrhoea, steatorrhoea and abdom- long‐term feeding as it gives them greater freedom and mobil-
inal cramps and help to promote weight gain. In children ity and can be adapted to fit in with family mealtimes.
with protracted diarrhoea and short bowel syndrome, con- There are situations where bolus feeding is recommended:
tinuous enteral feeding with a specialised formula often
forms the basis of medical management; continuous tube • Neonates requiring small volumes may need to be given
feeding is also a treatment option for children with Crohn’s their feed by hourly bolus as the length of tubing between
disease to induce remission of disease. Infants and chil- the reservoir and child creates a ‘dead space’ holding
dren with glycogen storage disease type I require a fre- feed; this can be particularly relevant in infants fed EBM
quent supply of dietary glucose to maintain their blood as some fat can be lost by adherence to the sides of the
glucose levels within normal limits. A continuous over- burette and tubing [33]
night nasogastric infusion of glucose polymer solution or • Children who have had a surgical anti‐reflux procedure
standard feed will maintain blood sugars when children are unable to vomit; large volumes of feed from a con-
are asleep. tinuous infusion can accumulate in the stomach and
The use of nasogastric tubes for overnight feeding can remain undetected in those who have gastric stasis or
achieve optimal nutritional intake but may be associated poor gastrointestinal motility, which can lead to gastric
with risks of entanglement and displacement of tubes when rupture; bolus feeding with a gravity feeding pack will
infants and children are not closely supervised. There are prevent over‐filling of the stomach as tubes are routinely
currently no national guidelines for overnight nasogastric aspirated before each feed; and further feed will be pre-
feeding of children, but some healthcare professionals no vented from entering the stomach from the feeding
longer advocate or support overnight nasogastric feeding in chamber if the stomach is already full
the community. Development of local policies should involve • Children who frequently try to remove their nasogastric
risk assessments undertaken by the multidisciplinary team tube risk aspiration if the end of the tube is dislodged
and should always consider the medical needs of the indi- into the airways; they will benefit from bolus feeding as
vidual child. they can be constantly supervised during the feed
Enteral Feeding Equipment 59
Table 4.5 Choosing a suitable feeding regimen.
Regimen Example
Bolus top‐up feeding Congenital heart disease

Bottle feeds are not completed due to breathlessness; the remaining feed is topped up via the
nasogastric tube
Exclusive bolus feeding Long‐term feeding for children with a neurological handicap
Daytime bolus feeding can allow flexibility and mobility and provide a regimen that can fit in with
family mealtimes
Post‐fundoplication
Bolus feeding is usually the method of choice for children following a surgical anti‐reflux procedure
Sham feeding
Children who are sham fed should receive a bolus feed to coincide with oral feeds
Combination of bolus Chronic illness
and continuous feeding Children with anorexia associated with chronic illness may receive a large proportion of their nutrition
via a nasogastric or gastrostomy tube. Daytime boluses allow for a normal meal pattern, and overnight
feeding with a feeding pump reduces the time commitment at night for parents and ward staff
Malabsorption syndromes (e.g. short bowel)
Slow continuous infusion optimises absorption with additional small bolus or oral feeds to encourage
normal feeding behaviour and to stimulate trophic hormones and bile
Overnight feeding only Supplementary nutrition
Children who require enteral feeding to supplement their poor oral intake or to meet their increased
nutritional requirements are usually fed overnight only. This allows the children to maintain a normal
daytime eating pattern while still providing the nutritional support they require
Continuous feeding only Primary disease management
Gastro‐oesophageal reflux
Severe Crohn’s disease
Glycogen storage disease
• Children with an oesophagostomy who are sham fed and cosmetically acceptable. Fine bore nasogastric tubes
should preferably receive bolus feeds to coincide with are the most commonly used tubes for children. These
their oral feeds tubes have a small internal diameter (1–2 mm) and are
• The continuous delivery of enteral feeds may interfere flexible and available in polyvinyl chloride (PVC) and
with the absorption of medications; bolus feeding will polyurethane.
provide periods when medication can be given on an PVC tubes are used for short‐term enteral feeding. They
empty stomach to allow optimal absorption are for single use only and require changing every week as
the tubes stiffen over time and may cause tissue damage.
A schedule of feeding regimens is given in Table 4.5.
These tubes are least likely to be displaced and so can be
used for children who are prone to vomiting.
Enteral feeding equipment Fine bore polyurethane or silicone tubes are designed
for longer‐term nasogastric feeding and are very much
An international standard was introduced in 2016 to govern softer and more comfortable than PVC tubes. Each tube
enteral feeding devices [34]. A new global connector, ENfit, comes with a guidewire or stylet to give the tube rigidity
was introduced to replace the Luer connector system to when passed. As a general guide tubes can usually
ensure patient safety and prevent misconnection to intrave- remain in situ for 4–6 weeks, but manufacturers’ instruc-
nous lines or other types of medical device. The ENfit range tions regarding usage should always be followed. Unlike
includes tubes, syringes and giving sets. PVC tubes that are for single use, these tubes can also be
used for overnight feeding and removed during the day-
time if storage and cleaning instructions are carefully
Nasogastric feeding tubes adhered to.
When passing polyurethane tubes, there is a high risk of
There is a wide range of paediatric feeding tubes of var- tracheal intubation in children who have an impaired
ying lengths and gauges to meet the requirements of swallow or who are ventilated. In these children, PVC
children of all ages. For children, the ideal tube should tubes may be preferable despite the need for longer‐term
be of a small gauge to make the tube more comfortable feeding.
Gastrostomy devices this purpose. Generally children require smaller reservoirs

than adults, especially when using a portable system. Infants
Gastrostomy devices have evolved considerably with an requiring small volumes of feed may have their feed decanted
increasing amount of equipment entering the specialised into a burette that has a small capacity; this is principally for
paediatric market. Gastrostomy tubes, whether inserted by hospital use.
an open surgical procedure, PEG, RIG or laparoscopic Bacterial contamination is common [35, 36]; if there is a
method, are manufactured from pliable biocompatible sili- need to decant feeds, this should always be done in a
cone. PEG and RIG tubes are held in place by a crossbar, clean environment. Sterilising and reusing feed reser-
plastic disc or bumper that anchors the device to the inside voirs potentially leads to contamination and is not
of the stomach wall, preventing inadvertent removal. They recommended.
require a repeated annual procedure for change of tube, or The length of time a feed can safely be left ‘hanging’ var-
they can be replaced with a gastrostomy button once the ies. While sterile RTH feeds may be delivered over a period
tract has formed. Surgically placed gastrostomy tubes are of up to 24 hours, local policy will determine the hanging
secured by an inflated balloon, which allows easy replace- time for reconstituted feeds. Hanging time is much shorter
ment of the tube. They also have a skin‐level retention disc and is generally no longer than 4–6 hours in the hospital
preventing migration of the tube. Foley catheters are not setting.
ideal, but may be used as gastrostomy tubes; they require
strapping securely in place, as they have no retention disc
and may easily migrate into the duodenum. Children Home enteral feeding
requiring long‐term gastrostomy feeding will usually elect
to have their tube replaced by a gastrostomy button once a When a decision is made to commence enteral feeding at
tract has been established. These devices are secured within home, it is important that the parents/caregivers undergo a
the stomach by an inflated balloon, facilitating removal and training programme that will teach them to look after all
replacement, and they should last 3–6 months. Parents and aspects of feeding and equipment. Correct procedures and
carers are provided with a spare button, so it can be changed adherence to safety are paramount, and help and supervi-
immediately should it fall out. sion must be given to familiarise the parents with the neces-
sary techniques prior to hospital discharge [37]. Pictorial
teaching aids may be used to help families for whom English
Enteral feeding pumps is not their first language and those unable to read and fol-
low written guidelines [38]. It is essential to identify and
Choice of feeding pumps will depend on the requirements of liaise with community teams who will be sharing care when
individual hospitals and individual children, but there are a a child is discharged; they will have a key role in supporting
number of features that are either essential or desirable: the child and family. While it is essential that the child
receives adequate nutrition, the enteral feeding regimen
• occlusion and low battery alarms
should be planned to fit in as much as possible with the fam-
• easy to operate
ily’s lifestyle.
• durable
Home enteral feeding companies can supply both feeds
• tamper proof
and feeding equipment directly to the patient’s home. With
• easy to clean
more companies providing a home delivery service, the
• low noise
market has become competitive; they may insist on the use
• small and lightweight if designed to be portable
of their own brand of equipment and feeds, so it is important
• long battery life if designed to be portable
to ensure the child gets a suitable pump and feed that have
• accurate flow rate setting (5%–10%)
been prescribed based on clinical need.
• small flow rate increments (1 mL/hour preferable)
NICE gives recommendations for infection control
• option of bolus feeding
during enteral feeding in the community [39]. These

• good servicing backup
include guidelines for education of patients, their caregiv-
ers and healthcare personnel; preparation, storage and
Feed reservoirs administration of feeds; and care of feeding devices. They
recommend that pre‐packaged ready‐to‐use feeds should
Many sterile ready‐to‐feed paediatric formulas are now be used in p reference to feeds requiring decanting, recon-
ready to hang (RTH) and come in pre‐filled plastic bottles or stitution or dilution and that reconstituted feeds, when
flexible packs that can be connected directly to the giving set. used, should be administered over a maximum 4 hour
This reduces the need for decanting and the consequent risk period. They acknowledge that the recommendations
of bacterial contamination. If using a closed RTH system, the need to be adapted and incorporated into local practice
feed reservoir and giving set can be used for up to 24 hours guidelines.
and then discarded. The social and emotional aspects of tube feeding are often
If it is necessary to decant a feed into a reservoir, there are overlooked. Studies have shown that families experience fre-
many different flexible and rigid containers on the market for quent problems with enteral feeding at home related to sleep
Monitoring Children on Enteral Feeds 61
Table 4.6 Feed intolerance.
Symptom Cause Solution
Diarrhoea Unsuitable choice of feed in children Change to hydrolysed formula or modular feed
with impaired gut function
Fast infusion rate Slow infusion rate and increase as tolerated to provide required
nutritional intake
Intolerance of bolus feeds Frequent, smaller feeds or change feeding regimen to
continuous infusion
High feed osmolarity Build up strength of feeds and deliver by continuous infusion
Contamination of feed Use sterile commercially produced feeds wherever possible
and prepare other feeds in clean environments
Drugs (e.g. antibiotics, laxatives) Consider drugs as a cause of diarrhoea before feed is stopped
or reduced
Review drugs
Nausea and vomiting Fast infusion rate Slowly increase rate of feed infusion or give over a longer
period of time
Slow gastric emptying Correct positioning and prokinetic drugs
Psychological factors Address behavioural feeding issues
Constipation Maintain regular bowel motions with adequate fluid intakes,
fibre‐containing feeds and laxatives
Medicines given at the same time as Allow time between giving medicines and giving feeds or stop
feeds continuous feed for a short time when medicines are given
Regurgitation and Gastro‐oesophageal reflux Correct positioning, anti‐reflux drugs, feed thickener,
aspiration transpyloric feeding, fundoplication
Dislodged tubes Secure tube adequately and test position of tube regularly
Fast infusion rate Slow infusion rate
Intolerance of bolus feeds Smaller, more frequent feeds or continuous infusion
disturbance, tube dislodgement, tube blockage and difficul- administration techniques and enteral feeding devices, it should
ties with home delivery of feed and equipment [40–42]. The be possible to minimise gastrointestinal symptoms. Some causes
additional psychosocial support needs of parents providing of feed intolerance and their resolution are given in Table 4.6.
home enteral feeding to children with neurodisabilities must
also be considered [43]. Dietitians and community nurses
need to explore solutions to the common problems associ- Monitoring children on enteral feeds
ated with overnight feeding. Regular review is necessary in
Children who are commenced on enteral feeds require moni-
long‐term patients to continue to identify and minimise
toring and review. There are at present no standards for the
problems.
monitoring of children on long‐term enteral feeding at home
Enteral feeds are usually prescribed by the general practi-
in the UK.
tioner although the costs for disposable equipment may be
At the initiation of enteral feeding, goals must be set
funded by a number of different agencies. These include
with respect to the aim of the nutritional intervention, e.g.
hospital, community and dietetic budgets.
an improvement in nutritional status, control of symptoms,
palliative care and the expected growth of the child taking
Feed administration and tolerance into account their underlying clinical disorder. Regular fol-
low‐up is required to monitor both short‐term and longer‐
The way in which a feed is administered ultimately depends term progress. Anthropometry, blood tests and control of
on the clinical condition of the individual child, and there any symptoms should all be included in the monitoring
are no set rules for starting enteral feeds. Neonates may need procedure. As children gain weight and get older, their
to be started on just 0.5 mL/hour infusion rates, whereas requirements change, and follow‐up is essential to ensure
older children may tolerate rates of 100 mL/hour. In most they continue to receive adequate nutrition. The EU
cases feeds can be started at full strength with the volume Regulation on Food for Specific Groups makes recommen-
being gradually increased in stages, either at an increased dations for the composition of FSMPs including minimum
infusion rate or as a larger bolus. and maximum content of vitamins, minerals and trace ele-
Gastrointestinal symptoms are the most common complica- ments [8]. A 2016 study compared the micronutrient con-
tions of enteral feeding, but with the wide choice of feeds, tent of 62 standard adult enteral feeds with dietary
reference values (DRVs). At a volume that met normal Hepatology and Nutrition (ESPGHAN) on paediatric
energy requirements, the micronutrients supplied in these enteral nutrition also discourages liquidised foods for tube
enteral feeds were often above the DRV for a healthy popu- feeding [30]. However, parents have a statutory duty of
lation, but were within the range of the European stand- responsibility giving them the right to make fundamental
ards [44]. Although enteral feeds are formulated to be decisions in their child’s life including healthcare [49], and
nutritionally complete, it is wise to check nutritional status dietitians need to remain sensitive to the choices made by
with biochemical monitoring, particularly if tube feeding is parents.
the sole source of nutrition [45]. There will be deterioration There is evidence of clinical benefit associated with a
of vitamin content throughout the shelf life and individual blended diet. One study looked at improvement in symp-
variation in the absorption of micronutrients. Routine toms in 33 children with gagging and retching following
checks of albumin, electrolytes and haemoglobin are useful fundoplication: 73% showed symptom reduction with a 50%
as well as assessment of micronutrient status. Blood tests increase in enteral intake [50]. Another study reported better
can also be helpful in assessing response to nutritional volume tolerance and improvements in GOR and constipa-
therapy, e.g. monitoring of inflammatory markers in chil- tion when changing from commercial formula to blended
dren with active Crohn’s disease. Both hospital and com- diet [51]. Additional benefits relate to the impact on the fam-
munity staff have a role to play in monitoring a child’s ily, giving them more control and allowing them to provide
progress and helping the family cope with tube feeding at food for their child and include them in family mealtimes.
home. The needs of a young infant are quite different from Gastrostomy feeding is commonly required to provide nutri-
those of a toddler or teenager, and the individual needs of tional support to children with complex needs, many with
each child should be considered at different stages of their life‐limiting neurological disorders. It is well recognised that
development. parents of such children have a strong instinct to nurture
Regular follow‐up can be important for the family as well [52]; gastrostomy feeding with a commercial formula can be
as the child. Home enteral feeding has a big impact on family seen to medicalise feeding practices [53].
life, resulting in both psychological and practical problems A 2019 BDA policy statement [54] aims to support dieti-
that should be addressed regularly. Good communication tians to ensure patients fed with a blended diet receive
between the family, hospital and community teams is essen- effective, evidence-based, equitable and quality care. For
tial, and the family must be given a contact for professional the majority of patients a commercially prepared formula
help in the case of any emergency. remains the first choice, however, dietitians can recommend
blended diet via gastrostomy where they believe there may
be potential benefit. When families are considering a
Oral feeding skills blended diet, it is important that dietitians provide the
information necessary for them to make an informed choice,
Another important aspect of follow‐up is the encourage- including the potential risks, tailored to the individual
ment to maintain oral feeding skills. Children who miss needs of the family.
out on early experiences of taste and texture are much Blended diets can be introduced at weaning age along-
more likely to develop feeding problems [46]. Offering a side breastmilk or formula and for older children either as a
small amount of food gives children the chance to use the sole source of nutrition or in combination with commercial
lips and tongue and develop their oromotor skills while feeds. Despite not previously recommending blended diets,
experiencing a range of tastes. This is particularly impor- the BDA developed a toolkit in 2015 to enable dietitians to
tant around the time of weaning when children are often support their patients and provide practical recommenda-
more willing to accept different foods. Studies have also tions on the use of blended diet and monitoring [55]. Further
shown that in long‐term tube‐fed children, even tactile practical guidance and decision-making tools are expected
stimulation of the face and mouth alone can help re‐estab- in 2020.
lish oral feeding [47].
Learning points: blended diets

Blended diets
Internationally, blended diets for tube feeding via gastros- • Dietitians can recommend blended diet via gastrostomy
tomy are becoming popular with families and some health- when they believe there may be potential benefit
care professionals, but in the UK the practice has been less • There is some evidence of clinical benefit associated with a
widely advocated. A 2015 BDA policy statement endorsed blended diet: reduction in gagging, retching and GOR and
the use of licensed, evidence‐based sterile feeds designed improvement in constipation and diarrhoea
specifically for enteral tube feeding as best practice [48], • Dietitians have a duty of care to provide information to
due to concerns regarding safety, nutritional adequacy and support parents who choose this method of feeding and
practical issues; the administration of blended food via a ensure adequate training
gastrostomy was not recommended. Current guidance • Individual risk assessment is required
from the European Society for Paediatric Gastroenterology,
Refeeding Syndrome 63
Refeeding syndrome hysical activity. Following a review of the literature, Afzal

p
et al. [57] suggest that the initial regimen should be limited to
Refeeding syndrome is a term used to describe the metabolic 75% of requirements and increased over 3–5 days. NICE
complications that can arise following the introduction of guidelines for adult nutrition support suggest that nutri-
nutrition to a malnourished patient. Shifts in fluids and elec- tional support is introduced at no more than 50% require-
trolytes can lead to life‐threatening complications, and the ments in patients who have had little intake for more than 5
potential for refeeding syndrome should be considered days and 5–10 kcal (20–40 kJ)/kg in high risk patients; these
whenever nutritional support is instituted orally, enterally guidelines may be relevant to adolescents [62].
or parenterally [55, 57]. During the first few days of feeding, it is recommended
Circumstances that put children at highest risk include that potassium, phosphate and magnesium levels be moni-
feeding: tored at least 12 hourly. This needs to be clearly documented
in care plans and discussed with the medical and nursing
• where the child has <70%–80% weight for height
team to ensure adherence to the regimen. In some high risk
• following rapid weight loss (including in obese patients)
children, 8 hourly blood testing is recommended. Any elec-
• after prolonged intravenous fluid therapy devoid of
trolyte disturbances need to be corrected before further steps
glucose
to increase energy intake are taken, which may mean fre-
• when there has been minimal intake for 7–10 days
quent adjustment to feeding plans. Once electrolytes are sta-
• where there are pre‐existing low levels of serum potas-
ble, blood testing can be reduced to once a day.
sium, phosphate or magnesium before the introduction
Reactivation of carbohydrate‐dependent metabolic path-
of nutrition
ways increases demand for thiamin, a cofactor required for
Malnutrition causes an adaptive reduction in cellular cellular enzymatic reactions. Thiamin is a water‐soluble
activity and organ function, with fat and muscle being the vitamin and, therefore, is not stored in appreciable amounts
major sources of energy in catabolic patients. Reintroduction so that any acceleration of carbohydrate metabolism can
of glucose for energy causes a rise in insulin and an intracel- lead to thiamin deficiency. There are no recommendations
lular uptake of glucose, potassium, phosphate and magne- for thiamin supplementation in paediatric refeeding, but in
sium and fall in serum concentrations. Reactivation of adults it is recommended that high dose prophylactic thia-
carbohydrate metabolism also requires thiamin as a cofactor. min is given before refeeding and for the first 3–10 days [62,
In addition to biochemical changes, clinical signs of refeed- 63]. High dosage thiamin supplements may be given orally
ing syndrome include oedema and disturbances to cardiac if tolerated or by the intravenous or intramuscular route.
function [58] or respiratory failure [59].
Recommendations for the introduction of nutrition in
patients at risk of refeeding syndrome vary and will depend Learning points: refeeding syndrome
on clinical condition, age, degree of malnutrition, route of
feeding and local guidelines. The management of refeeding • It is important to identify children at highest risk
in the paediatric intensive care unit is described in Chapter 6 • Close biochemical monitoring is essential before and after
and in patients with anorexia nervosa in Chapter 19. introduction of feeds
Before commencing nutrition, biochemical monitoring is • There is no clear evidence‐based guideline for the safe introduc-
essential with oral or intravenous correction of any electro- tion of nutrition in all children at risk of refeeding syndrome,
lyte disturbances. There is no clear evidence‐based guideline but there is consensus about cautious introduction of feeds and
for the safe introduction of nutrition in children at risk of achievement of full requirements in a stepwise fashion
refeeding syndrome, but there is a consensus that cautious • Refeeding regimens vary between centres, different clinical
introduction of feeds, gradual increase in intake and careful conditions and for individual children
biochemical and clinical monitoring are paramount. Great • Thiamin supplementation is recommended before feeding
Ormond Street Hospital guidelines [60] recommend a start- and during the introduction of feeds
ing energy intake equivalent to the basal metabolic rate
(BMR) in young children, increasing in increments to the
estimated energy requirement (EER) based on low physical
activity [61]. For older children the guideline suggests that
refeeding should be commenced at 40 kcal (165 kJ)/kg/day
increasing by 200 kcal (840
kJ)/day up to EER for low
5
Joanne Louise Price
Parenteral Nutrition
Introduction Seventy children and 264 neonates in 74 hospitals (as well as

877 adults) were surveyed. Good practice, defined as ‘a
Although parenteral nutrition (PN) in a paediatric patient standard that the reviewer would accept from themselves
was first described in 1944 [1], it first became available for and their trainees in their institution’, was found in only 24%
general use in the 1960s. Infusion of high concentration of those neonates surveyed. Areas of concern raised included
hyperosmolar carbohydrate solutions into peripheral veins delayed commencement of PN, inconsistent nutrient provi
meant that severe phlebitis limited the length of time PN sion and inconsistent monitoring and review.
could be used. However, in 1968, Wilmore and Dudrick [2] NCEPOD stated that it would be valuable to develop a
and Dudrick et al. [3] described the provision of intravenous team approach to parenteral nutritional support, recognis
nutrients to an infant via a central venous catheter (CVC). ing that this should be a multidisciplinary exercise with
Intravenous lipids have subsequently been developed, pro sharing of expertise. The report also recommended a large‐
viding improved energy density in iso‐osmolar solutions. scale national audit of PN care in children in the UK, which
The 1970s saw the development of crystalline amino acid should be undertaken to determine the quality of PN care in
(AA) solutions, reducing the risk of anaphylaxis. More this group of patients [7].
recently development of new lipid sources has further
improved the outcome for patients requiring PN.
PN is an established therapy to which many patients of all
Nutrition support teams
ages owe their lives. It has transformed the outcome for It is generally agreed that paediatric parenteral feeding
many previously fatal paediatric conditions including feed requires considerable clinical, pharmaceutical and nursing
ing preterm infants and post‐surgical neonates with short skills, with many centres now following the principle of a
bowel syndrome [4]. multidisciplinary nutrition support team (NST) facilitating
The composition of PN continues to be researched, devel treatment with PN [6, 8].
oped and refined. As with many lifesaving procedures, PN is Good interdisciplinary communication is paramount if
not without its risks, and it is associated with fatal complica patient care is to be of the highest standard. Improvement in
tions (Table 5.1). PN should, therefore, not be used casually, outcome of PN has been demonstrated where a multidisci
but in a disciplined and organised manner in carefully plinary NST is involved [8, 9–12]. The following are core
selected patients [5, 6]. Paediatric PN should be prescribed members of the team and their roles:
only where there is an experienced multidisciplinary team of
doctors, dietitians, pharmacists and nurses contributing to • paediatric consultant – often a paediatric gastroenterolo
the provision and monitoring of the PN therapy, preferably gist oversees patient care
in an experienced paediatric centre. • paediatric surgeon – inserts feeding lines and advises
However, practice among institutions varies. A report regarding surgical management as required; many PN‐
from the National Confidential Enquiry into Patient Outcome dependent children have a surgical diagnosis and will be
and Death (NCEPOD) of a case‐based observational peer under the overall care of a paediatric surgeon
review of PN clinical practice in England, Wales and • medical specialist paediatric registrar – advises on
Northern Ireland found wide variability in practice [7]. prescription of PN and many other aspects of care

Indications and Considerations for Parenteral Nutrition in Children 65
Table 5.1 Some complications of parenteral nutrition.
Gut related Solution related Line related
Villous atrophy Over/under‐delivery of nutrients Sepsis

Decreased digestive enzyme activity Hyperglycaemia Catheter occlusion
Cholestasis Hyperlipidaemia Accidental line removal
Bacterial overgrowth/bacterial translocation Micronutrient toxicity Site infection
Fluid/electrolyte imbalance Toxic effects of non‐nutrient components
Metabolic bone disease of solutions
Growth failure
Refeeding syndrome
Cholestasis
Metabolic bone disease
• paediatric dietitian – role described below • advise regarding suitable adjustments to feeding regi
• PN pharmacist – responsible for production and check mens to enhance intake and absorption and, if necessary,
ing of solutions; advises regarding prescription when advise on changes to feeds in cases of malabsorption or
necessary feed intolerance
• PN nurse – trains caregivers and staff, coordinates • review the nutritional biochemistry and contribute to the
patient care discussion and decision making regarding nutrient
• biochemist – advises on monitoring and interpretation of intakes and adjustments to the PN
blood biochemistry and appropriate biochemical tests
A scoping exercise was carried out by the National Institute
The NST usually reviews the child’s progress at least for Health and Care Excellence (NICE) in 2017, and new
weekly, with daily reviews by some specialties as necessary. guidelines for PN in neonates were published in February
In centres where NSTs have been established, reported ben 2020. Guidelines from the European Society for Paediatric
efits include a reduction in mechanical line problems, Gastroenterology, Hepatology and Nutrition/European
reduced sepsis, fewer metabolic complications, shorter Society for Clinical Nutrition and Metabolism/European
courses of PN (due to faster transition to appropriate enteral Society for Paediatric Research/Chinese Society of Parenteral
formulas) and savings on the cost of providing PN [9–11]. and Enteral Nutrition (ESPGHAN/ESPEN/ESPR/CSPEN)
The NST produces protocols and procedures and organises have been updated and published in 2018 and will be referred
audit and reviews of the PN service; it may be monitored by to as the ESPGHAN guidelines throughout this chapter [13].
the hospital’s nutrition steering committee.
Other key members of the NST to include as required are Learning points: overview of parenteral nutrition
psychologists, speech and language therapists and play
specialists. These have a particularly important role with • PN usage is increasing and practice varies widely across
children undergoing long‐term PN. the UK
• See neonatal PN NICE guideline 154, February 2020
The role of the dietitian • Research into PN lipids has improved the outcomes for PN
• Nutrition support teams improve outcomes in patients
As a key member of the NST [12, 13], the dietitian ensures receiving PN
the child’s nutritional requirements are met in order to main • Dietitians have a key role within the NST in ensuring
tain adequate growth and development. There is also a role adequate delivery of nutrients
in the development of the child’s oral feeding skills. The
dietitian will:
• set targets for enteral and parenteral feeding and devise Indications and considerations for parenteral
a feeding plan nutrition in children
• monitor that correct volumes of prescribed enteral feeds/
PN are received Indications for PN are given in Table 5.2. This is not an
• calculate total nutrient intake and compare with the indi exhaustive list. PN is a hazardous and expensive form of
vidual’s requirements nutrition support in children and is indicated only where
• use appropriate centile charts to plot the child’s height, enteral nutrition cannot prevent or reverse growth failure.
weight and head circumference; it is imperative that The timing and duration of PN is dependent upon the child’s
inadequate growth is recognised and discussed with the nutritional reserves, expected duration of starvation and
NST at the earliest opportunity severity of illness. PN is normally built up over 2–4 days,
66 Parenteral Nutrition
Table 5.2 Indications for parenteral nutrition in children.
Intestinal failure Other common indications Patients requiring additional nutrition support
Short bowel syndrome Functional immaturity in preterm infants Trauma, burns

Surgical and gastrointestinal abnormalities, Chemotherapy (leading to acute Chronic kidney disease
e.g. gastroschisis, intestinal atresia intestinal failure) Liver disease
Necrotising enterocolitis Pancreatitis Malignant disease
Protracted diarrhoea Chronic aspiration due to gastro‐ Pre‐surgical inflammatory bowel disease
Malabsorption syndromes oesophageal reflux
Inflammatory bowel disease
Chronic pseudo‐obstruction
and, therefore, it is neither reasonable nor clinically indi and measured regularly, and the measurements recorded
cated to routinely prescribe PN for less than 5 days [14]. and plotted on centile charts to ensure appropriate growth is
Some long‐term patients will require PN for several years, maintained.
sometimes into adulthood. Long‐term PN is generally Nutritional requirements and demands vary considerably
defined as PN of >4 weeks’ duration [13]. with age and size, with critical periods during infancy and
puberty when growth is fastest. Most brain growth occurs in
the last trimester of pregnancy and the first 2 years of life.
Considerations Extra special care should be taken to avoid malnutrition and
biochemical abnormalities at this time as poor nutrition dur
Enteral nutrition ing these critical periods not only results in slowing and
PN is associated with many complications, and for this rea stunting of growth but may also permanently affect neuro
son it is widely accepted that enteral nutrition should always logical development [20, 21].
be given where possible. If the gut works, it should be used, Infants are at considerable risk due to their limited energy
even if only minimal feeds are tolerated [15]. Absence of reserves, and the commencement of PN in a small infant
luminal nutrients has been associated with atrophic changes who cannot tolerate enteral feeds is a matter of urgency.
in the gut mucosa, and it is well recognised that enteral A preterm infant weighing 1 kg has only 1% body fat and
feeding is the single most effective way of preventing many may survive for only 4 days if starved [22].
gut‐related complications. Equally adolescents are at significant risk of not achieving
Nutritionally insignificant volumes of enteral nutrition have their growth potential if nutrient requirements are not met at
been found to have a trophic effect on the gut, encouraging the onset of and during puberty.
intestinal adaptation, and have been linked to enhanced gut
motility, decreased incidence of PN‐induced cholestasis and Cholestasis and liver disease
decreased bacterial translocation [16–18]. After gastrointestinal
The pathogenesis of PN‐associated liver disease (PNALD) is
surgery, particularly that resulting in short bowel syndrome,
not completely understood. The aetiology is thought to be
intraluminal nutrients and luminal substrates are essential for
multifactorial and can progress to cirrhosis and end‐stage
optimal intestinal adaptation [19]. Initiation of enteral feeding
liver failure in some cases [23]. With better management of
is strongly recommended early in the post‐operative period.
PN and earlier weaning from PN to enteral feeding, the
Breastmilk or standard infant formulas are indicated
reported prevalence of PNALD in infants has reduced from
unless there has been previous evidence of malabsorption or
around 65% [24] to around 25% [25]. The early introduction
feed intolerance. Short frequent breastfeeds or small boluses
of enteral feeding and weaning from PN without compro
of expressed breastmilk or infant formula, as little as 1–2 mL/
mising nutritional status is the most important measure that
hour, are beneficial. If there are signs of malabsorption, a
can be taken to help reduce the risk of cholestasis [25, 26].
hydrolysed protein feed, which is also lactose‐free and has a
In preterm neonates enteral feeding may be delayed or
proportion of its fat as medium chain triglycerides, may be
withheld in order to help prevent the development of necro
indicated, e.g. Pregestimil Lipil and Pepti‐Junior. It may be
tising enterocolitis (NEC); this has been an area of much
advantageous to deliver the feed continuously via an enteral
debate. A Cochrane analysis found that delaying enteral
feeding pump to aid absorption. (More detailed manage
feeds increased the length of hospital stay, prolonged use of
ment of intestinal failure is discussed in Chapter 9.)
PN and increased the incidence of cholestasis [27]. Results of
a UK multicentre trial, ADEPT (Abnormal Doppler Enteral
Growth
Prescription Trial), concluded that ‘Early introduction of
Malnutrition in children results in impaired growth and enteral feeds in growth‐restricted preterm infants results in
development. All children on PN should be weighed earlier achievement of full enteral feeding and does not
Nutrient Requirements and Solutions 67
appear to increase the risk of NEC’ [28]. Therefore, enteral PN‐related bone disease
feeding should be introduced as early as possible, even in
Children on long‐term PN can develop a type of metabolic
preterm infants. American guidelines recommend that all
bone disease. The aetiology is multifactorial and may be
preterm babies over 1000 g are commenced on minimal feeds
related to physical inactivity, underlying disease, disordered
(preferably mother’s milk) by the second day of life [29].
vitamin D metabolism, hypocalcemia, hypercalciuria, raised
In addition to lack of enteral feeds, pathogenesis of
alkaline phosphatase and hypophosphataemia.
PNALD is associated with intrauterine growth retardation,
Regular biochemical monitoring including measurements
prematurity, immature enterohepatic circulation, underlying
of urinary calcium, plasma calcium, plasma phosphorus,
disease, number of infections/septic episodes, number of
plasma parathyroid hormone, vitamin D concentrations and
surgical procedures and number of blood transfusions [13,
serum alkaline phosphatase activity along with dual‐energy
30, 31]. PN solutions themselves may have a role to play in
X‐ray absorptiometry (DEXA) scanning is recommended to
the development of liver disease; lipid emulsions have been
evaluate these children [13, 34]. Referral to an endocrine/
implicated and overfeeding of glucose has been associated
metabolic specialist may be necessary in cases of concern.
with hepatic steatosis [25, 26, 31]. High risk for PNALD is
also associated with PN dependency from a young age, very
short bowel length and prolonged PN duration.
Oral hypersensitivity
Cyclical, rather than continuous, PN and cycling of lipid Oral hypersensitivity occurs when the oral route is not estab
in particular and restricting lipid to certain nights of the lished from birth, or when there is a delayed introduction of
week afford some protection to the liver and are common solids, or when the oral route is not used for lengthy periods
practice in patients on long‐term PN, particularly those who of time. Lack of oral stimulation together with unpleasant
have PN at home. This usually involves giving the PN over oral procedures/experiences such as intubations, suction,
a shorter period allowing some hours off. There are obvious vomiting, choking and gastro‐oesophageal reflux may lead
implications to energy intake and tolerance of solutions, and to long‐term feeding problems. Steps to prevent oral feeding
this should be monitored carefully. Due to the implications aversion will help progress onto enteral feeding and subse
on growth, particularly where lipid is restricted, cycling quent reduction in PN.
should only be used in long‐term stable patients who have Early involvement of a specialist speech and language ther
an experienced NST looking after them. Effective treatment apist to advise regarding oral desensitisation is recommended,
and prevention of recurrent sepsis through translocation of particularly in cases of refusal to feed or distress during feed
bacteria across the gastrointestinal wall and via line infec ing. A play specialist can work with children around oral
tions is also known to be a significant factor in the avoidance desensitisation using messy play and play involving food. In
of PNALD [31, 32]. Other therapies include the use of urso addition to these specialist techniques, early and sustained
deoxycholic acid, a synthetic bile acid [33]. Cases of PNALD oral feeding when safe to do so, use of dummies (pacifiers),
that do not improve should be referred to a supraregional sips and tastes should always be employed (where safe to do
liver unit for assessment at the earliest opportunity [13]. so) to maintain oral function, especially in infancy.
In summary, increased risk of developing PNALD is
found:
Learning points: considerations in children on PN
• in premature infants
• in those with short bowel syndrome • Their continuing growth with key stages of development
• where there has been long‐term absence of enteral feeds • They have immature liver and bowel function with
• where there is loss of enterohepatic cycling of bile salts inefficient enzyme production
post‐operatively or due to obstruction • They are susceptible to PNALD
• where there are repeated septic episodes • Their immature immune system leads to increased
• where there is intestinal bacterial overgrowth susceptibility to infection
• They are vulnerable to central venous line infection
• There is a high risk of cross‐contamination due to inability
to self‐care
Learning points: prevention of PNALD • Oral feeding is often not established, so food aversion
common
• giving early enteral feeding, even if only minimal • There may be delayed weaning from PN due to an inability
• giving some oral feeds if possible to feed orally
• avoidance of line sepsis by rigorous line care
• prompt treatment of sepsis
• cyclical PN, particularly lipid
Nutrient requirements and solutions
• reduction of the dose of lipid
• use of ursodeoxycholic acid Recommended requirements vary and tend to be based on
• use of lipid solutions containing ω3 PUFA in some groups clinical experience [6, 8, 20, 34, 35]. The ESPGHAN guide
(Table 5.5) lines published in 2018 [13] are the most recent regarding
paediatric PN at the time of writing.
Fluid and electrolytes Electrolyte requirements vary with age, clinical condition

and blood biochemistry. Electrolyte solutions are usually
Infants have immature organ systems and require high added to PN in response to each individual child’s blood
volumes of fluid in order to excrete electrolytes sufficiently. biochemistry.
Young children are physiologically unable to concentrate The above requirements are a guide and are for use in sta
urine and conserve fluid as effectively as adults. Maximum ble infants and children on PN. Close daily monitoring of
urine concentrations are 550 mOsm/L in preterm infants and electrolytes should be undertaken and input adjusted
700 mOsm/L in term infants compared with 1200 mOsm/L accordingly, particularly in the first 5 days.
in adults [36]. Electrolyte requirements are often higher, but Due to very tight homeostatic mechanisms, sodium deple
dehydration and metabolic acidosis can occur if these are tion is not always reflected in blood biochemistry. Sodium
given without adequate fluid. Care should always be taken depletion can be a direct cause of poor growth. Monitoring
that fluid requirements are met. of urinary sodium excretion to assess total body sodium is
Age, size, fluid balance, the environment and clinical condi useful, especially in cases of high sodium losses such as high
tions are all factors affecting fluid requirements. Recom output fistula or cystic fibrosis. A low (<20 mmol/L) urinary
mendations are given in Table 5.3. Cardiac impairment, renal sodium concentration indicates the need for increased
disease and respiratory insufficiency are examples of condi enteral/parenteral sodium provision.
tions that may limit fluid volumes, whereas high fluid losses The available fluid volume for PN may influence the
due to diarrhoea, high output fistula/stoma and fever may all choice of nutrient solutions and the route of delivery. Some
increase fluid needs. Also, additional fluid may be needed if of the available fluid for PN may be taken up by medica
radiant heaters/phototherapy is used. tions. If concentrated PN solutions are needed to provide
adequate nutrition (due to fluid restrictions), then the
peripheral route for delivering the solutions may be con
Table 5.3 Summary of parenteral fluid and electrolyte requirements traindicated as there is a risk that they will cause thrombo
for children. phlebitis. Children who are severely fluid restricted will
only receive adequate nutrition with concentrated PN deliv
Fluid Na K Cl ered via a CVC.
(mL/kg/ (mmol/ (mmol/ (mmol/
Age/weight day) kg/day) kg/day) kg/day)
Macronutrients
<1500 g 160–180 2.0–5 1.0–2.0 2–5
>1500 g 140–160 2.0–5.0 1.0–3.0 2–5 Recommendations for macronutrient intakes are summa
Preterm to 140–160 2.0–5.0 1.5–5.0 2–5 rised in Table 5.4.
2 months
2 months 120–150 2.0–3.0 1.0–3.0 2–3 Energy
to 1 year
1–2 years 80–120 1.0–3.0 1.0–3.0 2–4 Diet‐induced thermogenesis reflects the amount of energy
3–5 years 80–100 1.0–3.0 1.0–3.0 2–4 needed for food digestion and absorption and usually
6–12 years 60–80 1.0–3.0 1.0–3.0 2–4 accounts for about 10%–20% of daily energy needs. Generally
13–18 years 50–70 1.0–3.0 1.0–3.0 2–4
parenteral energy requirements are approximately 10%–20%
less than enteral requirements for this reason.
Source: Adapted from [13]. Reproduced with permission of Elsevier. If energy intakes are inadequate, protein accretion falls
and dietary/intravenous protein will be metabolised for
Table 5.4 Summary of recommended daily intakes of macronutrients from PN.
Energy Amino acids Lipid CHO
Age (kcal/kg) Age (g/kg) Age (g/kg) Body weight (kg) (g/kg)
Preterm 90–120 Preterm 1.5–3.5 Preterm 3–4 Up to 3 Up to 17.3

0–1 year 75–85 Term 1.5–3.0 Infants 3–4 3–10 8.6–14
1–7 years 65–75 1 month to 3 years 1.0–2.5 Older children 1–18 years 2–3 11–30 4.3–8.6
7–12 years 55–65 3–12 years 1.0–2.0 31–45 4.3–5.8
12–18 years 30–55 3–18 years 1.0–2.0 >45 2.9–4.3
CHO, carbohydrate. 1 kcal = 4.18 kJ.

Source: Adapted from [13]. Reproduced with permission of Elsevier.
energy. The child may become catabolic using body tissue Lipid
protein stores for fuel. This results in linear growth failure.
Adequate energy intake will promote weight gain, but will Lipid preparations provide a concentrated source of
not always promote linear growth in the absence of adequate energy in an isotonic solution: 2 kcal (8 kJ)/mL in a 20% lipid
protein. solution compared with only 0.8 kcal (3 kJ)/mL in a 20% car
Many well infants and children will achieve their expected bohydrate solution. Lipid emulsions normally contribute
growth rate if the energy intakes shown in Table 5.4 are pro 25%–40% of non‐protein energy. Lipid emulsion, unlike high
vided. An appropriate gain in weight for the age, sex and concentration dextrose solutions, can be given via a periph
size of the individual child, taking the clinical condition into eral vein and helps in the provision of sufficient energy for
consideration, is likely to indicate that the prescription is growth, avoiding the complications associated with central
adequate. venous access, and may prolong the life of peripheral lines in
In the disease state these requirements will vary, and infants [46].
research suggests that actual energy requirements for many Intravenous lipid particles in solution resemble endoge
children are less than originally thought [13, 37]. It is recom nously produced chylomicrons in terms of size and are
mended that energy intakes should be adapted for those hydrolysed by lipoprotein lipase. Intravenous lipids pro
disease states found to increase resting energy expenditure, vide essential fatty acids (EFA) and improve net nitrogen
e.g. head injury, burn injury, pulmonary and cardiac disease balance compared with glucose alone as a source of non‐
[13]. Also, extremely low birthweight neonates requiring protein energy [27]. Current ESPGHAN guidelines [13]
ventilation have been found to have significantly increased specify that a minimum linoleic acid intake of 0.25 g/kg/
rates of energy expenditure [38]. Uncomplicated surgery day should be given to preterm infants and 0.1 g/kg/day to
does not significantly increase energy requirements [39, 40]. term infants and older children to prevent EFA deficiency.
Achievement of adequate growth is a significant outcome In premature infants, due to low stores, EFA deficiency can
target in the nutrition support of children. Growth presents occur within 72 hours of birth [47] and in term infants just
a significant energy burden; this will vary with age and is a few days.
highest in the neonatal period with 35% of energy being Intravenous lipid emulsions available in the UK that are
used for growth alone [41]. However, in the very sick child, considered safe for use in paediatric PN are given in Table 5.5.
the catabolic process inhibits growth, thereby temporarily All solutions contain glycerol and phospholipids and are
reducing this burden. available as 10% and 20% emulsions.
Previous recommendations for energy did not account Higher concentration emulsions (20% or more) are advan
for this [42]. Recent research has suggested that critically tageous where there is fluid restriction and they also deliver
ill children in the catabolic phase have better outcomes, less phospholipid per gram of triglyceride, leading to more
including reduced length of stay and infection rate, if PN normal plasma phospholipid and cholesterol levels [48]. In
is withheld in the initial days [43]. However, due to the children it is recommended that 20% or higher concentra
heterogenicity of the population studied, this research tions of lipid emulsions are used due to the higher phospho
cannot be extrapolated to individuals. It is the job of the lipid–triglyceride ratio found in 10% emulsions [13].
clinical team to prescribe PN according to the child’s indi Lipid emulsions currently used are either based on long
vidual needs. Guidelines suggest that in the acute phase, chain triglycerides (LCT) or long chain and medium chain
intakes should be limited [13]. Further recommendations triglycerides (MCT) combined. Both LCT and MCT/LCT
specifically relating to neonates can be found elsewhere, solutions are considered safe to use in paediatric practice.
www.nice.org.uk/guidance/NG154 [44, 45]. Soya oil emulsions have been available for many years and
Children on stable long‐term PN, particularly if approach were the first commercially available lipid solutions; they
ing the adolescent growth phase, should have individual are still commonly used. There have been some concerns
energy and protein requirements calculated to maintain ade over the effect of the highly polyunsaturated, unphysiologi
quate growth. This may require an extrapolation of enteral cal fatty acid supply from soybean oil. The development of
energy requirements based on 80%–90% of the estimated PNALD is possibly associated with the composition of soy
average requirement (EAR) for their age. bean oil‐based lipid emulsion. There is mounting evidence
Equations for calculation of resting energy expenditure that the pro‐inflammatory ω6 polyunsaturated fatty acids
are available (p. 87) and may also be used along with die (PUFA) most prevalent in soybean oil, along with the low
tetic principles of calculating energy requirements. Where ratio of antioxidants in the form of vitamin E (tocopherols),
dietetic estimations are usually needed for those children may in part have a role in the onset of liver injury [32].
with genetic reasons for growth failure, disability or meta Numerous ‘composite’ lipid emulsions have been devel
bolic disorders, calculated PN requirements for energy oped over recent years, and ongoing research is extremely
would normally be adjusted (usually downwards by active in this area. A recently published systematic review
5%–10%) due to bypassing enteral absorption and its [49] recommends that larger high quality trials are required to
associated losses. evaluate the effects of each type of lipid emulsion available.
In all children on PN, it is essential to monitor closely to Olive oil‐containing emulsions may produce more physio
ensure appropriate growth is achieved without adverse bio logical levels of linoleic and oleic acid, better antioxidant
chemical consequences. status and lower cholesterol levels [49].
Table 5.5 20% lipid emulsions*.
Energy Soya oil Olive Fish oil MCT α‐Tocopherol

Name Manufacturer Composition TG (g/L) (kcal/mL) (g/L) oil (g/L) (g/L) (g/L) (mg/L)
Intralipid Fresenius Kabi Soya 200 2 200 0 0 0 240

ClinOleic Baxter 80% olive 200 2 40 160 0 0 No data
20% soya
Lipofundin B Braun 50% soya 200 2 100 0 0 100 170 ± 40
MCT/LCT 50% coconut
SMOF Fresenius Kabi 30% soya 200 2 60 50 30 60 169–225
30% coconut
25% olive
15% fish
Lipidem B Braun 40% soya 200 2 80 0 20 100 190 ± 30
50% coconut
10% fish
Omegaven† Fresenius Kabi 100% fish 200 2 0 0 200 0 130–296
TG, triglycerides; MCT, medium chain triglycerides; LCT, long chain triglycerides. 1 kcal = 1.48 kJ.
*Some 10% emulsions are available, but are not recommended due to the high phospholipid–triglyceride ratio [13].
†
Omegaven is to be used as a supplement, not a complete source of lipid; not licensed in Europe.
Coconut oil‐containing emulsions (MCT) have the advantage and should be considered alongside other interventions to pre
of carnitine‐independent uptake by the mitochondria and, vent PNALD. The guidance also suggests that paediatric PN
therefore, have a more rapid clearance from the plasma after for greater than a few days should include a lipid emulsion
infusion. Solutions with 50% MCT have been used in containing a combination of oils (with or without fish oils) [13].
paediatric PN for many years. MCT solutions contain
It is important to note that in some children the biochemi
approximately 50% less EFA than LCT solutions alone, yet cal measurement of cholestasis does not detect the degree of
measured plasma EFA and their derivatives (linoleic and PN‐associated liver fibrosis. There are reports that fibrosis
alpha linolenic acid) were similar compared with LCT seen on liver biopsy may persist despite the improved liver
solutions [49–51]. function tests after using these products [57, 58].
Fish oil‐containing emulsions contain a significant amount Serum lipid levels should be monitored to ensure adequate
of anti‐inflammatory ω3 PUFA. These are probably now the clearance and, hence, utilisation [59]. Clearance of lipids
most widely adopted and routinely used combinant lipids from the plasma is limited by the rate of activity of lipopro
used in paediatric intestinal failure. tein lipase. The amount of fat infused should be adapted
SMOF (Fresenius Kabi) provides just 30% and Lipedem (B to the lipid oxidation capacity, approximately 3–4 g/kg/day
Braun) 40% of the EFA contained in Intralipid due to the [5, 13]. Hyperlipidaemia will result if the enzyme is saturated
relatively lower soya oil content of these solutions. EFA pro by excessive doses of fat or by rapid infusion [60]. Gradually
vision will be adequate when these are given at normal vol increasing the volume of the lipid emulsion by 1 g/kg/day
umes but may become inadequate if lipid intake is restricted. over 3–4 days and maintaining a steady rate of infusion help
There have been two randomised control trials to compare prevent possible hypertriglyceridaemia. Tolerance of lipid
the short‐term physiological effects of lipid preparations emulsions has been found to be improved if given continu
containing soya oil versus fish oil both in preterm and very ously in preterm infants [61], although it is usual practice to
low birthweight infants [25, 26]. There were no significant give 4 hours off the infusion per 24 hours to allow all admin
differences found in outcomes in this group of patients com istered fat to clear the circulation before the next infusion
pared with those using soya oil‐dominant lipid solutions. begins. Serum lipids should be monitored as the volume of
In children where cholestasis is already present, there fat given increases and should always be taken 4 hours after
have been several paediatric case reports citing improve the infusion is completed. Peak levels of triglyceride and free
ments in liver function tests and a drop in conjugated biliru fatty acids normally occur towards the end of the infusion,
bin and reversal of PNALD when patients were switched returning to fasting levels 2–4 hours later. Once stable,
from soya oil solutions to fish oil‐containing solutions [52– weekly monitoring is likely to be sufficient.
55]. An emulsion of fish oils alone (Omegaven) has been In malnourished children, it is good practice to assess
used temporarily as monotherapy, but due to risks of EFA baseline serum lipids prior to starting PN as children who
deficiency, it cannot be recommended for long‐term use (>15 have failed to thrive or lost weight due to suboptimal intake
days). It can be used as a ‘rescue therapy’ in PNALD [56]. frequently have raised triglyceride levels that return to nor
New guidance suggests that solutions containing a combi mal when sufficient energy is provided. Restricting lipid
nation of oils including fish oil may slow or reverse cholestasis and, therefore, energy would not be beneficial in this case.
Table 5.6 Amino acid solutions.
Name Manufacturer Total AA (g/L) Cysteine (g/L) Tyrosine (g/L) Taurine (g/L) Comment
Primene (10%) Baxter 100 1.89 0.45 0.6 For neonatal and infant PN
Vaminolact Fresenius Kabi 65 1.0 0.5 0.3 For neonatal and infant PN
AA, amino acids.
A reduced lipid dose may be indicated for children with a Amino acids
marked risk of hyperlipidaemia, e.g. low birthweight infants,
sepsis and catabolism. Reduction of the dosage of lipid emul Crystalline l‐AA solutions are used as the nitrogen source
sion can be considered if serum or plasma triglyceride con for PN. Despite routine use of PN, surprisingly few clinical
centrations during infusion exceed 3 mmol/L (265 mg/dL) efficacy data are available to guide total or specific AA dos
in infants or 4.5 mmol/L (400 mg/dL) in older children [13]. ing in paediatric (and adult) patients.
EFA deficiency can be prevented with as little as 0.5–1.0 g/ Commercially available mixed AA formulations provide
kg LCT/day [13, 62], although at this level of lipid intake both essential and non‐essential AA. All provide the nine
there is likely to be suboptimal energy intake. As discussed essential AA (histidine, isoleucine, leucine, lysine, methionine,
above, reduction in lipid intake may improve abnormal liver phenylalanine, threonine, tryptophan and valine). They also
function; however, this cannot be sustained over a long period contain varying amounts of classically non‐essential AA
due to suboptimal energy provision and a long‐term effect on that may become conditionally essential under certain cir
growth. If reducing intake for any reason, including treating cumstances. In children arginine, cysteine, glycine, proline,
PNALD, the source of lipid is an important consideration. taurine, glutamine and tyrosine may be conditionally
Some intravenous medication may be given in fat emul essential [13].
sions, e.g. the sedative propofol or the antifungal ampho The products designed for infants and children are
tericin. Consideration should be made of the fat (and, Vaminolact, which is based on the AA profile of breastmilk,
therefore, energy) content of this. and Primene, which is based on the profile of cord blood
(Table 5.6). The ideal AA profile for PN solutions for infants
α‐Tocopherol and children is still unclear. A solution that contains insuffi
cient quantities of essential AAs will inhibit protein synthe
Vitamin E (α‐tocopherol) is the most important lipid‐soluble
sis and may limit growth [64–66].
antioxidant; it helps prevent tissue damage by free radicals
Estimates of protein requirements are often based on 10%–
produced from peroxidation of the PUFA within parenteral
20% of the total energy intake (Table 5.4). All nitrogen can be
lipid solutions [63]. Most composite parenteral lipid solu
converted to energy (via the Krebs cycle), and where inade
tions have α‐tocopherol present in adequate amounts for this
quate energy is provided (from fat and carbohydrate), the
reason (Table 5.5). When these solutions are given to infants
child may become hypoproteinaemic as nitrogen is used for
and children <11 years old, the total vitamin E intake should
energy. The child subsequently will not grow. Sufficient
not exceed 11 mg/day [13].
energy intake is 30–40 kcal (125–165 kJ)/g AA or 250 kcal
(1.05 MJ)/g nitrogen [66], although in preterm infants this
ratio may indeed be less: 150–200 kcal (630–835 kJ)/g nitro
Learning points: lipid solutions gen [44].
Guidelines [13] are based on amounts required to main
• MCT, fish and olive oil solutions should be considered in all tain nitrogen balance and growth. While it is difficult to
patients on long‐term PN assess if nitrogen provision is adequate, it is generally agreed
• Fish oil may be beneficial as part of a treatment strategy in that inadequate nitrogen intake is reflected by a low plasma
the prevention or treatment of PNALD urea level and poor linear growth. (A high plasma urea level
• Pure soya oil solutions are not recommended in paediatric is more likely to be attributable to dehydration than over‐
PN provision of nitrogen.)
• 10% solutions not recommended due to the high ratio of
phospholipids to triglycerides
• 20% solutions most widely available ≡ 200 g TG/1000 mL
(20 kcal [85 kJ]/100 mL) Glutamine
• Lipids should provide 25%–40% of non‐protein energy Endogenous biosynthesis of glutamine may be insufficient
• 0.5–1 g/kg/day LCT is required to prevent EFA deficiency for tissue needs in states of metabolic stress. Trials in adults
• Solutions with lower LCT content will be lower in EFAs have suggested that glutamine supplementation improves
• Vitamin E is protective against PNALD, but intake should clinical outcomes in critically ill adults [67]. It has been sug
not exceed 11 mg/day [13] gested that glutamine supplementation may benefit preterm
infants, particularly very low birthweight infants. However, a
systematic review in 2016 concluded that glutamine supple hyperglycaemia, hepatic steatosis, excessive carbon dioxide
mentation does not have a statistically significant effect on production and impaired protein metabolism [44]. Insulin
morbidity or mortality [68]. Currently, there is insufficient resistance may occur in some situations, e.g. steroid use,
evidence to support the routine supplementation of glu very low birthweight, sepsis, trauma and stress. This is a
tamine in preterm infants, and there is no evidence for its rou protective mechanism to relieve the liver of excessive sub
tine use in PN in children under 2 years [13]. strates. In this acute phase the ESPGHAN guidelines recom
mended that glucose infusion rates should be limited in
order to prevent hyperglycaemia [13].
Carnitine
Glucose infusion should always be initiated gradually,
Carnitine is a nitrogen‐based compound and plays a role increasing over 3–4 days to maximum infusion rates. Rates
in the beta‐oxidation of long chain fatty acids and facili of glucose oxidation vary significantly with age and clinical
tates their transport across the mitochondrial membrane in status. In stable situations (post‐acute phase), it is recom
the form of carnitine esters. Carnitine is present in breast mended in term neonates and children up to 2 years of age
milk and formula feeds, but current PN formulations do that glucose intake should not exceed 14 g/kg/day [13].
not contain it. Carnitine can usually be synthesised in the Infusion rates exceeding glucose oxidative capacity result in
liver from lysine and methionine, and the ability to synthe conversion of carbohydrate to fatty acids and can consume
sise it is age dependent [69]. Non‐supplemented parenter up to 15% of the available energy from carbohydrate [71, 72].
ally fed infants have very low tissue carnitine levels, and In cyclical PN the increased rate of glucose infusion may
relative carnitine deficiency may impair fatty acid oxida exceed glucose oxidation rate so the maximal infusion rate
tion [70]. It is recommended that carnitine supplementa should not exceed 10 mg/kg/min [13].
tion (20–30 mg/kg/day) be considered on an individual
basis in premature infants or those on exclusive PN for
more than 4 weeks [13]. Learning points: carbohydrate
• Specific guidance for the management of the first days of

Learning points: amino acid solutions PN during the acute phase is described in the ESPGHAN
guidelines [13]
• Amino acid profiles are based on cord blood or breastmilk • In stable children carbohydrate should make up 60%–70%
so they are not necessarily the ideal profile for growing of the non‐protein energy provision
children • In stable children maximum infusion rates of 10 mg/kg/min
• They aim to provide 10%–20% of energy from protein glucose should not be exceeded
• Protein in PN is normally expressed as nitrogen (N) or • Solutions given cyclically should be ramped up and down
amino acids (AA) during the initial and final 2 hours of the infusion to pre-
1 g N ≡ 7.5 g AA ≡ 6.25 g protein vent hyperglycaemia and hypoglycaemia (Table 5.10)
• In order to ensure efficient protein utilisation and tissue
accretion, sufficient energy should be given alongside nitro-
gen ≡ 250 kcal (1.05 MJ)/g N
• Low plasma urea levels, particularly in preterm infants,
Micronutrients
may indicate inadequate nitrogen provision
A summary of reasonable intakes of micronutrients for pae
diatric PN can be found in Tables 5.7 and 5.8. These are guide
lines and should be used in conjunction with the document
Carbohydrate from which they are taken [13]. Requirements for intrave
nous vitamins in infants and children remain unclear. The
The major source of non‐protein calories in PN is d‐glucose last major publication on parenteral vitamin requirements in
(dextrose). Carbohydrate normally provides 60%–70% of the children was in 1988 [73]. A Cochrane review [74] in prema
total non‐protein energy intake. Glucose is an essential fuel ture infants <32 weeks’ gestation found an association
for infants and is the most important substrate for brain cell between supply of vitamin A and a reduction in death or oxy
metabolism; a continuous supply is essential for normal neu gen requirement at 1 month of age and of oxygen require
rological function. For this reason, there are minimal rates of ment at 38 weeks’ postmenstrual age. Current knowledge is
infusion that should be maintained in the absence of enteral based on the historical use of available vitamin and mineral
feeding. solutions and the apparent lack of deficiencies/complica
When the fluid volume is limited, higher concentrations tions associated with this. Optimal requirements in children
(>12%) of dextrose solutions are required to meet energy have not been determined, and there has been little published
requirements; this can only be achieved via a CVC. research on this topic in the last 30 years.
In the acute post‐operative or infectious phase, excessive Following current guidelines appears to maintain blood
intravenous glucose administration is more likely to lead to levels within acceptable ranges for infants and children and
Table 5.7 Vitamin solutions.
Suggested reasonable intakes

Water-soluble Fat-soluble Source: adapted from [13]
Solvito Vitlipid infant*

(Fresenius Kabi) (Fresenius Kabi) MVI paediatric Children
Vitamin per vial (10 mL) per vial (10 mL) (Hospira) Preterm (/kg/day) Infants (/kg/day) (per day)
Dose 1 mL/kg/day 10 mL/day 5 mL/day

Vitamin A (μg) 0 690 (2300 IU) 690 (2300 IU) 227–455 150–300 150 (500 IU)
(700–1500 IU) (500–1000 IU)
Vitamin D (μg) 0 10 (400 IU) 10 (400 IU) 2–10 (80–400 IU) 10 (400 IU) 10–15
(dose/day) (400–600 IU)
Vitamin E** 0 7 (7 IU) 7 (7 IU) 2.8–3.5 (2.8–3.5 IU) 2.8–3.5 (max 11 (max)
DL‐α‐tocopherol 11 mg/day)
acetate (mg)
Vitamin K (μg) 0 200 200 10 10 200
Thiamin B1 (mg) 2.5 0 1.2 0.35–0.5 0.35–0.5 1.2
Riboflavin B2 (mg) 3.6 0 1.4 0.15–2 0.15–0.2 1.4
Niacin B3 (mg) 40 0 17 4.0–6.8 4.0–6.8 17
Pantothenic acid B5 15 0 5 2.5 2.5 5.0
(mg)
Pyridoxine B6 (mg) 4.0 0 1 0.15–2 0.15–0.2 1.0
Cobalamin B12 (μg) 5.0 0 1 0.3 0.3 1.0
Vitamin C (mg) 100 0 80 15–25 15–25 80
Biotin (μg) 60 0 20 5–8 5.0–8.0 20
Folic acid (μg) 400 0 140 56 56 140
With the exception of vitamin E, no upper limits are given; care must be taken to avoid over‐delivery of individual nutrients. Where nutrient mixtures
are used, manufacturers’ guidelines should be followed.
*In 10% Intralipid.
**Vitamin E is also added to some lipid bags (see Table 5.5).
The following single vitamin preparations are available in the European and American markets:
vitamin A, vitamin D, vitamin K, thiamin, pyridoxine, cyanocobalamin, vitamin C and folic acid.
Provision and administration of these should be arranged by a specialist pharmacist as part of a multidisciplinary team.
is based on expert opinion [5, 13, 75]. The amount of intrave Calcium, phosphorus and magnesium are usually added
nous vitamins given is usually recommended to be higher to the PN prescription as individual solutions, and the sug
than that given enterally. This is to allow for losses of the vita gested intakes are listed in Table 5.9.
mins by adsorption onto the PN bag and giving set or bio Individual preparations of some (not all) trace elements
degradation due to light exposure, thus reducing the available are available where there is a need to exclude or increase
intake. Vitamin A is most affected by these problems [76]. doses of single trace elements. In cases where there is an
Addition of the vitamins to the lipid bag and protecting the apparent overload or deficiency, action should be taken after
bag from direct sunlight is the best method of preserving discussion with members of the NST.
the vitamin concentration. Artificial light has little effect on
the stability of the vitamins [13]. Table 5.7 shows the com
mercially available vitamin solutions for preterm infants Iron
and neonates, none of which fully meets neonatal guidelines
[13, 45]. Daily administration is recommended with the Current commercially available paediatric mineral solu
exception of vitamin K that may be given weekly [13]. tions do not contain iron (Table 5.8). Intravenous iron sup
Consideration should be given to cholestatic patients with plementation is controversial due to the risk of adverse
obstructive jaundice as they can accumulate copper and side effects [78]. Parenterally administered iron bypasses
manganese, which are normally excreted in bile [77]. Patients the normal homeostatic mechanism of the intestine, and
with renal dysfunction may not be able to excrete selenium, excess iron may lead to iron overload syndrome. Iron
molybdenum, zinc and chromium [36]. High fluid losses enhances the risk of Gram‐negative septicemia [79] and
result in greater losses of magnesium and zinc. has powerful oxidative properties; it may, therefore,
Table 5.8 Recommended intakes of trace elements.
Paediatric (<40 kg) Adult
Additrace
Peditrace (Fresenius Peditrace (Fresenius Tracutil (B Braun) Decan (Baxter) (Fresenius Kabi)
Trace element (atomic mass) Requirement (ESPGHAN 2018) [13] Kabi) (μg/1 mL) Kabi) μmol/1 mL) (μmol/1 mL) (μmol/1 mL) (μmol/1 mL)
Iron Preterm: 250 μg/kg/day 0 0 3.5 0.45 2.0

(55.9) (3.58–5.37 μmol/kg/day)
Not necessary in short‐term PN (<3 weeks Infant and child: 50–100 μg/kg/day
duration) (0.895–1.76 μmol/kg/day)
Monitor carefully to avoid toxicity (p. 73)
Zinc Preterm: 450–500 μg/kg/day 250 3.82 5.0 3.8 10
(65.4) Infant 0–3 months: 250 μg/kg/day
Preterm infants and children with thermal Infant >3 months: 100 μg/kg/day
injuries may have increased requirements Child: 50 μg/kg/day (max 5 mg/day)
Copper Preterm: 40 μg/kg/day 20 0.315 1.2 0.19 2.0
(63.5) Infant and child: 20 μg/kg/day (max
Requirements may increase with high 0.5 mg/day)
gastrointestinal losses or thermal injuries.
Toxicity risk in cholestasis
Manganese Max 1 μg/kg/day (max 50 μg/day) 1 0.0182 1.0 0.091 0.5
(55)
In toxicity CNS deposition of manganese
can occur without symptoms
Monitor regularly
Chromium Max 5 μg/day 0 0 0.02 0.007 0.02
(52)
A contaminant – not usually added to PN
Selenium Preterm: 7 μg/kg/day 2 0.0253 0.03 0.022 0.04
(79) Infant and child: 2–3 μg/kg/day
Optimal dose unclear (max 100 μg/day)
Iodine Preterm: 1–10 μg/kg/day 1 0.0079 0.1 0.0003 0.1
(126.9) Infant and child: 1 μg/kg/day
Molybdenum LBW: 1 μg/kg/day 0 0 0.01 0.0065 0.02
(95.9) Infant and child: 0.25 μg/kg/day
Where upper limits are not given, care must be taken to avoid over‐delivery of individual nutrients. Where nutrient mixtures are used, manufacturers’ guidelines should be followed.
PN, parenteral nutrition; CNS, central nervous system; LBW, low birthweight.
Source: Adapted from [13]. Reproduced with permission of Elsevier.
Administration of Parenteral Nutrition 75
Table 5.9 Suggested intakes of parenteral calcium, phosphorus Administration of parenteral nutrition
and magnesium.
A more detailed account of the techniques of PN administra
Calcium Phosphorus Magnesium
tion is available in other publications [4, 13]. PN may be
mg (mmol)/ mg (mmol)/ mg (mmol)/
Age kg kg kg infused via a peripheral vein or a CVC. Each route has
advantages and disadvantages [82, 83]. For the purpose of
Stable premature 64–140 50–108 5.0–7.5 providing PN, it is necessary to differentiate peripheral from
infant (1.6–3.5) (1.5–3.5) (0.2–0.3) central venous access.
0–6 months 30–60 20–40 2.4–5.0
(0.8–1.5) (0.7–1.3) (0.1–0.2)
7–12 months 20 (0.5) 15 (0.5) 4.0 (0.14)
Vascular access
1–18 years 10–16 6–22 2.4 (0.1)
(0.25–4.0) (0.2–0.7) Peripheral lines
A needle or short catheter is placed into a subcutaneous vein
Where upper limits are not given, care must be taken to avoid over‐
to gain peripheral access. Peripheral lines are rarely associ
delivery of individual nutrients. Where nutrient mixtures are used,
manufacturers’ guidelines should be followed. ated with septicaemia. They are useful in short‐term PN (7–10
Source: Adapted from [13]. Reproduced with permission of Elsevier. days’ duration) when the fluid allowance is not restricted and
the concentration of PN solutions is <600 mOsm/L and when
venous access is good. They are often used in neonates. One
major disadvantage is the risk of thrombophlebitis caused by
increase demand for antioxidants. Monitoring of serum the hypertonic solutions used. The maximum concentration
ferritin and reduction/removal of iron supplementation, if of glucose solution that should be used with these lines is
levels become too high, is recommended [13]. Ferritin is a 12%. Infiltration is also a common problem; the peripheral
poor measure of deficiency as growing children and ado line may penetrate the surrounding tissues, resulting in leak
lescents use most of the iron supplied almost immediately ing of the infusion. This leakage is known as extravasation
to accrete tissue and red blood cells, so they rarely have and if undetected can cause tissue necrosis and severe scar
any significant iron stores. Although iron reserves should ring. Line sites must be inspected frequently to avoid this.
be adequate to supply red cell production for 3–5 months Lines that fail must be re‐sited quickly to avoid the risks of
(much less in preterm infants), iron deficiency has been hypoglycaemia and suboptimal nutritional intake.
found to develop much sooner. However, this is very much
dependent upon the underlying condition and if there has
Central venous catheters
been a degree of blood loss due to sampling or bleeding or
inter‐operatively. A CVC, e.g. a Broviac or Hickman catheter, is one that is tun
Iron deficiency may lead to increased blood manganese nelled beneath the skin and inserted into the superior or infe
levels [77]. In the absence of iron, manganese binds to trans rior vena cava or outside the right atrium via a subclavian vein.
ferrin [80], and iron deficiency up‐regulates both iron and It can be inserted either surgically or percutaneously. It is made
manganese absorption from the intestine [81]. of silicone that helps decrease sepsis rates and inhibits fibrin
Oral iron supplementation when possible is preferable to production and is, therefore, less likely to block. It has a Dacron
intravenous iron; however, if required, iron preparations cuff planted subcutaneously that serves to fix the line in place
may be added to the intravenous solution or given as a sepa and inhibits the migration of microorganisms from the skin.
rate infusion. This must be done with care due to its poor The maximum concentration of glucose solution that can
solubility, and risk of anaphylaxis; additional iron is usually be given via a CVC is 25%. The line can remain in situ for
given by week 4 of receiving PN. months. The major disadvantages of a CVC are the risks
associated with insertion and catheter care. Complications
include sepsis, occlusion, infection of the line site and acci
dental removal. Loss of venous access can be a life‐limiting
Learning points: iron
factor in PN‐dependent children, e.g. those with intestinal
failure. It is, therefore, imperative that these lines are well
• Iron is not present in commercially available paediatric
cared for. The more frequently a line is accessed, the greater
intravenous mineral solutions
the risk of infection. Only PN or fluid (not drugs) should be
• Oral supplementation should be attempted where possible
given via a single lumen catheter [6, 82, 83].
• Iron should be added if PN is long term (>4 weeks)
For the taking of blood samples or the administration of
• Iron status (ideally transferrin and transferrin saturation)
blood products or medication, separate venous access should
should be monitored to avoid toxicity/deficiency
be organised. In the case of home PN, where monitoring is
less frequent, the line may be accessed as long as it is done
aseptically. Multiple lumen catheters are usually inserted
when frequent intravenous drug therapy is required as well
An example PN prescription is given in Table 5.10. as PN and where the child is critically unwell, e.g. following
Table 5.10 Case example: a parenteral nutrition prescription for a 1‐year‐old boy.
1‐year‐old boy with short bowel syndrome.

Weight = 7 kg, Length = 70 cm.
He has a CVC to provide his full requirements from PN. He requires some extra fluid due to high stool output.
Requirements
Energy = 65 kcal (270 kJ)/kg/day (non‐protein calories)
AA = 2 g/kg/day
Lipid = 2.5 g/kg/day
CHO = 10 g/kg/day
Fluid = 120 mL/kg
Solution Dose (mL) Energy (kcal) (kJ) CHO (g) Lipid (g) AA (g)
Glucose (20%) 350 280 (1170) 70

SMOF (20%) 88 175 (730) 17.5
Vaminolact 215 56 (235) 14
Vitlipid infant* 10 10 (40) 1
Solivito 7
Peditrace 7
Water 163
Total 840 521 (2175) 70 18.5 14
Per kg 120 66 (275) non‐protein 10 2.6 2
calories
*10% lipid. Electrolytes, calcium, phosphorus and iron need to be added in recommended doses.
Rates of infusion
The above is a typical PN content sheet and is supplied with the PN solutions; it is not a prescription. PN is prescribed by writing the rates of
‘aqueous’ and ‘lipid’ solutions on an intravenous (IV) prescription chart. The rates are usually specified/recommended by the PN pharmacist and
are calculated as follows:
Aqueous solution (Vaminolact and 20% glucose and trace elements; could also include water, electrolytes, calcium and phosphate and any IV
drugs given in the aqueous phase of the PN)
In this example volumes are calculated as follows:
Total = 380 + 215 + 163 = 728 mL = 30.3 mL/hour given for 24 hours
Lipid solution (Intralipid and vitamins; could also include any IV drugs given in the lipid phase of the PN)
In this case example volumes are calculated as follows:
Total = 88 + 10 + 7 + 7 = 112 mL = 5.6 mL/hour given for 20 hours
Lipid solution is usually given over 20 hours to allow time off for clearance of lipid from the blood prior to blood sampling.
When the boy becomes more stable, some enteral feeds are given. PN infusion rates are increased to give some hours off PN:
PN given over Aqueous phase (mL/hour) Lipid phase (mL/hour)
20 hours 36.4 5.6

18 hours 40.4 6.2
16 hours 45.5 7
Rates of infusion of glucose solution must be calculated and ideally should not exceed the maximum glucose oxidation rate of 10 mg/kg/min.
The PN in this case example provides 70 g glucose per 24 hours = 2.9 g glucose per hour or 10.4 mg/kg/min if given for 16 hours. With the boy’s
weight of 7 kg, this is just above the recommended rate.
(continued overleaf)
Administration of Parenteral Nutrition 77
Table 5.10 (continued)
Tapering or ‘ramping’ PN up and down

If the PN is to be given as ‘cycling PN’, it is recommended that it is tapered up and down over the first and final 2–3 hours of infusion. This will steadily
increase and reduce the glucose infusion in order to avoid hypoglycaemia and hyperglycaemia. For example,
How PN is given Aqueous phase (mL/hour) Lipid phase (mL/hour)
PN to be given 20 × 1 hour 4 × 1 hour

over
a total of 18 hours 30 × 1 hour 6 × 1 hour
with a ramping up 45 × 14 hours 6.6 × 14 hours
and down for the 30 × 1 hour 6 × 1 hour
first and final 2 20 × 1 hour 4 × 1 hour
hours of the Total = 728 mL Total = 112 mL
infusion
PN, parenteral nutrition; AA, amino acids; CHO, carbohydrate; IV, intravenous.
bone marrow transplantation or in intensive care. The rate of and dextrose solution as close as possible to the peripheral or
infection of these catheters is higher compared with single central line. All the components are compounded in a spe
lumen catheters [82], and this is probably a reflection of more cialist pharmacy unit under aseptic conditions in an isolator.
frequent catheter manipulation. Specialist pharmacists use computer‐based programmes to
Accidental damage to, or removal of, the catheter is com ensure that the nutrient content of the bag is appropriate for
mon. Young children will chew and pull their catheter, given the child’s age, condition and biochemistry. They also help
the opportunity, and it is important that nursing staff and to ensure that solution stability is assessed and drug–nutri
parents carefully loop and tape the catheter securely to the ent interactions are avoided [84].
skin. It is then best practice to cover with a vest and other Compounded PN is supplied from the manufacturing
clothing to keep the line out of reach. pharmacy in a premixed collapsible bag with an opaque
cover to protect nutrients in the solution from photodegrad
Portacath ation. When low rates of infusion are prescribed and the
solution remains in the burette for long periods, light protec
A portacath is a totally implantable device that requires nee
tive sets may also be used, although these have limited effec
dle sticking for vascular access. It has limited value for PN
tiveness and are most useful if solutions are exposed to direct
but is useful for vascular access for frequent medications,
sunlight rather than artificial light [13]. Home PN is often
e.g. prophylactic antibiotics in cystic fibrosis.
given during the night, thus reducing the risk of photodeg
radation further. Manufacturers’ guidelines advise on stabil
Learning points: central venous catheters ity, dosage and administration.
‘All‐in‐one’ mixes (containing AA and dextrose with and
• Examples are Hickman or Broviac catheters, also known as without lipid) are available. They are used more commonly
central lines in adults. Products that can be used in children >2 years are
• Maximum glucose concentration in a CVC = 25% (12% in Oliclinomel (Baxter) and Kabiven (Fresenius Kabi).
a peripheral line) There are two solutions (Table 5.11) that can be used from
• CVC can stay in situ for years if well cared for birth (whether preterm or term) to 2 years of age: Babiven
• CVC is high risk as a route of infection and source of sepsis (Fresenius Kabi) and Numeta (Baxter). These products do
• Central venous access, or lack of it, is a life‐limiting factor not contain vitamins or complete mineral profiles; these
for children with intestinal failure must be added to the bag before it is infused. Babiven does
not contain lipid, which must also be given separately.
Standard solutions such as these may be useful in order to
increase the capacity of a busy aseptic pharmacy unit and
Delivery methods decrease preparation time [85]. They may also help avoid
some areas of risk previously identified, such as delayed PN
PN can be delivered by a variety of systems. Infants and chil commencement where the pharmacy capacity or ordering
dren usually have a system in which AA and dextrose are may delay the provision of PN. They may also avoid inade
mixed and delivered over 24 hours. The fat emulsion is quacy in delivery of solutions as prescribing errors are mini
delivered from a separate container but mixes with the AA mised when ‘all‐in‐one’ bags are used at ‘standard’ rates.
Table 5.11 Standard paediatric parenteral nutrition bags.
Numeta G13% (preterm) (Baxter)

Activated 2 chamber (no lipid) Activated 3 chamber (with lipid)
mL/kg/day 102.3 127.9
Amino acids, g/kg/day 4.0 4.0
Glucose, g/kg/day 17.1 17.1
Lipid, g/kg/day 0 3.2
Numeta G16% (term to 2 years) (Baxter)

Activated 2 chamber (no lipid) Activated 3 chamber (with lipid)
mL/kg/day 72.3 96.2
Amino acids, g/kg/day 2.5 2.5
Lipid, g/kg/day 0 3.0
Babiven maintenance (Fresenius Kabi) no lipid

mL/kg/day 100 120
Amino acids (N), g/kg/day 2.6 (0.37) 3.1 (0.44)
Lipid, g/kg/day 0 0
Babiven term (Fresenius Kabi) no lipid

mL/kg/day 100 135
Amino acids (N), g/kg/day 2.19 (0.31) 2.96 (0.42)
Glucose, g/kg/day 11.1 15
Lipid, g/kg/day 0 0
N, nitrogen.
The stability of ‘all‐in‐one’ PN depends on the stability of • 0.22 μm for AA and dextrose solutions; this safely
the premixed nutrient solutions. The formulations cannot removes bacteria, endotoxins, air and particles (this is
be varied greatly; therefore, they are not suitable for unsta not used for lipid solutions as the pore size is too small
ble patients or those with unusually low or high require for lipid to pass through)
ments. As the mixing of the lipid and aqueous solutions • 1.2 μm for ‘all‐in‐one’ bags and lipids; this safely removes
shortens the shelf life of the PN, some solutions come in Candida, air and particles (the pore size is large enough
separate chambers that can be rolled together and mixed for the lipid to pass through); it is not a sterilising filter as
just before use. it will not remove bacteria
Best practice demands that children should have individ
ually prepared PN as ‘all‐in‐one’ solutions may not contain
sufficient calcium, phosphate and other electrolytes. ‘All in Cyclical parenteral nutrition
one’ is safe for use in short‐term PN; however, close monitor
ing of biochemistry is necessary. This refers to the intermittent administration of intravenous flu
ids with a regular break in each 24 hour period. There may be
advantages in terms of changes in insulin/glucagon balance
Equipment and decreased lipogenesis, time off to allow for physical activity
and reduction in the risk of development of liver disease [86].
A steady flow rate should be maintained when infusing PN. Infusion rates are usually built up gradually over a period
Hyperglycaemia and hyperlipidaemia will result if infusions of days or weeks. Often patients on long‐term PN will have
are delivered too quickly. If the line blocks or the infusion infusion rates increased to enable them to have the prescribed
stops suddenly, hypoglycaemia may occur [6]. Volumetric volume of solutions delivered overnight only, leaving them
pumps are sufficiently accurate for use in children; these free from PN during the day. However, this is very much
deliver measured volumes via a cassette with a syringe mech dependent upon the age of the child, e.g. infants, particularly
anism ensuring accuracy. Syringe pumps are used instead of preterm infants, have very low glycogen stores and need an
volumetric pumps when small volumes are required. These almost constant supply of glucose. Any breaks in PN require
have a linear drive mechanism and can be set to deliver as close monitoring to avoid hypoglycaemia. With increased
little as 0.5 mL/hour. Filters are needed to remove any poten rates of delivery, there is a risk of hyperglycaemia on com
tial bacterial or fungal contaminant and prevent air embolism mencement of PN and a risk of rebound hypoglycaemia on
and entry of particulate matter. It is considered good practice cessation of PN. For this reason, it is recommended that infu
to filter PN solutions with a pore size of: sion tapering may be warranted, particularly in children
Home Parenteral Nutrition 79
<2–3 years old to limit risk [87, 88]. Rates are ramped up and Home parenteral nutrition
down over the initial and final 2–3 hours of PN (Table 5.10).
Although most patients discontinue PN in the acute setting,
it is recommended that PN at home be considered for any
Weaning from parenteral nutrition patient likely to be dependent on PN for more than 3 months
In order to wean the child from PN, i.e. reduce the amount of [89]. Home parenteral nutrition (HPN) improves quality of
PN given, it is essential that some degree of enteral nutrition life for these patients and their families due to obvious psy
is maintained. The concentration and rate of delivery of chosocial benefits. It is also associated with lower risks of
enteral feed will be gradually increased, depending on toler catheter infection and a decreased risk of PNALD [90] and
ance and growth parameters. If fluid restriction is not a reduces the cost of caring for these children during long hos
major issue, once enteral feeds or diet provide at least 25% of pital admissions.
the total nutritional requirements, a corresponding reduc The demand for HPN services for children has risen over
tion can be made to the PN prescription. Once 50% of the past 30 years. Due to better understanding and manage
requirements are met enterally, the PN can be decreased to ment of complications, long‐term survival rates on PN have
50%, with a further decrease to 25% once the enteral route improved. Published surveys show a 200% increase in
meets 75% of requirements. When more than 75% of require patients registered on HPN since 2012 [91]. Short bowel syn
ments are achieved by enteral nutrition, the PN could be drome was the most common diagnosis with an increase
stopped in most cases [88]. These reductions depend upon from 27% to 63% of cases [90]. It is widely recognised among
satisfactory growth and development of the child. Weaning expert practitioners in this field that a national strategy is
from PN may take a few days where it has been used for needed to manage this expanding group of patients with
nutritional support in the short term, e.g. following acute chronic intestinal failure.
surgery, or be very gradual over months and sometimes Patients on HPN should be managed by a specialist centre
years where it has been used for long‐term support, such as with significant expertise in this area [91]. Dedicated special
in short bowel syndrome while waiting for gut adaptation. If ist nurses must train parents and caregivers in preparation
the PN is provided as separate lipid and aqueous (carbohy for discharge, with community services supporting the fam
drate and AA) solutions, it is important to decrease each ily by providing equipment and a suitable environment for
solution proportionally in order to maintain an adequate the administration of PN in the home. Home assessments
nitrogen-energy ratio. must be undertaken, and, if necessary, rehousing or struc
If fluid restriction is a complicating factor and the wean tural changes to housing must be made. Manufacturers of
ing period is prolonged, the PN should be made up as con PN solutions usually provide homecare packages that may
centrated as possible (depending upon the route of be funded by local health purchasers; contracts are often
administration and the solutions used). Thereafter, the PN agreed on a case need basis.
will usually need to be decreased by each millilitre that the
enteral nutrition is increased (although a greater fluid vol
ume is usually tolerated via the enteral route than the paren
teral route due to losses from the gut). Care and attention to
actual intake is necessary in these cases to ensure maximum
nutrition is achieved, as enteral feeds are often less concen
trated than PN. This is especially important in infancy or for
malnourished children.
6 Nutrition in Critically Ill Children
Rosan Meyer and Luise Marino
Introduction 28.2% in infants <1 year of age [13]. Both malnutrition and
faltering growth have been shown to have a significant
Data from the 2017 annual report from the Paediatric effect on: muscle strength [14]; reduced wound healing
Intensive Care Audit Network (PICANet) in the United due to altered immunity with increased rates of sepsis [3];
Kingdom (UK) indicate that only 150 children are admit- mechanical ventilation days with poorer post‐operative
ted to a paediatric intensive care unit (PICU) per 100 000 resilience [3]; longer length of hospital stay, particularly
(0.15% of all children), with the majority of those children amongst children post‐surgery [12, 13, 15–17]. Ensuring
(41.4%) being below 1 year of age (PICANet) [1]. Nutritional optimal nutritional support in critically ill children is
management of the critically ill child (CIC) is, therefore, a therefore crucial.
very specialist and challenging area in paediatric dietetic
practice. In addition to minimising the effects of starvation
associated with suboptimal nutrition and preventing Learning points: incidence of critical illness
nutritional deficiencies and excesses, its goal is to sustain
organ function and prevent dysfunction of the cardiovas- • Mortality rates are low (4.7%) in PICUs in the West
cular, respiratory and immune systems until the acute‐ • Persistent malnutrition is associated with a longer length
phase inflammatory response resolves (Table 6.1) [8]. Both of PICU stay
under‐ and overnutrition have the potential to compro-
mise this goal and significantly complicate and increase
the length of hospital stay [9–11]. Overfeeding can lead to
increased carbon dioxide production resulting in difficul-
ties with weaning from mechanical ventilator support,
Inflammatory and metabolic responses that
fatty liver, as well as diarrhoea associated with electrolyte impact on nutritional requirements
imbalances and other well documented metabolic and
physiological complications [4]. Underfeeding, however, Endocrine and inflammatory response
is a more common occurrence in PICU that has not
improved over the last 35 years, in spite of great medical Knowledge of metabolic changes and fuel utilisation during
advances. Pollack et al. [9] found in 1981 that 16%–20% of physiological stress can assist in commencing nutritional
critically ill children develop significant, acute protein support at an appropriate time, suggesting a suitable feed-
energy malnutrition (PEM) within 48 hours of admission ing route and feed composition. Critical illness is character-
to a PICU; in 2006, Hulst et al. found that 24% of children ised by a cascade of endocrine and metabolic reactions,
have PEM [3]. More recently Valla et al. [12] found that affecting all major organs (Figure 6.1) [8, 18].
23.7% of children were either malnourished on admission The reaction of the body to physiological stress changes
or developed faltering growth during a PICU admission. over time and can be divided into three phases. The acute
In addition, children with chronic diseases such as congen- phase is characterised by escalating organ support, includ-
ital heart disease may also have persistent malnutrition, ing the use of inotropes and mechanical ventilation, affect-
with a UK centre reporting a height for age z‐score <−2 in ing substrate (protein, carbohydrate and fat) metabolism.

Inflammatory and Metabolic Responses that Impact on Nutritional Requirements 81
Table 6.1 The effect of critical illness on the major organs.
Gastrointestinal system Cardiovascular system Respiratory system Renal system
• Gastroparesis (motility affected due to • Tachycardia • Respiratory deterioration • Renal impairment may
medication, e.g. morphine, inotropic • High cardiac output [5] leading to artificial occur during critical
agents and antibiotics, as well as the • Fluid shift from the ventilation [5] illness and may be as
disease process itself) [2] [3] intracellular, to the severe as acute renal
• Impaired digestive enzyme secretion extracellular failure requiring
• Cholestasis [4, 5] compartments [6] haemofiltration [7]
• Impaired lipid metabolism due to
affected liver function [5]
• Increased intestinal permeability [2]
• Poor gut perfusion [2]
Inflammation
Endogenous glucose production Catabolism
Protein turnover
Anabolism
Recovery
phase
Metabolic consequences
REE
REE
Stable
phase
Acute
phase Muscle protein synthesis
REE
Growth hormone
Reverse triiodothyronine
Muscle protein synthesis
Insulin-like growth factor 1
Time
Figure 6.1 Different phases of critical illness with corresponding neuro‐endocrine, immunologic and metabolic changes. REE, resting energy
expenditure. Source: Adapted from Joosten [8]. Reproduced with permission of Wolters Kluwer Health.
The stable phase is where physiological control has been receptors on the surface of target cells and organs mediating
achieved, but the stress response is not completely resolved the following responses:
although the child is stable and there is a process of stability
• up‐ or down‐regulation of gene expression influencing
or weaning of vital organ support, and finally the recovery
wound healing and immunocompetence
phase (which may not occur in PICU) involves clinical
• release of counter‐regulatory hormones
mobilisation, with normalisation of neuro‐endocrine, immu-
• cell to cell signalling orchestrating the inflammatory
nologic and metabolic alterations returning to anabolism.
response which affects substrate metabolism [8, 22, 23].
During this phase there will be the re‐accumulation of pro-
tein and fat stores, which may require a period of intensive
nutritional rehabilitation [2, 8, 19, 20].
During critical illness immune cells, e.g. macrophages, Learning points: pathophysiology of critical illness
lymphocytes and neutrophils, regulate the inflammatory
response through the release of: cytokines (in particular There are three phases of critical illness
interleukins (IL) such as IL‐1, IL‐6, IL‐8, IL‐10 and tumour
• acute phase – escalating organ support, e.g. the use of
necrosis factor alpha (TNFα); and chemokines such as heat
inotropes and mechanical ventilation, affecting substrate
shock protein 70 [21]. All are important mediators of the
(protein, carbohydrate and fat) metabolism
stress response (Table 6.2). Cytokines signal through
Table 6.2 Cytokines involved in the acute phase of injury and possible effects on substrate metabolism and nutrition.
Cytokines Relevant function Interaction between metabolism, nutrition and cytokines
Pro‐inflammatory cytokines
TNFα [9, 12, 13, 22–24] Pro‐inflammatory; release of leucocytes by Increases glucose transport and impacts on muscle lipolysis
bone marrow; activation of leucocytes and
endothelial cells
IL‐1 [23, 25] Involved in pyrexia; T‐cell and macrophage Impact on hepatic and muscle lipogenesis
activation
IL‐6 [23, 25] Growth and differentiation of lymphocytes; Impact on hepatic lipogenesis
activation of the acute‐phase protein response Increases during multi‐organ dysfunction and associated with
poor nutritional status
IL‐8 [9, 13, 22, 23] Chemotactic for neutrophils and T‐cells Concentrations during the first 24 hours are predictive of
worsening organ dysfunction
Anti‐inflammatory cytokine
IL‐10 [22, 25] Inhibits immune function Increases during multi‐organ dysfunction and associated with
poor nutritional status
Both excessive and under expression of IL‐10 is negatively
associated with outcome
Negatively correlated with resting energy expenditure:
increase in IL‐10 associated with lower energy expenditure
Inhibits pro‐inflammatory cytokine production by
macrophages, monocytes, neutrophils and natural killer cells
Attenuates the synthesis of TNF cell surface receptions
Controlling cytokine regulating the inflammatory response
IL, interleukin; TNFα, tumour necrosis factor alpha.
anabolic hormone insulin‐like growth factor 1 (IGF‐1)

• stable phase – physiological control has been achieved, but remained low until day 4 of PICU admission and T3 levels
the stress response is not completely resolved remained below normal at days 4 and 6 in 88% and 89% of
• recovery phase – this phase may occur following discharge the older children, respectively. It is clear that substrate
from PICU metabolism varies greatly during admission and that dur-
ing the early phase of illness hypometabolism is usual,
whereas in the recovery phase of illness hypermetabolism
predominates [8, 28]. This needs to be taken into account
Energy metabolism when calculating energy requirements and choosing feeds
for these patients, which may require changes being made
Although older studies have suggested a hypermetabolic to prescribed energy intake during the course of a PICU
state during the acute phase of illness [26], there is consen- stay [8].
sus that most children are hypometabolic during this phase.
This is supported by a study by Briassoulis et al. [25] who
found that on the first day of admission 48.6% of children Substrate utilisation
were hypometabolic (<90% of predicted basal metabolic
rate, BMR), 40.5% were normometabolic (90%–110% of pre- Several studies have focused on the relation between a
dicted BMR) and only 10.8% were hypermetabolic (>110% CIC’s metabolic state, their nutritional intake, substrate uti-
of predicted BMR). A hypermetabolic pattern (or, as more lisation and nitrogen balance. In a similar way to critically
recently described, the recovery phase) only emerged after ill adults the stress response and the severity of disease is
2 weeks of admission in 60% of children. This unique characterised by protein catabolism. In contrast to adults,
pattern of metabolism may be explained by a multitude of fat is the preferred fuel in children and is readily oxidised
factors, including the physiological response to stress, [4, 34]. Conversely carbohydrates are poorly utilised dur-
improved medical treatment as well as the unique nature of ing critical illness. Gluconeogenesis is also a characteristic
fuel utilisation in critically ill children (Tables 6.2 and 6.3) of paediatric critical illness and muscle mass is rapidly
[8, 20, 34]. depleted of amino acids, such as glutamine, which are uti-
In addition to the factors listed in Table 6.3 studies have lised in de novo glucose production [37, 38]. Considering
found that during the acute phase, growth most probably glucose oxidation and production has become one of the
does not take place and this energy is diverted into the most important factors to take into account in nutritional
recovery processes [8, 30, 35, 36]. This hypothesis is sup- support in CIC as this has a direct impact on morbidity and
ported by the data from Hulst et al. [35] who found that the mortality [39]. In CIC the maximal glucose oxidation rate
Inflammatory and Metabolic Responses that Impact on Nutritional Requirements 83
Table 6.3 Factors that influence energy expenditure.
Factor Influence on energy expenditure
Sedation [27] ↓ Energy expenditure (reduced brain activity)

Muscle relaxants [27, 28] ↓ Energy expenditure, but not of clinical significance
Ventilation (with humidified air) [29] ↓ Energy expenditure, reduces the workload of breathing as well as heat loss in fully ventilated
children, but where ventilatory support is minimal may have not impact
Thermoneutral environment [30, 31] ↓ Insensible losses, therefore lowers energy expenditure
Pyrexia [32] ↑ Energy expenditure (8%–12% increase in energy expenditure per 1°C above normal)
Paracetamol/NSAID [32] ↓ Energy expenditure as blunts response to fever; clinical relevance questionable
Severity of disease [28, 29, 31] Inconclusive evidence
Diagnosis [28, 29] No difference in energy expenditure in different diagnoses
Severity of disease [28, 29] No significant difference in energy expenditure
Movement/activity (33) ↑ Energy expenditure
NSAID, non‐steroidal anti‐inflammatory drugs.
for parenteral nutrition (PN) has been found to be 5 mg/ from intensive care almost all children showed nutritional
kg/min and in a study reducing this to 2.5 mg/kg/min recovery with regards to weight and height [3]. This study
during the acute phase reduced high glycaemic levels and did not consider body composition measures, so the type of
increased the rate of glucose production, mainly through nutritional rehabilitation achieved is not known, e.g. fat
glycogenolysis [40, 41]. mass vs. lean body mass. Recent work has corroborated this
It is, therefore, important to ensure that carbohydrate finding: 2 year follow up data from the PEPaNIC study indi-
intake in CIC is monitored, especially if PN is used [40]. cates that withholding early parenteral nutrition for 1 week
There is no data currently published on glucose oxidation in the PICU does not negatively affect survival, anthropo-
rates for enteral nutrition, however, as hyperglycaemia is an metrics, health status and neurocognitive development [54,
important complication, monitoring intake also from the 55]. It was, however, associated with improved inhibitory
enteral route and avoiding overfeeding is critical (see energy control 2 years after PICU admission [56, 57]. Nutritional
requirements, p. 86). outcomes should be defined for future use in daily clinical
work and as part of audit/research within and between
organisations, to ensure variation in practice is reduced and
Longer term outcomes nutritional outcomes are optimised.
As mortality rates continue to decline, there is an increasing
focus on PICU survivorship and improving outcomes in Mechanism for muscle wasting
children who are discharged. Disordered feeding is well
described in children with chronic diseases such as cystic There is often an imbalance between anabolism and catabo-
fibrosis [42], gastrointestinal disorders [43], food allergy [44] lism with protein turnover outstripping protein synthesis,
and congenital heart disease (CHD) [45] and has been leading to a net loss of muscle mass which occurs as a result
reported to affect up to 22% of post‐surgical infants with of de novo gluconeogenesis [37, 58].
CHD [46], and is the cause of significant parental distress [47, Sepsis associated muscle wasting is well described in the
48]. However, what is not known is the extent of feeding dif- adult ICU, although the prevalence is not known in children.
ficulties in PICU survivors who were healthy prior to admis- Causative factors include sepsis, muscle disuse, fasting, can-
sion. Risk factors for feeding difficulties and dysphagia in cer, cardiac failure and renal dysfunction. In ICU there is often
adult intensive care unit (ICU) survivors are endotracheal prolonged bed rest or immobilisation, use of sedatives and
tube intubation for longer than 48 hours, ICU associated mal- neuromuscular blockades, acute or chronic organ dysfunc-
nutrition and muscle weakness [49–52]. Furthermore, survi- tion, medication using steroids [58] and increased levels of
vors of adult critical care report significant changes to their cytokines, e.g. IL‐6, IL‐10, TNFα (which are associated with
ability to eat with reduced appetite, altered taste and food muscle degradation) amongst other factors [22, 58] (Figure 6.2).
preferences lasting up to 3 months post‐ICU discharge [53]. Muscle wasting and ICU induced myopathy has not been
With regards to nutritional risk Hulst et al. considered lon- described in children and it may be that the pathophysiology
gitudinal changes to anthropometry in critically ill infants/ of paediatric critical illness does not result in this phenome-
children (n = 293) from admission to PICU up to 6 months non. However, as a significant number of children admitted to
post‐discharge. At the time of admission 24% of the cohort PICU develop malnutrition it is likely that muscle wasting also
were undernourished. During PICU admission only infants occurs in children, although the correlation with strength and
(preterm/neonates), not older children, exhibited a decline function has not yet been studied in CIC [59]. Ultrasonography
in nutritional status. Of note at 6 months post‐discharge of various upper and lower body muscles, in particular the
Severe sepsis Bedrest, sedation, Insulin

systemic inflammation disuse, trauma resistance Pharmaceutical Pharmaceutical
Multiple Neuromuscular
Immobilization Hyperglycemia Corticosteroids
organ failure blockers
IFN-γ
IL-1, IL6
Complement
TNF-α C3a, C5a ICUAW
IL-10
TGF -β
Non-excitable
Predominant type II Selective myosin loss muscle membrane
muscle fibre atrophy
Protein degradation
Protein synthesis
Sepsis,
Muscle atrophy, disuse,
less fibre type specific Muscle wasting fasting,
cancer,
organ failure
Figure 6.2 Risk factors for muscle wasting and ICU associated wasting from Schefold et al. with permission [58]. IFN, interferon; IL, interleukin; TNF, tumour
necrosis factor; TGF, transforming growth factor; ICUAW, intensive care unit acquired weakness. Source: Reproduced with permission of John Wiley & Sons.
quadriceps femoris muscle in adults, has been studied as [64, 66] found that this formula underestimates the weight
proxy marker of muscle wasting [59]. So, although muscle significantly and that a new formula (weight = 3(age) + 7)
ultrasound may detect muscle wasting in CIC, the error of allows for a more safe and accurate estimation. A formula can,
margin is too large for it to be used in clinical practice [59, 60]. however, never replace an accurate weight measurement; it is
not only used in the assessment of nutritional status and cal-
culating nutritional requirements, but is also used for estimat-
Nutritional assessment ing fluid requirements and medication doses. Transfer and
hospital notes as well as the child’s personal health record
Growth failure is common amongst children admitted to PICU. (red/blue book) may have a recent accurate weight (often
It is, therefore, imperative to classify the type of growth impair- height and head circumference as well), which may be useful.
ment (i.e. wasting, stunting or faltering growth) to enable a tar- It is important that available accurate weight, height and head
geted nutritional care plan. Malnutrition in this population is circumference measurements are plotted on an appropriate
multifactorial and may be illness and non‐illness related and it growth chart [63, 67].
is important to identify the contributors (Figure 6.3). The multi- The use of both triceps skin fold thickness (TSF) and mid
factorial nature of malnutrition in this population makes nutri- upper arm circumference (MUAC) has been documented in
tional assessment in particular challenging [62]. this population. Although MUAC is less affected by oedema,
Anthropometry, biochemical markers, clinical and dietary both measurements have limited use in children with a short
review form part of the nutritional assessment in CIC [63]. PICU stay (4–5 days), however, should be considered for
This process, however, is notoriously difficult due to a mul- children who remain in PICU for a longer period of time (>1
titude of factors including oedema, ascites and severity of week). They are most helpful when followed over time and
disease, which often makes it challenging to obtain an accu- measured by the same trained person [63, 67]. Hulst et al.
rate body weight. In addition, the emotional impact of hav- [63] studied the feasibility of routinely performing nutri-
ing a child in PICU frequently makes the diet history from tional assessments using non‐invasive methods in CIC. It
the caregivers unreliable. was found that anthropometry was reliably obtained within
A UK study found that only 20.5% of CIC had an accurate 24 hours of admission in 56%–91% of patients. Unfortunately,
admission weight documented and it is common practice to the more seriously ill patients were those where measure-
estimate their weight on admission [64]. The Advanced ments were less feasible, but who might have benefited the
Paediatric Life Support formula ([age + 4] × 2) is most com- most from having them done. Vermilyea et al. [68] have pro-
monly used to estimate weight [65], however, Luscombe et al. posed the use of a subjective global nutritional assessment
Nutritional Assessment 85
Etiology and
Anthropometry chronicity Mechanism Imbalance of nutrients Outcomes
Starvation
Non-illness related Anorexia, socio-
Intake
Parameters economic, iatrogenic Loss of lean body
Behavioral, socioeconomic
or environmental feeding mass
Weight, height interruptions, or
or length, skin intolerance
Muscle weakness
folds, mid
upper arm Or
Malnutrition Developmental
circumference
or intellectual
Illness related delay
Malabsorption
Nutrient requirement
Statistic Infections
Acute (<3 months)
Z-scores e.g. infection, trauma, Intake < Requirement Immune
burns Nutrient loss
dysfunction
Energy +/– protein Delayed wound
Reference Chronic (<3 months) Hypermetabolism imbalance healing
charts e.g. cystic fibrosis, Energy expenditure
chronic lung disease, Prolonged
cancer
Micronutrient
WHO MGRS hospital stay
(0–2 years) deficiencies
+/–
CDC 2000 Altered utilization
(2–20 years)
of nutrients
Inflammation
Figure 6.3 Aetiology of illness and non‐illness related malnutrition in CIC [61]. Source: With permission from SAGE. Reproduced with permission of
Wolters Kluwer Health.
(SGNA) tool, specifically designed for PICU. That study are also influenced by impaired renal function, dehydration,
found, although not predictive of outcome, the SGNA was polyuria and severe sweating on admission. Children with
valid and strongly correlated with standard anthropometri- sepsis or cardiac anomalies in this study showed the highest
cal measurements. Although this does not replace an accu- prevalence of uraemia, which can be explained by the degree
rate measurement, healthcare professionals may consider of catabolism and impairment of renal function. Although
this in those children where measurements are not feasible. pre‐albumin, retinol binding protein, transferrin and nitro-
More recently the use of bioelectrical impedance spectros- gen balance studies have also been used in research on nutri-
copy (BIS) in predicting nutritional risk and PICU outcomes, tional status in CIC [70], their accuracy and the value of
such as length of stay, has been investigated. A phase angle routine use have been questioned by several authors.
of <2.7 on day 2 in PICU following cardiac surgery for con- However, a positive nitrogen balance does not reflect protein
genital heart disease was found to be associated with a four- or amino acid utilisation or stores, and although increasing
fold risk of staying longer in PICU. A low phase angle also amino acid intakes may result in a positive protein balance, it
appeared to precede anthropometrical changes and may be a leads to increased endogenous glucose production and lipol-
more sensitive predictor of nutrition risk [69]. Future work ysis, exacerbating insulin resistance and promoting glucone-
needs to focus on investigating the use of BIS in this setting ogenesis [72, 73]. Urinary nitrogen has been used in the past
as it may represent an inexpensive tool to identify those at as a marker of nitrogen balance. Urinary nitrogen as a bio-
risk of prolonged PICU stay, allowing for nutritional intake marker is challenging to collect in clinical practice (a full 24
to more carefully managed [17, 69]. hours of urine is needed) and more recently the isotope tracer
Most laboratory markers of nutritional status are affected technique has been more commonly used to determine whole
by the acute inflammatory response, renal impairment and body protein balance and synthesis [20, 74, 75]. Whilst this
fluid shifts. Hypomagnesaemia (20%), hypertriglyceridae- method has been shown to be very accurate, it requires spe-
mia (25%), uraemia (30%) and hypoalbuminaemia (52%) are cialist equipment and expertise to conduct these studies. It is,
commonly seen in CIC [70], but an association between therefore, important to select biomarkers for the assessment
anthropometric measurements was only found with urae- of nutritional status in the critically ill patient with care and
mia. Serum urea levels can indicate the degree of catabolic interpret them accordingly (Table 6.4).
stress and levels of protein breakdown associated with ill- Taking a diet history often gets neglected in PICU [67].
ness, surgery and trauma. Uraemia has been shown to be Although manipulation of oral intake is not practical or pos-
negatively correlated to MUAC and weight for age on admis- sible, many acute and chronic nutrition related problems,
sion and discharge, as well as increased risk of mortality [71]. e.g. food allergy, nutritional rickets, can be identified on
However, it is important to consider that serum urea levels admission and can assist in planning dietary input during
Table 6.4 Relevance of biochemical indices in critical illness.
Biochemical indices Comment
Serum urea • Indication of catabolism and protein breakdown associated with trauma [76] as well as impaired renal function,
dehydration, polyuria or severe sweating which will impact on fluid management [70]
• Although there is a link between muscle mass and urea, it is not a reliable marker to assess nutritional support
Glucose • There is currently a great deal of interest in the use of tight glycaemic control in critically ill children. There is,
however, no clear guidance on this topic from a nutritional perspective [77]
• It is important to monitor glucose levels, in particular in children on IV preparations and those with PN (p. 72) [40]
Albumin • Levels are likely to be low especially in those receiving intravenous saline
• Albumin is not a good marker of nutritional status, due to a long ½ life and is more a marker of inflammation,
intravascular/extravascular fluid shifts and catabolism [14, 15, 70, 76]
C‐reactive protein (CRP) • Is used as an index of the acute phase response and is usually measured serially
• Serum prealbumin and CRP are inversely related, e.g. serum prealbumin levels decrease and CRP levels increase in
proportion to the severity of illness, returning to normal (<5 mg/dL) once the illness has resolved
• In infants a value of <2 mg/dL is associated with a return of anabolism with a concomitant rise in prealbumin levels [78]
Magnesium/calcium • Hypomagnesaemia is commonly found in critically ill children [79]
• It is strongly associated with hypokalaemia and hypocalcaemia
Phosphorus • Hypophosphataemia (in up to 61% of critically ill children) [70, 80] and low levels of selenium, zinc [81] and
manganese are also commonly found in critical illnesses [70]
Lactate • Lactic acidosis is common in critically ill children and reflects hypoperfusion, including diabetic ketoacidosis, septic
shock and cardiogenic shock
• Lactic acidosis, base excess and a strong anion gap are associated with increased risk of mortality
• A level of >2 mg/dL may be used as a crude proxy for cell function and a resolution of lactic acidosis is correlated
with survival [82]
IV, intravenous; PN, parenteral nutrition.
the admission. The effects of long term feeding problems, Although current guidelines [1] recommend indirect calo-
e.g. obesity, constipation, can be addressed once the patient rimetry to establish energy requirements, there is a consider-
is extubated and transferred to a ward or local hospital. able cost related to running and maintaining them and most
PICU units do not have access to an indirect calorimeter [20–
23]. The guidelines from the Society of Critical Care Medicine
Nutritional requirements and the American Society for Parenteral and Enteral Nutrition
(ASPEN) [93] and the European Society of Paediatric and
Energy requirements Neonatal Intensive Care Society (ESPNIC) [94] recommend
that in the absence of indirect calorimetry the BMR,
Many predictive equations have been used and studied in
the paediatric critical care setting to calculate energy require- Table 6.5 Bias at 200 and 1000 kcal level introduced with different
ments including Harris‐Benedict [83], World Health predictive formulas [89].
Organization [84], Talbot [83], Schofield [85], Henry [86],
White [87] and Meyer et al.’s [28] prediction equation and the Bias at 200 Bias at 1000 Mean
simplified equation based on bedside volumetric carbon Predictive equation kcal (%) kcal (%) bias (%)
dioxide elimination method by Mehta et al. [88]. A recent Talbot tables −2 −5 −2
study by Jotterand Chaparro et al. [89] assessed all equations
Schofield WH −5 9 4
specifically recommended for PICU. That study found that
the equations by Mehta, Schofield and Henry had a bias Schofield W −8 6 1
<10%, however, the 95% confidence interval was large and Henry W −5 8 3
contained values well beyond ±10% of measured energy Henry WH 6 0 2
expenditure (MEE) (Table 6.5). A subsequent systematic Mehta −10 0 −3
review assessing the accuracy of predictive equations of
WHO −15 7 −1
2326 indirect calorimetry measurements in 1102 children
found that none of the equations predicted energy require- Meyer −18 −7 −10
ments within the recommended ±10%, but the Schofield and White 40 −15 11
Talbot equations predicted requirements within ±15% in Harris Benedict −40 −33 −33
50% of cases. infants
Most authors have found that the actual energy expendi- Harris Benedict 175 −3 76
ture is closer to the resting energy expenditure. These stud-
ies are summarised in Table 6.6. WH, weight and height; W, weight.
Nutritional Requirements 87
Table 6.6 Mean energy expenditure using the same indirect calorimeter (published studies since 2000).
Number of
Publication children enrolled Diagnosis Mean energy expenditure
Taylor et al. [30] 57 Mainly liver disease, some head 37.2 kcal/kg

injury and other disorders (155 kJ/kg)
Martinez et al. [90] 43 Post‐surgery, liver transplant, 47 kcal/kg
medical disorders (196 kJ/kg)
De Wit et al. [31] 21 Post‐cardiac surgery 67.8 kcal/kg
(283 kJ/kg)
Botran et al. [91] 46 Post‐surgery and medical 48.8 kcal/kg
(204 kJ/kg)
Meyer et al. [28] 175 Respiratory, surgical, sepsis, 44.6 kcal/kg
liver and cardiac (186 kJ/kg)
Mehta et al. [88] 94 Ventilated critically ill children 41 kcal/kg (171 kJ/kg) derivation data
(diagnoses not specified) set and 55 kcal/kg (230 kJ/kg)
validation data set
Jotterand Chaparro 75 Cardiac surgery, medical emergencies, 55 kcal/kg
et al. [92] ear and nose tract surgery (239 kJ/kg)
calculated by Schofield or World Health Organization/Food Table 6.7 Recommended predictive equations for calculating resting
Agriculture Organization/United Nations University equa- energy expenditure (REE) in critically ill children.
tions, can be used using an accurate body weight without any
Name of equation Equation (kcal/24 hours)
additional stress factor (Table 6.7) [93]. The Schofield equa-
tion is used most commonly in the UK and also in 55% of Schofield Males
European PICU [24], with some evidence of reasonable cor- (if accurate weight <3 years: (59.5 × W) – 30
relation with ventilated CIC. The use of physical activity fac- is available) 3–10 years: (22.7 × W) + 505
tor is described by van der Kuip et al. [33], however, this is 10–18 years: (17.7 × W) + 658
Females
difficult to estimate and apply in clinical practice. It is recom-
<3 years: (58.3 × W) – 31
mended to achieve at least two thirds of calculated energy 3–10 years: (20.3 × W) + 486
target within the first week of admission [95]. 10–18 years: (13.4 × W) + 692
If indirect calorimetry is considered, it is important to only
Schofield Males
use validated metabolic carts. The Deltatrac II (GE Healthcare) (if an accurate <3 years: (0.167 × W) + (1517.4 × H) − 616.6
has been validated in all populations, but is being used less weight and height 3–10 years: (19.6 × W) + (130.3 × H) + 414.9
as it has not been technologically updated. Several breath by is available) 10–18 years: (16.97 x W) + (137.2 x H) + 515.5
breath indirect calorimeters exist, however, many are not Females
validated and accuracy in small children (weighing <10 kg) <3 years: (16.252 × W) + (1023.3 × H) – 413.5
3–10 years: (16.25 × W) + (161.8 × H) + 371.2
is questionable [96]. As well as cost considerations and
10–18 years: (8.365 × W) + (465 × H) + 200.0
choosing the correct indirect calorimeter, ensuring there is
WHO/FAO/UNU Males
sufficient resource to provide a service [97], care should be
formula 0–3 years: (60.9 × W) − 54
taken to perform measurements only in a resting state and to 3–10 years: (22.7 × W) − 495
not perform any measurements if the FiO2 is >60%, or in 10–18 years: (17.5 × W) + 651
patients with an endotracheal tube leak >10%. Dietitians Females
need to be aware that measurements in patients on haemodi- 0–3 years: (61 × W) − 51
alysis/haemofiltration may not be accurate [98, 99]. 3–10 years: (22.4 × W) + 486
10–18 years: (12.2 × W) + 746
W, weight (kg); H, height (m).

Learning points: energy requirements
Protein requirements
• acute phase – hypometabolism – energy requirements do
not usually exceed BMR: Schofield equation with no activ- Although there are no specific guidelines on protein
ity factor requirements in ventilated CIC, research has shown that
• stable phase – energy requirements: Schofield equation patients with an adequate energy and protein intake have a
1.2–1.4 × BMR positive nitrogen balance, unlike patients that are underfed
• recovery phase – energy requirements: Schofield equation [4], although a positive nitrogen balance does not equate to
up to 2 × BMR protein utilisation [20, 100, 101]. Agus and Jacksic [102] sug-
gest that the critically ill infant and child should receive 2–3
and 1.5 g/kg of protein, respectively, and in severely in CIC. Low serum levels of micronutrients during the acute
stressed states may require even more (≥3 g/kg). The 2017 phase may be related to the impact of the inflammatory
ASPEN guidelines, based on expert opinion, recommend a response on micronutrient transporters (particularly those
minimum of 1.5 g/kg/day [95] for CIC. In contrast ESPNIC associated with albumin), over‐hydration and oxidative
reported there was insufficient evidence to recommend a stress [110]. As a result there are no specific recommenda-
protein/amino acid intake of 1.5 g/kg or higher during the tions for ventilated patients in PICU [111]. The pharmaco-
acute phase of disease and that more research is required to logical use of vitamins and trace minerals in paediatric
determine the exact threshold of protein which may be of illness is controversial due to reports of toxicity [80, 112].
benefit during critical illness as previous recommendations When energy and fluid requirements are met by commercial
may overestimate protein/amino acid requirements during enteral tube feeds, CIC should receive sufficient vitamins
the acute phase acute critical illness [71]. Increased amounts and minerals to meet the RNI for both. However, many
of protein/ amino acids may be required during rehabilita- patients require additional supplementation, depending on
tion [8] Disease specific protein recommendations, e.g. for diagnosis and treatment modality, e.g. premature infants,
renal failure, burns also provide useful guidelines for chil- haemofiltration [113]. This should be done under supervi-
dren in PICU. sion and monitored with blood biochemistry.
A recent study has suggested that during the acute phase
amino acid intake from parenteral nutrition exceeding age
related reference nutrient intakes (RNI) is associated with Nutrition care plans and outcomes
increased serum urea and harm [71] as well as shortened
leucocyte telomere length [103]. It is important to empha- Defining energy and protein requirements is integral to any
sise these results arise from one large randomised con- part of a nutrition care plan [114]. In addition, there is a
trolled study and additional studies are required to confirm growing focus on clinical outcomes as part of the nutrition
the association [104, 105]. These findings are in contrast care pathway [115]. A large multicentred retrospective study
from other observational studies which report that an in CIC investigated whether early documentation of nutri-
average daily total protein intake >1.5 g/kg and energy tion care plans had any effect on daily energy intake and
intake of 58 kcal (242 kJ)/kg was associated with lower route of nutrition support: 47.7% had energy requirements
mortality [106], although further research is required as documented in the medical notes and these patients had sig-
during the acute phase these levels may overestimate nificantly higher total daily energy intake and were more
requirements during the acute phase [94]. There is insuffi- likely to be fed enterally during the first 4 days of admission
cient data to determine the optimal structure and type of to a PICU compared with those without a nutrition care plan
protein used in CIC [75]. [114]. The implementation of nutrition practice guidelines
It is important to note from the PEPaNIC study [107] and and participation of dietitians in medical rounds improved
other studies that providing an excess of nutrients during the nutritional intake in some patients [116, 117]. In another
the acute phase may be detrimental to critically ill children, large international prospective study in adults increased
particularly during the acute phase of critical illness [94, 108] intake of energy and protein was associated with better clini-
and, therefore, age related nutritional requirements should cal outcomes [118]. As a result, the Faculty of Intensive Care
not be exceeded [8, 93]. It is also important to note that sub- Society has published minimum standards for intensive care
strate utilisation and effect on inflammatory mediators will units which recommend that a dietitian is part of an inten-
vary depending on the route and type of macronutrients sive care multidisciplinary team contributing to improved
administered, e.g. intravenous vs. enteral [71, 109]. delivery of nutrition support to all ICU patients [119].
Nutritional management
Learning points: protein requirements
When to commence nutrition support
• Expert opinion recommends 1.5 g/kg /day as a minimum
• ASPEN recommends 2–3 g/kg/day The aim of nutritional support in critically ill children is not
• PEPaNIC results suggest that it may be of benefit to to reverse the course of illness or pre‐existing malnutrition,
withhold PN for the first 7 days of critical illness (excluding but is to possibly minimise nutrient deficits and prevent a
preterm infants) further decline in nutritional status [117]. Traditionally, nutri-
tion support has been withheld in children in PICU until
metabolic and cardiopulmonary stability has been estab-
lished [120]. However, many units have changed their proto-
Vitamins and minerals cols and guidelines to include nutritional support at an earlier
stage. Early enteral feeds can be safely initiated within 6
Vitamin and trace mineral metabolism in critically ill and hours of admission and by 24 hours in CIC, including those
postoperative paediatric patients is not a well researched with single ventricle cardiac physiology [120–124]. Early
area. Valla et al. described significantly lower plasma levels of enteral feeing may improve nutritional delivery, particularly
selenium, copper, zinc, vitamin C, vitamin E and β‐carotene when used in conjunction with locally adapted feeding
Nutritional Management 89
protocols, and is also cost effective [117, 125]. Increasing feeds • Energy requirements in neonates treated with ECMO are
in a stepwise fashion has been shown to be an effective way equivalent to healthy subjects
to initiate and advance nutritional support until the goal vol- • Enteral feedings should be initiated when the patient on
ume and rate of feed delivery is achieved. [120, 123, 124, 126]. ECMO has clinically stabilised
There are four main hypotheses to justify early feeding in
Due to the nature of ECLS it is not possible to use indirect
CIC:
calorimetry and, therefore, predictive equations, e.g.
• Fasting has a deleterious effect on these patients Schofield, should be used without stress factors [134]. Fluid
• Energy supply plays an important role in the promotion is not usually restricted and if clinically stable it is usually
of energy metabolism possible to provide adequate amounts of enteral nutrition.
• The delivery of nutrients is important for gut maintenance
• Specific nutrients provide support for organ and system
functions
Route of feeding
The combination of decreased blood flow to the gut and Although it is an acknowledged fact that using the enteral
interactions with drugs can lead to a reduction of nutrient route is more physiological and beneficial to CIC, the debate
absorption and gastric motility, failure of gastric acid secre- of enteral vs. parenteral nutrition in critical care has changed
tion and increase in intestinal permeability and bacterial its focus to the delivery of nutrients in the most effective and
translocation [127, 128]. Early enteral nutrition support may safe way, using the most appropriate route for the individual
reverse these effects by reducing catabolism, promoting patient [123].
wound healing and, most likely, decreasing the frequency of Standard protocols have been shown to be useful in both
clinical sepsis [129]. improving the time taken to initiate feeding, as well as pro-
Extracorporeal life support (ECLS), or extracorporeal gression to full feeds [120, 135, 136]. Enteral feeding proto-
membrane oxygenation (ECMO), is used in children with cols guide medical and nursing staff through the choice of
refractory respiratory and heart failure in order to maximise tube feeds, the feeding rates depending on the child’s age
medical management. In a European survey of nutritional and weight, as well as guidelines for the continuous moni-
practices in CIC with CHD enteral nutrition support was rec- toring process.
ommended for those requiring ECLS [130]. With an increas-
ing number of centres commissioned to provide this type of
life support it is important that nutritional support during Nasogastric versus nasojejunal feeding
periods of ECLS is optimised in this vulnerable group of chil-
Nasogastric (NG) feeding is most widely used and is usually
dren. Previous concerns during periods of ECLS regarding
safe and well tolerated in CIC [93]. However, gastric delivery
the risk of decreased mesenteric blood flow and use of vaso-
of enteral feeds may be poorly tolerated due to disordered
active medication, e.g. inotropes, resulting in intestinal
gastric motility which may lead to aspiration. In addition, the
ischaemia, cardiac necrotising enterocolitis and gut haemor-
use of gastric residual volume as a marker of tolerance of NG
rhage delayed the introduction of enteral nutrition [131].
feeding has a poor evidence base and is often been blamed
Parenteral nutrition was the traditional mode of nutrition
for inadequate delivery of feed [91, 137]. Horn et al. [138]
support, however, this has been associated with increased
defined delayed gastric emptying in CIC as >5 mL/kg gastric
risk of catheter related line sepsis [132]; as such enteral nutri-
residuals every 4 hours. Although this provides some guid-
tion is regarded as the preferred route of nutritional support.
ance, this is still an arbitrary volume and may still lead to
Ong et al. [133] recently completed a retrospective cohort
feeds being inappropriately stopped. Therefore, interest has
study of children aged between 1 month and 18 years of age
focused on post‐pyloric feeding. Nasojejunal (NJ) feeding has
(n = 51) who required ECLS. Their average (range) intakes of
been shown by several centres to be safe and effective in this
energy and protein of 23.2 (16.0–35.9) kcal/kg/day and 0.8
subset of patients, enabling adequate delivery of nutrition in
(0.4–1.38) g/kg/day represented around 50% of estimated
a shorter period of time in the majority of patients and so
requirements. In this cohort intake of enteral nutrition was
reducing the problems had PN been used: hyperglycaemia,
affected by veno‐arterial compared with veno‐venous cannu-
hypertriglyceridaemia and hepatic dysfunction [139].
lation and vasoactive inotropes score (VIS). Greater enteral
However, in cyanotic patients it is important to note a risk in
nutrition adequacy remained associated with lower mortal-
the development of necrotising enterocolitis with enteral
ity after controlling for number of days of ECMO, need for
feeding, therefore, additional care in the monitoring of
continuous renal replacement therapies (CRRT) and number
haemodynamic status is warranted when NJ feeds are given
of vasoactive and inotropic drugs required. ASPEN have
to this subgroup of patients [140]. Many units avoid post‐
published clinical guidelines for the nutrition support of neo-
pyloric feeding as NJ tubes are extremely difficult to place
nates/infants supported on ECLS and provide the following
and become dislodged very easily [141]. Several blind (non‐
recommendations (levels of evidence D) [134]:
radiological guided) bedside techniques have been success-
• Timely nutrition support should be provided in neonates fully developed using weighted or unweighted polyurethane
treated with ECLS NG tubes with hydrophilic guide wires. Meyer et al. [142]
• Neonates treated with ECLS have protein requirements have shown that with continuous training and audit, a blind
of up to 3 g/kg/day placement technique can be maintained at 96% success rate.
Gastric feeding is considered to be as effective as post‐ Table 6.8 Case study: a child admitted to the paediatric intensive care
pyloric feeding in the majority of critically ill children and unit.
should be considered as the first choice of feeding route.
A 13 month old boy with meningococcal sepsis was admitted to PICU.
However, post‐pyloric feeding should be considered in those He received fluid resuscitation and after 5 hours of admission, the
CIC at high risk of aspiration or requiring frequent fasting for doctors deem him haemodynamically stable so he can commence
surgery or procedures (e.g. severely burned children and those enteral nutrition. He is fully sedated (including muscle relaxants) and
with traumatic brain injury or on non‐invasive ventilation). ventilated, requiring adrenalin.
Anthropometry
Continuous feeds versus bolus feeding Weight = 11.2 kg
Length = no recent length available
Both continuous as well as bolus feeding have been used in Biochemistry
paediatric critical care. The pros and cons of both are well Electrolytes are all within normal range, but in order to achieve this he
studied in the neonatal and adult setting [143, 144], but in is receiving potassium and magnesium corrections. Albumin is low,
paediatrics individual units have their preferred practice. urea is increased, creatinine is increased.
Although bolus feeding is more physiological difficulties Clinical
with monitoring the tolerance, as well as the additional nurs- Necrotic areas in all extremities: fingers and toes. Necrotic areas on the
ing input, has led to many PICUs preferring continuous feed- face as well.
ing. On the other hand, continuous feeding has been shown Diet history
to delay gastric emptying in adult ICU patients [145] and Parents report that he usually eats well at home and consumes
reduce gallbladder contraction [146]. Horn et al., however, 500–600 mL of full fat cow’s milk, has red meat twice per week and
otherwise has fish or chicken.
showed gastric residual volumes did not differ between chil-
dren on bolus or continuous feeds [138]. In the absence of Nutritional requirements
Activity: physiotherapy twice per day, he is turned four times per day
substantial clinical evidence, consensus is that the adequate
and is not fully ventilated.
delivery of nutrition support should be the main goal in feed- Energy requirements:
ing CIC and should not be hampered by the feeding route. A = (59.512 × 11.2) – 30.4
case study of a child admitted to PICU is given in Table 6.8. = 564.72 + 10%
= 636 kcal (2.66 MJ)
Protein requirements: 2–3 g/kg/day = 22.4–33.6 g/day
Type of enteral feed Enteral feed: 1 kcal/mL (4 kJ/mL) feed with a multifibre mix
Feeding route: trial NG. Likelihood of having gastroparesis is high
(adrenalin, shock) and may therefore require NJ.
Although there is a wide variety of types of enteral feed
available, there remains a paucity of data regarding optimal NG, nasogastric; NJ, nasojejunal.
enteral feed composition during critical illness in children.
Feeds range from human milk and standard infant formula
perceived feed intolerance the use of a peptide based energy
to various specialised infant and paediatric feeds, including
and nutrient dense feed in critically ill infants with a PICU
energy and nutrient dense formulas with varying protein
length of stay >7 days has been shown to promote weight
and fat sources [147–150]. However, the metabolic utilisation
gain and reduce the incidence of feeding interruptions due
and assimilation of proteins, carbohydrates, fats and other
to feed intolerance to 2% [159].
nutrients during critical illness may be affected by hypoxae-
There remains a paucity of data regarding optimal enteral
mia, dysbiosis and impoverishment of the microbiome [151–
feed composition during critical illness and further work is
153], affecting absorption, tolerance and utilisation of protein
required regarding the type and timing of feeds, particularly
[101], fats and energy [4, 19].
as tolerance to feeds [160] or metabolic adjustments for vari-
Traditionally polymeric enteral feeds or breastmilk are
ous macronutrient sources may change throughout the
used as first line in CIC [148]. Peptide based feeds are usu-
acute, stable and recovery phase of critical illness [161].
ally considered as second line, particularly following cardiac
surgery or where tolerance to polymeric feed is poor, e.g.
vomiting, diarrhoea [20, 147, 148, 150]. Energy and nutrient
dense whey based feeds have been successfully use in criti- Learning points: enteral feeding
cally ill infants during the first week of admission, resulting
in significantly higher de novo arginine synthesis and higher • Enteral feeds can be safely commenced within 12 hours of
nutritional intakes compared to standard infant feeds [154, admission
155]. These feeds have also been shown to be well tolerated • Gastric feeding is as effective as post‐pyloric feeding
from day 1 of admission [149, 155, 156] and are associated • Where there is tight fluid management, e.g. <4 mL/kg/hour,
with weight gain during a PICU admission [157] and, in the use of an energy and nutrient dense feed from day 1 may
post‐surgical infants with CHD, achievement of nutritional allow nutritional targets to be met more easily
goals of 92%–161% of BMR (51–89 kcal/kg/day) compared • Where there is poor feeding tolerance the use of a peptide
with 80%–100% of BMR (44–56 kcal/kg/day) in the control based energy and nutrient dense feed may improve feeding
group [158]. However, not all infants tolerate energy and outcomes
nutrient dense whey based feeds and where there is
Future Research and Unanswered Questions 91
Monitoring Complications
Ideally CIC should have their nutrition monitored daily. The Refeeding syndrome
clinical situation can change rapidly and may impact on
nutritional requirements. Nutrition is also impacted by: As the prevalence of malnutrition within the PICU population
is high, the risk for refeeding syndrome should be considered.
• fluid volume restriction – the main barrier to adequate When enteral or parenteral nutrition is commenced in children
nutrition delivery. The dietitian needs to establish who have not received optimal nutritional support for some
whether such strict fluid restriction is required in the time, e.g. ≥3 days, it is important to ensure there is a multidisci-
light of inadequate nutrient delivery and to change plinary approach to determine the risk of refeeding syndrome
the enteral feed (if necessary); also to negotiate in addition to an appropriate management strategy regarding
whether drugs running in intravenous (IV) fluids can electrolyte replacement, vitamin supplementation and energy
be made more concentrated, thus liberating volume and/or protein restriction [165–167]. Figure 6.4 provides a
for feeding [162]. management outline on refeeding syndrome in PICU [168].
• procedural interruptions – can account for 11%–57% of Baseline:
total interruptions affecting up to 62% of patients [137].
The most common interruptions arise from surgery, radi- • Before starting to feed complete baseline bloods for
ological procedures, attempts at extubation and the sodium, potassium, phosphate, magnesium, corrected
administration of medication. Often feeding rates are not calcium, creatinine, glucose, particularly vitamin D, par-
increased to compensate for time lost during the inter- athyroid hormone, alkaline phosphatase and albumin.
ruption making it challenging to achieve nutrition goals, • On day 0 supplement at least 30 minutes before starting
with the resultant large energy and protein deficits nega- or restarting feeding.
tively impacting on weight [162, 163]. • Give a daily dose of oral thiamin for 2 weeks: <1 year of
• interruption due to gastrointestinal intolerance – especially age 50 mg daily for 2 weeks; >1 year of age 100 mg daily
where there is vomiting, diarrhoea, large gastric residu- for 2 weeks.
als and abdominal distension which may occur in up to During feeding (days 0 to 4–10):
57% of patients [162].
• mechanical problems – such as NJ tube dislodgement, NG • Repeat laboratory testing every 12 hours of the follow-
blockage [162]. ing: potassium, phosphate, magnesium, and as indi-
cated: corrected calcium, albumin.
The dietitian’s role is critical to improving nutrient • For at least 4 days, continue if laboratory results are aber-
delivery and ensuring protocols and procedures are in rant or show clinically relevant variations.
place to allow for optimal nutritional support [164]. • Supplement with thiamin orally; if nil by mouth then
Table 6.9 shows how often aspects of nutrition support thiamin should be administered intravenously as an
need to be monitored. infusion or repeated intramuscular injections. Doses in
excess of 400 mg/day in adults have been associated
with anaphylaxis.
• Correct any other vitamin deficiencies with therapeutic
Learning points: monitoring doses, e.g. vitamin D.
• Give multivitamins and trace elements complex once
• Regular monitoring of anthropometry, biochemistry and daily: vitamins preferably at least 200% recommended
nutritional intake is essential daily intake (RDI); trace elements at least 100% RDI.
• Dietetic involvement improves nutritional intake • If there are no biochemical or symptomatic changes and
none appear later, the feeding can be increased more
quickly.
• If there is a clinical manifestation of the refeeding syn-
drome consider a slower approach particularly during
Table 6.9 Monitoring frequency in paediatric intensive care unit.
the first week [167].
2–3 times Once Table 6.10 shows recommended electrolyte supplementa-
Daily per week per week tion in the management of refeeding syndrome.
Anthropometry X* X* X*
Biochemistry X Future research and unanswered questions
Recalculation of X* X*
nutrient requirements Immunonutrition
Evaluation of delivery X
of feed The use of immune enhancing enteral feeding formulas is
well known in adult intensive care. In addition to the normal
* Frequency depends on the age of the child. macro‐ and micronutrients, these feeds contain: a mixture of
Patients at risk for refeeding syndrome

• Any child with a history of inadequate nutritional intake pre- or post-admission to hospital – for all at risk check base
line K, Ca, P, Mg levels
• If levels are low, deficits should be corrected using the appropriate age-related reference ranges as targets
• Record pulse (compensatory tachycardia/ bradycardia) and continuous ECG monitoring for arrhythmias, blood
pressure and respiratory rate hourly
• Record an accurate fluid balance, weigh daily
Day 1–5 Initial refeeding – Calculate energy / protein using the table below:
• Start feeding: at 60–75% normal requirements (see below) with standard 0.67 kcal/mL feed (infants) or 0.75–1.0 kcal/mL (children)
• Calorie and protein intake should betailored to each child and the above values may need to be adjusted down by as much as 30%
• Prescribe thiamin: <1 year of age 50 mg daily for 1 week or >1 year of age 100 mg daily for 1 week
• In addition to a multivitamin: <3 years of age 0.6 mL Dalivit daily for 3 weeks or >3 years of age Santogen A-Z 1 tablet daily/Forceval
Junior effervescent tablet 1–2 daily for 3 weeks
• Biochemistry: First 3–5 days, every 24 hours: 24 hourly U&E, Ca, P, Mg, LFTs and FBC, 4 hourly glucose
Day 1–5 initial energy

DRV (kcal/kg) Enteral PN Food Protein
kcal/kg* kcal/kg* g/kg*
• Birth to 1 year 90–110 75% = ≈80 45–55 — 1
• 1–7 years 80–100 75% = 60–75 35 ½ portions 0.6–1
• 7–10 y years 60–75 75% = 55 30–45 ½ portions 0.6–1
• 11–14 years 60 75% = 45 25–30 ½ portions 0.6–1
• 15–18 years 50 75% = 35 25 ½ portions 0.6–1
• >18 years 25–35 75% = 18 10 ½ portions 0.6–1
DRV = Dietary reference values
*Use actual body weight
Then 6–10 days:

• If blood biochemistry is stable, increase energy and protein intake to 100% of normal requirements – e.g. full
enteral feeds or parenteral nutrition or full portions if eating
• As there is still a risk of refeeding syndrome with increasing nutrient intake, continue to check blood biochemistry: 4 hourly
glucose, daily U&E, Ca, P, Mg, LFT & FBC
• Continue to observe for tachycardia/bradycardia, raised blood pressure, respiratory rate, positive fluid balance
Day 11 + Catch-up weight gain:

• For the younger child aim for 20 g/kg/day weight gain
• For older children aim for 1–1.5 kg weight gain per week (aim 2 500–3 000 kcal/day) — ensure protein energy ratio is achieved to
promote appropriate lean body mass accretion
Catch-up no; Energy kcal/kg* Protein g/kg* Protein energy ratio Food
Birth to 1 year 126 2.8 10–12%
1–7 years 126 2.8 10–12% 3 meals and 1–2 snacks/ONS
7–10 years 126 2.8 10–12% 3 meals and 2 snacks/ONS
11–14 years 80 1.5–2 15–20% 3 meals and 2 snacks/ONS
15–18 years 80 1.5–2 15–20% 3 meals and 2 snacks/ONS
> 18 years 80 1.5–2 15–20% 3 meals and 2 snacks/ONS
* Use actual body weight. Aimfor up to 10 years 20g/kg/day > 10 years 0.5 –1 –1.5 kg weight gain week
ONS = oral nutrition supplements, e.g. Fortisip
Figure 6.4 Management of refeeding syndrome in critically ill children.

Future Research and Unanswered Questions 93
Table 6.10 Recommended electrolyte supplementation in refeeding syndrome (NB adjust in case of renal insufficiency) [169].
Electrolyte Serum level Proposed supplementation Frequency of testing
Phosphate • For those children at risk of refeeding syndrome a phosphate of <0.8 mmol/L before initiating feeds should be
corrected to within normal range on the day of admission
Mild to moderate 15–30 mmol/day IV or oral Every 12 hours
0.3–0.8 mmol/L
Severe <0.3 mmol/L (with a rapid drop 0.25–1.0 mmol/kg over 8–12 hours IV Every 6 hours
(>0.3 mmol/L/day) or life‐threatening 4.5 mmol/hour for 3 hours IV followed by
hypophosphataemia) 2.0–3.5 mmol/hour IV with a maximum of 90
mmol/day + frequent testing
Potassium Mild to moderate 30–80 mmol/day IV or oral Every 12 hours
3.0–3.4 mmol/L
Severe <3.0 mmol/L 2–4 mmol/kg/day IV or 120–240 mmol/day IV Every 6 hours
or oral
Magnesium Mild to moderate 13–34 mmol/day oral or 10–15 mmol/day IV Every 12 hours
0.5–0.7 mmol/L
Severe <0.5 mmol/L 1.5–3.0 mmol/hour IV or with very severe Every 6 hours
hypomagnesemia 4 mmol/hour IV
IV, intravenous.
omega‐3 and omega‐6 fatty acids (which have pro‐ and anti‐ metoclopramide 10 mg every 12 hours. Initial analysis found
inflammatory properties); additional arginine and/or glu- no difference in the development of nosocomial infections/
tamine (which become conditionally essential amino acids sepsis. A post hoc analysis was completed according to three
during increased physiological stress); and increased levels categories of immune status on admission: immune compe-
of the antioxidants selenium and β‐carotene [170]. Although tent without lymphopenia (n = 134), immune competent
these enteral feeding formulas have all the ingredients to with lymphopenia (n = 79) and previously immunocompro-
improve outcome, results in the adult population have been mised (n = 27). There was no difference in the development
conflicting, as seen in a large multicentre randomised study of nosocomial infection and sepsis in the overall population.
where there have been higher mortality rates in the immu- However, there was some benefit in the immunocompro-
nonutrition group among patients with severe sepsis or mised group with fewer nosocomial infections/sepsis
septic shock [171, 172]. reported in the immune enhancing group compared to the
There are fewer studies completed in children using whey group: 1.57 per 1000 days compared with 6.33 per 1000
immune enhancing diets. Briassoulis et al. [173] used an days respectively (p = 0.01).
adult feed containing arginine, glutamine, omega‐3 fatty Jacobs et al. [175] considered the use of a feed enriched with
acids and antioxidants (vitamin C, selenium and zinc) com- γ‐linoleic acid and eicosapentaenoic acid (EPA) compared to
pared to a standard paediatric enteral feed. Mean intake standard paediatric enteral feed. The only outcomes reported
after 5 days for the immune enhancing diet group was 52 ± 6 that there were significantly higher levels of plasma phospho-
vs. 63 ± 6.3 kcal/kg in the paediatric feed group and 2.7 ± 0.4 lipids of γ‐linolenic acid and EPA, which would be expected.
vs. 2 ± 0.2 g/kg protein respectively. After 5 days IL‐6 levels This area of paediatric critical care nutrition is still very new
were significantly lower (11.8 ± 2.4 pg/mL vs. 38.3 ± 3.6 pg/mL and the limited evidence does not yet support routine use of
p < 0.0001) in the immune enhancing diet group compared to immune enhancing feeds or supplementation because of pos-
the paediatric enteral feed group; IL‐8 levels were signifi- sible deleterious effects. Until such data are available, specifi-
cantly higher at 65.4 ± 17 vs. 21±2.5 pg/mL p < 0.03. There cally for CIC, the following ad hoc additions to feeds or future
was no relationship between energy or protein intake and immune enhancing feeds should be used with caution.
inflammatory mediators. There were no differences in sec-
ondary infections, duration of mechanical ventilation, length
Glutamine
of stay or mortality rates, so although the use of an immune
enhancing diet may be anti‐inflammatory, this did not sig- Glutamine is thought to be able to alter the host response to
nificantly impact on any of the outcome measures chosen. stress [176], however, much of the work considering the use
Carcillo et al. [174] completed the paediatric Critical Illness of glutamine in critical illness has been completed in adults
Stress‐induced Immune Suppression (CRISIS) comparative [177–181]. Whilst initially considered to be safe and non‐toxic
effectiveness trial investigating the interaction between recent studies have found that in critically ill septic adults
immune enhancing nutraceuticals with intravenous (IV) supraphysiological levels of glutamine may increase the risk
metoclopramide on immune status compared to whey proof mortality [172, 182], although a recent meta‐analysis which
tein and IV saline in critically ill children In the treatment considered the administration of glutamine dipeptide as per
group children received enteral zinc 20 mg, an age depend- ESPEN (European Society of Clinical Nutrition and
ent dose of selenium 40–400 μg, glutamine 0.3 g/kg and IV Metabolism) recommendations (via the parenteral route at
0.3–0.5 g/kg/day; maximum 30% of the prescribed nitrogen expression of numerous genes either requires zinc and or has
supply) demonstrates significant reduction in length of hos- a role in regulating zinc homeostasis [202]. Critically ill chil-
pital stay, mortality and infectious complications rates [183]. dren have been found to have significantly lower plasma
Glutamine serves as a metabolic intermediate and precur- zinc levels in the first few days of their illness which is cor-
sor, providing carbon and nitrogen for the de novo synthesis related with markers of inflammation (IL‐6 and CRP levels).
of other amino acids, nucleic acids, fatty acids, nucleotides Persistently low plasma concentrations are also associated
and proteins [184]. During times of stress, skeletal muscle is with the severity (and number) of organ(s) dysfunction [81],
an active net exporter of free glutamine [37]. Glutamine’s increased mortality rate in septic shock [202] and pneumonia
functions within the cell can be broadly classified into four [203, 204], although the causality of this is not well under-
main categories: stood. Yuan et al. [205] investigated the use of zinc supple-
mentation in a non‐blinded randomised controlled trial in
1. nitrogen transport critically ill infants (n = 96) with severe pneumonia. There
2. maintenance of the cellular redox state through was no statistical difference in lung injury score, length of
glutathione hospital stay or duration of mechanical ventilation. Although
3. a metabolic intermediate zinc supplementation does not prevent infection in critically
4. a source of energy [184]. ill children, supplementation may benefit those who are
found to be deficient [203, 204, 206], particularly during the
In children, the use of glutamine remains largely unde- recovery phase, but has not been found to be of any benefit
fined with paucity of data regarding the benefits of glu- in children who are otherwise zinc replete [204–206].
tamine as a pharmacological agent in critical illness. Zinc absorption occurs in the small intestine which is facil-
Conflicting results with respect to the benefits of glutamine itated by zinc transporters and it is stored in the liver and
supplementation have been reported in preterm infants kidney. Zinc is excreted from the kidney (0.5–0.8 mg/day) or
[185–190], infants with gastrointestinal disease and surgery is recycled back into the intestine. Zinc is vital for linear
[191, 192], burns [177, 193] and malnutrition [194–196]. Three growth and is required in larger amounts during periods of
randomised studies have been completed in CIC, two of nutritional rehabilitation. In severe and moderate malnutri-
which considered glutamine supplemented parenteral nutrition zinc muscle concentration is reduced from 81 to 64 mg/
tion [19, 197] and one using glutamine supplemented enteral kg. This tissue deficit will require an additional retention of
nutrition [198]. Ong et al. administered IV glutamine (0.4 g/ 0.57 mg/kg/day and will take approximately 30 days to
kg/day), however, this study did not report any benefit with replete if a child is eating a normal amount of protein in their
no significant difference in sepsis, however, there was a diet [207].
highly significant weight loss in all groups (−1.0 z scores to
−1.3 z scores) suggesting that insufficient nutrients were pro-
vided to sustain growth in both study arms and this may be Selenium
in part the reason for the lack of efficacy seen [199].
Selenium is an essential trace element with antioxidant and
Jordan et al. investigated the effects of glutamine on heat
immunological functions. Selenium has been shown to inhibit
shock protein 70 (HSP70) and inflammatory mediators in
the expression of pro‐inflammatory genes, down regulating
critically ill children (n = 98). Those children who were septic
the inflammatory response. Decreased selenium levels are
or had undergone major surgery were randomised to PN
found in adults with systemic inflammatory response syn-
with glutamine supplementation (0.33 g/kg glutamine [=
drome (SIRS) and multi‐organ failure [208]. High doses of
0.5 g/kg Dipeptiven]) for a minimum of 5 days vs. standard
selenium given as an IV infusion of selenite (1000–1600 μg)
isocaloric and isonitrogenous PN [197]. In this study glu-
has shown: to be well tolerated, significantly increasing sele-
tamine supplementation upregulated the release of HSP70.
nium levels with resultant lower incidence of hospital
These children also had significantly lower levels of IL‐6,
acquired ventilator associated pneumonia; a reduction in
suggesting that glutamine supplementation was able to
infection risk; a decreased mortality in patients with severe
increase HSP70 release and modulate the release of pro‐
sepsis or septic shock [209]. Selenium given enterally as a feed
inflammatory mediators [197]. HSP70 is part of a family of
constituent has not been shown to be as effective, although the
highly conserved proteins involved in cell protection and
dose delivered was significantly lower at 300 μg [210]. There
modulation of the inflammatory response, in particular
are no studies considering the efficacy of selenium in CIC.
NF‐κB and MAPK pathway [200, 201].
The paediatric Critical Illness Stress‐induced Immune
At present there is insufficient evidence to recommend the
Suppression (CRISIS) trial is currently considering the effect
routine use of glutamine supplementation in paediatric criti-
of an enterally administered whey protein supplemented
cal illness.
with trace zinc, selenium and glutamine. These results are
awaited with interest and may change practice in relation to
Zinc
glutamine, zinc and selenium supplementation [174].
Zinc is an essential trace element which is required for the
function of numerous enzymes and transcriptional factors.
Vitamin D
Zinc homeostasis maintains immune function, oxidative
stress response, neurocognitive function and promotes There are numerous reports of low vitamin D levels in
growth and development [81]. During critical illness the critically ill children, which is associated with a greater

Future Research 95
severity of illness [211], although the causality and the microbial balance [219]. Altering enteric flora is a concept
impact of vitamin D on outcomes during critical illness gaining popularity throughout the world and the use of pro-
remain unclear [212]. Gottschlich et al. [213] completed a ran- biotic bacteria in PICU is developing too. Intestinal permea-
domised controlled trial of CIC with thermal injuries (n = 50) bility is increased during critical illness particularly after
aged 0.7–18.4 years, investigating the effect of vitamin D sup- burns, major trauma and sepsis. In addition, bacterial trans-
plementation. During the acute phase the authors reported location has been demonstrated in patients with bowel
there were no significant differences in serum vitamin D lev- obstruction. The administration of some probiotic strains
els between groups, although >10% of patients had low has been associated with a reduction in bacterial transloca-
serum 25(OH)D levels at the point of PICU discharge. The tion and intestinal inflammation [148].
proportion of children with vitamin D deficiency (defined as In critically ill patients, the main concern remains the
vitamin D < 30 nmol/L) increased in the group who received possibility of septicaemia related to the provision of live
no vitamin D supplementation at 1‐year follow up compared bacteria to patients that are relatively immunocompro-
to those who had received D2 and D3. The prevalence of mised, although there are some studies showing their
vitamin D deficiency in the groups was: no vitamin D sup- safety and beneficial effects in critical illness [220]. A ran-
plementation 75%; D2 supplementation 56%; and D3 sup- domised double blind placebo controlled study in CIC
plementation 25%. Although the study was not powered to with severe sepsis evaluated the effect of probiotics on
detect changes in clinical outcomes some non‐statistically cytokines, duration of PICU length of day and healthcare
significant improvements were demonstrated. A larger clini- associated costs. One hundred children with severe sepsis
cally powered randomised clinical trial is required to inves- aged 3 months to 12 years of age were enrolled to receive
tigate the effect of vitamin D supplementation in CIC both VSL#3 which contains Lactobacillus paracasei, L. plantarum,
during acute phase and rehabilitative phase. L. acidophilus, L. delbrueckii, Bifidobacterium longum, B. infan-
McNally et al. [214] undertook a meta‐analysis of published tis, B. breve, Streptococcus salivarius, maltose and silicon
papers to examine and estimate prevalence of vitamin D defi- dioxide (n = 50), or a placebo of maltose and silicon diox-
ciency in CIC compared to levels reported in healthy children. ide (n = 50). Probiotics or placebo was administered in a
The average 25(OH)D levels were significantly lower in criti- dose of one sachet twice a day for 7 days, orally or through
cally ill children (range 41.5–66.8 nmol/L) than in healthy nasogastric/orogastric tube depending on clinical status
children (61–99 nmol/L) with a pooled difference −17.3 nmol/ of patients. From day 1 to day 7 the probiotic group had
L, 95% CI −14.0 to −20.6. Length of stay was evaluated in 11 significantly lower levels of pro‐inflammatory cytokines,
studies, but only 3 published data were suitable for evalua- IL‐6, IL‐12p70, IL‐17 and TNFα, and higher levels of anti‐
tion (1.99 days, 95% CI 0.88–3.10, p = 0.001). Four studies eval- inflammatory cytokines, IL‐10 and transforming growth
uated association with culture positive sepsis (pooled OR factor‐β1, than the placebo group. There was a non‐signifi-
2.02, 95% CI 1.08–3.78, p = 0.03). Vitamin D was associated cant trend toward lower incidence of healthcare associated
with increased mortality (OR 1.62, 95% CI 1.11–2.36) and ill- infections (14% vs. 20%) and duration of ICU stay (6.5 vs. 9
ness severity. Vitamin D should be supplemented with thera- days) in the probiotic group. Mortality rates were similar
peutic doses in those children found to be deficient. in two groups. This study suggests a role for probiotics
supplements in immune modulation in critically ill chil-
dren. Further studies are required to confirm these results
Probiotics
as they may be strain and geographical location dependent
Critical illness is associated with gastrointestinal microbiome [221]. A recent systematic review aimed at answering the
dysbiosis, with a loss of healthy commensal bifidobacteria question of routine use of probiotics in CIC found that
and an overgrowth of pathogenic bacteria [215], which may in although there were positive results in some studies, rou-
turn impact on nutrient assimilation [216]. In children there is tine use of probiotics cannot yet be recommended [220].
increasing evidence that alterations in gut microbiota [217] Safety also needs to be taken into account, with data point-
may result in changes to the gut epithelium which may be ing towards caution in extreme premature infants and
associated with clinical outcomes in critically ill children [218]. those that are immunocompromised, in particular where
A probiotic is a live microbial feed supplement which the permeability of the gastrointestinal tract has been
beneficially affects the host by improving its intestinal impaired [222].
Future Research
A number of research priorities have been identified includ- intolerance; role of parenteral nutrition and longer term
ing the: impact of malnutrition during critical illness; outcomes [223].
development of nutrition risk assessment tools and bio-
markers; accurate assessment of nutritional requirements References, further reading, guidelines, support groups
in all phases of critical illness; type and role of protein; role and other useful links are on the companion website:
of immunonutrition and micronutrients; mode, type and www.wiley.com/go/shaw/paediatricdietetics-5e
delivery of enteral nutrition; management of feeding
7 Preterm Infants
Karen King and Lynne Radbone
Introduction Nutritional requirements
A preterm infant is one born before 37 weeks’ completed ges Preterm infants have limited stores of many nutrients as
tation. An infant born <2500 g is termed low birthweight accretion occurs predominantly in the last trimester of
regardless of gestation, <1500 g very low birthweight (VLBW) pregnancy [4]. They are born poorly equipped to with
and those <1000 g extremely low birthweight (ELBW). stand inadequate nutrition; theoretically, endogenous
Categorisation of infants born smaller than expected is more reserves in a 1000 g infant are only sufficient for 4 days if
contentious; however, they are often divided into small for left unfed [5]. In addition, the gastrointestinal system of a
gestational age (SGA) and/or intrauterine growth restricted preterm infant is immature; thus it is generally accepted
(IUGR). Classification of SGA infants is usually defined as that most infants of <30 weeks’ gestation and/or weighing
<9th centile for weight at birth (depending on the source of <1.25 kg will need some parenteral nutrition (PN), while
definition), and they constitute a heterogeneous group, i.e. enteral feeds are gradually increased to ensure an a dequate
those destined to be born small due to genetic influences and nutritional intake. The most recent comprehensive reviews
those who are IUGR. The former group tends to be propor and recommendations for enteral nutritional require
tionally small. Those who are IUGR will have a similarly low ments are those of Agostoni et al. [6] and Koletzko et al. [7]
birthweight but may show head and/or length sparing and for parenteral requirements are of the European
depending on the timing of intrauterine nutrient restriction. Society for Paediatric Gastroenterology, Hepatology and
These infants are at high risk of both perinatal and later prob Nutrition (ESPGHAN) [8] (Table 7.1). The interested
lems [1]. This chapter will deal predominantly with the reader is advised to refer to these publications for further
nutritional needs of preterm infants. information.
The early nutritional management of preterm infants may Precise requirements for infants with a birthweight
be vital to their later outcome but can be hampered by an between 1800 and 2500 g are not given in these enteral feed
immature or dysfunctional gastrointestinal tract and poor ing publications. This has led to varying interpretations of
tolerance of parenteral and enteral nutrition. the weight cut‐offs for feeding preterm formulas or fortify
Small term infants in general are mature with respect to ing breastmilk. Higher nutrient density feeds are not rou
oromotor function and can usually grow well if allowed tinely recommended for term SGA infants, so gestational
breastmilk or standard infant formula ad lib. Only where co‐ age as well as birthweight should dictate local feeding pol
morbidities exist may small term infants need specialised icy. In practice most infants born <2000 g and <34 completed
nutritional input. It is not recommended that these infants be weeks’ gestation will benefit from the higher nutrient
given any formula designed for preterm infants as there may intakes recommended by Agostoni et al. [6] and Koletzko
be adverse outcomes [2, 3]. et al. [7].

Table 7.1 Recommended enteral and parenteral nutrient intakes for very low birthweight infants.
Nutrient (per kg Agostoni et al. [6] Koletzko et al. [7] RNI (1991)* term ESPGHAN [8] preterm
per day) preterm infant enteral preterm infant enteral infant enteral infant parenteral
Energy (kcal) 110–135 110–130 96–120** Day 1: 45–55

Target: 90–120
Protein (g) <1000 g: 4.0–4.5 <1000 g: 4.0–4.5 2.1 Day 1: 1.5 g/kg amino acids
1000–1800 g: 3.5–4.0 1000–1800 g: 3.5–4.0 From day 2: 2.5–3.5 g/kg
amino acids
Carbohydrate (g) 11.6–13.2 11.6–13.2 N/S Day 1: 5.8–11.5
From day 2: 11.5–14.4
Maximum: 17.3
Fat (g) 4.8–6.6 (<40% MCT) 4.8–6.6 N/S Maximum: 4.0
Minimum linoleic acid:
0.25 g
DHA (mg) 12–30 18–60 N/S –
AA (mg) 18–42 18–45 N/S –
Sodium (mmol) 3.0–5.0 3.0–5.0 1.9† In stable phase
>1500 g: 3.0–5.0
<1500 g: 3.0–5.0 (7.0)
Potassium (mmol) 1.6–3.3 2.0–4.9 4.2† In stable phase
>1500 g: 1.0–3.0
<1500 g: 2.0–5.0
Iron (mg) 2.0–3.0 2.0–3.0 1.3‡ 2.0–2.5
Calcium (mmol) 3.0–3.5 3.0–5.0 13.1‡ In growing phase
1.6–3.5
Phosphate (mmol) 1.9–2.8 1.9–4.5 13.1‡ In growing phase
1.6–3.5
Magnesium (mmol) 8.0–15 0.3–0.6 2.2‡ 0.2–0.3
Zinc (mg) 1.1–2.0 1.4–2.5 4.0‡ 400–500
Selenium (μg) 5.0–10 5.0–10 0.1‡ 7.0
Folic acid (μg) 35–100 35–100 50‡ 56
Vitamin A (μg) 400–1000 400–1100 350‡ 227–455
Vitamin D (μg/day)‡ 20–25 10–25 8.5‡ 5–25
Vitamin E (mg) 2.2–11 2.2–11 10‡ 2.8–3.5
N/S, not specified; MCT, medium chain triglycerides; DHA, docosahexaenoic acid; AA, arachidonic acid.
Agostoni et al.’s recommendations are for stable growing preterm infants up to a weight of 1800 g. No recommendations are made for infants <1000 g
except for protein.
Koletzko et al.’s recommendations presented are for fully enterally fed, growing preterm infants with a birthweight up to 1500 g.
*Reference nutrient intake (RNI) for infants aged 0–3 months [9].
**Estimated average requirement (EAR) for energy for infants aged 1–2 months [10].
†
Sodium and potassium values per kg are based on weights given in [10].
‡
per day, not per kg.
Interpretation of requirements resting energy expenditure. In addition, as with other

recommendations for requirements, these are for whole
Caution must be exercised when interpreting recommen populations rather than individuals.
dations for nutritional requirements for two reasons. First, Recommended nutrient intakes are typically greater for
the evidence base for nutrient requirements in preterm enterally fed compared with parenterally fed infants and greater
infants is not robust with very few randomised controlled for preterm compared with term. The following provides fur
trials (RCTs) having been undertaken, particularly in ther information regarding certain key nutrients. Requirements
VLBW or ELBW infants. Recommendations for require refer to those via the enteral route unless specified.
ments are compiled from a variety of data sources includ
ing foetal tissue analysis, placental transfer studies, cohort
studies, case reports of deficiency or toxicity, breastmilk Fluid
composition and a few RCTs of controlled intake. Much of
the data for infants <1000 g is extrapolated. Second, pre During the initial phase of adaptation to extrauterine life,
term infants are a heterogeneous group, and requirements fluid management is complicated, as there is a delicate bal
are highly variable depending on post‐conceptional age ance between matching high transcutaneous losses and
(inversely related), accumulated nutrient deficit (prena avoiding fluid overload due to renal immaturity (although
tally and postnatally), body composition and variations in the former should be minimised by appropriate nursing
98 Preterm Infants
techniques). Very sick preterm infants are often fluid Table 7.2 Suggested upper limit of enteral feed volumes to provide
restricted; therefore, nutritional intakes should always be 4–4.5 g/kg protein.
optimised within the fluid allowed and restrictions lifted as
Suggested Energy
soon as clinical condition permits. Recommendations from
maximum fluid (kcal Protein
Agostoni et al. [6] suggest 135 mL/kg/day as the minimum volume (mL/kg) (kJ)/kg) (g/kg)
requirement with an upper reasonable limit of 200 mL/kg/
day. Between 150 and 165 mL/kg/day is likely to meet SMA Gold Prem 1 150 120 (500) 4.35
enteral requirements if an infant is fed fortified human milk Nutriprem 1 165 132 (550) 4.29
or the lower end of the range if preterm formula is given. Hydrolysed Nutriprem 165 132 (550) 4.29
Breastmilk with SMA Breast 150 129 (540) 4.11
Energy Milk Fortifier*
Breastmilk with Nutriprem 180 151 (630) 4.32
Recommended energy intakes vary according to a baby’s Human Milk Fortifier*
birthweight and postnatal age but are generally higher than
*Using mature breastmilk.
term requirements [11]. There are variations in resting energy
expenditure requirements between individuals with resting
energy expenditure increasing over the first few weeks of life nutrition is crucial to attain the high energy requirements of
[11]. Some IUGR babies may have increased needs to facili preterm infants and to provide essential fatty acids. Feeding
tate catch‐up growth, but this will vary between individuals with non‐heat‐treated breastmilk has the advantage of preserv
and can only be established by monitoring progress and ing endogenous lipase (bile salt‐stimulated lipase) activity,
adjusting intakes accordingly. Optimising body composition which ensures optimum fat absorption [18].
is essential, and excessive energy intake may lead to exces For many years studies have investigated the theory that
sive fat deposition. However, severity of illness rather than enteral medium chain triglycerides (MCT) lead to improved
diet appears to be most closely linked to increased abdominal fat absorption. However, a systematic review found no con
adiposity [12, 13]. It is recommended that >100 kcal (420 kJ)/ sistent advantage [19]. Agostoni et al. [6] recommend that fat
kg/day is generally appropriate for enteral formula feeding in the form of MCT should not exceed 40% of the total fat
as long as adequate protein, 3.0–3.6 g/100 kcal (420 kJ), is pro content of preterm formulas. Preterm formulas currently
vided [6]. There are currently only three preterm formulas contain: SMA Gold Prem 1, 40% fat as MCT; Nutriprem 1,
that meet this requirement: Nutriprem 1, Hydrolysed 10% fat as MCT; and Hydrolysed Nutriprem, 8% fat as MCT.
Nutriprem and SMA Gold Prem 1. Monitoring linear growth It has been recommended that the long chain polyunsatu
as a proxy for lean mass accretion is recommended. rated (LCP) derivatives of linoleic and α‐linolenic acids, namely,
arachidonic and docosahexaenoic acids, be provided in the diet
Protein of preterm infants [6]. However, controversy remains concern
ing their role, with recent reviews concluding that there were
Current recommendations for protein are significantly few significant benefits although no evidence of harm [19, 20].
higher in the preterm infant than that of the term infant, due Outcomes with respect to neurodevelopment have been incon
in part to increased demand for growth secondary to early sistent [21], which may be due to genetic variations between
delivery and relatively poor nutritional stores. In some of the individuals in their ability to manufacture LCP from precursors
sicker infants, there may be an accumulated nutrient deficit [22]. There also appears to be risk of greater adiposity and
due to an inability to provide full requirements during acute higher blood pressure for preterm girls supplemented with
episodes of illness and periods of fluid restriction. Table 7.2 LCP [23]. Conversely, research suggests that girls may show
shows the suggested upper limit of feed volumes to provide positive effects of LCP supplementation with respect to
4–4.5 g/kg/day protein. neurodevelopment [24]. Conclusions are made difficult by the
The benefits of early provision of amino acids (AA) in par heterogeneity of studies and the fact they also generally include
enterally fed preterm infants are well accepted. A staged only mature and healthy preterm infants. Despite this, all
approach is recommended by many authors [8, 14, 15] with current preterm formulas are supplemented with LCP.
guidance from ESPGHAN recommending starting with a Enteral requirements for fat are in the range 4.8–6.6 g/kg/
minimum of 1.5 g/kg AA on day 1, increasing up to 2.5 g/kg day [6]. Parenteral lipids should be started on day 1 of life
and then a maximum of 3.5 g/kg from day 2 [8]. [8], building up to a maximum of 3.5–4.0 g/kg/day of lipid
[8, 14], although some extremely premature or very low
birthweight infants may develop hypertriglyceridaemia;
Fat therefore, close monitoring is required. Recommendations
from ESPGHAN suggest that the use of pure soya bean oil
Fat absorption can vary between individuals, but the more lipid emulsions should only be for the initial few days of PN
immature the infant, the higher the risk of malabsorption due to and that infants who will be on PN longer than this should
low bile salt pools [16] and reduced pancreatic lipase levels [17]. be given a third‐generation mixed lipid source [8]. Preterm
Despite this, the fat component of both enteral and parenteral infants, particularly those born VLBW and ELBW, will
develop essential fatty acid deficiency very rapidly without that this higher amount of vitamin D is beneficial, and there is
an exogenous supply. This can be obtained from as little as some evidence that these higher levels will be excessive for
0.5 g/kg/day from soya bean emulsions and 1.5 g/kg/day some infants [27]. However, babies of mothers with docu
from third‐generation mixed lipid sources. mented vitamin D deficiency will benefit from the higher lev
els as the placental supply will have been compromised. This
will need to be given as a supplement as current breastmilk
Carbohydrate
fortifiers (BMFs) and preterm formulas do not contain suffi
cient vitamin D to match this recommendation. The ratio
Lactase activity is present from 10 to 12 weeks’ gestation and
between calcium and phosphorus is also important for ade
approaches levels expected at term at 36 weeks’ gestation.
quate bone mineralisation, and Agostoni et al. recommend an
Exposure to lactose may help to induce intestinal lactase
enteral Ca–P ratio of 1.5–2.0.
activity. In practice, lactose malabsorption is rarely seen in
In PN solutions, stability of these nutrients is a limiting fac
the preterm infant.
tor as calcium and phosphate can bind and precipitate,
A large range of oligosaccharides are present in breast
although the use of organic phosphate salts has led to improved
milk, with the highest concentration in colostrum and
solubility and allows greater amounts to be given. The ideal
decreasing with the duration of lactation. They may help to
Ca–P ratio should be in the region of 1:1 in PN solutions [8].
protect against gastrointestinal problems, both by encourag
ing growth of a beneficial intestinal flora and by inhibiting
binding of pathogens. They may improve feed tolerance and Iron
reduce stool viscosity [25]; however, a review by ESPGHAN
states that more research is required before firm conclusions At birth there is an abrupt reduction in erythropoiesis, leading
about their benefits can be drawn [26]. Oligosaccharides are to early anaemia of prematurity, which is unresponsive to iron
currently added to Nutriprem 1 and Nutriprem 2 feeds. supplementation. Preterm iron stores are low, and infants may
Carbohydrate recommendations in PN are based upon the also lose significant volumes of blood through phlebotomy;
provision of a safe lower limit to prevent hypoglycaemia and however this may be reduced in cases where delayed cord
the provision of an appropriate protein–energy ratio to facil clamping has occurred [28]. Iron in excess is toxic, and, there
itate protein accretion. Carbohydrate in the form of dextrose fore, supplementation needs to be carefully weighed up
should be started at 5.8–11.5 g/kg/day on day 1, increasing against potential overload. Infants receiving regular blood
to an upper range of 11.5–14.4 g/kg/day over a couple of transfusions may benefit from delayed iron supplementation.
days from day 2 [8]. Tolerance to carbohydrate load should Preterm infants will become iron deplete by 8 weeks without
be closely monitored especially in the sick or preterm infant. supplementation [29]. Current recommendations are that sup
plements should commence between 2 and 8 weeks of age as
either a supplemented formula or medicinal iron at a dose of
Calcium, phosphorus and vitamin D 2–3 mg/kg/day [6]. These recommendations can easily be met
by adequate volumes of currently available preterm infant for
The homeostasis of calcium, phosphorus and magnesium is mulas and SMA Breast Milk Fortifier. Nutriprem Human Breast
fundamental to the development of bone, and this in turn is Milk Fortifier and PN solutions do not provide iron, and, there
regulated by factors including hormones and vitamin D. fore, supplementation will be required if these are used.
Metabolic bone disease of prematurity is a recognised co‐
morbidity. Causes include an inadequate supply of nutrients
Conditionally essential nutrients
(calcium, phosphorus, vitamin D), prolonged PN, immobili
sation and medications. Immobilisation stimulates bone
Beta‐carotene, nucleotides and inositol are present in human
reabsorption, while steroids (which are occasionally used in
milk and are often added to preterm infant formulas and
the treatment of chronic lung disease [CLD]) reduce calcium
BMFs; however, there is currently no evidence of benefit in
absorption, increase urinary losses and have a direct effect
the preterm population.
on bone. Diuretics and methylxanthines such as caffeine,
used to optimise respiratory status, increase renal calcium
excretion. Premature infants are also born with poor reserves
of calcium, phosphorus and vitamin D and have a high Learning points: nutritional requirements
requirement in order to optimise bone mineralisation.
Infants born IUGR or SGA are also more likely to show signs • Preterm infants are those born before 37 weeks’ completed
of osteopenia due to poor placental supply. gestation
The recommendations provided by Agostoni et al. [6] for cal • Accretion of nutrients occurs in the last trimester of
cium and phosphate are similar to previous recommendations; pregnancy, and as a result preterm infants are often born
however, vitamin D recommendations from Agostoni et al. are with limited stores of key nutrients
significantly higher. They argue that since the prevalence of • Preterm infants born weighing <2000 g and <34 weeks’
maternal vitamin D deficiency is high, supplementation with gestation will benefit from higher nutrient intakes, as
800–1000 IU (20–25 μg) per day is required to achieve optimal recommended in published guidelines
serum levels of 25‐hydroxyvitamin D. There is no evidence
100 Preterm Infants
Parenteral nutrition Table 7.4 [14]. More frequent monitoring may be required
according to the clinical condition of the infant.
PN has become the cornerstone of neonatal nutritional care in
the very preterm infant, without which many infants would Parenteral nutrition‐related complications
not survive. PN is required when adequate nutrients to sustain
growth and development cannot be provided via the enteral Some of the smallest and sickest infants tolerate PN the least,
route. PN should, therefore, be given to all infants with [14]: while they also have the greatest nutritional needs; manag
• gestational age <30 weeks’ completed gestation ing the complications of PN administration while optimising
• birthweight <1.25 kg nutrition is, therefore, a significant challenge in this patient
• failure to establish enteral nutrition (e.g. 100 mL/kg) by group.
day 5 of life regardless of gestation or birthweight
• inability to tolerate enteral nutrition for a period likely to Hyperglycaemia
result in a significant nutritional deficit
Hyperglycaemia is common in small preterm infants and
PN can be started safely and effectively within the first 24 hours results from impaired glucose homeostasis and may be
after birth in the preterm infant [8, 14, 30]. The aqueous AA solu aggravated by carbohydrate provision from PN solutions or
tions used are the same as those for term infants and have an AA additional glucose in the form of intravenous drugs and
profile based on either breastmilk or cord blood. PN solutions flushes not being included in the total carbohydrate calcula
for preterm infants have improved in recent years, and there are tion. Often it is temporary, lasting only a few days, but it can
now standardised formulations available that meet the specific significantly affect total energy provision if the glucose infu
needs of the majority of preterm infants. An example of a build‐ sion rate or lipid rate (which can increase insulin resistance)
up regimen for PN using standard bags can be seen in Table 7.3. is lowered for a period of time. Early AA infusion alongside
glucose is associated with a lower incidence of hyperglycae
Monitoring mia [31]. Insulin can be used in these cases in order to protect
nutrient provision, but glucose infusions >12 mg/kg/min
Monitoring PN administration in preterm infants is imperative. should be avoided in very preterm infants as this may lead
A suggested guide for frequency of monitoring is given in to excessive fat deposition in the liver [8].
Table 7.3 Example parenteral feeding regimen for a preterm infant using standardised PN bags.
Day 3,
Nutrient (per kg per day) Day 1 Day 2 Day 3, fluid limited standard PN
150 mL/kg/
60 mL/kg/day 90 mL/kg/day 120 mL/kg/day day
Conc bag Standard bag Conc bag Standard bag Conc bag Standard bag Standard bag
Aqueous Aqueous Aqueous Aqueous Aqueous Aqueous Aqueous
vol: 50 vol: 55 vol: 80 vol: 80 vol: 100 vol: 105 vol: 130
Volume of PN Lipid vol: 10 Lipid vol: 5 Lipid vol: 10 Lipid vol: 10 Lipid vol: 20 Lipid vol: 15 Lipid vol: 20
Protein (g) 1.6 1.3 2.5 1.9 3.1 2.5 3.1

Nitrogen (g) 0.3 0.2 0.4 0.3 0.5 0.4 0.5
Glucose (g) 7.3 6.1 11.6 8.8 14.5 11.6 14.3
Lipid (g) 1.8 0.9 1.8 1.8 3.6 2.7 3.6
Sodium (mmol) 2.0 1.7 3.1 2.4 3.9 3.2 3.9
Potassium (mmol) 1.2 1.0 1.9 1.5 2.4 2.0 2.5
Phosphate (mmol) 1.0 0.8 1.6 1.2 2.0 1.6 2.0
Calcium (mmol) 0.9 0.7 1.4 1.0 1.7 1.4 1.7
Magnesium (mmol) 0.11 0.1 0.19 0.15 0.24 0.2 0.25
Solivito 1.0 mL/kg/day 1.0 mL/kg/day 1.0 mL/kg/day 1.0 mL/kg/day
Vitalipid infant 4.0 mL/kg/day 4.0 mL/kg/day 4.0 mL/kg/day 4.0 mL/kg/day
Peditrace 1.0 mL/kg/day 1.0 mL/kg/day 1.0 mL/kg/day 1.0 mL/kg/day
Total energy (kcal (kJ)/kg/day) 53.6 (224) 38.6 (161) 74.4 (311) 60.8 (254) 106.4 (445) 83.4 (345) 105.6 (441)
PN, parenteral nutrition; Conc, concentrated; vol, volume.

Parenteral Nutrition 101
Table 7.4 Guide for biochemical monitoring on parenteral nutrition [14].
Trace elements
(selenium, zinc,
copper, manganese)
Urea, creatinine Calcium and Fat‐soluble vitamins
and electrolytes Liver function tests phosphate Magnesium Triglycerides Glucose (A, D, E)
First week of Daily (or twice Daily (or twice Daily Twice Twice Urine: –
PN or unstable weekly depending weekly depending weekly weekly 6 hourly
infant on clinical status) on clinical status) Blood:
6–8 hourly
Stable PN* Twice weekly Weekly Twice Twice Twice Urine: daily Monthly once on
weekly weekly weekly Blood: daily PN >3 weeks
PN, parenteral nutrition.

*For very stable babies on long‐term PN, all biochemical monitoring may be reduced to once weekly or less at the discretion of clinical staff.
Hypertriglyceridaemia infants is limited but has been demonstrated to be safe in the

short term and to improve serum fatty acid levels [36].
ELBW, SGA and septic infants have lower lipoprotein lipase
Significant IFALD leads to reduced bile flow resulting in fat
activity and therefore struggle with lipid clearance, often
malabsorption and poor weight gain. Enteral formulas contain
leading to hypertriglyceridaemia. The significance of this is
ing MCT may be of benefit. SMA Gold Prem 1 meets the needs
unclear, but based on the limited evidence, available recom
of the preterm infant and contains 40% MCT so, therefore, can
mendations suggest that triglyceride levels >265 mg/dL
be used first line when a formula is required for a preterm
(3.0 mmol/L) should be avoided [8]. Reducing, rather than
infant with conjugated jaundice. If the infant is feeding breast
stopping, lipid infusions is advised in order to prevent
milk, the use of these formulas should be clearly justified, and
essential fatty acid deficiency [32].
they need to be introduced cautiously in infants at high risk of
necrotising enterocolitis (NEC) (p. 109). Maintaining a propor
Weaning off PN tion of the enteral nutrition (25%–30%) as breastmilk may help
with tolerance and deliver the immunological benefits of
Once infants are tolerating adequate volumes of enteral breastmilk over formula. In units where SMA Gold Prem 1 is
nutrition, PN can start to be reduced. PN weaning should not available, then a term formula with 50% of the fat as MCT,
occur proportionally to support optimal protein–energy e.g. Pepti‐Junior or Pregestimil, can be used. As usual, when
ratios. The rate of PN weaning will be dependent on local using a term formula for preterm infants, the fact that they will
feeding policy and vary in speed depending upon the clini not meet the nutritional needs of the preterm infant must be
cal stability of the infant. It is widely agreed that PN can be acknowledged. Term formulas should, therefore, only be used
stopped once infants are on an adequate amount of enteral strictly as clinically indicated and stopped as soon as liver func
feeds, typically >120 mL/kg [14]. tion improves. In order to optimise nutritional provision for
preterm infants, these formulas should ideally be concentrated
Parenteral nutrition-associated liver disease up to 15%–17% to provide a more energy‐ and nutrient‐dense
feed. In the case of infants nearer to term who have conjugated
Preterm infants are particularly vulnerable to intestinal fail jaundice and who are struggling to grow, Infatrini Peptisorb
ure‐associated liver disease (IFALD) due to functional and (1 kcal (4 kJ)/mL, 50% fat as MCT) can be considered. Additional
anatomical immaturity of the liver. IFALD development is supplementation of vitamins, particularly fat‐soluble vitamins,
associated with increased length of time on PN, sepsis, lack minerals and iron, will be required in order to support the
of enteral feeding, overfeeding and low birthweight [33]. requirements of the preterm infant.
Practices that may limit its severity or development include:
• limiting carbohydrate infusion to <17.3 g/kg/day
• introducing and maintaining at least minimal enteral Prescribing practice
nutrition
PN should ideally be prescribed by an experienced healthcare
• alternative lipid emulsions
professional and, where feasible, a nutrition team including a
There is currently some evidence to suggest that the type neonatal dietitian, neonatal pharmacist and neonatologist [14].
of lipid emulsion used may play a role in the development Input from other professionals including specialist nutrition
of IFALD. Lipid emulsions containing ω3 LCP, such as SMOFlipid nurses, gastroenterologists, hepatologists and surgeons may
(soya, MCT, olive and fish oils), have been developed, and small also be helpful. The use of standardised formulations, in order
studies suggest that they may be of benefit in ameliorating the to optimise nutritional provision and facilitate early initiation
development of IFALD or even the reversal of cholestasis seen in of PN, continues to be a growing area of practice within the UK.
long‐term PN use in children [34]; however, further research is Standardised bags have been shown to improve rates of
required in this area [35]. Evidence for using SMOF in preterm early PN administration and improve nutritional intake and
102 Preterm Infants
costs of care [37–39]. It is recommended that standardised safe to introduce feeds early in the higher risk infant [45, 46].
PN be used wherever possible [8, 14, 40], and up to 80% of There is no evidence that delaying enteral feeds (>4 days) in
preterm infants receiving PN will grow adequately on a VLBW infants reduces the risk of NEC [47] and that the
standardised PN bag [40]. Use of standardised concentrated severity of NEC is greatest if an infant has never received
formulations can support unstable and fluid‐restricted pre enteral feeds before diagnosis [48]. Both these factors sup
term infants. The benefits of standard bags include: port the practice of introducing early enteral feeds. The
ADEPT trial [46] investigated the effect of enteral feeding on
• availability from first day of life
the development of NEC in high risk growth‐restricted pre
• consistency of nutritional care
term infants with abnormal antenatal Doppler. The authors
• cost
concluded that early feeding (within 24–48 hours of birth) in
• accuracy (the end product is tested)
this group of infants led to a reduced time to full enteral
feeds compared with late feeding (within 120–144 hours of
Learning points: parenteral nutrition birth) without an increased risk of NEC. However, it is
important to note that infants with abnormal antenatal
• PN is required in all infants <30 weeks’ gestation and/or Doppler who were born at <29 weeks’ gestation in this study
<1.25 kg were approximately 4 times more likely to develop NEC
• PN should be started within 24 hours of birth irrespective of whether they were fed early or late. This
• Regular biochemical monitoring is required to monitor group of infants may, therefore, benefit from a more pro
tolerance to the PN longed period of minimal enteral nutrition and slower
• Proportionate weaning of aqueous and lipid PN phases is advancement of feeds [49].
required in order to ensure maintenance of the required The practice of giving oropharyngeal colostrum, where
protein-energy ratio; consideration for stopping PN can start small volumes of maternal colostrum are placed directly
once an infant is having at least 120 mL/kg/day of enteral feeds onto the inside of the infant’s cheeks, should be considered
• Preterm infants who are on long‐term PN are high risk for in all units. Maternal colostrum produced in the first few
developing IFALD days after birth is rich in cytokines and other immune agents
• Standardised PN provision is recommended for the majority that provide bacteriostatic, bactericidal, antiviral, anti‐
of preterm infants requiring PN inflammatory and immunomodulatory protection against
infection [50] and has been found to be protective against
clinical sepsis [51]. Giving oropharyngeal colostrum has
Minimal enteral feeding also been associated with sustained breastmilk feeding in
preterm infants [52].
Structural development of the gut in utero initially com
mences outside the body of the foetus. At 8–12 weeks’ gesta
tion, the primitive gut rotates and returns into the abdominal What to give
cavity. Villi develop from around 12 weeks’ gestation and
they mature from approximately 22 weeks. Functional matu See Enteral nutrition (p. 103).
ration occurs somewhat later with enzymes being produced
from around 8 weeks’ gestation and increasing in produc
tion from around 25 weeks. Motor function also begins to How to progress feeding
develop around 25 weeks’ gestation so that structure and
most functions are in place around this time [41] although A recent Cochrane review [53] examining studies looking at
immature motor function is likely to be the most common slow (15–20 mL/kg/day) versus rapid (30–35 mL/kg/day)
cause of enteral feed intolerance in the VLBW infant. advancements of feeds concluded that there was no signifi
A lack of enteral nutrition leads to the risk of gut atrophy and cant difference in risk of NEC but that the slow group took
impairs gut development. Minimal enteral feeding (also known longer to regain birthweight to establish full enteral feeds
as ‘non‐nutritive feeding’, ‘trophic feeding’ or ‘gut priming’) is and may have an increased risk of invasive infection. It
the process by which small volumes of milk (up to 24 mL/kg/ should be noted, however, that randomisation was at the dis
day) are provided enterally for up to 7 days to facilitate gut cretion of the clinician; therefore there is a possibility that
adaptation, rather than for nutritive gain. It is believed that only a smaller proportion of high risk infants may have been
these small amounts of milk can promote intestinal maturation, included. In practice, evidence suggests that caution should
stimulate enteral hormones that aid gut function and prevent or be exercised when increasing feeds in high risk infants and
reverse the mucosal changes seen during starvation [42, 43]. continual review of the literature is recommended [54]. The
initiation of trophic feeding followed by cautious increases
in feeds at a limit of 20 mL/kg/day is recommended in this
When to start patient group. Evidence in lower risk infants indicates
increases of 30 mL/kg/day are considered safe [48, 52].
Preterm infants should commence enteral feeding as early as Evidence also suggests that the number of days to full enteral
possible after birth unless there is a clinical contraindication feeds is reduced in VLBW infants if fed 2 hourly compared
[44]. There is increasing evidence to suggest that it is also with 3 hourly [55].
Enteral Nutrition 103
Enteral nutrition support mother’s own freshly EBM as the milk of choice for
preterm babies. Several studies confirm association with
Breastmilk mother’s EBM and lower risk of NEC [59–62]. There may also
be long‐term neurodevelopmental advantages [63–66].
The freshly expressed breastmilk (EBM) from a preterm baby’s Breastmilk may be nutritionally adequate in many respects
own mother is considered the optimal enteral feed [56]. Much for babies >34 weeks’ gestation when fed in sufficient vol
of the evidence supporting the benefits of EBM is gathered umes (up to 180–200 mL/kg/day in well infants), although
from studies other than RCTs as it is ethically inappropriate to iron supplements will be needed. However, in infants <34
randomise a baby not receive their mother’s own milk when it weeks, the provision of some nutrients will be limited from
is available. No RCTs were found to meet the criteria for a the start of feeding, e.g. phosphorus, sodium and most
Cochrane review [57], and those that do exist involved ran vitamins, particularly the fat‐soluble ones, or become lim
domising babies to donor breastmilk (DBM) or formula when ited after 2–3 weeks of feeding, e.g. protein, calcium and
their mothers chose not to provide breastmilk. When risk for zinc. A case study to illustrate this is given in Table 7.5.
NEC was examined separately, it was found that breastmilk in Preterm breastmilk during the first 2–3 weeks of lactation
the form of DBM did have a beneficial effect over formula usually has higher protein levels than later on [67, 68]. Protein
milk [58]. There are a large number of observational studies to fortification will eventually be needed for babies <34 weeks
Table 7.5 Case study to illustrate adequacy of enteral nutrition in a preterm infant.
Baby boy, born at 27/40, birthweight 800 g (9th centile). Spontaneous rupture of membranes, maternal antenatal steroids and magnesium
sulphate given.
Day Narrative Nutritional intervention
1 Mother visited by member of neonatal unit staff within 6 hours of Parenteral nutrition (PN) started 6 hours postnatally
delivery and provision of her breastmilk (BM) discussed; she is happy As soon as available oropharyngeal colostrum is started
to express
Advised on breast massage and hand expressing
2 Mother and father have long visits to baby PN given at 90–120 mL/kg
Mother encouraged to express after visiting Trophic feeds commenced at 10–20 mL/kg
3 Meconium passed and yellow seedy stools appear PN given at 120–150 mL/kg
Maternal milk production >20 mL at each hand expression so Trophic feeds not yet tolerated so continue
instruction in mechanical expression given
5 Trophic feeds now tolerated and included in total fluid volume PN decreased to 130 mL/kg
Maternal lactation checked: 200 mL/day and increasing Expressed breastmilk (EBM) 20 mL/kg
EBM increases by 20 mL/kg/day
8 Enteral feed well tolerated; minimal aspirates and bowels open PN decreased to 70 mL/kg
1–2 times per day EBM 80 mL/kg
Parents having skin‐to‐skin cuddles with baby Sodium and phosphate supplements started based on blood
Cotside expressing encouraged biochemistry results
9 Enteral feed tolerance as above PN decreased to <50 mL/kg and lipid component stopped
EBM 100 mL/kg
Supplements started: multivitamin supplement containing 400 IU
vitamin D and 5000 IU vitamin A and folic acid
10 Maternal lactation checked: <600 mL/day PN stopped
Further advice on expressing given EBM 120 mL/kg and building up towards 150 mL/kg
12 Maternal lactation improving with increase to 8–10 expressions per EBM 150 mL/kg
day, including at night Breastmilk fortifier started†
The need for breastmilk fortifier (BMF) discussed with parents and its
use explained
14 Enteral feed well tolerated; minimal aspirates and bowels open EBM 150 mL/kg with full‐strength breastmilk fortifier
1–2 times per day Sodium supplements kept the same
Maternal lactation now >700 mL/day Multivitamin and phosphorus supplements adjusted once on
Mother doing regular skin‐to‐skin cuddles full‐strength breastmilk fortifier
28 Baby now 31 weeks and beginning to nuzzle at breast during skin‐to‐ EBM 150 mL/kg + breastmilk fortifier
skin contact; will begin first attempts at suckling over next few weeks Sodium supplements stopped
Mother reports largest volumes of milk expressed after skin‐to‐skin (Iron supplement written up if infant on Nutriprem Human Breast
contact Milk Fortifier)
†
Could be half strength for 24–48 hours or full strength straight away; there is no consensus.
104 Preterm Infants
and <1.5 kg [69]. Some units start this routinely, while others does not contain iron, so a separate supplement is necessary.
wait until there are signs that additional protein is needed, Table 7.7 compares fortified breastmilk with the guidelines.
e.g. low serum urea levels [70]. A commercial multinutrient There is one commercially available protein supplement
BMF has many advantages over the addition of nutrients as for preterm infants. Nutriprem Protein Supplement is
separate supplements, e.g. reduced risk of excessively high designed to be added to Nutriprem 1 or Nutriprem Human
osmolality, reduced risk of errors in administration and Milk Fortifier to make up the additional protein require
reduced nursing time. Those currently available in the UK ments for those infants <1000 g as required. It should not be
are Nutriprem Human Milk Fortifier and SMA Breast Milk added to breastmilk without the prior addition of BMF as it
Fortifier. Typical composition of a BMF is given in Table 7.6. does not contain complete nutrition.
A systematic review concluded that BMFs promote short‐ Concerns around increased feed osmolality and bacterial
term growth and that, despite lack of longer‐term outcome growth with the use of BMF are not supported by current
data, it was unlikely that further trials would be carried out evidence [69]; neither is there evidence to suggest a link with
with an unfortified breastmilk group [71]. The BMFs available NEC [73]. One paper suggested that the use of a fortifier
in the UK provide nutrients sufficiently close to current recom based on human milk protein reduces the risk of NEC; how
mendations [6, 7]; however, Nutriprem Human Milk Fortifier ever questions over the design of this study weaken this pro
posal [74]. Despite the lack of evidence, it is advisable to add
Table 7.6 Typical composition of a multinutrient breastmilk fortifier. BMF to the minimum amount of breastmilk possible and to
feed as close as possible in time to the fortifier being added
Protein (hydrolysed) in order to avoid both prolonged storage and any potential
Carbohydrate
Calcium
disruption of immunological components, which has not yet
Phosphorus been quantified. All feeds should be handled and stored
Sodium, potassium according to current guidelines to avoid contamination [75].
Fat‐soluble vitamins including vitamin E Strategies are needed to ensure that mothers of preterm
Water‐soluble vitamins including folic acid babies are able to produce milk in time for their baby’s first
Trace elements, e.g. zinc, selenium, copper, magnesium, iodine, feed and, if planning to breastfeed on discharge, to provide
manganese
sufficient quantities to support the volume their baby will
Iron is provided from SMA Breast Milk Fortifier, but not Nutriprem
Human Milk Fortifier
need in the longer term [76]. Table 7.8 shows a sample check
list that can be used to ensure mothers are given appropriate
Table 7.7 Nutrients in fortified breastmilk compared with guidelines.
150 mL/kg mature 165 mL/kg mature

100 mL/kg 180 mL/kg EBM + SMA BMF EBM + Nutriprem Agostoni Koletzko et al.
Nutrient per kg mature EBM* mature EBM full strength HMF full strength et al. [6] [7] (enteral)
Energy (kcal) 69 124 129† 139† 110–135 110–130

(290 kJ) (520 kJ) (540 kJ) (580 kJ) (460–565 kJ) (420–545 kJ)
Protein (g) 1.3 2.3 4.1 4 3.5–4.5 3.5–4.5
Sodium (mg) 15 27 78 83 69–115 69–115
Potassium (mg) 58 104 159 134 66–132 78–195
Phosphorus (mg) 15 27 89 87 60–90 60–140
Calcium (mg) 34 61 165 165 120–140 120–200
Iron (mg) 0.07 0.1 3.1 0.1 2.0–3.0 2.0–3.0
Zinc (mg) 0.3 0.5 1.9 1.5 1.1–2.0 1.4–25
Selenium (μg) 1 1.8 7 4.5 5–10 5–10
Iodine (μg) 7 13 36 30 11–55 10–55
Folic acid (μg) 5 9 68 58 35–100 35–100
Vitamin A (μg) 58 104 657 479 400–1000 400–1000
Vitamin D (μg) 0.04 0.07 6 8.3 20–25‡ 10–25‡
Vitamin E (mg) 0.34 0.6 7 4.9 2.2–11 2.2–11
EBM, expressed breastmilk; BMF, breastmilk fortifier; HMF, human milk fortifier. 1 μg vitamin A = 3.33 IU. 1 μg vitamin D = 40 IU.
*Finglas et al. [72]. Vitamin D level taken from 5th edition.
†
Does not take account of high risk of fat loss on handling.
‡
Expressed as per day not per kg.
Enteral Nutrition 105
Table 7.8 Lactation and breastfeeding check list.

Tick when Print
Date
achieved/ name
1. To be completed within 6 hours of admission; during visit to mother by a staff member and
circle as and
time
appropriate initial
Interpreter required Y/N
Ask feeding intention and record here: ❑
Discuss the importance of colostrum as first feed and breastmilk for the preterm baby with
respect to the following
• Reduced risk of infection • Improved development ❑
• Improved gut tolerance • Reduced risk of NEC
For mother; reduced risk of breast and ovarian cancer, osteoporosis
Breastmilk expressing pack given and explained ❑
Advise watching Small Wonders DVD films:
Film 3. First hours ❑
Film 4. Expressing breastmilk ❑
Advise mother to start expressing now even if on medication (prescribed/non‐prescribed/herbal)

❑
Safety concerns can be checked before milk is given to baby. Ask pharmacist if unsure
Advise on the detrimental effects of alcohol and smoking on lactation ❑
If baby is a candidate, get verbal consent for donor breastmilk from mother. Obtained
Y/N
by............................................ (Name)
Is there a reason why feed at 6 hours is not appropriate in this baby? If not give feed
Y/N
Reason:........................................................................
Is the baby likely to feed at the breast within 6 hours of delivery? If yes move to section 7 Y/N
6 hours post‐delivery: Call to midwife to check mother has expressed – in this hospital or
one mother is in ❑
Name of midwife discussed with.
2. Within the first 24 hours: during mother’s first visit to the unit:
Highlight hygiene practice in relation to breastmilk expressing and skin‐to‐skin contact

❑
including regular bathing/showering
Importance of skin‐to‐skin contact with baby explained and check the mother has watched the
❑
film on the Small Wonders DVD: Film 5. Holding your baby
❑
Breast massage and hand expressing observed and breastmilk expressing log offered
Log taken Y/N
Benefits of using colostrum and breastmilk for mouth care explained ❑
Importance of frequent milk expression explained, i.e. 8–10 times in 24 hour (including once at
❑
night between 2 am and 4 am)
Benefits of non‐nutritive sucking explained (calming, maximising CPAP, sucking practice during
❑
tube feeds) (parent leaflet on shared drive)
If mother unable to visit the unit within 24 hours go down to visit her to complete this section
❑
or if in another hospital phone her midwife to check expression has commenced
Check mother is taking vitamin D (10 μg or 400 IU per day) ❑

106 Preterm Infants
3. Day 2–4
Safe collection and storage of expressed breastmilk explained, including guide to minimise
❑
contamination
Offer mother manual pump and demonstrate use when milk comes in ❑
❑
Use of electric breast pump demonstrated and breastmilk expressing log reoffered Log taken
Y/N
4. Day 5
Check that milk has come in and the volume of expressed breastmilk is increasing. If not, give
❑
support
Record volume expressed in last 24 hours here

Volume = mL
Document support given if needed:...................................................
5. Day 10
Check that production has increased and milk is being stored in the freezer (750 mL in 24 hours
❑
is optimal). If not, give support
Record volume expressed in last 24 hours here

Volume = mL
Document support given if needed:...................................................
6. Day 14
Discussion regarding the possible need for breastmilk fortifier to meet a preterm baby’s
❑ N/A
additional requirements (see guideline)
If appropriate advice has been given and followed by the mother but milk yield is not increasing,
Y/N
is she taking domperidone? Date started?:...................................................
Check frequently that mother’s milk supply is being maintained. If not, offer support early
7. Stable and ready to feed
Support the mother to watch the film on the Small Wonders DVD: Film 7. Feeding
❑
independently
Importance of mother’s availability for breastfeeding and rooming in discussed with support for
❑
any potential obstacles considered?
Breastfeeding observed, baby’s position and attachment has been supported and signs of milk
❑
transfer explained
Disadvantages explained reintroduction of bottles before breastfeeding is fully established

❑
(different technique, undermines confidence in breastfeeding success)
Consent for bottles given if necessary and developmentally supportive feeding demonstrated ❑
Source: Courtesy of Imperial College Healthcare NHS Trust Division of Neonatology.
support and information at the relevant times. Another is required, it may be useful for the baby to be preferentially
useful resource is the booklet produced by the UK‐based fed hindmilk [77].
charity for sick and preterm babies, BLISS (see the website If mother’s own milk is not available or there is a delay in
www.bliss.org.uk for the most recent publications). obtaining it, DBM is the feed of choice to initiate enteral feed
If mothers are advised to express 8–10 times per day ing in high risk infants as it is associated with a reduced risk
including once at night and to fully empty the breast of all of NEC than formula feeds [57]. There are guidelines from the
the fat‐rich hindmilk, they should produce milk of sufficient National Institute for Health and Care Excellence (NICE) for
energy content to preclude the need for energy supplemen the processing and handling of donor milk in the UK [78]. All
tation. However, human milk is prone to fat loss and should donor milk in the UK is pasteurised to ensure microbiological
be handled carefully to avoid this. If it is felt that more energy safety with the preservation of as many immunological
components as possible. However, pasteurisation leads to the other [82]. Bolus feeding has been associated with less
denaturation of bile salt‐stimulated lipase with subsequent feed intolerance [83] but may lead to a deterioration in
reduced fat absorption and, therefore, total energy provision. respiratory function (due to gastric distension) in very com
In order to achieve optimal growth, babies are usually graded promised infants when compared with continuous feeds
onto preterm formula once full feed volumes are established [84]. Continuous feeding of human milk can lead to excessive
using DBM, if mother’s milk remains unavailable [79]. fat loss due to adherence to tubing [85] and risk of sedimenta
Although not all units have a milk bank, any baby in the UK tion of added minerals. There is no evidence that there is a
can have access to DBM; it can be purchased from many of the beneficiary effect of transpyloric feeding and that there may
established milk banks and delivered to the requesting unit. be some evidence of harm in the preterm infant [86].
Further information is available on the UK Association for
Milk Banking (UKAMB) website (www.ukamb.org).
Transition to oral feeding
For some infants, particularly those who have been very

Preterm formulas
unwell, the transition to oral feeding, either to breast or bot
tle, can be difficult [76]. Despite inherent problems there has
For those babies <2000 g birthweight and <34 weeks’ gesta
been an increase in babies leaving the neonatal unit breast
tion who do not have access to human milk, either mother’s
feeding, even the most preterm, and this has been facilitated
own or donor, a preterm formula is the feed of choice.
by the use of different approaches including early support
However, if they are at high risk of NEC, every effort should
for lactation, promotion of skin‐to‐skin contact between
be made to secure the use of donor milk if there is no m
other’s
baby and mother and encouraging mothers to ‘room in’ on
own milk available. If there is no option but formula feeding,
the unit [76]. If a mother has chosen to breastfeed, the baby
there is evidence that preterm rather than term formula
can start early feeding attempts as soon as they show cues
reduces the risk of later poor developmental outcome,
during skin‐to‐skin contact. However, full nutritive oral
particularly in boys [79]. Where mother’s milk supply is

feeding is usually not attained until at least 35 weeks and
inadequate and there is low risk of NEC, preterm formula can
later in some infants [76]. Totally demand breastfeeding
be used to supplement the baby’s requirements. It is not
may not be possible even at 35 weeks as the baby may still
advisable to mix and store human milk with formula for pro
have immature sleep patterns and, therefore, need to be
longed periods, although mixing just before feeding may
woken to ensure at least eight breastfeeds per 24 hours.
help tolerance of the formula [80]. Hydrolysed protein for
Some neonatal units discharge babies on tube feeds with
mulas have not been found to be required routinely unless
support to facilitate breastfeeding and weaning off the tube
there are clear clinical indications [81].
at home.
Preterm formulas are highly specialised feeds designed to
Babies who develop CLD or have neurological impairment,
meet the increased nutritional needs of preterm infants with
gastro‐oesophageal reflux disease or other long‐term health
out exceeding volume tolerance; their composition is based
problems can find the transition to full oral feedings particu
on major published recommendations [6, 7]. Those available
larly challenging, and the input of a speech and language
in the UK are Nutriprem 1 (whole protein), SMA Gold Prem
therapist is recommended.
1 (partially hydrolysed protein) and Hydrolysed Nutriprem
(extensively hydrolysed protein).
There is a wide variation in practice as to the age and Learning points: enteral nutrition
weight at which feeding with preterm formula is stopped.
A suggested range is 1800–2000 g body weight or discharge • Minimal enteral feeding promotes intestinal maturation
from the neonatal unit, whichever is sooner. Babies can then and stimulates enteral hormones that aid gut function
be considered for standard term formula or a post‐discharge • Enteral feeding should start as early as possible in preterm
formula (see Post‐discharge nutrition, p. 110). It is important infants
to remember that each baby must be assessed to decide on • Freshly expressed mother’s breastmilk is the feed of choice
the optimum formula and this should not be arbitrarily for all preterm infants
based on age or weight alone. • Infants <34 weeks’ gestation and <1.5 kg feeding mother’s
EBM alone will require breastmilk fortification
• Preterm formulas are designed to meet the nutritional needs
Method of enteral feeding of the preterm infant when mother’s EBM is unavailable
Due to an immature suck–swallow–breathe pattern, preterm

infants usually require at least a proportion of their feed by
tube until around 35 weeks’ gestation, some for longer. Nutritional assessment
Methods of enteral feeding differ markedly around the world
[70]. There are advantages and disadvantages to both bolus The appropriateness and adequacy of nutritional manage
and continuous gastric tube feeding with a systematic review ment can be assessed through both serum biochemistry and
unable to give a firm recommendation of one method over growth.
108 Preterm Infants
Serum biochemistry less frequently due to the high risk of inaccurate measure
ments using inappropriate equipment. A simple measure
Protein status is difficult to assess, whereas adequacy of is available to take the length of preterm babies, both in
protein intake in the short term can be approximately incubators and in cots (the Leicester Incubator Measure
assessed via measurement of serum urea levels. In healthy available from Harlow Printing). It is accurate if used
preterm infants, after the first 2–3 weeks, serum urea is according to a protocol and by two observers and has
likely to fall to <1.6 mmol/L when intake of human milk been shown to lead to minimal disturbance of the baby
protein is <3.0 g/kg/day [87]. Adequate protein intake of [90]. The value of a length measurement is that it reflects
3.5–4.0 g/kg/day (up to 4.5 g/kg/day in infants <1000 g) growth of the skeleton and, therefore, body mass, includ
[6] will probably be indicated by maintaining serum urea ing lean mass as well as adipose tissue, and is not affected
levels >2.0 mmol/L. However dehydration, renal and by fluid balance changes. It is becoming apparent that
hepatic dysfunction, sepsis, steroid therapy and insufficient preterm babies are often more stunted than wasted by the
non‐protein energy can all raise serum urea levels despite time they are discharged from the neonatal unit, but this
protein intake being <3.0 g/kg/day and should be taken can only be evaluated if length measurements are rou
into account. In some circumstances therefore, it may be tinely carried out [91, 92].
appropriate to increase protein intake despite there being a Weekly measurements of length and head circumference
urea level >2.0 mmol/L. are sufficient to give information on growth. Weighing may
Calcium and phosphorus are essential for bone health; be carried out daily initially while on PN and during acute
phosphorus is also needed for soft tissue deposition. Serum episodes to estimate fluid balance; thereafter twice weekly to
phosphorus levels vary more than calcium levels, but both weekly should be sufficient to monitor growth.
are very useful for assessing needs. It is recommended that These anthropometric measurements can be plotted on a
supplements be titrated to keep serum calcium and phos growth chart for preterm babies, the UK Neonatal and Infant
phorus within normal levels. A supplement of 0.5 mmol Close Monitoring Chart (available from Harlow Printing).
phosphorus twice daily has been shown to be a good start This chart is based on cross‐sectional data on size at different
ing point should serum levels drop <1.8 mmol/L [88]. gestational ages at birth and does not necessarily represent
Alkaline phosphatase is a marker of both bone formation how babies at different gestational ages should grow. There
and reabsorption. Sudden very large increases in serum lev is data showing postnatal growth of babies in North America
els may indicate a fracture or be due to increasing levels of [93] that are based on a cohort of babies from 1994. Similar
the liver isoenzyme during an acute phase reaction. Levels data from UK babies has been published [94]; there are some
that gradually increase with time, but stay below the upper striking similarities with the North American cohort of 1994
normal range, usually reflect bone activity during growth with both showing an initial loss of weight and tracking
and are not a concern. along a lower centile.
It is important to monitor trace elements during long‐term All preterm babies experience a reduction in extracel
delivery of PN (Table 7.4), e.g. manganese and copper, as lular fluid that is usually demonstrated by a weight loss
they can build up to excessive levels in the liver when bile in the first few days after delivery, and it is debatable
flow is reduced. During prolonged renal dysfunction, sele whether this fluid should be regained and whether an
nium and molybdenum levels may accumulate, so it may be infant’s weight should rapidly go back up to their birth
advisable to assess these in this circumstance. centile or not. The perceived benefit or detriment of catch‐
Other parameters to check are haemoglobin and sodium. up growth is still being debated. There is a move towards
Sodium depletion has been associated with poor growth ensuring satisfactory growth early on so that less catch‐
[89]. Preterm babies have higher requirements for sodium up growth is needed later on. In general it is acceptable
than term babies due to renal immaturity whereby they are for a baby to drop 1 or 2 weight centiles in the first few
unable to conserve sodium initially and can quickly days and then grow along the new centile. Babies who are
become hyponatraemic. If they are on sodium‐wasting born growth restricted may cross centiles upwards even
diuretics, they are also at risk of depletion due to higher when fed according to standard preterm nutritional
renal losses. recommendations.
Rather than considering gains in weight, length and
head circumference in isolation, it is useful to look at pat
Growth terns of growth on a centile chart. There will be no loss of
head circumference or length per se, but there may be a lag
A healthy preterm baby’s growth rate rapidly responds to phase before these consistently follow a particular centile.
both poor nutrition and nutritional rehabilitation. It is difficult to quickly establish when growth is failing
Accurate weight measurement is essential in the neonatal unless weight, length and head circumference are all con
unit as it gives important information about fluid balance sidered together as babies may show weight faltering that
as well as changes in body mass. Head circumference is is mainly due to loss of fluid rather than other tissue.
also routinely measured as it can alert to abnormal brain Where there are concerns about growth, a wide range of
growth after certain insults as well as contributing to possible causes need to be evaluated alongside nutrition
growth monitoring. Length measurement is carried out (Table 7.9).
Feeding Issues in Special Conditions 109
Table 7.9 Possible causes of poor growth in preterm infants.
Causes Remedies
Inadequate nutrient input • Optimise volume and composition of parenteral nutrition and enteral feeding
• Ensure timely breastmilk fortification
Immature digestion and • Vomiting or diarrhoea – treat root cause
absorption • When MEBM unavailable and infant having DBM, consider introduction of preterm formula or
fortification of DBM in infants at low risk of NEC
• No benefit has been found in the use of medium chain triglycerides
Fluid restriction • Ensure that fluid restriction is clinically necessary and negotiate a liberalisation of fluid input as soon as
feasible
Inadequate sodium replacement • After early postnatal diuresis has occurred, monitor serum sodium levels and supplement when necessary
• Monitor serum sodium levels carefully during sodium wasting diuretic therapy
Breastmilk fat • Ensure all steps taken to avoid loss of fat on handling, e.g. avoid decanting cold breastmilk and leaving
fat residues in bottles
• If continuous feeding, ensure syringe tilted upwards to deliver fat first
• Consider the creamatocrit technique
• Consider preferential feeding of hindmilk
Postnatal steroids • Postnatal steroids are known to arrest postnatal linear growth; therefore caution is required to not
overfeed during this period
• Additional energy supplements are not recommended as there is a risk of excessive adiposity
• Additional protein is not recommended as baby will be catabolic and can increase urea levels
• Ensure liberalisation of nutritional input after steroids are finished to allow catch‐up growth
Renal/metabolic • Excess mineral loss due to renal immaturity – monitor biochemistry and supplement accordingly
• Metabolic acidosis needs prompt treatment as it interferes with protein synthesis
Inactivity • Not currently recommended but if further evidence shows benefit and no harm try gentle, passive
exercise
Suspected increase energy expenditure
1. Respiratory or cardiac disease • Trial of high energy density feeding, e.g. preferential hindmilk feeding for babies being tube‐fed
breastmilk, and/or use of high energy formulations in the near term and term infant
• Ensure adequate protein–energy ratio when using energy‐enhanced formulations
2. Other causes • Ensure that the infant is kept in a thermoneutral environment
• Ensure that methylxanthine (caffeine) levels are not excessive
• Ensure that infant is nursed to minimise energy expenditure
MEBM, mother’s expressed breastmilk; DBM, donor breastmilk; NEC, necrotising enterocolitis.
infants, that leads to acute inflammation of the bowel.

Learning points: nutritional assessment
Severity can range from low‐grade mucosal damage to bowel
perforation. In severe cases infants present with acute abdom
• Urea levels <2 mmol/L can be indicative of an inadequate
inal distension, feed intolerance, bloody stools and sepsis.
protein intake
Incidence is highly variable between units, but it affects
• Aim to maintain phosphate levels >1.8 mmol/L to support
approximately 5% of preterm infants <33 weeks’ gestation
bone development
[95], with one in four patients requiring surgery [96]. The
• Preterm infants should have regular weight measurements
aetiology is multifactorial and not well understood; however,
(daily initially and when on PN and then 2–3 times per
the majority of affected infants have received enteral feeds. It
week to monitor growth)
appears to be triggered by a combination of one or all of the
• Head circumference and length should be monitored weekly
following factors: prematurity, hypoxia leading to gut ischae
mia, gut bacterial overgrowth, sepsis, feeding of formula
milk and rapid advancement of enteral feeds.
Feeding issues in special conditions High risks for NEC include:
Necrotising enterocolitis • <28 weeks’ gestation

• <1000 g birthweight
Concerns regarding the introduction of enteral feeds to the • IUGR (birthweight < 2nd centile)
preterm gut relate to the risk of NEC, and this must be bal • abnormal antenatal Doppler (absent or reversed)
anced against the risks of not feeding. NEC is a potentially • circulatory redistribution leading to potentially altered
life‐threatening condition, predominantly affecting preterm blood flow to the gut, e.g. infants with hypoxic ischaemic
110 Preterm Infants
encephalopathy or cardiac anomaly such as patent duc administered directly into the baby’s lungs to improve com
tus arteriosus pliance and, more recently, more rapid transfer from
• congenital gastrointestinal abnormalities, e.g. gastroschisis mechanical intratracheal ventilation to non‐invasive airway
• unstable, ventilated and hypotensive infants support. It is now only the most immature and compromised
• altered gut microflora at birth who develop this disease.
There is evidence for some increase in energy require
Medically managed NEC is bowel rest and PN with slow
ments with CLD; however, this is probably restricted to
regrading of enteral feeds, ideally onto human milk. In the
babies with severe forms of the disease [111]. Most babies
most extreme cases, infants may require surgical manage
today have a milder form of CLD and grow well without
ment and gut resection, which can result in short bowel syn
routine energy supplementation.
drome if extensive gut resections are required. Severe NEC is
associated with a poor neurodevelopmental outcome and
high morbidity and mortality rates in those requiring sur Learning points: special conditions
gery [97, 98]. Standardised enteral feeding protocols appear
to reduce the incidence of NEC [99]. The use of probiotics in • NEC affects 5% of preterm infants <33 weeks corrected age
preterm infants in the prevention of NEC has been widely • The most severe form of NEC can lead to short bowel syn-
reviewed [100]; however, a recent study found no clear ben drome in patients who require extensive surgical resection
efit of giving probiotics for prevention of NEC and that fur • Feed intolerance is common in preterm infants and can be
ther research is required to identify the optimal probiotic reduced by feeding mother’s EBM and feeding at frequent
strain [101]. intervals
• Infants with severe forms of CLD may have an increased
requirement for energy
Feed intolerance
Feed intolerance is extremely common in the very preterm

infant and may occur independently of NEC. The more
immature the infant, the higher the risk of feed intolerance;
Post‐discharge nutrition
SGA, birth asphyxia and morphine administration also
Discharge criteria for preterm infants vary greatly across the
increase the risk.
UK, and this will play a role in nutrition and feeding at the
Definition of feed intolerance is difficult with signs often
time of discharge. Infants who are discharged home with a
described as vomiting, increased abdominal girth, abdomi
normal weight for post‐conceptional age are less likely to be
nal tenderness, absence or quality of bowel sounds and/or
at nutritional risk as opposed to those infants with subopti
the presence of abnormal stool, all of which can be observed
mal weight gain, ongoing increased requirements and/or
in healthy preterm infants [102]. Historically, the volume of
significant nutritional deficits [112].
gastric residuals and bile stained aspirates has been the main
All mothers are encouraged to continue breastfeeding
indicator for feed intolerance and, in isolation, may not be
for as long as they wish after discharge from hospital. Most
sufficient reason to withhold feeds as these should be
preterm infants attain maximal oral feeding by 35–37
assessed as part of the whole clinical picture. Gastric residu
weeks’ gestation, and, therefore, many may be discharged
als alone are an unreliable marker of feed tolerance as they
home before oral feeding is fully achieved [113]. It has been
are impacted by many factors including the size and position
common practice to stop BMF in all babies once feeding
of nasogastric tubes and the infant’s position between feeds.
fully from the breast and the feeding tube has been
Most authors would recognise gastric residuals of more than
removed. A recent Cochrane report found no benefit for
50% of the previous feeding as being a possible marker for
use of BMF when used for 3–4 months’ post‐discharge,
feed intolerance [103–107].
with no effects on neurodevelopment [114]. As healthy pre
While feed intolerance is almost unavoidable, in some
term babies reach term, their feeding skills improve and
babies the risks can be reduced by giving mother’s milk [108,
mature, allowing them to take large enough volumes to
109], having clearly defined parameters for feeding intoler
satisfy energy and possibly protein needs, precluding the
ance [110] and feeding at frequent intervals.
need for BMF.
However, there is a small group of preterm infants who
Chronic lung disease will benefit from being discharged home on a BMF.
Depending on how the infant is feeding at the time of dis
CLD was first described following the survival of mechani charge will dictate how this is delivered. Infants who are still
cally ventilated preterm babies. It appears that this condition being nasogastrically fed at home continue to have the BMF
is now on the decline due to a number of factors including delivered via the tube feeds; as the nasogastric feeds
more widespread use of prenatal steroids to help accelerate decrease, the infant correspondingly takes less of the BMF,
maturation of the baby’s lungs, postnatal surfactant i.e. is ‘weaned off’ the BMF. For infants who are feeding
Weaning onto Solids 111
orally, each sachet of BMF can be dissolved in a small amount Table 7.10 Cues for weaning healthy preterm babies.
of breastmilk and given via a teat or syringe just before a
breastfeed, the aim being to avoid introducing a bottle Behaviours
where possible and risk any interference with breastfeeding. • Alert and appears ready for a new type of feeding
There is an argument that BMF could be given at half the • Shows an interest in others eating
• Leans forward and opens their mouth towards a spoon or food
usual dose as a ‘step‐down’ to gradually reduce the nutri
tional concentration, as happens when changing from a pre Positioning
term formula to a nutrient‐enriched post‐discharge formula • Can hold their head in a stable position
(NEPDF). This approach has not been investigated in clinical • Can be supported easily in a sitting position on a lap, bouncy or high
trials, but has been advised by various units, and anecdo chair
tally it has been found not to interfere with breastfeeding, • Caution should be taken when starting to wean preterm babies who
which has been voiced as a concern [115]. BMF is currently cannot be assisted to achieve the above positioning skills
not prescribable in the community in the UK and depends Oral skills
on the individual neonatal unit to supply it. • Has started to bring their hands to their mouth and explore fingers
Babies who are exclusively or predominantly breastfed and/or toys with their mouth
(with or without BMF) will need a multivitamin preparation • Is demonstrating a ‘munching’ or up down jaw movement when
containing vitamin D, which should continue as long as mouthing non‐food items
breastmilk is the main drink. An iron supplement is also • Can breast, bottle or cup feed efficiently
needed until around 1 year of age but may be stopped earlier This is desirable although some babies who are not managing
milk feeds efficiently can still be tried with weaning foods.
if there is sufficient iron in the diet. The practice of giving a
A specialist speech and language assessment should be initiated for
single dose of iron daily throughout the first year (e.g. such babies
5.5 mg/day) allows the baby to gradually grow out of the
dose per kilogram so that when the supplement is finally Some factors have been used in the past, but are now not
recommended
stopped, it is a relatively small dose, as the diet becomes the
predominant source of iron. • That a certain target weight is reached
• Demanding feeds more frequently; this will often be due to a growth
Some babies will leave hospital on formula feeds whether
spurt and should be managed initially by offering more milk rather
fully feeding or as a top‐up to breastfeeding. There has been than starting solid foods
much discussion recently over the appropriate formula for
preterm infants at the time of discharge, with a recent Some factors may only develop once weaning has begun; their absence
should not prevent a baby’s progression with weaning
Cochrane review suggesting that recommendations to pre
scribe NEPDF are not supported by available evidence [116]. • Managing to clear the spoon with their lips; this skill develops with
However, the cohort in this review either lacked or under‐ experience
• Presence of teeth, as they are not essential for chewing
represented the infants at highest nutritional risk and those
with additional requirements at discharge, e.g. those going
home on supplemental oxygen [7].
It could be surmised then that infants with good weight for
have lower nutrient density per kilocalorie (kilojoule) com
post‐conceptional age and nutritional status will not require
pared with NEPDF, so as babies tend to feed to meet their
an NEPDF and should be considered for discharge home on a
energy requirements and then stop feeding once achieved,
term formula. These infants will require additional vitamins
they are at risk of having a lower nutrient intake.
and iron supplementation until around 6 months corrected
After NEPDF is stopped, a term formula can be used up to
age. However, it needs to be acknowledged that there is still a
12–18 months of age. Iron status should be adequately main
cohort of preterm infants, e.g. those high risk for nutritional
tained without supplementation [118], although some
deficits and with increased requirements who would still
infants with limited dietary intakes may still need extra iron.
benefit from a going home with an NEPDF.
When unmodified cow’s milk is given at 12–18 months
The nutritional composition of NEPDF falls between pre
instead of formula or breastmilk, the toddler should be
term and term formulas. There are two brands of NEPDF
started on Healthy Start Children’s Vitamin Drops as per
available on prescription in the UK: Nutriprem 2 and SMA
Department of Health guidelines (Table 1.22).
Gold Prem 2. These formulas are prescribable to 6 months
corrected age, which may benefit those who have accrued
the greatest nutritional deficit while on the neonatal unit; for Weaning onto solids
others their use up to 3 months corrected age is probably suf
ficient [117]. Although NEPDFs are currently prescribable Introduction of solids is not recommended before 6 months
for low birthweight term as well as preterm infants, there is for the general population; however, these UK government
no evidence that they are of any benefit for small term infants guidelines are not intended for special groups such as pre
[2]. High energy formulas designed for term infants are not term babies [119]. There is limited evidence on weaning in
recommended for preterm babies post‐discharge as they preterm infants. The decision of when to start weaning is
112 Preterm Infants
based on observing each individual baby and following their

Learning points: post‐discharge nutrition
cues for readiness for weaning, as advised in the new recom
mendations produced by BLISS. Table 7.10 shows some sug
• Most preterm infants will not require breastmilk fortifier or
gested cues for weaning.
nutrient‐enriched post‐discharge formula at home
Although age recommendations for weaning are
• A small proportion with ongoing raised nutritional
still
mentioned in the updated guidance, less emphasis
requirements or requiring catch‐up growth may benefit
is placed upon it in order to focus parents on develop
from a period of supervised supplementation at home
mental cues rather than starting at a particular age. The rec
• Vitamin and iron supplements should continue as per
ommendations now suggest 4 months corrected age as the
hospital policy on discharge
youngest age to start weaning. This is based upon observa
• Preterm infants should commence solids once demonstrating
tion data from parents and healthcare professionals, sup
recognised cues for readiness to wean; this is often around
ported by a recent RCT [120].
4 months corrected age
It is important to remember, though, that these recommen
dations are targeted towards healthy preterm infants. Those
infants with ongoing needs are likely to require more indi
vidualised advice to support them through the weaning
period. Once weaning has started, it should proceed accord
ing to normal guidelines with particular attention being paid
to ensuring appropriate nutrient‐dense foods.
8 Gastroenterology
Sarah Macdonald and Joanne Louise Price
Introduction
Sarah Macdonald
Gastroenterology is one of the most interesting and challeng- malabsorptive condition will have high to very high require-
ing areas in paediatric dietetics. The medical conditions ments. Table 8.1 can be used as a guide for requirements for
encountered are diverse and require an understanding of such infants who are fed enterally and are based on actual
normal gastrointestinal (GI) function before correct dietetic rather than expected weight. For all the clinical conditions
advice can be given. described, the assessment and monitoring of the child’s
Manipulation of feeds and diet may be the primary treat- nutritional status is paramount. Anthropometric measure-
ment for the underlying condition. Careful documentation ments should be plotted serially on appropriate growth
and monitoring of symptoms is needed to assess the response charts and feeding regimens adapted as needed.
to alterations in the feeding regimen. It is important to work In conditions resulting in malabsorption, or in those
closely with the child’s family to ensure that the planned requiring a very restrictive diet, iron indices, trace elements,
feeding regimen is possible for them to continue at home. vitamins (particularly fat‐soluble vitamins and B12) and
Once this is established the child’s caregivers need accurate urinary sodium levels should be monitored, with additional
explanation and written advice for discharge. It should be supplements prescribed as necessary. The inflammatory
recognised that GI symptoms are open to exaggeration and response is known to affect many micronutrient levels, and
manipulation by the patient and their family. In perplexing it is recommended that C‐reactive protein (CRP) should also
cases hospital admission with close monitoring of symptoms be measured at the same time to assess the accuracy of the
may be needed. A multidisciplinary team (MDT) approach results [3].
to the management of such cases is vital [1, 2].
Disorders of absorption and digestion
Nutritional requirements Acute gastroenteritis
Nutritional requirements vary according to the underlying Acute gastroenteritis (AGE) remains one of the leading
disorder. Normal requirements for most nutrients will suf- causes of childhood morbidity and mortality in developing
fice for GI disorders that do not result in malabsorption, with nations, with an estimated 5–18 million deaths attributed to
additional energy and protein required for catch‐up growth. this each year. In industrial nations the mortality rate is
When malabsorption is present, requirements for all much lower. Infants and children are particularly vulnerable
nutrients are raised to allow for stool losses particularly
to the effects of AGE because of their greater relative fluid
fluid, energy, protein and electrolytes. Most infants with a requirements and their susceptibility to faecal–oral agents.

114 Gastroenterology
Table 8.1 Suggested requirements for infants with malabsorption Table 8.2 Oral rehydration solutions (mmol/L).
per day.
Na+ K+ Cl− CHO
Energy High 120–150 kcal/kg
(500–630 kJ/kg) Dioralyte* 60 20 60 90
Very high 150–200 kcal/kg (Sanofi) (glucose)
(630–840 kJ/kg) Electrolade* 50 20 40 111
Protein High 3–4 g/kg (Electrolade) (glucose)
Very high Maximum 6 g/kg Dioralyte Relief*,† 60 20 50 30 g
Sodium High 3.0 mmol/kg (Sanofi) (rice starch)
Potassium High 2.4–4.5 mmol/kg (age dependent) WHO formulation
Fluid High 180–220 mL/kg Oral rehydration salts 75 20 65 75
(glucose)
Flavoured preparations are not suitable for young infants.

The causative mechanisms in the GI tract are: *Reconstitute 1 sachet with 200 mL water.
†
Not licensed for use in children under 3 months of age.
• increased secretion
• decreased absorption
of Paediatric Gastroenterology, Hepatology and Nutrition
Often these coexist to produce an increased fluid load that (ESPGHAN) in 1992 [6]:
exceeds the colonic absorptive capacity, resulting in diarrhoea.
• Carbohydrate should be present as either glucose or glu-
Both viral and bacterial pathogens can affect the gut in this
cose polymer at concentrations between 74 and 111 mmol/L
way. Diarrhoea and vomiting can also be due to other infec-
• ORS should contain 60 mmol/L sodium, compared
tions, such as urinary tract infections, food hypersensitivity or
with 75 mmol/L recommended by the World Health
surgical causes, which should be considered on presentation.
Organization (WHO) and United Nations Children’s
Transport of glucose and amino acids is an active process
Fund (UNICEF) in developing countries, to minimise the
and requires the presence of a sodium gradient across the
risk of hypernatraemia
brush border membrane maintained by the Na+/K+ ATPase
• Potassium should be added to replace stool losses
pump. The movement of water in the gut is a passive event
• Osmolality should be low (200–250 mOsm/kg H2O) to
driven by the movement of solute. The regulation of electro-
ensure optimal water absorption
lyte transport is controlled by several mediators, and inhibi-
tion of these pathways results in poor absorption and active Systematic reviews have confirmed that this is still the
chloride secretion into the gut. best composition of ORS to use in children admitted to hos-
Infective diarrhoea may lead to loss of absorptive area and pital with diarrhoea [7]. The ORS available in the UK are
active secretion. The defective electrolyte and nutrient trans- summarised in Table 8.2.
port and functional impairment may be severe, and this situ-
ation is worsened by cycles of fasting and starvation
Feeding during acute gastroenteritis
commonly seen in infants and children with acute diarrhoea
in developing countries. For many years it was common practice to stop feeds during
AGE is defined as a decrease in stool consistency (loose or diarrhoeal episodes. It was thought that decreased lactase
liquid) and/or an increase in the frequency of bowel actions activity, chiefly associated with rotavirus gastroenteritis,
with or without fever or vomiting. The diarrhoea should not last would cause lactose malabsorption if milk feeds were intro-
longer than 14 days. In Europe the incidence ranges from 0.5 to duced too early. There was also concern that food proteins
2 episodes per child per year in children younger than 3 years, could be transported across an impaired mucosal barrier and
with rotavirus being the most frequent infective agent in coun- cause sensitisation [8]. As a consequence, bottle‐fed infants
tries that do not use routine vaccination programmes. Norovirus with gastroenteritis were given ORS alone for 24 hours fol-
is considered to be the second leading agent of AGE [4]. lowed by the introduction of dilute feeds. This advice resulted
in a reduced nutritional intake at a time when requirements
were increased due to infection [9].
Oral rehydration solutions
A multicentre European study showed that the complete
Reduced osmolality oral rehydration solutions (ORS) should resumption of a child’s normal feeding after 4 hours of rehy-
be used as first‐line therapy for the management of AGE. dration with ORS led to a significantly greater weight gain
The sodium–glucose coupled transport mechanism stimu- during hospitalisation and did not result in worsening or
lates water and electrolyte transport, and this process is pre- prolonged symptoms [10]. A meta‐analysis showed the same
served in acute diarrhoeal disorders. Flavoured versions of outcomes [11]. This is especially important in developing
ORS are available; however, if the child cannot drink suffi- countries where children may already be malnourished.
ciently, then a nasogastric (NG) tube should be passed to ESPGHAN recommendations for the management of AGE
ensure that the oral ORS can be given [5]. include fast oral rehydration with rapid reintroduction of
Specific recommendations for the composition of ORS for normal feeding [4]. Formula dilution and gradual reintro-
European children were published by the European Society duction of feeding is not indicated. Supplementing the usual
Disorders of Absorption and Digestion 115
Table 8.3 Low lactose, cow’s milk protein‐based formulas. Table 8.4 Brush border enzyme activity in the small intestine.
Aptamil Lactose Free (Nutricia) Enzyme Substrate Product

Enfamil O‐Lac (Mead Johnson)
SMA LF (SMA Nutrition) Sucrase‐isomaltase Sucrose Glucose
(accounts for 80% α1–6 glucosidic bonds Fructose
For lactose content see Table 29.7. maltase activity) in starch molecule
(approximately 25%)
Isomaltose
feeds with ORS (10 mL/kg/liquid stool) can prevent further
Maltose
dehydration. Breastfeeding should be continued at all times Maltotriose
with supplementation of ORS. In addition to appropriate Maltase‐glucoamylase Maltose Glucose
rehydration, administration of effective probiotic strains (accounts for 20% Maltotriose
Lactobacillus rhamnosus GG and Saccharomyces boulardii maltase activity) Starch
reduces the length of hospital stay and may be considered in Lactase Lactose Glucose
children admitted with AGE [12]. Galactose
Trehelase Trehalose Glucose
Use of lactose‐free formula

A Cochrane review included 33 trials of 2973 children with
AGE in high‐ and middle‐income countries. It found that
changing to lactose‐free feeds in non‐breastfed infants and
children requiring hospital admission may reduce the dura- intestine and stimulates peristalsis, resulting in pain, bloat-
tion of acute diarrhoea by 18 hours. These feeds may also ing, abdominal distension and diarrhoea. The severity
reduce treatment failures by about one half [13]. Lactose‐free depends on the quantity of ingested CHO, the metabolic
formula should be recommended in children with chronic activity of colonic bacteria (which is reduced after antibiotic
diarrhoea (>14 days) following AGE [5]. Lactose‐free formu- therapy) and the absorptive capacity of the colon for water
las have been shown to support normal growth in infancy and short chain fatty acids. The infant is at a disadvantage
[14]. Low lactose formulas based on cow’s milk protein compared with the adult as the small intestine is shorter
(CMP) are given in Table 8.3. and the reserve capacity of the colon to absorb luminal flu-
ids is reduced. Because of a faster gut transit time there is
less time for alternative paths of CHO digestion to be
effective.
Learning points: acute gastroenteritis
• Rehydration with a low osmolality ORS remains the Congenital sucrase‐isomaltase deficiency
mainstay of treatment of AGE Congenital sucrase‐isomaltase deficiency (CSID) is an auto-
• An NG tube should be used if the child will not drink the ORS somal recessively inherited disease, which is a rare, but fre-
• Breastfeeding should not be stopped quently misdiagnosed cause of chronic diarrhoea in infants
• Normal feeding should be introduced rapidly after rehydration and children. It results in a deficiency in the ability to hydro-
• In infants and children admitted to hospital with AGE, lyse sucrose, maltose, short 1–4 linked glucose oligomers,
there is low quality evidence that the use of low lactose feeds branched (1–6 linked) α‐limit dextrins and starch. The cur-
reduces the duration of acute diarrhoea rent gold standard method of diagnosis is measuring the
• Administration of effective probiotic strains may also be con- intestinal disaccharidase activity in small bowel biopsy spec-
sidered in children requiring hospital admission with AGE imens, which show normal morphology.
Patients with CSID have different phenotypes and enzy-
matic activities that range from mild reduction of sucrase
activity to complete absence. Isomaltase is the only enzyme
Disaccharidase deficiencies to possess the α1–6 glucosidic activity needed to cleave the
linkages present in the branch points of the α‐limit dextrins
Deficiencies of disaccharidase enzymes can be primary in found in high concentrations in amylopectin [15]. Although
nature, due to a congenital enzyme defect, or secondary to considered rare, the prevalence of CSID may have been
some other GI insult. In the brush border of the small intes- underestimated, and it is likely that the disease remains
tine, there are four disaccharidase enzymes with the highest undiagnosed in numerous patients with a history of chronic
level of activity occurring in the jejunum (Table 8.4). When a diarrhoea, some of whom are diagnosed with CSID as adults.
carbohydrate (CHO) intolerance is suspected, a careful diet The sucrase‐isomaltase gene has been identified, and more
history, which includes the timing of introduction of sugars than 25 mutations discovered, which raises the possibility of
into the diet and the onset of symptoms, can aid in the diag- genetic screening in the future. Current estimates of the
nosis of these disorders. prevalence of CSID in the North American and European
The net result of sugar malabsorption is to increase the populations range from 1 in 500 to 1 in 2000 among non‐
osmotic load of GI fluid. This draws water into the small Hispanic Caucasians [16].
Table 8.5 Low sucrose, low starch solids (<1 g per 100 g). Table 8.6 Sucrose content of some common fruits (per 100 g edible
portion) [17].
Protein Meat, poultry, egg, fish
<1 g sucrose <3 g sucrose <5 g sucrose
Fats Margarine, butter, lard, vegetable oils
Avocado, bilberries, Galia melon, Apples,
Vegetables Most vegetables except potato, plantain, yam, sweet
potato, parsnip, carrots, peas, onion, sweetcorn, blackberries, grapefruit, apricots,
beetroot, okra, beans and lentils [17] blackcurrants, cherries, kiwi fruit, oranges,
Fruits Initially use fruits <1 g sucrose per 100 g fruit (Table 8.6); cooking apples, passion fruit, clementines,
most fruits contain negligible amounts of starch
damsons, dates, plums, satsumas
Milk Breastmilk, infant formula (free of glucose polymer
and sucrose) gooseberries, grapes, watermelon
Cow’s milk, unsweetened natural yoghurt, cream lemons, loganberries,
Others Marmite, Bovril, vinegar, salt, pepper, herbs, spices, 1–2 lychees, melon
teaspoons of tomato purée used in cooking, gelatine,
(cantaloupe,
essences and food colourings, sugar‐free jelly, sugar-free
drinks, fructose, glucose honeydew), pears,
raisins, raspberries,
redcurrants, rhubarb,
While being breastfed or given a normal infant formula
strawberries, sultanas
(where the sugar is lactose), the infant remains asympto-
matic and thrives. The introduction into the diet of starch or Source: Reproduced with permission of John Wiley & Sons.
sucrose in weaning foods or a change in formula to one con-
taining sucrose or starch (sucrose is added to the extensively
hydrolysed formula [EHF], Similac Alimentum, and starch is sucrose‐containing foods should improve until, by the age
found in pre‐thickened formulas) initiates symptoms. The of 2–3 years, the restriction of starch may no longer be
clinical presentation of CSID is very variable. Chronic watery needed.
diarrhoea and faltering growth are common findings in An international support group based in the USA tracks
infants and toddlers. A delay in the diagnosis may be related children with CSID and provides further information on this
to the empirical institution of a low sucrose diet by parents, disorder (www.csidinfo.com). It has followed 7433 individu-
which controls symptoms. Some children attain relatively als and has identified 5 different phenotypes who can toler-
normal growth with chronic symptoms of intermittent diar- ate varying amounts of starch in the diet [18].
rhoea, bloating and abdominal cramps before diagnosis. In The sucrose content of fruits is shown in Table 8.6. Fruits
older children such symptoms may result in the diagnosis of containing higher amounts of sucrose can be added to the
irritable bowel syndrome (IBS). diet according to tolerance [19]. If children have problems
tolerating starch in reasonable quantities, soy flour can be
Treatment used in recipes to replace wheat flour as it only contains 15 g
In the first year of life, treatment usually requires the elimi- starch per 100 g compared with 75 g per 100 g in wheat flour.
nation of sucrose from the diet. Starch is excluded initially Parents need reassurance that occasional dietary indiscre-
and then increased to tolerance (Table 8.5). The lactose in tions will not cause long‐term problems.
normal infant formula, breastmilk and mammalian milks is Newly diagnosed older children should initially be
tolerated. Such a diet is very restrictive, and care needs to be advised to avoid dietary sources of sucrose only. Advice
taken to ensure an adequate energy and vitamin intake. It should be given about alternative sweeteners that are suita-
may be beneficial to continue an infant formula after 1 year ble. The following have been found to be tolerated: crystal-
of age. Oral nutritional supplements (ONS) (sip feeds) for line glucose, dextrose, corn syrup and crystalline fructose.
older children should not be prescribed as these all contain None of the phenotypes identified by the CSID Parent
sucrose as a sweetener. Fructose and glucose can be added to Support Group could tolerate hydrogenated glucose syrup,
foods and low calorie drinks to provide extra energy if galactose/maltose/malt sugar, acesulfame K, maltitol and
needed. Butter, margarine and oils can be added to savoury brown rice syrup. If avoidance of sucrose does not lead to a
foods. All medications should be sucrose‐free; Ketovite liq- prompt improvement in symptoms, then the starch content
uid and tablets are a suitable complete CHO‐free vitamin of the diet should be reduced, particularly those foods with
supplement. a high amylopectin content such as wheat and potatoes.
Once the infant or child is symptom‐free, the tolerance Glucose tablets may be included in the diet.
for the excluded CHO should be tested by slowly increasing
dietary intake; if the capacity to absorb CHO is exceeded, Enzyme substitution therapy
this will cause osmotic diarrhoea or a recurrence of abdom- Sacrosidase, a liquid preparation containing high concentra-
inal symptoms. Reducing the CHO to the previously tions of yeast‐derived invertase (sucrase), has been used
tolerated level will result in normal stool production. With with good results and is available, as Sucraid, on a named
increasing age the tolerance of starch and the lower patient basis. It is stable if refrigerated and tasteless when
mixed with water. This formulation has been shown to be Secondary disaccharidase deficiency
resistant to acidic pH. Degradation by intragastric pepsin is
Carbohydrate malabsorption can result from secondary
buffered by taking the enzyme with protein foods. Unlike
damage to the GI mucosa and can present at any age.
human intestinal sucrase‐isomaltase, it has no activity on
Examples include rotavirus‐induced villus damage and
oligosaccharides containing 1–6 glucosyl bonds.
enteropathies of assorted aetiologies. Lactase deficiency is a
A controlled, double‐blind trial of sacrosidase in 14
more common clinical problem than sucrase‐isomaltase
patients with CSID consuming a sucrose‐containing diet
deficiency as its expression is restricted to the villi, whereas
with ongoing symptoms (diarrhoea, abdominal cramps and
sucrase‐isomaltase is expressed in the crypts of the small
bloating) resulted in the absence of, or less severe, problems.
intestine.
One other study showed that, in six patients with confirmed
CSID, dietary advice resulted in little improvement in symp-
toms, whereas sacrosidase administration resulted in a
Treatment
Treatment is to eliminate the offending CHO and treat the
marked improvement with no adverse events reported [20].
primary disorder causing the mucosal damage. Clinical
The recommended dose is 1 mL with each meal for
course depends on the underlying disease, but studies in
patients weighing <15 kg and 2 mL for those weighing
infants with rotavirus infections have shown an incidence of
>15 kg. This allows the consumption of a more normal diet
30%–50% lactose intolerance that recovers 2–4 weeks after
by children with CSID and decreases the high incidence of
the infection.
chronic GI complaints seen in this condition [21, 22]. It is
Infants requiring a lactose‐free formula and diet can use
suggested that the product is introduced when the child’s
either lactose‐free, CMP‐based formula (Table 8.3) or soy for-
tolerance of sucrose is known. Doses should be split, with
mula if older than 6 months (Table 8.14). A milk‐free diet
half the dose given at the start and the other half midway
(Table 8.17) is necessary although mature cheese can be
through the meal, to maximise the enzyme’s activity. Sucraid
included. Medications need to be checked as these can con-
should not be heated, added to hot drinks or mixed with
tain lactose as a bulking agent.
fruit juice. Data from 229 patients using Sucraid showed
that 65% of patients were able to consume either a normal or
mildly restricted diet. However, 27% is still needed to main-
tain a strict sucrose restriction with some level of starch Learning points: disaccharidase deficiencies
restriction to maintain acceptable suppression of their GI
symptoms. The addition of enzymes to enhance maltase • Deficiencies of disaccharidase enzymes can be a primary
and glycoamylase activity in the future may help these problem or secondary to gut damage
patients to cope with the continued problem of starch mal- • All are characterised by osmotic diarrhoea that stops when
absorption [16]. the offending carbohydrate is removed
• Dietary treatment of congenital CSID requires the elimina-
tion of sucrose (unless enzyme substitution therapy is given)
Lactase deficiency and removal or reduction of all foods containing starch
Congenital lactase deficiency is very rare, the largest group • A primary adult‐type lactase deficiency occurs from around
of patients being found in Finland. Severe diarrhoea starts the age of 3 years in approximately 70% on the world’s
during the first days of life, resulting in dehydration and population
malnutrition, and resolves when either breastmilk or normal
formula are ceased and a lactose‐free formula is given
(Table 8.3).
Lymphatic disorders
Primary adult‐type lactase deficiency is found in approxi-
mately 70% of the world’s population. Lactase levels are nor-
Intestinal lymphangiectasia
mal during infancy but decline to about 5%–10% of the level
at birth during childhood and adolescence. These popula- Intestinal lymphangiectasia is a congenital, acquired or
tion groups are common in East and South East Asia, tropi- inherited disorder characterised by dilated enteric lymphatic
cal Africa and Native Americans and Australians. The age of vessels, which rupture and leak lymphatic fluid into the
onset of symptoms varies but is generally about 3 years or gut, leading to protein loss. The presentation is variable,
later and only if a diet containing lactose is offered. In the but diarrhoea, hypoproteinaemic oedema and decreased
majority of Europeans, lactase levels remain high, and this levels of immunoglobulins are commonly seen. Peripheral
pattern of a declining tolerance of lactose with age is not lymphoedema of the limbs is reported in 22% of cases.

seen. Failure to thrive can also be a significant problem. Children
In ethnic groups with this problem, a moderate reduc- usually present in the first 2 years of life although cases diag-
tion of dietary lactose will be sufficient, using either lac- nosed as late as 15 years of age are documented [24]. The
tose‐reduced milks available from the supermarket or milk diagnosis is definitively established by a small intestinal
substitutes based on soya, oats and rice milks. It is impor- biopsy demonstrating the characteristic lymphatic abnor-
tant to ensure that children meet their requirements for mality although, as the lesion is a patchy one, negative
calcium [23]. biopsy does not exclude the diagnosis [25]. Techniques that
Table 8.7 Composition of minimal fat, cow’s milk protein‐based infant formulas per 100 mL.
Energy
Osmolality
Dilution (%) (kcal) (kJ) Protein (g) CHO (g) Fat (g) Na (mmol) K (mmol) (mOsm/kg H2O)
Monogen 16.8 75 315 2.2 11.6 2.2 1.6 1.8 235

(Nutricia) (84% MCT)
Lipistart 15 69 277 2.1 8.3 3.1 1.7 1.9 180
(Vitaflo) (81% MCT)
allow visualisation of the small intestine, such as video Ensure Plus Juce and Fresubin Jucy are useful to ensure ade-
capsule endoscopy or double balloon enteroscopy, may be quate protein intake in older children (Table 12.5).
required to diagnose this disorder [26]. As the dietary restrictions are required long term, it is par-
ticularly important to ensure that the recommended amounts of
Treatment essential fatty acids (EFA) are included in the diet once the vol-
Treatment is by diet unless the lesion is localised and selec- ume of complete infant formula is reduced. Walnut oil provides
tive surgical excision is possible. A reduced long chain tri- the most concentrated source of EFA and can be given as a
glyceride (LCT) diet is needed to control symptoms. This measured amount as a daily dietary supplement. Recommended
reduces the volume of intestinal lymphatic fluid and the amounts would be at least 0.1 mL per 56 kcal (235 kJ) provided
pressure within the lacteals. It has been recommended that from foods and drinks not supplemented with EFA (Table 30.4);
the amount of LCT should be restricted to 5–10 g/day [25]. A however, there are no data as to how well this is absorbed in this
very high protein intake with sufficient energy to ensure its disorder. It may be prudent to give double the normal amount
proper utilisation is also recommended. Enteric protein loss of walnut oil as a divided dose mixed with food or as a medi-
can be monitored by measuring faecal α1‐antitrypsin levels. cine. This needs to be included in the daily fat allowance.
Medium chain triglycerides (MCT) can be used as an energy Fat‐soluble vitamin supplements (A, D, E) to meet at least
source and to increase the palatability of the diet as these are the reference nutrient intake (RNI) for age should be given
absorbed directly into the portal system and not via the lym- separately. The above ONS are fortified with these vitamins,
phatics. Supportive albumin infusions and, occasionally, so separate supplementation may not be required if they are
parenteral nutrition (PN) may also be needed [27]. used. Blood levels should be monitored. A 4‐year‐old girl
Papers reviewing nutritional treatments in this condition presenting with tetany caused by hypocalcaemia due to vita-
have shown that 63%–85% of paediatric cases having dietary min D deficiency has been described [30].
intervention showed improvement in clinical symptoms and
laboratory parameters. The exact composition of the diet in
Congenital intestinal transport defects
terms of fat and protein content is not reported [28, 29].
Suitable feeds in infancy and early childhood are Monogen
Glucose–galactose malabsorption
or Lipistart (Table 8.7). If additional protein is needed to help
maintain plasma albumin levels, protein supplements, such This is an extremely rare congenital disorder resulting from a
as Protifar or Renapro, can be added to a complete feed. The selective defect in the intestinal glucose and galactose/sodium
fat and electrolyte content of these products should be calcu- co‐transport system in the brush border membrane. Dietary
lated in addition to the quantities supplied by the feed. intake of glucose, galactose, lactose, sucrose, glucose polymers
and starch are all contraindicated. It presents in the neonatal
Minimal fat diet period with the onset of severe watery, acidic diarrhoea, leading
Minimal fat weaning solids should initially be introduced to rapid dehydration and metabolic acidosis. The diarrhoea can
and gradually expanded aiming to keep the total LCT intake be so profuse and watery that it may be mistaken for polyuria
<10 g/day, certainly in the first 2 years of life. Details of mini- [31]. Glucose–galactose malabsorption is a heterogeneous condi-
mal fat diets are given elsewhere (p. 302). Attention needs to tion in its expression, and older children seem to have consider-
be given to protein intake, and extra very low fat, high pro- able variation in their tolerance of the offending carbohydrates.
tein foods should be included.
As the problem is lifelong, it is necessary to continue die- Treatment
tary restrictions, certainly until the end of the pubertal growth Initial intravenous (IV) rehydration is required. The use of
spurt. Maintaining such a low intake of fat becomes increas- ORS, all of which are glucose or starch based, is contraindi-
ingly difficult as the child becomes older. There is no infor- cated. A fructose‐based complete infant formula, Galactomin
mation about the degree of fat restriction required in older 19, should be introduced slowly to ensure tolerance, initially
children, and some relaxation of the diet should be possible as quarter and half strength formula with IV carbohydrate
so long as symptoms are controlled and growth is adequate. and electrolyte support to avoid metabolic acidosis (Table 8.8).
Minimal fat or fat‐free ONS such as Meritene shakes, which Once the infant is established on feeds and gaining weight,
can be made up with skimmed milk, or PaediaSure Plus Juce, it is important to discuss with the child’s doctor a suitable
Table 8.8 Composition of Galactomin 19 per 100 mL.
Energy
Osmolality
Dilution (%) (kcal) (kJ) Protein (g) CHO (g) Fat (g) Na (mmol) K (mmol) (mOsm/kg H2O)
Galactomin 19 12.9 69 288 1.9 6.4 4.0 0.9 1.6 407

(Nutricia)
protocol for oral rehydration should the child become Infants and children are very dependent on Galactomin 19
unwell. Plain water or a 2%–4% fructose solution can be to meet their energy requirements, and parents should be
given, but this does not have the same effect on water absorp- encouraged to continue this formula for as long as possible.
tion as ORS. Fructose is absorbed through the facilitative It can also be useful for older children entering adolescence
transporter, GLUT5, which is not coupled to sodium and who find it difficult to meet their increased energy require-
water absorption. In severe infectious diarrhoea the infant ments from eating a low starch diet. If sufficient formula is
will need IV fluids. taken, a vitamin supplement should not be needed.
Fructose is available on prescription for this condition and
can be used to sweeten foods for older children and as an Table 8.9 Foods allowed in children with glucose–galactose
additional energy source. It is important to ensure that all malabsorption (<1 g glucose and galactose per 100 g)*.
medicines are CHO‐free.
First weaning solids should contain minimal amounts of Protein Meat, poultry, egg, fish
starch, sucrose, lactose and glucose (Table 8.9). Manufactured Fats Margarine, butter, lard, vegetable oils
baby foods are not suitable, and it is necessary for weaning Vegetables Ackee (canned), asparagus, bamboo shoots, beansprouts
solids to be prepared at home. All foods should be cooked (canned only), broccoli, celery, cucumber, endive,
without salt and initially blended to a very smooth texture. fennel, globe artichoke, lettuce, marrow, mushrooms,
To save time parents can prepare foods in advance and freeze spinach, spring greens, steamed tofu, watercress,
preserved vine leaves
in clean ice cube trays.
With increasing age children gradually begin to tolerate Fruits Avocado pear, rhubarb, lemon juice
more of the offending CHO due to colonic salvage. The foods Milk Galactomin 19 formula
in Table 8.10 are grouped to allow a gradual increase in the substitute
amount of glucose and galactose in the diet. These lists can Others Marmite, Bovril, vinegar, salt, pepper, herbs, spices, 1–2
be used as a guide by parents. Small amounts of new foods teaspoons of tomato purée used in cooking, gelatine,
can be introduced cautiously and increased as tolerated. Too essences and food colourings, sugar‐free jelly, sugar‐free
much of these foods will exceed the individual’s tolerance drinks, fructose
and cause diarrhoea. In this situation the child should return
*The lists of foods have been compiled calculating the amount of glucose
to the diet previously tolerated, and food introductions tried and galactose as g starch + g glucose + g lactose + 0.5 g sucrose [17].
again a few months later. Source: Reproduced with permission of John Wiley & Sons.
Table 8.10 Glucose and galactose content of foods (per 100 g edible portion) [17].
1–2 g glucose + galactose 2–3 g glucose + galactose 3–5 g glucose + galactose
Protein
Quorn, all ‘hard’ cheeses, cream cheese, brie,
camembert
Vegetables
Aubergine, beans (French and runner), Brussels Carrots Sugar snap peas, butternut squash,
sprouts, cabbage, cauliflower, celeriac, courgettes, mange tout
gherkins (pickled), leeks, okra, onions (boiled),
green peppers, radish, spring onions, swede,
tomatoes (including tinned), turnip
Fruits
Gooseberries, redcurrants Apples (cooking, sweetened with fructose Apricots, blackcurrants, cherries,
or artificial sweetener), blackberries, clementines, peaches, pineapple,
loganberries, melon (all types), pears, grapefruit, nectarines, oranges,
raspberries, strawberries satsumas, tangerines
Other
Ordinary mayonnaise (retail) – not reduced calorie Double cream Whipping cream
Source: Reproduced with permission of John Wiley & Sons.

Congenital chloride‐losing diarrhoea necessitating this being administered over 24 hours. Trace
mineral deficiencies have been reported, so it is important to
This is a selective defect in intestinal chloride transport in
carefully monitor nutritional parameters [35]. Trophic feeds
the small intestine and colon, which is inherited as an auto-
should be offered so long as the resulting osmotic diarrhoea
somal recessive trait. Lifelong secretory diarrhoea occurs
does not further complicate fluid balance. Many babies in
with high chloride concentrations. It has been reported in
this group have early‐onset cholestatic liver disease. A case
most populations including the UK; however, it is most com-
series of three infants with MVID and cholestasis showed
monly seen in Finland, the Arabian Gulf and Poland [32].
improvement with the substitution of conventional IV lipid
In the past it generally resulted in severe lethal dehydration.
sources with an emulsion based on fish oil [36].
Watery diarrhoea is present prenatally as polyhydramnios
Small bowel transplantation is the only curative treatment in
and after birth often goes unnoticed as the fluid in the nappy
the early‐onset form of the disease; however, the decision and
is thought to be urine. Dehydration occurs rapidly followed
timing should be carefully assessed due to recent improvements
by disturbances in electrolyte concentration causing hypoka-
in PN management. A case series of 24 patients, detailing the
lemia and hypochloraemia with mild metabolic alkalosis.
complexity of managing these patients, has been published [37].
Treatment
As the intestinal defect cannot be corrected, treatment requires Tufting enteropathy
replacement of the diarrhoeal losses of chloride, sodium, This is a rare autosomal recessive enteropathy of neonatal
potassium and water. The rationale behind this therapy is the onset that presents with intractable diarrhoea, poor growth
normal jejunal absorption of these electrolytes. Initially this and intestinal failure. The intestinal histology shows ‘tufts’
may need to be given IV, but this should gradually be changed of closely packed epithelial enterocytes due to poor entero-
to the oral route. Insufficient salt substitution causes chronic cyte adhesion. Genetic associations include a mutation in the
dehydration, salt depletion and activation of the renin– epithelial cell adhesion molecule (EpCAM) gene. There is a
aldosterone system, which may lead to chronic kidney higher prevalence in areas with a high degree of consanguin-
disease [33]. Dietary manipulation is not required in this
ity and in patients of Arabic origin [38].
disorder other than to ensure a normal intake for age in con- Children with tufting enteropathy, also known as intesti-
junction with the prescribed electrolyte and fluid therapy. nal epithelial dysplasia, have a highly variable clinical phe-
notype. Infants require PN support, but there appears to be a
Congenital enteropathies and protracted diarrhoea range of severity in these disorders with some children
becoming less dependent on, and even stopping, PN as they
The causes of protracted diarrhoea in the first few months of progress through childhood [39, 40]. The enteral manage-
life are mostly post‐infectious and food allergic enteropathies. ment of tufting enteropathy is limited to the exclusion of
Rare, and usually early onset, congenital enterocyte disorders major food allergens if there is concurrent inflammation in
include microvillous inclusion disease (MVID) and tufting gut biopsies and additional tailored micronutrient supple-
enteropathy (intestinal epithelial dysplasia) [34]. Congenital ments in cases weaning from PN.
glucose–galactose malabsorption, congenital chloride‐losing
diarrhoea and congenital sodium‐losing diarrhoea also mani- Defects of lipolysis
fest from birth, but villous morphology is normal in these babies.
Shwachman–Diamond syndrome
Microvillous inclusion disease
Shwachman–Diamond syndrome (SDS) is a rare autosomal
MVID is a congenital enterocyte defect that requires PN for recessive disorder characterised by congenital abnormalities,
fluid and nutritional maintenance. Small bowel biopsy shows exocrine pancreas dysfunction, bone marrow failure and a
accumulation of secretory granules within the enterocytes, predisposition to myelodysplasia and leukaemia. It is a
and electron microscopy confirms the diagnosis, showing the multisystem disorder with potential manifestations in the
typical inclusions of microvilli in the cytoplasm. It does not skeletal, hepatic, cardiac, immune and central nervous sys-
manifest in utero with hydramnios (as a result of intrauterine tems. Deficits in cognitive abilities across many domains of
diarrhoea), but commonly becomes apparent in the first few functioning are seen in the majority of individuals with this
postnatal days. Early‐onset MVID is almost invariably fatal condition, although the extent of the problems varies [41].
without PN support. A later onset form of MVID has been The heterogenicity of presenting symptoms means that one
described in a few patients who appear to have a better prog- American study of 37 children found that only 51% of patients
nosis, with one reported case weaning off PN. presented with the classical picture of neutropenia associated
Early‐onset MVID is characterised by secretory diarrhoea with diarrhoea while 73% presented with failure to thrive.
(typically 200–250 mL/kg/day) and intolerance of any oral The median age at clinical presentation was 3.5 years [42].
nutrition. The management of the PN is difficult with the
infants having very high fluid and electrolyte requirements Treatment
and experiencing frequent complications of acute dehydra- Children with SDS and pancreatic insufficiency (PI) have
tion and metabolic imbalance. Some young children fail to normal sweat chloride tests, unlike those children with cystic
tolerate any breaks in the administration of PN, fibrosis (CF). Dietary treatment consists of enteric coated
Coeliac Disease 121
pancreatic enzyme replacement therapy (PERT) (p. 219) in Children with SDS are generally shorter than their peers,
those with PI. This should be titrated with stool consistency, and it is thought that this is related to their skeletal prob-
fat‐soluble vitamin levels and weight gain. Due to the rarity of lems. Some children do need additional nutritional support
the condition and the lack of evidence‐based treatment, a as sip or gastrostomy feeds to achieve normal weight gain and
recent review concluded that medical treatment for malab- growth velocity, and a high number are recorded as requiring
sorption in SDS should aim to improve fat absorption and support for oral motor skills by specialist speech and language
stool output; however, it is unclear whether this improves therapy [44].
prognosis [43]. Micronutrient levels, including trace elements and fat‐
In the author’s experience these children need less PERT per soluble vitamin levels (A, D, E), should be monitored and
kg body weight than age‐matched children with CF. It is appropriate supplements taken to correct any deficiencies.
appropriate to start with a small initial dose of 2000 units Prothrombin time can be used as a surrogate marker of
lipase/kg body weight/day distributed between feeds, meals vitamin K levels. It is important to ensure that fat‐soluble
and snacks containing protein, fat or complex carbohydrates. vitamin supplements are taken at the same time as PERT to
This can then be gradually increased as needed, but should not ensure optimum absorption. One study found that 16 of 21
exceed the upper dosage guidelines for children with CF [41]. children with SDS had low levels of vitamin A and 4 of 21 had
It is generally not necessary to teach families to titrate the a low vitamin E. A variable number also were also found to
dosage of PERT using fat exchanges. Advice to give a set PERT have deficiencies in zinc, copper and selenium possibly related
dosage with each meal and snack alongside suggestions to to the abnormal GI histology seen in 7 of these children [44].
increase slightly if more fat than usual is consumed generally The long‐term management of these children should be
suffices. Unlike children with CF, pancreatic function may undertaken by an MDT that includes a gastroenterologist,
improve such that 50% children can stop their PERT as they haematologist and dietitian with appropriate referrals to
get older. In most European centres faecal elastase is used as an dental services. Care should be individualised due to the
indicator of PI, and this should be reassessed every few years. heterogenicity of the underlying condition.
Immune Enteropathies
Joanne Louise Price
Coeliac disease Symptoms associated with CD in children are:

• persistent non‐specific GI symptoms
Coeliac disease (CD) is a systemic, immune‐mediated
• iron deficiency anaemia
disorder characterised by a variable combination of clinical
• other micronutrient deficiencies, e.g. B12 and folate
manifestations, specific antibodies and enteropathy [45].
• chronic diarrhoea
The onset of CD follows ingestion of gluten‐containing
• constipation
grains in genetically susceptible individuals. The prevalence
• prolonged fatigue
of CD in the UK is estimated to be 1 in 100. There are at least
• weight loss
two prerequisites for developing CD: a genetic predisposi-
• skin rashes
tion (associated with human leukocyte antigen [HLA] mol-
• growth failure
ecules DQ2 and DQ8 found in at least 98% of patients) and
• children present with an elevated or normal body mass
ingestion of gluten. More than one member of a family may
index at diagnosis
be affected, and the incidence in families is increased to 1 in
10. There is considerable variation in the age of onset and in
Screening
the mode of presentation, with an increasing number being
diagnosed in adulthood as the disease may be atypical or In addition to children with unexplained symptoms as listed
clinically silent in apparently healthy individuals. above, serological testing is recommended for asymptomatic
Undiagnosed and, therefore, untreated CD is associated children with a known increased risk of CD. These include
with an increased risk of long‐term complications such as those with type 1 diabetes mellitus, autoimmune thyroid
osteoporosis and infertility. There is also a higher incidence disease, Down’s syndrome and first‐degree relatives of those
of non‐Hodgkin’s and Hodgkin’s lymphoma and small with CD. This is summarised in the NICE guidelines [45].
bowel cancer, but overall rates are low. Children should be consuming sufficient gluten in their
Campaigns by a charity, Coeliac UK, to raise awareness of diet at the time of testing (see gluten challenge p. 125). It
symptoms and the recommended use of screening by the should also be noted that a negative result on a serological
National Institute for Health and Care Excellence (NICE) screen at one point in time does not exclude CD for life; as it
[45] are slowly increasing rates of diagnosis from only 15% may develop later, repeat tests may be necessary.
10 years ago [46], yet it is estimated that only 30% of people CD is an immunological disorder mediated by T cells and
are clinically diagnosed today (Coeliac UK). local and systemic production of autoantibodies against
structural proteins of the small intestine mucosa and other Table 8.11 Gluten‐free diet.
organs, in association with a specific pattern of cell‐mediated
damage in the small intestine. CD‐specific antibody tests Foods permitted Foods to avoid Check ingredients
measure IgA tissue transglutaminase (tTG) and IgA anti‐ Milk, butter, cream, Cheese spreads
endomysial antibodies (EMA) (the same antibody measured cheese and savoury
by different methods). These antibodies may not be raised spreads, yoghurts,
in IgA deficient individuals, so IgA should always be meas- custard
ured at the same time, and most laboratories will incorpo- Meat, fish, eggs, Products with pastry, Sausages, tinned
rate this into their coeliac screen. pulses thickened gravies and meats
The gold standard for diagnosis was previously a small sauces, breadcrumbs,
intestinal biopsy demonstrating mucosal damage followed batter
by a clinical response to gluten withdrawal. New guidelines Rice, corn (maize), Wheat, rye, barley, Oats
recommend that: buckwheat, millet, bread, crumpets, cakes,
tapioca, soya, gram biscuits, crackers,
• symptomatic children can be diagnosed accurately flour, arrowroot chapattis, nan bread,
without biopsy. Diagnosis based on a level of tTG‐IgA 10 pasta, noodles,
times or more of the upper normal limit, a positive result semolina, couscous
from the EMA tests in a second blood sample, and the Special gluten‐free Wheat‐based cereals, Corn and rice‐
presence of at least one symptom could avoid risks and flours, breads, e.g. Weetabix, based cereals
costs of endoscopy [47]. Current guidance also suggests biscuits and pasta Shredded Wheat
HLA testing, but this is no longer felt to be necessary and Vegetables, potato, Potato croquettes Flavoured potato
is likely to be removed from future guidance. New fruit and nuts crisps, dry‐
European guidelines for the diagnosis of CD in children roasted nuts
can be found at www.espghan.org. Sugar, jam, honey, Liquorice Filled chocolates,
• for asymptomatic children and/or where tTG is raised some chocolates boiled sweets
on screening, but is less than 10 times the upper normal Tea, coffee, drinking Malted milk drinks, e.g.
limit, a small bowel biopsy is still recommended to diag- chocolate, fizzy Horlicks and Ovaltine
nose the condition; the histology should be interpreted drinks, juice, squash Barley water, beer
using the Marsh grading system [47]
Learning points: diagnosis of coeliac disease diet, including topics as diverse as eating out to travelling
abroad. It also produces many helpful publications such as
• Adequate gluten must be consumed for all tests (see the Food and Drink Guide in electronic and paper form plus a
challenge guidance p. 125) ‘food checker’ barcode scanner app for smart phones.
• A negative test result can change to positive over time Membership is free for the first 6 months and then costs £24
• In the UK only 30% of all those with CD are clinically (£12 concessionary) per year or £42 for 2 years for the
diagnosed caregivers of a child with CD (www.coeliac.org.uk).
• Symptomatic children can be diagnosed on blood tests alone
if the markers are high enough Gluten‐free diet
The diet should be followed for life. All possible sources of
gluten including wheat, rye, barley and contaminated oats
should be excluded from the GF diet (Table 8.11). This
includes a number of staple foods such as bread, pasta, bis-
Treatment
cuits and cakes; parents will need support in finding suitable
Currently the only treatment for CD is the exclusion of all die- substitutes. Children tend to be high consumers of savoury
tary sources of gluten, a protein found in wheat, rye and barley snack foods and processed foods, which also need to be
and contaminated oats. Gluten can be divided into four sub- excluded and substituted. Wheat flour is commonly used in
classes: gliadin, glutenins, albumins and globulins. In wheat processed foods as a binding agent, filler or carrier for fla-
the injurious constituent is the prolamin fraction of α‐gliadin. vourings and spices, and these also need to be excluded and
The equivalent in rye is secalin and in barley hordein. Oats is suitable GF substitutions made.
discussed in more detail (p. 123). Enzymatic degradation stud-
ies have suggested that the damaging fraction is an acidic Commercially produced gluten‐free foods
polypeptide with a molecular weight <1500 Da. Many proprietary GF foods are available, and the standards
for their manufacture are governed by the Codex
Coeliac UK Alimentarius Commission [48], established by the Food and
This is an independent registered charity established over 50 Agriculture Organization of the United Nations (FAO) and
years ago. All parents/caregivers of children with CD should the WHO to provide international food standards, guide-
be encouraged to join. The society acts as an invaluable lines and codes of practice to ensure the safety and quality of
resource on all aspects of management of the gluten‐free (GF) the international food trade.
Coeliac Disease 123
Labelling randomised double‐blind paediatric study where 177 chil-

Gluten in foods can now be easily identified due to food dren (70% female, average age 9 years) completed the trial;
labelling legislation (Regulation (EU) No. 78/2014), which oats that are specifically grown to be a non‐reactive strain
means that all foods containing a source of gluten must be and are uncontaminated with other gluten‐containing cere-
clearly labelled. These are usually highlighted, often written als appear to be safe to use in a GF diet [53].
in bold on the ingredients list. Due to the low level of gluten NICE guidelines state that uncontaminated oats may be
deemed safe for people with CD, any food with ‘may con- introduced into the diet at any time [45]. Coeliac UK recom-
tain’ statements should also be avoided. It should be noted mends that the introduction of oats should be considered on
that incorporating an allergy box on the label of manufac- an individual patient basis. At the time of writing, caution is
tured foods is not compulsory and may not be reliable. still practised in many paediatric centres. The author’s current
Ingredients made from a gluten‐containing grain that is practice is to advise initial avoidance of oats. Once the serum
processed to remove all the gluten are exempt from the above tTG level has fallen into the normal range and growth param-
labelling; however, sometimes manufacturers still state the eters are as expected, GF oats may be introduced. Coeliac UK
grain source in the ingredient list. Parents should be reas- produces a comprehensive list of uncontaminated oat prod-
sured that glucose syrups derived from wheat or barley and ucts and GF oats. A repeat tTG could be offered if there are any
wheat‐based maltodextrins are safe to include in the GF diet. concerns regarding symptoms after introduction of oats [45].
The most recent guideline for the labelling of GF foods It should be noted that there is also additional legislation
(EU Directive No. 828/2014, 30 July 2014, enforced July 2016) regarding food containing oats (EU Directive No. 828/2014,
uses these Codex Alimentarius Commission definitions: 30 July 2014):
• gluten‐free – ‘the statement “gluten‐free” may only be • ‘oats contained in a food presented as gluten‐free or very
made where the food as sold to the final consumer con- low gluten must have been specially produced, prepared
tains no more than 20 mg/kg of gluten’ and/or processed in a way to avoid contamination by
• very low gluten – ‘the statement “very low gluten” may wheat, rye, barley, or their crossbred varieties and the
only be made where the food, consisting of or containing gluten content of such oats cannot exceed 20 mg/kg’
one or more ingredients made from wheat, rye, barley,
oats or their crossbred varieties which have been spe- Barley malt
cially processed to reduce the gluten content, contains no Barley malt extract in malt vinegar is safe to consume as the
more than 100 mg/kg of gluten in the food as sold to the amount of gluten in the end product is extremely small and
final consumer’ (at the time of writing these foods are is well below a level that is safe for people with CD. However,
not marketed in the UK) tests using a more sensitive analysis method have shown
that some breakfast cereals containing malt flavourings
Oats derived from barley exceed the accepted threshold allowed
Oats, rye, barley and wheat are members of a subfamily of by the international Codex Standard and are no longer con-
grains, the Pooideae. Based on the structure of the grains’ sidered suitable for inclusion in the GF diet. Foods suitable
storage proteins, this subfamily is further divided and are listed in the Food and Drink Guide from Coeliac UK.
includes the Triticeae (wheat, rye and barley) and Avinea
(oats). The prolamin fraction of the storage protein contains Codex wheat starch
gliadin in wheat and avenin in oats. Avenin has some sequence GF wheat starch is known as Codex wheat starch. Prior to
homology with gliadin, and recent studies suggest that some the reduction of gluten levels in foods considered safe for
oat varieties may show a degree of residual toxicity in vitro, people with CD, there may have been a small number of
suggesting that there are differences between oat varieties in ‘supersensitive’ individuals who appeared to be sympto-
relation to their safety or toxicity for people with CD [49, 50]. matic when eating foods containing wheat starch. However,
Oats avenin is also present as only 5%–15% of total oat pro- this was most probably as a result of the level of acceptable
tein, as opposed to the prolamin content of wheat, rye and bar- residual gluten previously set at 200 ppm. Since the 2012 leg-
ley, which is as high as 50%. This suggests that there could also islation, Codex wheat starch complies with the international
be a threshold of exposure to oats that needs to be exceeded standard for GF foods for residual gluten content at <20 ppm.
before symptoms occur. Guidance for intakes in adults is This level of gluten should no longer cause a problem for
based on this assumption [45, 51]. Oats are also often contami- people with CD. In those reporting a reaction to products
nated with wheat, rye or barley at various stages of produc- containing Codex wheat starch, a thorough dietary assess-
tion: in fields, transportation, storage, milling and processing. ment is recommended to help identify any causative issues.
There is a large body of evidence to support the safe use of
oats in children with CD, summarised in a 2017 systematic Cross‐contamination
review and meta‐analysis [52]. Problems with early studies Cross‐contamination is probably the biggest risk factor in
to determine the safety of oats in the diet included the use of ensuring provision of a GF diet. It should be explained that
contaminated oat products, small patient numbers, insensi- crumbs in toasters, bread boards, pots of butter and jam are
tive functional tests and intestinal biopsies that were all potential sources of significant amounts of gluten.
difficult to interpret. However this meta‐analysis contains Separate toasters, utensils and spreads should be provided
some larger more convincing studies and a recent for the GF diet. Where possible GF food should be regularly
prepared that is suitable for the whole family to enable GF foods can be found in the British National Formulary or in
everyone to eat together. Coeliac UK’s Food and Drink Guide. A dietitian may support
and request additional items on prescription and should do
Eating out so especially in exceptional circumstances, for example,
Children should be taught to check with parents/caregivers where dietary intake is poor, income is low, there are multi-
before eating foods outside the home or when foods are ple family members with CD or the child with growth failure
offered by siblings or friends. Children’s parties are a source may benefit from additional foods to supplement their diet.
of concern due to the buffet style table, high volume of Foods will only be prescribed at the discretion of the general
wheat‐based products and risk of cross‐contamination. If GF practitioner and within the limits of the local CCG.
food cannot be guaranteed, the child with CD should take Availability of GF foods that may be purchased in the UK
suitable foods of their own to eat. has increased greatly over the past 10 years with most popu-
For eating out and takeaways, food outlets providing GF lar supermarket chains producing their own brands of GF
alternatives who comply with strict guidance are listed on foods. They cost more, with some specialist GF products
the Coeliac UK website. This is an important aspect to con- 76%–518% more expensive than their gluten‐containing
sider in teenage years when adolescent children begin to counterparts [56]. Naturally GF foods should not be mar-
socialise independently. keted to mislead the consumer by suggesting that the food
possesses special characteristics when in fact all similar
Travelling abroad foods possess such characteristics; the dietitian can help
Insurance companies tend not to increase the cost of insurance for parents identify these and avoid paying inflated prices.
people with CD; however, it should still be declared. CD is very Product taste and textures vary, and children should be
common in European countries, and local organisations may pro- encouraged to try different food items.
vide lists of hotels, restaurants and shops that supply GF foods. Some specialist GF food manufacturers will provide trial packs
Coeliac UK also provides information on over 50 countries. to newly diagnosed patients on application. Manufacturers’
Taking sealed packs of GF products may not be necessary contact details can be found on the Coeliac UK website.
due to the excellent provision of these foods in Europe; how-
ever, if travelling further afield, it is advisable to contact the
Learning points: prescriptions and products
airline or tour operator before packing these items in luggage.
Airlines may sometimes also give additional baggage allow-
• Prescriptions are generally issued for bread and mixes only
ance if requested, and a medical/dietetic letter in support of
• Other foods are still prescribable and may be requested in
this should be provided if requested.
special cases
• Gluten‐free manufactured products are expensive, and
Learning points: labelling there may be naturally gluten‐free alternatives available
• Coeliac UK resources can be used to identify naturally
• Gluten‐free means a gluten content of <20 g/kg (<20 ppm) gluten‐free products to buy
in a food or drink
• Foods containing levels >21–100 ppm are labelled very low
gluten, but this is not currently used in the UK
• Some foods with barley malt extract are suitable and some Bone health
are not One of the main complications of CD in adults is reduced
• Uncontaminated oats can be introduced into the diet with bone mineral density (BMD), leading to osteoporosis. It is
caution unclear if this is due to calcium malabsorption for prolonged
periods prior to diagnosis. One study found that while the
bone mineral content of coeliac children was s ignificantly
Prescriptions lower than control subjects at diagnosis, after 1 year on a GF
NHS England has published guidance for clinical commis- diet it had returned to normal. The calcium intake of the
sioning groups (CCG) on the prescribing of GF foods in children was not assessed during this time [57]. Another
England [54]. This follows the Department of Health and longitudinal study found that, although there was an

Social Care (DHSC) recommendation to retain access to GF improvement after 1–2 years on the GF diet, BMD scores
foods on prescription in England but to restrict these prod- were still lower than expected for the normal population
ucts to GF breads and flour mixes and to remove access to all [58]; BMD has also been found to be lower in children with
other GF foods such as GF pasta and breakfast cereals. CD with poor dietary adherence [59]. Suboptimal vitamin D
Currently in England only bread and GF mixes are routinely and K status may contribute to the increased risk of poor
prescribed for those with a diagnosis of CD. Furthermore, in bone health in childhood CD, and careful consideration
some CCG the type and brand of GF foods are also limited. should be given to supplementation with these vitamins at
Dietary compliance is known to be enhanced by the ease the time of diagnosis [60]. Although there are no formal rec-
with which patients can obtain suitable amounts of GF foods ommendations, it would appear sensible to ensure that chil-
on prescription [55]. Several other staple foods remain pre- dren’s intake is at least equal to the RNI for calcium for their
scribable for patients with CD; a complete list of prescribable age. Some GF products are fortified with calcium.
Eosinophilic Gastrointestinal Diseases 125
Gluten challenge Two to three grams of gluten is found in one medium slice
of bread, two rusks or digestive biscuits, four tablespoons of
Gluten challenge may be necessary when there is some doubt
cooked pasta or one Weetabix. Parents are often anxious that
at the time of initial diagnosis. This should always be pre-
the inclusion of normal foods in the diet will make returning
ceded by HLA typing and assessment of mucosal h istology
to the GF diet difficult if the diagnosis of CD is confirmed.
and should be avoided in children under the age of 5 years
Reassurance is required, and an explanation of the proce-
and during the adolescent growth spurt, where p ossible [47].
dure to the child is very important in ensuring its success.
Challenge may also be necessary when a patient has com-
menced a GF diet prior to a formal diagnosis.
For challenge purposes gluten can be introduced into the Associated food intolerances
diet in two forms: either as gluten powder that can be mixed
Due to the gluten‐induced enteropathy, a secondary disac-
in foods such as yoghurt or as gluten‐containing foods. Both
charidase deficiency may occur at the time of diagnosis. It is
need to be given daily in sufficient amounts for 4–6 weeks to
occasionally necessary to exclude lactose from the diet of a
ensure an adequate challenge [47]:
child newly diagnosed with CD. Infants may sometimes
• 10 g gluten per day in young children have an associated CMP intolerance and require a CMP‐free
• 10–15 g per day in older children formula (Table 8.15). This usually resolves with mucosal
healing after commencement of a GF diet.
Eosinophilic Gastrointestinal Diseases

Sarah Macdonald
Eosinophils are customary inhabitants and key effector high rates of concurrent asthma, allergic rhinitis, eczema and
cells of the innate immune system within the GI tract. They food allergy (FA)/anaphylaxis. It is more common in boys.
protect against parasitic infections, the rate of these having Young children typically present with symptoms of gastro‐
decreased markedly in the developed world. It is thought oesophageal reflux disease (GORD), food refusal or growth
that hypersensitivity reactions to allergens may now be the faltering, while adolescents tend to present with dysphagia.
driving force for recruitment and activation of gut eosino- It is a chronic, relapsing disease with only a small amount of
phils. When activated they release multiple cytotoxic long‐term data available on which to assess outcomes. There
agents and immunomodulatory cytokines resulting in local is a complex relationship between EoE and GORD, and these
inflammation and tissue damage [61]. disorders are not mutually exclusive and may exacerbate
Eosinophilic gastrointestinal diseases (EGID) are a hetero- each other [64]. Complications include food impaction,
geneous group of diseases (eosinophilic oesophagitis [EoE], oesophageal stricture formation and perforation. Serum
eosinophilic gastroenteritis, eosinophilic colitis) character- immunoglobulin E (IgE) and skin prick tests for IgE‐medi-
ised by GI symptoms and increased eosinophils in the ated FA are warranted to identify comorbid food‐induced
absence of other causes. Apart from EoE the diagnosis of allergic disease. However, these tests alone are not sufficient
these disorders is unclear due to the uncertainty as to the nor- to make the diagnosis of food allergy‐driven EoE.
mal number of eosinophils seen in different parts of the GI
tract and their distribution within the mucosa [62]. The latter
Treatment
may differ with geographical environment.
The goals of treatment are symptom resolution and reversal
EGID are classified based on the location of the inflamma-
of the histological abnormalities. First‐line therapy is a trial
tory response, even though their symptoms, prognosis and
of a protein pump inhibitor (PPI) followed by a second
treatment vary considerably. In view of the close relation-
biopsy to assess histological response to this treatment and
ship between food allergies and some EGID, controlling
differentiation of the diagnosis between GORD and EoE. If
antigen exposure is one of the most widely used strategies.
symptoms fail to improve, then dietary therapy should be
In one study 80% of patients with EGID were found to have
tried as sole treatment or in conjunction with topical
coexisting atopy, and anaphylaxis to foods was present in a
swallowed corticosteroids (steroids that are usually inhaled
significant number [63].
but are taken orally).
Dietary therapy has been shown to be an effective treat-
Eosinophilic oesophagitis ment when assessing the histopathology of patients, and
three different elimination regimens have been used:
EoE is the most common and best described of the EGID and
is seen in both children and adults. It is a chronic immune/ • Complete amino acid‐based formulas (AAF) have been
antigen‐mediated disease characterised clinically with shown to induce remission in 96% of patients, the
symptoms related to oesophageal dysfunction and histologi- majority of whom needed an NG tube to complete the
cally by eosinophil‐predominant inflammation. There are treatment. The trial of feeds is followed by an extended
period of food reintroductions to identify specific aller- Treatment

gens [65]. There are no consensus guidelines on which to base
• Dietary restrictions based on allergy testing or the empir- therapies due to the rarity of this diagnosis and it depends
ical exclusion of the most common food antigens have on whether associated FA can be confirmed. Four‐food
also been used. The former was successful in 69% of exclusion diets (milk, egg, wheat and soya), few foods diets
patients and is recommended as first‐line therapy if or exclusive elemental (amino acid‐based) enteral feeds can
allergy to specific foods is suspected by history and sen- be tried [73, 74]; however, a systematic review looking at
sitisation supported by formal testing [66]. the effectiveness of such treatments in inducing disease
• An empirical six‐food exclusion diet (cow’s milk [CM], remission concluded that there was a lack of evidence to
soy, wheat, egg, peanut, fish and seafood) has demon- support their use [75]. If there is a limited response to these
strated a 74% success rate [67]. therapies, then medical treatment, usually with steroids, is
unavoidable [76].
A retrospective case series of patients treated with one of
these three elimination diets showed the greatest efficacy
with complete AAF (elemental feeds) with 96% remission. Learning points: eosinophilic gastrointestinal diseases
Empirical removal of the most common allergens from the
diet was as successful as a directed diet based on skin prick • Controlling antigen exposure is a therapeutic strategy for
tests and patch testing alone (remission rates of 81% and children with EGID but is best described in EoE
65%); however, the treatment chosen was not randomised • For patients with proven EoE, recommended first‐line
and depended on negotiations with the family [68]. dietary therapy is an empirical elimination diet (milk, egg,
A recent paper has been published exploring the use of a wheat, soya, +/− peanuts and fish/shellfish)
step‐up dietary regimen, where two foods were initially • There is now some evidence that a step‐up approach
excluded and the symptomatic response assessed before fur- towards the use of dietary exclusions may be a more effica-
ther food exclusions was introduced. The authors suggest that cious therapy in EoE. This practice has not yet been
such an approach may avoid unnecessary dietary restrictions, adopted in international guidelines and needs further
reduce the number of endoscopies required, and shorten the evaluation
diagnostic process [69]. A similar result was found using com- • In EoE exclusive enteral AAF as a treatment is reserved for
puter modelling of reported studies of patients with EoE [70]. treating children with multiple allergies, faltering growth,
As with many dietary treatments, the optimal duration of and severe disease where an exclusion diet has been ineffective
elimination diet to achieve remission is unclear, and current or impossible to implement
recommendations suggest an 8–12‐week therapeutic trial of
the planned exclusion diet. It is also poorly defined which
dietary intervention is associated with better mucosal heal-
Food protein‐induced enterocolitis syndrome
ing of the oesophagus [64].
Current consensus recommendations suggest that the spe-
Food protein‐induced enterocolitis syndrome (FPIES) is a
cific therapy prescribed should take into account the family
non‐IgE‐mediated FA that typically presents in infancy with
lifestyle, adherence to therapy and resources [64]. Multiple
repetitive, protracted vomiting that starts 1–4 hours after
food exclusions are difficult for the family to m anage and
food ingestion. The vomiting is often accompanied by leth-
expose the child to the dangers of dietary inadequacy.
argy and pallor and may be followed by watery or bloody
Careful monitoring is required with amino acid‐based sup-
diarrhoea. In at least 15% of cases, this can lead to shock with
plemental feeds or vitamin and mineral supplements pre-
haemodynamic instability and hypotension. It occurs once
scribed as needed. Once the disease is in remission, foods
CM‐based or soy feeds and/or solid foods are introduced
should be reintroduced sequentially with careful monitoring
into the infant’s diet.
so that only the foods the child is allergic to continue to be
The manifestations and severity of FPIES depend on the
excluded. In one study CM was found to be the most com-
frequency and dose of the trigger food as well as the age and
mon allergen followed by wheat, egg and soy [71].
phenotype of the child. In acute FPIES, symptoms usually
resolve within 24 hours after ingestion of the causative food,
Eosinophilic gastroenteritis
and most children with this disorder are well between
Eosinophilic gastroenteritis is a rare chronic inflammatory dis- episodes and grow normally. Chronic FPIES is rare and less
order of the GI tract characterised by eosinophil accumulation well understood. It is seen in infants less than 4 months of
in the mucosa or in deeper layers of the GI wall. Symptoms age fed with CM or soya‐based infant formula, and the
vary according to the part of the intestine and the layer of the affected infants have symptoms of chronic or intermittent
GI wall affected. Under healthy conditions the stomach and vomiting, diarrhoea and poor weight gain [77].
the small intestine show detectable baseline numbers of The most common food allergens reported in this disorder
eosinophils, but their number is increased in eosinophilic are CM, soy, rice and oats although a wide array of other
gastroenteritis. Symptoms may include pain, dysmotility, foods have been implicated. There are geographical differ-
nausea, vomiting, diarrhoea, blood loss, malabsorption, ences in foods that trigger FPIES, with fish-induced FPIES
protein‐losing enteropathy and faltering growth [72]. being common in Italy and Spain, but less common elsewhere.
Autoimmune Enteropathies and IPEX Syndrome 127
Local inflammation has been demonstrated on biopsy, and it sensitised to CM were also more likely to have their FPIES
is thought that this leads to increased gut permeability and persist beyond 3 years of age. IgE testing may, therefore, be
fluid shifts resulting in emesis, diarrhoea and lethargy. important for decision making about when and where to
Diagnosis is primarily based on the clinical history with perform an OFC [78].
improvement after exclusion of the causative food. As
FPIES is not an IgE‐meditated process, specific IgE levels
Food protein‐induced allergic proctocolitis
are not useful to identify food triggers. Diagnostic criteria
for patients presenting with possible FPIES are listed in
Food protein‐induced allergic proctocolitis (FPIAP), also
the recent international consensus guidelines by Nowak‐
known as allergic colitis of infancy, is a non‐IgE cell‐
Wegrzyn et al. [77].
mediated food allergic disorder predominantly seen in
infancy. The classical presentation is of blood streaked
Treatment stools in an otherwise healthy child. It is a benign, transient
condition and is considered to be one of the major causes
Acute FPIES should be considered a medical emergency
of colitis under 1 year of age. Diagnosis relies on a history of
with 15% of patients having hypovolaemic shock and need-
rectal bleeding, exclusion of infections and other causes of
ing aggressive fluid resuscitation and other supportive ther-
rectal bleeding, and response to an elimination diet [79].
apies. Once the child is stable, advice to ensure dietary
elimination of the trigger food(s) and support for the family
with introduction of new foods into the diet is required. Treatment
Infants with suspected CM or soy‐induced FPIES should
Elimination of the causal protein is usually followed by a
be advised to avoid all forms of these foods, unless baked
rapid resolution of symptoms [80]. In FPIAP the most com-
and processed foods containing these proteins are already
mon causal proteins are CM and soy. As a large number of
included in the diet and tolerated. In this instance it would
infants with this disorder are breastfed, this necessitates a
be safe to continue the baked form of the food. If the infant is
maternal exclusion diet [73]. Maternal ingestion of egg and
breastfed, this should continue, and, as the majority of infants
corn has also been identified as potential triggers in the
with FPIES do not react to food proteins in human milk,
breastfed infant [79]. In one series of 95 breastfed infants
maternal dietary elimination is only warranted if the infant
with FPIAP, dietary exclusions were successful in 89% of
remains symptomatic while exclusively breastfeeding. Most
cases. Of the remainder, seven responded to an EHF, and
non‐breastfed infants with this disorder will tolerate an EHF
the remaining four (all of whom had eczema) needed an
with only 10%–20% requiring an AAF.
AAF [81]. The majority of infants with FPIAP achieve clini-
In the majority of children, FPIES is caused by a single
cal tolerance of the food by 1 year of age [79].
food, most commonly CM; however, one US centre reported
5%–10% children who reacted to more than three foods with
some as many as six. Children with CM or soy‐induced Autoimmune enteropathies and IPEX syndrome
FPIES may react to both foods with a higher likelihood of
this occurring if they developed symptoms in the first month Autoimmune enteropathies are a heterogeneous group of
of life. They also have an increased risk of reacting to a solid disorders characterised by immune‐mediated damage to the
food, most commonly rice or oat. GI tract causing severe and intractable diarrhoea. Anti‐
A guideline for weaning these infants suggests that first enterocyte antibodies are seen in some patients with this
solids introduced should be low risk fruit and vegetables problem, but not all. Patients may have other associated
(avoiding legumes and banana) followed by red meats and autoimmune conditions including liver, renal, endocrine,
cereals made from quinoa and millet. In infants with severe pulmonary, haematologic and musculoskeletal system
CM and soy‐induced FPIES, supervised oral food challenges involvement. Treatment with immunosuppression is usually
(OFC) can be considered to support the family. Tolerance of required. These patients do not respond to dietary allergen
one food from a particular food group is considered to be a exclusion as would those with a CM sensitive enteropathy,
favourable indicator that the child will tolerate other foods and some will require PN as supportive treatment to correct
from the same group [77]. malnutrition [82–84].
The age of development of tolerance to food triggers in Immunodysregulation polyendocrinopathy enteropathy
this disorder is variable and depends on the type of food X‐linked (IPEX) syndrome is a monogenic autoimmune
and country of origin of the child. There is currently no disease caused by FOXP3 mutations. Type 1 diabetes and
agreement about ideal timing of OFC to determine symptom eczema are frequently seen in these children. The median
resolution, and this varies considerably by country and indi- age of onset is 2 months with most infants experiencing diar-
vidual preference. It is agreed that patients should be evalu- rhoea and faltering growth. Some children will have an
ated at regular intervals, and, in the USA, diagnostic OFC extremely high blood IgE level and eosinophil infiltrate in
are usually attempted 12–18 months after the most recent the bowel; others will have a severe enteropathy. Treatment
reaction to a specific food. It should be noted that, in a large is with immunosuppressive therapy and nutritional support
US cohort, 41% of patients with CM FPIES transformed into (enteral or parenteral) or with hematopoietic stem cell trans-
an IgE‐mediated phenotype over time. Those who were plantation [85].
Inflammatory Bowel Disease

Joanne Louise Price
Paediatric inflammatory bowel disease (PIBD) encompasses a a team approach with many specialist centres developing
spectrum of inflammatory bowel diseases (IBD), the most prev- dedicated MDT. According to published standards of care
alent being Crohn’s disease (CrD) and ulcerative colitis (UC). In [94], the IBD team should include:
childhood these conditions are more extensive and associated
• consultant gastroenterologists
with a more aggressive disease course than adult‐onset disease.
• consultant specialist surgeons
In paediatric‐onset CrD the genetic component is more domi-
• clinical nurse specialists with a special interest and com-
nant, and, therefore, recurrence within the family is more fre-
petency in IBD
quent than in adults [86]. IBD is more common in urban than
• clinical nurse specialist with a special interest and com-
rural areas and in northern developed countries, though the
petency in stoma therapy
incidence is beginning to increase in developing nations.
• dietitian allocated to gastroenterology
A genetic predisposition for IBD was first identified in
• administrative support for IBD meetings, IBD database
2001 on the NOD2 gene. Since then 200 other loci have been
recording and audit
found, however, this genetic susceptibility only accounts for
• named histopathologist with a special interest in
up to 26% of cases [87]. The aetiology of IBD is not fully
gastroenterology
understood, but is thought to involve a dysbiosis of the gut
• named radiologist with a special interest in gastroenterology
microbiota [88] and/or an abnormal response to environ-
• named pharmacist with a special interest in gastroenterology
mental triggers such as diet, infection, drugs or other agents.
Researchers have hypothesised that modification of the gut In addition to the IBD team, PIBD patients will often be
microbiota to influence the dysbiosis will induce remission, referred to several other specialties due to various systemic
and this could be the mode of action of future treatments. manifestations, e.g. ophthalmology, endocrinology, derma-
Understanding that environmental factors have a more sig- tology and rheumatology.
nificant role to play in the susceptibility of individuals to
develop PIBD is a continuously evolving area of research.
Ulcerative colitis
Most cases of PIBD are insidious in onset with nonspecific
GI symptoms, often leading to a significant delay in diagno-
UC is a chronic, relapsing inflammatory disease of the intes-
sis and growth failure [89, 90]. To aid diagnosis certain sero-
tine that is confined to the colonic and rectal mucosa.
logical inflammatory markers (erythrocyte sedimentation
Childhood‐onset UC has a worse disease course compared
rate [ESR], platelets, albumin and stool faecal calprotectin
with that in adults with a 30%–40% colectomy rate at
tests) can indicate the possibility of IBD. Faecal calprotectin
10 years, compared with 20% in adults.
testing is recommended as an option to support clinicians
Drug therapy is used to induce and maintain disease
with the differential diagnosis of IBD or non‐IBD (including
remission. There is no evidence to support the use of
IBS) in children with suspected IBD. It is also used to moni-
enteral nutrition or diet as methods to induce remission in
tor CrD [91].
UC. The nutritional problems found in UC are not as severe
Diagnosis of PIBD should always be carried out by a paedi-
as in CrD because of sparing of the small intestine [95].
atric gastroenterologist and requires endoscopic confirmation
Height velocity is usually normal unless there is excessive
with biopsy and histological interpretation; the presence of
steroid use. As patients with PIBD are at risk of vitamin D
granuloma within the biopsies is a unique diagnostic feature of
deficiency, it is recommended that serum levels are rou-
CrD and helps distinguish it from UC. Due to the preponder-
tinely measured and supplemented when appropriate.
ance of small bowel disease in CrD and its transmural pattern
Nutritional support is needed if there is growth failure or
of inflammation, diagnosis requires full assessment of the mid
weight loss.
gut, particularly the terminal ileum, and this is intrinsically
reliant on imaging techniques. Ultrasound (US), computed
tomography (CT) and magnetic resonance imaging (MRI) are Crohn’s disease
the most widely employed imaging methods [92].
It should be noted that PIBD is a systemic disease and is The incidence of CrD in children is increasing worldwide,
also associated with other inflammatory conditions affecting ranging from 2.5 to 11.4 per 100 000 [96]. It is a chronic,
the joints (arthritis), skin (pyoderma gangrenosum) and eyes transmural (infiltrating all layers of the intestinal wall)
(uveitis and episcleritis). inflammatory process that may affect any part of the GI
tract from the mouth to the anus. It is not usually continu-
ous and is characterised by skip lesions. It can occur ran-
The IBD team domly, and inflammation can move from one area to another
within the same individual. It is an extremely heterogene-
Appropriate organisation and delivery of services are an ous disorder with great anatomical and histological diver-
integral part of good care in PIBD [93]. Management requires sity, so no two cases are the same. However, the small
Inflammatory Bowel Disease 129
intestine, and particularly the terminal ileum, is involved in therapy in paediatric CrD are to induce remission and
up to 90% of cases [86]. therefore relieve symptoms, prevent adverse longer‐term
The presentation of CrD in children depends largely on outcomes such as stricture and fistula formation, optimise
location within the GI tract and extent of the inflammation. growth and improve quality of life (QoL) while minimising
It is a chronic relapsing and remitting condition, and this drug toxicity. At a cellular level achievement of sustained
aggressive cycle of inflammation and healing can lead to and deep mucosal healing is the ultimate goal of treatment.
ulceration and fistula formation. In more chronic and severe Surgery is not curative and should only be indicated in
disease, fibrosis of the bowel and strictures can occur. refractory short segment ileal disease (without colonic
involvement) and in those with stenotic disease unrespon-
sive to treatment. Planning for surgery should be discussed
Nutritional issues
within the MDT with a paediatric surgeon experienced in
Symptoms of nausea, anorexia and malabsorption result in IBD. If indicated it is suggested that surgery should be com-
the mean energy intake of patients with active CrD up to pleted prior to the onset of puberty to prevent complications
420 kcal (1.75 MJ)/day lower than in age‐matched controls of growth failure and give the best chance for catch‐up
[97]. This is associated with insufficient nutrient intake, growth and normal development [111].
which can contribute to both macronutrient and micronutri- Remission can be induced using exclusive enteral nutri-
ent deficiencies. The energy and protein deficit results in tion (EEN) or corticosteroids followed by maintenance ther-
weight loss, occurring in over 80% of children with CrD, apy with an immunosuppressant, usually azathioprine or
and a decreased height velocity. In addition to a reduced 6‐mercaptopurine.
oral intake, pro‐inflammatory cytokines are increased in They act slowly over several months and may take 6–12
CrD and have been shown to adversely affect growth [98, weeks before benefit is noticed. Methotrexate may be used
99]. Growth failure occurs in 15%–40% children with CrD, and is given as an injection or a tablet each week. It can take
and final adult height can be up to 7 cm shorter than up to 3 months before becoming effective.
expected [100]. In persistent relapsing disease, EEN can be repeated, and/
Specific nutrient deficiencies, such as calcium, magnesium, or a combination of drugs known as biologics (anti‐tumour
zinc, iron, folate, B12 and fat‐soluble vitamins, are common necrosis factor monoclonal antibodies) may be commenced.
findings at diagnosis, with antioxidant trace elements and They are relatively expensive and have been used increas-
vitamins being consistently reported at suboptimal concen- ingly and successfully over the past 15 years. The longer‐term
trations [101, 102]. As some of these levels are affected by the effects of biologics have yet to be seen. The original biologics
acute phase response in inflammatory conditions, the true are infliximab, given intravenously in hospital usually every
significance of the findings is not understood; however, 8 weeks; adalimumab, given via subcutaneous injection
there is good evidence that IBD patients experience increased every 2 weeks that can be given at home; and vedolizumab,
oxidative stress [103]. During periods of active inflamma- given intravenously in hospital usually every 8 weeks. The
tion, there is often enteric leakage of protein, resulting in timings of the infusions/injections depend on response.
hypoalbuminaemia. Protein requirements can be increased Before a child receives any of these medications, it is neces-
by 25% in some cases [102]. sary to test if they are clear of tuberculosis using a chest X‐ray
Accompanying this is retarded bone mineralisation and and serum QTB (QuantiFERON‐TB). There are now many
development and delayed puberty [104]. It is well recog- less expensive ‘biosimilar’ drugs available on the market that
nized that children with IBD have an increased risk of may also be used. Recent guidance also suggests biologics
reduced BMD [105–107]. Interpretation of BMD should be may be considered first line in children with a high risk of
adjusted according to the child’s bone age as it is known that poor outcome and a ‘top‐down’ approach could be used in
these patients have delayed skeletal maturation [108]. It is these more difficult cases [111].
prudent to supplement with calcium if estimated dietary
intakes do not meet the normal requirements for age. Vitamin
D should be supplemented as per normal guidelines [109]. Exclusive enteral nutrition
Once in remission, self‐imposed dietary restrictions
The most recent consensus guidelines recommend EEN as
among patients with PIBD are often associated with
first‐line therapy in paediatric CrD [111] and should be used
insufficient nutrient intake, which can contribute to both
where there is involvement of the small intestine and/or
macronutrient and micronutrient deficiencies. A study of
colon [112]. This therapy for active CrD was initially identi-
78 patients with inactive or mild CrD, compared with
fied in the 1970s by surgeons treating patients with nutrition
80 non‐IBD controls, identified inadequate nutrient intake
support perioperatively, and finding the inflammation
due to exclusion of various food groups, particularly grains,
became quiescent [113]. It involves the administration of a
milk and vegetables [110].
liquid diet, for a defined period, with the exclusion of all
other food. Since the 1970s many trials have been completed
with the aim of establishing its efficacy. To date there has
Management of Crohn’s disease
been no trial of EEN vs. placebo.
Treatment options are comprehensively presented in a 2014 The mechanism by which EEN exerts a therapeutic effect is
consensus document from the European Crohn’s and Colitis still not understood. The anti‐inflammatory effect of EEN is
Organisation (ECCO) and ESPGHAN [111]. The aims of recognised and precedes nutritional restitution [114]. The fat
content of the feed could potentially affect the production of A survey of IBD centres in the UK, Europe, the USA and
pro‐ or anti‐inflammatory mediators. EEN is known to Asia‐Pacific showed wide variations in EEN protocols used
induce mucosal healing in the affected GI tract, while corti- throughout the world; 93% used polymeric formulas, with
costeroids do not do so [111]. EEN has been shown to improve flavourings commonly added to enhance acceptability [125].
QoL outcomes [115]. Research into this therapy is continu- Polymeric feeds have the advantage of being more palatable
ously evolving with the latest studies hypothesising that it is and cheaper than the elemental alternatives. One centre
the withdrawal of a normal ‘Western diet’ and replacing it found that the use of the former significantly decreased the
with enteral feeds that is the mode of action. Enteral feeds are need for NG tubes in their patients, and this did not affect
known to alter the intestinal microbiome [116]. adherence to the EEN regimens prescribed [126]. Amino
A 2019 systematic review of paediatric randomised con- acid‐based feeds (elemental feeds) need only be used in indi-
trolled trials (RCT) [117] and 2018 Cochrane review [118] both viduals where CM allergy is suspected.
concluded that EEN is the most effective treatment for induc- Partial enteral nutrition (PEN) is not currently recom-
ing remission in active paediatric CrD; it also has the benefit mended as a treatment to induce remission [111]. A ran-
of improving nutritional status and growth when compared domised paediatric study compared children on EEN with
with steroids. As children with CrD are often chronically children who received 50% of their nutritional require-
malnourished, enteral feeds support nutritional repletion. ments from feeds and were allowed to eat normally. On
Feeds are also preferable as a first‐line treatment because of analysis nutritional parameters improved equally in both
the deleterious effect of steroids on growth; the use of ster- groups; however, blood indices of inflammation failed to
oids in puberty results in lower adult height [119, 120]. improve in the PEN group, showing that a significant
There are many studies investigating the effectiveness of amount of food affects the anti‐inflammatory response to
feeds with differing nutritional profiles and components. enteral feeds [127].
Protein content and sources (amino acids, peptides and
whole protein), LCT fat and carbohydrate components
Learning points: treatment of Crohn’s disease
have all been scrutinised. The protein composition (includ-
ing the addition of glutamine) does not appear to influence
• Enteral feeds promote mucosal healing and alter the
the effectiveness of EEN [118], with similar efficacy demon-
bacterial flora in the bowel
strated between a polymeric and elemental amino acid‐
• EEN has a steroid sparing role, avoiding the adverse effects
based feed in a paediatric RCT [121]. Two large single‐centre
steroids have on growth
cohort studies with more than 100 subjects achieved
• Partial enteral nutrition (PEN) should not be used for
approximately 80% remission rates using both polymeric
induction of remission
and elemental feeds [122, 123].
• Nutrition support is often required alongside other treatments
In a 2007 systematic review, a non‐significant trend was
and can enhance the effectiveness of other interventions
seen favouring feeds with a very low LCT content with the
• It is usual to have a form of immunosuppressant therapy as
recommendation that larger trials are needed to explore this
part of treatment
further [124]. The 2018 review [118] included 7 trials with 209
• Biologics are expensive but are indicated in particular patients
patients treated with EN formulas of differing fat content
• Surgery is only indicated in specific circumstances but
(low fat < 20 g/1000 kcal vs. high fat > 20 g/1000 kcal); there
should be carried out in a timely manner in order to preserve
was no difference in remission rates. Very low fat content
optimum growth and development
(<3 g/1000 kcal) and very low LCT demonstrated higher
remission rates than EN formulas with a higher content. No
recommendations for the fat content of feeds have been
made [118]. Nutritional requirements and monitoring on EEN
Two feeds, Modulen IBD and Alicalm, have been marketed Most studies have failed to show increased basal energy
for the treatment of CrD. The former claims immunomodu- requirements in patients with CrD unless the patient has a
latory effects purportedly due to the presence of transform- fever [128, 129]. One study confirmed that measured resting
ing growth factor‐β, an anti‐inflammatory cytokine, present energy expenditure (REE) in children with CrD fed with PN
in casein. The latter is an energy dense (1.35 kcal/mL, 5.6 kJ/ correlated well with the predicted REE using FAO/WHO/
mL) polymeric feed with 50% fat present as MCT and addi- UNU equations and was not increased [130].
tional fish oil. There are no published trials comparing these Guidelines suggest that EEN should provide 100% EAR for
feeds against standard paediatric polymeric feeds. The mean age for energy and the RNI for protein from the full feed [111].
remission rate for EEN for all feed types from all published It is important to check that all vitamins and minerals are pre-
meta‐analyses is approximately 70% [111, 117]. Relapse rate sent in amounts at least equivalent to the RNI. Children
outcomes are less well reported, but in two separate studies should be advised to take a larger feed volume than pre-
in paediatric centres in the UK, 30% of patients relapsed scribed if they are still hungry. They should be weighed
within 1 year of completing a course of EEN; however, 60% weekly and monitored by telephone or email contact. A
remained in remission for at least 2 years [121, 122]. In terms follow‐up appointment should be arranged approximately
of duration of feeding, most studies find remission occurs half way through the treatment to ensure that the patient is
after 6–8 weeks of EEN [111]. responding and that appropriate weight gain is achieved.
Inflammatory Bowel Disease 131
Commencement of EEN energy and calcium intake. Patients with persistent narrow
Regardless of the type of feed, the following protocol can strictures, due to fibrosis rather than inflammation, may
be applied: require a low fibre diet or liquid diet to control symptoms
until the stricture is surgically removed.
• Aim 100% EAR for energy plus allow more to appetite
It has been reported that continued use of supplementary
• Feeds should be gradually introduced over 3–5 days
feeds in addition to a normal diet is associated with pro-
depending on symptoms. In severely malnourished
longed periods of disease remission. A Cochrane review
patients, there is a risk of refeeding syndrome (p. 63), and
identified two adult RCTs that suggest supplementary
daily biochemical monitoring with appropriate electro-
enteral nutrition may maintain disease remission [131]. A
lyte and mineral supplementation should be instituted
retrospective study found that a subgroup of patients who
until the patient has reached their target nutritional
are not commencing azathioprine or similar maintenance
intake and is metabolically stable
treatments can successfully continue PEN supplements fol-
• In cases of severe disease symptoms, an NG tube should
lowing induction of remission with EEN; this can be an
be used to deliver the feed more slowly or enable the
effective maintenance treatment [132].
feed to be established without pressure to drink. The
Some patients require continued nutritional support by
tube can be removed in a few days or weeks once
NG tube, gastrostomy or orally if appetite remains poor.
tolerance and oral intake is established
The routine use of supplements to support growth, par-
• Exclusive enteral feeds should provide complete
ticularly in puberty, is usual practice in some UK paediatric
nutrition for a 6–8‐week period
centres.
• If the feed is well tolerated, the concentration of
powdered feeds may be increased to lower the volume of
enteral feed required Learning points: exclusive enteral nutrition
• Clear fluids, boiled sweets and chewing gum can be
taken alongside the feed. There is no evidence to inform • Use standard polymeric feeds for 6–8 weeks
best practice, but these do not appear to have any adverse • Aim for 100% EAR for energy plus allow increased volume
effects to appetite
• Use NG tubes if indicated
As paediatric CrD presents more frequently in adoles-
• Reintroduce food over 2 weeks
cents, this process can be particularly difficult for them, and
• Amino acid‐based feeds and exclusion diets should only be
they require a high degree of support and motivation to
used in those with associated allergies
complete the treatment. Despite this, feeds are well tolerated
• PEN may be used as a maintenance therapy or as ongoing
by most patients, and the full 6 weeks is usually adhered to.
nutrition support in children, particularly during times of
If the patients are sure that they will be able to manage orally,
rapid growth or increased nutritional demands, but not for
feeds can be introduced at home. If an NG feeding regimen
induction of remission
is required, this should be commenced as an inpatient.
Once the feed choice and prescribed volumes have been
decided, the aim is to give as much control to the patient as
possible. Feeds should be tried orally with different flavour- Special diets for Crohn’s disease
ings to enhance compliance; the daily volume required must
At the time of writing, special diets are not routinely used for
be explained carefully so that it is understood that the pre-
therapeutic management of IBD or recommended in any
scribed volume must be completed every day. If the patient
guidance in the UK and are used for research purposes only:
needs or chooses to have an NG tube, they can be taught to
pass this each night and remove it in the morning to cause • CD‐TREAT diet – a trial diet undergoing research in the
minimum inconvenience to their daily routine. Some UK, based on the hypothesis that the aetiology of CrD is
patients choose to drink the full feed volume. Others opt for influenced by dysbiosis of intestinal flora. The diet mim-
a combination approach (some orally and the remainder via ics the profile of the carbohydrate in EEN, reducing the
the tube). carbohydrate and fibre in the diet and increasing the pro-
tein. In preliminary studies it had similar effects to those
of EEN on the gut microbiome and metabolome of
Introduction of foods healthy participants and reduced ileitis in a rat model of
There is no agreement about the best methods of food intro- disease. The results of an initial study using this diet in
duction to patients completing a period of EEN. The most children with active CrD were recently published [133].
recent guidance document states it would appear prudent to In this initial small population sample, three of five pae-
reduce feed volume over a period of 2–4 weeks and gradu- diatric patients with active CrD achieved remission after
ally introduce a normal diet every 2–3 days, ensuring that 8 weeks on the diet. Further larger studies are planned.
continued weight gain is maintained [111]. Many centres • Crohn’s disease exclusion diet – excludes dairy, wheat
exclude high fibre foods in the initial stages [125]. Atopic and most processed foods. It has been used alone and in
patients requiring an elemental feed should be advised to combination with PEN (Modulen) and in one prospective
exclude suspected food allergens, ensuring an adequate uncontrolled paediatric study showed 70% remission
rates. The published study did not include all of the recognised systemic condition. It is a rare condition charac-
details of the diet; however, in general this diet includes terised by chronic disfiguring oral and facial inflammation
limited meat, rice and potatoes, fresh fruits and vegeta- in the form of severe lip and cheek swelling, and skin lesions
bles. There are larger studies in process [134]. are commonly seen. The incidence, geographical distribu-
• specific carbohydrate diet – restricts all carbohydrates tion and cause of this disease are not known, but are thought
(starch, polysaccharides and disaccharides) except mon- to involve an allergic component, the trigger for which is not
osaccharides (glucose, fructose and galactose). The diet always clear.
results in a high protein and high fat intake. There have Three potential dietary triggers are thought to be cinna-
been two low quality paediatric studies with small num- mon, benzoates and chocolate. Treatments can, therefore,
bers. Success was limited, and the evidence for using this include dietary avoidance of these, and when this fails, and
diet in paediatric IBD is lacking [102, 135, 136]. no other trigger can be identified, immunosuppressive ther-
• low FODMAP diet (fermentable oligosaccharides, disac- apy is sometimes used.
charides, monosaccharides and polyols) – described on Clinical features vary with OFG and oral CrD may be on
p. 138. The literature supports the use of this diet to treat the same disease spectrum. Some patients appear to
IBS but not IBD. This diet can be helpful with those respond to the exclusion of certain items from their diet
patients with IBD who have symptoms from IBS [102]. [139]. A systematic review of the literature identified
common hypersensitivities to benzoic acid, benzoates,

The ‘Western diet’ has been implicated in the aetiology of
cinnamaldehyde, cinnamon and chocolate. EEN, using an
IBD. In a Canadian study, higher intakes of meats, fatty
amino acid‐based formula, followed by single food intro-
foods and desserts were found to increase the risk for devel-
ductions to identify specific dietary triggers may also be
oping CrD in females, whereas the consumption of vegeta-
successful [140]. Information sheets for professionals
bles, fruits, olive oil, fish, grains and nuts was associated
working with children with this diagnosis can be obtained
with a decreased risk for developing CrD in both males and
on request from the King’s College London website (www.
females [137], suggesting diet may be a significant environ-
kcl.ac.uk).
mental factor. A recent Australian population‐based study
demonstrated an increased risk for CrD with frequent con-
sumption of fast food before diagnosis [138]. Transition
Until results of RCTs pertaining to diet become available,
current best practice advice regarding diet should focus on fol- Transition should be an integral part of any IBD service,
lowing healthy eating guidelines with an emphasis on a reduc- preferably with joint clinics held between adult and paediat-
tion in processed foods and an increase in fresh fruit, vegetables ric gastroenterology teams. However, it is a challenging pro-
and fibre (in the absence of stricturing disease) while meeting cess where practical realities do not always match official
energy, protein and micronutrient requirements. guidance. A tool has been developed by the Childhood
Research Association (CICRA) with young people with IBD
to equip them as they approach transition from paediatric to
adult services. It includes a symptom tracker that helps
Orofacial granulomatosis
young people become more confident about managing their
Orofacial granulomatosis (OFG) is a condition where there condition. Generic transition guidance can be found in
are granulomas in the orofacial region in the absence of any guideline 43 from NICE [141].
Disorders of Altered Gut Motility

Sarah Macdonald
Integration of the digestive, absorptive and motor functions action that grinds food to 1–2 mm particle size. Gastric emp-
of the gut is required for the assimilation of nutrients. In the tying can be modulated by feed components via hormonal
mature gut, motor functions are organised into particular secretion.
patterns of contractile activity that have several control In the small intestine, motor activity is effected by smooth
mechanisms. Disturbances in this coordinated system can muscle contraction, which is controlled by myogenic, neural
occur in all parts of the GI tract. and chemical factors. In the fasting state the gut has a con-
After swallowing, a bolus of milk or food is propelled tractile activity (the migrating motor complex) that propels
down the oesophagus by peristalsis; this action differs from the luminal bacteria and food residue into the colon.
the motility of the rest of the intestine in that it can be induced Abnormalities of this phasic activity can result in bacterial
voluntarily. The lower oesophageal sphincter relaxes to overgrowth of the small intestine and malabsorption. Post‐
allow food or fluid to pass into the stomach, which acts as a prandial activity is initiated by hormones, which produce
reservoir and also initiates digestion. It has a contractile peristalsis in the gut. This allows the relaxation of the GI
Disorders of Altered Gut Motility 133
muscle coats below the bolus of food and contraction above, Treatment
propelling the bolus of food through the intestine.
Positioning
Postural treatment of infants has been demonstrated to help,
Gastro‐oesophageal reflux and a prone‐elevated position at 30° is the most successful in
reducing GOR [144]. This cannot be recommended as sev-
Gastro‐oesophageal reflux (GOR) is defined as the passage of eral studies have shown an increased risk of sudden infant
gastric contents into the oesophagus, with or without regur- death syndrome in the prone sleeping position. A more
gitation and vomiting. It is a normal physiological process practical approach is to avoid positions that exacerbate the
that occurs several times a day in healthy infants, children situation. In older children head elevation or left lateral posi-
and adults. Most episodes of GOR in healthy individuals tioning can be used [142].
occur after meals, last less than 3 minutes, and cause few or
no symptoms [142]. Approximately 50% of infants regurgi- Feeding
tate at least once a day, and, in the majority of c hildren, this The infant should not be overfed and should be offered an
can be considered as an uncomplicated self‐limiting condi- age appropriate volume of milk. Small volume, frequent
tion, which spontaneously resolves by 12–15 months of age. feeds may also be beneficial by reducing gastric disten-
This is due to the lengthening of the o esophagus and the sion, e.g. 150 mL of formula/kg/day as 6–7 feeds [145]. In
development of the gastro‐oesophageal sphincter. Parental practice frequent feeds may be difficult for parents to man-
reassurance is very important and should preclude the need age, and reduced feed volumes may cause distress in a
for any further investigations or treatment [143]. hungry baby.
More severe forms of this problem occur when an infant Commercial anti‐regurgitation (AR) formulas and feed
with regurgitation does not respond to simple treatment and thickeners decrease visible regurgitation episodes, but the
develops GORD. Acid‐induced lesions of the oesophagus impact on non‐regurgitation symptoms is less clear [142].
and oesophagitis may develop and are associated with other Although the actual number of reflux episodes may not
troublesome symptoms such as faltering growth, haemate- decrease with AR formulas, the reduction in regurgitation
mesis, respiratory symptoms, apnoea, irritability, feeding may improve QoL for caregivers.
disorders and iron deficiency anaemia. GORD is a common There are four pre‐thickened infant formulas based on
finding in premature infants, children with neurological CMP available in the UK (Aptamil Anti‐Reflux, Cow &
problems, obesity and previous oesophageal atresia and Gate Anti‐Reflux, Enfamil AR with Lipil, SMA Staydown).
congenital diaphragmatic hernia. Recent clinical practice They contain either a high amylopectin pre‐gelatinised
guidelines from the North American and European Societies rice starch, precooked cornstarch or carob (locust) bean
for Paediatric Gastroenterology, Hepatology, and Nutrition gum. The manufacturers’ instructions should be followed
(NASPGHAN, ESPGHAN) describe symptoms and signs when reconstituting these feeds. Feeds containing starch
that may be associated with GORD to try and prevent under‐ thicken on contact with the acid pH of the stomach, while
or overdiagnosis of this condition. Diagnosis of GORD in those containing carob bean gum thicken on mixing.
infants and toddlers is complicated by the fact that there is The EC Scientific Committee for Food has accepted the
no symptom or group of symptoms that is diagnostic or pre- addition of starch to a maximum of 2 g/100 mL in infant
dicts response to therapy. Investigations that may be used to formula.
understand the underlying disorder include oesophageal A variety of feed thickeners are available on prescrip-
pH monitoring with the aim of correlating symptoms with tion, based either on locust (carob) bean gum or modified
GOR events and to determine the effect of acid suppression maize starch (Table 8.12). Locust bean thickeners are
therapy [142]. approved for use in infants after 42 weeks’ gestation.
Table 8.12 Feed thickeners.
Added energy per 100 mL

Suggested dilution
Thickening agent (g/100 mL) (kcal) (kJ)
Instant Carobel (Cow & Gate) Locust bean gum (carob) 1–3 3–8 13–33
Thick and Easy (Fresenius Kabi)** Precooked maize starch 1–3 4–12 17–50
Thixo‐D (Sutherland Health)*
Vitaquick (Vitaflo)*
Multi‐thick (Abbott)*
Nutilis Powder (Nutricia)**
Resource ThickenUp (Nestle)*
*Only prescribable for children <1 year of age in cases of failure to thrive.
**Only prescribable for children over the age of 3 years.
These can cause the passage of frequent loose stools in a without GORD [151]. These problems often persist after
minority of infants; however, they have the flexibility of medical or surgical treatment.
being able to be mixed as a gel and fed from a spoon before Where there are severe feeding problems, it may be nec-
breastfeeds. essary to instigate NG or gastrostomy tube feeding to
Where there is faltering growth a maize‐based thickener ensure an adequate nutritional intake. Wherever possible
can be used to provide extra energy. These products are clas- an oral intake, however small, should be maintained to
sified as ‘not suitable for children under 1 year except in minimise later feeding problems. The child’s feed should
cases of failure to thrive’. Their use in infants should be be administered as oral or bolus day feeds or with contin-
under the supervision of a healthcare professional. The uous feeds at a slow rate to avoid feed aspiration. The feed
lowest amount of thickener recommended should be added volume may need to be reduced below that recommended
initially, and the amount gradually increased to the maxi- for age to ensure tolerance, with feeds fortified in the
mum level if there is no resolution of symptoms. Feeding usual way to ensure adequate nutrition for catch‐up
through a teat with a slightly larger hole, or a variable flow growth. If using a fine bore NG tube to administer bolus
teat, is recommended. feeds, thickening agents should be kept to the minimum
concentration recommended to prevent the tube blocking
Other treatments and an inappropriate length of time being taken to admin-
Non‐pathological reflux is normal and does not require ister the feed. Transpyloric feeding can be tried where
treatment. PPI are recommended as first‐line treatment of GORD continues to be a problem; however, one study
reflux‐related erosive oesophagitis in infants and chil- showed that reflux can still occur during feeding times
dren with GORD. H2 receptor analogues may be used if and aspiration events and reflux‐related hospital admis-
PPI are contraindicated. Infants and children prescribed sions are still possible [152].
with these medications should have regular assessment The requirement for tube feeding can continue for pro-
with the aim of stopping the medication as soon as longed periods of time, as long as 36 months [153]. Parents
tolerated. of infants with feeding problems secondary to GORD need
Symptoms of GORD, particularly in infants, may be con- a great deal of support. Optimal management should
fused with those of FA as these infants may also experience employ a multidisciplinary feeding disorder team including
regurgitation, vomiting and distress. 30%–40% of infants a psychologist with experience of children with these prob-
with GORD resistant to treatment have CM allergy, with lems, a paediatrician, a dietitian and a speech and language
symptoms significantly improving on a CMP‐free diet [146, therapist.
147]. Although the mechanism is still poorly understood,
Borrelli et al. suggest that foregut dysmotility is affected by
neuro‐immune interactions induced by food allergens [148]. Paediatric intestinal pseudo‐obstructive disorder
In food allergic children, CM has been shown to cause gas-
tric dysrhythmia and delayed gastric emptying that may Paediatric intestinal pseudo‐obstructive disorder (PIPO) is
exacerbate GORD and induce reflex vomiting [149]. When characterised by the chronic inability of the GI tract to propel
GORD fails to respond to simple treatment, a therapeutic its contents, mimicking mechanical obstruction in the
change of formula to EHF or AAF can be tried for 2–4 weeks absence of any lesion occluding the gut. It is an extremely
followed by reintroduction of CMP to see if symptoms reoc- rare disorder, and children with PIPO experience significant
cur. Breastfed infants should have a trial of maternal CM morbidity and repeated hospital admissions. Half to two
exclusion [142]. thirds of patients present within the first year of life.
In extreme cases that do not respond to the above treat- A recent expert group published consensus‐based recom-
ment transpyloric/jejunal feeding should be considered mendations to aid consistent definition, diagnosis and man-
as an alternative to surgery [142]. Anti‐reflux surgery agement of the disorder. It is hoped that this will contribute
includes fundoplication that wraps the fundus of the to a better understanding of the problem and more effective
stomach around the lower oesophageal sphincter (p. 152). treatments in the future [154]. Primary causes of PIPO
A gastrostomy is usually inserted for venting gas from include sporadic or familial forms of myopathy, neuropathy
the stomach and, occasionally, for feeding purposes. or abnormal development of the interstitial cells of Cajal,
There can be considerable morbidity associated with this mitochondrial neurogastrointestinal encephalomyopathy
operation. (MNGIE) and total intestinal aganglionosis. The urinary
tract may also be involved.
Feeding problems in GORD Stasis of intestinal contents is common, and the chronic
Feeding difficulties are not uncommon in this disorder, dilatation leads to decompensation and elongation of the
especially when the reflux has an allergic aetiology. They bowel, further impairing motility. Dehydration and malnu-
are characterised by food refusal, distress during feeding, trition are often not recognised, and the child’s weight may
poor appetite, and negative feeding experiences by the be unreliable due to significant amounts of fluid pooling
caregivers [150]. Infants with GORD are significantly more within distended gut loops. The management goals for this
demanding and difficult to feed and have been found disorder are to improve GI motor activity where possible,
to ingest significantly less energy than matched infants relieve symptoms and restore nutrition and hydration.
Functional Gastrointestinal Disorders 135
Treatment
Learning points: paediatric intestinal pseudo‐obstructive
Nutritional support is vital for these children. In one series disorder
of 44 patients, 72% required PN for a relatively long period
of time, 7 children died of PN‐related complications with a • Liquids are easier for the dysmotile gut to process than
further 10 remaining dependent on long‐term home PN highly textured foods; it may be beneficial to minimise the
[155]. In a second series of 105 children, only 18 were able to intake of solids even if tolerated, although long‐term evi-
be enterally fed throughout their illness, and 11 patients dence of outcomes is currently lacking
died [156]. Nutritional management of these children is • Enteral feeds are more likely to be tolerated as a continuous
challenging and has a poor evidence base. The ability to infusion than as bolus feeds
maintain an oral intake is influenced by the extent of GI • Feed constituents influence gastric emptying; it would
disease. Children with gastroparesis are more likely to have appear prudent to avoid casein‐dominant feeds in children
difficulty eating food than those with predominantly small with gastroparesis
bowel involvement [157]. In children fed via the gastric • Care should be taken to ensure that enteral feeds are made as
route, it is known that a number of factors influence gastric cleanly as possible to prevent the introduction of microorgan-
emptying including the type of protein, amount and type of isms into the gut, which could contribute to bacterial over-
fat, energy density and osmolality. A recent meta‐analysis of growth; in older children the use of sterile feeds is preferable
the available literature suggests that breastmilk has a faster • Fluid balance and sodium requirements should be accu-
gastric emptying rate than any infant formula. Whey‐dominant rately assessed, and supplements given as needed
formulas empty more rapidly than casein‐dominant feeds • Foods that are low in fibre with a semi‐solid or bite‐dissolvable
due to the predominance of β‐lactoglobulin. This remains consistency are more likely to be tolerated as non‐bite‐
soluble in the stomach and, therefore, transits more rapidly dissolvable foods may increase the risk of bezoar formation
into the small intestine. The effect of protein hydrolysis on • Additional anthropometric measurements should be taken in
the gastric emptying of feeds remains unclear [158]. this group of children to assess and monitor nutritional status
Oral diet and gastric and jejunal feeds tailored to the indi-
vidual child should all be trialled. In the long term one third
of patients with PIPO require PN (partial or total), one third
will need feeds via an artificial device, and one third will be Functional gastrointestinal disorders
able to tolerate sufficient nutrition orally. For those that can
manage oral diet, it would appear prudent to recommend Functional gastrointestinal disorders (FGID) are a heteroge-
small frequent meals and snacks avoiding high fibre foods neous group of symptom based conditions that cannot be
that can result in bezoar formation. Such children are advised explained on an organic basis. They are usually classified
to eat low residue and bite and dissolve foods and soft diets according to their predominant presenting symptoms and
to minimise the contractile activity needed for digestion the age of the child [161, 162]. They are recognised by mor-
[154]. High fat foods may need to be avoided in order to phological and physiological abnormalities that often occur
limit delay in GI transit. in combination and that can include motility disturbances,
Some children with PIPO have an ileostomy fashioned to visceral hypersensitivity, altered mucosal and immune
decompress the gut. The loss of sodium‐rich effluent through function, altered GI microbiota and altered central nervous
the stoma can result in high sodium requirements, and this system processing [163]. They include infantile colic, regur-
needs careful monitoring. Enteral feed can be pooled in the gitation, constipation, functional diarrhoea, functional
intestine for a prolonged period of time before passing abdominal pain (FAP), cyclical vomiting syndrome, rumi-
through the stoma, resulting in a lack of appreciation of the nation syndrome and IBS. FGID have a complex aetiology
relatively high fluid requirements of these children. When that includes biological and psychosocial factors. A recent
unwell, children often need additional IV fluids to prevent meta‐review reported that worldwide prevalence of the
dehydration. In certain children (especially those with two most common FGID in infants, regurgitation and func-
impaired gastric motor function), jejunal feeding may be tional constipation (FC), is approximately 25% and 18%,
successful if a trial of gastric feeds has failed [159]. QoL has respectively [164].
been shown to be poor with a reduction in school attendance Most of the algorithms devised for practical management
and GI pain being common findings. Parents’ QoL is affected of these conditions are based on parental support, reassur-
by having to be vigilant in assessing their child’s fluid ance and nutritional advice. Despite this there is evidence of
balance and the need to follow complicated and time‐
discrepancies between these guidelines, what physicians
consuming nutritional support protocols [160]. recommend and what parents may do, resulting in many
Where there are life‐threatening complications of PN such different treatments and approaches to the management of
as loss of IV access, end‐stage liver disease or an intolerable these conditions. This comes at a considerable financial cost
QoL, multivisceral transplantation is an option. Early dis- to parents and healthcare systems and a decreased QoL
cussion with a transplant centre combined with an MDT reported by parents [165, 166].
approach to decide about the optimal timing of assessment The nutritional status of children with FGID may be
is recommended. affected with one study of 102 children showing that those
with IBS were more likely to be overweight, while children treatment; FC should be treated with laxatives and a com-
with FAP were more likely to be underweight compared with bination of age‐appropriate behavioural interventions.
reference data [167]. Treatment should involve disimpaction with polyethlyene
The Rome Foundation is an independent not‐for‐profit glycol or enemas if needed, followed by maintenance ther-
organisation that provides support for activities to assist in the apy. Movicol Paediatric Plain (Norgine), containing poly-
diagnosis and treatment of FGID. It has published textbooks ethylene glycol ‘3350’ with electrolytes, should be first‐line
to update knowledge and diagnostic criteria of these disorders treatment with a stimulant laxative (senna, docusate
with the 2016 Rome IV series being the most recent; all func- sodium, bisacodyl, sodium picosulfate) added as required
tional disorders in infants and toddlers are included [168]. Only [169, 170].
three of the functional GI disorders are described here. Dietary fibre can be classified into water‐soluble and
water‐insoluble forms. The former includes pectins, fructo‐
oligosaccharides (FOS), gums and mucilages that are fer-
Functional constipation mented by colonic bacteria to produce short chain fatty
acids. This has been shown to increase stool water content
Constipation is a symptom rather than a disease and can be and volume. Insoluble fibre mainly acts as a bulking agent in
caused by anatomical, physiological or histopathological the stool by trapping water in the intestinal tract and acting
abnormalities. FC is not related to any of these abnormalities like a sponge. Both soften and enlarge the stool and reduce
and is thought to be most often due to the intentional or sub- GI transit times.
conscious withholding of stool after a precipitating acute event. Surveys have shown that constipated children often eat
Peak incidence occurs at the time of toilet training with an considerably less fibre than their non‐constipated counter-
increased prevalence in boys. Constipation has been found to parts. Even when advised to increase their fibre intake by a
account for 3% of visits to general paediatric outpatient clinics physician, the fibre intake was only half the amount of the
and 10%–25% of visits to a paediatric gastroenterologist [162]. control population. It appears that families can only make
Average stool frequency in children has been estimated to the necessary changes with specific dietary counselling
be four stools per day in the first week of life, two per day at [171, 172]. Behavioural intervention can significantly
1 year of age, decreasing to the adult pattern of between increase dietary fibre intake at 3 months, but this increase is
three per day and three per week by the age of 4 years. Within not sustained at 6 months and 1 year [173], confirming the
these patterns there is a great variation. The Rome III criteria difficulties initiating and maintaining high fibre diets in
for diagnosis are used in the evidence‐based ESPGHAN and children. Children with FC have been shown to have lower
NASPGHAN guidelines published in 2014 [169] and are energy intakes and a higher incidence of anorexia. It is dif-
based on history and physical examination. FC is defined as ficult to know if this was pre‐existing and predisposed to
the occurrence of two or more of the following characteristics the condition or whether it is caused by early satiety sec-
for at least 1 month in children up to the age of 4 years and at ondary to constipation [174]. No RCT has shown an effect
least 2 months in children older than 4 years: on stools in constipated children of any of the above dietary
• less than two bowel movements per week measures. The fact that FC is uncommon in societies that
• at least one episode of faecal incontinence per week after consume a high fibre diet has been used to justify this
the acquisition of toileting skills treatment.
• large stools in the rectum or palpable on abdominal The Scientific Advisory Committee on Nutrition (SACN)
examination recommends daily amounts of dietary fibre: 15 g for 2‐ to 5‐
• passing of stools so large they obstruct the toilet year‐olds, 20 g for 5‐ to 11‐year‐olds, 25 g between the ages of
• a history of excessive stool retention 11 and 16 years and 30 g from the age of 16 years (Table 2.18).
• a history of painful or hard bowel movements, retentive In infancy and childhood it is important to ensure that
posturing and withholding behaviour in a child older adequate fluids are taken. As a guide, children should have
than 4 years [169] 6–8 drinks a day, preferably as water. For children who drink
insufficient amounts, foods with a high fluid intake should
In FC prolonged stretching of the rectal walls, associated be encouraged such as ice lollies, jelly and sauces. Fruit, veg-
with chronic faecal retention, leads to an atonic and desensi- etables and salad have a high fluid content as well as being
tised rectum. This perpetuates the problem as large volumes desirable because of their fibre content. The ESPGHAN/
of faeces must be present to initiate the call to pass a stool. NASPGHAN guidelines recommend that normal fibre, fluid
Faecal incontinence (previously described as encopresis or and physical activity levels should be achieved in children
soiling) is mostly as a result of chronic faecal retention and with FC but that additional fluid or fibre supplements such
rarely occurs before the age of 3 years. as glucomannan or cocoa husk should not be recommended.
There is also no evidence to support the use of pre‐ or probi-
otics [175] or MDT working, involving a dietitian or psychol-
Treatment
ogist, in the treatment of FC [169].
The 2010 NICE guidelines (updated in 2017) and 2014 In a select group of children with constipation who fail to
ESPGHAN/NASPGHAN guidelines emphasise that die- respond to conventional treatment, CMP‐free diets have
tary interventions alone should not be used as first‐line been shown to be beneficial [176]. Motility studies in these
Functional Gastrointestinal Disorders 137
patients have indicated that the delay in faecal passage is a Treatment

consequence of stool retention in the rectum and not of a
All sources agree that parental reassurance is of primary
generalised motility disorder [177]. It has, therefore, been
importance. The role of diet in this disorder is controversial
proposed that all children with chronic constipation who fail
[183]. Advice is needed to correct any dietary idiosyncrasies.
to respond to normal treatment as outlined above should be
Excessive fluid intake, particularly of fruit juices and squash,
considered for a 2–4‐week trial of a CMP‐free diet (Table 8.17)
should be discouraged. Fibre intake has frequently been
[169]. One study showed that, of 52 patients with chronic
reduced by parents in an attempt to normalise stools; there-
constipation, 58% had an eosinophilic proctitis caused by an
fore, increasing this to normal levels should be recom-
underlying FA. The response to dietary exclusion was con-
mended. Often parents try excluding foods from the child’s
firmed by double‐blind food challenges. The majority of
diet, mistakenly believing the problems to be due to food
children were allergic to CMP only; however, six patients
hypersensitivity. Once the diagnosis is established, these
had multiple food allergies identified by the use of a few
foods should be reintroduced.
foods diet [178]. A systematic review concluded that the
available evidence does support a causal link between CMP
and FC in some children [179]. Abdominal pain‐related functional
For children with FC referred to a paediatric gastroenter- gastrointestinal disorders
ologist, 50% will recover and not be taking laxatives after
6–12 months of treatment. A total of 80% of children have Abdominal pain‐related functional gastrointestinal disor-
recovered after 10 years with most no longer taking medica- ders (AP‐FGID) are defined as chronic or recurrent abdom-
tion [169]. inal pain, not explained by an underlying organic disorder.
They are thought to affect up to 20% children worldwide
and include functional dyspepsia, IBS, abdominal
Functional diarrhoea migraine and FAP. They have a significant impact on QoL,
daily functioning and school attendance and can have
Functional diarrhoea, previously known as toddler diar- long‐term psychological implications. Children and ado-
rhoea, is the most frequent cause of chronic diarrhoea in chil- lescents with these problems are at risk of the symptoms
dren between the ages of 1 and 5 years of age. Symptoms continuing into adulthood [184]. It is thought that paediat-
include more than four watery stools, often containing undi- ric AP‐FGID are associated with stress and psychological
gested foodstuffs, in a child who is otherwise well and thriv- disorders such as anxiety and depression and are found in
ing [168]. These children will usually have rapid gastric children who have a lower coping strategy than those of
emptying before the foods have been ground completely in healthy children.
the stomach and will often need to open their bowels during
a meal. It is a disease of exclusion, and treatable causes such
as post‐enteritis syndrome, infections, CD and IBD should Treatment
be considered. Despite the children generally presenting in a A recent review looking at the role and prevalence of CMP
good nutritional state, parental anxiety is high. The diar- and other food allergies in FGID found limited data to
rhoea ceases spontaneously, generally between 2 and 4 years support their role in the pathogenesis of these disorders. The
of age [180]. A primary problem has still not been identified. authors concluded that an elimination diet could be trialled
Children with this disorder are known to have a rapid GI for a limited period to verify if the symptoms improve,
transit time, and intestinal motility is generally thought to be followed by OFC [185]. A systematic review looking at phar-
abnormal, although it is unsure whether this is due to a macological interventions for recurrent abdominal pain in
reduced colonic transit time or a disturbance of small intesti- childhood found no evidence to support the use of medica-
nal motility. tions as treatment in these disorders [186]. High quality
Carbohydrate malabsorption, particularly of fructose, has studies of non‐pharmacological treatment in these disorders
been extensively investigated in this disorder. Fructose is are lacking, and the first step in management is reassurance
known to be slowly absorbed in the small intestine and is and education. In the 30% of children who continue to
often present in large amounts in fruit juice. Young children experience symptoms hypnotherapy, cognitive behavioural
may have an increased amount of fruit squash and fruit therapy [187] or probiotics (Lactobacillus GG and VSL#3) can
juices as their drink of choice [181]. Apple juice, particularly, be considered [184].
has been implicated in causing toddler diarrhoea, and
studies have been completed using hydrogen breath tests
to measure carbohydrate malabsorption. What seems to be Irritable bowel syndrome
evident is that non‐absorbable monosaccharides and oligo-
saccharides, such as galacturonic acid, are produced by Irritable bowel syndrome is the name given to a longstand-
enzymatic treatment of the fruit pulp in clear fruit juices, ing functional GI disorder that consists of frequent abdomi-
including apple, grape and bilberry juices. It is thought that nal discomfort and bowel symptoms that cannot be explained
these may cause problems in sensitive individuals, rather by any other disease. The symptoms include abdominal
than fructose [182]. cramps, bloating, diarrhoea and constipation.
Treatment study evaluated symptoms after 48 hours on a low FODMAP

diet compared with the same length of time on a typical
In adults it has been demonstrated that a diet low in ferment-
American diet, with a 5‐day washout period between the two
able oligosaccharides, disaccharides, monosaccharides and
diets. All the meals were provided for the families, and the diet
polyols (FODMAP) can be beneficial in treating the symp-
analysis showed no difference in macronutrient provision
toms of IBS [188]. FODMAPs are short chain carbohydrates
other than the low FODMAP diet being lower in carbohy-
(e.g. fructans, galacto‐oligosaccharides, polyols, fructose and
drate. The study diet appeared to ameliorate GI symptoms in
lactose) that are poorly absorbed in the small intestine.
the children; however, they only followed the diet for 48 hours,
Ingestion of FODMAPs leads to alterations in fluid content
which would not be long enough to see the full effect [191].
and bacterial fermentation of carbohydrate in the colon trig-
There is concern that such a restricted diet may lead to inade-
gering functional gut symptoms in susceptible individuals.
quate nutritional intake in children and also the development
The low FODMAP diet originated at Monash University,
of poor eating behaviour with so many dietary exclusions
Melbourne, Australia. It has been successfully adapted in the
involved [192]. Further studies are needed to show outcomes
UK by researchers at King’s College London and imple-
in the paediatric population. Resources for health profession-
mented in the adult population at Guy’s and St Thomas’
als interested in the low FODMAP diet are available to pur-
NHS Trust in London. Removing FODMAPs from the diet
chase via the King’s College London website (www.kcl.ac.uk).
has been shown to be effective at improving the symptoms
of adults with IBS. There have been numerous systematic
reviews looking at the diet’s efficacy in adults, the most Learning points: functional gastrointestinal disorders
recent including nine RCTs of 596 subjects comparing their
symptoms with others consuming habitual, Western or other • FGID are a mixed group of disorders based on symptoms
diets recommended for IBS. The conclusion was that short‐ where no organic cause can be found
term efficacy and safety was shown in adults; however, there • They have a complex aetiology that includes biological and
need to be more studies looking at the long‐term effects of psychosocial factors
following this diet [189]. One potential hazard of following a • Management guidelines are based on reassurance, parental
low FODMAP diet is altering the gut microbiome with stud- support, and, in some cases, nutritional advice
ies showing a reduction in Bifidobacteria species concentra- • A low FODMAP diet has been shown to be beneficial in
tion, the long‐term effects of this on colonic health being treating IBS symptoms in adults; however, there is scant
unknown [190]. data to show its efficacy in children; care is needed to ensure
The only published study in children by Chumpitazi et al. nutritional adequacy
enrolled 52 children with only 33 completing the trial. The
Food allergy in gastroenterology

A food allergy is defined as a reproducible immune‐mediated Non‐IgE GI FA are characterised by subacute and/or
adverse reaction to a specific food. Food allergies are most chronic symptoms and include FPIES, FPIAP and food pro-
common in childhood due to the immaturity of the gut tein‐induced enteropathy (FPE). FA may also be considered
mucosal barrier and immune system. Allergic sensitisation in a subset of children with constipation, GORD, abdominal
involves a failure to develop oral tolerance and an immuno- pain, colic, dysphagia, food impaction, protein losing enter-
logic response induced by food proteins in contact with the opathy, faltering growth and non‐coeliac wheat sensitivity
gut‐associated lymphoid tissue. One common cause of this is refractory to optimal medical management [193, 195].
the post‐enteritis syndrome where a loss of barrier function Allergic reactions can affect GI secretion, absorption (with or
and the breakdown of normal immune tolerance follow a GI without mucosal damage) and motility. Interactions between
infection. Deficiency of immunoglobulin A (IgA), which is the allergic cells and the mucosal nervous system are impor-
involved in the immune defence of mucosal surfaces, is a tant in mediating alterations in GI secretion and motility.
common associated finding in allergic infants. The prevalence Both interleukin‐5 (IL‐5) (a Th2‐produced cytokine) and the
and prognosis of FAs in childhood is described elsewhere chemokine, eotaxin, play a role in allergic responses that can
(p. 334). FA is classified on the basis of the involvement of IgE present as delayed gastric emptying, GOR and constipation
antibodies in the allergic pathophysiology, either as classic [196]. GI conditions that may be caused by allergic reactions
IgE, mixed pathophysiology (EoE or EGID), or non‐IgE‐medi- to dietary proteins are summarised in Table 8.13.
ated FA [193]. Lack of awareness of non‐IgE‐mediated gastro- In the clinical setting dietary manipulations may be used
intestinal food allergies (non‐IgE GI FA) often results in to treat symptoms before any formal GI investigations are
delayed diagnosis; however, care is needed to avoid overdi- carried out. The current tests available (skin prick tests,
agnosis as there are currently no definitive biomarkers and GI patch tests and specific IgE) are of limited use in identifying
manifestations attributed to these disorders [194]. Pathological food allergens causing GI disease. Diagnosis is based on an
inflammatory changes can be seen in the GI tract. Cells and allergy focused history that includes a first‐degree family
mediators of the immune system such as eosinophils and history of atopy (hay fever/allergic rhinitis, asthma,
lymphocytes may be found in biopsies of inflamed sites. eczema), allergies and organ‐specific autoimmunity
Food Allergy in Gastroenterology 139
Table 8.13 Gastrointestinal disorders that can be caused by allergy Removal of dietary antigens as treatment for
to dietary proteins.
GI allergic disorders
Eosinophilic oesophagitis (EoE)
Eosinophilic gastroenteritis Exclusion of cow’s milk protein
Food protein‐induced enterocolitis syndrome (FPIES)
Gastro‐oesophageal reflux (GOR)
CMP is the most common food protein to cause a reaction in
Food protein‐induced enteropathy (FPE) infant. The natural history of CMA is described elsewhere
Food protein‐induced allergic proctocolitis (FPIAP) (p. 334).
Constipation
Alternative infant formulas
It is vital that an infant is given a nutritionally complete milk
combined with the age at presentation of symptoms and substitute to replace a CMP‐based formula. Except in FPIES,
food intake at that time. Diet history is often an unreliable the maternal diet in breastfed infants should be modified by the
indicator of the offending allergen(s) due to the delayed removal of CMP and any other foods allergenic to the infant.
reaction to the food. The efficacy of the exclusion of a par- Care needs to be taken to ensure that the maternal diet contin-
ticular food antigen should be evaluated, and, when there is ues to include adequate amounts of calcium, vitamin D, energy,
symptom improvement, an OFC should be performed to protein and fluid. It has been found that breastfed infants can
see if symptoms reoccur [197]. If there is no improvement be sensitised to multiple allergens including egg, soy, wheat
on an exclusion diet, a normal diet should be reintroduced. and fish [205]. Recommendations from ESPGHAN are that the
In non‐IgE GI FA, this diagnostic pathway is generally dietary trial should be continued for up to 14 days if delayed GI
undertaken at home and relies on accurate parental report- reactions are suspected. If there is no improvement, then the
ing of symptoms [198]. infant should be further evaluated. If multiple food allergies
Although the most common foods to cause GI FA prob- are suspected, then an EHF or AAF can be tried. The mother
lems are CM, egg, wheat and soya, any food ingested could should be encouraged to express her milk while the clinical
be allergenic [199]. Sometimes a number of dietary manipu- response to the hypoallergenic feed is evaluated [202, 206].
lations need to be tried before the correct dietary restriction
for the individual is achieved. In the presence of multiple
Mammalian milks
food allergies, a few foods diet (p. 320) or exclusive use of a
hypoallergenic feed may be needed. Mammalian milks are not suitable to be used as an infant
The timing of symptom resolution varies between a few feed without modification due to their high renal solute load
hours for acute FPIES to several weeks for FPE. A review of and inadequate vitamin and mineral content. The proteins in
symptom response to the exclusion diet followed by OFC goat’s and sheep’s milks share antigenic cross‐reactivity
to confirm the diagnosis needs to be undertaken by the cli- with CMP [201, 206]. Infant formulas based on goat’s milk
nician or dietitian [200]. A 4‐week dietary trial has been are not recommended for use in GI FA [207].
shown to be sufficient to determine symptom improve-
ment in 98% of children with non‐IgE‐mediated FA
Soy protein‐based formulas
responding to dietary antigen exclusion [198]. When multi-
ple foods are excluded from the diet, it is important to Soy formulas are based on soy protein isolate supplemented
sequentially challenge the excluded foods (p. 325) to iden- with l‐methionine to give a suitable amino acid profile for
tify those the child is reacting to in order to avoid over‐ infants. They are lactose‐free with glucose polymer as the
restricting the diet. most common source of carbohydrate. The fat is a mixture of
While there are internationally recognised guidelines on vegetable oils that provide long chain fatty acids, including
the management of cow’s milk allergy (CMA), these do EFA. Feeding soy formulas to infants is associated with nor-
not encompass children with possible multiple food mal growth, protein status and bone mineralisation [208, 209].
allergies [201–203]. It is known that unnecessary food
In the UK the use of soy formulas in infants under the age of
exclusions can lead to nutrient deficiencies as well as 6 months has been advised against by the Chief Medical
affecting QoL. One study showed that the families of chil- Officer due to their high phytoestrogen content, unless there is
dren with non‐IgE GI FA had worse scores in emotional a specific medical indication [210]. There appears to be less risk
and physical domains than families of children with intes- to the infant after 6 months of age as the reducing dependence
tinal failure [204]. It is, therefore, important that children on formula decreases the amount of isoflavones, per kilogram
are diagnosed and correctly managed on as few dietary body weight, ingested. The infant’s potentially vulnerable
exclusions as possible. organ systems are also likely to have matured by that age.
Exclusion diets are difficult to manage at home and are Soy protein has a very large molecular weight and after
expensive. Selection of suitable patients is important. The digestion can generate a large number of potential allergens.
use of anti‐allergic or anti‐inflammatory drugs as a thera- Severe GI reactions to soy protein formula have been
peutic alternative to dietary restriction should be considered described for more than 30 years and include enteropathy,
in situations where the family will not cope with a strict enterocolitis and proctitis. In FPIES caused by CMP, 25%–
exclusion diet. 50% of children in the USA had concomitant soy‐induced
Table 8.14 Composition of soy infant formula per 100 mL.
Energy
Osmolality
Dilution (%) (kcal) (kJ) CHO (g) Protein (g) Fat (g) (mOsm/kg H2O)
SMA Wysoy 13.2 67 280 6.9 1.8 3.6 204

(SMA Nutrition)
enterocolitis, which responded to the use of hypoallergenic hence in their residual allergenic activity (Table 15.6). Feeds
feeds. This frequency of sensitisation is not reported in other with peptides >1500 Da have been demonstrated to have
countries [77]. It has been suggested that an intestinal residual allergenic activity [215, 216]. The degree of hydroly-
mucosa damaged by CMP allows increased uptake and sis does not predict the immunogenic or the allergenic
increased immunological reaction to soy protein. Conversely, effects in the recipient infant. It has been recommended that
one study of children with CMA (both IgE and non‐IgE dietary products for treatment of CMP allergy in infants
mediated) found that soy formula was tolerated by 90% of should be tolerated by at least 90% of infants with docu-
children [211]. The American Academy of Pediatrics (AAP) mented CMA [207].
states that soy formulas are not recommended in the man- Table 8.15 shows the composition of EHF available in the
agement of CMP enteropathy or enterocolitis; however, most UK. Feed choice may be influenced by:
children can resume soy protein consumption safely after
• palatability, which is affected by the presence of bitter
5 years of age [208]. EPSGHAN concluded that the use of
peptides. This is particularly important in infants older
EHF (or AAF if EHF is not tolerated) should be preferred to
than 3 months of age
soy protein feeds and the latter should not be used before the
• coexisting fat malabsorption, where a feed with some of
age of 6 months. If soy formulas are used therapeutically
the fat as MCT may be indicated
after the age of 6 months, tolerance to soy protein should
• cost, some hydrolysates being twice as expensive as
first be established by clinical challenge [212]. The more
others
recent ESPGHAN and European Academy of Allergy and
• religion and culture, where parents do not wish their
Clinical Immunology (EAACI) guidelines for the manage-
children to be given products derived from pork
ment of CMA both state that soy formulas may be tolerated
after the age of 6 months [202, 213].
Soy formula has the benefit of being at least half the cost of Introduction of hydrolysate formulas
EHF and is much more palatable. Prospective studies looking These feeds may need to be introduced slowly to infants
at the incidence of soy allergy in patients with GI conditions with severe GI symptoms as they have a higher osmolality
are required. The soy infant formula available in the UK is than normal infant formulas. If severe diarrhoea is present in
given in Table 8.14. an older infant, it is preferable to stop all solids while a new
feed is being introduced to assess tolerance.
In an outpatient setting, where symptoms will be less
Feeds based on protein hydrolysates
severe, full strength formula can usually be introduced from
Infants with CMA need an alternative infant formula to the outset. In infants older than 6 months, there may be an
ensure nutritional adequacy. The allergenicity or antigenicity advantage in initially mixing one part EHF to three parts of
of a particular protein is a function of the amino acid the usual formula to slowly introduce the new taste and
sequences present and the configuration of the molecule. An encourage acceptance. The proportion of EHF can be
epitope is the area of a peptide chain capable of stimulating increased over the next three days when full strength feeds
antibody production. During the manufacture of a hydro- are achieved. Milkshake flavourings at 2%–4% concentration
lysate, the protein is denatured by heat treatment and hydro- (2–4 g per 100 mL) can also be used in this age group if
lysed by proteolytic enzymes, leaving small peptides and sucrose is not contraindicated.
free amino acids. The enzymes are then inactivated by heat If an infant refuses to drink the EHF, an NG tube needs to
and, along with residual large peptides, are removed by fil- be passed to ensure adequate volumes are taken. Where fal-
tration [214]. The proteins used to make a hydrolysate vary, tering growth coexists, feeds can be fortified in the usual
and production methods also differ between manufacturers. manner by increasing formula concentration or the judicial
The profile of peptide chain lengths between different feeds use of carbohydrate and fat modules [217] (p. 13). All changes
will not be identical, even when the initial protein is the same. should be made slowly to ensure they are tolerated.
Potential problems with hydrolysate formulas

Amino acid‐based infant formulas
Despite the rigorous conditions employed in the manufac-
ture of these feeds, there are still potential sequential Only pure amino acid mixtures are considered to be non‐
epitopes present that can be allergenic to a sensitised infant. allergenic as there are no peptide chains present to act as
EHF vary considerably in their molecular weight profile and epitopes. In infants who fail to tolerate an EHF, this is the next
Table 8.15 Extensively hydrolysed infant formulas per 100 mL.
Energy
Dilution CHO* Protein Fat† Na K Osmolality
(%) (kcal) (kJ) (g) (g) (g) (mmol) (mmol) (mOsm/kg H2O)
Casein
Nutramigen 1 with LGG‡,a 13.6 68 280 7.5 1.9 3.4 1.4 2.1 287
(Mead Johnson)
Pregestimil Lipil 13.5 68 280 6.9 1.9 3.8 1.3 1.9 279
(Mead Johnson) (55%)
Similac Alimentum 12.8 68 283 6.6 1.9 3.8 1.3 1.8 274
(Abbott) 20% (33%)
sucrose
Whey
Aptamil Pepti‐Junior 12.8 66 275 6.8 1.8 3.5 0.8 1.7 210
(Nutricia) trace (45%)
lactose
Aptamil Pepti 1^ 13.6 67 280 7.0 1.6 3.5 0.9 2.0 280
(Nutricia) 41%
lactose
SMA Althera 13.2 67 280 7.3 1.7 3.4 0.9 1.8 281
(Nestle) 52%
lactose
Infatrini Peptisorb§ — 100 420 10.3 2.6 5.4 1.4 2.8 350
(Nutricia) trace (50%)
lactose
*Carbohydrate is present as glucose polymers unless otherwise stated.

†
Figures in parentheses indicate the percentage of fat present as medium chain triglycerides (MCT).
‡
Nutramigen 2 with LGG is available for infants >6 months of age.
a
Feed contains probiotic Lactobacillus rhamnosus GG. Care is needed in certain infant groups where live bacteria may be contraindicated. Water to
reconstitute the feed should be <40°C.
^
Aptamil Pepti 2 is available for infants >6 months of age.
§
Liquid feed, designed for infants <9 kg body weight requiring a nutrient‐dense feed. Not suitable for cow’s milk allergy.
Table 8.16 Infant formulas based on amino acids per 100 mL.
Energy
Dilution CHO Protein Na K Osmolality
(%) (kcal) (kJ) (g) (g) Fat (g) (mmol) (mmol) (mOsm/kg H2O)
Neocate LCP 13.8 67 279 7.2 1.8 3.4 1.1 1.8 340
(Nutricia) (4% MCT)
Neocate Syneo* 14.7 68 286 7.2 1.9 3.4 1.2 1.9 360
(Nutricia) (4% MCT)
Puramino 13.6 68 286 7.2 1.9 3.6 1.4 1.9 350
(Mead Johnson) (33% MCT)
Alfamino 13.8 70 291 7.9 1.9 3.4 1.1 2.0 332
(SMA) (24% MCT)
*Feed contains a synbiotic (pre‐ and probiotic). Care is needed in certain infant groups where live bacteria may be contraindicated. Water to
reconstitute the feed should be <40 °C.
logical step, so long as there is no coexisting fat or carbohy- For the majority of infants with non‐IgE gastrointestinal
drate intolerance; in this circumstance a modular feeding FA, an EHF would be the first‐line treatment, with an AAF
approach should be used (p. 145). Infant AAFs available in the used if the child fails to tolerate this feed There are differ-
UK are summarised in Table 8.16. Neocate Spoon, which con- ences between the EHF and AAF brands that are shown in
tains highly refined rice starch as a thickener, can be offered as Tables 8.15 and 8.16. An EHF that contains Lactobacillus rham-
a nutrient‐dense hypoallergenic weaning food if required. nosus GG has been shown to reduce the time taken for a child
Table 8.17 Milk‐free diet.
Foods permitted Foods to be excluded Check ingredients
Milk substitute All mammalian milks, cheese, yoghurt, Margarines

Vegetable oils fromage frais, ice cream, butter
Custard made with milk substitute, sorbet
Meat, poultry, fish, shellfish (fresh or Sausages, pies, foods in batter or breadcrumbs
frozen), pulses Baked beans
All grains, dry pasta, flour Pasta with cheese or milk sauce, milk bread, Tinned pasta
Most breads, most breakfast cereals nan bread Bought cakes or biscuits
Cream cakes, chocolate cakes
Fruit and vegetables Instant mashed potato
Plain crisps, nuts Flavoured crisps
Sugar, jam, jelly Milk chocolate, toffee Plain chocolate
Marmite Ketchup, salad dressings, soups
Milkshake syrups and powder Malted milk drinks
Fizzy drinks, juice, squash
to acquire oral tolerance of CMP (p. 337). There is a differ- their packaging, but, as this is not compulsory, caregivers
ence in cost between EHF and AAF with the latter being should always be advised to check the ingredients. Foods
more than twice as expensive. It should be noted that one labelled ‘may contain’ do not generally need to be avoided
retrospective study found that up to 30% of food allergic by children with non‐IgE GI FA. Parents need clear advice
infants, many with delayed reactions to foods, were intoler- about this due to the increasing number of foods carrying
ant of EHF [199]. Intolerances to hydrolysate formulas, this label (p. 329). For foods manufactured outside the EU, it
resulting in GI disturbances have also been described by is still necessary to teach families about the following ingre-
Vanderhoof et al. [216]. dients that indicate the presence of CM in a manufactured
food: casein, hydrolysed caseinates, whey, hydrolysed
whey, lactose, milk solids, non‐fat milk solids and butter fat.
Milk‐free dietary information is summarised in Table 8.17.
Learning points: cow’s milk‐free formulas for infants
• Soy‐based formulas should not be used under the age of Exclusion of soy protein
6 months, but may be tolerated by a significant number of
infants with CMA over this age In conditions where soy allergy is present in addition to
• Consideration when selecting an EHF for an infant with CMA, foods containing soy and milk protein should be
CMA would include cost, enzymes used in manufacture excluded from the diet (Tables 8.17 and 8.18). Vegetable or
and taste in the older in infant soy oils and soya lecithin are normally tolerated by individu-
• AAF are at least twice as expensive as EHF and, in most als sensitive to soy protein and should not need to be
cases, should only be used when a trial of EHF fails excluded except in severely affected individuals [218, 219].
• The addition of selected pre‐ and probiotics may influence
outcomes in infants with CMA
Milk, egg, wheat and soy exclusion diets
In conditions where a simple exclusion diet has not worked

or where there is a diet history suggestive of multiple food
Milk‐free diet intolerances, this empirical dietary regimen may be tried.
It is important that the caregivers of infants requiring a

CMP‐free feed are given appropriate advice to enable them Table 8.18 Foods containing soya protein.
to exclude CM from solid foods. Weaning should take place
at the usual age. EU law (Directive 2003/89/EC, November All soy‐based products including tofu, tempeh and soy sauce
2005) regarding labelling of ingredients ensures that prod- Texturised vegetable proteins
ucts containing CMP are clearly identifiable. Exceptions Breads, biscuits and cakes containing soy flour
Baby foods containing soy protein
include foods that are not pre‐packed such as bread from a
Soy margarines
bakery. Many manufacturers print an allergy statement on
Table 8.19 Milk, egg, wheat and soya-free diet.
Foods permitted Foods to be excluded Check ingredients
Milk substitute All mammalian milks and products, soya Margarines

Vegetable oils milks and soy products, shredded suet
Eggs
All meat, poultry, fish, shellfish (fresh or frozen), Meat or fish dishes with pastry, Sausages, beef and vegetarian burgers,
pulses breadcrumbs or batter hot dogs, ready meals
Tofu, tempeh, soy beans, Quorn
Rice, rice noodles or pasta, maize, corn pasta, Wheat, rye and soya flour, spelt flour, Gluten free bread, cakes, biscuits, pasta
cornflour, tapioca, sago, arrowroot, buckwheat, wheat bran or germ, semolina, couscous, Oatcakes
barley, oats, gram flour, potato flour, rye, tabouleh, pancakes, batter, pizza,
ground almonds, carob, teff, amaranth, millet stuffing mixes, ordinary pasta, e.g.
spaghetti
Breakfast cereals made from rice, corn and Wheat based breakfast cereals Poppadoms
oats, rice and corn cakes Bread, crispbreads, crackers, chapatti,
croissants, biscuits, cake
Jelly, plain custard powder, rice, tapioca or sago Pies, pastries, mousse, trifle, cheesecake, Sorbet, blancmange powders
pudding (made with milk substitute) instant desserts
Fruit and vegetables Potato croquettes Vegetables in dressing, e.g. coleslaw,
potato waffles, instant mashed potato
Plain crisps Flavoured potato crisps
Marmite, Bovril Ordinary mayonnaise, salad creams, soy Stock cubes, gravy mixes, soups, sauces
sauce
Sugar, jam, honey, syrup, plain fruit lollies, Chocolate spread, lemon curd, milk Plain chocolate, jelly sweets,
milkshake syrup and powder, cocoa chocolate, instant milk drinks marshmallows, baking powder,
drinking chocolate, malted drinks
Soy, eggs and wheat are also covered by EU law (Directive hypoallergenic feed was continued until the age of 2 years
2003/89/EC, November 2005) and must be clearly labelled [220]. In situations where a large percentage of the child’s
on all pre‐packed foods. Families need a lot of help and nutrition comes from a formula, it will either need fortifica-
information about commercial foods to enable them to tion to meet nutritional requirements, or a feed designed
adhere to this regimen. Suitable wheat‐free products that for older children should be used. If an infant formula is
are available via the Advisory Committee on Borderline modified, care needs to be taken to ensure an appropriate
Substances (ACBS) for CD cannot be prescribed for wheat protein to energy ratio. Rather than addition of energy sup-
allergy. Many of these products contain milk, egg or soya, plements, it is often preferable to concentrate the feed. This
so families need help to identify suitable substitutes. should be done slowly, taking into account individual tol-
Supermarkets produce many foods suitable for exclusion erance [217]. When a concentrated infant formula is used to
diets that can help families to expand the diet. For foods feed an older child, consideration should be given to the
manufactured outside the EU, it is still necessary to teach sodium intake, especially where there are increased stool or
families about the following ingredients that indicate the stoma losses. Most feeds in Table 8.20 have been designed
presence of egg, wheat and soya in manufactured foods: egg to meet the requirements of older children requiring
albumin, wheat flour, wheat starch/bran, edible starch, hypoallergenic feeds. Adult feeds based on soy or hydro-
modified starch, hydrolysed wheat protein, rusk, batter, lysed protein should be used with care in older children
breadcrumbs, thickener (unless specified as being made and may require modification or vitamin and mineral sup-
from another cereal), soy protein isolate, soya grits, tofu, plementation. Not all the feeds are categorised as EHF, and
hydrolysed/spun/textured vegetable protein, miso and care needs to be taken when selecting a feed for children
tempeh (Tables 8.19 and 15.8). with CMA.
Children over the age of 2 years consuming a balanced
diet and tolerating soy protein may be given liquid soy
Suitable feeds for older children drinks as an alternative to CM. Those with added calcium
and vitamins help to ensure nutritional adequacy. For chil-
A suitable infant formula should be continued for as long dren intolerant of soy and CM, there are alternative drinks
as it is nutritionally indicated in children on an exclusion made from foods as diverse as oat, nut and coconut.
diet and is preferable under the age of 2 years [201]. One Many brands of rice drinks are available, but these are not
study showed significantly better micronutrient intake if a recommended for children under the age of 5 years due to
Table 8.20 Hydrolysate and amino acid‐based feeds for older children per 100 mL.
Energy
Dilution Protein Fat† Na K Osmolality
(%) (kcal) (kJ) CHO* (g) (g) (g) (mmol) (mmol) (mOsm/kg H2O)
Whey hydrolysates
Peptamen Junior ∼ ‡ 22 100 420 13.8 3 3.8 2.9 3.6 370
(Nestle) (60)
Peptamen Junior Advance∼ f ‡ 150 631 18 4.5 6.6 4.1 4.6 450
(Nestle) (60)
Nutrini Peptisorb§ — 100 420 13.6 2.8 3.9 2.5 2.8 345
(Nutricia) trace (46)
lactose
Nutrini Peptisorb Energyf § 150 630 16.7 4.2 6.6 4.1 4.3 510
(Nutricia) trace lactose (55)
Amino acid feeds
Neocate Junior¶ 21.1 100 420 12 2.8 4.6 2.6 2.9 600
(unflavoured) (35)
(Nutricia)
Elemental 028 20 89 374 11.8 2.5 3.5 2.7 2.4 502
Extra¶ †† (35)
(unflavoured)
(Nutricia)
Emsogen¶ †† ‡‡ 20 88 370 12 2.5 3.3 2.6 2.4 580
(unflavoured) (83)
(SHS)
*All present as glucose polymer.

†
Figures in parentheses show percentage fat present as MCT.
‡
Also available as a liquid feed.
§
Liquid feed.
¶
Flavoured versions also available.
††
Use with caution for children between 1 and 5 years.
‡‡
Patients who are receiving a significant proportion of their nutrition from Emsogen may need to supplement their intake of α‐linolenic acid to meet UK
DRV 1991 guidelines [221].
∼
Protein is not extensively hydrolysed, therefore not suitable for cow’s milk allergy.
f
Contains fibre.
concerns about their arsenic content [222]. These alternative CMP‐free diet [225], and it is likely that this may be a
drinks are available in supermarkets and health food shops problem in older children as well. Optimal dietetic man-
and can be useful as a social replacement for CM. agement of exclusion diets ensures that these do not sig-
Most of these drinks contain very little protein. nificantly impact on a child’s growth parameters [226].
Although fortified with calcium and vitamins, calcium
supplements may need to be given if the RNI is to be
achieved [221]. Calcium intakes below recommended Learning points: formulas and milks for older children
amounts have been identified in a number of children
who are limiting CM in their diet, and this may affect • For children under 2 years of age who do not take a
bone density [223]. A study in Norway showed that hypoallergenic formula, a detailed dietary assessment
children aged between 31 and 37 months following CMP is needed, and appropriate nutritional supplementation
free diets had significantly lower intakes of energy, fat, given as necessary
protein, calcium, riboflavin and niacin than age‐matched • Formulas based on partially hydrolysed proteins are not
controls [224]. Careful monitoring of dietary adequacy suitable for children with CMA
and supplementation with calcium and vitamins, if • EHF and AAF for the older child have very different
needed, is required together with ensuring adequate nutritional profiles and should be carefully selected for the
energy and protein intake from food. Suitable calcium individual
supplements may be found in Table 29.10. Iodine status • Alternative drinks to cow’s milk, such as soy, coconut and
should also be considered in children on a CMP‐free diet oat ‘milks’, can be included in the diet of the older child and,
who are not having a complete feed. One study found if fortified, are a useful source of calcium
reduced iodine levels in breastfed infants following a
Modular feeds for intractable diarrhoea and short nutritional requirements. The following parameters need to
bowel syndrome be considered:
Intractable diarrhoea can be defined as chronic diarrhoea in • total energy content and appropriate energy ratio from
the absence of bacterial pathogens of greater than 2 weeks’ fat and carbohydrate
duration, together with failure to gain weight. Some infants • protein, both type used and quantity
with severe enteropathy, allergic GI disorders or short • EFA intake
bowel syndrome fail to respond to feed manipulation using • full vitamin and mineral supplementation, including
EHF or AAF, as previously described, and a modular feed trace elements
is necessary [227]. This allows individual manipulation of • suitable electrolyte concentrations
ingredients resulting in a tailor‐made feed for a child. • feed osmolality
Careful assessment and monitoring is important to prevent
nutritional deficiencies and to evaluate the response to feed
Practical details
manipulation. The grading of stools using the Bristol stool
chart is important to help assess the response to feed altera- • Accurate feed calculation and measurement of ingredi-
tions [228]. The use of modular feeds can also assist in the ents is required to make the necessary small daily feed
diagnosis of the underlying problem. alterations. Scoop measurements are not accurate enough,
and ingredients should be weighed on electronic scales.
• Infants with protracted diarrhoea or short bowel
Feed ingredients syndrome will tolerate frequent small bolus feeds given
Some of the possible choices of feed ingredients and their one to two hourly, or continuous feeds via an NG tube,
advantages and disadvantages are listed in Tables 8.21–8.24. better than larger bolus feeds.
Before starting there needs to be a discussion with the medi- • Attention needs to be given to the combination of ingre-
cal staff regarding the appropriate feed composition for the dients as these will affect the feed osmolality. The smaller
individual infant and to establish good medical support for the molecular size, the greater the osmotic effect. Most
the dietitian managing the baby’s nutrition. The aim is to hospital chemical pathology laboratories will analyse
produce a feed that is well tolerated and meets the infant’s feed osmolality on request.
Table 8.21 Protein sources for use in modular feeds.
Suggested
dilution* Protein equivalent ACBS
Protein type (g/100 mL) (g/100 mL) prescribable Comments
Hydrolysed Whey Protein/ Hydrolysed 4 2 N At this dilution: 1.5 g glucose

Maltodextrin Mixture whey polymer, 0.8 mmol Na, 0.6 mmol K
(SHS)
Complete Amino Acid Mix L‐amino acids 2.5 2.0 N Amino acids increase feed osmolality
(Nutricia) No electrolytes
ACBS, Advisory Committee on Borderline Substances; SHS, Scientific Hospital Supplies.

*This is a suggested dilution only. Quantities can be varied according to the desired protein intake, age of child, and feed tolerance.
Table 8.22 Carbohydrate sources for use in modular feeds.
Suggested concentration ACBS

(g/100 mL) prescribable Comments
Glucose polymer*, e.g. Maxijul 10–12 Y Carbohydrate of choice as has the lowest osmolality
(Nutricia), Polycal (Nutricia),
Vitajoule (Vitaflo)
Glucose 7–8 Y Use when glucose polymer intolerance is present
Fructose 7–8 Y Monosaccharides will increase final feed osmolality
A combination of the two monosaccharides can be
used to utilise two transport mechanisms
ACBS, Advisory Committee on Borderline Substances; SHS, Scientific Hospital Supplies.

* Intolerance to glucose polymers has been documented in the literature. This may be due to a deficiency of pancreatic amylase or of the disaccharidase
glucoamylase. Monosaccharides become the carbohydrates of choice in this situation. It may be possible to use sucrose as an alternative carbohydrate.
Table 8.23 Fat sources for use in modular feeds.
Suggested concentration*
(g/100 mL) Comments
Calogen (canola, sunflower oil emulsion) 6–10 50% LCT emulsion

(Nutricia) Contains linoleic acid (C18:2) + α‐linolenic acid
(C18:3) in a 5:1 ratio
Liquigen (coconut, palm kernel oil 4–8 50% MCT emulsion
emulsion) (Nutricia) MCT increases feed osmolality
Does not contain EFA
If used in a modular feed, consider a separate
supplement of EFA rich oil, e.g. walnut
Vegetable oils, e.g. olive, sunflower† 3–5 Not water miscible
An emulsion can be prepared by mixing 50 mL oil with
50 mL water and liquidising with 1–2 g gum acacia
MCT, medium chain triglycerides; LCT, long chain triglycerides; EFA, essential fatty acids.
*The amount of fat used will depend on tolerance and nutritional aim.
†
These ingredients are not Advisory Committee on Borderline Substances listed.
Table 8.24 Vitamin and mineral supplements that may be used use a modular feed with, say, a different fat source (in this
in modular feeds.
case wholly MCT instead of the mainly LCT found in
Paediatric Seravit Contains glucose syrup which may be
Neocate LCP), then the full strength modular feed can be
(Nutricia) contraindicated introduced more rapidly:
Does not contain electrolytes (Table 1.23)
• Before starting a modular feed, it is necessary to assess
Phlexy‐Vits Designed for children >11 years the infant’s symptoms and current nutritional support. If
(Nutricia) Reduced dose to be given for younger children PN is not available, feeds should be introduced rapidly
May need additional vitamins and minerals
to prevent long periods of inadequate nutrition.
prescribed separately according to requirements
Does not contain electrolytes (Table 1.23) • In the absence of IV glucose, the carbohydrate content of
the feed should never be less than 4 g/100 mL because of
FruitiVits Designed for children aged 3–10 years of age
the risk of hypoglycaemia. A higher percentage of energy
(Vitaflo) 0.5 g maltodextrin per 6 g sachet
Contains orange flavouring and artificial from fat than from carbohydrate may result in excessive
sweeteners acesulfame K, sucralose ketone production.
Does not contain electrolytes (Table 1.23) • An example of the slow introduction of an amino acid‐
based modular feed (the case study detailed in Table 8.25)
can be applied to other protein sources. Suggested
• Infants requiring a modular feeding approach may have incremental changes can take place every 24 hours. If well
high requirements for all nutrients depending on the tolerated this process can be accelerated.
underlying disorder. • The infant’s response to each change of feed should be
• Vitamin and mineral supplements used in conjunction assessed daily before making any further alterations.
with a fat emulsion, such as Calogen or Liquigen, cause Where possible making more than one change at a time
the fat to separate out. For feeds given as a continuous should be avoided.
infusion, it is recommended that these products are • Feed changes should be avoided during intercurrent
administered separately. infections as these tend to worsen GI symptoms and
• There is no carbohydrate‐free complete vitamin and make it difficult to assess feed tolerance.
mineral supplement for infants in the UK. If intolerance
of glucose/glucose polymer is suspected, then Paediatric
Seravit cannot be used. Phlexy‐Vits could be used in Preparing and teaching for home
small quantities with specific nutrients added according
to individual requirements. After a period of time on a modular feed, a nutritionally
complete feed should be tried again to see if this is now toler-
ated. The formula nearest in composition to the modular
Introduction of modular feeds
feed should be chosen and challenged slowly, either by sub-
Depending on the clinical situation, feeds are often intro- stituting one or two small feeds or by regrading over 4 days,
duced very slowly, and the concentration of the individual starting with a quarter strength complete feed mixed with
components is gradually increased (Table 8.25). Occasionally, three quarter strength modular feed. If this is not possible or
if an infant is already taking a full strength complete feed the complete feed is not tolerated, the aim should be to sim-
such as Neocate LCP and the necessary dietary change is to plify feed ingredients as much as possible in readiness for
Table 8.25 Case study: a female infant requiring a modular feed.
Anthropometry: Baby girl born at term, weight = 3.2 kg (25th centile). On admission to hospital at 2.5 weeks of age, she has failed to regain her birth
weight and current weight = 2.8 kg.
Biochemistry: On admission her biochemical results show her to be dehydrated and have severe metabolic acidosis.
Clinical: The baby is started on IV fluids and is allowed 20 mL/kg of Dioralyte orally. On this regimen she has 4 stools per day, grade 6 on the Bristol
stool scale. Stool samples are sent to the lab to rule out an infectious cause of the diarrhoea, and these come back negative. An endoscopy is planned.
Dietary: A careful feeding history shows that mum has breastfed the baby at home. When she failed to gain weight, she changed her to a standard
infant formula. This was not been tolerated (diarrhoea resulting in acidosis). After rehydration and correction of the acidosis, the focus is to
nutritionally rehabilitate the infant and find an enteral feed that she can tolerate. A central venous catheter is inserted to start PN. The constituents are
increased slowly over 5 days with careful biochemical monitoring because of the risk of refeeding syndrome. After the PN is established, a trial of
small volumes of an AAF results in increased stool output.
Environment: The baby is the second child of consanguineous parents. The sibling has known autoimmune enteropathy.
Focus: The aims of the dietetic intervention are now to ensure normal growth and weight gain and to find an enteral feed that the infant can tolerate
that will allow the PN to be gradually reduced and stopped. As she has failed a trial of AAF and no specific abnormalities are found on her small
bowel biopsy that can be treated, it is decided to trial a modular feeding approach. The older sibling had previously done well on this method of
feeding. The introduction of her modular feed based on Complete Amino Acid Mix is shown.
Slow introduction of modular feed based on Complete Amino Acid Mix.
Complete Amino NaCl and Glucose polymer,

Time Acid Mix KCl e.g. Maxijul Fat Volume
Days 1–3 1
∕2 strength increasing Full strength 2% Nil 20 mL/kg
to full strength
Days 4–9 Full strength Full strength Increase in 1% Nil No change
increments daily to
total of 7%
Days 10–12 Full strength Full strength 7% Calogen is added No change
in 2% increments
to 6%
Day 12+ Full strength Full strength 7% 6% Increase volume and
titrate with PN
reduction
An age appropriate vitamin and mineral supplement, Paediatric Seravit, is added as a separate medication when the PN is reduced to half volume
to ensure nutritional adequacy of the regimen. It is not added to the feed as this will result in the fat emulsion separating. Her full strength
modular feed based on Complete Amino Acid Mix is shown.
Full strength modular feed using Complete Amino Acid Mix per 100 mL.
Energy
Protein CHO Fat Na K
(kcal) (kJ) (g) (g) (g) (mmol) (mmol)
2.5 g Complete Amino Acids 8 34 2 – – – –

10 g Maxijul 38 160 – 9.5 – – –
6 mL Calogen 27 113 – – 3 0.1 –
1.4 mL NaCl (1 mmol/mL) – – – – – 1.4 –
0.8 mL KCl (2 mmol/mL) – – – – – – 1.6
Final feed per 100 mL 73 307 2 9.5 3.0 1.5 1.6
Paediatric Seravit
administered separately
Outcome
The baby does well on the modular feed, which she takes orally from a bottle, and the PN is successfully stopped. Before she is discharged, an
alternative AAF to the one offered initially is trialled again. This is because of the complexities of making modular feeds in the home environment,
and it is hoped that, now she is more clinically stable, she will tolerate an appropriate complete formula.
The new feed is introduced very slowly (¼ strength AAF mixed with ¾ strength modular feed for 24 hours, then ½ strength AAF mixed with ½ strength
modular feed, etc.). Once the full strength AAF is introduced she starts to vomit, her stool frequency increases, and the amount of oral feed she is taking
decreases. As a result she loses weight. She has no other cause for her GI symptoms to deteriorate such as an intercurrent infection, teething, etc. She is,
therefore, changed back to her modular feed, and the GI symptoms settle again, and the parents are taught to make this feed at home.
Discharge from hospital
She is discharged at 16 weeks of age, weight = 5 kg (2nd to 9th centile), length = 60.4 cm (25th centile). Her parents are advised not to introduce
solids until she is 6 months old, and these are to be started slowly, one hypoallergenic food at a time, until her tolerance to these can be established.
Management at home
In the first few weeks at home, the dietitian keeps in touch with the family regularly to ensure the feed is being made correctly and that she is taking
enough. The infant is weighed weekly by her health visitor and plotted on a centile chart to ensure appropriate weight gain. Her micronutrient levels
and urinary sodium levels are monitored monthly at the hospital to ensure that no additional supplements are required and that she is receiving
adequate amounts of electrolytes, vitamins and minerals.
IV, intravenous; PN, parenteral nutrition; AAF, amino acid formula; GI, gastrointestinal.
discharge home. Many preparation errors in the home envi- practitioner will be needed to arrange a supply of the
ronment have been noted including poor recipe adherence, product. A supply of these items may need to be given
incorrect use of measuring equipment, and errors in ingredi- from the hospital.
ent measurement [229]:
• Electronic scales should be used that measure in 1 g
Introduction of solids in infants on modular feeds
increments. If this is not possible to arrange at home,
ingredients need to be converted into scoop measure- Where possible solids should be introduced after the infant
ments, using the minimum number of different scoops or child is established on a nutritionally complete feed. The
possible to avoid confusion. restrictions imposed will depend on the underlying diagno-
• Syringes need to be supplied for accurate measurement sis. If this is not practical, then two or three items should be
of electrolyte solutions. chosen, and these should be allowed daily without varia-
• A 24 hour recipe should be given to reduce inaccuracies tion. Often it is necessary to introduce food items singly to
in feed reconstitution, paying due care to issues of determine tolerance of different foods.
hygiene and refrigeration of feed until it is used. It is
important to demonstrate the method for making the
feed to the infant’s caregivers on at least one occasion
before discharge.
• A laminated recipe and wipe‐off pen for home is useful
so that parents can tick off ingredients as they are added. References, further reading, guidelines, support groups
• Not all the suggested ingredients for modular feeds are and other useful links are on the companion website:
ACBS listed. A separate letter to the child’s general www.wiley.com/go/shaw/paediatricdietetics-5e
9 Surgery in the Gastrointestinal Tract
Danielle Petersen and Tracey Johnson
Congenital Malformations
Danielle Petersen
Introduction without OA (‘H’ fistula) occurs in approximately 4%. The aeti

ology of OA is unknown with environmental and ethnic dif
There are a number of congenital malformations that require ferences suggested to play a role [2, 4].
surgery during the neonatal period. These malformations OA is associated with other anomalies, associations or
may affect the oesophagus, stomach and small and large syndromes in 50%–66% of cases [2]. Pedersen et al. [1] con
intestines. The type of feed and the method by which it is ducted a population‐based study using data from a large
administered will be determined by the area of gut affected, European database for the surveillance of congenital anoma
the surgery performed to correct the defect and the condi lies over 20 years; 1222 cases of OA were identified. The most
tion of the remaining gut. common associated anomalies in these infants were congeni
tal heart defects (29.4%), urinary tract anomalies (16.4%),
other gastrointestinal anomalies (15.5%) and limb anomalies
Oesophageal atresia and tracheo‐oesophageal fistula (13.1%). VACTERL association (vertebral, anorectal, cardiac,
tracheo‐oesophageal, renal and limb defects) occurred in
Oesophageal atresia (OA) is one of the most common congen 9.6% of the infants and CHARGE syndrome (coloboma,
ital gut malformations and has a prevalence of 1 in 2500 to 1 in heart defects, choanal atresia, retarded growth and develop
4500 births [1–3]. The oesophagus ends blindly in a pouch, ment, genital hypoplasia and ear abnormalities) in 1% of
resulting in a non‐continuous route from the mouth to the infants. Stoll et al. [5] found similar incidences of anomalies
stomach. Diagnosis is made antenatally or at time of birth. At from data collected over 29 years, with 116 cases of OA iden
birth infants are unable to swallow properly and have exces tified. Associated anomalies were seen in 46.6% of infants,
sive salivation and feeding difficulties. Aspiration of saliva or chromosomal abnormalities in 7.8% (including VACTERL in
feed may cause choking and cyanotic attacks and requires 10.3% and CHARGE syndrome in 1.7%), congenital heart
surgical correction within 24–48 hours [2]. The majority, 69%– defects in 25%, gastrointestinal anomalies in 22.4% and
86%, of infants with OA also have a distal tracheo‐oesopha urinary anomalies in 15.5%.
geal fistula (TOF) where the proximal end of the distal Over the last 60 years the mortality rate of infants with OA
oesophagus is confluent with the trachea (Figure 9.1). In this has decreased dramatically due to improvements in surgical,
case any reflux of stomach contents will enter the trachea and anaesthetic and neonatal care. Infants with a birth weight
hence the lungs. Isolated ‘pure’ OA, where there is no fistu greater than 1500 g and with no major cardiac problems
lous connection with the trachea, occurs in 7%–26% of infants should have a near 100% survival rate. In those infants with
and the rarer presentation of a tracheo‐oesophageal fistula a very low birth weight (<1500 g) or a major cardiac anomaly,

Zani et al. [9] conducted an international survey among

178 surgeons, including 18 trainees, regarding practices in
the treatment of OA (78% of respondents were from European
countries). Results showed that post‐operatively 90% left a
TAT in situ. Only 2% of respondents created a gastrostomy at
the time of initial repair, and PN was routinely used by 54%
Oesophageal of surgeons. Enteral feeding via the TAT was started on or
atresia before day 2 post‐operatively in 40% of respondents, day 3–4
Trachea Tracheo-oesophageal post‐operatively in 35% and day 5 or later in 25% of respond
fistula ents. The majority of surgeons (89%) started oral feeds after
post‐operative day 5.
A recent retrospective review of 57 infants with OA and
TOF seen at a single institution between 2005 and 2015 found
that 61.4% of infants were discharged home on full oral
Distal oesophagus
feeds. Predictors for full or supplementary enteral tube feed
ing being necessary on discharge were having a structural
Stomach cardiac anomaly and younger corrected gestational age at
discharge. Only 46% of infants with a structural cardiac
anomaly were discharged home on full oral feeds versus
79% without a cardiac anomaly. This study showed that a
significant number of children (31.6%) with OA and TOF
Figure 9.1 Oesophageal atresia and tracheo‐oesophageal fistula.
were discharged home receiving some or full enteral nutri
tion and 3.6% continued to require PN at discharge [10].
the survival rate is reduced to 82%, and in those with a very
low birth weight and a major cardiac problem, the survival
rate is 50% [6, 7]. A prospective, multicentre cohort study of Delayed or staged repair
all infants born with OA in the UK and Ireland in 2008 and In infants with long‐gap OA, the oesophageal repair is more
2009 found that after 1 year the mortality rate was 8.6% [8]. complicated, and delayed repair is often necessary as the
Following diagnosis, the upper pouch should be suctioned two ends of the oesophagus are too short to be anastomosed
using a Replogle tube to reduce the risk of aspiration. initially. There is no consensus in the literature regarding
Treatment of OA, whether associated with TOF or not, is the definition of long‐gap OA. Van der Zee et al. [11] define
undertaken soon after birth. In most cases it involves the it as any OA that has no intra‐abdominal air; therefore no
repair of the oesophagus by anastomosing the upper and distal tracheo‐oesophageal fistula. Typically, the distance
lower ends, after closing any TOF if present, so that both the between the upper and lower ends of the oesophagus
oesophagus and trachea are separate and continuous. Until exceeds more than three vertebrae. The optimal surgical
the lesion is corrected surgically, the infant cannot be fed repair for infants with such long‐gap OA remains controver
orally. Depending on the length of the gap and the surgical sial, with no clear consensus, and practices differ between
management, either enteral or parenteral nutrition (PN) centres [6, 11, 12]. In the study by Zani et al. [9], only 80 of
(p. 52, 68) will be commenced [6]. the 178 surgeons and trainees provided accurate data for
long‐gap OA. Results showed that for surgical repair of
Surgical interventions and feeding in the first long‐gap OA:
months of life • 60% of surgeons delay primary anastomosis and insert a
gastrostomy without oesophagostomy
Primary repair • 24% attempt primary anastomosis (no gastrostomy or
oesophagostomy)
A primary anastomosis is performed when the distance
• 16% delay primary anastomosis and form an oesophago
between the proximal and distal ends of the oesophagus is
stomy and gastrostomy
short enough for the two to be joined in one procedure. This
is possible in the majority of patients, especially when a dis The median age of the infant when delayed anastomosis is
tal fistula is present. Most surgeons pass a transanastomotic performed is 3 months. In long‐gap OA, 47% of surgeons
tube (TAT) that allows gastric decompression in the early attempt elongation of the oesophagus, with the following
post‐operative period and a route for nasogastric feeding. It interventions most commonly used: 43% use growth by trac
has also been suggested that feeding via a TAT leads to tion (Foker technique), 41% serial dilation with bouginage,
reduced duration of PN [9, 10]. 8% suture both ends to encourage spontaneous fistula for
Feeds are often started 48–72 hours after corrective sur mation, 5% fashion an oesophagostomy for external elonga
gery and may be given orally once the infant is swallowing tion of the upper end and 3% perform a circular myotomy of
saliva [4]. Ideally, breastfeeding should be initiated or the proximal oesophagus. If the gap between the two ends of
expressed breast milk (EBM) given. If this is not possible, the oesophagus is 4–7 cm long, 67% of surgeons would
then a standard infant formula is used. always attempt an oesophageal anastomosis. The other 23%
Introduction 151
would not attempt an anastomosis, but would rather making it difficult to coordinate sham with gastrostomy
perform oesophageal replacement surgery [9]. feeding. However, this problem rapidly corrects itself
In a small number of cases, the oesophagus is temporarily when the feed volume is increased.
abandoned, and a cervical oesophagostomy is formed. This
If an oesophagostomy was not formed, there would be no
allows the infant to safely swallow saliva, and a gastrostomy
route for sham feeding, and infants would be deprived of
is inserted for feeding [4]. In these infants the oesophagus is
oral feedings for the first few weeks to months of life. This
left for a few months before attempting to join the upper and
should not be a major problem if oral feeding is established
lower ends. Although cervical oesophagostomy prevents
within 2–3 months of life, but if oral feeding is delayed
growth in the upper pouch of the oesophagus, the lower
longer than this, it may be associated with feeding difficul
pouch hypertrophies and shortens the distance between the
ties. Infants who are not used to oral feeds often initially
two ends. However, a recent position paper on long‐gap OA
experience gagging and vomiting and may avert their head
suggests that a cervical oesophagostomy should be avoided
at the very sight of the breast/bottle or push out the nipple/
as it may increase the difficulty of a delayed primary anasto
teat with their tongue. Desensitisation to this oral aversion is
mosis or jejunal interposition [11].
a long, slow process, and it is important to remember that
If primary oesophageal anastomosis is not possible, then
feeding does not only provide nutrition; infants are very
an oesophageal replacement technique (p. 152) is used [11].
alert at feeding time and develop cognitive and motor abili
Feeding infants undergoing a delayed or staged repair often
ties while feeding as well.
presents more of a challenge than in those with a primary
Infants with OA with or without TOF can grow well on
anastomosis.
breastmilk and standard infant formulas, if adequate volumes
are taken. If there is a problem with weight gain, feeds can be
Feeding the young infant concentrated or a high energy formula used (Table 1.18).
When corrective surgery is delayed and the oesophagus is

Feeding the older infant and toddler
not joined up, the infant must be fed by gastrostomy. Either
EBM or infant formula can be used and given at the same
To promote normal development, infants with OA should be
volume and frequency as the infant would receive had they
weaned at the recommended age of around 6 months. When
been fed orally. Infants with cervical oesophagostomies
a primary repair is performed soon after birth without com
should start sham feeding as soon as possible, which will
plications, feeding is initiated early, and normal feeding
allow the infant to experience normal oral behaviour. To
progression should be achieved. However, in infants with
facilitate normal development and coordination, the sham
long‐gap OA, the primary anastomosis is often delayed, and
feed should be of the same volume as the gastrostomy feed,
these infants often experience feeding difficulties. The
and the feed should be of the same duration and frequency
change from receiving full enteral nutrition to maintaining
so that the baby learns to associate sucking with hunger
an adequate intake orally is slow, and there is often a long
and satiety. Ideally the feed that is offered with sham feed
period where the child needs supplementary enteral feeds
ing should have the same taste as that being put down the
while learning to eat and drink orally. If gagging is experi
gastrostomy so that there is no refusal of feeds on the
enced when solids are introduced, oral intake may be
grounds of taste once the infant has a continuous oesopha
reduced to just tastes of food rather than giving large
gus later. However, it is more common practice for mothers
amounts in order to dispel the association between solid
who choose to give their babies breastmilk to express and
food and gagging. Foods need to be moist, and fibrous foods
give EBM via the gastrostomy and infant formula by mouth
should be avoided. It may also take infants longer to take
for the sham feed. The sham feed seeps out of the
foods with chunks, and certain foods, such as white bread,
oesophagostomy, along with saliva, and is usually man
can be problematic. Infants with feeding difficulties should
aged by wrapping a towel or other absorbent material
remain on ‘stage 2’ foods (puree with soft lumps) for longer
around the infant’s neck. There are, however, problems
than usual to reduce the risk of choking. Feeding should also
with sham feeding:
be done under close supervision to reduce the risk of cough
• It is difficult to coordinate holding the baby, feeding from ing and choking. Fluid should be given at mealtimes to help
a bottle and mopping‐up feed from the oesophagostomy food move down the oesophagus. Both mother and child
while giving a gastrostomy feed. This event may defeat need to build up confidence about eating. As the infant or
nursing staff let alone the mother coping single‐handedly child’s oral intake increases, enteral feeds should slowly be
at home. reduced while monitoring intake and growth closely.
• One‐third of infants with OA suffer from cardiovascular Standard infant formulas and high energy formulas (SMA
complications and may need ventilating, making sham High Energy, Infatrini or Similac High Energy) may safely be
feeding impossible. used up to the age of 1 year or so but will need to be replaced
• Infants may tire quickly and not be able to suck for long by a more nutritionally adequate feed such as PaediaSure,
enough to take the same volume orally as is going Nutrini or Frebini to promote optimal growth in the older
through the gastrostomy. child if enteral feeds continue (Table 4.3). If the infant is still
• Many infants have small stomachs and initially require sham fed, weaning solids should also be sham fed and a
small volumes of gastrostomy feed frequently, e.g. 2 hourly, nutritionally adequate feed given via the gastrostomy.
Oesophageal substitution procedures similar rate as the child; it has a similar diameter to the
oesophagus and maintains intrinsic motility well. In the long
Long‐gap OA occurs in about 10% of infants with OA. term, the risk of GOR is less than that seen in gastric and
Repairing the continuity of the oesophagus in these infants is colonic interposition. However, the main disadvantage is
more complex than those with distal tracheo‐oesophageal fis that the blood supply is often precarious [11, 13].
tulas. There is consensus among centres that the first choice
in correction is to preserve the native oesophagus and per
form a primary repair, with delaying primary anastomosis or Feeding post‐oesophageal substitution
using traction/growth techniques to achieve anastomosis if
needed. If primary anastomosis is not possible, various The oesophagostomy, if present, is closed at the time of the
oesophageal replacement techniques are used. These include oesophageal substitution. If a gastric transposition is per
jejunal interposition and, more commonly, colonic interposi formed, the pre‐existing gastrostomy can no longer be used
tion and gastric pull‐up/interposition, with no clear evidence and is removed with a jejunostomy formed as a route for
regarding which has better outcomes [11, 12]. In the study by enteral nutrition. Gastrostomy feeding can continue if
Zani et al. [9], results showed that 51% of surgeons perform colonic or jejunal interposition has been performed. Oral
gastric interposition, 36% colonic interposition, 9% jejunal nutrition is introduced as soon as possible, but supple
interposition and 4% gastric tube reconstruction. mentary overnight gastrostomy/jejunostomy feeds may
be indicated until an adequate intake is taken by mouth.
Oesophageal replacement procedures may have their prob
Gastric interposition
lems when feeding recommences. The advantage of the gas
In gastric interposition the whole stomach is mobilised and tric transposition is that there is only one anastomosis in the
moved into the chest. The proximal end of the oesophagus is gastrointestinal tract, but the stomach is now sited in a much
joined to the top of the stomach in the neck. Advantages of smaller place in the thorax than it usually occupies in the
this technique are that the blood supply is excellent, and abdomen. The volume of feed or meals that can be taken
only one anastomosis is required; therefore the rate of leak comfortably may be greatly reduced, imposing a feeding
age and strictures is low [11, 13]. Disadvantages of this tech regimen of little and often. The problem with colonic inter
nique, gastro‐oesophageal reflux (GOR), dumping syndrome position is that two areas of the gut have undergone surgery
(p. 155) and poor gastric emptying, are often seen in the and anastomosis. Over time the transplanted colon makes a
short term; and Barrett’s esophagitis may develop in the rather ‘baggy’ oesophagus because of the nature of its mus
long term [13]. A single institution review of gastric interpo culature, and the repaired oesophagus may not have normal
sition in 236 children (177 with OA) reported that more than peristaltic function. The colon may suffer temporary dys
90% of patients were highly satisfied with the procedure, function because of surgical trauma and malabsorption may
and there did not appear to be any long‐term deterioration ensue, necessitating a change to a hydrolysed protein feed
in function. Anastomotic leak was seen in 12% of patients, (Table 8.15). The end result of these most commonly used
strictures developed in 20%, delayed gastric emptying was a surgical interventions may be oesophageal continuity, but
problem in 8.9% and 3% developed dumping syndrome. not necessarily normal oesophageal function.
Post‐operatively, 55 patients (23%) had significant swallow
ing difficulties, of which 47% was classified as moderate and
53% severe. Follow‐up showed that height was normally Problems with oesophageal function following repair
distributed, and weight was in the lower centiles for age.
There was a 2.5% procedure‐related mortality rate [13]. Gastro‐oesophageal reflux
Gastro‐oesophageal reflux (GOR) is the most common
Colonic interposition gastrointestinal tract complication following repair, with a
reported incidence of 22%–45% [14–17]. Medical manage
Colonic interposition involves removing a piece of the colon
ment may include the administration of proton pump inhibi
and transposing it into the chest between the oesophagus
tors (PPI) and H2 receptor antagonists, the thickening of
above and the stomach below. The advantages are that the
fluids (Table 8.12) and positioning the baby appropriately
required length of the graft is available, and the diameter of
after feeding. PPI, e.g. omeprazole and lansoprazole, are rec
the lumen of the transposed colon is appropriate for joining
ommended as first‐line therapy for acid‐related GOR due to
to the oesophagus. The disadvantages of this procedure are
their acid blocking abilities. The reduction in gastric acid out
that the blood supply to the colon is poor; the transposed
put is beneficial as reflux is then less damaging to the oesoph
colon does not have very good peristaltic function to propel
ageal mucosa. If GOR is severe and unresolved by these
food down to the stomach; with time the transposed colon
methods, surgical correction may be considered by perform
may lose its muscular activity, and there is a high rate of
ing a fundoplication [17]. Literature suggests that a fundopli
anastomotic leaks and strictures [13].
cation is performed in 10%–45% of patients with OA [18].
Anti‐reflux operations may be either a partial (Thal,
Jejunal interposition
Toupet or Belsey) or a complete fundoplication (Nissen) [18].
The jejunum can also be used for oesophageal replacement. The choice depends on what the surgeon believes to be
This interposition has the advantage that the graft grows at a the best procedure for the individual child. The Nissen
Introduction 153
fundoplication is the most common and involves mobilising has undergone a primary repair in the first few days of life, a
the fundus of the stomach and wrapping it around the lower delayed repair or a staged procedure, a circular scar will
oesophagus, thus fashioning a valve at the junction of the form where the upper and lower segments of the oesopha
oesophagus and stomach. In particular children with long‐ gus are sutured together. With perfect healing the scar will
gap OA and recurrent anastomotic strictures may benefit have the same diameter as the oesophagus and will grow
from such surgery [17]. with the child. However, if there is a long gap between the
Anti‐reflux surgery is, however, not without its post‐ upper and lower oesophageal ends, the tissues will have
operative complications. Children who experience poor been stretched to meet, and the repair will be put under ten
motility and oesophageal clearance prior to the surgery may sion. This tension is thought to increase the risk of an anasto
find their symptoms get worse after a fundoplication. This is motic stricture developing. Some studies also suggest that
due to increased oesophageal stasis and decreased gravity‐ GOR is a major factor for recurrent anastomotic strictures, as
driven oesophageal clearance, which may also worsen the reflux of acidic stomach contents back up into the
respiratory symptoms, including aspiration. Therefore, the oesophagus can inflame the healing scar [17]. The presence
decision to perform a fundoplication for respiratory symp of an oesophageal stricture has been reported in 52% of
toms only should be made with caution [17]. Holschneider patients with GOR as opposed to 22% of patients with no
et al. [19] found that following fundoplication children with reflux [23].
OA had higher rates of post‐operative dysphagia and/or Other factors that have been suggested to influence stricture
stenosis than children without OA (17.2% vs. 6.5%). While formation include a reduced blood supply in the lower oesoph
preventing reflux into the oesophagus, the fundoplication agus following repair, the type of suture material used and the
may also stop the child from burping, and gas bloat can be suture pattern employed [6]. Allin et al. [8] reported that of 105
very uncomfortable in the stomach. Parents should be taught infants with OA/TOF, 39% had post‐operative complications
how to ‘wind’ their child through the gastrostomy tube if of oesophageal strictures within the first year of life, with most
they have one. Although the child should not be able to infants requiring multiple dilatations. Legrand et al. [14] had
vomit, they often experience severe retching, which is very similar findings, reporting that of 57 patients with OA and
distressing for both child and parent, but this usually disap TOF, 46% presented with anastomotic stenosis, which required
pears after a few weeks or months. Fundoplication can also dilatation. These strictures prevent the normal passage of food
cause dumping (p. 155). Sometimes the wrap performed with bread, meat, poultry, apple and raw vegetables being the
during the fundoplication weakens over time (commonly foods most often cited as getting stuck. Children with these
after 1.5–2.5 years but occasionally after a few months), and problems will often show difficulty in feeding and a reluctance
GOR returns. If this cannot be managed medically, the fun to swallow; they will choke and splutter. Strictures require
doplication has to be ‘redone’. It has been suggested that repeated dilatations to soften the scar tissue and allow the eas
between 20% and 45% of fundoplications fail [18]. Koivusalo ier passage of solid food [17]. The oesophagus may also go into
et al. [20] reviewed data from 262 patients with OA who spasm at the site of the anastomosis, and particular foods like
received fundoplication. In 31% of patients the fundoplica mince and peas may get stuck.
tion failed, with 15% undergoing a redo operation. The fail
ure rate was highest in those with long‐gap OA. Transpyloric Dysphagia
feeding may also reduce reflux and retching. Studies have
shown similar rates of reflux and retching between those Dysphagia is common in infants, children and adolescents
who had a fundoplication and those who received jejunal with OA following repair of the oesophagus. The reported
feeds [21]. incidence ranges from 21% to 85% and may remain a prob
lem for many years following repair [17, 21]. Little et al. [24]
reported that within a group of 69 patients with OA, 45%
Eosinophilic oesophagitis had dysphagia after 5 years, 39% at 5–10 years and 48% after
It is suggested that children with OA may have a higher risk more than 10 years, indicating that dysphagia may not
of developing eosinophilic oesophagitis (EoE) than the gen decrease over time. It has also been suggested that the
eral paediatric population [17]. One study of 103 patients incidence of dysphagia may be higher than that reported as
reported an incidence of 17% from the retrospective review children in particular may not identify their symptoms as
of biopsies, compared with 1 in 10 000 children in the general abnormal [17]. Children with OA will often eat very slowly
paediatric population. They also reported that the risk of or drink large quantities of water with their food. These and
developing EoE is much greater among those with long‐gap other significant changes to their eating habits have been
OA [22]. Possible reasons for the increased risk of EoE within reported in 73% of patients with dysphagia. The nutritional
the OA population include genetic associations, impairment management of dysphagia includes the adaptation of feed
of oesophageal mucosal barrier function by acid reflux and ing habits to help manage symptoms, and gastrostomy feeds
prolonged exposure to acid‐suppressive medication [17]. may need to be considered in some cases [17].
Feeding difficulties following surgical repair

Strictures
Anastomotic strictures are also a common post‐operative Prior to being joined up, the child will not have experienced
complication in OA [8, 17]. After repair, whether the child the sensation of a bolus of food passing the entire length of
the oesophagus. Although the child may have been exposed Adequate nutrition can usually be achieved with small fre
to sham feeding, this method of feeding does not always quent meals that are energy dense and the provision of fluids
lead to successful swallowing. Therefore, many children at mealtimes to help wash down the food. Such are the prob
panic when offered any food other than in liquid form, and lems associated with eating that families need help, advice
the establishment of normal feeding has to proceed through and encouragement from all professionals with appropriate
stages of gradually altering the consistency of foods, from experience, including dietitians, speech and language thera
purées to finely minced and mashed foods and then to a nor pists, clinical psychologists and medical and nursing profes
mal diet. The frightening experience of repeated choking sionals. The Tracheo‐Oesophageal Fistula Support Group
and/or possible delayed introduction of solids may lead (TOFS) is a self‐help organisation where carers of these chil
to fraught mealtimes that both parents and children come dren can share their experiences and offer advice.
to dread.
Feeding difficulties such as dysphagia, coughing, choking,
aspiration, vomiting during meals, food aversion, excessive Outcomes
fluid intake with meals and slow eating are seen in up to 75%
of patients with OA. The reasons for these may include dys Growth studies within the OA population are often limited by
motility, GOR, anatomic abnormalities, oesophageal outlet a lack of adjustment for comorbidities, e.g. cardiac, genetic or
obstruction, oesophageal inflammation, anastomotic steno neurological, which may have a large impact on growth. Early
sis, laryngeal clefts, vocal cord paralysis or paresis, neuro nutritional support and advances in neonatal and surgical
muscular dyscoordination and developmental delay in care of these infants and children have decreased the preva
swallowing function [17, 21]. Infants who are at risk of aspi lence of long‐term growth faltering in this population [17].
ration or those with retching or oropharyngeal dysphagia A review in 2006 of 15 children with OA and TOF who had
may benefit from a thickened formula [21]. primary repair at birth found that all were between the 50th
Menzies et al. [25] conducted a retrospective review of all and 75th centile of expected growth at 12 years of age [26]. A
75 children attending their multidisciplinary OA clinic from later review in 2012 of 57 children with OA and TOF (mean
2011 to 2014. Median age at initial appointment was 3.7 age 13 years) found that 75% had experienced normal growth
years. Twenty‐eight percent of children had an associated patterns, 9% of patients were underweight and 16% were
syndrome, and 96% had at least one associated gastroin overweight, according to weight/height z‐scores [14].
testinal or respiratory complication: most commonly GOR Vergouwe et al. [27] reviewed 96 children with OA at 5 years
disease in 87%, chest infections in 67% and EoE in 38%. of age (genetic syndromes associated with growth disorders
Twenty‐four children (32%) had a history of gastrostomy were excluded). Stunting (>2 SD below normal height for
feeding, and 10 children (13%) were still using their gastros age) was present in 5%–8% of children depending on their
tomy at the time of the initial appointment (median age 15 age, and wasting (>2 SD below normal weight for height) in
months). At the initial appointment 18% of children were 3%–12%. In children 1–8 years old, weight and height were
wasted (weight for age), 9% were malnourished (weight for significantly lower than the general population, but by
length/BMI), 9% were stunted (height for age) and 3% were 12 years of age, it had normalised in most children. Low
overweight. Results showed that infants had poorer growth birth weight and fundoplication were found to be negatively
than children >1 year old. Other risk factors for poor growth associated with growth.
included having had a fundoplication, those at risk of aspi Due to improvements in surgical and post‐surgical care,
ration or children who had had an additional surgery (other the focus of research in these patients has more recently
than OA repair) in the first year of life. Regarding eating been on quality of life (QoL) issues; OA is not just a neonatal
behaviour 54% of children did not consume age‐appropriate problem, but can often cause lifelong issues [17]. Ongoing
textures (most commonly seen in those <2 years old), 29% gastrointestinal problems are frequently reported in adults.
demonstrated extreme food selectivity (<20 foods in diet) Studies have found that 39%–85% of adults reported symp
and 25% had lengthy mealtimes (>45 minutes). Results may, toms of dysphagia and 29%–63% experienced symptomatic
however, be falsely elevated in this study as children were reflux [17].
reviewed from a specialist clinic and not a general OA popu Legrand et al. [14] studied 81 patients with OA and TOF
lation, therefore possibly containing a higher proportion of who were treated in their institution from 1989 to 1998. In
more complex cases. 2008, 57 of these patients returned for nutritional status,
Mealtimes can become very antisocial as choking and digestive and respiratory symptoms and QoL assessments.
vomiting are common when eating, and children may need The mean age was 13.3 years: 61% had dysphagia; 35% had
hefty pats on the back to dislodge food that has become GOR disease and only 19% of patients had no digestive
stuck. Eating can be a very slow process for the child, as symptoms. Their QoL was good but was lower than in
foods have to be thoroughly chewed before swallowing can healthy controls and was lower in patients born prematurely,
be attempted. Parents understandably feel inhibited about with symptoms of GOR disease and a barky cough. The
eating out of the home, which curtails the social experience association between complaints of dysphagia and GOR dis
of the child. It is often difficult for parents and carers to ease, oesophageal function and QoL was also investigated in
understand the problems with swallowing following repair 25 adults who had previously undergone correction of OA
of OA, and force feeding the child may be a temptation. [15]: 48% reported complaints of dysphagia and 33% of
Introduction 155
GOR. Manometry showed low oesophageal contractions in accelerated, the result is that hyperosmolar foodstuffs leave
20% of patients, and pH measurements showed pathological the stomach very rapidly and hence draw large quantities of
reflux in 14%. Patients reporting dysphagia more often had fluid into the small bowel. This produces the ‘early’ symp
disturbed motility and appeared affected by these symp toms of distension, discomfort, nausea, retching, tachycar
toms in their QoL. No association was found between QoL dia, pallor, sweating and dizziness. This may be associated
and GOR complaints. The authors’ hypothesis was that this with hyperglycaemia. ‘Late’ symptoms may occur from 1 to
may be because these patients had grown up with these 4 hours later as a result of hypoglycaemia and may be indis
symptoms and had got used to them. tinguishable from early symptoms [33].
Dellenmark‐Blom et al. [28] conducted a literature review
regarding health‐related quality of life (HRQOL) studies
Dietary interventions
among children and adults with OA. Overall HRQOL was
found to be reduced in five out of seven studies comparing There are no large studies on children with dumping syn
overall HRQOL in OA with a healthy reference population. drome, and most of the published papers are case histories;
Reports of the impact of OA on physical, psychological and all report it as difficult to treat. Various dietary interventions
social HRQOL differed between studies, and no conclusions have been tried to overcome the symptoms of dumping, but
could be drawn. no one treatment has been agreed on. The aim is to avoid
swings in blood sugar levels. Some children respond to a
combination of treatments. In summary these are:
Dumping syndrome
• giving small frequent meals [29, 33]
Following oesophageal replacement • taking fluids separately from solid foods [29, 34]
• avoiding a high glucose intake [29, 34]
Dumping syndrome is often seen in infants and young chil
• adding uncooked cornstarch to feeds at a concentration
dren following gastric transposition. Studies have shown
of 3.5%–7% [31] or 50 g/L of feed [35]
that children with OA often have abnormal gastric empty
• adding pectin to the diet: 5–10 g (<12 years) or 10–15 g
ing. This alone, or together with damage to the vagus nerve
(>12 years) divided into six doses [34]
during oesophageal anastomosis, is thought to cause dump
• administering continuous feeds with added fat (both
ing syndrome [17, 29].
long‐chain and medium‐chain fats are used) or small
Ravelli et al. [30] studied gastric emptying in 12 children
frequent meals enriched with fat [35–37]
who had undergone gastric transposition using electrical
impedance tomography. Gastric emptying was normal in one Borovoy et al. [38] described eight children with dumping
patient, delayed in seven and accelerated in four. Like the syndrome fed by gastrostomy and found that uncooked
repaired oesophagus, the transposed stomach does not cornstarch controlled glucose shifts, resolved most of the
behave normally. The stomach retains its function as a reser symptoms, allowed bolus feedings and enhanced weight
voir, but its emptying is extremely irregular. Spitz [29] found gain. A guideline for the administration of uncooked corn
that the dumping experienced in the early post‐operative starch could be taken from the treatment of glycogen storage
period was short lived, although it lasted for as long as disease (p. 612).
6 months in some children and recurred periodically in one
child. Michaud et al. [31] reported two children who under
went primary repair of their OA and presented a few months
later with dumping syndrome. Neither child had undergone Learning points: oesophageal atresia
anti‐reflux surgery nor had known precipitating factors. They
suggested that dumping syndrome can occur after primary • Surgical repair of the OA and/or TOF needs to be performed
anastomosis of OA without anti‐reflux surgery, and it should before oral feeding can commence
be considered in children with OA when they present with • The first choice in correcting OA is to preserve the native
gastrointestinal symptoms, faltering growth or refusal to eat. oesophagus and perform a primary repair
• Infants with long‐gap OA often have a delayed introduc-
tion of oral feeds and commonly experience more long‐term
Following Nissen fundoplication feeding difficulties than other children with OA
Dumping can also occur in children following Nissen fun • GOR, anastomotic strictures and dysphagia are common
doplication for severe GOR. Holschneider et al. [19] found post‐operative complications in children and adults
that following fundoplication dumping syndrome was seen • Infants should be weaned onto solids at the recommended
in 18.3% of children with OA post‐operatively compared age of around 6 months and weaning modified according to
with 1.6% in the non‐OA group. Pacilli et al. [32] measured tolerance and symptoms
gastric emptying in eight children before and after laparo • Other associated anomalies occur in 50%–66% of infants
scopic Nissen fundoplication. Their results showed that gas with OA, over 50% of infants with duodenal atresia, 23%
tric emptying was accelerated in all but one patient and of infants with Hirschsprung’s and 17% of infants with
concluded that gastric emptying for liquids is accelerated gastroschisis
following Nissen fundoplication. When gastric emptying is
Duodenal atresia successfully be managed without PN; however, in their

study a third of these infants received delayed PN and expe
Duodenal atresia (DA) is a cause of congenital intestinal rienced a significant decrease in weight z‐scores (from the
obstruction and occurs in about 1 in 10 000 births [39]. In time of surgery to full feeds being established), with poor
most cases the atresia occurs below the ampulla of Vater. catch‐up weight gain following discharge. This highlights
Radiography demonstrates the typical ‘double bubble’ of the the need for ongoing nutritional management and weight
dilated stomach and duodenum proximal and distal to the monitoring, ensuring that either feeds or PN is started soon
atresia. DA most often presents as bilious vomiting with after surgery, helping to optimise growth.
secreted bile unable to pass down the intestine. Less com Breastfeeding is often possible within a week of surgery. If
mon presentations include feeding difficulties, faltering bottle fed, EBM or standard infant formula should be given
growth, gastric distension, aspiration and delayed passing and, if administered correctly, should provide adequate
of meconium. The obstruction is corrected by cutting the nutrition. If weight gain is poor, the usual methods of feed
blind end of the duodenum and connecting it to the lower fortification can be used (Table 1.18). These same feeds
intestine. There are other anomalies associated with this should be used if enteral feeding needs to be continued.
atresia: Down’s syndrome, structural cardiac defects, tra
cheo‐oesophageal fistula, imperforate anus and malrotation Feeding problems post-surgery
occur in over 50% of infants with duodenal atresia [40, 41].
Mortality is related to the severity of the associated anoma The feeding problems following repair of DA are usually
lies, and the prognosis for this condition has significantly associated with the motility of the duodenum. In utero, the
increased since early 1970s. Mooney et al. [42] reported an duodenum proximal to the atresia is stretched because
improvement in survival from 72% in 1973 to 100% in 1983. ingested material cannot get past the atretic area of gut. The
Burjonrappa et al. [40] reported a 100% survival rate in a musculature may not function properly once the obstruction
review of 59 infants with DA born between 1983 and 2008. is removed, resulting in a baggy proximal duodenum. The
Choudhry et al. [41] reported a 96% survival rate in 61 infants infant may feed normally, but milk will accumulate in the lax
born between 1995 and 2004. duodenum rather than continuing its passage down the gut.
Following corrective surgery PN is often used to feed This can result in large vomits, up to 200 mL at a time. Feeds
these infants (p. 68), until enteral feeds are established. need to be small and frequent to overcome this problem.
Post‐operatively a nasogastric (NG) tube will be left on free If GOR is present, feeds can be thickened, and the baby
drainage, and once gastric aspirates decrease (indicating that should be positioned correctly after feeding. As the gut
the lower gut is patent), enteral feeds can commence via the grows and matures with the infant, problems should resolve
NG tube. PN is then titrated down as enteral feeds are slowly so that the older child should feed normally.
increased. Bairdain et al. [43] found that median time to
establish full enteral feeds was 12 days and that delayed
transition to full enteral nutrition was more likely to occur in Hirschsprung’s disease
patients who also had congenital heart disease, malrotation
or prematurity. A TAT may sometimes be passed post‐ Hirschsprung’s disease (HD), also known as congenital
surgery to help in the delivery of feeds [44]. In a study of megacolon or aganglionic megacolon, is a congenital disor
17 babies undergoing upper gastrointestinal surgery (10 with der where there is an absence of ganglion cells in the affected
DA, six with malrotation and one with jejunal atresia), part of the large intestine. This results in a loss of peristalsis
enteral feeding was started via transgastric transanastomotic and causes functional distal intestinal obstruction. In the
feeding jejunostomy tubes by day two post‐surgery in 14 majority of cases, only the rectum or sigmoid is involved, but
cases; the authors concluded that this method of feeding was in about 10% of infants, a longer segment of colon is affected,
well tolerated and preferable to PN [45]. However, complica which can often be the whole colon, referred to as total
tions have also been reported with the use of these tubes, colonic aganglionosis. A population‐based cohort study of
and they have been associated with increased time to reach all live born infants with HD born in the UK and Ireland
full feeds and/or longer hospital stay [44]. Bishay et al. [44] between October 2010 and September 2012 identified an
conducted a retrospective study of 54 children who under incidence of 1 in 5500 live births. Results showed that the
went surgery for DA (35 patients) and duodenal stenosis (19 male to female ratio was 3 : 1, and 23% of infants had an asso
patients). They found that in 19 children (35%) PN was com ciated anomaly. Of these 15% had a recognisable syndrome
menced within 3 days of surgery, 13 (24%) received delayed with Down’s syndrome being the most prevalent [46]. These
PN that was commenced on average 7 days post‐operatively results are similar to those reported from other studies [47].
and 22 (41%) never received PN. Children who never The aganglionic parts of the colon cannot pass faeces; there
received PN reached full feeds quicker and had a signifi fore, infants commonly present around 48 hours of life with
cantly shorter hospital stay than those who did receive PN. bilious vomiting, abdominal distension and failure to pass
At the last follow‐up (median 19 months), the children who meconium. Some infants and children can present later with
initially started PN and those who never started PN regained a history of constipation, abdominal distension, vomiting,
their baseline growth centiles, but those who received diarrhoea and/or poor growth [47]. Following diagnosis of
delayed PN had not yet regained their baseline centiles. HD, the initial supportive management would include either
They concluded that children with DA and stenosis can rectal washouts or the formation of a stoma to maintain
Abdominal Wall Defects 157
colonic decompression. A pull‐through procedure would Exomphalos

then be performed by resecting the aganglionic colon and
anastomosing the ganglionic bowel to the anorectum [46]. The overall incidence of exomphalos in England and Wales
Zani et al. [48] found that 33% of surgeons would perform a over the 7‐year period 2005–2011 was 1 in 2600 births. Thirty‐
pull‐through at diagnosis and 67% would delay this until the seven percent of these are isolated cases of exomphalos, 31%
infant was 4 months old or weighing >5 kg. Bradnock et al. occur with other anomalies and 32% with a chromosomal
[46] found that in 305 infants with HD, 86% were initially abnormality. The most common anomalies associated with
managed with rectal washouts and 13% with stoma forma exomphalos are Edwards’ syndrome, congenital heart defects
tion. Of those having rectal washouts, 27% failed this man and nervous system anomalies [52]. Springett et al. [52]
agement plan and required a delayed stoma. Therefore, a reviewed 234 infants born in England and Wales between 2005
total of 40% ended up requiring a stoma [46]. This study con and 2011 and found the overall 1‐year survival rate of all live
firms what other studies have shown that rectal washouts born cases was 84%. The 1‐year survival of infants born with
and then a primary pull‐through procedure has become the isolated exomphalos was 92% compared with 81% for those
preferred method of management [46, 48]. with multiple anomalies and 27% for chromosomal cases.
Following surgery many infants and children continue to An exomphalos can be small or large and occurs when the
have long‐term problems with bowel function. Jarvi et al. lateral folds of the abdominal wall fail to meet in utero, result
[49] assessed bowel function and gastrointestinal QoL ing in incomplete closure of the abdominal wall and hernia
among 92 adults with previously operated HD. These tion of the midgut. Not only bowel but also solid viscera like
patients reported increased incidence of inability to hold the liver, spleen, ovaries or testes may be exposed, contained
back defaecation (40% vs. 17% in controls), faecal soiling in a translucent membrane composed of amnion and perito
(48% vs. 22%), constipation (30% vs. 9%) and social problems neum. Surgery is necessary soon after birth to place the intes
related to bowel function (29% vs. 11%). Gastrointestinal tine and other organs back into the abdomen. If the exomphalos
QoL, however, was only slightly lower in the Hirschsprung’s is small, a primary closure can be performed: the bowel is
group than the control group. Collins et al. [50] studied QoL placed back inside the abdomen, and the abdominal wall is
in 60 children with HD (median age 6.4 years). They found then closed and a navel fashioned. If the exomphalos is too
that they experienced significantly lower psychosocial large for this procedure, a staged repair is performed. The
QoL and significantly higher levels of faecal incontinence exposed intestines and other organs are covered with a pros
compared with healthy children. Increasing age, increasing thetic mesh sac (‘silo’) to protect them. The silo is suspended
severity of faecal incontinence, constipation and dysfunc above the child and is tightened regularly as the intestine
tional elimination negatively affected QoL. However, there gradually moves back into the abdominal cavity by gravity.
were no significant differences in physical and total QoL The abdomen is then closed and a navel fashioned [53].
between healthy children and those with HD.
Most infants and children follow a normal diet and require
no dietary restrictions. However, Stathopoulos et al. [51] Gastroschisis
recently studied 10 patients who presented with long‐term
persistent faecal incontinence. Anatomical defects were The overall birth prevalence of gastroschisis is 1 in 2380 total
excluded and rapid intestinal transit was proven by nuclear births in the UK [54]. An increasing incidence has been seen
transit studies. Eight of these children (mean age 9.6 years) worldwide and is associated with younger maternal age, low
underwent a hydrogen breath test for fructose and/or socioeconomic status, poor nutrition, smoking and substance
lactose malabsorption and seven tested positive. Exclusion abuse [53, 54]. Gastroschisis is classified as either simple or
diets for protein allergens, lactose or fructose were then tri complex. Complex gastroschisis occurs in approximately
alled, and resolution or improvement in faecal incontinence 17% of cases and is commonly associated with at least one of
was seen in nine of the 10 children. This study suggests that the following: intestinal atresia, perforation, necrosis or vol
reactions to food may contribute to poor bowel function in vulus. In simple gastroschisis, none of the above associations
some patients and dietary restrictions should be considered are seen, and the bowel is intact, uncompromised and con
in those with rapid intestinal transit. tinuous [55]. A study of 301 infants with gastroschisis showed
In long segment Hirschsprung’s disease (the most severe a 96% survival rate after the first year of life [56].
form of HD), there is small bowel involvement. Resection of In gastroschisis, a rupture of the umbilical cord in utero in
all aganglionic bowel is necessary, often leaving the infant early pregnancy allows the intestine to escape outside the
with a shortened length of small bowel. The dietary manage abdominal wall; in this case, unlike in exomphalos, the intes
ment for this condition is as described for short bowel syn tine has no covering membrane. Surgical strategies for clos
drome (SBS) (p. 159). ing the defect consist of primary or staged and operative or
non‐operative techniques. In a staged closure, the defect is
Abdominal wall defects reduced by a preformed silo, and the abdomen is later closed
either with operative or non‐operative techniques [56, 57].
Exomphalos and gastroschisis are not abnormalities of the There is limited evidence or consensus between experts
gastrointestinal tract but are abdominal wall defects involv regarding which approach has more favourable outcomes. A
ing the exposure of the infant’s intestine, and in some cases study involving all 28 surgical units in the UK and Ireland
other organs, to the outside world. identified 393 cases of gastroschisis born between October
2006 and March 2008. Eighty‐five percent had simple gastro Kitchanan et al. [61] found that neonates with gastroschisis
schisis, 11.5% complex and 3% not categorised. Within the had significant delays in reaching full enteral feeds com
simple gastroschisis group, 51% of infants underwent opera pared with those with exomphalos (24 vs. 8 days) and
tive primary closure, and 36% staged closure after a pre required prolonged support with PN (23 vs. 6 days). The age
formed silo had been placed. Outcomes for infants with at which the infant with gastroschisis is first given enteral
complex gastroschisis were significantly poorer than those feeds affects the length of stay in hospital and the duration of
with simple gastroschisis [57]. Bradnock et al. [56] found PN; each day delay in starting enteral feeds was associated
that infants managed with preformed silos took on average with an increase hospital stay of 1.05 days and increased PN
5 days longer to reach full enteral feeding compared with duration of 1.06 days. Median day of first enteral feeds was
those managed with primary closure. Other outcome meas day eight post‐surgery (range 3–40 days) [58]. A follow‐up
ures for both groups were similar. study of 301 infants found that infants with complex gastro
schisis required PN for an average of 51 days, compared
with infants with simple gastroschisis who required PN for
Feeding the infant with abdominal wall defects an average of 23 days. Mean length of stay was 84 days for
complex gastroschisis and 36 days for simple gastroschisis
Impaired gastrointestinal function is common in infants [56]. Bergholz et al. [55] found that infants with complex gas
with abdominal wall defects, especially in those with gastro troschisis were started on enteral feeds later, took longer to
schisis. The pressure of the silo or the closed abdominal wall reach full feeds and therefore continued PN for longer than
forces the intestine back into the abdomen, but this continual infants with simple gastroschisis. Their risk for sepsis (pos
pressure may upset normal intestinal function, including sibly PN related), SBS and necrotising enterocolitis was also
intestinal motility, resulting in a prolonged functional ileus. higher. Infants with complex gastroschisis also had longer
Most of these infants will need PN (p. 68) for several weeks hospital stays and were more likely to be sent home on
or months before bowel function returns. enteral feeds and PN.
Enteral feeding is considered when bowel sounds return, A recent study of 50 infants with exomphalos found that 37%
and nasogastric aspirate has decreased. Expressed breast milk of infants with exomphalos major and 17% with exomphalos
or infant formula is usually tolerated if given as small fre minor still required nasogastric feeding at discharge [62].
quent boluses or as a continuous feed. Large boluses are not
tolerated as the intestinal tract is under constant pressure and
cannot accommodate a large amount of fluid at once. If the Outcome
baby can be handled normally and does not need to be nursed
flat, breastfeeding is possible. In one study 70% of babies with Henrich et al. [63] followed up 22 survivors of gastroschisis
gastroschisis were breastfed on discharge, 28% were bottle fed and 15 of exomphalos who were treated between 1994 and
and 2% were taking solids (median hospital stay was 24 days, 2004. Developmental delays were rapidly made up after
range 6–419 days) [58]. If there is malabsorption, then a hydro treatment, and 75% of these children had no gastrointestinal
lysed protein feed is indicated (Table 8.15). problems or suffered from these rarely. Most children were
Burge et al. [59] conducted a retrospective review of 111 of normal weight and height, with physical and intellectual
infants with gastroschisis. In 50 infants (45%), symptoms development delay seen in a third. The initial gastrointesti
suggesting non‐IgE‐mediated cow’s milk protein allergy nal problems and developmental delays were most often
(CMPA) were recorded and resulted in the feed being made up during the first 2 years of life, and, except for those
changed. Median age of diagnosis of suspected CMPA was with severe defects, the children had good QoL scores.
44 days. In 44 infants follow‐up data was available. All expe Fifty infants with gastroschisis were followed up at a
rienced improvement in symptoms after their feed was median age of 9 years (5–17 years); of these 10 infants 20%
changed to either an extensively hydrolysed formula, an had complex gastroschisis. Growth data was available for 42
amino acid‐based formula or breastmilk while the mother children. Most children showed significant catch‐up growth
was taking a cow’s milk protein‐free diet. The majority from birth to follow‐up. At follow‐up one child (2%) was
showed a significant reduction in symptoms within 2 weeks underweight, 10 children (24%) overweight and four chil
of this feed change. This study suggests that infants with dren (9.5%) obese. Bone mineral density was measured in
gastroschisis and symptoms suggestive of CMPA may ben 41 children, and results suggested that three children
efit by changing to a milk‐free formula. (7%) had significant bone density deficiency. Laboratory
A retrospective study of 79 infants with simple gastroschisis investigations showed the most prevalent micronutrient
found that those exclusively fed with breastmilk (28%) had a deficiencies were iron deficiency anaemia (12%), vitamin D
significantly shorter time to reach full enteral feeds (median 5 (13%) and vitamin B12 (6%, both children having lost signifi
vs. 7 days) and a shorter time to discharge after feeds where cant small bowel) and fasting cholesterol was elevated in
initiated (median 7 vs. 10 days) compared with non‐exclusive 24% of children, with no correlation to BMI. This study sup
breastmilk fed infants. Interestingly, the same benefits were ports what others have suggested that good catch‐up growth
not seen in infants receiving a mixture of breastmilk and for is seen in older children with gastroschisis [64].
mula, suggesting that the use of exclusive breastmilk is most Twenty infants with gastroschisis (four complex) born
beneficial for infants with simple gastroschisis [60]. between October 2006 and August 2011 were reviewed.
Introduction 159
Mean gestational age was 35.7 weeks and mean birth

Learning points: abdominal wall defects
weight 2.29 kg. Fourteen underwent primary closure,
and Hirschsprung’s disease
three silo reduction and three multiple staged closure.
Median duration of PN was 21.5 days and median time to
• In infants with exomphalos 37% are isolated cases, 32%
start feeds 7.5 days. Growth and development were
have a chromosomal abnormality and 31% have other
reviewed in 18 infants at 1 year of age. Weight was <10th
abnormalities
centile in 28% of children compared with 50% at birth, and
• Infants with gastroschisis have significant delays in reaching
there was no significant difference in development
full enteral feeds compared with those with exomphalos
between the study and control group. Infants born <10th
• Complex gastroschisis is associated with longer durations
centile for weight did however have significant receptive
of PN, delayed introduction of enteral feeds and longer hos-
and expressive language delay. This study suggests
pital stays than simple gastroschisis
that neurodevelopmental outcomes at 1 year of age are
• In Hirschsprung’s disease rectal washouts followed by a
associated more with being small for gestational age than
primary pull‐through procedure are the preferred method of
having gastroschisis [65].
management
Intestinal atresia occurs in 10%–20% of infants with gas
• Long‐term problems with bowel function are commonly
troschisis, and they may also develop intestinal necrosis.
reported in children and adults with previous operated
This may lead to SBS, the management of which is described
Hirschsprung’s disease
below.
Short Bowel Syndrome

Tracey Johnson
Introduction Although it is important, the length of remaining bowel is

not the only factor determining outcome; the quality of the
SBS is a collection of disorders where a loss of intestinal remaining gut, the site of resection, the presence or absence
length has occurred that compromises the ability to digest of the ileo‐caecal valve (ICV), the presence or absence of
and absorb nutrients. Accurate estimates of SBS incidence are colon, the primary diagnosis and any ensuing complications
difficult to determine due to variation in the definition of will also influence the prognosis.
SBS. SBS in children may occur at any age, but the majority of The key to survival after an extensive small bowel resec
cases result following extensive bowel resection in the early tion is the ability of the remaining bowel to adapt and take
neonatal period. Resection may be required in infants born over the functions of the resected segment of bowel.
with congenital abnormalities, e.g. gastroschisis, bowel atre Adaptation begins within 24–48 hours after resection. The
sias and malrotation, or in infants who develop necrotising remaining small bowel hypertrophies, increasing the surface
enterocolitis. In older children SBS may result from extensive area and the absorptive function. The absorptive functions
resection following volvulus, trauma, intestinal malignancy of the jejunum and ileum are given in Table 9.1.
or Crohn’s disease. Even in the absence of resection, children Although the jejunum is the site of absorption of the
may have conditions leading to a ‘functional short bowel’ majority of nutrients, the loss of jejunum is better tolerated
including long segment Hirschsprung’s disease, gastroschi than the loss of ileum. The reasons are as follows:
sis without resection and radiation enteritis.
• The ileum has a greater capacity for adaptation than the
After an extensive bowel resection, there are many factors
jejunum; the ileum can adapt and compensate for the
determining outcome. All these factors will have a bearing
absorptive functions of the jejunum, but the jejunum
on the management of the individual patient.
does not have the same potential for adaptation and can
Infants are born with a small bowel length of 250 ± 40 cm
not develop the specialist functions of the ileum, namely,
[66]. Loss of intestinal length results in loss of surface area
bile salt and vitamin B12 absorption
for absorption and loss of digestive enzymes and transport
• Transit time in the ileum is slower than in the jejunum,
carrier proteins, leading to malabsorption. In general, loss of
allowing luminal contents to be in contact with the
up to 50% of small bowel can be tolerated without any major
mucosa for longer periods of time
nutritional problems, and clinical features of SBS usually
• The ileum has the capacity to absorb fluid and nutrients
result when more than 75% of the small intestine has been
against an osmotic gradient, leading to favourable
resected. The small bowel length doubles in length in the last
absorption compared with the jejunum
15 weeks’ gestation, which gives preterm babies a physio
logical advantage as their bowel has great potential to The presence or absence of the ICV also has an important
increase in length [67]. part to play in determining outcome in patients with SBS.
Table 9.1 Absorptive functions of the jejunum and the ileum.

Learning points: factors determining outcome of short
Jejunum Ileum bowel syndrome
Glucose Vitamin B12 • length of bowel

Disaccharides Bile salts
• quality of bowel
Protein Fluid
Fat Electrolytes
• jejunum versus ileal resection
Calcium • presence or absence of ICV
Magnesium • presence or absence of colon
Iron • complications
Water soluble vitamins
Thiamin
Riboflavin
Pyridoxine
Folic acid diarrhoea and minimise complications. Nutritional therapy
Ascorbic acid
needs to be tailored to the individual child and is ideally
Fat soluble vitamins
Vitamin A managed by a multidisciplinary nutrition team comprising a
Vitamin D paediatric gastroenterologist, dietitian, pharmacist, special
Vitamin E ist nurse and biochemist.
The development of PN is the most significant factor in
the improved survival of children with SBS. PN assures
adequate balanced nutrition to maintain hydration and
nutritional status (p. 68) and allows time for intestinal
The valve slows transit time, which increases the duration of
adaptation to occur. Although PN provides essential fluid
contact of luminal nutrients with the mucosal surface and
and energy, prolonged exclusive PN can lead to complica
minimises fluid and electrolyte losses. It also serves as a bar
tions, so it is important to aim to give PN in the longer
rier to prevent bacterial overgrowth that can interfere with
term as nutritional support rather than as the total source
nutrient and fluid absorption.
of nutrition.
The colon has a crucial role in absorption of fluid and elec
Enteral feeds may not be nutritionally significant, but
trolytes. In patients with no or minimal colon in continuity,
intraluminal nutrients are the single most important factor
fluid losses slow progression with enteral feeds.
in promoting intestinal adaptation in SBS [75]. Trophic feeds,
Residual disease may worsen the prognosis of infants
which may be as little as 1 mL/hour, should therefore be
following small bowel resection, e.g. after resection for
commenced as soon as the post‐surgical ileus has resolved.
necrotising enterocolitis, the remaining bowel may not
Enteral feeds:
be of good quality. This may affect function and reduce
the potential for adaptation. A diagnosis of gastroschisis • promote pancreatic secretions, hormones and bile
may be associated with intestinal dysmotility resulting • are important in preventing intestinal failure related
in poor feed tolerance, even in infants with a good length liver disease [76]
of bowel. • may also help to prevent bacterial translocation [77]
Dependence on PN appears to be most governed by
Although children with SBS may require PN for long peri
the remaining intestinal length and absence of the ICV.
ods, there is potential for progression to full enteral nutri
This was first recognised by Wilmore in 1972 [68] and has
tion. Figure 9.2 illustrates the progression from parenteral to
since been confirmed by other studies [69–72]. It has also
enteral nutrition. Managing this transition is challenging as
been shown that enteral autonomy is more likely to be
progression can be both prolonged and unpredictable. As
achieved in patients with necrotising enterocolitis as
feeds are increased, PN can be reduced with the ultimate aim
their underlying diagnosis and when there is a multidis
of independence from PN. The process may take months or
ciplinary approach to intestinal rehabilitation [72–74].
even years to complete and can involve changing feeds and
Rehabilitation programmes utilise the skills of different
trials with trophic factors.
healthcare professionals important in managing intestinal
The ability to advance enteral feeds results from the pro
failure. Good education, individualised nutritional sup
cess of intestinal adaptation. There are various strategies that
port and early treatment of complications improve health
can help this process. As already discussed it is important to
outcomes and QoL.
put some feed into the bowel, and if the distal bowel is not in
continuity, this should include feeding stoma effluent into
Nutritional support a distal mucous fistula to maintain function. The recycled
proximal content stimulates mucosal growth, intestinal
The aims of management are to maintain nutritional status, adaptation and absorption and prevents atrophy of the
facilitate adaptation of the remaining bowel, control distal bowel [78]. There is an associated risk of sepsis due to
Nutritional Support 161
Intestinal resection
retrospective analysis of case series. As a result, in individual
centres, practices depend more on years of personal experi
ence than on research.
Malabsorption
Protein
Commence total Infants with SBS might be expected to benefit from an exten
parenteral nutrition
sively hydrolysed protein feed because of the insufficient
luminal surface area for digestion and absorption, but pro
tein digestion and absorption is completed in the upper small
Introduce enteral Continue parenteral gut and is generally not a significant problem in SBS. There is
nutrition nutrition probably little absorptive benefit from using amino acid‐
based or hydrolysed protein feeds [83], and complex proteins
Adaptation
may in fact be superior in stimulating adaptation. However,
Increase enteral Wean parenteral cow’s milk protein intolerance can occur in surgical neonates
nutrition nutrition and has also been reported in SBS, so there may be a role for
extensively hydrolysed protein or amino acid‐based feeds
when inflammation is present [84, 85]. Children with SBS,
Achieve enteral autonomy especially young infants, may have a risk of secondary non‐
IgE‐mediated intestinal allergic disease. Secondary protein
intolerance is a common phenomenon after mucosal injury
Figure 9.2 Progression from parenteral to enteral nutrition.
[86], and increased permeability to food antigens in SBS may
lead to an enteropathy or inflammatory colitis [87].
high levels of pathogenic bacteria in effluent samples, and it

is recommended the effluent should not be used beyond Fat
90 minutes from collection [79]. A similar compromise is needed when considering dietary
fat. LCT has the greatest potential for stimulating adaptation,
is a source of long‐chain polyunsaturated fatty acids and
Learning points: nutritional support essential fatty acids and has a lower osmolarity than medium‐
chain triglycerides (MCT). However, many children with SBS
• Nutritional support needs to be tailored to the individual have significant fat malabsorption, and feeds with a high
child content of LCT may result in steatorrhoea. In contrast MCT is
• Nutritional support requires the skills of a multidiscipli- water soluble and, therefore, efficiently absorbed. The disad
nary nutrition team vantage of MCT is its higher osmolarity, and experimental
• PN is essential to maintain hydration and nutritional evidence has shown that formulas containing MCT stimulate
status less intestinal adaptation than those containing LCT [88]. A
• Enteral feeds are the single most important factor in pro- mixture of LCT and MCT, to combine the physiological
moting adaptation and should be started early, although advantage of MCT and the positive effects of gut adaptation
they may provide insignificant nutrition from LCT, may be the best compromise [89].
Carbohydrate
Carbohydrate has the greatest intraluminal osmotic effect
Choice of feed but potentially can be well absorbed as brush border enzyme
activity can be induced according to the composition of the
The choice of nutrients may be important. Complex nutri feed. Feeds containing sucrose will induce sucrase, and those
ents, especially long‐chain triglycerides (LCT), stimulate containing glucose polymer will induce isomaltase [90]. The
adaptation better than simple nutrients, the hypothesis exception to this is lactose.
being that the more work the bowel has to do to digest a Monosaccharides need no digestion, but have a higher
nutrient, the greater the stimulus to adapt [80]. There is no osmotic load than polysaccharides. Just as with protein and
consensus regarding the best formula for infants with SBS. fat, it can be suspected that polysaccharides may stimulate
Two systematic reviews of nutritional therapies in paediatric intestinal adaptation better than monosaccharides. Intact
SBS showed the evidence was limited and of poor quality starch can also be fermented to short‐chain fatty acids in the
[81, 82]. There is a lack of randomised trials, and most human colon, stimulating sodium and water absorption and provid
data on the nutritional management of SBS are derived from ing a primary energy source for the colonocytes.
Breastmilk
Learning points: choice of feed
Breastmilk may not seem the ideal feed as it contains whole
protein and lactose; however, it is associated with good gas • Breastmilk is recommended when feeds are first introduced
trointestinal tolerance. In addition to the psychological ben • If breastmilk is not available or not tolerated, a protein
efits for the mother of using her breastmilk, it contains high hydrolysate feed with 50% fat as MCT is usually
levels of IgA, nucleotides, epidermal growth factor (EGF) recommended
and leucocytes [91]. Glutamine, LCT and growth hormone in • Amino acid‐based feeds are not indicated unless inflamma-
breastmilk may play a role in intestinal adaptation, and there tion is present
may also be benefits associated with protective colonic bac • Feed changes should be guided by stools/stoma fluid: quan-
teria. Importantly, studies have shown that the use of breast tity, consistency, reducing sugars, pH and fat
milk correlates highly with a shorter duration of PN and that • Modular feeds can be used to establish a feed that is
highly specialised formulas confer no advantage over breast tolerated
milk [92]. It is the practice in most centres managing infants
with SBS to use mother’s EBM in the initial stages of feeding.
In the early stages of enteral feeding, expressed milk is usu
Trophic factors
ally preferred so it can be given in the small measured
amounts that are tolerated, but breastfeeding can usually be
There are few studies conducted in infants and children
introduced when feed volumes are increased and if the
regarding trophic factors, and, like other aspects of manag
infant is at least 35 weeks’ gestation.
ing SBS, more controlled studies are required to justify their
widespread use. Their current use is based on trial and error,
but as a non‐invasive inexpensive intervention, a trial of pec
Formula feeding
tin or glutamine may be useful.
It is important to have a flexible approach to feeding, and Pectin is a water‐soluble fibre. In animal experiments pec
knowledge of gut anatomy and physiology allows informed tin has been shown to slow gastric emptying, slow transit
decisions about nutritional management to be made. In the through the small bowel and enhance adaptation. Following
absence of EBM, or when there is intolerance of EBM, the fermentation to short‐chain fatty acids by colonic bacteria,
most appropriate feed to try would be a protein hydrolysate pectin may also improve colonic absorptive function [94–97].
feed with approximately 50% of the fat as MCT [89]. Suitable Slower transit allows a longer nutrient contact time with the
feeds would be Aptamil Pepti‐Junior and Pregestimil Lipil intestinal mucosa, and in children with a preserved colon,
(Table 8.15). pectin may also stimulate water and sodium absorption [98].
As feed volumes are advanced, malabsorption frequently A dose of 1 g/100 mL feed has been suggested [99]. Pectin is
occurs. It may be helpful to formulate a feed to suit the indi no longer manufactured by pharmaceutical companies in
vidual child with a choice of ingredients not predetermined by the UK. Suitable products designed for use in the catering
the composition of a commercial formula. A modular feeding industry can be obtained and need to be free from added
system allows this flexibility giving a choice of protein, fat and sugar and tested for microbiological safety.
carbohydrate so that ingredients can be manipulated individu Partially hydrolysed guar gum has also been shown to
ally to find a feed composition that is tolerated. Modular feeds reduce stool frequency in children with SBS when added to
can be successfully used in the management of children with enteral feeds and solids [100].
SBS, leading to improved absorption, advancement of enteral Glutamine (available as Adamin G) is considered to be
feeds and ultimate independence from PN [93]. an important energy source for rapidly dividing cells such
Tables 8.21–8.23 show some of the components that may as the cells of the intestinal mucosa. The benefit is unclear,
be used in a modular feed. The protein source can be a whole but glutamine supplements may enhance adaptation,
protein, hydrolysed protein or amino acids. The carbohy have an anabolic effect on body tissues and improve
drate source may be polysaccharides, disaccharides (sucrose, enterocyte glucose absorption [101, 102]. The ideal dose is
lactose) or monosaccharides (fructose, glucose), and in prac unclear, but animal studies suggest that increasing the
tice a combination of carbohydrate sources may be beneficial glutamine content of feeds to 25% total amino acids may
so as not to saturate the capacity of a single brush border enhance adaptation [98].
enzyme. The ratio of LCT to MCT can also be manipulated to
tolerance. Electrolytes and micronutrients are added to make
Route of feeding
the feed nutritionally complete (Table 8.24). An example
modular feed is shown in Table 8.25.
Continuous tube feeding
Establishing a modular feed involves systematic stepwise
changes to feed concentration and volume. Careful descrip Infants and children with SBS frequently tolerate continuous
tion of volume and consistency of stools needs to be docu enteral feeds better than oral bottle or enteral bolus feeds. A
mented, and serial analysis of stool or stoma fluid for slow infusion of feed allows constant saturation of brush
reducing sugars, pH and fat is crucial to make informed border enzymes and carrier proteins, leading to improved
decisions about feed composition. absorption. Luminal nutrients are the single most important
stimulus for adaptation, so maximising the time during Cholestyramine

which nutrients are in contact with the intestine will opti
Resection of the terminal ileum can result in bile salt malab
mise the potential for adaptation. While continuous enteral
sorption. Bile salts are conjugated to bile acids by colonic bac
feeding can be associated with improved tolerance, exces
teria, leading to diarrhoea. Cholestyramine may help to bind
sive feeding by this route could lead to abdominal distension
the bile salts. Improvement will be seen within 24–48 hours.
and small bowel bacterial overgrowth if unabsorbed feed
collects in dilated bowel loops [103]. It is, therefore, impor
tant not to push feeds beyond the limit of tolerance. Growth factors
Growth factors can be used to facilitate intestinal adaptation
Oral feeding after surgery in patients with SBS, thus enhancing fluid, elec
Continuous feeding allows for maximum nutrient absorp trolyte and micronutrient absorption.
tion, but infants need to learn to suck, swallow and chew. Growth hormone has been used to promote intestinal
Small intermittent breast or bottle feeds should be initiated autonomy, but there is little evidence to support its use to
to maintain oral feeding skills and to lessen the likelihood of improve weaning from PN. Reduced dependence on PN has
feeding difficulties commonly seen in children who are tube been shown in some patients, but further evaluation is
fed for extended periods [104]. Oral feeding will also stimu required [101, 102, 106].
late gall bladder contraction and perhaps, therefore, contrib Teduglutide is an analogue of endogenous human gluca
ute to a reduced risk of intestinal failure‐associated liver gon‐like peptide‐2 (GLP‐2), which has recently been used in
disease. Oral feeding will also promote the release of EGF, the management of SBS. Following surgery, the concentra
increasing gastrointestinal secretion of trophic factors [105]. tion of endogenous GLP‐2 is decreased, which may contrib
Solids should be introduced at the appropriate time ute to the reduced digestive and absorptive function of the
around 6 months of age. There is no consensus on the type of remaining intestine. Exogenous GLP‐2, given by daily sub
solids offered, but it seems sensible when infants are receiv cutaneous injection, has been shown in adults to improve
ing a special formula that they are cow’s milk protein and fluid and nutrient balance by stimulating intestinal adapta
lactose‐free. There is no evidence to support the avoidance of tion [107]. Paediatric trials have shown teduglutide is well
other foods such as egg, gluten, wheat or disaccharides, but tolerated and is associated with a trend towards reduction in
in individual cases it may be necessary to exclude other PN requirement [108]. The National Institute for Health and
foods if intolerance is suspected. Care Excellence (NICE) is currently evaluating the benefits
and costs of teduglutide for national commissioning by NHS
England for adults and children with SBS.
Learning points: feeding route
Short bowel syndrome in older children
• Continuous feeding allows for maximum nutrient
absorption It has been estimated that 20% of SBS in the paediatric popu
• Oral feeding skills need to be maintained with intermittent lation develops outside of the neonatal period [109] and chil
breast or bottle feeds dren acquiring SBS require nutritional management and
• Solids should be introduced around 6 months of age enteral feeds appropriate to their age. A paediatric protein
hydrolysate feed with 50% fat in the form of MCT is often
used in this age group.
Children born with congenital abnormalities will usually
Pharmacological agents achieve enteral autonomy. Intestinal adaptation begins 24–48
hours after resection and can continue for up to 3 years. As
H2 receptor antagonists and proton pump inhibitors children get older, their feeds need to be reviewed regularly:
Gastric hypersecretion frequently occurs after massive bowel feeds need to be age appropriate and always given at the
resection. This will increase gastric aspirates and stool and maximum level of tolerance. Children often have voracious
stoma output but more importantly can impair absorption by appetites, particularly after PN is stopped, and will consume
inactivation of pancreatic enzymes. Treatment with drugs vast amounts of food to compensate for malabsorption. It is
such as ranitidine and omeprazole is frequently required. often impossible for children to consume adequate nutrition
Gastric hypersecretion is a transient phase, and treatment in their waking hours, and for this reason overnight tube
with these drugs should cease once hypersecretion has feeds are often continued to provide additional nutritional
resolved; it is important to restore an acid environment in the support via nasogastric tube or gastrostomy.
stomach to inhibit the growth of microorganisms.
Weaning from parenteral nutrition
Anti‐diarrhoeal agents
The transition to full enteral nutrition may take many
Loperamide can be used to slow transit time and control months or years to complete, but the majority of children
diarrhoea. with SBS can eventually be weaned from PN. It is important
to always provide the maximum amount of enteral nutrition develop symptoms of nausea, bloating, vomiting and diar
and minimum amount of PN while maintaining hydration rhoea resulting from nutrient malabsorption and an
and nutritional status. This requires careful adjustment as increased number and/or type of bacteria in the small intes
advancing enteral nutrition too quickly will result in malab tine [119]. It can be controlled with antibiotics that are fre
sorption and osmotic diarrhoea. In this circumstance feeds quently given in ‘cycles’, changing the antibiotic given at
can be reduced to the level at which they were tolerated and regular intervals.
attempts made to advance again in subsequent days and d‐Lactic acidosis presents as a severe metabolic acidosis
weeks. Failure to attempt to advance feeds may lead to with neurological manifestations that can include slurred
longer dependence on PN with the risk of associated speech, ataxia, irritability and drowsiness. In patients with
complications. SBS carbohydrates can reach the colon in undigested or
As feed tolerance improves PN can usually be reduced. partially digested form and are fermented there to produce
Initially the number of hours on PN and the volume infused organic acids. This results in a progressive decrease in
are reduced, aiming to deliver the PN at night over 12–14 intraluminal pH, which favours the overgrowth of acid‐
hours. With time it is usually possible to reduce the number resistant bacteria such as Lactobacillus acidophilus. These
of nights children receive their PN, providing adequate bacteria produce d‐lactate, which is poorly metabolised in
enteral fluid is tolerated to maintain hydration. Careful humans. Antibiotic treatment can resolve the acidosis by
monitoring is required during the period of transition both treating the bacterial overgrowth, but it may also be neces
to ensure optimal growth and to prevent micronutrient sary to modify the type and/or amount of carbohydrate in
deficiencies. the diet.
Complications Monitoring
Intestinal failure‐associated liver disease Monitoring is an important part of the management of chil
dren with SBS receiving PN and is even more important as
PN has improved the outcome for children with SBS, but
they are weaned from PN. As previously mentioned assess
paradoxically it is associated with many potentially fatal
ment of stool output is crucial to monitor feed tolerance. This
complications. These complications include intestinal fail
is the best indicator to assess the potential to increase enteral
ure‐associated liver disease (IFALD). The prevalence of
feeds and reduce PN.
IFALD is unknown. Two cohort studies report an incidence
Serial anthropometric measurements are useful to evalu
of 22%–23% [110, 111], but an incidence of 40%–60% of chil
ate nutritional status and track progress. These should
dren on long‐term PN has also been reported [112]. The
include not just weight and length but head circumference,
cause of liver disease in children on PN is multifactorial with
mid‐upper arm circumference and skinfold measurements.
risk factors including:
Nutritional blood tests are also needed. Micronutrients
• prematurity [113] may be poorly absorbed, and deficiencies are commonly
• nutrient excess seen in children who are weaning from PN and in those who
• bacterial infection [114] are exclusively enterally fed. The most common deficiencies
• failure to tolerate enteral feeds [115] seen are fat‐soluble vitamins, calcium, magnesium, zinc,
• failure to establish continuity of the gut iron and selenium. Oral supplements should be started to
avoid clinical signs of deficiency.
Prevention and management of IFALD involves aggressive
Vitamin B12 receptors are restricted to the terminal ileum,
use of enteral nutrition, prevention of line sepsis, the use
and if this has been resected, children will require lifelong
of ursodeoxycholic acid and ‘cycling’ of PN to reduce the
injections of B12 to prevent deficiency. Regular monitoring is
number of hours, or days, that a child receives PN (p. 67).
needed to assess the appropriate time for commencement of
There has been recent interest in the use of novel intrave
vitamin B12.
nous lipid sources containing fish oil to treat IFALD. There
Sodium depletion can also occur in children with either
are no randomised controlled trials looking at these lipid
high stoma output or watery diarrhoea and is a common
sources (SMOF lipid, Omegaven), but several case series
cause of poor weight gain. Urinary electrolytes are a good
report reversal of cholestasis and suggest a potential
indicator of sodium status and should be measured regu
benefit in preventing and treating IFALD in young children
larly, aiming to maintain a urinary sodium concentration
[116–118].
>20 mmol/L and a sodium–potassium ratio of approxi
mately 2 : 1.
Small bowel bacterial overgrowth and d‐lactic acidosis
Small bowel bacterial overgrowth (SBBOG) occurs com Home parenteral nutrition
monly in SBS. It results from anatomical and physiological
changes associated with the condition where there is dilata Many children with SBS can eventually be weaned from PN.
tion of the small bowel associated with the adaptation pro However, if PN is required for extended periods of time,
cess and changes in motility. Patients with SBBOG typically it is appropriate to continue the treatment in the home
environment, and there is good evidence that catheter sepsis who can be safely managed on PN with low mortality and
is reduced when children are discharged home [120] and good QoL [121, 125].
mortality is low [121]. The graft usually comes from a size‐matched child that
results in a long waiting time on the transplant list. The small
bowel can be transplanted alone or with the right colon if the
Surgery disease also involves the colon; this occurs in congenital
enteropathies and motility disorders rather than SBS.
Non‐transplant surgery Combined liver and small bowel transplant is necessary in
A number of surgical interventions have been tried to alter cases of intestinal failure‐associated liver disease [126].
intestinal transit and promote adaptation in children with Feeding protocols vary between transplant centres, but
SBS. The aim of surgery is not only to improve nutrient enteral feeds are commenced as soon as possible and deliv
absorption by increasing food contact time with the intesti ered either into the stomach or, if necessary, into the jejunum.
nal lumen but also to reduce stasis and bacterial overgrowth. The lymphatic circulation of the graft takes time to re‐estab
Procedures require a dilated segment of small bowel to be lish, and a feed containing at least 50% MCT is recom
present and include longitudinal intestinal lengthening and mended. There is a risk that food antigens may increase the
tailoring (Bianchi procedure) and serial transverse entero risk of acute graft rejection, so protein hydrolysate feeds are
plasty procedure (STEP) [122, 123]. usually used initially [127], but normal diet and independ
ence from nutritional support is possible.
Transplant surgery
Learning points: longer‐term management
Some children who develop end‐stage liver disease as a
result of IFALD, but have the potential to eventually achieve • Home parenteral nutrition is the treatment of choice
independence from PN, may benefit from isolated liver • Enteral feeds should be reviewed regularly and always
transplantation [124]. given at the maximum level of tolerance as most children
Small bowel transplantation has developed over the past can be weaned from PN
20 years to become a lifesaving option for children with SBS • Monitoring of anthropometry, nutritional biochemistry,
who develop the complications of intestinal failure. For chil stool/stoma output and sodium balance is essential
dren with an extremely short bowel, permanent intestinal • Monitoring for associated complications is important
failure is almost inevitable. Long‐term PN remains the treat • Bowel lengthening procedures can alter intestinal transit
ment of choice for this group, but intestinal transplantation and promote adaptation
may be indicated for those children who develop irreversi • Small bowel transplant may be indicated when irreversible
ble liver disease or impaired venous access. In 2015 the complications occur, and home PN is no longer possible
International Transplant Registry reported on 3067 patients,
including 1697 children: the 10‐year graft survival was
40%–60%. Advances in surgical techniques and immuno
suppression have improved the outcome of intestinal trans
plantation with a consistent improvement in the survival of
children transplanted within the last 10 years, but the sur
vival rate does not yet justify transplantation for children
10
Sara Mancell
The Liver and Pancreas
The Liver
Introduction while MUAC and TSF measurements can be useful measures

of nutritional status as they are not affected by organomeg-
The nutritional management of an infant or child with liver aly or ascites.
disease depends on whether the disease is acute, chronic or
metabolic. Potential problems warranting nutritional
attention occur when there is a disturbance in the usual Biochemistry
metabolic functions of the liver. These include glucose
homeostasis, protein synthesis, bile salt production, lipid Liver function tests and other blood tests routinely used to
metabolism and vitamin storage. Dietary therapy is pri- investigate the liver are described in Table 10.1.
marily aimed at managing the consequences of these
disturbances.
Clinical
Nutritional assessment The clinical assessment of a child with liver disease should
include signs of malnutrition (muscle wasting), cholestasis
Patients with liver disease require regular nutritional assess- (dark urine, pale/oily stools, micronutrient deficiencies), the
ment. The frequency of assessment is determined by the clinical condition, the presence of ascites or organomegaly
stage and severity of liver disease, the age of the child and and the impact of medications on nutrition, e.g. cholesty-
nutritional status. ramine. Scans and procedures commonly used in the clinical
assessment of a child with liver disease are described in
Table 10.2.
Anthropometry
Children with liver disease require frequent measurements Dietary

of weight and height and head circumference if under 2
years of age. As organomegaly and ascites may affect weight Dietary assessment should explore how symptoms of liver
measurements in liver disease, additional measures such as disease may be impacting on intake, absorption and
abdominal circumference, mid‐upper arm circumference utilisation of nutrients. Examples of symptoms that may
(MUAC) and triceps skinfold (TSF) should be included in cause nutritional difficulties include nausea, vomiting,
the assessment (p. 3). Abdominal circumference measure- diarrhoea, pale/oily stools, pruritus (itching), organomeg-
ments can be used to help interpret weight measurements, aly and ascites.

Table 10.1 Blood tests used to investigate the liver.
Test Reference range* Explanation
ALP Alkaline phosphatase 62–209 IU/L An enzyme found in the osteoblast cells of the bone and in liver cells. It is
excreted via the biliary tract. High levels can indicate bile duct inflammation;
however, as it is not specific to the liver, abnormal levels can be due to
processes occurring in other parts of the body (e.g. raised due to bone growth)
ALT Alanine transaminase 5–55 IU/L An enzyme predominantly found in the liver. Used to detect hepatocellular
injury. It is most specific in the detection of acute hepatitis from viral, toxic or
drug induced causes. The serum level can rise to 20 times the normal level in
these cases. The level may be mildly to moderately elevated in cases of
obstructive jaundice, cirrhosis and liver tumours
AST Aspartate transaminase 3–35 IU/L An enzyme found in the heart, but also highly concentrated in the liver. A raised
AST can indicate liver inflammation. Isolated increases are more characteristic of
hepatitis. A raised AST in a transplanted patient may indicate rejection
GGT Gamma‐glutamyl 1–55 IU/L A biliary enzyme found in the kidney, liver and pancreas. High levels can
transferase indicate bile duct inflammation or obstruction. It can provide information
about bile production
APPT Activated partial 0.85–1.15 ratio A medical test of blood clotting. Also used to monitor treatment effects with
thromboplastin time heparin, a drug that reduces blood’s tendency to clot
INR International 0.9–1.20 ratio A measure of the time needed to form a clot. Clot formation is dependent on
normalised ratio coagulation factors, of which four are dependent on vitamin K. Raised levels
may mean there is less vitamin K due to obstructive jaundice or poor utilisation
of vitamin K due to liver damage
Bilirubin 3–20 μmol/L Raised unconjugated bilirubin occurs when the liver is unable to conjugate the
bilirubin, usually due to excessive red blood cell haemolysis. Raised
conjugated bilirubin is where the total serum bilirubin is raised and the
conjugated fraction is >20% of the total bilirubin (normally <5%). Raised
conjugated bilirubin indicates reduced flow of bile out of the liver
Albumin 35–50 g/L This is the major circulating protein and is synthesised in the liver. It is
responsible for maintaining plasma osmotic pressure. Hypoalbuminaemia is
found in advanced chronic liver disease. Low levels may be due to decreased
synthesis in the liver or through losses in the stool
Total protein 60–80 g/L A test used to determine the concentration of protein in the plasma. Liver
disease is one source of abnormal values, but there are many more
Globulin 25–35 g/L This refers to a group of globulin proteins. The two affected by liver disease are
alpha globulin and gamma globulin
AFP Alpha‐fetoprotein <7k IU/L These levels are useful in the diagnosis of primary hepatocellular cancer
because only primary liver tumours secrete AFP
Cholesterol 1–5 mmol/L Levels may become increased in chronic biliary obstruction, especially
intrahepatic bile duct hypoplasia
Ammonia 12–50 μmol/L Ammonia is formed from protein metabolism and protein degradation by
colonic bacteria. The liver converts ammonia to urea. Increased levels indicate
that there is liver damage or an underlying metabolic condition
Bile acids <14 μmol/L Bile acids are formed in the liver from cholesterol, enter the intestine via bile
and are reabsorbed into the portal circulation and returned to the liver. In liver
disease serum levels may be high because of reduced hepatocytes (which are
able to extract bile acids from the blood) or shunting of blood past hepatocytes
* Ranges may vary according to age.
Learning points: nutritional assessment of liver disease • Clinical assessment of the child with cholestasis should
include assessment for jaundice, dark urine, pale/oily stools
• Nutritional management will depend on whether the liver and micronutrient deficiencies
disease is acute, chronic or metabolic • Dietary assessment should explore how liver disease
• Measurement of MUAC, TSF and abdominal girth may aid symptoms impact on nutrition
in assessment where there is organomegaly or ascites
168 The Liver and Pancreas
Table 10.2 Common liver investigations.
Procedure Description
Liver ultrasound Non‐invasive scan measures dimensions of the liver, spleen, portal vein, gallbladder, cysts, stones
or tumours. Blood flow in portal vein, hepatic artery and hepatic veins can be assessed using a
Doppler attachment
HIDA (hepatobiliary iminodiacetic acid) scan A dye is injected by nuclear medicine and a series of scans are then performed to examine bile
excretion
CT (computerised axial tomography) A 2D scan of the liver and any focal lesions, e.g. tumours, abscess, cysts or bleeding. A radioactive
dye may be injected to demonstrate gastrointestinal tract, blood vessels, bile ducts and kidneys
MRI (magnetic resonance imaging) A 3D scan using magnetic frequency to obtain cross‐sectional images of the liver
Liver biopsy A small piece of liver is taken with a needle and sent for analysis
PTC (percutaneous transhepatic Dye injected under X‐ray control showing the flow through the liver and biliary tracts to evaluate
cholangiography) biliary duct obstructions. Debris and stones can be flushed out
ERCP (endoscopic retrograde cholangio‐ An endoscope is passed through to the duodenum and contrast medium is injected into the
pancreatography) common bile and pancreatic ducts to examine the structure and identify obstructions/narrowing/
debris/stones. It can help diagnose problems such as sclerosing cholangitis or pancreatitis
MRCP (magnetic resonance cholangio‐ A 3D scan of the hepatobiliary and pancreatic systems including the liver, gallbladder, bile ducts,
pancreatography) pancreas and pancreatic duct
Angiography An invasive test that uses an injection of contrast medium to visualise the hepatic artery, portal
venous system and intrahepatic vessels
Transient elastography (FibroScan®) A non‐invasive procedure assessing how elastic (or how stiff) the liver is. An ultrasound probe is
used to create a 2D picture of the liver. The level of fibrosis can be measured in relation to the
stiffness of the liver (with increased stiffness indicating more fibrosis)
HARI (hepatic artery resistance index) Used to evaluate portal venous blood pressure. A low HARI indicates reduced arterial blood flow,
which may result from hepatic artery narrowing. A high HARI may result from chronic
hepatocellular disease or transplant rejection
Paracentesis (ascitic tap) A needle is used to drain ascitic fluid. A therapeutic tap is done where ascites stretches the
abdomen, causing discomfort/distress/increased work of breathing. A diagnostic tap is where the
fluid is sent for testing (i.e. for infection)
Acute liver failure Common causes of ALF include:

• infective, e.g. hepatitis A, B or C and cytomegalovirus
Acute liver failure (ALF) is the severe and sudden impair- (CMV)
ment of liver function. Damaged liver cells secrete sub- • IMD, e.g. haemochromatosis, galactosaemia and
stances that initiate a cascade of events resulting in tyrosinaemia
multi‐organ failure [1]. The presence of hepatic encepha- • toxins/drugs, e.g. chemotherapy and paracetamol overdose
lopathy (HE) may indicate ALF in adults, but is a less use- • irradiation, e.g. radiotherapy
ful marker in children as it is difficult to detect [1]. A • ischaemic, e.g. Budd–Chiari syndrome
definition developed by the Paediatric Acute Liver Failure • infiltrative, e.g. leukaemia
Study Group (PALFSG) removes the need for HE to be • autoimmune, e.g. autoimmune hepatitis and autoim-
present [2]: mune sclerosing cholangitis
• a high PT (prothrombin time) (20 seconds) or INR (1.5) • trauma, e.g. non‐accidental injury, fall from horse/
not corrected by vitamin K in the presence of HE or an bicycle and seat belt laceration
INR >2 regardless of whether there is HE Common symptoms of ALF by disease and age group are
• evidence of acute liver injury shown in Table 10.3.
• no known chronic liver disease (CLD)
It can be difficult to determine the cause of ALF, particularly Clinical management
in infants with inherited metabolic disorders (IMD) as the
liver may be sufficiently damaged to produce secondary If the onset of ALF is rapid, there is a possibility of the
biochemical abnormalities [3]. A thorough investigation is critical life‐threatening complication of cerebral oedema,
necessary although a cause for ALF is not always found. In requiring treatment in intensive care. For those with
one study, a cause was not determined in 47% (n = 329) of increasing levels of bilirubin, INR and APPT, despite
cases [4]. declining AST (which at this stage often indicates
Acute Liver Failure 169
Table 10.3 Common clinical symptoms at first presentation of ALF by restriction (⅔ maintenance) is generally used to avoid cere-
age group. bral oedema. Dietetic management is focused on avoiding
hypoglycaemia, avoiding the build‐up of toxic by‐products
Age group Common symptoms Possible disease
of metabolism and maintaining nutritional status until there
Neonate Hypoglycaemia Neonatal iron storage disease is some clinical improvement.
Jaundice Inborn error of bile acid A child with a suspected IMD may be protein restricted
Poor feeding synthesis initially, aiming for full requirements in the first 24–48 hours
Vomiting Alpha‐1‐antitrypsin depending on advice of the metabolic team. Where a disor-
Diarrhoea deficiency
der of amino acid metabolism is diagnosed, the metabolic
Lethargy Niemann‐Pick type C
Sepsis Galactosaemia
team will advise on the upper tolerable limit of the offending
Lactic acidosis Tyrosinaemia amino acid to limit toxic by‐products. In practice, a standard
Haemolysis Glycogen storage disease formula or feed is usually used to provide up to the first 1 g/
Hypotonia kg protein. Glucose polymer is added to meet the glucose
Seizures oxidation rate (Table 10.5).
Liver failure The nutritional requirements in ALF are outlined in
Infant Hypoglycaemia Fructosaemia Table 10.5.
Jaundice Cystic fibrosis
Faltering growth Progressive familial
Vomiting intrahepatic cholestasis Hypoglycaemia
Fever Alpha‐1‐antitrypsin
Cataracts deficiency Hypoglycaemia may be present in 40% of patients with ALF
Hepatosplenomegaly Alagille’s syndrome [5] due to increased plasma insulin levels secondary to
Deranged liver
function tests
reduced glucose uptake and gluconeogenesis. The aim in
Chronic liver disease ALF is not only to avoid hypoglycaemia but also to help
prevent catabolism (and the associated accumulation of toxic
Child/ Hepatomegaly Wilson’s disease
adolescent Faltering growth Autoimmune hepatitis
metabolites). In the presence of hypoglycaemia, if there is no
Developmental delay suspicion of an IMD, a standard or high energy feed may be
Short stature started (depending on whether fluids are restricted), and a
glucose polymer may be added if blood sugar levels are low.
If normoglycaemia cannot be achieved by continuous feed-
increasing hepatocyte necrosis), there is a poor prognosis. ing, or it is contraindicated, a continuous intravenous (IV)
These patients may be placed on the super urgent liver dextrose infusion is started. Once feeds are commenced,
transplant (LT) list. LT is the only proven treatment that they may then be gradually titrated against the IV infusion.
may improve outcomes in ALF [1]. Table 10.4 illustrates If an IMD is suspected, an emergency regimen (ER) is
the biochemical profiles of two different presentations of started (p. 673) using either IV dextrose or a glucose polymer
ALF. These examples show the blood biochemistry results added to water for enteral use. Following the ER phase, a
in the days prior to and at 1‐week post‐LT when there is a suitable formula can be used for the suspected condition on
return to normal (or near normal) levels. the advice of the metabolic team. Glucose management for
ALF is as described in Table 10.6.
Learning points: clinical management of ALF
Hepatic encephalopathy
• The definition by PALFSG removes the need for HE to
diagnose ALF HE is where there is brain dysfunction ranging from minor
• It can be difficult to determine the cause of ALF and often a changes such as confusion to coma. As it is due, in part, to
cause is not found altered ammonia metabolism, treatment aims to reduce
• Liver transplant is the only proven treatment that may ammonia production and absorption from the gut. Almost
improve outcomes in ALF half of the body’s ammonia is endogenously produced by gut
flora and is primarily managed with medical interventions
(e.g. sodium benzoate). A dietary protein restriction is not
recommended [1] as it could result in increased endogenous
Dietetic management ammonia production from protein catabolism. Sufficient
energy from other macronutrients needs to be supplied with
The clinical presentation of ALF varies and requires specific close consideration to the protein–energy ratio to prevent
dietary treatment. If presentation is rapid, infants and chil- protein breakdown. Branched chain amino acid (BCAA) sup-
dren are often well nourished. In children with severe ALF, plementation may be beneficial in encephalopathy as BCAAs
nutrition support will be managed in the intensive care unit, detoxify ammonia and limit the efflux of aromatic amino
and adjustments to ventilation, sedation and fluid allowance acids across the blood–brain barrier [6]. BCAAs are discussed
will be needed. If there is no evidence of dehydration, a fluid further in the section on faltering growth in CLD.
Table 10.4 Examples of biochemistry results pre‐ and post‐liver transplant.
3‐year‐old female unknown aetiology 10‐year‐old male unknown aetiology
1 week 1 week
Day 1 Day 2 Day 3 post‐LT Range Day 1 Day 3 Day 5 post‐LT Range
Albumin 31 25 24 46 35–50 g/L 30 26 26 35 35–50 g/L

Bilirubin 330 300 344 38 3–20 mmol/L 268 291 327 47 3–20 mmol/L
AST 1140 328 474 80 8–43 IU/L 1513 894 469 100 7–36 IU/L
GGT 35 32 34 76 1–55 IU/L 66 55 55 218 1–55 IU/L
ALP 315 312 350 106 129–291 IU/L 830 783 802 138 120–488 IU/L
ALT 1763 944 750 – 5–55 IU/L 1931 – 940 – 5–55 IU/L
INR 3.04 7.6 8.75 1.10 0.9–1.2 ratio 2.76 4.60 3.40 1.18 0.9–1.2 ratio
APPT 1.590 2.060 2.230 0.970 0.85–1.15 ratio 1.51 1.60 1.65 1.02 0.85–1.15 ratio
Ammonia 122 – 140 – 12–50 μmol/L 108 126 164 – 12–50 μmol/L
LT, liver transplant; AST, aspartate aminotransferase; GGT, gamma‐glutamyl transferase; ALP, alkaline phosphatase; ALT, alanine aminotransferase;
INR, international normalised ratio; APPT, activated partial thromboplastin time.
Table 10.5 Nutritional requirements in acute liver failure. Table 10.6 Glucose management in ALF.
Energy 120%–150% EAR Steps to take

Intensive care: basal metabolic rate with/without stress 10–20%* IV dextrose is started immediately
factors depending on ventilation If no IMD is suspected
Glucose Glucose oxidation rates: • If able to feed give standard/high energy feed ± glucose polymer and
wean IV fluids
• Infants: 8–9 mg/kg/min
• Toddlers and children: 7 mg/kg/min If IMD is suspected
• Adolescents: 4 mg/kg/min • Glucose polymer in water or oral rehydration solution may be used
Protein 100%–120% RNI (avoid excessive protein) • Once able to feed give suitable formula on advice of metabolic team
If severe ALF may need to limit to 1.5 g/kg Increase the amount of glucose slowly according to tolerance
If inherited metabolic disorder (IMD) suspected: Monitor blood glucose hourly and then 4 hourly once stable
• Start at 0.8–1 g/kg and increase according to metabolic team Aim for target blood glucose level of 4–8 mmol/L
• May need to avoid specific amino acids Example: Formula‐fed infant weighing 3.5 kg, fluid restricted to
Fat If no IMD meet age‐appropriate requirements 100 mL/kg on intensive care
If IMD suspected maximise according to metabolic team Give 100 L/kg of 12.5% dextrose via a central vein until feeds start
recommendations Start high energy feed and gradually titrate with IV fluids
If cholestatic use age appropriate medium chain triglyceride If blood glucose <4 mmol/L either add 1%–3% glucose polymer to feed
formula (Table 10.9) (1–3 g/100 mL of feed) or increase dextrose concentration in IV fluids
EAR, estimated average requirement; RNI, reference nutrient intake. * Dextrose concentrations >10% require central venous access due to
risk of thrombophlebitis.
Dietetic management
Learning points: dietetic management of ALF
• The ER should be initiated, if necessary, aiming to keep
blood glucose levels between 4 and 8 mmol/L (and • Children with ALF are often well nourished if presentation
meeting the glucose oxidation rate) is rapid
• Nasogastric (NG) feeding should be introduced as soon • Management is focused on avoiding hypoglycaemia, avoid-
as possible ing the build‐up of toxic by‐products of metabolism and
• Adequate energy intake must be ensured: maintaining nutritional status
Feeds can be concentrated or energy supplements added • A protein restriction is not recommended for HE due to its
• Adequate protein must be ensured: impact on nutritional status and the risk of increasing
Initially a minimum of 1 g/kg ammonia production through catabolism
Protein intake maximised as soon as possible to pre- • BCAAs may be beneficial as they detoxify ammonia and
vent catabolism limit the efflux of aromatic amino acids across the blood–
Consideration of using a formula with supplementary brain barrier
BCAAs
Chronic Liver Disease 171
Table 10.7 Case study: a young child with acute liver failure.
Chronology
Admission A male aged 2 years and 9 months, previously well and healthy
Weight = 15.5 kg (75th–91st centile), height = 95 cm (<75th centile)
Presentation history: Deranged liver function, INR of 6.0 with acute liver failure, grade 1–2 encephalopathy, jaundice, pale stools,
dark urine, lethargy, loss of appetite
Impression: Post‐viral hepatic failure with encephalopathy and neutropenia
Acute interventions: Admitted to intensive care, intubated and sedated
Clinical concerns: Blood glucose = 3.3 mmol/L. Raised bilirubin, INR rapidly increased along with a declining AST indicating
hepatocellular death. Albumin declined indicating worsening synthetic liver function. Listed for super urgent liver transplantation
Management on intensive care unit

Day 1 Blood glucose levels 3.3–4.0 mmol/L on 2∕3 fluid restriction of 70 mL/kg 10% IV dextrose. IV dextrose increased to 12.5%
Day 2 Continued on 12.5% dextrose. Energy requirements for ventilation calculated as 58 kcal (240 kJ)/kg (BMR, Schofield*). Started
standard paediatric 1 kcal (4 kJ)/mL feed via NGT at 10 mL/hour and increased by 10 mL/hour every 6 hours. Target fluid = 37 mL/
hour per 24 hours
Day 3 Feeds held at 20 mL/hour due to high gastric aspirates. Continued on 12.5% IV dextrose. Then made NBM for probable liver
transplant
Day 4 Liver transplantation performed. Returned to intensive care intubated and sedated
Post‐transplant
Day 1–5 On IV fluids. NBM due to new Roux loop surgery. Extubated day 2
Day 5 Weight = 14.7 kg (50th–75th centile). Energy requirements for extubation calculated as 82 kcal (343 kJ)/kg (EAR). Started standard
1 kcal (4 kJ)/mL feed via NGT at 10 mL/hour and increased by 10 mL/hour every 6 hours. Target fluid = 53 mL/hour. Target energy
82 kcal (343 kJ)/kg
Day 6 Transferred to high dependency unit on continuous NG feeding
Day 7 Chyle fluid in abdominal drain confirmed in lab. Chyle leak secondary to chylous ascites. Changed to 80% medium chain
triglyceride (MCT) feed via NG
Day 8 Allowed oral intake. Commenced sips of fat‐free fluids and restricted long chain triglyceride diet alongside high MCT feed
via NG
Day 10 Transferred to liver ward. NG feeding overnight to allow appetite for solid foods in the day
Week 2 Weight = 14.7 kg (50th–75th centile). Chylous ascites resolved. NGT removed as taking oral diet well. Fat content of diet
liberalised
Week 4 Weight = 15.4 kg (>75th centile). Discharged with advice about short‐term high energy/protein snacks and meals as not yet eating
full meals. Given advice regarding monitoring for excessive weight gain in view of nutrient‐dense diet and steroids
Outpatient clinic
3 months Weight = 16.0 kg (75th–91st centile). Growing well. No longer on nutrient‐dense diet
1 year Weight = 18.0 kg (75th–91st centile). Doing well. No concerns
INR, international normalised ratio; AST, aspartate aminotransferase; IV, intravenous; BMR, basal metabolic rate; NGT, nasogastric tube; NBM, nil by
mouth; EAR, estimated average requirement.
* Schofield equation (p. 87).
A case study of the management of a young child with ALF Learning points: malnutrition in CLD
is given in Table 10.7.
• There is a high risk of malnutrition in CLD
• Malnutrition in CLD is strongly linked to morbidity and
Chronic liver disease mortality
• Malnutrition may be due to malabsorption, reduced intake,
CLD involves a process of progressive destruction and increased requirements and altered metabolism
degeneration of the liver leading to fibrosis and cirrhosis.
Children with CLD are at risk of malnutrition, which is
strongly linked to morbidity and mortality [7]. Common CLD manifests as a range of symptoms shared by different
factors contributing to malnutrition in CLD are listed in types of liver disease and can be grouped into the complica-
Table 10.8. tions below. These symptoms may either be the direct result
Table 10.8 Potential causes of malnutrition in chronic liver disease. Fat malabsorption
Causes Factors that may contribute
The absence or shortage of bile results in malabsorption of
Malabsorption Reduced or absent bile flow/bile salts long chain triglycerides (LCT) from the gastrointestinal
Pancreatic insufficiency (GI) tract. If left untreated, it can result in faltering growth,
Portal hypertension‐related enteropathy fat‐soluble vitamin deficiency and essential fatty acid (EFA)
Malnutrition‐related villous atrophy deficiency. Many cholestatic infants compensate for the
Reduced nutrient Anorexia loss of energy from fat malabsorption by consuming high
intake Nausea and vomiting volumes of breastmilk or infant formula. Intakes can be
Early satiety as a result of ascites, enlarged liver/ more than twice normal fluid requirements. Where there is
spleen
fat malabsorption, medium chain triglycerides (MCT)
Behavioural feeding problems
Hospitalisation‐related depression
should be given as they do not require emulsification by
Unpalatable diet/feeds bile; their partial water solubility allows them to diffuse
Taste changes easily into intestinal cells for direct absorption into the
Fluid restriction bloodstream. As MCT is not a source of EFA, it is important
Timing of medication interfering with meal times that children continue to have LCT in the diet. There is a
Fatigue, prolonged sleeping lack of evidence for the ideal MCT content of formulas, but
Increased nutrient Respiratory effort increased due to most contain approximately half of their total fat content as
demands organomegaly or ascites MCT (Table 10.9).
Stress such as infection
Increase in metabolically active cells [8]
Altered metabolism Increased oxidation of fat and protein stores Dietetic management
Reduced glycogen storage
• Infants – dietetic management is described in Table 10.10
Insufficient protein synthesis
Impairment of gluconeogenesis
• Toddlers and children – normal solids with MCT sup-
plementation as formula/oral nutritional supplements
(ONS)/emulsion/oil
• Fat‐soluble vitamins should be provided in order to pre-
of disordered metabolism or a physiological manifestation vent deficiency (Table 10.11).
of liver disease [9]. • Although there is limited research on the need for sup-
plementing water‐soluble vitamins, twice the recom-
Jaundice mended daily allowance may be required due to altered
hepatic metabolism [7]. This may be achieved with ONS.
Jaundice, a condition that causes the complexion and whites
of the eyes to appear yellow, is classified as either unconju-
gated or conjugated. Unconjugated jaundice is characterised Learning points: fat malabsorption
by a jaundiced appearance without bilirubin in the urine.
This may be physiological in the newborn due to an increase • Fat malabsorption is due to the absence of bile, which is
of bilirubin production, decreased bilirubin clearance or a required for fat emulsification
combination of both. Dietetic intervention is not usually • MCT does not require emulsification as it is partially water
required. In contrast, conjugated jaundice or conjugated soluble
hyperbilirubinaemia (CHB) represents cholestatic liver dis- • Infants may compensate for fat malabsorption by i ncreasing
ease and requires dietetic intervention. It results when bile is consumption of breastmilk/formula
reduced either due to an obstruction (e.g. biliary atresia [BA]) • As MCT does not contain essential fatty acids, the diet
or reduced bile formation (e.g. progressive familial intrahe- should continue to include some LCT
patic cholestasis [PFIC]). Normally, conjugated bilirubin is • There is limited evidence on the ideal MCT content of
made water soluble by the addition of glucuronide in the formulas; most formulas contain 50% fat as MCT
liver and enters the bile. If there is an absence or reduction in • Fat‐soluble vitamins are routinely given in CLD
bile, the conjugated bilirubin glucuronide passes into the
serum and is then excreted as dark urine, and as a result the
stools lack pigment.
Pancreatic enzyme insufficiency
Dietetic management
Some types of liver disease (Alagille’s syndrome, PFIC,
For unconjugated jaundice:
choledochal cysts) may be accompanied by pancreatic
• No dietetic intervention is required enzyme deficiency that aggravates malabsorption. Since bile
salts are required to activate pancreatic lipase, a functional
For conjugated jaundice:
deficiency may be present in cholestasis. The finding of a
• Dietetic management is as described for fat malabsorption low stool elastase may support a deficiency.
Table 10.9 Formulas and supplements high in medium chain triglycerides (per 100 mL).
% fat Energy kcal CHO Fat Protein

Product as MCT (kJ) (g) (g) (g) Protein type Age/weight Comments
Heparon Junior 49 86 (360) 11.6 3.6 2 Whole 0–3 years Supplemented with BCAA
Pregestimil Lipil 55 68 (285) 6.9 3.8 1.89 Peptide 0–1 year Clinically lactose‐free (<5 mg
lactose/100 mL)
Aptamil Pepti‐Junior 46 66 (275) 6.8 3.5 1.8 Peptide 0–1 year
Puramino 33 68 (290) 7.2 3.6 1.89 Amino acid 0–1 year
Peptamen Junior 60 100 (420) 13.2 4.0 3.0 Peptide 1–10 years
PaediaSure Peptide 50 100 (420) 13.0 4.0 3.0 Peptide 8–30 kg
Infatrini Peptisorb 50 100 (420) 10.3 5.4 2.6 Peptide 0–18 months or <9 kg
Nutrini Peptisorb 46 100 (420) 13.7 3.9 2.8 Peptide 1–6 years or 8–20 kg
Monogen 84 74 (310) 11.6 2.2 2.2 Whole 0–1 year* Used for chylous ascites
Lipistart 80 69 (290) 8.3 3.1 2.1 Whole 0–10 years Used for chylous ascites
Emsogen 83 88 (368) 12 3.3 2.5 Amino acid >1 year** Used for chylous ascites for those
needing a milk‐free diet
Liquigen 96 450 (1880) 0 50 0 n/a From birth MCT emulsion. Not a sole source of
nutrition
MCT Oil 100 855 (3575) 0 95 0 n/a From birth MCT oil. Useful in cooking, low
smoke point. Not a sole source of
nutrition
Betaquik 95 189 (777) 0 21 0 n/a >3 years MCT emulsion. Not a sole source of
nutrition
MCTprocal 96 703 (2907) 20.6 63.5 12.2 Whole >3 years Use in cooking/baking or add to foods/
drinks. Not a sole source of nutrition
MCT, medium chain triglyceride; BCAA, branched chain amino acids.

* Complete for age <1 year or can be used as a supplement to diet for age >1 year.
** Not suitable as sole source of nutrition for 1‐ to 5‐year‐olds.
Table 10.10 Summary of dietetic management for infantile conjugated hyperbilirubinaemia/cholestatic jaundice.
1. Is galactosaemia suspected?
• No, proceed to step 2 below
• Yes, change to clinically lactose‐free MCT formula* (Table 10.9). Stop breastfeeds and give advice on how to maintain milk supply while awaiting
diagnosis. If diagnosed with galactosaemia change to soya infant formula and refer to a metabolic centre. If galactosaemia excluded, proceed
with step 2 below
2. Is the infant breastfed?

• No, use MCT formula
• Yes, either breastfeed with 3–5 mL Liquigen × 8 per day OR
• Give 100 mL/kg MCT formula with remainder as breastmilk in the following way:
◦◦ Give MCT formula at the beginning of each feed and top‐up with breastfeed
◦◦ Breastfeed at every third feed
◦◦ Breastfeeds overnight and MCT formula during the day
3. Is cholestasis resolving?
• No, remain on above regimen
• Yes, stop MCT formula and give full breastfeeds and/or a suitable infant formula
4. Are blood sugar levels maintained?

• No, consider adding glucose polymer up to 3% concentration. Feed 2–3 hourly day and night or continuously via pump if necessary. N.B. the
addition of energy supplements reduces the protein–energy ratio
• Yes, continue management
5. At weaning
• Encourage normal weaning
• Add MCT formula when making up dried baby foods instead of water or cow’s milk
• Add cream/butter/cheese and/or glucose polymer/fat supplement to increase energy content of foods
6. If there is faltering growth, is the child taking an adequate volume of feed?

• No, commence NG feeding and give advice regarding promoting oral feeding
• Yes, increase the nutrient density, e.g. increasing concentration of formula, adding high energy/protein supplements and foods to diet
7. Continue to review and monitor closely
* Caution. For preterm infants receiving breastmilk who are at high risk of necrotising enterocolitis, await a definitive diagnosis of galactosaemia before
stopping breastmilk. If diagnosed with galactosaemia, liaise with metabolic team.
Table 10.11 Practice guide for vitamin supplementation at King’s College Hospital, London.
Vitamin Product Age Daily oral dose
Multivitamins Abidec/Dalivit Birth–1 year 0.6 mL

(containing A and D) (Abidec preferred as lower vitamin A content. >1 year 1.2 mL
Dalivit used if patient has peanut allergy)
Forceval capsule >12 years 1 capsule
Vitamin E Alpha‐tocopheryl Birth to 12 years 10 mg/kg up to 100 mg/kg
(max 200 mg/kg/day)
>12 years 1 capsule (286 mg vitamin E)
(max 200 mg/kg/day)
Vitamin K Phytomenadione <1 year 1 mg
1–5 years 2 mg
Menadiol tablets 5–12 years 5 mg
>12 years 10mg
Vitamin D Colecalciferol 1–12 months 1000 IU (max 3000 IU daily)
1–12 years 6000 IU in solution or 6400 IU if can
swallow capsules (max 25 000 IU daily)
>12 years 9600 IU daily (max 40 000 IU daily)
Alfacalcidol <1 month 20 ng/kg
(second line or in severe cholestatic liver 1 month–12 years <20 kg: 15–30 ng/kg (max 500 ng/day)
disease) >20 kg: 250–500 ng (max 500 ng/day)
>12 years 250–500 ng
Ergocalciferol (intramuscular) n/a Dose based on Vitamin D level (nmol/L):
<10: 60 000 units
10–20: 45 000 units
>20 < 50: 30 000 units
>50: use oral supplementation
Dietetic management Carbohydrate content of feeds should be increased using a

glucose polymer:
Pancreatic enzyme replacement therapy (PERT) should be
started and continued if a clinical benefit is seen (refer to • starting with the addition of 1% and increasing in 1%
p. 219 for PERT dosing). increments thereafter
• beware of rebound hypoglycaemia due to high glucose load
Hypoglycaemia
Faltering growth
Hypoglycaemia may occur in CLD as the liver’s ability to
store glycogen and mobilise glucose during fasting is In CLD there may be faltering growth with wasting of lean
impaired. Muscle glycogen homeostasis may also be dis- body mass and fat stores, despite aggressive nutrition support.
rupted. An acute‐on‐chronic presentation may require an Supplementation of the branched chain amino acids leucine,
ER (p. 673) to control blood sugar levels while a feeding valine and isoleucine has been shown to improve nutritional
regimen is established. Frequent or even continuous feeds status in liver disease [10]. Unlike other amino acids they are
may be required with a high carbohydrate content to ensure metabolised in muscle and, therefore, are available for protein
blood glucose levels are maintained. For some infants care synthesis even when there is poor hepatic function. Leucine, as
is needed to avoid giving excess glucose, which can lead to a ketogenic acid, may be used preferentially as an energy sub-
hyperinsulinaemia. strate, while valine and isoleucine are diverted towards gluco-
neogenesis [11]. The result is preservation of precious reserves
Dietetic management of fat and lean body mass. There is little evidence on the ideal
amount of BCAA supplementation in liver disease. The only
To manage hypoglycaemia, a consistent supply of exoge- formula currently available with supplementary BCAA in the
nous glucose needs to be ensured: UK is Heparon Junior, which contains 30% BCAA.
• infants – 2–3 hourly breast or bottle feeding
• children – regular meals and snacks with low glycaemic Dietetic management
index carbohydrates
The main points are to:
• uncooked cornstarch (UCCS) may be useful for children
over 2 years (p. 613) • aim for increased energy and protein intakes (Table 10.12)
• consider NG continuous feeding • increase nutrient density of the diet
Chronic Liver Disease 175
Table 10.12 Energy and protein requirements for chronic liver disease. Dietetic management
Energy Protein This will depend on the extent of the varices:
Infants 120–150 kcal/kg (500–630 kJ/kg) 3–4 g/kg • continue to feed orally where possible

• a soft diet is recommended following sclerotherapy/
Older children 130%–150% of the estimated average 3–4 g/kg
requirement for age oesophageal banding
• consider PN if unable to feed enterally for an extended
period
• use a formula supplemented with BCAA (Table 10.9)
• give aggressive and early nutrition support with NG Hepatosplenomegaly and ascites
feeding or parenteral nutrition (PN) if necessary
Hepatosplenomegaly (enlarged liver and spleen) and
ascites (fluid retention in the abdomen) are features of
Learning points: branched chain amino acids decompensated liver disease. As portal hypertension wors-
ens, the pressure in the portal vein (which connects the
• Leucine, valine and isoleucine are branched chain amino liver and spleen) increases, causing the spleen to enlarge.
acids This increased pressure, as well as a reduced ability of the
• BCAA may improve nutritional status as they are liver to make albumin, results in ascites. The most pro-
metabolised in muscle and are available for protein synthesis found effect on nutritional status from hepatosplenomeg-
even when there is poor hepatic function aly and ascites is loss of appetite and early satiety due to
• There is limited evidence for the ideal amount to include in abdominal discomfort and reduced gastric capacity. Ascites
the diet in chronic liver disease is managed with diuretics in preference to fluid restriction
in order to allow adequate nutritional intake. Therapeutic
paracentesis may be required (Table 10.2), usually resulting
in immediate improvement of appetite secondary to the
Portal hypertension reduction of intra‐abdominal pressure on the stomach. The
discouragement of salty foods may help to reduce thirst.
Portal hypertension is where a hardening of the liver (fibro- A rigid restriction is not recommended as it is difficult to
sis) results in increased resistance to blood flow from the impose and may result in a corresponding reduction in
intestines and spleen into the liver through the portal vein. It oral intake.
can also occur when there is a thrombus in the portal vein
(portal vein thrombosis). There may be an associated enter- Dietetic management
opathy and malabsorption due to an increased pressure in
the mesenteric venous system, i.e. oedema of the mucosa of This will centre on the degree of abdominal discomfort:
the small intestine. Oesophageal varices, splenomegaly, • a change to small, frequent, nutrient‐dense meals and
ascites and thrombocytopenia are clinical and biochemical snacks may help
features of portal hypertension and can accelerate the need • considering NG bolus feeds or continuous feeding if oral
for liver transplantation if uncontrolled. intake is poor
• concentrating feeds or using a high energy formula/
Dietetic management ONS if there is a fluid restriction
• limiting sodium intake in feeds and avoiding salty foods
Portal hypertension may be managed by considering:
• using a peptide‐based feed (Table 10.9)
• continuous rather than bolus feeds
Cirrhosis
• PN if there is severe malabsorption
Cirrhosis represents the end stage of CLD. CLD results in
a repetitive sequence of cell injury and repair, resulting in
Oesophageal varices necrosis and fibrogenesis and irreversible damage. The
liver can compensate for the damage such that the cirrho-
Oesophageal varices develop when blood flow to the liver is sis is asymptomatic. Decompensated cirrhosis occurs
blocked, causing blood to flow into smaller blood vessels when damage within the liver causes blood flow to be
(such as those in the lower oesophagus), which can leak or impaired, resulting in symptoms such as portal hyperten-
rupture. This may result in haematemesis or melaena. sion, ascites and varices. As decompensation occurs, there
Oesophageal varices are not a contraindication to oral feed- is likely to be a decline in nutritional status despite maxi-
ing. Where varices are large and bleed frequently, NG tube mal nutritional support, and this may highlight the need
placement may be contraindicated, and PN may be needed. for transplantation. Malnutrition adversely affects the
Following sclerotherapy or oesophageal banding, a soft diet outcome of liver transplantation [12], and improving
is usually initiated in the first 24 hours. nutritional status prior to transplant can help to reduce
complications [13]. Once a decision is made to consider a Table 10.13 Types of liver transplants.
child for transplantation, a detailed assessment (including
a full nutritional review) is carried out to determine Type of transplant Description
whether the child should be placed on the transplant wait- Partial graft • A split liver is the most common transplant.
ing list. Waiting time on the transplant list is unpredicta- The donor liver is split into two lobes, with the
ble and depends on the potential recipient’s severity of right lobe going to an adult or older child and
disease, disease type and blood type. The median (95% CI) the left lobe or a left lateral segment (part of
waiting time to LT for children in the UK between 2013 the left lobe) going to a young child
• A cut down or reduced graft is where there is
and 2016 was 107 (29–135) days [14].
one recipient. The liver is cut down to size to
fit the child
Dietetic management Whole liver • More common in children over 5 years
• The whole liver may be used if it is the right
Management for cirrhosis is as described for CLD above, size for the child
depending on the symptoms that the child presents with.
Auxiliary • A partial donor liver graft is transplanted onto
For those being considered for transplant:
a resected native liver
• a detailed nutritional assessment is carried out • Used where there is a possibility of the native
• pre‐ and post‐transplant nutrition information is dis- liver recovering, e.g. in acute liver failure,
some metabolic diseases
cussed with the family/caregivers:
◦◦ the importance of good nutritional status prior to Hepatocyte • Novel technique used in some metabolic
disorders and acute liver failure
transplant
• Hepatocytes are infused into the liver engraft
◦◦ the timing and type of nutrition initiated after and support liver function
transplant
◦◦ possible post‐transplant complications (e.g. chylous
ascites)
• close monitoring of progress is required after transplant, and referral to a specialist feeding clinic
may be required.
Liver transplantation can be curative for many metabolic
Learning points: cirrhosis diseases, enabling a normal diet after transplant. For those
patients who have been on a lifelong dietary protein restric-
• Cirrhosis represents the end stage of liver disease tion, self‐restriction of protein intake following transplanta-
• Compensated cirrhosis is where the liver compensates for tion is common [16]. For conditions where transplant is not
liver damage so that cirrhosis is asymptomatic curative (e.g. propionic acidaemia and methylmalonic aci-
• Decompensated cirrhosis occurs when liver damage causes daemia), continued dietary restriction may be required [17].
blood flow to be impaired, resulting in symptoms such as In these patients PN is usually given initially to avoid catab-
portal hypertension, ascites and varices olism and limit production of toxic metabolites, e.g. ammo-
• Nutritional status is likely to decline despite maximum nia and organic acids.
nutrition support
Dietetic management
Liver transplantation
This depends on whether an LT is curative or not.
Where transplant is curative:
LT may be from a deceased or a living donor. Survival rates
have been reported as 95% at 1 year, 93% at 2 years and 92% • after 3–5 days NBM a standard NG formula or feed is
at 5 years (2010–2012) [15]. The types of LT are outlined in started
Table 10.13. • some older children are able to commence a normal diet
The biliary ducts are either rerouted directly to the without tube feeding
small bowel (i.e. a new Roux loop is formed), or if the
Where transplant is not curative (i.e. for some metabolic
graft liver has an intact bile duct, it may be surgically
conditions):
joined to the native bile duct. Following transplant there
is usually a period of between 3 and 5 days nil by mouth • PN is given while NBM immediately after transplant
(NBM): 5 days NBM where a new Roux loop is formed with 1.0–1.5 g/kg protein restriction
due to the risk of small bowel perforation. The clearing of • once enteral feeing is started, PN is gradually weaned
long‐standing jaundice, reduction in abdominal pressure down
and the introduction of high dose steroids (as antirejec- • in some cases it may be necessary to continue dietary
tion treatment) can play an important role in promoting protein restriction either immediately post‐transplant or
good appetite. In children with pre‐existing oral aver- at a later stage. The metabolic team caring for the child
sion, NG feeding may be required for an extended period should be consulted
Liver Transplantation 177
Both cyclosporin and tacrolimus lower serum magnesium

Learning points: liver transplant
levels. Serum magnesium needs to be monitored, and sup-
plementation may be required, as much as 0.5–1 mmol/kg/
• Survival figures for liver transplant are very high, with
day orally. Once serum tacrolimus levels are consistently
92% survival at 5 years
within the therapeutic range, the need for magnesium sup-
• There are different types of liver transplant: partial graft,
plementation generally resolves at around 6 weeks’ post‐
whole liver, auxiliary and hepatocyte
transplantation. Magnesium supplements are typically not
• Feeds are usually started between 3 and 5 days after
well tolerated initially, causing diarrhoea; protein‐bound
transplant
magnesium is better tolerated. Grapefruit (including juice),
• For methylmalonic acidaemia and propionic acidaemia, PN
pomegranate and blood oranges need to be avoided as they
is given immediately after transplant, and there may be a
may induce toxicity.
continued need for a protein‐restricted diet
Safe food handling is necessary (p. 51) and must be
adhered to lifelong due to immunosuppression.
Complications after liver transplant Infection
Bowel perforation Infection is the most common cause of post‐transplantation

mortality and morbidity. Epstein–Barr virus (EBV), CMV
The risk of bowel perforation after transplant is higher in and herpes simplex virus are the primary viral infections. A
children with BA who have had surgery previously and may majority of paediatric liver recipients are seronegative to
be linked to malnutrition, portal hypertension, CMV enteri- EBV and CMV and often receive a liver from donors who are
tis, sepsis, steroids and use of inotropes [18]. Where there are seropositive for these viruses. GI perforation and bleeding
GI complications, an extended period of NBM is likely to be are severe consequences of EBV and CMV infection.
required, and PN may be needed. Depending on the virus, medical management is successful
in the majority of cases. However, if unsuccessful, and in the
Chylous ascites case of EBV infection, post‐transplant lymphoproliferative
disorder (PTLD) can result. Treatment for advanced PTLD
Chylous ascites may develop as a result of damage to lymph includes chemotherapy and radiotherapy, further exacerbat-
vessels during transplant surgery. The leaking chyle, a tri- ing poor nutritional status, delaying growth and signifi-
glyceride‐rich fluid, has a milky appearance in the abdomi- cantly increasing mortality risk.
nal drain fluids and can resolve spontaneously. A low LCT
diet (ideally <20% total fat as LCT) is generally required for
1–2 weeks in order to reduce the flow of lymph (p. 302). Rejection
This may be achieved with 80% MCT formulas (Table 10.9) Moderate to severe acute rejection after transplant is treated
in young children or very low fat foods in older children. with steroid boluses [18]. In the event of hyperglycaemia due
Fat‐free and MCT supplements may be needed to meet to high dose steroids, a short‐term reduction in sugary foods
requirements. If a strict low LCT diet is given for an and advice about low glycaemic index foods may be required.
extended period of time, walnut oil may be needed to A positive side effect of steroids may be an increase in appetite.
ensure adequate provision of EFA (p. 648). Chronic rejection occurs less frequently and is often treated
with adjustments to immunosuppression, however, if unsuc-
Learning points: chylous ascites cessful retransplantation may be required. If there is progres-
sive cholestasis, MCT supplementation may be required.
• A chyle leak may occur due to damage to lymph vessels
during transplant
Donor size mismatching
• A low LCT diet and/or formula is used (80% MCT formula)
• The ideal amount of time to remain on a low LCT diet is not The nutritional management of small‐sized recipients can be
clear, but in practice is usually 1–2 weeks a challenge in the immediate period post‐transplantation.
The sheer bulk of a large piece of liver can mean that much
of the intra‐abdominal cavity is occupied, which can delay
abdominal closure. The associated risks of an open abdo-
Immunosuppression
men, such as slower weaning off ventilation, an increased
The commonly used antirejection medication tacrolimus risk of gut ischaemia, portal hypertension and friable gut
(and to a lesser extent cyclosporin) can present nutritional integrity, can all delay transition onto enteral feeding. These
challenges. Tacrolimus is preferentially used but can be children are at higher risk of being NBM for more than
nephrotoxic or contraindicated by cardiac complications. 5 days, increasing the risk of gut bacterial translocation,
The pharmacokinetics of tacrolimus is affected by the decreased bile flow and subsequent compromised graft
presence of food in the gut; therefore, consistency with the hepatic function. Where PN is used, some enteral feeds
timing of meals and taking the medication is needed. should also be given where possible.
Transplant‐acquired food allergy Intestinal failure‐associated liver disease

Transplant‐acquired food allergy (TAFA) is seen in up to 17%
Intestinal failure‐associated liver disease (IFALD) is a com-
of children post‐transplant [19], which is approximately
mon complication for children on long‐term PN (p. 66).
double that seen in the general paediatric population and
IFALD may present at an early stage when it may still be pos-
may occur days or months after transplant [20]. The mecha-
sible to reverse it through intestinal rehabilitation or at an
nism for TAFA is not known, but may be related to Th2
advanced stage resulting in end‐stage liver disease. It is the
skewing, the transfer of lymphocytes or IgE or increased
main indication for intestinal transplantation in children [29].
intestinal permeability secondary to immunosuppressant
The exact pathogenesis of IFALD remains unknown; it may
medication [20]. While some children have been reported to
be due to the toxic effects of PN or the underlying aetiology
develop tolerance to some TAFA over time, other children
of intestinal failure [30]. The main risk factors for IFALD
may need a long‐term dietary restriction [21].
include prematurity, catheter‐related bloodstream infections,
PN management and lack of enteral nutrition [30].
Obesity Dietetic management for the prevention of IFALD is
described on pp. 67 and 164. Where IFALD has progressed to
There is a risk of obesity with post‐transplant metabolic end‐stage liver failure, the dietetic management is as
syndrome (PTMS) thought to be associated with the use of described for CLD above, in consultation with the intestinal
corticosteroids, calcineurin inhibitors and immunosup- failure team caring for the child.
pressants and risk factors such as non‐alcoholic fatty liver
disease (NAFLD) [22]. Monitoring after transplant is
important and should include diet and lifestyle advice
Common disorders leading to chronic
for overweight children [22]. liver disease
There are many disorders that lead to CLD and the most
Nutrition support in liver disease common causes are described below.
Causes presenting in infancy:
Nasogastric tube feeding
• metabolic, e.g. glycogen storage disease, urea cycle
NG feeding has been shown to improve body composition in defect and galactosaemia
paediatric liver disease [23] and should be commenced early • genetic, e.g. alpha‐1‐antitrypsin deficiency, Alagille’s
to optimise nutritional status. Feeds may be administered as syndrome and PFIC
boluses, top‐up feeds or continuous pump feeding. It is • infections, e.g. hepatitis
important to promote oral feeding alongside tube feeding to • biliary malformations, e.g. BA, choledochal cysts and
reduce the risk of oral aversion. inspissated bile syndrome
• vascular lesions, e.g. hepatocellular carcinoma and
haemangioma
Gastrostomy feeding
Causes presenting in older children:
The placement of a gastrostomy is often not possible in • immune related, e.g. sclerosing cholangitis and autoim-
CLD. There is an increased risk of bleeding during tube mune hepatitis
placement due to portal hypertension or intra‐abdominal • genetic, e.g. Wilson’s disease
varices [24] and a risk of puncture if the liver/spleen is • biliary malformations, e.g. choledochal cyst
enlarged. There is also a risk of inadequate tract formation • lifestyle disorders, e.g. NAFLD and non‐alcoholic steato-
with ascites [24]. It may also create potential problems hepatitis (NASH)
with access to the abdominal cavity (due to adhesions)
during liver transplantation. However, placement of a
percutaneous endoscopic gastrostomy (PEG) has been Neonatal hepatitis
successful where there is no portal hypertension, ascites or
varices [25]. Neonatal hepatitis is inflammation of the liver in the first
few months of life. The cause is most often unknown or sus-
pected to be from a virus. Severity varies and rarely results
Parenteral nutrition in cirrhosis, with bile flow usually resolving with time.
PN may be beneficial in children with advanced end‐stage
liver disease who are listed for LT, where the risk of PN exac- Galactosaemia
erbating the liver disease is outweighed by improvement in
nutritional status prior to transplantation [26, 27]. The nutri- Galactosaemia is a metabolic disorder resulting from the
tion support team plays an important role in optimising PN inability to metabolise galactose (p. 599). As a common clini-
and promoting enteral nutrition [28]. cal presentation of galactosaemia is conjugated jaundice, all
Common Disorders Leading to Chronic Liver Disease 179
infants with CHB are screened for this condition. Where failure to export the glycoprotein alpha‐1‐antitrypsin
galactosaemia screening is not done at birth, the blood galac- from hepatocytes, resulting in hepatic inflammation and
tose‐1‐phosphate uridyltransferase (Gal‐1‐PUT) is meas- eventually cirrhosis [36]. The severity of this condition,
ured. If the infant has received a blood transfusion within six degree of liver involvement and nutritional management
weeks of testing, a false result can occur, in which case both vary significantly.
parents will need testing.
Alagille’s syndrome
Biliary atresia
This syndrome is a genetic autosomal recessive condition
BA is the inability to excrete bile due to obstruction, destruc- and can present as a spectrum of disorders including intra-
tion or absence of the extrahepatic bile ducts, which leads to hepatic biliary hypoplasia (paucity of the intrahepatic bile
bile stasis in the liver with progressive inflammation and ducts) and cardiovascular, skeletal, facial and ocular abnor-
fibrosis. It is a rare progressive disease occurring in 1 in 9 000– malities. It is a rare condition that is typically diagnosed in
16 000 births [31] but is the most frequent hepatic cause of 7% of all neonatal cholestasis cases [37]. Infants present with
death and requirement for transplantation [12]. At least 50% CHB followed by pruritus and finally, if severely affected,
of children with this condition are likely to receive LT in the xanthelasma (yellowish deposits of fat underneath the skin,
first 2 years of life [32] with a further 20%–30% likely to require usually on or around the eyelids), which usually appears by
a transplant later in life [26]. Up to two thirds of BA survivors 2 years of age. Some children have cyanotic heart disease as
who have not received liver transplantation may develop por- their main problem.
tal hypertension but maintain adequate growth [33]. The nutritional management of Alagille’s syndrome can
Bile drainage can be restored by the Kasai operation, be challenging. Frequent problems include poor growth,
which involves bypassing the blocked ducts. Native liver vomiting, appalling appetite (fussy eating), pancreatic insuf-
survival rate and jaundice clearance are reported to be ficiency, malabsorption, severe itching and renal acidosis.
improved when the Kasai procedure is performed earlier Malnutrition and severe itching may be the main indications
than 60 days of age, with outcomes showing better results for transplantation.
the earlier the Kasai is performed [34]. A late Kasai opera-
tion, i.e. after 60 days of age, is associated with a poor prog-
nosis [35]. A Kasai procedure is considered to have been Learning points: Alagille’s syndrome
successful if jaundice has cleared and LFTs have normalised
3 months after the procedure. • A rare genetic condition presenting as a spectrum of
Given the high requirement for transplantation, a focus on disorders including lack of intrahepatic bile ducts
nutrition is extremely important in these patients. They • Growth is a major problem and most children require NG
require close monitoring and aggressive nutrition support as feeding
studies have shown that improvement of nutritional status • Malnutrition and severe pruritus may be the main
in the pre‐transplant period may improve outcomes after indications for transplantation
transplantation [31, 33]. Their management is as described
for CLD.
Haemangioma
Learning points: biliary atresia
Haemangiomas are benign vascular tumours of the liver. If
• BA is the most frequent hepatic cause of death and require- large in size, they are supplied by wide blood vessels taking
ment for transplantation a large proportion of the cardiac output, resulting in imme-
• A Kasai operation can restore bile flow and should be per- diate medical treatment to decrease blood pressure, increase
formed in the first 8 weeks of life cardiac output and reduce the risk of fluid overload. In
• A Kasai operation is considered to have been successful if young infants where cardiac failure develops, hepatic artery
jaundice has cleared and LFTs have normalised 3 months ligation is essential to restrict the tumour’s blood supply. If
after the procedure surgical intervention is not curative or where ligation cannot
• Close monitoring is required due to the high likelihood of be performed, liver transplantation may be required. These
transplantation cases may be dramatic, presenting with hepatomegaly and
worsening cardiac function; these children may struggle to
meet nutritional requirements.
Alpha‐1‐antitrypsin deficiency
Inspissated bile syndrome
Alpha‐1‐antitrypsin deficiency is an IMD that can cause
varying degrees of liver disease in infancy and can pre- Inspissated bile syndrome is where a plug of thick bile
sent with cholestasis. Liver disease is secondary to the blocks the bile ducts and causes conjugated jaundice.
Table 10.14 Types of progressive familial intrahepatic cholestasis.
PFIC 1 PFIC 2 PFIC 3

Familial intrahepatic cholestasis Bile salt export pump Multi drug resistance 3
(FIC 1) or Byler’s disease (BSEP) deficiency (MDR3) disease
Disease progression Progresses quickly to cirrhosis Cirrhosis often before age Slow progression of cirrhosis and
in infancy 10 years. Higher incidence liver disease
of hepatocarcinoma
Symptoms Jaundice, severe pruritus, Severe pruritus, diarrhoea, Pruritus tends to be milder,
diarrhoea, poor growth, poor growth, gallstones gallstones, high risk portal
gallstones. Some have hypertension
pancreatic insufficiency
Biochemical or Normal GGT, high serum bile Normal GGT Elevated GGT, normal bilirubin,
functional hallmarks acids low phospholipids in bile
GTT, gamma‐glutamyl transpeptidase.
Resolution may occur naturally with time, or with the Table 10.15 Surgical procedures used to manage itching and possible
help of ursodeoxycholic acid (enhancing bile flow), or nutritional consequences.
under percutaneous transhepatic cholangiography (PTC)
Procedure Description
(Table 10.2), or in rare cases surgical excision. The syn-
drome often occurs in infants who have been NBM, e.g. Partial external Stoma created from gall bladder to remove some
after surgery and long courses of PN. biliary of the bile produced. This may worsen
diversion malabsorption and vitamin deficiencies
Partial internal Similar to external diversion except a piece of
Choledochal cysts biliary drainage bowel connects the gall bladder to the large
intestine (no stoma). Diarrhoea may result as bile
Choledochal cysts are dilatations of all or part of the extrahe- enters the large intestine
patic biliary tract. They may occur in infants (and can be Internal ileal A bypass is created around the distal ileum
detected in utero) and children. They may remain undiag- exclusion (where bile salts are usually reabsorbed) to
reduce reabsorption. Diarrhoea may result and
nosed for years. Ursodeoxycholic acid improves bile flow
there may be nutrient malabsorption
and may enable a small cyst to disappear requiring no fur-
ther treatment, while other cysts may require surgical Liver transplant Most will eventually require a liver transplant. In
PFIC1 the defective gene is also expressed in
removal. Indeed some are so large and invasive that the
organs outside the liver, and therefore symptoms
extrahepatic bile ducts have to be removed and a Kasai pro- may persist after transplant
cedure has to be performed. Post‐surgery, any required
catch‐up growth, should occur quickly, negating further
nutritional intervention.
Learning points: PFIC
• Growth is a major problem and most children require NG

Progressive familial intrahepatic cholestasis feeding
• Fat malabsorption may occur without significant jaundice
PFIC is a group of liver diseases involving a defect in the
due to lack of bile salts in bile
membrane transport proteins required for the formation of
• Where there is diarrhoea an MCT formula with hydrolysed
bile (Table 10.14). It is a rare disorder affecting 1 in 50 000–
protein may be helpful
100 000 births. Pruritus is a major symptom, especially for
• Pruritus can be difficult to manage and impact on nutrition
PFIC 1 and 2, due to the increased level of bile acids in the
• PFIC1 is also expressed in organs outside the liver, and
blood. Itching is very difficult to control and may disturb
therefore the response to liver transplant may be poor
sleep and contribute to fatigue, irritability, reduced appe-
tite, nausea and vomiting. Several surgical procedures may
be used to manage itching, but these may cause diarrhoea
and worsening of malabsorption (Table 10.15). Growth is a Autoimmune hepatitis
major problem, and most children have short stature and
reduced muscle and fat mass. Fat malabsorption may occur Children who present with autoimmune hepatitis are typically
in PFIC without significant jaundice due to an inability to older with good nutritional status. Remission is achieved in
produce bile salts. 80% of children with prednisolone in combination with
Transition to Adult Care 181
azathioprine [38] and rarely necessitates dietetic intervention, transplantation, in some cases. The main nutritional compli-
unless associated with inflammatory bowel disease. Some of cations include severe vomiting and diarrhoea.
these children will need liver transplantation due to failure to
prevent progression to CLD secondary to cirrhosis.
Non‐alcoholic fatty liver disease and non‐alcoholic
steatohepatitis
Wilson’s disease
NAFLD may result in mild fatty infiltration of the liver
Wilson’s disease is a genetically inherited disease where there and mild inflammation, advancing to NASH, which
is a defect in copper metabolism. It leads to an accumulation leads to cirrhosis and eventually end‐stage liver failure
of copper in the liver, brain, kidney and cornea. Accumulation [42]. It is typically diagnosed around 12 years of age in
can take years and, hence, presentation is delayed. In advanced children with obesity. With the increase in childhood
disease or acute onset, LT may be required. Oral chelating obesity, prevalence of NAFLD may range from 36% [43]
agents, e.g. penicillamine, bind dietary copper and negate the to 80% [44].
need for a copper‐restricted diet. There is no conclusive evi- Weight reduction through diet and exercise is the main
dence that a lifelong dietary restriction of copper is beneficial treatment but can be difficult to achieve for many patients
in patients whose serum transaminases (ALT, AST) have nor- [45]. The aim is to correct metabolic disturbances by revers-
malised and who are compliant with drug therapy. A strict ing insulin resistance, reducing visceral fatness and reducing
low copper diet may negatively impact on the nutritional oxidative stress and inflammation [46]. Evidence for other
value of the diet and should be reserved for patients who are treatment options including metformin, vitamin E and anti‐
uncompliant with or unresponsive to drug therapy [39]. inflammatory fats [47] have thus far produced equivocal
results.
Learning points: Wilson’s disease
• A copper‐restricted diet should be followed until there is Learning points: NAFLD/NASH

remission of symptoms and normalisation of liver enzymes
• Chelating agents negate the need for a copper‐restricted diet • NAFLD is fatty infiltration and inflammation of the liver
• NASH is a serious condition that can progress to cirrhosis
• The prevalence of NAFLD is increasing alongside rising
obesity levels
Cystic fibrosis‐related liver disease • Treatment is weight loss through diet and exercise
Liver disease is a known complication of cystic fibrosis (CF).

Signs of CLD are seen in 25% of CF patients, but fewer than
10% will progress to cirrhosis [40]. Significant portal hyper- The dietetic management of these common disorders lead-
tension and associated malnutrition are characteristic of ing to CLD is summarised in Table 10.16.
severe cystic fibrosis‐related liver disease (CFLD). Jaundice A case study describing the management of a baby with
is rarely seen. Liver function tests are not reliable markers CLD is given in Table 10.18.
for disease severity.
Transition to adult care
Liver tumours
The transition from paediatric to adult services can be diffi-
Tumours rapidly infiltrate the liver whether benign or malig- cult for many young people with liver disease [48]. Non‐
nant. Medical management includes the use of steroids and adherence to medications and appointments post‐transplant
chemotherapy to reduce tumour size. Resection may then be is more prevalent in adolescents than young children; it has
possible allowing the liver to regenerate; otherwise, trans- been reported to be >50% in adolescents [49]. They may find
plant may be the only option and is regarded as a successful it difficult to plan due to the unpredictable time of adoles-
treatment in those without extrahepatic disease [41]. cent life and may not have a clear view of the future [50].
This should be considered when setting nutritional goals.
Bone marrow transplantation: immune Adolescents require consistent and ongoing education, and
deficiency disorders the communication between staff of both paediatric and
adult services needs to be seamless [51]. Institutions should
Immune deficiency causing liver destruction has led to a provide a pre‐transition clinic that takes place in the adult
need for bone marrow transplantation followed by liver service [52–54].
Table 10.16 Dietetic management of common disorders leading to chronic liver disease.
Disorder Dietetic management
Neonatal hepatitis Ensure adequate growth:

• Breastmilk (with fortifier if appropriate) or preterm/high energy formula
• Some MCT formula may be required in order to optimise weight gain and growth
Where jaundice persists after discharge from hospital:
• Dietetic management is as for infantile CHB (Table 10.10)
Galactosaemia While awaiting the Gal‐1‐PUT result to exclude galactosaemia:

• Stop breastfeeds and give advice to mother on how to maintain breastmilk supply
• Commence a lactose‐free MCT formula (Table 10.9)
If the test is positive for galactosaemia:
• Change to a soya infant formula
• A lifelong galactose restriction will be required (p. 602)
Biliary atresia • Initial dietetic management is the same as described in Table 10.10

• Following the Kasai operation, feeds are gradually introduced as described in Table 10.17
Alpha‐1‐antitrypsin • Some children require no nutritional intervention and are clinically well
deficiency • Severely affected children (who may come to transplantation before the age of 1 year): dietetic management is as
described for CLD
Alagille’s syndrome If there is faltering growth without symptoms of CLD:

• Consider NG feeding
• Consider PEG feeding in the absence of organomegaly and portal hypertension
• In children severely affected with xanthelasma, there is no evidence to restrict saturated fats
If there is faltering growth with advancing CLD:
• Dietetic management is as described for CLD
Haemangioma For a small haemangioma:

• Nutrition intervention is often not required
For a large haemangioma:
• There is likely to be a fluid restriction
• Energy and nutrient density of the diet should be increased
• In severe cases continuous NG feeding will be required
Inspissated bile syndrome Supplementing the diet with MCT may be necessary until PTC is performed
Choledochal cysts Infants or children with significant CHB or fat malabsorption:

• MCT supplementation
Those requiring a Kasai procedure:
• Infants – see the post‐Kasai procedure (Table 10.17)
• Children – age‐appropriate diet (MCT supplementation may be required)
Progressive familial For symptoms of fat malabsorption:

intrahepatic cholestasis
• MCT supplementation is required when bile flow is poor
• MCT supplementation may also be required where there is good bile flow, but poor bile quality due to a lack of
bile salts
• Where medication is given to bind bile acids (cholestyramine), MCT and fat‐soluble vitamin supplementation is required
For symptoms of diarrhoea:
• There may be benefit from an MCT formula based on hydrolysed protein (Table 10.9)
When there is faltering growth:
• NG feeding may be needed
• Gastrostomy tube feeding should be considered
Consideration of pruritus:
• The nutrition plan should take into account that itching may cause general irritation and distraction from eating,
and feeding tubes may become dislodged due to scratching
Disorder Dietetic management
Autoimmune hepatitis Presenting symptoms that may need dietetic input range from faltering growth and malabsorption to obesity
aggravated by steroid therapy
Wilson’s disease On diagnosis and initiation of drug therapy or where there is poor compliance with drug therapy [39]:
• Avoidance of foods high in copper until there is remission of symptoms and raised liver enzymes:
◦◦ Offal, particularly liver
◦◦ Animals/fish eaten whole (which contain the liver, e.g. shellfish)
◦◦ Mushrooms
◦◦ Cocoa, chocolate
◦◦ Energy drinks
Once there is remission of symptoms and normalising of serum transaminases (ALT, AST):
• Normal diet
Cystic fibrosis‐related Assessment and treatment needs to take into account that:
liver disease
• Body mass index (BMI), the standard measure of nutritional status in CF, may be affected by ascites or
organomegaly
• An increase in malabsorption with progressive CFLD is most likely to be as a result of portal hypertension
enteropathy. Increases in PERT above 10 000 units lipase/kg are thus unlikely to be helpful
• High feed volumes may not be tolerated due to organomegaly and ascites
• Restriction of sodium intake may not be needed as requirements are greater in CF
• A peptide‐based MCT formula should be used where portal hypertension enteropathy is suspected
Dietetic management is further described on p. 232
Liver tumours Nutritional support and monitoring is required throughout the course of treatment
Bonemarrowtransplantation – Nutrition support in the form of enteral and parenteral nutrition may be required throughout the critical course of
immune deficiency treatment
disorders
Non‐alcoholic fatty liver • Energy‐restricted diet
disease and non‐alcoholic • Incorporate regular physical activity
steatohepatitis
MCT, medium chain triglycerides; CHB, conjugated hyperbilirubinaemia; Gal‐1‐PUT, galactose‐1‐phosphate uridyltransferase; CLD, chronic liver
disease; NG, nasogastric; PEG, percutaneous endoscopic gastrostomy; PTC, percutaneous transhepatic cholangiography; ALT, alanine aminotransferase;
AST, aspartate aminotransferase; PERT, pancreatic enzyme replacement therapy.
Table 10.17 Post‐Kasai protocol.
Day post‐Kasai Management
Day 1–2 IV fluids

Day 3 Commence hourly feeds of Dioralyte, gradually increasing to 120 mL/kg
Day 4–5 1. Change to 120 mL/kg of feed*
2. Change to 2 hourly feeds
3. Increase volume by 5 mL every 4 hours up to 150 mL/kg feed
4. Progress to 3 hourly feeds if good tolerance and maintaining blood sugars
Day 6 Allow demand feeding
Give target volume of feed to aim for each day
Worked example Infant weighing 4 kg. Day 4 post‐Kasai and has been tolerating 20 mL Dioralyte hourly (120 mL/kg). Mum has EBM available
and wishes to breastfeed.
• Change to feed* and give 20 mL for one feed (120 mL/kg)
• Then 40 mL × 2 hourly for two feeds (120 mL/kg)
• Finally, allow demand feeding aiming for minimum 400 mL/day MCT formula (100 mL/kg) and remainder as EBM/
breastfeeding
IV, intravenous; EBM, expressed breastmilk.

* Feed should be 100 mL/kg MCT formula and the remainder as EBM if available. If mum wishes to breastfeed, wait until the infant is taking 150 mL/kg
in order to demonstrate tolerance. Feeds can then be changed to 100 mL/kg MCT formula and the remainder as breastfeeds.
Table 10.18 Case study: an infant with chronic liver disease.
Chronology
Admission An 8‐week‐old female with conjugated hyperbilirubinaemia, dark urine and pale stools. Weight = 3.75 kg (<2nd centile)
Presentation: Excessive feeding on breastmilk and standard infant formula = 260 mL/kg. Galactosaemia excluded
Impression: Possible biliary atresia
Changed to 100 mL/kg MCT formula and breastfeeding
Kasai operation performed
Management post‐Kasai
Day 1–2 NBM, on IV fluids
Day 3 Commenced hourly feeds of Dioralyte, gradually increasing to 120 mL/kg
Day 4–5 Changed to feeds and gradually increased to 150 mL/kg MCT formula. Once tolerating, changed to 100 mL/kg MCT formula
and breastfeeds
Day 7 Discharged home with advice to call liver team weekly to discuss progress and provide a weight measurement
Readmitted after 8 weeks
Admission 17 weeks old. Increased abdominal girth, remained jaundiced. Increased HARI, splenomegaly and ascites. Paracentesis
performed
Day 1 Weight = 5.78 kg (<25th centile) MUAC = 11 cm (<2nd centile). Weight affected by increased girth. Feeding: 100 mL/kg MCT
formula via bottle and breastmilk in addition
Day 2–3 Not managing full feed volume, so NG tube inserted to provide top‐up feeds. Breastfeeding continued
Day 4–7 Kasai procedure considered to have failed in view of worsening liver disease. Liver transplant assessment completed (to
determine suitability for transplant). Taking 100 mL/kg via bottle with NG top‐ups. Mum breastfeeding
Day 8 18 weeks old. Weight = 5.8 kg (9th–25th centile) MUAC = 10.8 cm (0.4th centile). Listed for transplant. Discharged from
hospital on bottle feeding and NG top‐ups providing 150 mL/kg. Formula concentration increased to provide 1 kcal (4 kJ)/mL.
Mum breastfeeding occasionally
Outpatient management
Week 1 Telephone review. 19 weeks old. Weight = 5.8 kg (9th–25th centile), static. Only managing 130 mL/kg feed. Advised to take
150 mL/kg by increasing NG top‐ups. Occasional breastfeeds
Week 2 Telephone review. 20 weeks old. Weight = 5.8 kg (>9th centile), static, increased abdominal girth, poor appetite, early satiety.
Unable to tolerate more than 130 mL/kg feed. Arranged to see in clinic
Week 3 Clinic. 21 weeks old. MUAC = 10.3 cm (<0.4th centile). Rapid progression of end‐stage liver failure. Continued on bottle feeds
with NG top‐ups. Still only managing 130 mL/kg feed. Formula concentration increased to 1.2 kcal (5 kJ)/mL. Mum no longer
breastfeeding
Week 4 Clinic: 22 weeks old. Weight = 5.82 kg (9th centile) MUAC = 10.2 cm (<0.4th centile). Poor oral feeding tolerance due to
organomegaly and ascites. Not always managing 130 mL/kg feed. Formula concentration increased to 1.5 kcal (6 kJ)/mL. Started
on complementary foods
Week 5 Admission: 23 weeks old. Received liver transplant
NBM, nil by mouth; IV, intravenous; HARI, hepatic artery resistance index; MUAC, mid‐upper arm circumference; NG, nasogastric.
The Pancreas
Introduction • production of hormones to regulate nutrient use and

storage
The pancreas is involved in three primary functions associ-
Inflammation within the parenchyma of the pancreas leads
ated with digestion and regulation of macronutrients:
to pancreatitis, and this impacts on all of the above pancre-
• production of bicarbonate fluid to neutralise gastric acid atic functions. Dietetic management of pancreatitis depends
in the duodenum on the type of disease, which may be acute, acute‐recurrent
• synthesis and secretion of digestive enzymes or chronic.
Nutrition Assessment 185
Diagnosis Causes of pancreatitis
Diagnostic criteria for acute, acute‐recurrent and chronic Causes for pancreatitis in children differ from those of
pancreatitis [55] are outlined in Table 10.19. Ranges of serum adults where lifestyle factors such as alcohol and
levels of enzymes used in the diagnosis and monitoring of smoking are common. Common causes of pancreatitis in
pancreatitis are given in Table 10.20. children are:
• idiopathic
• drugs and toxins, e.g. valproic acid and azathioprine
• biliary tract, e.g. gallstones, biliary tract malformations
Table 10.19 Diagnostic criteria for pancreatitis. choledochal cysts, pancreas divisum, pancreatic ductal
abnormalities and annular pancreas
Type of pancreatitis Diagnostic criteria
• genetic, e.g. mutations in PRSS1, CFTR and SPINK1
Acute pancreatitis Requires at least 2 of 3 criteria: • autoimmune
Lipase/amylase greater than three times the • metabolic disorders, e.g. glycogen storage disease and
upper normal limit hypertriglyceridaemia
Epigastric/abdominal pain • trauma, e.g. non‐accidental injury, fall from horse/bicy-
Imaging findings compatible with acute cle, seat belt laceration and endoscopic retrograde chol-
pancreatitis
angio‐pancreatography (ERCP) complication
Acute‐recurrent Requires 2 distinct episodes of acute
pancreatitis pancreatitis:
Complete resolution of pain ≥1 month Nutrition assessment
between episodes OR
Complete normalisation of serum amylase/ Patients with pancreatitis require regular nutritional assess-
lipase between episodes with resolution of
ment. The frequency of assessment is determined by the
pain symptoms irrespective of time interval
between episodes type and severity of pancreatitis.
Chronic pancreatitis Requires at least 1 of 3 criteria:
Abdominal pain consistent with pancreatic Anthropometry
origin and imaging suggesting pancreatic
damage Routine anthropometric measurements should be under-
Exocrine or endocrine pancreatic
insufficiency and suggestive pancreatic
taken for children with chronic pancreatitis including
imaging findings weight, height and BMI with screening for signs of impaired
Surgical or pancreatic biopsy showing growth every 3–6 months [56].
histopathological features of chronic
pancreatitis
Biochemistry
Blood tests routinely used to investigate the pancreas are

shown in Table 10.20.
Table 10.20 Serum enzymes used in pancreatitis.
Clinical
Reference
Test range* Explanation
The clinical assessment of a child with pancreatitis should
Serum amylase 25–125 IU/L Amylase is used to diagnose acute include signs of malnutrition, the clinical condition (sever-
pancreatitis as it is elevated when ity and type of pancreatitis), the presence and severity of
the pancreas is inflamed abdominal pain, diabetes and pancreatic exocrine insuffi-
Serum lipase 5–65 IU/L Lipase is used to diagnose acute ciency. It is recommended that screening for diabetes and
pancreatitis as it is elevated when pancreatic exocrine insufficiency occur every 6–12 months
the pancreas is inflamed [56, 57]. Many of the scans and procedures used as part of
Faecal elastase >200 μg/g Used for the diagnosis or the clinical assessment for the child with pancreatitis are
exclusion of pancreatic exocrine as described for liver disease (Table 10.2).
insufficiency that can be caused by
chronic pancreatitis, cholelithiasis
(gallstones) and pancreatic tumour Dietary
(should be performed on a formed
stool as it may be falsely low with a
watery stool) Dietary assessment should explore how symptoms of
pancreatitis may be impacting on intake and absorption
* Ranges may vary according to age. of nutrients. Examples of symptoms that may cause
nutritional difficulties include nausea, vomiting, abdomi- Table 10.21 Severity of acute pancreatitis.
nal pain and steatorrhoea (if there is pancreatic exocrine
insufficiency). Mild No organ failure
No local or systemic complications
Resolves in first week
Moderately severe Transient organ failure resolving in <48 hours, or
Learning points: nutritional assessment of pancreatitis
exacerbation of co‐morbid disease or local
complications
• Nutritional management will depend on whether the pan-
Severe Organ failure for >48 hours
creatitis is acute, acute‐recurrent or chronic
• Anthropometric measurements (weight, height, BMI)
should be repeated every 3–6 months
• Assessment should include signs of malnutrition, diabetes, enteral nutrition (oral/NG/nasojejunal) following any nec-
pancreatic exocrine insufficiency, the clinical condition essary fluid resuscitation and to commence PN only in chil-
(severity and type of pancreatitis) and the presence and dren unable to tolerate enteral nutrition [56, 57]. Table 10.22
severity of abdominal pain shows the dietetic management of acute pancreatitis.
• Dietary assessment should explore how pancreatitis symp-
toms are impacting on nutrition Acute‐recurrent pancreatitis
Acute‐recurrent pancreatitis is where there are at least two

episodes of acute pancreatitis with resolution of pain or nor-
Acute pancreatitis malisation of measured serum enzyme levels between epi-
sodes. PERT, previously used in acute‐recurrent pancreatitis,
Acute pancreatitis is sudden inflammation of the pancreas. is not recommended as these patients are, by definition, pan-
Children commonly present with abdominal pain, weight creatic exocrine sufficient [56].
loss and nausea or vomiting on eating. Management depends
on the severity of pancreatitis, which may range from mild Dietetic management
to severe (Table 10.21). Severe acute pancreatitis is associated
with increased morbidity in children [56]. Acute pancreatitis The dietetic management of the acute pancreatitis episodes
can present initially with mildly elevated serum markers is as described in Table 10.22. For children with acute‐
and low levels of pain but can worsen rapidly due to surgical recurrent pancreatitis caused by hypertriglyceridaemia,
interventions or the natural course of the disease. Most chil- a low fat diet is required [67]. Otherwise a normal fat‐
dren recover from acute pancreatitis with the pancreas containing diet should be given, with a low fat diet only
returning to normal [58]. The main aims of treatment are to being used if there is vomiting or abdominal pain [56]
manage pain and restore metabolic homeostasis.
Nutrition support is particularly important in acute pan-
creatitis caused by trauma. Trauma severity can range from Table 10.22 Dietetic management of acute pancreatitis.
minor lacerations to complete transection of the pancreas
and damage to the main pancreatic duct [59]. There may also Timing of initiating In mild acute pancreatitis: within 48 hours
nutrition In severe acute pancreatitis: within 72 hours
be injuries to other structures including the liver, intestine,
spleen and kidneys [59]. Depending on the type and extent Route of nutrition Commence oral/nasogastric feeding
of trauma, surgery may be required, resulting in an extended Consider nasojejunal feeding if oral/
nasogastric feeding not tolerated
period of NBM, which may impact on nutritional status.
Consider parenteral nutrition alongside
enteral nutrition if enteral not well tolerated
Dietetic management Type of nutrition If oral feeding
• Normal oral diet
The practice of treating patients with acute pancreatitis with • A fat restriction is not recommended
a period of NBM to suppress pancreatic enzyme secretion, If tube feeding
thus ‘resting’ the pancreas, has been shown to provide no • Standard feed
benefit [60–63]. In addition, the risk of bacterial overgrowth
If receiving parenteral nutrition
and gut translocation due to prolonged periods of NBM may
• Standard PN should be given (p. 67)
exacerbate pancreatic infection risk [64]. Enteral nutrition
has been reported to be well tolerated in mild acute pancrea- Surgical interventions ERCP (Table 10.2): NBM for 1–2 days may
titis and is associated with shorter length of stay, reduced be required
Puestow procedure (anastomosis of pancreatic
critical care admissions and reduced progression to severe duct to jejunum): NBM for 5 days may be
acute pancreatitis [65]. In severe acute pancreatitis enteral required
nutrition has been associated with reduced complications
and mortality [66]. Recommendations are to commence early ERCP, endoscopic retrograde cholangio‐pancreatography.
Chronic Pancreatitis 187
Table 10.23 Dietetic management between episodes of acute Table 10.24 Dietetic management of chronic pancreatitis.
pancreatitis.
Type of nutrition Normal oral diet
Timing of initiating A regular diet should be started within one week Pancreatic exocrine Require:
nutrition after the onset of acute pancreatitis insufficiency • Pancreatic enzyme replacement therapy
Type of nutrition A diet with normal fat content should be initiated • More frequent follow‐up to monitor for
A low fat diet should be initiated if: malnutrition
• There is abdominal pain/vomiting on a normal Consequent diabetes Require:
fat diet
• Pancreatitis is caused by hypertriglyceridaemia • Specialist diabetes input
• More frequent follow‐up to monitor for
malnutrition and complications
Table 10.25 Case study: an adolescent with pancreatitis.
Chronology
Admission A 15‐year‐old male. Fell off bike onto handlebars, vomited once, then vomited upon eating meal at home with significant
abdominal pain. CT scan: tear in tail of pancreas. MRI scan: swelling with fluid around tail of pancreas
Presentation: Active and physically fit with good nutritional status. Wt = 52.3 kg (25th–50th centile) Ht = 160.5 cm (9th–25th
centile) BMI = 20.3 kg/m2 (9th–25th centile)
Impression: Acute pancreatitis secondary to abdominal trauma
Acute interventions: IV fluids and standard analgesia
Dietetic intervention: Normal oral diet started
Week 1 Wt = 49.9 kg (25th centile). Amylase level increasing, no pain on standard analgesia. Poor appetite, eating less than half of meals.
Started on two cartons ONS per day
Week 2 Wt = 46.3 kg (9th–25th centile). Amylase level increased to 1400 IU/L, but no abdominal pain. Appetite slightly improved. Having
half of meals. Discharged on two cartons ONS per day with advice to have high energy/protein foods
Readmitted a week later
Week 3 Wt = 45.3 kg (>9th centile) (13% weight loss since injury). Amylase level >1700 IU/L, severe abdominal pain. Poor appetite and
pain on eating. Made NBM
Received stenting to tail of pancreas. Remained NBM
Two days later started NG feeding using 1.5 kcal (6 kJ)/mL polymeric feed at 10 mL/hour, increasing by 10 mL/hour every 4 hours
to target of 67 mL/hour × 24 hours: 1600 mL, 2400 kcal (10 MJ), 96 g protein/day
Did not tolerate NG so changed to NJ feeding after 1 day
Week 4 Wt = 46 kg (>9th centile). Started normal oral diet alongside NJ feeding, but made NBM again due to pain on eating
Week 5 Wt = 46.5 kg (>9th centile). Vomiting and increased pain. Pancreatic collection identified. NJ feeds stopped. PN commenced
providing 2000 mL, 2320 kcal (9.7 MJ), 81 g protein/day
Week 6 NJ feeding restarted at 5 mL/hour increasing by 10 mL/hour every 4 hours. PN titrated down as feeds increased. Kept NBM
Week 7 Wt = 49 kg (<25th centile). PN stopped as NJ feeds at full rate of 100 mL/hour × 16 hours. NBM
Month 2 Discharged to local hospital on full NJ feeds. NBM as trials of eating causing pain
Outpatient management
Month 3 Clinic: Wt = 52.5 kg (25th–50th centile). Having 1600 mL NJ feeds at home. Started normal oral diet the week before with no pain
or vomiting. NJ feeds reduced to 800 mL/day. Advised to remove NJ within 1 month if eating well
Month 5 Clinic: Wt = 54 kg (25th–50th centile). NJ tube removed following previous clinic appointment. Tolerating normal diet with no
abdominal pain
CT, computerised tomography; MRI, magnetic resonance imaging; BMI, body mass index; ONS, oral nutritional supplement; NBM, nil by mouth;
NG, nasogastric; NJ, nasojejunal; PN, parenteral nutrition.
(Table 10.23). There is little evidence on how restricted in Chronic pancreatitis

fat the diet should be. Low fat diets can increase the likeli-
hood of weight loss as fat is such a significant source of Chronic pancreatitis is the result of irreversible damage to
energy, and as a result these children may require high the anatomy and function of the pancreas. It initially pre-
energy low fat nutritional supplements or advice on sents as acute pancreatitis manifesting into recurring epi-
increasing the energy density of the diet. sodes before progressing to irreversible fibrosis as a result
of long‐standing inflammation [55]. Exocrine insuffi- Future research needs/unanswered questions

ciency may be seen in one third of children due to a loss of
acinar cells [68], and there is an increased risk of type 3c • the ideal MCT content of formulas/feeds for liver disease
diabetes due to a loss of islet cells [69]. The endocrine • extent of copper restriction required for Wilson’s
defect is insufficient insulin secretion (the abnormality in disease
type 1 diabetes) rather than insulin resistance (as in type 2 • ideal amount of BCAA to use in formula and the impact
diabetes) [57]. on nutritional status in liver disease
• the extent of fat restriction and the duration a fat‐
restricted diet required for chylous ascites
Dietetic management • the ideal route of feeding for pancreatitis (NG, oral or
jejunal feeding)
Children with chronic pancreatitis are at increased risk of • the impact of a low fat diet vs. a normal diet on outcomes
malnutrition [70, 71]. This may be due to a higher resting and pain in pancreatitis
energy requirement; however, there is limited evidence for • early enteral nutrition vs. delayed nutrition in pancreatitis
this in children. Children with chronic pancreatitis should • the resting energy expenditure of children with
have a normal fat‐containing diet. Those with pancreatic pancreatitis
exocrine insufficiency are at risk of fat malabsorption,
micronutrient deficiencies and poor bone health and should
have PERT [56] (p. 219). Fat‐soluble vitamin levels should Acknowledgements
be measured every 6–12 months, and bone mineral density
should be measured in children with malnutrition and Thank you to the authors of previous versions of this chapter:
persistently low serum vitamin D levels or a history of frac- Stephanie France and Jason Beyers. A special thank you to
tures [56]. It is recommended that children with pancreatic King’s College Hospital, London paediatric dietitians: Gillian
exocrine insufficiency and/or diabetes have more frequent Geaney, Helen Mortimer, Karishma Manwani and Kate
follow‐up due to the high risk of malnutrition and micronu- Arnold for their support and helpful feedback on the chapter.
trient deficiencies [56].
The dietetic management of chronic pancreatitis is sum-
marised in Table 10.24.
A case study of an adolescent with pancreatitis is described
in Table 10.25.
11 Endocrinology
S. Francesca Annan and Sarah Price
Diabetes Mellitus
S. Francesca Annan
Introduction 2016–2017. Scottish data [3] from 2017 reports the new
iagnosis incidence as 18 per 100 000 for children under
d
Diabetes mellitus describes a collection of complex meta- 5 years and 45 per 100 000 in 5‐ to 9‐year‐olds. There were
bolic disorders resulting from defects in insulin production 715 reported type 2 diabetes cases in England and Wales,
and secretion, insulin action or both. Diabetes is classified with an increase in the number of newly diagnosed reports.
into the following forms: Other forms of diabetes make up a very small percentage of
the total numbers of children with diabetes.
• type 1: β‐cell destruction, usually leading to absolute
The 2017 International Diabetes Federation (IDF) Diabetes
insulin deficiency; may be immune mediated or
Atlas [4] reports worldwide incidence and prevalence
idiopathic
for type 1 diabetes; the UK is in the top 10 countries in the
• type 2: insulin resistance with relative insulin deficiency,
world with 40 300 cases of diabetes in under 20‐year‐olds.
leading to hyperglycaemia
• other specific types: for example, monogenic forms of
diabetes; neonatal diabetes; genetic defects of insulin Key practice recommendation documents
secretion; drug‐induced forms of diabetes; secondary
to other genetic syndromes; exocrine pancreatic dis- The following publications are essential reading for dieti-
eases, e.g. cystic fibrosis‐related diabetes (CFRD) and tians practising in the care of children and young people
endocrinopathies with diabetes:
A detailed explanation of all forms of diabetes in child- • National Institute for Health and Care Excellence (NICE).
hood can be found in the International Society for Pediatric Diabetes (type 1 and type 2) in children and young people:
and Adolescent Diabetes (ISPAD) Consensus Practice diagnosis and management, NG18 [5]
Guidelines [1]. • International Society of Pediatric and Adolescent
In childhood the commonest form is type 1 diabetes [1]. Diabetes (ISPAD). Clinical practice consensus guidelines
The latest reported data from England and Wales collected in compendium 2018 [6]
the National Paediatric Diabetes Audit (NPDA) [2] shows • American Diabetes Association (ADA). Standards of
that overall prevalence rates for type 1 diabetes have been Medical Care in Diabetes 2019 [7]
stable since 2013/2014. Prevalence of type 1 diabetes under • Scottish Intercollegiate Guidelines Network (SIGN).
15 years of age was 194.2 per 100 000 population; a new diag- Management of Diabetes, A National Clinical Guideline,
nosis incidence rate of 25.4 cases per 100 000 was reported in SIGN 116 [8]

190 Endocrinology
Stage 1 Multiple insulin Stage 2 Multiple insulin Stage 3

antibodies antibodies Autoimmunity
Normal glucose levels Abnormal glucose levels Abnormal glucose levels
Presymptomatic Presymptomatic Symptomatic
Figure 11.1 Stages of type 1 diabetes.
Table 11.1 Summary of current national and international glucose and HbA1c targets.
NICE 2015 [5] ISPAD 2018 [6] ADA 2019 [7]
Waking/preprandial 4–7 mmol/L 4–7 mmol/L 5–7.2 mmol/L

glucose
Postprandial glucose 5–9 mmol/L 5–10 mmol/L N/a
Bedtime/overnight 4–7 mmol/L 4.4–7.8 mmol/L 5–8.3 mmol/L
glucose
HbA1c <48 mmol/mol <53 mmol/mol <58 mmol/mol
A lower goal of 48 mmol/mol if achievable A lower goal of <52 mmol/mol may
without increase in hypoglycaemia or during be applicable if achievable without
honeymoon phase increased risk of hypoglycaemia
N/a, not applicable.
Overview of type 1 diabetes management account for the impact not only of carbohydrate amount on
glucose levels but also carbohydrate type and quality, along
Type 1 diabetes is now described in stages with increased with meal composition [13]. Increased understanding of glu-
recognition of the process through which a person with cose responses to food has also created groups of healthcare
increased genetic risk progresses through to diagnosis [9]. professionals who believe a low carbohydrate diet should
TrialNet [10] is an international collaboration, leading be used to lower glycated haemoglobin (HbA1c) [14]. There
the work on early detection and trials to prevent or delay the is currently no evidence to recommend low carbohydrate
development of type 1 diabetes. At the current time there diets for children with type 1 diabetes.
are no nutritional recommendations for stages 1 and 2. The To provide safe and effective nutrition advice, paediatric
stages of type 1 diabetes are shown in Figure 11.1. diabetes dietitians need to be familiar with current and
The management of type 1 diabetes in childhood is chang- future technology and incorporate its use into routine
ing rapidly; development of insulin pumps and closed‐ clinical practice [13].
loop/artificial pancreas systems, using both single (insulin)
and dual hormones (insulin and glucagon) along with Current treatment options
improvements in glucose sensing technology and the devel-
opment of smart insulin pen devices, will continue rapidly There are recommendations from a number of bodies, includ-
over the next 2–3 years. In addition to the systems currently ing NICE [5], ISPAD [6] and ADA [7]. There is broad consen-
being researched worldwide, there has been an increased sus worldwide that the optimal insulin replacement is one
use of do it yourself (DIY) artificial pancreas systems, with which mimics normal physiology as closely as possible.
families building their own systems based on open‐source
algorithms [11].
The increased use of continuous glucose monitoring Glycated haemoglobin and glucose targets
(CGM) has had a significant impact on the understanding of
how food affects glycaemia [12] and has resulted in recogni- The recommended HbA1c target in England was lowered
tion of the need for whole food approaches to education that by NICE [5] in 2015 to 48 mmol/mol or 6.5%. The HbA1c
Overview of Type 1 Diabetes Management 191
Table 11.2 Commonly used insulin preparations in the UK and expected insulin action profiles.
Name Manufacturer Onset of action Peak action Duration of action Licensed for use
NovoRapid (insulin aspart) Novo Nordisk 15 minutes 60–90 minutes 3–5 hours Age 2 years and over
Humalog (insulin lispro) Lilly Age 2 years and over
Apidra (insulin glulisine) Sanofi 6 years and over
Lantus (insulin glargine) Sanofi 2–4 hours 8–12 hours 22–24 hours* Age 2 years and over
Levemir (insulin detemir) Novo Nordisk 1–2 hours 4–7 hours 20–24 hours* Age 1 year and over
Toujeo (insulin glargine U300) Sanofi 2–6 hours No peak 30–36 hours Age 18 years and over
Tresiba (insulin degludec) Novo Nordisk 0.5–1.5 hours No peak >42 hours Age 1 year and over
* Insulin action may be considerably shorter.
level in a person without diabetes is <42 mmol/mol. To injections of fast‐acting insulin with food and for the man-
achieve this target level of glycaemic management, an aver- agement of high glucose levels (correction doses); or insulin
age blood glucose level of 8 mmol/L or below is needed. pump therapy. Twice daily and three times daily (split even-
Current recommendations for the assessment of glycaemic ing insulin) regimens are not recommended for routine use
management are moving towards measuring time spent in in clinical care. Commonly used insulin preparations and
target glucose levels with a focus on minimising exposure their expected action profiles are given in Table 11.2.
to both hypoglycaemia (<3.9 mmol/L) and hyperglycaemia Newer insulin pump technologies, described as hybrid
(>10 mmol/L) [15]. closed‐loop systems, are currently undergoing clinical tri-
A number of glucose target recommendations are als in the newly diagnosed child. Hybrid closed loop inte-
available and are summarised in Table 11.1. grates the glucose sensor information into an insulin dosing
algorithm, which adjusts insulin according to sensor glu-
cose levels of every 5 minutes. These systems currently
Glucose monitoring
require meals to be ‘announced’, and carbohydrate count-
NICE guidelines recommend that blood glucose levels ing and meal boluses remain essential parts of manage-
should be checked a minimum of five times a day [5]. ment [22]. The use of insulin pump therapy from diagnosis
International recommendations [16] based on more recent is recommended by ISPAD for children under the age of
data suggest 6–10 glucose checks are required a day. They 7 years [23]. The use of pumps from diagnosis has been
also recommended that a meter with an integrated bolus reported to be associated with improved treatment satisfac-
calculator is provided to children using intensive therapy tion, but not glucose management. A 2016 study comparing
(p. 199) [13, 16, 17]. the use of insulin pump therapy between three large
CGM is currently not uniformly widely accessible across paediatric registries, namely, England and Wales (NPDA),
the UK. NICE guideline 18 provides guidance on when CGM Germany and Austria (DPV registry) and the USA
should be offered in England. The use of CGM allows a (T1Dexchange), showed a much lower percentage of the
child/family to have information about glucose levels every population with type 1 diabetes in the NPDA registry using
5 minutes with the additional benefit of alarms and alerts to insulin pump therapy, 14%, compared with 41% and 47% in
indicate the onset of hypoglycaemia (p. 200). CGM may be DPV and T1Dexchange, respectively [24]. However, the use
real time, the use of which has been demonstrated to improve of insulin pumps in 2017 in England and Wales was 32.2%
time in target range for people using both insulin pump ther- and in Scotland was 35.7%, representing an increase in use
apy and multiple daily injections (MDI) when used for more over the last 2 years.
than 90% of the time [17–19]. Intermittent use of CGM does
not lead to sustained benefits beyond the period of use. Flash
glucose systems (p. 200) are also available that allow glucose Care delivery and teamwork
to be measured without finger prick calibration, but do not It is recommended that children and young people with type
offer alarms and alerts. The currently available system 1 diabetes attend a specialist children’s clinic and are cared
requires the sensor to be read at least every 8 hours for the for by an appropriately trained paediatric multidisciplinary
information about glucose levels to be reviewed [18]. diabetes team (MDT), providing ongoing integrated educa-
tion and support [25, 26]. This team should include a paedi-
atric endocrinologist or diabetologist, diabetes nurse
Insulin management
specialists and a paediatric diabetes dietitian; children and
It is recommended that intensive insulin regimens (intensive young people should have access to psychological services
therapy) are introduced from diagnosis [5, 20, 21]: either and social workers in addition to services offered in primary
multiple daily insulin injections, using a combination of a care. The MDT should work collaboratively with the child
long‐acting insulin given once or twice a day, in addition to and their family to optimise diabetes management while
192 Endocrinology
enabling them to deal with their diabetes day to day and • to balance food intake and insulin action profiles to
reduce the risk of acute and long‐term complications. optimise glycaemic management
Teamwork and target setting have been shown to have a • to reduce the risk of micro‐ and macrovascular complica-
greater impact on clinic outcomes than the treatment regimen tions, particularly cardiovascular disease
used [27]. Teams that are consistent with the messages and • to develop a supportive relationship to facilitate behav-
information given by all team members, in addition to aiming iour change
for lower blood glucose and HbA1c targets, have better out- • to use diabetes technology to aid education about nutri-
comes and have a greater influence on parental expectations. tion and inform insulin adjustments for food and activity
To be successful, nutrition education must be tailored to management
the individual clinical, social, psychological, cultural and
economic needs of the child and family, and dietitians should
Distribution of macronutrients
convert the scientific knowledge about food into practical,
feasible advice that can be delivered by the whole MDT.
Children with diabetes have the same overall nutritional
Current guidance recommends regular review of nutrition
requirements as their peers. Energy requirements will depend
and growth as part of multidisciplinary clinics, with an addi-
on age, sex, size and activity levels. Individual assessment of
tional annual review [13]. Annual review is recommended
energy requirements will support education about the appro-
for all children with diabetes, and the following additional
priate amount and distribution of carbohydrate in the diet.
investigations are usually performed: liver function tests,
The suggested macronutrient distribution is:
renal function, urine albumin to creatinine ratio, lipid pro-
file, thyroid screening, screening for coeliac disease (CD) • carbohydrate 45%–55% energy with moderate sucrose
and retinopathy screening from age 12 years. Children with intake up to 10% total dietary energy
abnormal lipid levels will need additional advice about • fat 30%–35% energy with <10% from saturated and trans
management of dyslipidaemia. Positive coeliac screening fatty acids
will require further investigation for the diagnosis of CD. • protein 15%–20% energy
Nutritional management of type 1 diabetes Energy intake

Across the UK consensus guidelines published by the It is important to ensure that total energy intake matches
International Society for Pediatric and Adolescent Diabetes requirements and growth is regularly reviewed. Following
(ISPAD) are used to guide clinical practice. Nutrition guide- diagnosis there is usually a period of weight gain to correct
lines are published by Diabetes UK for adults only [28]. the loss of weight in the period prior to diagnosis. Appetite
A key recommendation of the ISPAD guidelines is that may be increased for 2–4 weeks. Providing a guide to appro-
more research and evidence on the role of nutrition and spe- priate portion sizes along with promotion of regular physical
cific paediatric diabetes dietary management and education activity should help prevent excess weight gain. It is impor-
is required. However, there is robust evidence for the nutri- tant to monitor energy intake and growth to identify when
tional requirements of children on which the nutrition advice on prevention of overweight and obesity is needed.
recommendations from ISPAD are based. Food choices
The rate of overweight and obesity reported for children
appropriate for health and growth and development are a aged 10–11 years in the latest National Paediatric Diabetes
key part of nutrition advice. Audit (NPDA) report was 35.3% compared with 34.3% in the
national child measurement programme in England [2].
Aims of management
Carbohydrate amount and type
The aims of management (adapted from ISPAD) are:
• to encourage healthy lifelong eating habits and appropri- Carbohydrate requirements in childhood should be individ-
ate eating behaviour within the context of the social, cul- ually determined based on weight, height, sex and activity
tural and psychological well‐being of the child and family levels. Calculation of energy needs allows determination of a
• to establish or maintain eating routines based on a wide target daily carbohydrate intake.
range of nutritious foods and provide a framework for
regular meals with minimal snacking to allow regular Example:
monitoring of glucose levels and administration of insu-
Boy aged 10 years (50th centile weight and height)
lin doses
Dietary reference value for energy [29]
• to meet the energy and other nutrient requirements for
= 1935 kcal (8.1 MJ)/day
normal growth, development and good health
Expected carbohydrate intake (45%–55% energy)
• to avoid restrictive eating behaviours that may impact on
= 217–266 g/day
growth and psychosocial well‐being
• to achieve and maintain an appropriate body mass index Regular monitoring of growth should include advice on
(BMI) maintaining an age‐ and activity‐appropriate intake. Healthy
Nutritional Management of Type 1 Diabetes 193
sources of carbohydrate including wholegrains, legumes, Carbohydrate counting

fruit and vegetables and low fat dairy products should be
Carbohydrate counting is a recognised teaching strategy to
promoted.
enable insulin to be adjusted to the amount and type of car-
Education about carbohydrate counting allows the adjust-
bohydrate eaten. Introduction of intensive therapy with
ment of prandial insulin to achieve post‐meal glucose
carbohydrate counting from diagnosis has been shown to
targets. Carbohydrate accounts for about 80%–90% of the
improve outcomes. A number of methods of carbohydrate
glucose response to a meal when preprandial insulin is given
counting education are used internationally. Studies in chil-
[30]. Carbohydrate management education should include
dren and adolescents have shown that accuracy and consist-
information about glycaemic index (GI) to facilitate under-
ency are important, meal routines and avoidance of grazing
standing about the differing glucose responses families may
should be encouraged and quality of carbohydrate food
observe when consuming the same quantity of carbohydrate
choice matters [37–39]. The three methods of carbohydrate
from different food sources [5, 13]. Foods with a lower GI
counting commonly described are:
have been shown to decrease post‐meal hyperglycaemia and
improve overall glucose management [31, 32]. • counting in grams
GI is a ranking of the effect of a carbohydrate food on • 15 g exchanges
blood glucose levels. The reference food is glucose, which • 10–12 g carbohydrate portions
has a numerical value of 100. Foods ranked as high GI > 70
impact glucose levels quickly, medium GI 55–70 less so, and No differences in outcome have been demonstrated
foods ranked as low GI < 55 impact glucose levels the least between the methods. The commonly used method in the
quickly. As GI is influenced by a number of factors, includ- UK is counting in grams.
ing the amount of fat and protein in the food, type of sugar, Studies have shown that families are able to carbohydrate
type of starch and type of fibre, the body’s processing of a count very accurately when food is labelled and packaged
low GI food is not always the same as the processing of a and less accurately when foods are ‘loose’, for example, rice,
‘healthy’ food. Perceived ‘healthy’ foods do not always have pasta and potato [38]. It is important that whichever method
a low GI. Foods with a lower GI value may be swapped for is used, families are enabled to calculate carbohydrate in
higher GI foods. Families should receive guidance in how to homemade/freshly prepared foods and do not feel they
use GI to understand glucose responses, swaps to make to need to make changes to usual food choices to enable carbo-
improve glucose responses, and when to use high GI foods, hydrate counting. Families should be taught to be consistent
e.g. in the treatment and prevention of hypoglycaemia [33]. as both precision and consistency impact on glycaemic
Ideas for families for swapping low GI foods are given in outcomes.
Table 11.3. In addition to the methods recognised above, there are
Carbohydrate education should also cover the role of fat also innovative ways being developed in less resourced
and protein on both glucose responses to mixed meals and countries to support children and families with assessment
overall dietary quality. Children should be encouraged to of carbohydrate, using hand size and local utensils to meas-
have carbohydrate sources that are lower in saturated fat. ure foods. A number of these methods are currently being
There is evidence from Europe and the USA that a focus on evaluated.
carbohydrate amount alone can result in food choices that Carbohydrate counting is used alongside an insulin to car-
are higher in saturated fat and meal and snack patterns that bohydrate ratio (ICR) to allow insulin dose adjustment. There
carry a greater risk of dyslipidaemia [34–36]. are a number of methods for calculating ICR [40]. A number
of rules have been proposed to assist calculation of ICR. The
rules use current total daily dose (TDD) of insulin to derive
the amount of carbohydrate covered by 1 unit of rapid‐acting
Table 11.3 Low glycaemic index (GI) food swap ideas. insulin. The original work on these rules comes from adults
Breakfast Choose lower GI cereals or porridge; have fruit and yoghurt
converting from MDI to pump therapy. To calculate the ICR
in place of cereal. Swap to wholegrain and sourdough the number from the rule is divided by TDD. The commonly
breads. Add fruit to breakfast cereal used rule in adult practice is the 500 rule, which is usually
Lunches Use pitta, wraps and flatbreads for sandwiches. Swap to insensitive in the paediatric population [40].
oat‐based crackers. Try pasta and rice salads, use Alternative rules in paediatric practice are 150, 200 and
homemade cereal bars that include oats and seeds in place 250 rules in younger children and the 300 and 350 rules in
of bought snacks. Have fruit and vegetable sticks as extras older children and adolescents.
Main Swap sweet potato or new boiled potato for baked or Younger children have higher bolus insulin requirements
meals mashed potato. Use more pasta and noodles and rice. Add and usually need relatively bigger insulin doses with food
beans and pulses to cooked dishes, replace some meat than older adolescents and adults [40]. The amount of bolus
with beans and lentils
insulin and the strength of the ratio will be affected by the
Snacks Fruit all types, vegetable sticks, low fat yoghurt and amount of basal insulin used. It is recommended that 30%–
popcorn as alternatives to biscuits and crisps 50% of the insulin should be basal insulin with an increasing
If a bedtime snack is needed, swap to milk, yoghurt and
body of evidence indicating that lower total basal insulin is
yoghurt drinks
linked to improved outcomes [41]. It is usual for ICR to vary
194 Endocrinology
Table 11.4 Impact of adjusting ICR on actual dose delivery according to device.
Meal amount (CHO) Ratio Calculated dose (units) Pen delivery (0.5 unit pen) Pen delivery (1 unit pen) Pump delivery
30 g 1 unit to 15 g 2 2 2 2

30 g 1 unit to 12 g 2.5 2.5 2 or 3 2.5
30 g 1 unit to 10 g 3 3 3 3
30 g 1 unit to 8 g 3.75 3.5 or 4 3 or 4 3.75
30 g 1 unit to 6 g 5 5 5 5
ICR, insulin to carbohydrate ratio; CHO, carbohydrate.
across the day, reflecting the pattern of insulin sensitivity management of mealtime insulin can be provided based on
seen. Typically, ratios are stronger on waking for breakfast results seen by families.
and weaker at midday and bedtime. Care is needed in Fat has been shown to produce delayed hyperglycaemia
explaining ratio adjustment. In most pump and meter bolus when consumed with carbohydrate [42]. The impact of high
calculators, ratios are expressed as 1 unit to cover an amount protein or high fat with carbohydrate is less than the com-
of carbohydrate, e.g. 1 unit to 8 g carbohydrate. To increase bined impact of high fat and high protein [43]. Protein, when
insulin dose the carbohydrate value is lowered, and to consumed with carbohydrate, blunts the rise in glucose levels
reduce the insulin dose, the carbohydrate value is increased. at 90 minutes and causes a delayed rise in glucose levels
The ability to deliver the actual calculated dose will depend between 2 and 5 hours [44]. Protein consumed in the absence
on the treatment regimen as illustrated in Table 11.4. of carbohydrate has also been shown to cause a delayed rise in
glucose levels when consumed in high quantities, 75 g or
more protein per serving [45]. The impact of fat and protein is
Fat and protein
likely to be more noticeable when smaller amounts of carbo-
hydrate are consumed. It is suggested that meals containing
Population‐based recommendations for fat intake are 30%–
more than 20 g fat and 25 g protein per serving may cause
35% total dietary energy. The goal of management is to
delayed postprandial hyperglycaemia and will require addi-
ensure that saturated, trans and total fat intake fall within
tional food insulin dosing [13]. Examples of meals that can
recommendations for the population. There is an association
cause these problems include pizza, pasta with creamy sauces,
between high saturated fat intake and increased insulin
fish and chips, rice with curry, fish pie and takeaway foods.
requirements, as well as increased risk of cardiovascular dis-
A variety of methods of calculation of additional insulin
ease and obesity [34, 42]. Children should be encouraged to
have been proposed:
reduce saturated fat intake. Where appropriate this can be
replaced with unsaturated fats; consumption of oily fish two • Pańkowska et al. [46–48] suggested the use of a formula
to three times a week should be promoted. to calculate fat and protein units (FPU) to determine both
Protein requirements for growth are the same as for the increase in insulin dose and duration of insulin delivery
general population, and intake will vary with age and rates of for patients using insulin pump therapy.
growth. There is likely to be benefit from encouraging vegeta- • The food insulin index (FII) has also been proposed as an
ble protein sources, such as legumes, as part of a healthy diet. alternative to carbohydrate counting in adults [49].
Detailed information about advice on fat and protein can be • A recent study comparing carbohydrate counting, FPU
found in the ISPAD guidelines chapter on nutrition [13]. formula and FII demonstrated increased time in target
Education about the impact of fat and protein on post- range for blood glucose levels with the FPU formula and
prandial glycaemia should also be given. There is clear evi- increased incidence of later hypoglycaemia [50].
dence that meals higher in total fat and/or protein increase • Data from the studies suggests that at least 20% more
insulin requirements for at least 5–6 hours after eating insulin is needed for the higher fat/protein meals.
[42–44]. A number of post‐meal glucose effects have been Increases of 60% are associated with increased hypogly-
observed and studied; the commonly reported issues by caemia incidence [51].
families are a post‐breakfast glucose spike around 60–90 • For all mixed meals, insulin delivered using a combina-
minutes after eating and raised glucose levels overnight tion bolus on insulin pump therapy has been demon-
after meals eaten in the evening [12]. strated to be more effective at controlling postprandial
Mealtime insulin dosing based solely on amount of carbo- glycaemia [52–55].
hydrate is likely to be insufficient to maintain postprandial • For patients using MDI it is suggested that a second
glycaemia for many [42]. Significant individual differences injection is given after the meal to provide the additional
exist in the requirement for additional insulin, and, there- insulin needed [56].
fore, advice should be based on observation of effect of
meals. Initial education should raise awareness of the foods Practical advice for managing post‐meal glucose levels is
likely to create an issue, and individual review of given in Table 11.5.
Education and Review 195
Table 11.5 Practical advice for managing post‐meal glucose levels. effect (sugar alcohols) and are higher in fat than the product
Use a combination bolus with at least 60% immediate bolus and
they are replacing.
extended over 3 hours
Give an additional dose of insulin 20% for meals causing delayed Salt
hyperglycaemia.
Increase carbohydrate amount used in a bolus calculator by 20% on Children with diabetes should follow the same recommen-
pump therapy.
dations for salt intake as the general population (Table 2.1).
Give an additional injection of 20% of calculated insulin dose on MDI
Reduce saturated fat content of meals to improve glucose profiles
Add low fat protein sources to breakfast to blunt postprandial
Education and review
glucose spike
It is recommended that all children receive a process of
MDI, multiple daily injections. education from diagnosis through the ages and stages of
development so that the young person has the necessary
knowledge and diabetes self‐management skills as they
Fibre transition to adult services [26].
A number of studies have looked at the impact of educa-
Children’s diets should contain a variety of fibre containing tion programmes on glycaemic outcomes. These studies
foods including fruit, vegetables, wholegrains and legumes. were all conducted in children and adolescents with estab-
Both soluble and insoluble fibre sources should be con- lished diabetes and had little or no impact in terms of
sumed. High fibre diets are associated with reduced risk of improving HbA1c, but reported some benefit to quality of
cardiovascular disease and improved digestive health. life [58, 59]. No studies have evaluated the same education
Dietary fibre modulates bowel function, fermentation and processes from diagnosis. Both NICE and ISPAD [5, 26] have
effects of the gut microbiota. Eating an age‐appropriate recommendations for education at diagnosis with ongoing
amount of fibre is important for glycaemic management, gut review. Nutrition education is part of the wider diabetes
health and reduction in cardiovascular risk. Children with education package. Education that embeds solution focused
diabetes should be encouraged to meet the current UK pop- and motivational interviewing techniques is beneficial [60].
ulation guidelines on fibre intake (Table 2.18) [57]. Practical Structured education packages for use from diagnosis
ways do this include higher fibre breakfast cereals, addition have been developed using educational theory and offer a
of beans, pulses and lentils to cooked dishes and the use of variety of learning styles, but not all of these have been eval-
raw vegetables and fruits as between meal snacks. uated by clinical trials. These are summarised in the box
below.
Sucrose
GOALS of diabetes education (Novo Nordisk) – education
Sucrose can be consumed within the context of a healthy curriculum available from www.novonordisk.co.uk/
diet. Isocaloric quantities of sucrose and starch increase glu- content/dam/UK/AFFILIATE/www‐novonordisk‐co‐uk/
cose levels by the same amount. Foods containing high Home/Health%20Care%20Professionals/Documents/
amounts of sucrose should be discouraged as a regular com- GoDe_Book_v7_INTERACTIVE.pdf
ponent of the diet in line with population guidelines. Routine SEREN structured education programme (Welsh
use of sugar‐sweetened beverages should be avoided except Paediatric Diabetes Network) – details available from
for the treatment and prevention of hypoglycaemia. www.cypdiabetesnetwork.nhs.uk/regional‐pages/
wales/network‐projects/seren‐structured‐education‐
Sweeteners and specially labelled products programme/
Deapp diabetes digital education – details available
Non‐nutritive sweeteners used commercially can assist in from http://deapp.nhs.uk/home
reducing total sucrose intake. Advice should be given to
avoid excessive consumption, and water should be encour-
aged as the first‐choice drink rather than diet fizzy drinks. Management at diagnosis
Fructose is not recommended as a sweetener in place of
sucrose. Recent changes to UK food taxation have reduced Education about nutrition and diabetes management should
the sugar content of drinks, though in some cases this has begin as soon as possible post‐diagnosis. Withholding edu-
resulted in increased use of non‐nutritive sweeteners to cation and information can lead to increased anxiety and dif-
maintain a sweet taste. Reduced sugar products are widely ficulties with glucose management. Surveys conducted by
available and can be useful. the Families with Diabetes National Network highlight the
Internationally, products labelled ‘diabetic’ are not recom- importance of education about food, and specifically man-
mended for routine use in the diets of children. They are agement of carbohydrate, on receiving the diagnosis of dia-
often expensive, contain sweeteners that have a laxative betes [61]. Education may occur within the hospital setting
196 Endocrinology
or at home depending on local practice. The Delivering Early MDT review in addition to annual educational review. Key
Care in Diabetes Evaluation (DECIDE) study compared points for education for both the family and child/young per-
management at home vs. management in hospital at diagno- son are at transition to nursery, primary school, secondary
sis; this showed no difference in outcomes and explored par- school and university and how to manage exam times. Age‐
ent preferences. Education can be successfully delivered in specific considerations are given below.
either setting [62].
Education at diagnosis is the beginning of a process and
Babies and toddlers
should enable a family to understand the role of amount and
type of carbohydrate, calculate insulin doses for carbohy- A detailed review of the management of preschool children
drate in meals, understand the importance of timing of insu- can be found in the ISPAD guidelines [23]. Diabetes manage-
lin and meal routines, appreciate the impact of the whole ment in babies and toddlers is best supported by establish-
meal on postprandial glucose levels, introduce GI and sup- ing eating routines. Supportive advice allows normal
port the management of food and activity in school. In addi- weaning and development of intake of solid foods. Insulin
tion, for children commencing pump therapy at diagnosis should be given preprandially or as a split dose with some
education about bolus type is needed. The use of diabetes insulin given before the meal and some during. Glucose lev-
education checklists can help to provide consistency of edu- els are more difficult to manage when frequent grazing
cation as well as a record of teaching for both the family and occurs [37]. Parental behaviours at mealtimes have been
diabetes healthcare team. An example of the nutrition com- shown to impact on glycaemic outcomes [63]. Dietitians
ponents of an education programme at diagnosis is given in need to support parents to establish mealtime routines and
Table 11.6. A case example of a girl newly diagnosed with reduce parental anxiety.
diabetes is given in Table 11.7 Advice on normal eating behaviours and the variability of
appetite in this age group should be given. Food refusal can
Ongoing review cause significant anxiety due to fear of hypoglycaemia [64];
it is helpful to provide guidance on appropriate carbohy-
Ongoing management depends on the age and developmental drate amounts at meals to avoid issues arising from parents
stage of the child or young person. General recommendations trying to feed too much carbohydrate to a young child. They
encourage at least 3 monthly contact with a dietitian as part of can be advised that eating 5–7 g less or more carbohydrate
than the mealtime dose calculation should not cause a sig-
nificant problem. When less than half the meal is consumed,
Table 11.6 Example of nutrition components of an education
due to insulin action, there is time to offer additional carbo-
programme at diagnosis.
hydrate. It is important that treats/sweets/desserts are not
Topic Date Sign used as replacement carbohydrate foods. It is possible to
achieve glycaemic management with both MDI and pump
Food and carbohydrate counting therapy, though there may be a preference for pump therapy
• Assess usual dietary habits due to the number of insulin injections required with MDI.
• Check ward carbohydrate counting information
Anxiety about hypoglycaemia may be helped by the use of
available at bedside
• Explain role of food in diabetes management CGM systems.
How carbohydrate, protein and fat impact of glucose In the younger age group, it is suggested that the follow-
levels ing ‘rules’ are used for calculation of insulin doses: breakfast
Recommend changes if needed, e.g. replace sugar‐ 150/TDD and other meals 250 or 330/TDD [23]. Education
containing drinks with water/no added sugar drinks, and support may be needed for the management of food in
timing of sweets/treats
nursery.
• Introduce principles of lower fat, lower GI
wholegrain food choices
• Explain carbohydrate counting including use of School‐age child
scales/weighing foods/food labels/portion pots
• Explain use of insulin to carbohydrate ratio to The routine of starting school brings more structured days
calculate insulin doses and mealtimes, which can help diabetes management rou-
• Discuss school meal management tines. Education about food in school will be needed. The
Observation of carbohydrate counting and insulin dose availability of information about carbohydrate content of
calculation on ward at mealtime before discharge school foods depends on the catering providers. Education
Exercise/physical activity is also needed about the management of activity in school.
• Assess the ‘normal’ levels of physical activity As a child begins to engage in more activities with friends,
undertaken across the week school and clubs, appropriate advice about eating away
• Advise on regular PA as part of healthy lifestyle
from home should be given [65]. Prior to the transition to
• Advice on extra fast‐acting carbohydrate prior to/
during exercise and advice on reduction of insulin as
secondary school education, to support the child to become
appropriate more independent in managing their food is essential as lev-
els of support change dramatically in secondary school for
GI, glycaemic index; PA, physical activity. the majority of children.
Ongoing Review 197
Table 11.7 Case example: Management of a girl newly diagnosed with diabetes.
A 7‐year‐old female. Her first language is Arabic

Presentation: Admitted following GP referral with symptoms of tiredness, thirst, excessive urine production and weight loss. Blood glucose level on
arrival 42 mmol/L, pH 7.32, blood ketones 5 mmol/L
Diagnosis: Type 1 diabetes
Initial medical management: Diabetes ketoacidosis protocol
Insulin treatment regimen: Multiple daily injections
Levemir 4 units morning 7 am and 4 units evening 7 pm NovoRapid
Breakfast 1 unit to 8 g carbohydrate
Midday meal 1 unit to 12 g carbohydrate
Evening meal 1 unit to 10 g carbohydrate
Nutritional diagnosis: New diagnosis type 1 diabetes, caused by autoimmune destruction of pancreatic β-cells, evidenced by presenting blood
glucose and ketone levels, auto‐antibodies and HbA1c on screening blood tests
Dietetic assessment: Establish family meal routines and usual foods eaten, school routines and regular activities
Initial management plan: Nutrition and diabetes education (days 1–6) covering:
Session 1 Food choices for health, understanding food and glucose levels, introduction to carbohydrate counting
Session 2 Review and recap session 1 plus carbohydrate counting, use of insulin to carbohydrate ratio, preprandial insulin dosing, use of insulin
sensitivity factor
Session 3 Review and recap session 2 plus glycaemic index, role of fat and protein, management of activity, food in school
Follow‐up 1 week post‐discharge: Joint nurse and dietitian review
Follow‐up 2 week post‐discharge: Multidisciplinary diabetes clinic
Insulin doses at clinic review
Levemir 3 units and 3 units pm
Insulin to carbohydrate ratios:
Breakfast 1 unit to 9 g carbohydrate
Midday meal 1 unit to 12 g carbohydrate
Evening meal 1 unit to 12 g carbohydrate
Example of glucose profile at clinic review:
Glucose: Standard day

mmol/L
20
18
16
14
12
10
8
6
4
2
00:00 02:00 04:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 24:00
Monday Tuesday Wednesday Thursday Friday Saturday Sunday
Statistics
Number of values: 59 Values above goal (9 mmol/L): 4 Highest value (mmol/L): 13.9
Values per day: 7.4 Values within goal (4–9 mmol/L): 45 Lowest value (mmol/L): 2.7
Period average (mmol/L): 6 Values below goal (4 mmol/L): 10 Standard deviation: 2.2
Follow‐up education plan:

Insulin adjustment
Review of carbohydrate counting
Education for insulin pump therapy
198 Endocrinology
09:00–10:00
Median (50%): 16.4 mmol/L
IQR (25–75%): 12.5–19.4 mmol/L
10/90 percentile (10–90%): 8.3–22.2 mmol/L
35
Min/max (0–100%): 4.3–24.2 mmol/L
30
25
20
mmol/L
15
10
0
00:00 02:00 04:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00
Figure 11.2 Impact of missed meal and snack injections in a 14‐year‐old boy on multiple daily injections.
Adolescents doses and energy intake. Increased body weight is associated

with increased insulin resistance; in addition to reviewing
During adolescence, pubertal growth challenges diabetes
nutritional intake review of medical management and the
management. Meal routines are often disrupted by lifestyle;
use of insulin sensitising, therapies may be of benefit.
however, routine remains important to achieving glucose
Management of both disordered eating and obesity
management targets. Missed meal and snack insulin boluses
will require an MDT approach that includes psychology,
have a negative impact on overall glycaemia [66–68], as illus-
medical, nursing and dietetic members of the team.
trated in Figure 11.2.
Specialist care may be needed for the management of
Support with the management of exams, school trips, activ-
eating disorders.
ity, eating away from home and alcohol will be needed. Where
paediatric diabetes services care for young people through to
19 years of age, advice for transition to university will be
Festivities, fasting and special events
essential. This should include practical aspects of food and
diabetes management including encouragement to develop Lifestyle advice needs to incorporate the management of
cooking skills alongside carbohydrate counting ability. events that occur through the year in a child’s/family’s life:
Monitoring weight in this age group may identify issues parties and special occasions, religious events and festivals
with both excess weight gain and also weight loss and disor- including fasting. Though younger children may be exempt
dered eating behaviours. Insulin omission in order to lose from fasting, they will often wish to participate in family
weight is not uncommon in this age group. A number of events, and supportive advice should be provided. Often
screening tools are available for use in clinical settings. The special occasions mean that different foods are eaten at dif-
risk for eating disorders increases with duration of diabetes. ferent times of day to usual. Advice may need to include
Frequent admissions in diabetic ketoacidosis (DKA) and the impact of the types and timing of foods on glucose lev-
deteriorating glucose levels are potential indicators of disor- els, adjustments to insulin dosing for the specific occasion
dered eating and body image concerns. and the prevention of hypo‐ and hyperglycaemia. Detailed
Overweight and obesity challenge diabetes management. management about Ramadan and fasting can be accessed
A pattern of increasing weight will need addressing with from the International Diabetes Federation (IDF) Ramadan
review of activity levels, frequency of hypoglycaemia, insulin guide [69].
Different Treatment Regimens and Continuous Glucose Monitoring Technology 199
Different treatment regimens and continuous to occur [39]. If food refusal is a concern, parents can be
glucose monitoring technology reassured that additional carbohydrate can be given; in
most cases a falling glucose level will cause hunger. If
Twice daily and split evening insulin food refusal is a significant concern, then insulin pump
therapy may be a more suitable treatment option.
Twice daily insulin using premixed insulin does not mimic • Advice to avoid post‐meal insulin injection can include
physiological insulin production. A mix in the morning with giving insulin split into two doses, one at the start of the
a rapid‐acting insulin for the evening meal and intermediate meal and one towards the end of the meal.
acting insulin before bed is also not optimal. These insulin • ICR will need to be reviewed regularly; it is usual to need
regimens are not recommended for routine clinical care. If different carbohydrate ratios at different times of the day
used then education about consistent carbohydrate intake, as insulin sensitivity varies across the day. Usually the
mealtime routines and snacks between meals and before bed breakfast ratio needs to be significantly ‘stronger’ than
to offset the risk of hypoglycaemia and match the insulin those used at midday and evening meals.
action profiles will be needed [13]. • It is recommended that a glucose meter with a bolus cal-
culator is used to reduce the burden of the family having
to do the calculation and the risk of insulin stacking
Intensive therapy causing hypoglycaemia.
• The effectiveness of the ICR can be assessed by looking at
Intensive therapy delivered as both MDI and insulin pump the change in glucose levels. As a guide a glucose level
therapy should have the following components: above target (9 mmol/L) in the first hour is due to insulin
• an ICR timing; a raised level at 2–3 hours is likely to be due the
• an insulin sensitivity or correction factor (ISF) ICR; and a raised level at 3–5 hours indicates the need for
• a duration of insulin action or active insulin time adjustment in insulin distribution for the meal type.
• a target glucose level used for calculations
• a bolus dose calculator incorporating all the above fac- Insulin pump therapy
tors, which displays information about active insulin
(bolus insulin already delivered) The current options for insulin pump therapy are:
1. stand‐alone insulin pump with or without a continuous

Multiple daily injection therapy or flash glucose sensor (p. 200)
MDI are recommended from diagnosis alongside carbohy- 2. sensor‐augmented insulin pump therapy
drate counting and insulin adjustment using an ICR and 3. hybrid closed‐loop insulin pump therapy
insulin sensitivity factor:
Insulin pump therapy is recommended for younger chil-
• Insulin is needed for both meals and snacks. The amount dren as it offers advantages over injected insulin in the man-
of insulin should be calculated using the ICR. The small- agement of eating behaviour. Insulin pump therapy will
est dose of insulin it is possible to give with an insulin require the same education about the use of ICR, timing of
pen is 0.5 unit. Families should be advised that all food insulin delivery and appropriate mealtime routines as MDI.
containing carbohydrate, whether eaten as a meal or As with MDI it is important to cover all carbohydrate foods
snack or drink, requires insulin if the calculation of dose with insulin; missed meal and snack boluses are a significant
is 0.5 unit or more. cause of increased time spent in hyperglycaemic ranges. The
• It is helpful to provide guidance on appropriate amounts use of an insulin pump allows mealtime insulin dosing to be
for snacks. Children with diabetes can follow current more easily adjusted to the glycaemic effect of the food con-
public health guidance on the amount of food for a snack. sumed. Nutrition education should include the use of
Current analogue insulins used in MDI do not require advanced bolus techniques to help increase time spent in
between meal or bedtime snacks. Children should be range post‐meals. Information as previously discussed about
able to omit snacks without hypoglycaemia if basal insu- the impact of protein and fat in meals along with strategies
lin doses are correct. If carbohydrate is needed to prevent to manage their glycaemic effects should be discussed for
hypoglycaemia between meals, this is an indication that families using options 1 and 2 above.
insulin doses need reviewing. Current options for insulin delivery using a pump are a
• Advice on optimal timing of the pre‐meal rapid‐acting standard or normal bolus, an extended or square wave bolus
insulin should be given. Rapid‐acting insulin should be and a combination bolus, illustrated in Figure 11.3. Evidence
given 15 minutes before eating; post‐meal insulin deliv- shows that the square or extended bolus is not effective in
ery results in postprandial glucose levels that are up to the paediatric population for dealing with meals, as insuffi-
5 mmol/L higher than pre‐meal dosing [70, 71]. Hypo‐ or cient insulin is active in the first 60–120 minutes [72]. For
hyperglycaemia, as a result of a mismatch between insu- most mixed meals the combination bolus has been shown to
lin dose and carbohydrate amount, usually takes 2 hours be more effective than a standard bolus. The optimal split of
200 Endocrinology
Currently available bolus insulin delivery options using insulin pumps

Insulin dose
Normal
Combination
Square or extended
Time
Figure 11.3 Bolus insulin delivery options.
insulin in the combination bolus varies from individual to activity, including active play and movement, are also avail-
individual. It is suggested for most children at least 50% of able for the under 5s. Children and young people should be
the insulin needs to be given in the immediate bolus, and doing aerobic exercise and exercise to strengthen bones and
this may be as high as 70% for some specific meals [51]. The muscles daily. The health benefits of regular activity include
duration of insulin delivery will also vary; however, a sensi- maintenance of healthy weight, reduced cardiovascular risk,
ble starting point is 2–3 hours. Families should be taught improved bone health and increased well‐being. Lower lev-
how to assess the impact of meals on glucose levels and els of physical activity and physical fitness in children and
adjust bolus insulin delivery to maximise the benefits of adolescents with type 1 diabetes have been reported [75].
using insulin pump therapy. The current hybrid closed‐loop Physical activity in type 1 diabetes can be challenging as
system does not have advanced bolus functions as basal the normal physiological responses to exercise are disrupted
rates are adjusted according to glucose changes post‐meals. due to the inability to adjust insulin in response to acute
changes in glycaemia. Detailed explanations of exercise
physiology and type 1 diabetes can be found in the Juvenile
Continuous and flash glucose monitoring Diabetes Research Foundation (JDRF) Performance in
The use of real‐time and intermittent CGM systems is Exercise and Knowledge (PEAK) consensus paper on exer-
increasing understanding of mealtime glucose responses. cise and type 1 diabetes management and the ISPAD guide-
The effects of foods are immediately obvious to both families lines [76, 77].
and healthcare professionals. As part of nutrition education, Activity advice should be underpinned by an understand-
it is helpful to explain the normal glucose responses to meals ing of exercise types, normal exercise physiology and the
in the population without diabetes. Parents and young peo- impact of type 1 diabetes on the usual physiological pro-
ple should understand that glucose levels fluctuate, and the cesses. Exercise can be broadly classified into three types
aim of treatment is not a flat line. Dietitians should be able to based on the predominant energy systems used: aerobic,
interpret sensor downloads and provide appropriate man- mixed and anaerobic exercise. The usual glucose responses
agement advice to families. Rate of change (ROC) arrows in type 1 diabetes are summarised in Figure 11.4.
that predict the direction of change in glucose levels are Children, young people and families need advice based
increasingly being incorporated into decision making. on an understanding of how the usual physiological
Resources are available to help families use this information responses to different types of activity may impact glucose
to adjust insulin doses to increase time in spent in target [73]. levels and factors that alter glucose responses to exercise
alongside management strategies, including nutrition and
glucose monitoring, to promote appropriate levels of physi-
Physical activity and exercise management cal activity.
Type 1 diabetes disrupts usual exercise physiology as
Regular physical activity is important for long‐term health. insulin cannot be adjusted in response to activity; addition-
Children with diabetes aged over 5 years should be advised ally, insulin delivered by either injection or insulin pump is
to achieve the World Health Organization recommendation delivered to the peripheral circulation, whereas pancreatic
of at least 60 minutes moderate to vigorous activity a day insulin production is via the portal circulation. This can pro-
[74]. Specific recommendations on promotion of physical duce the effect of insulin being in the ‘wrong’ place at key
Physical Activity and Exercise Management 201
Aerobic Mixed Anaerobic

For example, For example, For example,
walking, jogging, cycling team sports – football, sprint based events –
basketball, rugby, hockey swimming, cycling, track and
field athletics
Usual glucose trend
Glucose level usually falls
Glucose level usually

rises
Glucose may rise or fall
Figure 11.4 Usual glucose responses to exercise. Source: Adapted from Riddell et al. [78]. Reproduced with permission of John Wiley & Sons.
Table 11.8 Factors associated with the effect of activity on blood • an insulin adjustment strategy to prevent hypo‐ and
glucose levels. hyperglycaemia
• management of the post‐activity period
Blood glucose falls Blood glucose rises
Aerobic or low intensity Anaerobic or high intensity exercise Blood glucose targets for activity
exercise
Excess insulin Insufficient insulin Regular glucose monitoring before, during and after activ-
Prolonged duration Short duration ity is important to guide both insulin and nutrition adjust-
Insufficient carbohydrate Excess carbohydrate ments. This may be done by the use of finger prick glucose
checks or a glucose sensor. Trends in glucose levels help
Extremes of temperature Heat stress
(cold or hot environment) direct actions; understanding if glucose levels are stable,
rising or falling will enable targeted advice to be used more
Activity within 2 hours of Competitive nature of the sport
unadjusted insulin bolus (adrenalin will increase the blood
effectively. A change in glucose level of more than 2 mmol/L
glucose level) over 30 minutes when using finger prick values indicates
that glucose level is rising or falling. For glucose sensors
the ROC arrows should be explained to families to allow
points during exercise and recovery. As the duration of dia- them to interpret how glucose levels are changing. It is use-
betes increases, there may a loss of glucagon production by ful to give an example of what the change in glucose levels
α-cells of the pancreas; however, a study in recently diag- means in real terms. For example, if a finger prick glucose
nosed adolescents has demonstrated glucagon production level is 7.5 mmol/L 30 minutes before exercise and
during exercise at similar levels to matched controls without 5.5 mmol/L immediately before exercise, if that pattern
diabetes [78]. continues, then the glucose level will be 3.5 mmol/L in the
Hypoglycaemia is often cited as a barrier to exercise [79]; next 30 minutes.
however, many young people also experience significant Families should be advised that starting exercise with a
hyperglycaemia during exercise. Education should focus high glucose level does not protect from hypoglycaemia;
on strategies to maintain glucose levels between 5 and in fact the opposite appears to be true. The higher the start-
10 mmol/L during activity [76]. Factors associated with the ing glucose level, the greater the fall [80]. Starting with a
effect of activity on blood glucose levels are given in glucose level in target is optimal for hypoglycaemia
Table 11.8. prevention.
Education about physical activity management should Children and families should be advised:
include:
• the starting glucose level will need to be interpreted in
• an explanation of exercise types and the expected glu- the context of the timing of any pre‐exercise food and
cose responses; however, as studies on type of exercise insulin
report the mean responses, it is important to explain that • to start exercise with a glucose level above 5 mmol/L
glucose responses are individual and may differ from • to aim for a glucose level between 5 and 10 mmol/L
those expected during exercise
• a blood glucose monitoring strategy to enable under- • to check glucose levels before activity at least twice
standing of the individual responses within the preceding hour, every 30 minutes during and
• a nutrition strategy to prevent hypoglycaemia and immediately after activity and then 1–2 hourly, overnight
support performance if appropriate if activity has been very strenuous
202 Endocrinology
• to check blood ketones if glucose level is above need to be adjusted between 9 pm and 3 am for pump users
13.9 mmol/L or with a reduced night‐time injection on MDI. Insulin
• to stop or avoid exercise if glucose level is above requirements have been shown to be at least 20% lower
13.9 mmol/L and blood ketones are above 1 mmol/L during this period.
Nutrition advice for activity

Insulin adjustment advice for activity
Nutrition advice may be needed for either hypoglycaemia
Bolus insulin prevention or sports performance with the majority of stud-
Aerobic activity undertaken within 90–120 minutes of an ies on nutrition and activity in type 1 diabetes focusing on
injection or bolus of fast‐acting insulin will carry an increased the former. When hypoglycaemia prevention is the priority,
risk of hypoglycaemia. For this reason, it is generally recom- energy balance and the avoidance of overconsumption of
mended that insulin is reduced with any meal or snack or energy should be considered. If weight management is a
correction dose within 2 hours of starting exercise. The mag- concern, then hypoglycaemia prevention should focus on
nitude of reduction needed varies between 25% and 75% and insulin adjustment and appropriate adjustment of distribu-
will be influenced by the duration of the activity, and how tion of usual food around activity sessions. For sports per-
close the insulin delivery is the start of the activity. A good formance an increase in energy intake may be appropriate
starting point is to make a 50% dose reduction and keep a for training and adaptation. Children undertaking the
record of the impact of this advice for specific activities. recommended 60 minutes a day of moderate to vigorous
Often if activity is anaerobic or competitive, a reduction in activity should not need an overall increase in energy intake
pre‐activity meal insulin may not be needed. The insulin compared to reference intakes for the general population.
dose reduction may also vary with the time of day the activ- Those children/young people who undertake high volumes
ity is undertaken, with early morning exercise carrying a of activity should have an individual assessment of their
lower risk of hypoglycaemia than midday or evening exer- energy, carbohydrate and protein intake [13]:
cise. Families will notice that the need for insulin adjust- • Most aerobic activity lasting more than 30 minutes will
ments will change during periods of rapid growth when need additional carbohydrate if insulin has not been
insulin requirements are higher. Bolus insulin adjustments adjusted:
are also likely to be needed after exercise due to the increase ⚬⚬ Carbohydrate requirements vary between 0.5 and
in glucose transporters in the post‐exercise period. Lower 1.5 g/kg body weight and depend on duration and
insulin doses are likely to be effective in managing both food type of activity and prior insulin adjustments.
and corrections for between 6 and 24 hours post‐exercise. • Carbohydrate and protein should be consumed at the
If glucose levels are elevated (>10 mmol/L) immediately meal before planned activity lasting 60 minutes or longer
before exercise or during exercise, it may be appropriate to and post‐activity to replace hepatic and muscle glycogen
use a reduced correction dose to prevent further hypergly- stores. Ingestion of protein before activity has been shown
caemia especially during anaerobic or competitive sports. to reduce hypoglycaemia risk during the active period.
This should be evaluated, taking into account previous insu- • Carbohydrate snacks for exercise should be low in fat.
lin delivery. A high glucose level in the presence of active Fruit and dried fruit, fruit juice and low fat homemade
insulin may not require additional insulin. granola bars are good options. Attention to the amount
of exercise snacking is necessary to ensure that overall
dietary quality is not reduced by less healthful snack
Basal insulin
choices. For many children 10–15 g carbohydrate will be
Prior adjustment of basal insulin is possible for planned sufficient to prevent hypoglycaemia.
activity on insulin pumps or twice daily long‐acting basal • An isotonic drink containing 6% simple sugar such as
insulin injection. The use of a temporary basal reduction can glucose, fructose or sucrose is ideal if additional carbo-
be useful for aerobic activity. Basal reductions on the insulin hydrate is required for short duration exercise. Advice
pump should be started at least 30 minutes and probably about dental health should be given to reduce the impact
60–90 minutes before the activity to produce a meaningful of these drinks on the teeth.
reduction in basal insulin levels during exercise. At the start • For some children additional pre‐exercise carbohydrate
of exercise, the increase in capillary blood flow to active may necessitate bolus insulin if the exercise is high inten-
muscle may mean, despite a decrease in basal insulin levels, sity or strenuous or anaerobic [76]. Hyperglycaemia will
circulating insulin levels rise transiently due to increased occur during exercise if insufficient insulin is available,
insulin absorption. When reductions in basal insulin are particularly if the exercise is anaerobic. Performance is
required, a starting point of 20%–50% is suggested. As with influenced by glucose levels.
bolus adjustments these should be monitored and adjusted • Brief high intensity anaerobic exercise, such as sprinting,
according to glucose responses. When exercise is under- may not need carbohydrate beforehand but may result in
taken in the afternoon or evening, there is an increased risk a dramatic fall in blood glucose afterwards during mus-
of delayed hypoglycaemia overnight. Basal insulin may cle recovery. In this case it is preferable to prevent
Hypoglycaemia 203
hypoglycaemia by taking additional carbohydrate after Table 11.9 Case example: Exercise management in a 15‐year‐old boy.
the sport.
• Fluid intake should be adequate as dehydration can A 15‐year‐old boy on insulin pump therapy
He plays club football at under 18 level
impair performance. High glucose levels will increase
fluid requirements. Concerns: Avoiding hypoglycaemia during matches causing high blood
• Following moderate or intense exercise of 45 minutes glucose levels post‐exercise overnight.
duration or longer, carbohydrate stores must be replen- HbA1c = 51 mmol/mol.
Hyperglycaemia following football matches on Thursday evenings
ished to lower the risk of hypoglycaemia, as insulin
6–9 pm.
sensitivity remains raised for several hours. Usual management temporary basal rate (TBR): 50% set 90 minutes
• To minimise post‐exercise hypoglycaemia lower GI before the start of match until the end of the match.
foods, protein and a reduction in basal insulin, and a
Assessment and cause of issues: The team is picked on the day of
lower than usual bolus dose, with the post‐exercise meal
match, but the boy is not told if he is starting the game or on the bench.
can be helpful. If on the bench the TBR was not being stopped, resulting in
• Hypoglycaemia treatment must be available during hyperglycaemia.
activity. Adults supervising children with diabetes,
Management advice: Usual insulin until 30 minutes before game. If
including teachers, coaches and activity holiday staff,
playing check glucose, have a snack according to blood glucose level,
should all be aware of the possibility of hypoglycaemia suspend pump if below 10 mmol/L and recheck glucose at half‐time. If
and know how to treat it. on the bench, suspend the pump when he starts to play and have an
additional snack.
Additional strategies for managing glucose levels
during and after activity
anaerobic or competitive. Where the pump cannot be worn,
10 second sprint it may be necessary to replace missing basal insulin with a
long‐acting insulin analogue, for example, in multi‐round
The 10 second sprint has been demonstrated to increase glu-
competitions where performance is impacted by glucose lev-
cose levels and reduce hypoglycaemia risk [81]. Further work
els rising. Post‐pump disconnection, children can experience
has shown that the order of different exercise types within an
periods of hyperglycaemia, which can be managed by
activity session can influence the pattern of glucose levels. For
employing strategies to replace missing insulin; this may be
some young people providing advice about the order in which
by giving a bolus of half the missing basal insulin at the end
different exercises are performed may be helpful [82–84].
of the activity or reconnecting the pump and using a higher
basal rate than normal. This phenomenon may also occur
Cool down when temporary basal rates are used for long periods and
can be managed by returning to usual basal rates about 30
Hyperglycaemia post‐exercise is commonly reported. One of
minutes before the end of activity or using a temporary basal
the potential causes is the production of lactate during exer-
rate increase for a period of time post‐exercise.
cise, which is not removed at the end of activity by an active
Hybrid closed‐loop pumps do not have a temporary basal
cool down. Lactate is then managed through the Cori cycle
rate feature, and hypoglycaemia prevention is facilitated
and converted to glucose by the liver. Introducing 10 min-
through using higher glucose targets. It is likely that aerobic
utes of cool down exercise at the end of activity can be help-
activity using these systems will still require carbohydrate to
ful in reducing post‐activity hyperglycaemia [76, 77].
prevent hypoglycaemia during the exercise [86].
A case example of the management of exercise is given in
Insulin treatment specific considerations Table 11.9.
Multiple daily injections

Hypoglycaemia
A once daily long‐acting insulin makes insulin adjustment
more challenging. For young people doing high volumes of Hypoglycaemia is a common acute complication of the treat-
activity, twice daily long‐acting insulin may offer greater ment of diabetes, which can interfere with daily life [87]. It is
flexibility. To date there is only study on insulin adjustment often cited as a barrier to intensifying management. A review
of the ultra‐long‐acting analogue insulin degludec in adults, of management of children under 5 years in one large
which showed insulin could be adjusted when exercise was Australian centre over the last 10 years has shown both a
performed two to three times per week on non‐consecutive reduction in mean HbA1c and the incidence of severe hypo-
days [85]. glycaemia [37]. This data is supported by diabetes registries
across the world, which also show a decline in rates in severe
hypoglycaemia alongside an improvement in glycaemic out-
Pumps
comes [88–90]. The latest consensus on hypoglycaemia now
Exercise with the insulin pump taken off can present chal- defines glucose levels between 3.0 and 3.9 mmol/L as alert
lenges if the exercise lasts longer than 60 minutes and is levels and levels below 3.0 mmol/L as an indication for
204 Endocrinology
immediate action [87]. Glucose targets vary internationally, level or treat and override the system. Predictive low glucose
with some centres recommending near‐normal glycaemia, suspend algorithms stop basal insulin delivery when hypo-
aiming for fasting and preprandial glucose levels of 3.6– glycaemia is predicted in the following 30 minutes. Children
7.0 mmol/L; others recommend levels of 4.0–7.0 mmol/L. and families using CGM systems may also intervene to stop
The use of technology allows safer lowering of glucose hypoglycaemia by giving additional carbohydrate or sus-
targets. pending the pump. If this is a frequent occurrence, it may
Clinical factors linked with hypoglycaemia are: indicate a need to adjust insulin doses.
Glucose is the preferred carbohydrate for the immediate
• excess insulin
treatment of hypoglycaemia as it does not require digestion or
• reduced food consumption
metabolism. Chocolate, milk and other lower GI items are dis-
• exercise
couraged to treat hypoglycaemia due to the slower rate of
• alcohol consumption
absorption of glucose they contain. Twice the amount of carbo-
• sleep
hydrate from fructose (in the form of fruit juice) has been shown
The signs and symptoms of hypoglycaemia can be to be needed compared with glucose tablets to raise blood glu-
described as: cose by similar amounts. Sucrose and milk also require greater
amounts to provide the same rise in blood glucose.
• autonomic (adrenergic) activation, e.g. shaking, pound-
It is advised that a rescue treatment for hypoglycaemia is
ing heart, pallor, cold sweatiness
available at all times. It can be useful to view the hypo rescue
• neurological dysfunction (neuroglycopenia), e.g. diffi-
as a ‘treatment’ and to always carry glucose tablets or a
culty concentrating, disturbed vision and hearing,
glucose drink.
slurred speech, dizziness and, in severe episodes, loss of
A guide to the amount of treatment needed based on age
consciousness and seizure
and average weight is given in Table 11.10. The introduction
• behavioural changes and mood swings including irrita-
bility, erratic behaviour, becoming upset and tearful
• non‐specific symptoms such as hunger, headache, tired- Hypoglycaemia treatment steps (the 15 minute rule)
ness and nausea though these may be present when the
blood glucose level is high Glucose level below hypoglycaemia threshold
Treat with 0.3 g/kg glucose
Children often find it difficult to describe their own symp- Act
toms but might experience shaky or wobbly legs or a ‘funny’
feeling. Wait 15 minutes – repeat glucose check
Hypoglycaemia may be categorised as mild, moderate or Glucose level above 5.5 mmol/L – no further action
severe depending on symptoms and the ability of the indi- Check
vidual to treat the ‘hypo’ themselves. However, this is not
applicable to younger children who are unable to self‐treat. Glucose level below treatment target – repeat rescue
The aim of hypoglycaemia treatment is to restore glucose treatment
levels to the euglycaemic range. While the general principles Repeat
include confirming the glucose value (i.e. that blood glucose
level is in the hypoglycaemic range), giving immediate treat-
ment and checking treatment effectiveness, the treatment Figure 11.5 Hypoglycaemia treatment steps.
steps may vary with the use of technology (insulin pump
therapy and CGM systems, as described below). Table 11.10 Hypoglycaemia treatment amounts.
The amount of glucose needed for treatment of a hypo
depends on the size of the child and may also depend on the Hypoglycaemia treatment dose (g of glucose)
severity of the hypo and ROC of blood glucose levels. The
aim is to restore the blood glucose level to 5.6 mmol/L (eug- 2 g 5 g 10 15
lycaemia) [88]. The recommended amount of carbohydrate (<2 years) (2–5 years) (5–10 years) (>10 years)
is 0.3 g/kg body weight as glucose. It is important to avoid Lucozade – 60 mL 120 mL 180 mL
overtreatment of hypoglycaemia with consequent rebound Energy
high glucose levels. The amount of carbohydrate required to Lucozade 1 2 3 5
restore euglycaemia will also depend on the type of insulin Energy tablets
therapy and time since its administration, recent activity and (3 g/tablet)
starting blood glucose level. Dextrosol 1 2 3 5
Figure 11.5 shows the steps for treating hypoglycaemia. (3 g/ tablet)
Insulin pump therapy allows the introduction of an addi-
GlucoTabs – 1 2 or 3 4
tional treatment step of suspension of the insulin pump. (4 g/tablet)
Children using insulin pumps with continuous glucose sen-
Lift 10 mL 20 mL 40 mL 60 mL
sors and a predictive low glucose suspend algorithm should (GlucoJuice)
be advised to either allow the system to manage the glucose
Type 2 Diabetes 205
of the UK government sugar tax has created a number of advice on a GFD according to current management of CD
challenges for families in treating hypoglycaemia. As the guidelines. Additional advice on the potential effects on
‘sugar’ content of drinks is reduced, the volume of drink glucose levels and insulin adjustment will be required
required for treatment increases. The dietitian and diabetes [93]. Higher postprandial glucose levels have been
team need to monitor changes in composition of commer- observed with GF alternative foods. Annual review of
cially available suitable glucose containing drinks to review management of the GFD should be conducted alongside
treatment amounts. the diabetes annual review.
Severe hypoglycaemia Type 2 diabetes

In the case of severe hypoglycaemia:
Type 2 diabetes is increasing in the paediatric population.
• parents should have access to an emergency supply of a There is little evidence for nutritional interventions in type 2
GlucaGen HypoKit for severe hypoglycaemia diabetes in childhood. The largest study to examine treat-
• this is a glucagon injection for use if the child is uncon- ment options, the Treatment Options for type 2 Diabetes in
scious or if the parents are unable to resolve hypoglycae- Adolescents and Youth (TODAY) study, showed that inten-
mic symptoms by other means sive diet and lifestyle support alone was not sufficient to sus-
tain target glycaemia. Due to the relatively small numbers of
children in UK with type 2 diabetes, it has been suggested
Intercurrent illness that they should be managed in larger centres with access to
clinical trials of newer medications [5]. Currently the only
A complete guide to the management of intercurrent illness
licensed drug treatments for type 2 diabetes in children in
in type 1 diabetes is available in the ISPAD guidelines [91].
the UK are insulin and metformin. Detailed advice on the
Episodes of illness usually cause raised glucose levels with
medical, psychological and nutritional management of type
the exception of vomiting illness, particularly in younger
2 diabetes can be found in the 2018 ISPAD Clinical Practice
children. To avoid the development of DKA, insulin should
Guidelines [94].
not be stopped even though children often do not wish to eat
The aims of management of type 2 diabetes are:
during periods of illness and infection. Instructions for the
management of illness are based on glucose and ketone • the child and family should understand the health impli-
monitoring. cations of both obesity and type 2 diabetes
To prevent the formation of ‘starvation’ ketones, advice • diabetes healthcare professionals should understand
on replacement carbohydrate should be included in patient the health beliefs and behaviours of the family to sup-
information. Suitable alternative carbohydrate sources port the development of an effective management plan
include isotonic sports drinks, sugar‐containing drinks, and achieve optimal blood glucose levels and normal
easily tolerated foods like soup, jelly and toast. HbA1c
Insulin requirements are often increased during illness as • to promote a healthy lifestyle through behaviour change
the stress responses to illness contribute to insulin resistance. including nutrition, weight management, activity and
Insulin doses are adjusted based on glucose levels and blood smoking
ketone levels. Both basal/background and fast‐acting insu-
Specific nutritional aims are:
lin doses may need to be increased.
• to prevent further weight gain in those with a BMI
between the 85th and 95th centile
Coeliac disease • to promote weight loss for those with a BMI > 95th cen-
tile with normal linear growth
CD is more common in children with type 1 diabetes than
• to deal with comorbidities such as hypertension and
the general population. Worldwide incidence is reported
dyslipidaemia
between 1.6% and 16.4% of clinic populations [92]. The
NPDA [2] reported an incidence of 4.4% in England and The majority of children with type 2 diabetes are over-
Wales in 2016. weight; the NPDA data reported 78.6% of the children with
CD is usually picked up on annual screening, with many type 2 diabetes in England and Wales to be obese [2]. A
families reporting their children to be asymptomatic prior focus of nutrition intervention is, therefore, to achieve
to diagnosis. CD may be associated with poor growth, weight loss or keep weight static with normal linear growth.
delayed puberty, nutritional deficiency and hypo‐ and Education and support should encompass the whole family,
hyperglycaemia. as eating behaviours are reinforced in the home environ-
Treatment is with a gluten‐free diet (GFD). The pres- ment. Families should be counselled about reducing total
ence of CD with type 1 diabetes increases the risk of energy intake, increasing physical activity and decreasing
micro‐ and macrovascular complications, and untreated sedentary behaviours [13]. Older adolescents may benefit
CD is linked to adverse lipid profiles. Following a diag- from some of the adult programmes offering very low calo-
nosis of CD, children with type 1 diabetes should receive rie diets. Low carbohydrate diets may be appropriate in this
206 Endocrinology
group. There is some evidence that substitution of low GI with the use of high dose steroids and tacrolimus (p. 266).
foods for high GI foods may help with weight control, lipid Dietary management depends on how the diabetes is
levels and control of appetite. medically managed. In some instances, instruction about
Strategies to lower total dietary energy intake include: avoiding glucose loads, e.g. avoiding sugary drinks and
foods, and healthy eating is sufficient. Other children are
• reduction in portion size
commenced on daily long‐acting analogue insulin and
• reduction in consumption of high fat, high sugar food
require additional information about eating regularly, hav-
and drinks. Cutting out sugary soft or fizzy drinks
ing a bedtime snack and hypoglycaemia prevention and
and fruit juices completely can make the most signifi-
management. MDI or insulin pump therapy can also be ini-
cant change and result in weight loss. These drinks
tiated, and the advice is similar to that given to those with
can be replaced with water, diet drinks and sugar‐free
type 1 diabetes.
beverages.
Children needing insulin should have appropriate
Summary
advice on carbohydrate counting and avoidance of
hypoglycaemia.
The nutritional management of children and young people
with diabetes is complex and reaches beyond simple carbo-
Diabetes secondary to pancreatic disease hydrate management. As technology continues to develop,
so nutrition management strategies will continue to change
CFRD has a complex pathophysiology, which includes loss and develop. Increased exposure to information about glu-
of pancreatic islet cells causing insulin and glucagon defi- cose levels in real time will need to be supported by nutri-
ciency, variable insulin resistance, disrupted gut function tional management strategies that allow children to eat and
and liver disease. Medication may also contribute to enjoy food as well as manage glucose responses. Both health-
impaired glucose tolerance and diabetes. The use of CGM care professionals and families face the challenge of keeping
demonstrates abnormal glucose profiles in those with up to date and being able to apply the latest evidence to day‐
reported normal glucose tolerance tests. Presentation is often to‐day management of glucose levels. Healthcare profes-
at times of illness or metabolic stress. The aim of manage- sionals should also be mindful of the recent advice about the
ment is to achieve glucose targets while following CF nutri- impact of the use of language on people living with diabetes
tion guidelines [95]. It has been documented that early [96]; for dietitians this means following the National Health
initiation of insulin therapy may have value for growth, Service guidance, Language Matters, in both face‐to‐face
weight and pulmonary function. Insulin doses and types consultations and in the production of written information.
may need to be adjusted when nutritional supplements, The role of the team in supporting families living with diabe-
overnight or continuous enteral feeding are being used and tes to achieve the best possible outcomes is well recognised.
during times of acute infection. Dose adjustment should take The biggest single factor in determining a clinic outcome is
priority over dietary restriction. the teamwork and targets set by the clinical group. It is
Dietary management includes: important, therefore, that the dietitian is an integral member
of the diabetes MDT. However diabetes is managed, a
• meeting CF nutritional guidelines (p. 217) healthy lifestyle with high quality food choices is associated
• avoiding sugary drinks/glucose loads in drinks between with improved outcomes.
meals
• advice about the effect of carbohydrate on blood
glucose levels and carbohydrate counting and insulin Learning points
adjustment
• Nutrition education from the point of diagnosis and
Diabetes secondary to medication thereafter should take a whole food approach
• Education about carbohydrate counting should happen
Some drugs, such as high‐dose steroids, can cause transient immediately following diagnosis
hyperglycaemia for the duration of the prescription, and • Physical activity should be promoted in line with
others, such as tacrolimus and cyclosporin, may cause islet recommendations for the general population
cell destruction in which case the diabetes becomes perma- • Advances in technology will continue to influence and
nent. In oncology protocols some chemotherapy drugs change the nutritional management of type 1 diabetes
induce diabetes, which coincides with the cyclical nature of • Using the right language should be central to all contact
the chemotherapy (p. 379). Following organ transplantation with people with diabetes
such as kidney transplant, diabetes most commonly occurs
Genetics 207
Congenital Hyperinsulinism
Sarah Price
Introduction copy in certain areas from the other parent. This results in

the formation of a focal lesion [103]. In focal CHI only an
Congenital hyperinsulinism (CHI) is a rare condition in isolated area of the pancreas overproduces insulin while
which the body produces an unregulated, excessive the rest of the pancreas is normal [104]. Hyperinsulinism
amount of insulin, leading to severe hypoglycaemia. The can also be caused by mutations in the glutamate dehy-
condition is strongly linked with specific genetic muta- drogenase gene, GLUD1 on 10q. This causes a leucine‐
tions, but can also occur in response to perinatal stress triggered production of ATP, which is independent of
and certain maternal factors. The incidence in the general circulating glucose levels. This in turn causes closure of the
population is 1 in 50 000 births but increases significantly KATP channel, and insulin is released. Alongside the hypo-
in consanguineous parents to 1 in 2500 [97–99]. However, screen bloods typical of CHI, a raised ammonia would
neither of these figures take into account those who diagnose this condition. CHI caused by GLUD1 10q muta-
present late (up to 10% of patients) nor those who have tions generally respond well to medication, and surgery is
transient CHI [100]. not required [105]. Other rarer genetic mutations have been
identified with up to 12 known mutations. Despite this,
there are a significant number of CHI patients for whom a
Mechanism for CHI genetic cause is never identified [106].
Whether CHI is described as diffuse or focal depends on
In the healthy individual insulin is produced in response to two distinct histopathological types [107, 108]. As men-
circulating serum levels of glucose, mediated by the ATP‐ tioned above a focal lesion is where a distinct area of the
sensitive potassium channel KATP. The production of ATP pancreas is enriched with insulin‐producing beta cells
from glucose (via the Krebs cycle) causes the closure of the while the rest of the pancreas is histologically and function-
KATP channel. This in turn leads to the depolarisation of the ally normal. In diffuse disease the whole pancreas has
pancreatic beta cell membrane and activation of the calcium affected beta cells [104]. This variety in types highlights the
(Ca2+) channels. The entry of Ca2+ into the beta cells triggers importance of genetic testing. F‐DOPA positron emission
Ca2+‐dependent insulin secretion [101]. In CHI this feedback tomography (PET) computerised tomography (CT) scan-
regulation is dysfunctional due to errors in, or the complete ning can be used to identify those suspected of having focal
absence of, the potassium channel KATP. This leads to an disease [109]. Radioactive 18‐fluoro-DOPA is injected into
excessive and unpredictable production of insulin, which is the body under general anaesthetic. In focal CHI a small
disproportionate to the level of plasma glucose. The insulin area within the pancreas takes up the dye and retains it.
is said to be blind to the amount of glucose circulating in the This shows as an area of ‘brightness’ on the CT imaging. In
blood because the feedback mechanism is absent. The result diffuse CHI the whole pancreas takes up the dye, but the
is dangerously high levels of circulating insulin causing dye is not retained [107, 109].
severe hypoglycaemia, the risk of which is compounded by It is important to identify whether a child has diffuse or
the absence of ketone production [102]. focal CHI as surgery to remove the focal lesion is often cura-
tive and is, therefore, the preferred management option in
these children [109, 110]. At present the scan is only available
Genetics at two specialist centres in the UK: Royal Manchester
Children’s Hospital and Great Ormond Street Hospital for
Mutations in the genes ABCC8 and KCNJ11 are the most Children, London.
common genetic causes of CHI. These genes are responsi-
ble for the function of the KATP channel and are usually
recessively inherited. Whether they are inherited from the Learning points: genetics
mother or the father is helpful to know in determining
whether the CHI is likely to be diffuse or focal. Some genes • there are two types of CHI: diffuse and focal
have heterozygosity, which means there are two different • the most common genetic mutations are ABCC8 and
alleles for the same gene, one from each parent. Where KCNJ11
there is loss of heterozygosity, the loss of one parental allele • early genetic testing is important
means that areas within a chromosome will only have one • 18‐fluoro-DOPA PET CT scanning is crucial where genetic
copy of the allele. When a paternal heterozygous mutation results indicate to distinguish between the types
in ABCC8/KCNJ11 occurs, together with a loss of corre- • focal lesions can be removed by surgery, which is often
sponding maternal genes (loss of heterozygosity), the child curative
inherits a faulty copy from one parent and loses the healthy
208 Endocrinology
Table 11.11 Risk factors for transient hyperinsulinism. Table 11.12 Hyposcreen measurements and results to confirm
a diagnosis of CHI.
Risk factor Mechanism
Measurement Result
Uncontrolled The baby may or may not be macrosomic but
gestational produces too much insulin in response to the Serum glucose <3.0 mmol/L
diabetes mother’s high blood sugar levels. Post-birth, the Serum insulin Detectable or raised
infant’s blood sugars usually stabilise within a week,
during which time they may require additional C‐peptide Detectable or raised
carbohydrate to maintain their blood sugar levels Free fatty acids Low
Maternal use The exact mechanisms are not known, but Beta‐hydroxybutarate (ketones) Low
of labetalol sympathetic inhibition of the infant’s counter‐
regulatory responses may be responsible
Perinatal The mechanism is not known, but anaerobic suppressed at the time of hypoglycaemia. In children with
stress metabolism to maintain blood glucose CHI, insulin continues to be produced regardless of hypo-
concentration may be responsible glycaemia. Therefore, any insulin that is detectable at the
Small for A small for gestational age infant will have poor time of hypoglycaemia suggests the diagnosis of CHI [102].
gestational glycogen stores and will therefore be more likely to The absence of an elevated C‐peptide may raise concerns
age drop their blood sugar below a safe level. However, over the origin of the insulin, e.g. the child could have
why some children who are born small develop
received insulin via an injection deliberately to cause a low
hyperinsulinism is not explained. Whether
intrauterine stress plays a part in insulin blood sugar level. In a hyposcreen for a child with CHI, a
overproduction remains to be seen finding of low levels of free fatty acids and little or no ketone
bodies would be expected. This is because the presence of
high levels of circulating insulin suppresses lipolysis and
ketogenesis [103]. Table 11.12 shows the results of hypo-
Presentation screen measurements that confirm a diagnosis of CHI.
Most infants present within the first few days of life, but some
may present later during the first year, and, very rarely, an
Glucose infusion rate
older child may present with hypoglycaemic symptoms. The
Calculating the glucose infusion rate (GIR) can be helpful in
first indications of CHI include non‐specific features of hypo-
identifying babies that may have CHI. GIR is the amount of
glycaemia including floppiness, jitteriness, reluctance to feed
carbohydrate (CHO) expressed as milligrams (mg) required
and lethargy [111]. If these symptoms are left unrecognised in
per kilogram per minute over a 24 hour period. In a full‐term
CHI, they can lead to severe prolonged hypoglycaemia, which
newborn baby, the GIR is 4–6 mg/kg/min, but in CHI this
can result in permanent neurological damage or death.
figure can be much higher [114]. A GIR > 8 mg/kg/min is a
Hyperinsulinism can also occur in response to perinatal
good indicator of insulin‐driven hypoglycaemia [100]. GIR
stress and certain maternal factors. In such cases, hypogly-
is both helpful at diagnosis and a useful indicator of the
caemia due to hyperinsulinism is usually transient. Some
severity of CHI throughout the acute management phase. A
of the risk factors for transient CHI are given in Table 11.11
reduction in GIR with stable blood glucose levels can indi-
[112, 113].
cate an improvement in the condition as long as other factors
remain consistent, e.g. medication.
Diagnosis
How to calculate GIR
Hyposcreen
GIR calculation for intravenous (IV) fluids alone:
Hypoglycaemia in CHI is defined as a blood sugar level % dextrose infused mL/hour
of <3.0 mmol/L. The blood sugar cut‐off indicating hypogly- mg/kg/ min
weight kg 6
caemia has been defined variably, with some sources relying
on a level of 2.6 mmol/L. Most centres now accept that Fluid rate mL/hour
investigations should be carried out when the blood sugar CHO requirement mg/kg/ min weight kg 6
drops below 3.0 mmol/L [100]. In a baby or child experienc-
% dextrose
ing hypoglycaemic episodes, it is important to conduct a
hypoglycaemic screen (hyposcreen) when a heel prick blood GIR calculation for enteral feeds (can also be used for IV
sample of <3.0 mmol/L is found in order to understand the fluids if the total amount of CHO is worked out first):
reason for this low blood sugar. The hyposcreen measures
the level of plasma glucose to confirm if the child is truly Total CHO g 1000 mg weight kg 24 hours
hypoglycaemic. It also measures serum levels of insulin 60 minutes mg/kg/min
and C‐peptide, both of which would be raised in a child
with CHI. In normal individuals, insulin production is This calculation is for a 24 hour period.
Surgical Management of CHI 209
Medical management of CHI catheter should be considered to allow a higher dextrose con-
centration infusion (>12.5% dextrose) [116]. These IV infu-
The aims of medical management are: sions often impact on the volume of enteral feeds that can be
given in the early days. Consideration must be given as to
• prevention of hypoglycaemic brain damage, allowing for what impact this will have on the infant’s nutritional status.
normal psychomotor development Despite receiving large volumes and high concentrations
• establishment of a normal feeding regimen appropriate of IV dextrose, the infant’s blood glucose levels often remain
for the age of the infant/child: volume, frequency, type unstable. Medications are often used alongside IV dextrose,
• ensuring normal and safe tolerance to fasting that is and CHO supplemented feeds in order to bring blood glu-
appropriate for age, without developing hypoglycaemia cose levels into a safe stable range. A summary of the drugs
• optimal growth used in CHI is given in Table 11.13. First‐line medications are
• maintenance of family unit and quality of life [115] diazoxide and chlorothiazide, which are often given together
These aims can only be effectively achieved with the input due to their synergistic mechanism. Chlorothiazide is a diu-
of a multidisciplinary team of health professionals including retic that reduces the risk of fluid retention, a common side
doctors, specialist nurses, dietitians, speech and language effect of diazoxide [100].
therapists and psychologists [100].
Blood glucose monitoring
CHI services
Parents need to be taught how to measure and interpret fin-
Early support from a specialist centre should not be under- ger/heel prick blood glucose levels, using a handheld device,
valued and has been found to have positive effects on the prior to going home. The specialist nurse and/or ward nursing
neurological outcomes for patients with CHI [103]. In the UK staff should help with this. It is important to carry out blood
there are two specialist centres for CHI. In the north, the glucose monitoring prior to every feed and at other times
Northern Congenital Hyperinsulinism Service (NORCHI) is when clinically indicated. Parents need to be advised on what
a joint service between the Royal Manchester Children’s is suitable for their child as management is highly individual.
Hospital and Alder Hey Children’s Hospital in Liverpool. In The flow chart in Figure 11.6 shows the ‘hypo’ manage-
the south, there is a service at Great Ormond Street Hospital ment advice given to the parents of children with CHI at
for Children in London. Royal Manchester Children’s Hospital, together with clear
The management of CHI is a team effort comprising pae- instructions on how to use it. Alongside this they are also
diatric endocrinology and supporting services, of which given an ‘emergency regimen’ by the dietitian (p. 673). This is
dietetics is a key part. CHI specialist dietitians play an designed to give a solution of glucose polymer during peri-
important part in determining feeding regimens to ensure ods of illness when the child may not be feeding/eating as
maintenance of glucose levels. While CHI dietitians acquire normal and is, therefore, at greater risk of their blood glucose
knowledge and skills in the essential clinical management of level dropping. The regimen is designed to give an amount of
hypoglycaemia in the hospital setting, they continue to pro- CHO appropriate for the child’s age based on average nutri-
vide support when children are managed at home with the tional requirements and should be used during illness with
support of local dietetic services. the aim of preventing (rather than treating) hypoglycaemia.
Local dietitians may have initial contact with a newly diag-
nosed infant if their condition is manageable in a district gen- Surgical management of CHI
eral hospital or prior to transfer to a specialist centre. Upon
discharge they may also have shared care with the specialist In focal CHI surgical removal of the lesion is the treatment of
centre dietitian. Advice from the specialist dietitian should choice as this will usually resolve the hyperinsulinism with
be sought early, given the complexity of the condition and no long‐term side effects [106, 108].
acknowledging that a local dietitian’s experience of CHI will Children with diffuse disease should be considered for
usually be limited due to the rareness of the condition. surgery (subtotal pancreatectomy) if they are unresponsive
to medical treatment. Traditional opinion was that these
Acute management children should be considered for surgery sooner rather
than later. However, more recently there is a motion for pre-
In CHI blood glucose concentrations should be kept above serving the pancreas where possible due to post‐surgery
3.5 mmol/L with a consensus that neuroglycopenia can occur and long‐term side effects. In the post‐operative period, a
at level <3 mmol/L [100, 103]. In severe neonatal hypoglycae- significant proportion of children with diffuse CHI continue
mia, oral feeds alone are unlikely to maintain safe blood glu- to have hypoglycaemia due to over‐secretion from the
cose levels. In most instances IV access is required to provide residual pancreas. In the long term, as the remnant pancreas
additional CHO. An infusion of 10% dextrose at a standard fails, diabetes becomes inevitable, which then places a life-
volume of 90–120 mL/kg/day provides a GIR of 6–8 mg/kg/ long disease burden on the individual [117]. A decision for
min, which again may not be enough to maintain blood glu- surgery should be undertaken with the input of the whole
cose levels in an infant [100]. For this reason a central venous CHI team, including parents, and should be weighed up
210 Endocrinology
Table 11.13 Drugs used in the management of CHI.
Drug Mechanism Side effects/limitations
Diazoxide – oral Opens KATP channels and stabilises Fluid retention – fluid is often restricted to 120–150 mL/kg and can
pancreatic beta cells therefore have implications on nutritional status
Taste changes
Ineffective in CHI mutations where the potassium channel is absent
Pulmonary hypertension – echocardiogram recommended prior to
commencement
Excessive hair growth
Rarely leukopenia and thrombocytopenia
Chlorothiazide – oral Acts synergistically with diazoxide by Acts as a diuretic, which helps with the side effect of fluid retention with
activating non‐KATP channels diazoxide
Hyponatraemia
Hypokalaemia
Octreotide – subcutaneous Activates G protein‐coupled rectifier K Suppression of growth hormone
injection channel Delayed gastric motility
Steatorrhoea
Cholelithiasis
Abdominal distention
Hepatitis
Hair loss
Sirolimus Rapamycin (mTOR) inhibitor, beta cell No longer in regular use in CHI due to its immunosuppressive side
suppressor effects
Used in rare cases when other treatment options have failed
Glucagon – intravenous Increased glycogenolysis/gluconeogenesis Nausea
Vomiting
Increased growth hormone
Increased myocardial contractility
Decreased gastric acid and pancreatic enzymes
Helpful in allowing the reduction of IV dextrose/fluid requirement
Not used long term as drug delivery is unreliable through subcutaneous
injection
against the risks of persistent hypoglycaemia and subse- Pancreatic exocrine insufficiency
quent brain damage. The quality of life for the child and
Some children may become reliant on pancreatic enzyme
family should remain central to decision making [100].
replacement therapy (PERT) due to pancreatic insufficiency,
Subtotal pancreatectomy removes 95% of the pancreas.
and so faecal elastase should be measured post‐subtotal
The remaining 5% is left largely due to its involvement with
pancreatectomy [120]. Some children found to be pancreatic
other major structures including the bile ducts. Post‐surgery
insufficient in the immediate months following surgery have
there is a higher risk of pancreatic endocrine and exocrine
gone on to demonstrate normal exocrine function a year or
insufficiency.
two down the line. For this reason it is important to reassess
exocrine function periodically. PERT is usually an area that
Complications after surgery the dietitian will lead on in terms of calculating doses and
monitoring symptoms.
Diabetes
Infants will often require insulin post‐operatively due to
Chylothorax
hyperglycaemia, although this can usually be titrated down
in the first few days. Children who have a subtotal pancrea- Chylothorax is another complication that can arise in the
tectomy have a high risk of developing diabetes [118, 119]. immediate post‐operative period. It can be treated conserva-
Most will go on to develop insulin‐dependent diabetes, tively using a minimal long chain triglyceride diet or feed for
usually by their teenage years [100]. as long as is required (p. 299).
Dietetic Management 211
Flow chart for Blood Glucose (BG)

Monitor BG levels as Monitoring:
directed
BG levels below 3.5 BG levels below 3.5

BG levels above mmols and asymptomatic? mmols/l and clinically
3.5 mmols/l symptomatic (floppy,
drowsy)
Immediately
Yes No
Pre-feed
Re-check to ensure
Give correct reading Check ketones
feed
BG level still below 3.5

Re-check in mmols/l
Continue to monitor BG 30 minutes Seek medical
3.5 mmols/l
levels as Assistance/ring 999
directed
Give GlucoJuice 30–60 ml, or Glucogel if your child is conscious and able to swallow.
Or give 20% Vitajoule/maxijul (1 scoop that comes in the tin) in 50 mls water
Orally or via Gastrostomy/NG tube
Then offer feed/diet as normal
Rechek in
15 minutes
BG level still
Seek medical assistance/advice
Below 3.5 mmols/l?
Figure 11.6 Blood glucose monitoring in CHI. Source: Reprinted with permission from Royal Manchester Children’s Hospital.
Ongoing hyperinsulinism Dietetic management

Despite 95% of the pancreas being removed, some children
still produce inappropriately high amounts of insulin from Acute considerations
the remaining 5%. In these cases the child may still need a
combination of CHO supplementation and medication to In the acute stage of CHI management, dietetic input can
control their hypoglycaemia, although this will usually be a be difficult due to limitations imposed by the medical man-
lot less severe and more manageable when compared with agement. The infant is often fluid restricted due to the com-
pre‐surgery management [120]. mencement of diazoxide, or the fluids available for feeds are
limited due to high IV dextrose volume requirements. If the
infant is on 10% dextrose via a peripheral line, the placement
of a central line will allow the concentration of dextrose to be
Learning points: medical and surgical management of CHI increased, and, therefore, more fluid maybe become availa-
ble for enteral feeds. If the infant is unlikely to meet their
• a hyposcreen to confirm or rule out CHI should be per- nutritional requirements via enteral feeds, consideration
formed with a blood sugar level <3.0 mmol/L should be given to the use of parenteral nutrition (PN) along-
• an infant with CHI should maintain their blood sugar level side enteral feeds within 7 days [116]. The PN could be made
above 3.5 mmol/L to include the dextrose requirement up to a limit of approxi-
• surgery is the option of choice for focal CHI mately 25% before the stability of the bag is affected. This
• surgery for diffuse CHI should be considered if medical should be discussed with the team and pharmacist where
management cannot safely maintain safe blood sugar levels appropriate to ensure optimal nutrition.
• children with CHI become less severe over time and may The frequency of feeding will depend greatly on the age
eventually grow out of the condition of the child at presentation. Where possible the child’s
normal feeding/eating pattern should be maintained.

212 Endocrinology
The first choice of feed should be as for normal infants, i.e. dehydrogenase deficiency. Glutamate dehydrogenase hyper-
mother’s breastmilk [121]. In the absence of breastmilk, a insulinism is also be known as hyperinsulinism–hyperammo-
suitable standard infant formula should be used. naemia syndrome and is a milder form of hyperinsulinism
In the neonate feeding should be started as an hourly that is more likely to present in late infancy or early childhood
bolus. This may be orally or via nasogastric tube (NGT) rather than the newborn period. In this patient group intake
depending on their willingness to feed. The interval between of protein particularly without carbohydrate can cause hypo-
feeds should be ‘stretched’ equally as blood glucose levels glycaemia [105]. If, on dietary assessment, the child’s protein
and tolerance allow. This is usually done in hourly stages, intake is significantly above the reference nutrient intake
e.g. 1 hourly, 2 hourly, 3 hourly and 4 hourly. Prior to ‘stretch- (RNI), it may be helpful to suggest ways of reducing or spac-
ing’ an interval, the infant should receive the next interval’s ing their protein more evenly throughout the day. Any reduc-
volume, e.g. if stretching from 1 hourly to 2 hourly, the baby tion in dietary protein, which may form part of the medical
should receive the 2 hourly volume 1 hour after their last treatment, must maintain at least the safe minimum protein
feed. This is to ensure they do not go a longer period of time intake so that growth and development is not compromised.
on the smaller feed volume, which could put the baby at risk Depending on requirements for carbohydrate, energy,
of hypoglycaemia. Aiming for 4 hourly feeds would be the fluid and growth history, it may be more effective to use an
ideal for an infant prior to discharge, although this will energy‐dense feed, e.g. Infatrini, Similac High Energy, SMA
depend on their age and size at discharge. All infants with High Energy, or a standard infant formula can be concen-
CHI should undergo a 6 hour ‘safety fast’ prior to discharge trated to better meet their nutritional needs (p. 13).
to ensure they are safe to go home and maintain their blood
glucose level [100].
Some infants may need to go home on a combination of Long‐term feeding difficulties and strategies
daytime bolus feeding and night‐time continuous feeding to
achieve stable blood glucose levels. This requires a gastros- Feeding difficulties are common and persistent in the CHI
tomy to be placed prior to discharge to ensure they are not at cohort: 75% will require nasogastric (NG) tube feeding, and
risk of tube migration during sleep. A bolus feed may need 93% will require anti‐reflux medications [124]. Recent
to be given soon after the overnight feed stops as the blood research has found that the more severe the hyperinsulin-
glucose level can drop quite quickly after the cessation of the ism, the worse the feeding problems appear to be [100].
continuous feeding period. The same rule should also be Feeding problems is a term used to encapsulate a range of
applied when starting the night‐time feed after the last bolus difficulties, and there are a number of suggestions for their
of the day. occurrence.
Quite often infants with CHI require an additional sup- The presence of excessive insulin contributes to gut dys-
plementation of CHO in their feed to allow the medical team motility, which could explain why babies with CHI often
to wean them off the IV dextrose. Glucose polymers such as suffer from GOR and have poor tolerance of large feed vol-
Vitajoule, Polycal and Maxijul can be added to a feed to umes, with frequent vomiting. Some studies have also linked
increase the CHO concentration [100]. The glucose polymer excessive insulin production with the suppression of the
should be started at a small amount (1%–2.5% concentra- appetite‐stimulating hormone ghrelin, which could further
tion) and increased as required/tolerated up to a maximum explain the baby’s apparent reluctance to feed [125].
of approximately 5% (5 g/100 mL feed). Further increases in Although there are clear physiological explanations for
concentration are not tolerated due to the increase in osmotic poor feeding, it is well recognised that in reality feeding
load in the feed. This causes delayed gastric emptying, con- problems are multifactorial in origin. In the case of babies
tributing to gastro‐oesophageal reflux (GOR) and possibly a with CHI, their feeding problems are further compounded
higher incidence of necrotising enterocolitis [122]. by the nature of the medical management of CHI. The
Consideration needs to be given to the protein-energy adverse side effects of medication (Table 11.13) could further
ratio of the feed, which should be maintained between 7.5% exacerbate feeding difficulties. Some studies found that
and 12% (p. 14). This can become easily reduced in CHI those on a higher dose of diazoxide were more likely to have
treatment with the addition of a glucose polymer and has the persistent feeding difficulties [124, 126]. Whether the higher
potential to affect growth. However, in CHI the protein- dose of diazoxide is causally linked to appetite suppression
energy ratio is usually already greatly distorted through the or rather an indicator of the severity of CHI is unclear [124].
use of IV dextrose, which to a large extent cannot be altered The use of IV fluids and need for a regimented feeding
as it is part of the medical management. For this reason if the routine to maintain blood glucose levels interrupts the estab-
protein-energy ratio cannot be improved through dietetic lishment of normal oral feeding in a newborn infant. The
manipulation, it is more important to ensure the child is at effect of this disruption should not be underestimated.
least meeting their safe minimum protein intake, which will It is well recognised in medical conditions where there is fre-
vary depending on age [123]. quent exposure to unpleasant sensory stimuli from an early
A case study of a baby newly diagnosed with CHI is given age such as intubation and frequent passing of NG tubes that
in Table 11.14. the infant’s facial/oral sensitivity and, therefore, their oral
Some children with CHI can experience a hypoglycaemia feeding experiences are affected. Infants with CHI fit this
sensitive to protein intake, particularly those with glutamate description, and oral feed aversion is a common problem [127].
Table 11.14 Case study: Dietary management of a baby with CHI.
Anthropometry: Male born at term weighing 3.9 kg, 75th–91st centile, length 53 cm, 75th–91st centile. Growth history:
1 week, 4.2 kg, 91st centile
4 weeks, 4.8 kg, 75th–91st centile
2.5 months, 7.5 kg, <98th centile at discharge
6 months, 9.5 kg, 75th centile
11 months, 10.2 kg, 75th centile, length 75 cm, 50th–75th centile
Comments: Baby’s weight increased beyond the trajectory of his birth centile due to excessive CHO intake forming part of the medical management
up until 6 months of age. Weight at 11 months of age shows the rate of weight gain slowed down as the need for additional CHO had ceased
Biochemistry: Blood sugar level <2.6 mmol/L, insulin level raised, no ketones present
Clinical: Baby presented with poor feeding and lethargy in the hours after birth, which prompted a blood sugar level check at the local hospital where
he was born
Dietary: Initially fed 110 mL/kg EBM, unable to increase further due to IV fluids with dextrose required to maintain blood sugar levels. At day 10 EBM
was fortified with 2.5% glucose polymer to help stabilise the baby’s blood sugar levels, while medication was weaned down. Mum was supported to
breastfeed the baby after and in between bottle feeds. Bottle feeds given first to ensure the required volume containing the glucose polymer was taken.
Baby was stretched from 3 hourly bottles to 4 hourly bottles and went home on this regimen. He started weaning at 6 months of age and stopped
glucose polymer fortification at 7.5 months of age due to stable blood sugars
Environment: The baby was the first child of healthy parents. He had diffuse disease heterozygous ABCC8 mutation, which he had inherited paternally.
He spent the first 2 weeks of his life on HDU before being stepped down to a medical ward for 3 months. He was then discharged home
Focus: The dietetic aims were to meet the baby’s nutritional requirements while providing a dietary regimen that was safe from a blood sugar level
perspective. His blood sugar levels were frequently reassessed by the dietitian once home to ensure the baby did not continue to receive an excessive
CHO intake for longer than required as this would have led to further accelerating weight gain. The dietitian also maintained a focus on supporting
breastfeeding throughout the baby’s treatment to ensure it was considered by the medical team in their treatment planning
Age Medical intervention Dietetic comments
10 days Transferred to HDU from local district general hospital neonatal unit
due to uncontrolled hypoglycaemia. He had a hyposcreen performed
locally, which showed high circulating levels of insulin; hence
diazoxide and chlorothiazide were commenced prior to transfer
Birth weight = 3.9 kg. Once on HDU he was commenced on 10% This feeding regimen did not meet his nutritional requirements,
IV dextrose at 6.5 mL/hour and oral feeds of EBM 54 mL × 3 hourly, but fluids could not be increased further given that he had just
total fluid intake 150 mL/kg with 110 mL/kg as EBM commenced diazoxide. Feed fortification was not considered at
Calculation of GIR this point due to the potential changes in medical management
Amount of CHO received from 10% IV dextrose:
6.5 mL/hour × 24 hours = 156 mL × 10% = 15.6 g CHO
Amount of CHO received from EBM (7 g CHO/100 mL average
content of EBM)
54 mL × 8 feeds in 24 hours = 432 mL × 7/100 = 30.2 g CHO
Total CHO intake per 24 hours = 45.8 g
GIR (mg/kg/min) =
45.8 g × 1000 mg ÷ 3.9 kg = 11 744 ÷ 24 hour = 489.33 ÷ 60 minutes
= 8.155
Round up to 8.2 mg/kg/min
12 days A central line was placed to obtain IV access that would allow a
higher concentration than 10% IV dextrose, due his blood sugars
being continually <3.5 mmol/L on the current regimen
Blood sugars did not improve on diazoxide; therefore, he was
commenced on octreotide and weaned off diazoxide and
chlorothiazide
Current regimen: 15% IV dextrose at 5 mL/hour and glucagon at
3 mL/hour to stabilise his blood sugars; feeds 50 mL EBM × 3 hourly.
Current weight = 4.2 kg.
Calculation of GIR
IV fluids 15% dextrose: 5 mL/hour × 24 hours = 120 mL × 15% = 18 g GIR had decreased due to the baby’s weight increasing, but he
CHO was also on glucagon, which would have helped stabilise his
Feeds EBM: 50 mL × 8 in 24 hours = 400 mL × 7/100 = 28 g CHO blood sugar levels
Total CHO intake per 24 hours = 46 g At this time Mum had a strong wish to breastfeed; it was agreed
GIR (mg/kg/min) = that he could latch on for ‘comfort feeds’ after the 50 mL EBM
46 g × 1000 mg ÷ 4.2 kg = 10 952 ÷ 24 hour = 456.34 ÷ 60 minutes feed. This was to ensure it did not impact on his appetite for his
=7.6 mg/kg/min set feed volumes via the bottle. It was important that his feed
remained quantifiable given the instability of his blood sugar
levels. Had he had more stable blood sugars breastfeeding may
have been recommended before top‐up feeds (if required
depending on blood sugar levels)
214 Endocrinology
Age Medical intervention Dietetic comments
20 days 10 days after admission he was still experiencing hypos 2.5% glucose polymer concentration was added to the EBM.
<3.5 mmol/L. The medical team discussed with the dietitian the To make this practical on the ward, 1 small blue SHS scoop
introduction of a glucose polymer to help stabilise the blood sugar Vitajoule (1.3 g) was added to 50 mL EBM, providing 2.6%
levels while weaning down the glucagon concentration. Tolerance to this addition of CHO was monitored
Over the next few days, with the addition of this extra CHO, he was by stool frequency, amounts of vomits and whether the baby
weaned off glucagon as his blood sugars were consistently remained settled
>3.5 mmol/L. This allowed the baby to be stepped down to a
general ward
On admission a sample had been obtained for genetic testing.
When the results came back two weeks later, they showed the baby
had diffuse disease heterozygous ABCC8 mutation. Despite a
diagnosis of diffuse disease, the plan was for medical management
as the baby’s blood sugars were more stable
24–78 While he was on the ward, it was planned to lengthen his feed His GIR had increased significantly over the course of his
days interval from 3 hourly to 4 hourly by giving the new increased treatment. At this time it was important to assess his nutritional
volume after a 3 hour fast, then allowing him to go 4 hourly. After intake:
the 4 hour interval, his blood sugars were on the low side
Protein intake
(<4 mmol/L); therefore the Vitajoule in the EBM was increased to
P:E ratio was greatly distorted at 4% due to his high CHO
5% rather than going back to more frequent feeds. IV fluids were
requirements; however, his protein intake of 1.65 g/kg was above
stopped. Current weight = 4.8 kg
the safe minimum protein intake of 1.3 g/kg
Calculation of GIR
Energy intake 142 kcal (595 kJ)/kg and, as is common with
Feeds EBM + 5% Vitajoule: 165 mL/kg × 4.8 = 792 mL
many babies with CHI, weight gain at a rapid rate would be
Total CHO intake per 24 hours = 792 mL × 12% CHO (7% from
feeds + 5% from Vitajoule) = 95.04 g expected
GIR = It is important to regularly assess the stability of blood sugar
95.04 × 1000 = 19 800 = 825 = 13.75 mg/kg/min levels and reduce CHO intake where possible. Dietary
4.8 kg 24 hour 60 minutes changes should not be made at the same time as medication
changes. The baby was discharged home on this regimen at
3 months of age
The parents were also given an emergency regimen to use during
periods of illness when he could not tolerate his usual feeds
6 months The baby continued on octreotide injections The baby commenced weaning foods without any dietary
manipulations and eventually stopped all CHO supplementation,
which allowed Mum to solely breastfeed
11 months The baby came back into hospital for a controlled fast off He continued to have his emergency regimen for use during times
medication and demonstrated that he was now producing ketones of illness when his dietary intake may decline, and he will be at
and his CHI had become less severe and progressed to ketotic risk of a hypo
hypoglycaemia
CHO, carbohydrate; IV, intravenous; EBM, expressed breastmilk; HDU, high dependency unit; GIR, glucose infusion rate.
For this reason it is important to involve a speech and language family from the multidisciplinary team, including the dieti-
therapist from an early stage to help the family with techniques tian and speech and language therapist, with a focus on
to overcome aversion or limit its development. feeding throughout their treatment process is crucial.
Anecdotally the CHI cohort has a high prevalence of cow’s Children are often in hospital for long periods of time, which
milk protein allergy (CMPA). Changing to an extensively adds to the stress of illness upon families. The support of a
hydrolysed protein formula or amino acid‐based formula, skilled and experienced psychologist is often necessary,
where indicated, could help to alleviate some of the feeding given the burden of managing a complex medical condition
problems such as GOR, vomiting and to a certain extent oral over long periods of time [100].
feed aversion. Consideration should be given to the increased
gut transit time of these formulas vs. a whole protein feed
and, therefore, their effect on blood glucose stability. Establishing feeding in the young infant
However, if the symptoms associated with CMPA are more
effectively managed through this change, it may actually The infant with CHI should be given the chance to establish
lead to better blood glucose control. oral feeding as soon as possible. Although there is no pub-
Feeding difficulties often place an unbearable burden on lished data, the NORCHI service has found through experi-
the family of an infant with CHI. Accessible support for the ence that the more an infant is allowed to respond to their
Acknowledgements 215
own feeding cues without being regimented with feeding supermarkets. It can also be prescribed as Glycosade,
volumes and times, the better their long‐term feeding although the cost implications of this should be considered.
outcomes. This approach has to be weighed up against the If a child is taking multiple doses of uncooked cornstarch in
stability of the infant’s blood glucose levels so as not to a day, the dietitian should give consideration to the impact
compromise their safety. this may have on their appetite and, therefore, overall nutri-
Breastfeeding should be promoted and supported by the tional intake, particularly if there are concerns regarding
dietitian [128]. Initially, when the baby is unstable, the weight gain and growth.
mother may have to express breastmilk for all the feeds. As the child gets older, their condition usually becomes
Latching on after feeds or in between for comfort should be less severe, and they may eventually grow out of it. During
encouraged as soon as it is safe. Expressing breastmilk is this time they may progress from CHI to another form of
highly demanding, and steps should be taken to ensure the hypoglycaemia called ketotic hypoglycaemia. This is a con-
mother is well supported including education on optimal dition where a child’s blood sugar levels may still drop, par-
times and frequency of expression. Recently, continuous ticularly during periods of illness or prolonged fasting, but
glucose monitors have been used in individual cases; this they can now produce ketones, which will provide an alter-
has allowed parents to be less regimented with the infant’s native source of fuel for the brain. For children that go on to
feeding and has had positive outcomes in relation to oral develop ketotic hypoglycaemia, their emergency regimen
feeding and weaning. (p. 676) is still used for times of illness, but their eating on a
Weaning in infants with CHI is encouraged at around six daily basis is usually free from dietary manipulations.
months of age as for the normal population [129]. Early
weaning may be considered in the orally averse child who
does not make progress with accepting bottles to ensure that
Learning points: dietetic intervention
oral acceptance is encouraged through a different medium.
This should be done with the supervision of a speech and
• the dietitian should be involved as early as possible to
language therapist and dietitian [127].
ensure the impact of medical treatment on nutritional sta-
tus is minimised as much as possible
• the aim should be for normal infant feeding while providing
Feeding the older infant and child
a regimen that is safe for the individual
• there is high incidence of feeding problems including gas-
As the infant gets older, every effort should be made by the
tro‐oesophageal reflux, oral aversion and feed intolerance
dietitian to ensure their feeding progresses as expected for a
• all children should have an emergency regimen to be
child of their age, e.g. dropping a night feed if their blood
used during times of illness, with the aim of preventing
glucose levels are stable enough to do so. This should be
hypoglycaemia
done by increasing the volume of feed prior to their night‐
time fast and then stretching the period slowly by 30 min-
utes to 1 hour at a time while monitoring blood glucose
levels over a period of days/weeks.
Acknowledgements
The older child with CHI may benefit from the introduc-
tion of uncooked cornstarch. This can be particularly helpful
Thanks to the NORCHI team at Royal Manchester Children’s
in stretching times between meals/feeds and snacks or to
Hospital for their comments, particularly Dr I. Banerjee and
allow a longer fast period overnight. Uncooked cornstarch
dietetic colleague Niamh Gilligan, and also to Annaruby
can help with blood glucose stability because of its structure
Cunjamalay, CHI dietitian at Great Ormond Street Hospital
as a complex carbohydrate and therefore slow digestion
for Children, London.
time, which ranges from 4 to 9 hours [130]. A start dose of
5 g/dose is recommended with a maximum dose of 2 g/kg/
dose. It is not recommended in children under 1 year of age
and may be less effective in the younger child due to the
immaturity of intestinal amylase [131]. Cornstarch can be
bought in the form of cornflour from most UK
12 Cystic Fibrosis
Carolyn Patchell and Katie Stead
Introduction function is less affected in classes IV and V, so these are more

likely to result in atypical CF; however, there is significant
Cystic fibrosis (CF) is a recessively inherited life‐limiting individual variation between patients.
multi‐organ disease with around 10 400 people recorded as
having CF on the 2017 UK Cystic Fibrosis Registry Annual
Report [1]. About 1 in 25 of the UK population are carriers Diagnosis
for the condition (www.cysticfibrosis.org.uk).
Early diagnosis, new treatments and extreme vigilance in Newborn screening
the management of symptoms, with regular reviews by a
multidisciplinary team (MDT) experienced in the manage- Newborn screening for CF has been in place across the UK
ment of the condition, have resulted in improvements in since 2007.
quality of life and life expectancy, with a larger proportion of All parents of newborn infants are offered screening by
the population surviving into adult life. 60.6% of the CF pop- heel prick test on the fifth day of life. Since screening was
ulation are now adult with a median age at death of 31 years, introduced, 93% of cases of CF are identified through this
rising from 57.6% adults and median age of death of 28 years programme. Diagnosis should be confirmed by sweat test
in 2012. Predicted median survival for infants diagnosed in and identification of CF mutations by 4 weeks of age.
2017 is 47 years, rising from 44 years in 2012, with males sur- In countries that have a national screening programme,
viving an estimated 2–3 years longer than females [1]. infants are diagnosed before 2 months of age [2], enabling
CF is caused by a mutation in cystic fibrosis transmem- early initiation of preventative respiratory and nutritional
brane conductance regulator gene (CFTR), resulting in dys- care and regular follow‐up in a CF centre. Early instigation
function in the regulation of salt and water across membranes of treatment is recommended to delay the onset of respira-
of secretory epithelial cell and thickening of secretions in all tory disease [3] and to confer improved outcomes including
organs with epithelial cells. growth, respiratory disease and survival [4–6]. The diagno-
There are over 2000 different genotypes that cause CF. It is sis of CF through newborn screening, however, is not always
possible to have two of the same (homozygous) or two dif- clear, and some infants are diagnosed through the screening
ferent (heterozygous) mutations. The most common of these programme whose sweat test and/or CFTR analysis is not
is DF508, with 89% of the UK population having one copy consistent with a diagnosis of CF, nor with a negative screen.
and 49.1% having two copies [1]. The genotype affects the This group of infants has been classified as CF screen posi-
production and function of the CFTR protein and, therefore, tive inconclusive diagnosis (CFSPID). The possible outcomes
the severity of the disease. Genotypes are traditionally sepa- of screening are shown in Figure 12.1. The clinical outcomes
rated into five classes depending on the different protein of CFSPID patients are not predictable, so they will require
defects they produce (Table 12.1). In class I, II and III produc- follow‐up in a CF centre. Long‐term data reports good nutri-
tion of the protein is more severely affected, so they are more tional status for this group, and the majority will not require
likely to cause classic or more severe CF. The CFTR protein pancreatic enzyme replacement therapy (PERT) [7].

Diagnosis 217
Table 12.1 Classification of CF genotypes.
Class I Class II Class III Class IV Class V
Function No synthesis Reduced trafficking Reduced gating Decreased conductance Reduced synthesis
Mutation Nonsense, frameshift and stop Poor processing; On cell surface, protein Wrong shape so chloride Reduced protein
mutations: no CFTR is made protein does not get unstable, chloride cannot pass through easily, synthesis; reaches
due to miscoding in DNA to cell surface transport not effective but sits on cell surface cell surface, but
limited numbers
Genotype G542x F508del G551D R117H A455e
example
False Positives True Positive CF

Anxiety in parents Early initiation of
prior to exclusion of treatment
diagnosis
CF Newborn
Screening
False Negative CF
CFSPID Less than 5% of CF infants
Unclear clinical may be interpreted as not
outcome having CF through screening
and will be identified later in life
through clinical presentation
CFSPID, CF screen positive inconclusive diagnosis.
Figure 12.1 Possible outcomes of newborn screening for cystic fibrosis. CFSPID, CF screen‐positive inconclusive diagnosis.
Clinical consequences of cystic fibrosis inflammation [8, 9]. Chest treatment aims to prevent infec-
tion and remove secretions so delaying the rate of lung dam-
The clinical consequences of CF include: age. This is done by:
• chronic respiratory disease with recurrent respiratory • regular chest physiotherapy

infection, inflammation, bronchiectasis and respiratory • regular surveillance of bronchial secretions and prompt
failure treatment of infections with oral, aerosol or intravenous
• exocrine pancreatic dysfunction (pancreatic insufficiency (IV) antibiotics
[PI]) affecting approximately 84% of the CF population • use of bronchodilators to open up the airways
• nutritional consequences, including a risk of malnutri- • encouragement of an active lifestyle with regular physi-
tion and fat‐soluble vitamin deficiency due to increased cal exercise
energy requirements and fat malabsorption • cross infection measures to keep CF patients separate
• bowel obstruction including meconium ileus (MI) in to avoid transmission of bacteria, which is harmful to
infants and distal intestinal obstruction syndrome (DIOS) people with CF
in older patients
• impaired glucose tolerance or cystic fibrosis‐related dia- Overview of nutritional management
betes (CFRD) Nutritional management is an essential part of the care of
• CF‐related liver disease (CFLD) with or without portal people with CF. Malnutrition is a frequent co‐morbidity and
hypertension nutritional status is strongly associated with both pulmo-
• reduced bone mineral density (BMD), osteopenia and nary function and survival. Nutritional management should
osteoporosis begin at diagnosis, and regular and thorough follow‐up
• infertility in most males should be given by a dietitian experienced in the manage-
• CF arthropathy ment of CF. A focus on detail and early intervention if there
• behavioural and psychological problems as a result of are signs of decline offer the best outcomes [10–16].
severe life‐limiting disease and burden of treatment The aims of dietetic intervention are:
• achievement and maintenance of normal growth and
Chronic respiratory disease
development in childhood
The lungs are normal at birth, but may become affected early • control of symptoms of malabsorption
in life due to abnormal secretions, chest infection and • maintenance of normal serum vitamin levels
218 Cystic Fibrosis
• maintenance of good bone health dehydration should be taken into consideration when
• normal eating behaviour assessing weight.
• control of blood glucose levels in the presence of CFRD Infants will initially require more frequent weighing,
every 1–2 weeks after diagnosis to inform adjustments to
The nutritional status of people with CF has improved
feeding and treatment. This can be done in the community
since a high fat and high energy diet has become a standard
by the health visiting team. Once the infant is thriving and
element of care since the early 1980s.
there is stability in abdominal symptoms, the frequency of
Factors associated with poor nutrition include:
weighing can be reduced.
• increased stool energy losses due to PI; untreated PI will
lead to significant fat, fat‐soluble vitamin and, to a lesser
Length/height
degree, protein malabsorption leading to poor nutri-
tional status
Supine length should be measured for children under 2 years
• reduced pancreatic bicarbonate secretion, reduced bile
of age at each clinic visit and admission, and the measure-
acid secretion and abnormal gastric and intestinal motil-
ment plotted on the child’s growth chart. Standing height,
ity may also contribute to malabsorption
using a correctly installed and calibrated stadiometer, should
• increased energy requirements as a result of infections,
be measured for all children over 2 years of age.
inflammation and declining lung function; individual
energy requirements vary significantly depending on the
severity of the disease and requirements should be Head circumference
assessed on an individual basis
• reduced oral energy intake due to infection‐related ano- Head circumference should be measured, using a non‐
rexia, sputum production leading to nausea, abdominal stretchable disposable tape measure, in infants at each
pain, vomiting, gastro‐oesophageal reflux (GOR) and clinic visit and admission throughout the first 1–2 years and
disordered eating behaviour plotted on the child’s growth chart.
• co‐morbidities, for example, CFRD and impaired glucose
tolerance resulting in energy losses through glycosuria Body mass index (BMI)
The body mass index (BMI) centile is considered the most

Learning points: nutritional management
appropriate measure of nutritional status in CF, the aim
being to achieve and maintain a BMI on the 50th centile.
CF patients are at risk of malnutrition as a result of
In children, BMI centile is a sensitive marker of nutritional
increased energy expenditure, malabsorption and poor
status; however, BMI can mask stunting, and it is important
intake.
that BMI is not used in isolation, but is considered alongside
Dietetic aims:
height velocity. BMI cannot be used in children under 2 years
• achievement and maintenance of normal growth and of age due to a lack of reference values.
development in childhood A BMI ≤20th centile has been shown to be associated with
• control of symptoms of malabsorption reduced lung function and a BMI ≥50th centile with better
• maintenance of normal serum vitamin levels lung function [12].
• maintenance of good bone health
• development and maintenance of normal eating behaviour
Table 12.2 Frequency of measurement in infants and children.
Infants and children up to Children 2–18

Assessment of Nutritional Status Measurement 2 years of age years of age
Regular assessment of nutritional status is essential as part Weight Every 1–2 weeks until a stable 2‐monthly in
treatment plan established, then clinic, twice
of clinical assessment. Longitudinal measurements should
monthly or on admission, then weekly on
be made and measurements of growth should be plotted on twice weekly admission
age‐specific growth charts: UK‐WHO Growth Chart 0–4
Length/height Monthly in clinic/on admission 2‐monthly in
years and UK Growth Chart 2–18 years. clinic and on
admission
Weight Head Monthly in clinic/on admission n/a
circumference
All children should be weighed at each clinic visit and regu- BMI n/a Each clinic visit
larly during admission to hospital using category III elec- and on admission
tronic scales. Weight should be plotted on an age‐appropriate
growth chart. Factors such as ascites, organomegaly and n/a, not applicable; BMI, body mass index.
Management of Malabsorption 219
Assessment of body composition childhood, or if there are signs of malabsorption, fat‐soluble

vitamin deficiency or a decline in nutritional status.
Lower fat‐free mass status may be associated with poor lung
function [16], and body weight and BMI do not distinguish Pancreatic enzyme replacement therapy
between fat and lean body mass.
Assessment of body composition is, therefore, important, Untreated PI will result in malabsorption of dietary fat and
but in clinical practice is difficult to do due to a lack of vali- some dietary protein, contributing to suboptimal nutritional
dated low cost equipment that is easy to disinfect between status and fat‐soluble vitamin deficiency.
each patient’s use; therefore, it is not routinely done outside The aims of PERT are to:
of a research setting.
A summary of frequency of measurement is given in • control signs of malabsorption such as loose, frequent
Table 12.2. stools, bloating, wind and abdominal pain, aiming for a
normal stool frequency and consistency
• promote growth and maintenance of normal nutritional
Learning points: assessing nutritional status status
• achieve normal serum levels of fat‐soluble vitamins and
• Nutritional advice and interventions are aimed at achieving fatty acids
and maintaining normal growth and development in infants
and a BMI on 50th centile for children over 2 years of age
• Weight and height/length should be measured at each clinic Types of pancreatic enzyme replacement therapy
visit and hospital admission and plotted on an age‐appro- There are a number of pancreatic enzyme preparations avail-
priate growth chart able in the UK.
• Head circumference should be measured in children under 2 Full details can be found on the British National Formulary
years of age at each clinic visit or hospital admission and website (www.BNF.org).
plotted on a UK‐WHO Growth Chart 0–4 years It is recommended that enteric‐coated microspheres be
• No single measurement of weight or height/length should used; these are acid‐resistant preparations, the enteric coating
be used to evaluate nutritional status reducing the effect of gastric acid on the efficacy of the pancre-
atic enzymes. Pancreatic enzymes are available in a range of
strengths and presentations, including a granular form for
infants and young children, and in capsule form for older chil-
Management of malabsorption dren. Table 12.3 shows the preparations available in the UK.
PI affects around 84% of people with CF. There is a relation-

ship between CF genotype and pancreatic status. People Table 12.3 Pancreatin preparations available in the UK.
with class I–III CF mutations are likely to be PI; however,
there is still a requirement for objective assessment of pan- Protease Amylase Lipase
creatic status. Pancreatic function can be assessed by the Preparation units units units
presence of signs of malabsorption; however, it is recom-
Creon 10 000 capsule, e/c 600 8 000 10 000
mended that pancreatic function be tested formally in all
granules
newly diagnosed patients. Of the tests available, the one
most routinely used in clinical practice is faecal pancreatic Creon Micro e/c granules (per 200 3 600 5 000
100 mg/1 scoop)
elastase (FPE‐1). This test has a high degree of sensitivity, is
easy to perform on a single stool sample and is unaffected by Pancrex granules (per gram) 300 4 000 5 000
the presence of PERT and so can be done after PERT has been Pancrex V capsule, powder 430 9 000 8 000
commenced, if necessary. Pancrex V ‘125’ capsule, powder 160 3 300 2 950
FPE‐1 levels <100 μg/g stool are predictive of severe PI, Pancrex V e/c tablet 110 1 700 1 900
requiring treatment with PERT; levels of 100–200 μg/g stool
Pancrex V Forte e/c tablet 330 5 000 5 600
indicate reduced pancreatic function; and PERT should be
considered if there are abdominal symptoms or growth Pancrex V powder (per gram) 1 400 30 000 25 000
failure. Creon 25 000 capsule, e/c pellets 1 000 18 000 25 000
PI develops when more than 90% of acinar cell function is Creon 40 000 capsule, e/c 1 600 25 000 40 000
lost. Damage begins in utero, and approximately 92% of granules
infants are PI by 12 months of age. Secretion of pancreatic Nutrizym 22 capsule, e/c 1 100 19 800 22 000
amylase, protease and lipase is reduced or absent, resulting in minitablets
malabsorption of fat, protein, bile and fat‐soluble vitamins.
Pancrease HL capsule, e/c 1 250 22 500 25 000
It is important to remember that pancreatic function may minitablets
deteriorate over time and regular assessment should be done
in those assessed as pancreatic sufficient (PS) annually during e/c, enteric coated.
220 Cystic Fibrosis
Dosage recommendations and administration • The total dose of PERT used in CF should not exceed
10 000 units lipase/kg body weight daily
All pancreatic enzyme preparations contain a mixture of
• Patients developing new abdominal symptoms while
lipase, protease and amylase, the strength of which degrades
using PERT should be reviewed by their specialist team
over time. The dose of lipase stated per capsule or scoop is a
to exclude the possibility of colonic damage
minimum taking into account degradation; capsules that are
• High strength preparations Pancrease HL and Nutrizym
close to their use by date will have less potency than those
22 should not be used in children under 15 years of age
with a longer use by date.
• No association with FC was found in those using Creon
All pancreatic enzyme preparations are derived from pork,
25 000 and Creon 40 000
and currently there are no forms of PERT available that are
• It is important to ensure adequate hydration in those
halal or kosher. This should be discussed with families before
using high strength preparations
initiation of PERT. Families can be reassured that Islam and
Judaism allow the use of non‐halal and non‐kosher medicinal Some patients require higher doses than 10 000 units of
products that are lifesaving, if there is no acceptable alterna- lipase/kg body weight to achieve good control of abdominal
tive. Families may wish to discuss this with a hospital chap- symptoms. It is more likely to occur in infants, as they con-
lain or their own religious leader before starting PERT. sume a higher percentage of energy from fat in their diet
Pancreatic enzyme preparations are heat sensitive and than older children, and in those on a very high fat diet or
should not be stored in a hot place or mixed with hot food. requiring enteral tube feeding (ETF).
Doses should be advised individually and adjustments Children who need high doses of PERT should be closely
made based on clinical symptoms, appearance and frequency monitored, checking the titration relative to the fat content of
of stool, presence of abdominal pain, bloating, flatulence and the diet and ensuring that PERT is given with all fat‐containing
weight gain. foods. Adjunctive therapies may also be required (See
below). Dietary fat should not be limited to restrict the PERT
dose required as this may impact on nutritional status.
Enzyme dose
The dose of PERT should be adjusted according to the quan-
tity and composition of the food eaten. The lower strength
Efficacy of PERT
The timing of enzyme dosing may be an important factor in
preparations are recommended for infants and young chil-
maximising efficacy, and the recommendation is to split the
dren to allow fine adjustment of the dose.
dose throughout the meal to allow thorough mixing of the
As the majority of lipase is secreted by the pancreas, and
enzymes with food, although some children will achieve
amylase and protease are secreted elsewhere in the gastroin-
control of symptoms when the enzymes are all given prior to
testinal (GI) tract, doses are adjusted based on the fat content of
a meal.
the meal or snack consumed. Cohort studies [17, 18] suggest
Splitting the dose before, during and after the meal is a
that the requirement for lipase ranges from 400 to 5000 units
helpful strategy for children with variable intakes to ensure
lipase/g of fat consumed with a mean requirement of 1800
that too many enzymes are not given if the meal is refused.
units lipase/g fat consumed to achieve optimal absorption:
Adjunctive therapies such as H2 antagonists and proton
• Enzyme doses should be individually determined and pump inhibitors (PPI) may be required to reduce gastric acid
adjusted based on fat intake, abdominal symptoms and secretion to optimise PERT efficacy. Recent guidance from the
weight gain; requirements will vary considerably UK National Institute for Health and Care Excellence (NICE)
between patients recommends that PPI should be used with caution and the use
• Parents and caregivers should receive practical advice to of H2 antagonists or PPI should be regularly reviewed [20].
manage their PERT dose independently. The advice
should not be strictly based on lipase/g fat consumed, Practical administration
and there should be avoidance of an excessive focus of Infants
measuring the fat content of food due to the recognised Creon Micro is the most suitable PERT preparation to use in
variation in potency of enzymes, lack of accurate data infants, although Creon 10 000 capsules may be used and the
on fat content of home‐prepared foods and variability of capsules opened to administer the contents. The enzyme
appetite and intake for young children granules should be given orally mixed with a small amount
• Other GI disorders such as coeliac disease, inflammatory of the infant’s usual feed or fruit puree on a spoon. Enzyme
bowel disease and food allergies may also occur and doses should be given before and, as necessary, during feeds
should be considered if there are ongoing symptoms of of long duration. Doses will vary. A guide when starting
malabsorption despite optimising enzyme doses, timing enzymes is given in Table 12.4. Doses should then be adjusted
and titration based on volume of feed, bowel symptoms and weight gain.
Safety of PERT Children

Points to note are the following:
Following a number of serious cases of fibrosing colonopa-
thy (FC) in the 1990s, the Committee on Safety of Medicines • The gelatine capsule protects the pancreatic enzyme
issued some safety recommendations [19]: granules from gastric acid, and, therefore, they should be
Table 12.4 A guide to starting PERT in infants.

• Enzyme dosing advice should be used as a guideline due to
Nutrient‐dense the variability in bowel function and potency of enzyme
Breastfed Formula fed infant formula preparations
• Adjunctive therapy should be considered in those with high
¼–½ scoop Creon Micro ¼–1 scoop Creon ½–1 scoop Creon
enzyme requirements
for breastfeeds <20 Micro per 50–100 mL Micro per 100 mL
minute duration feed feed

½–1 scoop Creon Micro
for breastfeeds >20 Nutritional management
minute duration
Preventative nutritional advice
swallowed whole as soon as the child is able to swallow Dietetic advice should be given from diagnosis and at each
capsules (around 3–6 years of age) subsequent review with the aim of achieving normal rates of
• Chewing or crushing the capsules should be avoided as weight gain, growth and a healthy BMI centile; controlling
this reduces efficacy malabsorption; maintaining normal serum fat‐soluble vita-
• The granules should not be mixed with hot food as this min levels; and developing and maintaining normal feeding
reduces efficacy behaviours.
• The dose should be split throughout the meal
• Suggested starting dose: 1–2 capsules Creon 10 000 per
Infants
meal, 1 capsule per fat‐containing snack
The majority of infants diagnosed through newborn screen-
Pancreatic enzymes with enteral feeds ing will thrive well with exclusive breastfeeding for the
The dose and timing of enzymes depend on the timing and first 6 months of life, and this should be encouraged due to
duration of enteral tube feeds. Feeds administered slowly by the well‐documented immunological and nutritional ben-
continuous infusion, either overnight or during the day, may efits breastfeeding gives. A standard infant formula can be
require a lower dose of enzymes than anticipated. This is used for infants whose mothers cannot or choose not to
due to the stimulation of gastric lipase [21] and the slow rate breastfeed.
of fat infusion. Pancreatic enzymes are usually given at the Infants should be weighed every 1–2 weeks after diagno-
start and end of the infusion in a split dose [22]. Bolus feeds sis, and once adequate growth has been achieved, every
may require more pancreatic enzyme, similar to that required month. Infants not demonstrating adequate growth and
per gram of fat for meals and snacks, as a larger amount of weight gain will require an increased energy intake.
fat is given over a short time period.
For patients unable to swallow enzyme capsules while Pancreatic enzymes
being tube fed, e.g. those who are ventilated, a powdered All infants should be screened for PI at diagnosis and those
preparation of pancreatic enzymes dissolved in water, or showing signs of malabsorption should be started on PERT
enteric‐coated granules dissolved in sodium bicarbonate while results are awaited. A review of bowel symptoms
solution, may be used. The administration of sodium bicar- should be done every 1–2 weeks initially and then at each
bonate should be given with caution in young children due review, adjusting PERT to achieve a normal bowel habit.
to the risk of excess bicarbonate intake. A PPI will be required
if preparations are dissolved to avoid the enzymes being
destroyed by gastric acid.
Sodium supplementation
A urinary sodium–creatinine ratio (UNa–Cr) should be
assessed and sodium supplementation started at a dose of
1–2 mmol/kg if UNa–Cr ratio is low (reference range
Learning points: pancreatic enzyme therapy 17–52) [23].
• PERT is required for the majority of children with CF

Gastro‐oesophageal reflux
• Enteric‐coated microspheres should be used and given with
GOR is common in infants with CF and can contribute
all fat‐containing drinks, snacks and meals
to poor nutritional status, increased abdominal symptoms
• The dose and timing of enzymes should be individually
and discomfort and increased respiratory symptoms. GOR
assessed and regularly reviewed by a specialist CF
should be managed by the use of feed thickeners (p. 133)
dietitian
and H2 antagonists or PPI.
• The presence of other conditions such as coeliac disease,
food allergy and inflammatory bowel disease should be con-
Weaning
sidered in those with ongoing symptoms despite adequate
Normal weaning guidance should be followed with solid
use of PERT
foods being introduced by 6 months of age and no earlier
222 Cystic Fibrosis
than 17 weeks. Giving fruit and vegetables as first foods team to help support the child at school, and this will give
allows the infant to get used to feeding from a spoon in guidance on dosing and timing of pancreatic enzymes.
advance of Creon being required. Meat, pulses, cheese, Parents can request information about the school lunch
yoghurt and cereals should be introduced at 6 months of age, menu in order to give guidance to school staff on the dose of
with advice given on the appropriate dose of Creon to use for PERT required for each meal.
fat‐containing solids. Salt need not be restricted and can be Independence in self‐medication should be encouraged as
used in cooking; normal gravy and sauce mixes can be given. the child gets older. Some schools are reluctant to allow this
By the age of 12 months, the infant should be weaned onto and may need a telephone call or visit to give reassurance
mashed and chopped family foods, maintaining a healthy and advice.
balance of foods and often requiring three meals plus small
mid‐meal snacks. Full‐fat cow’s milk can be introduced as a
Adolescents
drink at 12 months of age and should be encouraged
throughout childhood to help maintain an adequate intake Adolescence is a time of increased growth and nutritional
of calcium. requirements. There is often a clinical decline during this
period, increasing nutritional requirements even further, and
Establishment of healthy eating behaviour in infants co‐morbidities such as CFRD are more likely to develop. Many
and toddlers adolescents will require more aggressive nutritional manage-
Establishing healthy feeding behaviour is important, and ment in order to achieve and maintain a healthy BMI centile.
feeding times and mealtimes should be a positive experi- Adolescence is also a time of increasing independence,
ence. Parental awareness of the need to maintain a healthy and parents often struggle to allow the young person to
weight for their child, however, can put undue focus on eat- become independent in the management of their diet and
ing, and food selectivity or refusal can be used effectively by treatment. Young people are more likely to experiment with
the child as a means of getting attention. Advice and support risk‐taking behaviour including choices of food, eating pat-
should be given to minimise the duration of any feeding terns and adherence to treatment such as pancreatic enzymes.
difficulties, and expert input from a psychologist may be Young people with chronic health conditions are more
needed for the more persistent cases. likely to develop disordered eating [24], and this is common
Simple advice that can be given by the dietitian include: in CF [25].
Maintaining a positive and supportive relationship with
• encouraging positive behaviour and ignoring bad the young person is important in facilitating adherence.
behaviour
• encouraging family meals and avoiding distractions
such as TV and IT devices such as phones and tablets Learning points: preventative nutritional advice
• making food attractive
• offering small portions; more can be given if the child • Infants diagnosed by newborn screening should be breast-
eats well fed or receive normal infant formula
• allowing the child to play with food; it is an important • Infants presenting with severe growth deficit or meconium
part of learning about food ileus will require more specialist intervention
• if the child refuses to eat, removing the food without • Solid foods should be introduced between 17 and 26 weeks
comment and not offering an alternative of age and follow a normal weaning pattern
• avoiding threats and bribes at mealtimes • Infants should be fed on a mashed or chopped family diet by
• limiting mealtimes to around 30 minutes, as after this the age of 12 months
time little additional food will be eaten • Regular counselling and advice should reduce the risk of
• all caregivers should be consistent in the management of behavioural feeding difficulties
feeding difficulties • School‐age children should be encouraged to learn about
their food and enzymes
• Adherence difficulties in adolescents are common, and
School‐age children
maintaining a positive and supportive relationship will
Normal school meals or packed lunches should be given, help to reduce the risk or duration
ideally adhering to the school food policy unless there are
nutritional difficulties; the child with CF should not be made
to feel any different to their peers.
Management of moderate nutritional deficit
Pancreatic enzymes
Most school‐age children will be able to swallow their cap- Early recognition and treatment of nutritional deficits is
sules whole and should be encouraged to learn the doses important for optimal outcomes. Addressing nutritional dif-
they require for different foods. Young children will still ficulties will require a full clinical review of not only dietary
need guidance from school staff to administer correct doses. intake, but doses and timing of PERT and, in older children,
A care plan will be developed by the CF specialist nursing screening and exclusion of CFRD.
Infants and toddlers Oral nutritional supplements

If weight gain remains poor despite increasing the energy
Infants and toddlers demonstrating poor weight gain should
intake of the diet, optimising PERT, addressing eating behav-
have the following assessment undertaken:
iour and excluding CFRD, then oral nutritional supplements
• feed and types of solids, amounts and timing (ONS) should be offered (Table 12.5). A Cochrane review [26]
• PERT dose and timing demonstrated that the use of ONS should not be considered
• stool frequency and description routine in the nutritional management of CF; although it is
• UNa–Cr ratio to assess the need for or adequacy of effective for some, there is a lack of consistent evidence of
sodium supplementation in infants their efficacy.
• presence of GOR In clinical practice ONS are often used and should be pre-
• feeding behaviour scribed on an individual basis, and their efficacy assessed
regularly. Ideally, they should be used as a short‐term meas-
Control of malabsorption is important to optimise growth;
ure to address poor nutritional intake and stopped as soon
doses of enzymes may need frequent adjustment. Assessing
as practical to avoid over‐reliance and taste fatigue. They
the presence of malabsorption based on stool description
may be particularly helpful during acute illness to prevent
alone can be difficult; however, the presence of frequent
weight loss. The quantity and timing of ONS is important,
stools with a large intake of feed per kilogram body weight,
and they should not be given to replace meals, but as a sup-
frequent feeds or meals and snacks in toddlers and inade-
plement to meals.
quate weight gain would indicate that the enzyme dose
needs to be increased.
Creon Micro, the enzyme preparation most commonly Learning points: moderate nutritional deficit
used in infants and toddlers, is vulnerable to the effects of
gastric acid, and, in some infants and toddlers, it is difficult • Control of malabsorption, GOR and sodium depletion is
to control malabsorption despite a dose of Creon Micro of important in the management of poor weight gain
≥10 000 units lipase/kg. The use of an H2 antagonist or PPI • In infants, increased frequency of feeds or introduction of a
to suppress gastric acid secretion may be helpful in these nutrient‐dense formula may be necessary
situations. • A high energy diet should be encouraged in all children
Growth failure may also be due to sodium depletion; with poor weight gain using unsaturated fats where
UNa–Cr should be measured in infants and sodium supple- possible
mentation started or adjusted as necessary. • Oral nutritional supplements may be helpful; however,
Significant GOR will result in growth failure and should their efficacy should be regularly assessed, and they should
be managed appropriately (p. 133). be discontinued if not effective or once nutritional aims
Inadequate feed intakes should be addressed, and advice have been achieved
given on the timing and volumes to offer. Some infants • ONS should not be used as a meal replacement, but may be
will require a nutrient‐dense formula to achieve adequate helpful during acute illness to reduce weight loss
weight gain (Table 1.18). These are approved by the
Advisory Committee on Borderline Substances (ACBS) for
prescription in the community in the UK for faltering
growth. Management of significant nutritional deficit
School‐age children and adolescents If nutritional status is deteriorating, or not improving,

despite a high fat high energy diet and ONS being taken,
High energy diet
then ETF should be commenced. It is widely used in CF to
When there is poor weight gain, the dietary intervention
improve weight gain and growth; around 31% of all people
should be ‘food first’.
with CF receive supplementary feeding via nasogastric (NG)
The energy density of the diet should be increased by the
or gastrostomy (G) tube [1].
use of high fat foods, ideally offering unsaturated fats as
There are a number of non‐randomised studies that
well as saturated fats, offering small frequent meals with
demonstrate the use of ETF to improve weight gain [27–30]
high energy mid‐meal snacks and increasing the intake of
and to stabilise or slow the rate of decline in lung function
full‐fat dairy foods. The following is suggested:
[28, 31]. Early intervention in correcting nutritional deficits
• foods fried in unsaturated oils is important to improve outcome, so ETF should be
• increased use of unsaturated spreads on bread and considered early in care where there is a worsening of
added to vegetables nutritional status.
• use of nut butters or ground nuts
• increased use of full‐fat dairy foods
Routes of feeding
• addition of a high energy dessert after the main meal
• offering snacks between meals such as cheese, nuts, The route of feeding should be the choice of the patient and
dried fruits, boiled egg, cereal bars, flapjacks and crisps family unless there are contraindications to the use of any
Table 12.5 Oral nutritional supplements.
Manufacturer Energy (kcal) Energy (kJ) Protein (g) Fat (g) CHO (g) Fibre (g)
Fortified ready‐to‐feed milkshake style ONS (per 100 mL)

Altraplen Compact Nualtra 240 1008 9.6 9.6 28.8 0
Aymes Complete Aymes 150 630 6 6 18 0
Ensure Compact Abbott 240 1008 10.2 9.35 36 0
Ensure Plus Milkshake Style Abbott 150 632 6.25 4.9 20.2 0
Ensure Plus Yoghurt Style Abbott 150 632 6.25 4.92 20.2 0
Frebini Energy Fibre Drink Fresenius 150 630 3.8 6.7 18.75 1.1
Fresubin Energy Fresenius 150 630 5.6 5.8 18.8 0
Fortini Nutricia 153 630 3.3 6.8 18.8 0
Fortini Compact Multifibre Nutricia 240 1005 5.7 10.9 28.5 2.4
Fortini Multifibre Nutricia 150 630 3.4 6.8 18.8 1.5
Fortini Smoothie Nutricia 150 640 3.4 6.4 19.0 1.4
Fortini 1.0 Multifibre Nutricia 100 420 2.4 4.5 11.8 1.5
Fortisip Nutricia 150 625 5.9 5.8 18.4 0.3
Fortisip Compact Nutricia 240 1010 9.6 9.3 29.9 0
Fortisip Yoghurt Style Nutricia 150 640 5.9 5.8 18.7 0
PaediaSure Abbott 101 422 2.8 4.98 11.2 0
PaediaSure Compact Abbott 240 1007 6.72 11.9 26.2 0.73
PaediaSure Plus Abbott 150 628 4.2 7.47 16.7 0
PaediaSure Plus Fibre Abbott 152 635 4.2 7.47 16.4 1.1
Resource Energy Nestle 150 630 5.6 5 21 <0.5
Resource Junior Nestle 150 631 3 6.2 21 0
Powdered high energy milkshake style ONS (estimated per 100 mL reconstituted milkshake)
Aymes Extra Shake Aymes 196 820 4.2 10.4 21.6 0
Foodlink Complete Nualtra 159 671 8.8 6.3 17 0
Scandishake Nutricia 195 820 4 9.8 9.9 0
Juice style ONS (per 100 mL)

Ensure Plus Juce Abbott 150 638 4.8 0 32.7 0
Fortijuce Nutricia 150 635 3.9 0 33.5 0
Fresubin Jucy Nestle 150 630 4 0 33.5 0
PaediaSure Plus Juce Abbott 150 638 4.2 0 33.3 0
Fortified semi‐solid supplements (per 100 g)

Aymes Creme Aymes 150 632 7.5 4.9 19.0 0
Ensure Plus Crème Abbott 137 574 5.68 4.47 18.4 0
Fresubin 2 kcal Creme Fresenius 200 840 10 7.8 22.5 0
Forticreme Complete Nutricia 160 675 9.5 5 19.2 <0.5
Fortini Creamy Fruit Nutricia 150 630 3.5 6.1 19.4 1.9
Nutricreme Nualtra 180 756 10 7.2 18.8 0
Glucose polymers (per 100 g/100 mL)

Liquid Polycal Nutricia 247 1050 0 0 61.9 0
Polycal Powder Nutricia 384 1630 0 0 96 0
Super Soluble Maxijul Powder Nutricia 380 1615 0 0 95 0
Vitajoule Powder Nestle 380 1615 0 0 95 0
High energy low volume liquid ONS (per 100 mL)

Calogen Nutricia 450 1850 0 50 0.1 0
Fresubin 5 kcal Shot* Fresenius 500 2100 0 53.8 4 0.4
Pro‐Cal Shot* Vitaflo 334 1385 6.7 28.8 13.4 0
Fat and carbohydrate powder energy supplement (per 100 g)

Duocal Powder Nutricia 492 2061 0 22.3 72.1 0
* Not suitable for children <3 years.

particular route, e.g. the presence of gastric varices in CFLD For feeds given overnight, enzymes are usually given
may preclude the use of a G device. NG and G tubes are the orally as a split dose at the start and end of the feed, although
most commonly used route of feeding. Nasojejunal and gas- if there are signs of malabsorption using this method a
tro‐jejunal feeding can be considered in the presence of smaller third dose can be given midway through the feed.
severe GOR. The impact of disturbing sleep should be considered and
children should not be woken to give enzymes.
Nasogastric feeding For bolus feeds, given over a short period of time, enzymes
NG feeding is usually considered a less permanent choice of may be given at the start of the feed only.
feeding than other routes and is preferred by some children
and young people. With concerns about their body image, Other considerations
some choose to remove the feeding tube for special events; Following initiation of ETF, weight, height, BMI and abdom-
some may even remove the tube daily, with replacement of inal symptoms should be monitored, and the feeding and
the tube each night prior to commencing feeding. This needs enzyme plan adjusted as necessary, with the aim of increas-
considerable motivation to be successful. NG feeding may ing lean body mass, not just adipose tissue. Weight gain,
also be used for short episodes of feeding, such as during therefore, should not be too rapid.
inpatient admissions for IV antibiotics, or to support recov- Glucose tolerance should also be carefully monitored on
ery of weight following acute illness. commencement of ETF to ensure it has not resulted in noc-
NG feeding tubes may be easily dislodged during cough- turnal hyperglycaemia. Blood glucose levels should be
ing or vomiting and, therefore, may not be suitable for all checked mid‐ and post‐feeding and ideally repeated monthly
patients. NG feeding can cause nausea, vomiting, disturbed at home with insulin being commenced if required.
sleep and negative changes in body image.
Local hospital policies and national guidance should be
adhered to when introducing NG tube feeding. Learning points: significant nutritional deficit
• Enteral tube feeding should be introduced in patients who

Gastrostomy feeding
are failing to reach optimal BMI, despite the use of a high
G feeding is the preferred route of feeding for many patients
energy diet and ONS
who require long‐term ETF. Like NG feeding it can cause
• The choice of feeding tube and timing of feeds should be
nausea, vomiting, disturbed sleep and negative changes in
agreed for the individual child
body image, although most complications are mild and short
• Sterile ready‐to‐use high energy age-appropriate polymeric
term.
1.5–2.0 kcal (6–8 kJ)/mL feeds are suitable for the majority
Local hospital feeding policies and national guidance
of patients
should be adhered to when commencing G tube feeding.
• Pancreatic enzymes should be administered with feeds; the
timing and dose should be determined individually
Choice of feed and administration • The rate of feeding and volume administered should be
adjusted to ensure accrual of lean body mass; therefore,
Most patients with CF will tolerate a high energy paediat- weight gain should not be too rapid
ric polymeric 1.5 kcal (6 kJ)/mL feed, with or without fibre • Blood glucose measurements should be done at the start and
(Table 4.3), given as a continuous infusion via an enteral midway through the feeding period to check for nocturnal
feeding pump. Occasionally patients may fail to tolerate hyperglycaemia; this should be repeated monthly at home
these feeds, and, in this situation, a hydrolysed protein • Nocturnal hyperglycaemia should be treated with insulin
(semi‐elemental) or amino acid‐based (elemental) feed under the guidance of a diabetes team
can be considered (Tables 8.20), although the need for
these is rare.
Vitamins and minerals
Administration of pancreatic enzymes with tube feeding
Pancreatic enzymes will be required with polymeric, protein Fat‐soluble vitamins
hydrolysate or amino acid‐based feeds. Feeds with a high
Children with PI are at risk of malabsorption of fat‐soluble
medium chain triglyceride (MCT) content should be used
vitamins, with evidence of biochemical deficiency in infants
(Table 8.20). The dose and the timing of PERT should be con-
at the time of diagnosis by newborn screening [32–35].
sidered individually, taking into account the choice of feed,
Factors contributing to deficiencies include:
rate of infusion and usual enzyme requirement. Enteric‐
coated enzymes should be given orally and not put down • fat malabsorption and bile salt deficiency
the feeding tube due to the risk of blockage. • suboptimal dose or poor adherence to PERT
Feeds given slowly over a long period of time, e.g. over- • poor dietary intake
night, may need less enzyme than those given as a bolus due • inadequate dosing or poor adherence to fat‐soluble vita-
to the slower infusion rate of fat. min supplements
226 Cystic Fibrosis
• increased utilisation and poor bioavailability Vitamin E

• short bowel syndrome due to previous resection Vitamin E acts as an antioxidant reducing the effect of free
• cystic fibrosis‐related liver disease (CFRLD) radicals, produced as a result of infection and inflammation,
and helping to protect the cells from oxidative damage. Low
Avoidance of fat‐soluble vitamin deficiency is important,
levels of vitamin E have been identified in newborn screened
not just in the context of overt deficiency symptoms, but in
infants, irrespective of pancreatic function [41], and vitamin
the avoidance of subclinical deficiency, which is important
E deficiency has been associated with haemolytic anaemia in
for optimal health outcomes.
infants [42], it may cause ataxia and neuromuscular degen-
Fat‐soluble vitamin levels should be measured in all chil-
eration [43], and it may impact cognitive function.
dren annually. Ideally these should be done in a fasting state;
however, for practical reasons, this is often not possible in
paediatric patients. Vitamin K
Most patients with PI will require supplementation that Vitamin K plays a role in blood clotting and bone health.
should be taken with food and PERT to optimise absorption. Deficiency can result in bleeding and may contribute to low
Patients who are PS should be monitored closely as some BMD. Studies show that subclinical deficiency of vitamin K
will also require supplementation, despite having pancreatic is common in CF [44, 45], and it is now recommended that all
function within normal limits. patients with CF receive a daily vitamin K supplement. This
is a change in practice from that advised in previous nutri-
tional consensus guidelines. Evidence from randomised
Vitamin A controlled trials on the benefits of routine vitamin K supple-
Vitamin A plays a role in retinal health. Low levels can result mentation for people with CF is currently weak and limited
in night blindness and proceed to xerophthalmia. Vitamin A to two small trials of short duration. However, no harm was
also has a role in maintenance of mucus‐secreting epithelial found, and until further evidence is available, the present
cells and is an antioxidant. There are many reports of night recommendations should be adhered to [46].
blindness in CF, with both conjunctival xerosis and night The monitoring, toxicity and supplementation of fat‐soluble
vision problems reported [36]. Close monitoring and atten- vitamins are given in Tables 12.6 and 12.7.
tion to maintaining normal serum levels will prevent the
development of symptoms of deficiency.
Vitamin A is absorbed in the small intestine and circulates Sodium and fluid intake
in the serum, attached to retinol binding protein (RBP). It is
There is a risk of sodium depletion in CF as a result of
stored in the liver as retinol esters and serum retinol levels
increased losses in sweat, the risk increasing during hot
reflect body stores only when liver stores are severely
weather and during exercise. Infants are also at risk due to
depleted or extremely high. Serum retinol levels should be
their high surface area relative to body weight and low
used as a guide only; however, they are the only practical
intake of sodium from breastmilk or formula feeds.
assessment in the clinical setting.
Sodium depletion will result in hyponatraemia, decreased
appetite, nausea, vomiting, lethargy, headaches, muscle cramps
Vitamin D and suboptimal weight gain in infants [47]. Hyponatraemia
Dietary sources of vitamin D do not contribute signifi- may also contribute to thicker secretions in both the lungs and
cantly to vitamin D status. Exposure of 7‐dehydrocholes- bowel and may contribute to the development of DIOS [48].
terol present in the skin to sunlight or UV irradiation In routine clinical practice, UNa–Cr should be used to
produces vitamin D3 (cholecalciferol), which impacts more assess sodium status, and supplementation given or adjusted
on serum vitamin D levels than dietary intake. In the UK, if levels are abnormal.
vitamin D production usually occurs only between April Urinary sodium in isolation may be used as an approxi-
and October. mation of status, and levels <30 mmol/L require supplemen-
Vitamin D deficiency causes rickets in children, and low tation to reduce the risk of hyponatraemia and low weight
levels are a contributing factor in the low BMD seen in CF. gain in infants.
Low serum levels of 1,25‐dihydroxyvitamin D increase pro- All children with CF should be encouraged to have a high
duction of parathyroid hormone (PTH), resulting in salt diet. Salt should be used in cooking, added to foods at
increased bone turnover and bone loss. the table, and salty snacks and food should be encouraged.
Vitamin D deficiency is prevalent in CF and is due to: Sodium‐supplemented sports drinks may be useful. A high
fluid intake should also be encouraged, especially for those
• reduced absorption of vitamin D due to PI requiring additional sodium supplements.
• low BMI leading to reduced ability to store vitamin D in
adipose tissue Infants
• reduced levels of vitamin D binding protein The need for supplementation should be assessed on an
• impaired hydroxylation in the liver individual basis, taking into account sodium losses and cli-
• reduced exposure to sunlight due to ill health mate. Those at risk or with low UNa–Cr should be
Vitamin D status is positively associated with lung func- supplemented with 1–2 mmol Na/kg daily, divided into
tion [37–40]. 2–4 daily doses, added to feeds.
Table 12.6 Monitoring, toxicity and supplementation of fat‐soluble vitamins.
Vitamin Monitoring Toxicity Supplementation
A Annually during a period of stability and not during an acute Acute toxicity causes vomiting, Retinol is the preferred source,
exacerbation. abdominal pain, anorexia, blurred starting with a low dose and
Samples should be processed promptly and protected from vision, headaches and irritability. increasing according to serum
light to avoid degradation. Chronic toxicity causes levels
If levels are low RBP, zinc and a marker of infection should be headaches, muscle and bone
measured (e.g. CRP) as levels of vitamin A may be falsely pain, ataxia, alopecia, liver
depressed in acute infection and inflammation and in children toxicity and dyslipidaemia
with liver disease
D Serum 25‐hydroxyvitamin D levels should be measured. There is evidence that vitamin D3
This need not be a fasting sample; however, seasonal variation (cholecalciferol) is more effective
should be taken into account when interpreting the results than ergocalciferol at sustaining
adequate serum levels [36]
E Serum vitamin E levels represent only a proportion of total Hypervitaminosis E is rare and Supplementation should be
vitamin E, which is found mostly in cell membranes. occurs only when large started in patients who are PI and
Serum levels will vary according to levels of carrier lipoproteins supplementary doses are given. in patients who are PS if low
so vitamin E concentrations should be reviewed in relation to It may result in bruising and serum levels are seen.
serum lipid levels, which requires a fasting sample. bleeding and increased Supplements should be taken
A minimum ratio of α‐tocopherol to cholesterol of 5.4 mg/g has prothrombin time with food and PERT
been suggested
K Plasma vitamin K levels and deranged prothrombin time are Vitamin K1 (phytomenadione) is
both unreliable and insensitive markers of vitamin K status. considered the safest form to use.
The most reliable measure of is protein induced by vitamin K Routine supplementation is
absence (PIVKA II). recommended for all patients
This is not routinely available in clinical practice and it is, who are PI
therefore, difficult to routinely assess status
RPB, retinol binding protein; CRP, C‐reactive protein; PI, pancreatic insufficient; PS, pancreatic sufficient; PERT, pancreatic enzyme replacement therapy.
Table 12.7 Recommendations for supplement doses of fat‐soluble Table 12.8 Recommendations for sodium supplementation [49].
vitamins.
Age Daily sodium supplementation
Vitamin Daily supplement
0–12 months 1–2 up to 4 mmol/kg in those with increased losses
Vitamin A >1 year Up to 4 g in divided doses
<1 year <1500 IU (0.45 mg)
Adolescents Up to 6 g in divided doses
>1 year 1500–10 000 IU (0.45–3.0 mg)
Vitamin D
<1 year 400–2000 IU (10–50 μg)
• when dietary intakes are low
• before strenuous exercise
>1 year 400–5000 IU (10–125 μg)
• during episodes of pyrexia
Vitamin E
• when there is excessive sweating
<1 year 40–80 IU
1–3 years 50–150 IU
Sodium supplements can be added in a liquid form to
infant formula and expressed breastmilk or into fruit squash
4–7 years 150–300 IU
or fruit juice for toddlers. Sodium tablets are usually pre-
8–18 years 150–500 IU scribed for older children and young people. Recommendations
Vitamin K for sodium supplementation are given in Table 12.8.
<2 years 300 μg/kg
2–7 years 5 mg Calcium
>7 years 5–10 mg
A number of factors affect calcium balance in CF including:
Source: Adapted from www.cysticfibrosis.org.uk • malabsorption and increased faecal loss
• inadequate intake
Older children • glucocorticosteroid treatment
Supplementation should be given: • increased gastric acid reducing the solubility of calcium
salts
• in hot weather
• if there are excessive GI losses, such as stoma losses or Calcium deficiency will result in bone demineralisation
prolonged diarrhoea and low BMD is a common feature in adults with CF. A high
228 Cystic Fibrosis
Table 12.9 Recommendations for calcium intake. Serum magnesium levels should be monitored annually,
and individuals identified as having low serum levels should
Age Daily calcium intake (mg) be prescribed supplementation.
0–6 months 210
7–12 months 270 Iron
1–3 years 500
Iron deficiency is common in CF and risk factors include:
4–8 years 800
• malabsorption
9–18 years 1300
• low dietary intake of iron rich foods
Source: Adapted from www.cysticfibrosis.org.uk • chronic infection and inflammation
• use of PPI
• blood loss due to haemoptysis or GI losses
calcium intake is a positive predictor of bone health in
adolescents with CF [45]. Iron status should be assessed annually and supplementa-
Intake of calcium is generally good; however, due to the tion prescribed in those with low serum iron levels. All
factors affecting calcium absorption, a high calcium intake is patients should be counselled regarding an adequate dietary
advised, particularly during adolescence. intake of iron [49].
Individuals with a high intake of milk in addition to There have been concerns regarding iron supplementa-
enteral feeds or calcium supplements may exceed the safe tion in CF as iron can increase the virulence of bacteria, and
upper limit of 1500 mg/day for the healthy population. studies suggest that increased iron may facilitate infection
Calcium requirements in CF are higher; however, extremely with Pseudomonas aeruginosa [55]. A randomised double‐
high intakes should be monitored and reduced if possible. blind placebo‐controlled study in which a trial of low dose
Recommendations for calcium intake are given in Table 12.9. ferrous sulphate was given daily for 6 weeks did not
identify an increase in respiratory exacerbation or sputum
microbiome [56, 57].
Learning points: calcium
Water‐soluble vitamins
• A high intake of calcium should be encouraged for all, espe-
cially adolescents Water‐soluble vitamins are well absorbed and routine sup-
• A diet rich in milk and dairy produce should be encouraged plementation is not required.
throughout childhood; intake should be assessed at each
review
Essential fatty acids, probiotics, antioxidants
• Calcium supplements should be prescribed if dietary intakes
are suboptimal There is no firm evidence for routine supplementation with
antioxidants, essential fatty acids or probiotics in CF, and
further research is required before recommendations can
be made.
Zinc
Zinc deficiency can result in growth retardation in children, poor Case studies
appetite and impaired immune function and should be consid-
ered in children with poor oral intake and suboptimal growth. A case study describing the dietetic management of an infant
Low serum zinc levels can also contribute to secondary vitamin who screened positive for CF with newborn screening is
A deficiency, as it is required for the synthesis of RBP [50]. shown in Table 12.10. A case study of a boy with significant
Fasting plasma zinc levels are the most sensitive marker of nutritional deficit is shown in Table 12.11.
deficiency and should be assessed in those where zinc defi-
ciency is considered, such as those with poor growth or poor
oral intake. Individuals with low serum zinc levels should
Co‐morbidities
receive oral supplementation to correct deficiency. The North
American CF Foundation recommends 1 mg zinc/kg daily in
Cystic fibrosis‐related diabetes
children under 2 years of age who are not growing despite a
CFRD is a common co‐morbidity with around 12% of chil-
high energy intake and control of malabsorption [51].
dren between 10 and 15 years requiring treatment, rising to
around 34% of adults. The diagnosis of CFRD reduces life
Magnesium
expectancy by an estimated of 10 years, and there is often a
Risk factors for magnesium deficiency include treatment decline in nutritional status and respiratory function during
with N‐acetylcysteine (to treat abdominal symptoms) and the year prior to diagnosis [58]. CFRD shares clinical features
diatrizoate sodium powder or Gastrografin (to treat DIOS) of both type 1 and type 2 diabetes; however, it is a distinct
[52], CFRD [53] and use of PPI [54]. condition [59].
Co‐morbidities 229
Table 12.10 Case study: an infant screened positive for cystic fibrosis.
At diagnosis
A female infant 16 days old. Second child of a school teacher and an IT consultant. Older sister aged 3 years old has no medical history.
Remains under midwife care as not yet regained birthweight.
Genetics: dF508 homozygous.
Birthweight = 3.1 kg (25th centile)
Assessment
Anthropometry
Weight = 2.89 kg (2nd–9th centile) Length = 51 cm (9nd centile)
Head circumference = 36 cm (50th–75th centile)
Feeding and stools
• Breastfeeding approximately 12 times per day, feeding well at most feeds from both breasts
• 6–8 loose, yellow stools per day with visible oil
Nutritional diagnosis
• Nutritionally compromised: not regained birthweight by 14 days
• Potential for catch‐up growth: head circumference centile is higher than weight and length centiles
• Malabsorption: weight loss despite frequent feeding; oily, yellow offensive stool, therefore, likely pancreatic insufficient
Management plan
PERT
• Check pancreatic function; send stool for FPE‐1
• Initiate PERT based on clinical symptoms of weight loss, malabsorption, frequent stool, excessive feeding and genetics indicative of PI. This will
prevent further weight faltering while waiting for FPE‐1 result
• PERT dosage: ¼ scoop of Creon Micro approx. 1250 units lipase per feed, 8500 units lipase/kg
• Practical PERT advice:
◦◦ Put Creon Micro granules on top of a drop of formula/EBM on baby weaning spoon
◦◦ Advise not to give Creon Micro granules dry because there is a risk of inhalation
◦◦ Give parental reassurance about dosing of Creon Micro; the scoop provided is small to allow gradual increase of dose, but precision can be
difficult and it takes practice to master
◦◦ Give parental reassurance that it is expected that feed volumes taken may reduce and stool consistency, colour and frequency may change
Feeding
• Assess attachment and positioning during a breastfeed and direct to local breastfeeding support networks if further help is needed
• Give parental reassurance that many babies with CF can successfully breastfeed. There is no need to change to infant formula or express breastmilk
to enable assessment of fat intake
Micronutrients
• Provide family with fat‐soluble vitamins that may be started at home before the next clinic visit, with either a home visit or telephone advice from
the CF MDT; this is part of a staged introduction of CF treatments
• Check UNa–Cr to assess the need for sodium supplementation
Monitoring/follow‐up
• Weekly weighing; this can be with community agencies such as the health visitor or with the CF nursing team
• Weekly telephone contact with the family to assess feeding pattern, weight gain, stool consistency and frequency, dose of PERT needed
• Increase Creon Micro by ¼ scoop per feed during phone contact if indicated by ongoing malabsorption symptoms to a maximum dose of 10 000
units lipase/kg
• Review in CF clinic appointment in 2 weeks
At second clinic visit
Infant is now 1 month old
Assessment
Anthropometry
Weight = 3.3 kg (9th centile) Length = 51 cm (9th centile)
Head circumference = 36.8 cm (50th–75th centile)
Feeding and stools
• Breastfeeding – 8 feeds per day, feeding well at most feeds from both breasts
• 4 large orange stools, mousse like consistency
PERT
• ½ scoop of Creon per feed (2500 units lipase per feed, 6250 units lipase/kg)
Biochemistry
• Urinary Na: <20 mmol/L
• Nutritional status improving
• Malabsorption improved: stools less frequent, darker and less liquid. Feeding has also reduced because nutrients are being absorbed and utilised.
However, stools remain abnormal
• Low urinary sodium levels
Management plan
PERT
• Increase Creon to ¾ scoop per feed (3750 units lipase per feed, 9375 units lipase/kg), based on stool frequency and appearance and to promote
further catch‐up growth
Micronutrients
• Start sodium supplementation 2 mmol/kg, e.g. 3 mL BD 1 mmol/mL NaCl solution
• Practical advice for sodium solution:
◦◦ Put in a bottle of EBM/formula, it can be given in one dose per day if tolerated
◦◦ NaCl can be given undiluted via syringe, but this is not well tolerated and often causes vomiting
• Continue weekly weighing in the community to monitor nutritional recovery closely
• Continue weekly phone contact to assess bowel symptoms and feeding pattern, increase Creon dose by ¼ scoop if indicated (to a maximum 10 000
units lipase/kg).
• Review at clinic appointment in 1 month
At third clinic visit
Infant is now 2 months old
Assessment
Anthropometry
Weight = 4.5 kg (9th–25th centile) Length = 55.2 cm (9th–25th centile)
Feeding and stool history
• Taking fewer feeds – 6 breastfeeds per day, feeding well at most feeds from both breasts plus one bottle of EBM with added NaCl
• 2–3 orange/light brown pasty stool per day
Biochemistry
• UNa–Cr ratio: 42
• Vitamin A: 1.3 μmol/L (0.7–1.5 μmol/L), Vitamin E: 16.2 μmol/L (7–21 μmol/L), Vitamin D: 78 nmol (>50 nmol/L), figures in brackets normal range
PERT
• 1¼ scoop Creon Micro per feed (6250 units lipase per feed, 8578 units lipase/kg)
• Consider giving it in fruit purée instead of formula/EBM, as it holds granules in a gel so is easier to give
• Nutritional status recovering
• Malabsorption significantly improved and excessive feeding reduced
• Sodium status normalised
• Serum vitamin levels normal
Management plan
• No vitamin adjustments needed
• Continue sodium supplementation, maintain dose at 1–2 mmol/kg, will need adjusting with weight gain
• Increase Creon Micro: 1½ scoops (7500 units lipase per feed, 10 290 units lipase/kg)
• Reduce frequency of weight measurements and telephone reviews with the family because weight gain is recovering and PERT does not need
adjusting as frequently
At seventh clinic visit
Infant is now 6 months old
Assessment
Anthropometry
Weight = 7.3 kg (50th centile) Length = 63 cm (25th centile)
Feeding and stool history
• 4 breastfeeds per day, feeding well at most feeds from both breasts plus one bottle of EBM with added NaCl
• 2 meals of a variety of fruit and/or vegetable purée with some finger foods
• 2 light brown, soft, large stools
PERT
• 2 scoops Creon Micro per breast or bottle feed (10 000 units lipase per feed, 7024 units lipase/kg)
• Nutritional status recovered
• Malabsorption improved and feeding reduced
Management plan
• Introduce fat‐containing solids, e.g. meat, dairy, egg – appropriate textures
• ½ scoop Creon Micro with fat‐containing solids
• Give parental reassurance that stool appearance and frequency may change with the introduction of solids, discuss signs of malabsorption and
encourage parents to contact dietitian by telephone if concerned
• Telephone call to parents 2 weeks after clinic to advise:
◦◦ Titration of Creon Micro if indicated by symptoms of malabsorption
◦◦ Progression of normal weaning
◦◦ Review in clinic in 1 month
PERT, pancreatic enzyme replacement therapy; FPE‐1, faecal pancreatic elastase; PI, pancreatic insufficient; EBM, expressed breastmilk; UNa–Cr,
urinary sodium–creatinine ratio; BD, twice daily.
Table 12.11 Case study: a boy with cystic fibrosis with significant nutritional deficit.
A 9‐year‐old male
He lives with mum, a homemaker, and dad, a finance officer. No siblings
Genetics: Homozygous delta F508
Diagnosed by newborn screening, weight was faltering at diagnosis with his weight 2 centiles below his length. Good catch‐up growth was achieved
by 12 months and his weight tracked on 50th centile from then, with his height around 25th–50th centile
The CF MDT have no concerns around his CF treatment compliance. Unable to increase oral intake due to poor appetite and dislike of ONS
Lung function (FEV1) is stable around 100% predicted; no recent clinically significant pulmonary exacerbations
Assessment
• Baseline lung function (FEV1) stable: 103% predicted
• Static weight = 23 kg (9th centile) for 9 months, previously had a slow decline from 50th to 25th centile over 12 months
• 12 months ago: BMI = 25th–50th centile, 18 months ago BMI = 50th percentile, current BMI = 9th centile
• Oral nutritional strategies have been maximised, including food fortification
• Poor tolerance of ONS, currently taking 60 mL Pro‐Cal Shot daily, providing 200 kcal
• No signs of malabsorption: stools described as normal, type 3 or 4 on Bristol stool chart, brown, once per day (parents agree: not excessively
frequent, offensive or difficult to flush)
• No recent clinically significant pulmonary exacerbations
• Recent OGTT normal
• Faltering growth despite attempts to maximise oral intake
• No malabsorption
• Glucose tolerance normal – no CFRD
Management plan
• Discuss enteral feeding with family and MDT
• Start nasogastric feeds
• Blood glucose levels should be checked mid‐ and post‐feeding and repeated monthly at home with insulin being commenced if required
Calculating feed regimen
• EAR energy = 63 × 23 = 1449 kcal
• Aim to give approximately 50% energy using overnight feed = 725 kcal/day
(500 mL standard age‐appropriate energy fibre containing feed)
Calculating enzymes dose
• Feed contains 6.3 g fat/100 mL (aiming for 500 mL of feed)
= 6.3 × 5 = 31.5 g fat in total feed volume
• Estimate PERT dose from average of patient’s usual enzyme dosing
1 Creon 10 000 capsule/5 g fat therefore 31.5 ÷ 5 = 6.3 = 6 Creon 10 000 capsules in total
Feeding plan:
Tentrini Energy Multifibre: 55 mL/hour × 9 hours
Creon 10 000: 4 capsules at the start and 2 capsules at the end/on waking
Initial monitoring
• Stool consistency: check for any changes indicating malabsorption
• Feed tolerance: ensure no new reporting of vomiting, abdominal pain, diarrhoea or other signs of feed intolerance
Follow‐up
• Check weight 1 month post‐discharge; this can be in community, e.g. GP surgery or community nurse, to ensure nutritional recovery
• Review in CF clinic review every 2 months with full nutritional assessment
At 6 month clinic review

Assessment
Weight = 28.4 kg (25th centile) Height = 131.2 cm (9th centile) BMI = 50th–75th centile
• Achieved catch‐up growth. Can now aim for normal growth along centile
Management plan
Reduce feeds to 5 nights per week
• Likely to need long‐term enteral feeding to maintain optimal nutritional status, discuss option of gastrostomy
MDT, multidisciplinary team; ONS, oral nutritional supplement; BMI, body mass index; OGTT, oral glucose tolerance test; CFRD, cystic fibrosis‐related
diabetes; EAR, estimated average requirement; PERT, pancreatic enzyme replacement therapy.
232 Cystic Fibrosis
Table 12.12 Dietary recommendations for CFRD.
Dietary recommendations Low BMI BMI 25th–75th centile Overweight/obese
Complex carbohydrate Regular intake, include at all meals Regular intake, include at all meals Regular intake, include at all
meals
Simple sugars Include at meals, avoid high sugar Include at meals, avoid high sugar snacks Avoid
snacks and drinks and drinks

Fat No limit No limit Reduce intake

Carbohydrate counting Consider in those with poor or Consider in those with poor or variable Consider in those with poor or
variable appetite appetite variable appetite
BMI, body mass index.
The main driver of CFRD is insulin deficiency. Insulin individualised, depending on the pattern of hyperglycaemia
secretion in people with CF appears to decline from child- i dentified through CGM or serial blood glucose monitoring.
hood, even in individuals with normal blood glucose lev- The dietary recommendations for type 1 and type 2 diabe-
els [59]. The insulin response to a glucose load is reduced tes are not usually appropriate, and advice should be indi-
and delayed, resulting in high glucose levels that can nor- vidualised based on nutritional status. Insulin regimens
malise within 2 hours. Basal insulin secretion is usually need to be modified for those receiving overnight enteral
initially preserved, so fasting levels may remain normal feeding to optimise glycaemic control at night and may need
despite a diagnosis of CFRD. Insulin sensitivity is usually adjusting to account for patients who do not receive enteral
normal in CF, but other factors common in CF may cause feeding every night. Dietary recommendations for CFRD are
insulin resistance, e.g. infection, inflammation or systemic given in Table 12.12. A case study describing CFRD is given
corticosteroid use. There is evidence that starting insulin in Table 12.13.
therapy early improves respiratory and nutritional health
and reduces the development of diabetes‐related compli-
Learning points: CF‐related diabetes
cations [58–61].
Collaborative MDT working between CF specialists and
• Annual OGTT is required to screen for CFRD after 10
diabetes specialists is important to optimise outcomes.
years of age
• Glycaemic control should be optimised to minimise the
Screening for CFRD impact on nutritional status and respiratory health
Annual oral glucose tolerance tests (OGTT) are advised for • Insulin injections are required and the regimen should be
all children over 10 years of age as a screening tool. As sig- individualised based on the pattern of hyperglycaemia
nificant numbers of children with CF have a degree of • Standard dietetic advice for type 1 and type 2 diabetes is not
impaired glucose tolerance, the standard WHO OGTT may suitable for CFRD
not identify all of those with a degree of impaired glucose • Dietary advice depends on nutritional status and patterns
tolerance requiring treatment. A 4‐point OGTT, with blood of eating
glucose measurements taken at T0, T30, T60, T90 and T120, • MDT working between the CF team and the diabetes team
may be a more sensitive screening tool due to abnormalities is important for optimal outcomes
in insulin secretion.
Abnormal glucose tolerance identified through screening
should be followed by serial blood glucose monitoring or
continuous glucose monitoring (CGM) (p. 191) to assess the Cystic fibrosis‐related liver disease
need for treatment.
CFRLD includes fatty liver (steatosis), which is a relatively
benign condition with no evidence that it leads onto cirrho-
Treatment
sis, and biliary cirrhosis.
The aim of treatment is to normalise blood glucose levels, to The development of steatosis is not linked to a high dietary
avoid the long‐term complications of diabetes and to opti- fat intake, and there should be no dietary restrictions if BMI
mise nutritional status and respiratory function. is either suboptimal or healthy. For patients who have a high
Insulin injection is the recommended treatment for CFRD. BMI, advice should be given to reduce energy and fat intake
Control of blood glucose levels has been shown to have a with the aim of reducing BMI to within the healthy range.
positive impact on respiratory function, nutritional status Biliary cirrhosis is a more serious complication leading to
and mortality [58–62]. Insulin regimens should be portal hypertension in 5%–15% of cases [63–65], and
Table 12.13 Case study: an adolescent boy diagnosed with cystic fibrosis‐related diabetes.
A male aged 13.5 years

Lives with mum, a florist, and brother aged 11 years
Genetics: heterozygous DF508 and G542x
Baseline lung function (FEV1% predicted): 75%
Has elective hospital admissions every 4 months for IV antibiotics
Fed via gastrostomy since infancy due to poor oral intake
At the time of review was having an overnight feed four times per week: 800 mL given over 10 hours, 2 kcal/mL (8 kJ/mL) feed
Assessment
• Weight loss of 1.5 kg over 2 months, but gradual decline of 4 kg over the past 9 months
• Weight previously on 75th centile, at time of review just below 50th centile
• BMI dropped from 50th–75th centile to 25th at time of review in 9 months
• Height tracking 75th centile
• Lung function (FEV1% predicted) slowly decreased by approx. 15% (baseline approx. 75%) to 57% over previous 6 months
• No changes in dietary intake, gastrostomy feeds, stool or PERT
• No severe respiratory exacerbations
• No malabsorption symptoms reported
• OGTT 18 months ago was normal
• Overnight hyperglycaemia on routine blood glucose monitoring
• Weight faltering despite gastrostomy feeding, adequate PERT management and good oral intake
• Decline in pulmonary and clinical status without significant pulmonary exacerbations or other clinical explanation
Management plan
• To have OGTT
OGTT results:
• 0 minute: 4.5 mmol/mL
• 30 minutes: 11.0 mmol/mL
This is diagnostic of impaired glucose tolerance
Management plan
5‐day CGMS to include:
• School and non‐school days
• Days with and without overnight gastrostomy feeds
CGM results:
• 23% of readings >7.8 mmol/mL (see Figure 12.2)
• Demonstrating five peaks of >11.1 mmol/mL and other peaks >7.8 mmol/mL following consumption of sweets or full sugar fizzy drinks at morning
break, after school and in the evening
• Readings >7.8 mmol/mL overnight, occurring on days on and off overnight gastrostomy feeds, but higher levels and longer duration when on
gastrostomy feeds overnight
Joint review with endocrine consultant:
• Initiate insulin, 1 dose of long‐acting insulin given in the evening
◦◦ 4 units Levemir when not on gastrostomy feeds
◦◦ 6 units Levemir when on overnight gastrostomy feeds
• Swap full sugar drinks for diet, zero or no added sugar alternatives
• Maximum of one portion of sweets after meals, not to be eaten in isolation
• No other dietary alterations, maintain a high energy diet
Assessment 4 months after start of insulin
• Weight tracking 75th centile (increased by 3 kg)
• Lung function back at baseline (FEV1% predicted: 75%)
• Repeat CGMS after 3 months is normalised (see Figure 12.3)
◦◦ 4% reading >7.8 mmol/mL
◦◦ No peaks >11.1 mmol/mL
IV, intravenous; PERT, pancreatic enzyme replacement therapy; OGTT, oral glucose tolerance test; CGMS, continuous glucose monitoring system.
234 Cystic Fibrosis
20
15
10
7.8
5
3.9
2.2
0
00:00 02:00 04:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 00:00
Figure 12.2 Continuous glucose monitoring before insulin started.
20
15
10
7.8
5
3.9
2.2
0
00:00 02:00 04:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 00:00
Figure 12.3 Continuous glucose monitoring 3 months after insulin started.
end‐stage liver disease is a late complication affecting mainly that BMD is normal in well‐nourished children with CF
adults. Data from the 2017 UK CF Registry [1] shows that with well‐preserved lung function, but many patients fail
7.9% of all CF patients under 16 years of age have evidence to gain bone mass normally and/or experience premature
of liver disease, with or without portal hypertension. bone loss in adolescence or early adult life. Osteoporosis
The only therapeutic option to give ursodeoxycholic acid affects around 0.7% under 16 year olds, rising to 18.5% in
(p. 180) has been shown to improve serum liver enzymes adults [1].
levels. A small proportion of CF patients will require a liver The aetiology of low BMD is multifactorial and major risk
transplant. factors include:
Significant CFRLD may increase energy requirements by a
• overall disease severity, including links to FEV1 (forced
further 20%–40% due to increased fat malabsorption as a
expiratory volume in 1 second)
result of cholestasis. This will not be improved by changes in
• the frequency and duration of IV antibiotic therapy
PERT, and care should be taken to ensure that pancreatic
• corticosteroid use
enzyme doses are not increased inappropriately.
• exercise tolerance and levels of physical activity
ETF may be required to optimise nutritional status, and
• DF508 genotype
advice should be taken regarding the suitability of NG or G
• CFRD
feeding devices if oesophageal varices are present. NG feed-
• delayed puberty
ing may be preferred if there is a risk of gastric varices.
Assessment of nutritional status should be undertaken Peak growth velocity is associated with high bone mass
with care as there may be ascites, oedema or significant orga- accrual, and low BMD in CF is thought to be due to subopti-
nomegaly leading to overestimation of body weight and mal peak bone mass accrual during childhood [66]. In
BMI. Serial mid-arm circumference and triceps skinfold healthy populations, peak bone mass accrual occurs at 11.7
thickness should be measured, ideally by the same observer years in girls and 13.4 years in boys. Puberty may be delayed
to reduce error. in CF, and this is associated with a reduction in bone age and
delay in peak height velocity.
There are also nutritional factors:
Osteoporosis/osteopenia
• nutritional status and lean body mass
Patients may develop low BMD through either osteoporo- • vitamin D status may result in impaired bone mineralisa-
sis or vitamin D deficiency osteomalacia. Studies suggest tion and increased loss
• vitamin K deficiency may contribute by altering the bal- Distal intestinal obstructive syndrome
ance of bone formation and resorption
• calcium intake DIOS is a common complication. It is characterised by accu-
mulation of sticky mucofaecal matter in the terminal ileum
Diagnosis of low BMD and caecum, often presenting as abdominal pain and pres-
ence of a right iliac fossa mass. Patients may present acutely
European guidelines for bone mineralisation recommend with intestinal obstruction with bilious vomiting. It affects
that BMD should be measured in the lumbar spine from mainly patients who are pancreatic insufficient; factors pre-
around 8 to 10 years of age [67]. Dual‐energy X‐ray absorp- disposing to DIOS include fat malabsorption and impaired
tiometry (DEXA) scans should ideally be done in a centre gut motility. Risk factors include poorly controlled malab-
with a clinical team experienced in performing and sorption and dehydration.
interpreting bone densitometry in children. These scans Medical management is usually effective in treating
should be repeated every 1–5 years; serial measurements the condition and includes rehydration with oral or IV
will allow for identification of peak bone mass, and this fluids and administration of an osmotic laxative contain-
may influence treatment options if premature bone loss ing polyethylene glycol, administered either orally or
occurs. via NG tube. In more severe cases Gastrografin enemas
may be required, and in very severe cases surgery may be
required.
Recommendations to optimise bone health
A dietetic review should be done for patients suffering
Low BMD in adults has its origins in childhood, and factors from DIOS to ensure optimal use of PERT and avoidance of
to optimise bone health should be considered in paediatric dehydration.
care. Dietary factors play a significant role, and it is impor-
tant that patients are regularly reviewed by an experienced
paediatric dietitian with the aim of achieving normal weight, Meconium ileus
height, body composition, optimal vitamin D and K status
and adequate calcium intake. Around 20% of infants born with CF will present with MI,
Weight‐bearing physical exercise and safe sun exposure where the intestine is obstructed with inspissated meconium
should be encouraged. Children and adolescents should be in the small bowel [1]. It can also be associated with other
encouraged to exercise for 20–30 minutes three times per complications, such as intussusception, volvulus, atresia and
week, and exercises should include high‐impact weight‐ perforation.
bearing exercises. Management varies according to the severity of obstruc-
Glucocorticosteroid use should be minimised, and CF pul- tion and anatomical changes, from conservative manage-
monary exacerbations should be promptly treated to mini- ment in the form of bowel washouts to laparotomy; in severe
mise the systemic inflammatory effect on bone. Pubertal cases bowel resection and formation of a temporary ileos-
delay should be recognised and treated. tomy may be necessary.
Infants requiring surgery present significant nutritional
difficulties, and it is recommended that these be managed in
a tertiary CF centre post‐operatively. These infants will
Learning points: bone mineral density require a period of parenteral nutrition (PN) until oral or
enteral feeds can be introduced. Use of PN is associated
• Vitamin D levels should be monitored annually and normal with a number of risks in all patients and oral or enteral
serum levels maintained feeds should be introduced as soon as it is safe to do so. The
• Advice should be given to optimise calcium intake; supple- choice or feed depends on whether a stoma has been formed
ments may be required in patients who dislike milk and and the position of the stoma and the extent of any bowel
dairy produce resection. Breastmilk, either as breastfeeds or EBM given
• Weight‐bearing exercise and exposure to sunlight should be orally or by enteral feeding tube, should be encouraged
encouraged post‐operatively. If breastmilk is not available, then an
extensively hydrolysed infant formula containing MCT
should be considered (Table 8.15).
In conservatively managed infants, breastmilk and stand-
Gastro‐oesophageal reflux ard infant formula are recommended.
Management of MI, either conservative or surgical, may
GOR is common, affecting around 6% of children with CF result in suboptimal weight gain, and there may be a require-
[1], and can compromise growth and increase respiratory ment to give higher volumes of feed or a high energy for-
symptoms. Treatment includes the use of thickened infant mula (Table 1.18) to optimise weight gain and ensure
formula (p. 133) and reducing gastric acid secretion either catch‐up growth.
with H2 antagonists or PPI, although these should be used MI is associated with PI and all infants presenting with it
with caution [20]. will require PERT when feeds are introduced. FPE‐1 levels in
236 Cystic Fibrosis
the stool should be assessed to confirm the requirement; 90th centile [70]. The evidence is limited currently, but
however a sample taken from stoma fluid may be too liquid increased longevity may put patients with CF at risk for
for analysis. some of the metabolic complications due to excess body
Supplementation with sodium should be considered in weight seen in the general population.
infants with a stoma due to increased losses in stoma fluid. Individualised advice should be given to prevent exces-
sive weight gain and ensure a well‐balanced diet. It is impor-
tant to ensure that height velocity is not affected by energy
restriction in children and aiming for weight maintenance
Learning points: meconium ileus
may be preferable before and during the pubertal growth
spurt. Effective communication to the families and the wider
• Infants requiring surgery for MI should be managed in a
MDT is essential to prevent conflicting advice about energy
tertiary centre specialising in neonatal surgery and CF
needs. It may be useful to counsel early on in treatment that
• Breastmilk and standard infant formula are recommended
dietary advice may change throughout life.
for infants managed conservatively
• Breastmilk or a hydrolysed protein formula containing
MCT should be used in those requiring surgery Learning points: Overweight and Obesity
• Some infants have suboptimal weight gain during the
period of management of MI and require increased volumes • Families should be counselled early on that the aims of die-
of feed or a high energy feed to ensure catch‐up growth tetic management may change with time
• All infants with MI will require PERT • Individualised advice should be given to prevent excessive
• Sodium supplementation should be considered in all weight gain, aiming for a healthy BMI
infants, especially in those with a stoma • Communication about the aims of dietetic management to
• If there is nutritional deficit, attention should be given to the wider MDT is necessary to ensure a consistent message
volume and type of feeds to achieve catch‐up growth is given
Constipation CFTR modulator therapies
Constipation should be differentiated from DIOS. It is These therapies target the underlying defect in the trans-
defined as a reduced stool frequency and increased consist- membrane conductance regulator (CFTR) protein. The defect
ency, often with abdominal pain and distension. The aetiol- in the protein varies depending on the specific genetic muta-
ogy is unknown, but it may be due to changes in gut motility tions (genotype) that the individual has because the different
and intestinal fluid. genetic mutations code for different defects in the protein.
There is no consensus on the cause of constipation; a high This is why each modulator therapy is only effective for
dose of pancreatic enzymes is often cited, although one specific genotypes.
study failed to find an association [68] and other studies The two types of modulator therapies currently available
have shown no association with fibre or fluid intake [69]. are ‘correctors’ and ‘potentiators’:
Constipation can be effectively treated with polyethylene • CFTR potentiators keep the chloride channel on the
glycol, which is well tolerated in CF. CFTR protein open so the chloride can pass through to
the other side of the membrane.
• CFTR correctors help the CFTR protein to form the cor-
Other nutritional considerations rect three‐dimensional shape so that it can be trafficked
to the cell surface.
Obesity and overweight
Early diagnosis, improvements in care, and new therapies Ivacaftor

have resulted in an increasing number of people with CF
becoming overweight and obese. Traditionally, overnutri- Ivacaftor (Kalydeco) is a corrector molecule. Due to its
tion has been seen in older PS patients, but it is increasingly mechanism of action, it is licensed for use in patients over
being seen in PI and paediatric populations [70]. 2 years old with one class III mutation, e.g. G551D. This
Preventing malnutrition has been the primary focus of accounts for approximately 6% of UK CF population [1].
nutritional care in CF because of the benefits to lung function It is the longest‐standing modulator therapy and has been
and clinical outcomes; however, a large longitudinal study approved by NICE.
in adults demonstrated that being overweight or obese Treatment with ivacaftor has shown significantly
does not confer additional benefit to lung function [71]. decreased sweat chloride, improved lung function (FEV1)
Overweight and obesity have also been shown in a smaller and much improved BMI z‐score in children aged 6–11 years
paediatric study where 23% of patients had a BMI above the [72]. Similar improvements were seen in weight and sweat
CFTR Modulator Therapies 237
chloride in younger children, and they additionally had an needed, and most families choose to give it at breakfast
increase in faecal elastase levels [73, 74]. This suggested that and a later evening meal, or with a fat‐containing snack
starting modulator therapy in younger patients may support before bed.
the recovery of exocrine pancreatic function, but further Due to drug nutrient interactions, it is recommended to
investigation is needed. avoid grapefruit and Seville orange (found in marmalade)
when on ivacaftor-containing therapies.
Some centres are choosing to regularly monitor faecal
Lumacaftor/ivacaftor
elastase levels in children <6 years of age who are started on
modulator therapies.
Lumacaftor/ivacaftor (Orkambi) is a combination therapy
Due to the significant weight gain in patients seen with
containing two active molecules: ivacaftor, a corrector, and
some modulator therapies, in well‐nourished individuals,
lumacaftor, a potentiator. Treatment with Orkambi has dem-
weight monitoring and individualised advice to support
onstrated a small significant increase in BMI z‐score, lung
optimal BMI may be advisable.
function (FEV1) (by 2%–4%) and reduction in exacerbations
[75, 76]. These improvements were not as substantial as
those seen with ivacaftor. Learning points: CFTR modulator therapies
Due to its mechanism of action, Orkambi is licensed in
Europe for individuals aged 2 years and over who are • Modulator therapies should be taken with fat‐containing
homozygous for dF508, approximately 49% of the current foods every 12 hours
UK CF population [1]. NICE has recommended Orkambi for • Weight gain should be monitored and pre‐emptive dietary
use in the National Health Service. advice given to ensure optimal BMI is maintained, espe-
There are many other modulator therapies currently in cially in well‐nourished individuals
production, which offers great promise for future therapeu- • Monitoring faecal elastase levels is advised in younger chil-
tic options. dren, initially at 6 months and then annually after starting
therapy or if new abdominal symptoms are described
Practical nutritional management with modulator
therapies
Modulator therapies are given as tablets or granules.
They need to be taken twice a day, 12 hours apart, with
fat‐containing food to optimise the absorption of the drug.
There is no specific recommendation for the amount of fat
13 Kidney Diseases
Leila Qizalbash, Shelley Cleghorn and Louise McAlister
Acute Kidney Injury and Chronic Kidney Disease

Leila Qizalbash
Introduction worldwide experiencing AKI during a hospital admission

has been suggested [2]. It is more common for those children
The kidneys play an essential role in the maintenance of requiring intensive care and is an independent risk factor for
homeostasis by excreting waste products, such as urea and mortality and severe morbidity [3]. The incidence and causes
uric acid, and purposely adjusting the urinary excretion of differ between developing countries and developed coun-
water and electrolytes (solute) to counter dietary intake and tries. Premature infants are also at significant risk of AKI
the body’s endogenous production of these from metabo- because of high rates of infection and exposure to nephro-
lism. The kidneys have a major role in the secretion of hor- toxic medications; however, the exact incidence of AKI in
mones. This includes erythropoietin for red blood cell this population is unknown [4]. The causes of AKI in chil-
production, renin and angiotensin II affecting renal and sys- dren are classified as pre-renal AKI, intrinsic AKI or obstruc-
temic haemodynamics and hydroxylated vitamin D affecting tive AKI [5, 6] (Table 13.1).
calcium, phosphate and bone metabolism. Other functions A shift has been seen in the causes of paediatric AKI from
include peptide hormone catabolism and gluconeogenesis. primary renal disease, e.g. haemolytic uraemic syndrome
A variety of diseases can affect the kidneys leading to a (HUS), dehydration and burns to renal ischaemia (often after
sudden deterioration in renal function (acute kidney injury cardiopulmonary surgery), use of nephrotoxic medications
[AKI]) or an irreversible deterioration of renal function and sepsis [7]. This change could be due to increased severity of
(chronic kidney disease [CKD]). Impairment of excretory, illness, more complex treatments and invasive procedures [8].
regulatory and endocrine functions is seen as kidney func-
tion deteriorates, and the management of these impairments
Management of AKI
is the foundation of treatment.
The initial management of AKI focuses on the correction of
Acute kidney injury fluid balance and biochemical abnormalities. This includes
hyponatraemia, hyperkalaemia and acidosis, which can be
The definition of AKI has changed in recent years; it is life threatening. Further injury to the kidney should be pre-
defined as an abrupt decrease in kidney function that encom- vented through maintaining adequate blood pressure and
passes both injury to the kidney (structural damage) and avoiding nephrotoxic medication. Transfer to a tertiary neph-
kidney impairment (loss of function). Diagnosis is now rology centre is indicated in those children requiring renal
mostly based on monitoring creatinine levels with or with- replacement therapy (RRT), if they are failing to respond to
out urine output [1]. An incidence of one in three children medical management. Such indications for RRT include [9]:

Acute Kidney Injury 239
Table 13.1 Causes of acute kidney injury in children [5, 6].
Pre‐renal AKI Intrinsic AKI Obstructive AKI
Loss of effective blood volume Renal artery damage Congenital malformations

• Absolute losses: haemorrhage gastrointestinal, renal, skin Renal vein damage Imperforate anus
• Relative losses: capillary leak, vasodilation, sepsis, Acute tubular necrosis Urethral stricture
antihypertensives, hypoalbuminaemia Interstitial nephritis Posterior urethral valves
ECMO Glomerular causes Urethral diverticulum
Impaired cardiac output • Post‐infectious Ureterocoele
Bilateral renal vessel occlusion • IGA nephropathy Megaureter
Pharmacologic agents, e.g. cyclosporin, diuretics, ACE • Membranoproliferative Ureteropelvic junction obstruction
inhibitors, ARB, indometacin Renal vascular causes Extrinsic compression
• Renal artery thrombosis • Carcinoma
• Renal vein thrombosis Intrinsic obstruction
Myoglobinuria • Calculi
Intrarenal obstruction • Tumour
Infections (pyelonephritis) Neurogenic bladder
Nephrotoxins
Radiation
Chemotherapy
Tumour infiltrate
Lupus
HUS
ECMO, extracorporeal membrane oxygenation; ACE, angiotensin‐converting enzyme; ARB, angiotensin receptor blockers; HUS, haemolytic uraemic
syndrome.
• hyperkalaemia Table 13.2 Indications for choice of renal replacement therapy in acute

• metabolic acidosis kidney injury.
• symptoms or complications of uraemia (pericarditis or
encephalopathy) Indication for Clinical
• fluid overload dialysis condition Modality indicated
• pulmonary oedema Solute removal Stable HD
• fluid removal to allow the provision of nutrition [6]
Unstable CRRT, PD
Fluid removal Stable PD, isolated ultrafiltration
Choice of renal replacement therapy on HD
The selection of RRT in acutely ill children depends upon the Unstable CRRT
availability of treatment modalities, ventilatory support, the Solute and fluid Stable/unstable HD, PD, CRRT
patient’s requirements for fluid and solute removal and haemo- removal
dynamic stability. The choice is between peritoneal dialysis Tumour lysis Stable/unstable HD followed by CRRT
(PD), continuous renal replacement therapy (CRRT) and inter- syndrome
mittent haemodialysis (IHD). Factors determining the choice of Toxin or drug Stable/unstable CRRT, IHD for some drugs
RRT include the desired outcome of therapy and clinical condi- removal
tion of the child as indicated in Table 13.2 [10]. PD is the pre-
ferred modality in children as it is well tolerated and there are HD, haemodialysis; CRRT, continuous renal replacement therapy; PD,
peritoneal dialysis; IHD, intermittent haemodialysis.
no rapid fluid shifts. IHD is used when there is an urgent need
for solute removal. For the critically ill child in the paediatric
intensive care unit (PICU), CRRT is the favoured treatment.
prescription varies with clinical management and the stage
of the illness [11].
Nutritional management of AKI
Nutritional support aims to provide sufficient energy to
avoid catabolism, starvation and ketoacidosis as well as to
Children with AKI are highly catabolic. This is usually mul-
control metabolic abnormalities. The provision of nutrition
tifactorial manifesting as anorexia. The catabolic nature of
is easier once dialysis is initiated since the fluid removed by
the underlying disorder, increased breakdown and reduced
ultrafiltration allows larger volumes of feed to be given.
synthesis of muscle protein, increased hepatic gluconeogen-
Nutritional intervention for children with AKI depends on:
esis, nutrient losses in drainage fluids or dialysis and
impaired access to food can all impact the child’s nutritional • clinical management: conservative vs. RRT (and modality)
status. Input from a paediatric dietitian with experience in • biochemical assessment: serum levels of sodium, potas-
renal disease is essential from the onset as the dietary sium, bicarbonate, urea, creatinine, albumin, glucose,
240 Kidney Diseases
calcium, magnesium and phosphate should be regularly often unsuitable for the child with AKI because of their
monitored and reviewed e lectrolyte composition and the amount of fluid they pro-
• cause of AKI including the involvement of other organs vide. An appropriate daily nutritional prescription to meet
• gastrointestinal functioning individual requirements should be agreed by the dietitian,
• growth parameters: height (if available) and weight plot- pharmacist and medical staff. When formulating PN, nitro-
ted on a growth chart; weight recordings prior to the gen and electrolyte modified solutions, together with
onset of AKI will help determine a more accurate estima- increased energy from carbohydrate and fat solutions where
tion of dry weight fluid allowance is limited, need to be considered. On CRRT
• dietary history: if the child is eating. the loss of nutrients through filtration and dialysis needs to
be compensated for in the replacement fluids (p. 243); levels
Table 13.3 shows the normal range for serum levels of
need to be greater than those found in standard PN regi-
creatinine.
mens. For many children PN is temporary and the enteral
route is re‐established as soon as gut function returns.
Methods of feeding
Enteral feeding Nutritional considerations
The child with AKI may initially take oral fluids readily,
driven by thirst. Some children fail to achieve nutritional tar- There are few data on the nutritional requirements of criti-
gets through diet alone. As the duration of the acute illness cally ill children with AKI and on RRT. Most of the informa-
can be prolonged, the passing of a fine bore nasogastric tube tion is derived from adult data.
(NGT) is recommended. The tube can be passed at the time
of sedation or when anaesthetised for procedures including Energy
the insertion of a PD catheter or arterial line [11]. This allows
the provision of early nutritional support because anorexia, Little is known about the energy requirements of infants and
vomiting or food refusal can impair management and may children with AKI [12]. A minimum of the estimated average
increase parental anxiety. requirement (EAR) for energy [13] for healthy children of the
A continuous 24 hour feeding regimen using an enteral same chronological age provides a guide. These recommen-
feeding pump at a slow rate (10–20 mL/hour) is advantageous dations can be difficult to achieve during acute treatment; it is
in the initial stages of treatment if vomiting is present. As oral important to provide the maximum energy intake tolerated
intake improves, the transition from continuous to overnight within the prescribed fluid allowance. The early addition of
feeding provides the outstanding nutritional prescription until glucose polymers to water (flavoured with squash or cordial
appetite improves sufficiently to allow tube feeding to be if desired) or to drinks of choice is recommended. It is pru-
discontinued. Those children with persistent diarrhoea may dent to start at a concentration of 0.5 kcal (2 kJ)/mL, building
tolerate a hydrolysed protein‐based feed (Tables 8.15 and 8.20) up to a concentration of 1 kcal (4 kJ)/mL, or 25% carbohy-
before considering parenteral nutrition (PN). drate (CHO) concentration, depending on individual toler-
ance. Liquid glucose polymer preparations can also be used,
Parenteral nutrition but require dilution with water to be tolerated by children. It
The parenteral route is only considered when enteral nutri- is recommended to start with a 1 : 5 dilution of liquid glucose
tion is not tolerated. Standard hospital PN regimens are polymer, building up to a final 1 : 3 dilution. Neutral tasting
preparations can be flavoured with squash or cordial. When
fluid is severely restricted, ice cubes and lollies can be pre-
Table 13.3 Guidelines for normal serum creatinine values. pared with these energy‐dense solutions and offered at fre-
quent intervals. Energy‐rich CHO drinks including original
Age Serum creatinine (μmol/L)
bottled Lucozade Energy (8.4%–8.9% CHO concentration)
<1 week <100 and Mountain Dew (12.3% CHO concentration) and some
full sugar squashes (6%–10% CHO concentration) can be
1–2 weeks <80
useful alternatives for those children who refuse to drink
2–4 weeks <55
prescribed energy supplements.
1 month to 1 year <40 A list of energy supplements that can be considered is
1–3 years <40 given in Table 13.4. These can be successfully added to infant
4–6 years <46 formulas to increase energy density:
7–9 years 10–56 • In infants up to 6 months of age, 0.85–1.0 kcal/mL
10–12 years 30–60 (3.6–4 kJ/mL) is usually tolerated
• In infants from 6 to 12 months of age, 1.0–1.5 kcal/mL
13–15 years 40–80
(4–6 kJ/mL) should be tolerated
16 years to adult male 40–96
16 years to adult female 26–86
In children over 12 months of age, or whose weight is
>8 kg, a nutritionally complete paediatric feed can be consid-
Ketones interfere positively. Bilirubin interferes negatively. ered and modified as necessary to meet individual
Table 13.4 Nutritional supplements.
Supplement Suggested use
Energy
Glucose polymers
Powder, e.g. Polycal, Super Soluble Maxijul, Vitajoule Add to infant formula, baby juice, cow’s milk, squash, fizzy drinks, tea,
milk shake, ice cubes and lollies
Liquid, e.g. Polycal Dilute with water, cordial or fizzy drinks of choice (unless fluid
restricted); add to jelly
Fat emulsion
Calogen, Liquigen, Carbzero, Betaquik Add to infant formula, cow’s milk, nutritionally complete supplements or
take as a supplement
Combined fat and carbohydrate
Powder, e.g. Super Soluble Duocal Powder Add to infant formula, cow’s milk, nutritionally complete supplements
Liquid, e.g. Liquid Duocal Add to infant formula, cow’s milk, nutritionally complete supplements or
take as a supplement
Protein
Powder, e.g. Protifar, Renapro*, ProSource TF* Add to infant formula, modular feed components
Liquid, e.g. Renapro Shot* Add to cow’s milk, squash, tea, milkshake, supplements, feeds, modular
feed component or take as a supplement
Combined fat, carbohydrate and protein
Powder, e.g. Pro‐Cal* Add to cow’s milk, squash, tea, milkshake, milky puddings, supplements,
feeds, modular feed component
Liquid, e.g. Pro‐Cal Shot*, ProSource*, ProSource Plus* Add to cow’s milk, squash, tea, milkshake, supplements, feeds, modular
feed component or take as a supplement
Renal specific infant formulas
Kindergen
Powder per 100 g: 7.5 g protein, 503 kcal (2104 kJ), 93 mg phosphorus,
3 mmol potassium, 10 mmol sodium
20% solution (20 g powder made up to 100 mL with water): 1.5 g For infants with CKD or conservatively managed AKI
protein, 101 kcal (421 kJ), 18.6 mg phosphorus, 0.6 mmol potassium, Suitable from birth to 10 years of age
2 mmol sodium
Renastart Not nutritionally complete for all age groups, nutritional assessment
Powder per 100 g: 7.5 g protein, 494 kcal (2066 kJ), 92 mg phosphorus, needed
3 mmol potassium, 10.4 mmol sodium
20% solution (20 g powder made up to 100 mL with water): 1.5 g protein,
99 kcal (413 kJ), 18.4 mg phosphorus, 0.6 mmol potassium, 2.1 mmol sodium
Nutritionally complete feeds
Nutrini per 100 mL: 2.8 g protein, 100 kcal (420 kJ), 50 mg phosphorus,
2.8 mmol potassium, 2.6 mmol sodium
PaediaSure per 100 mL: 2.8 g protein, 101 kcal (422 kJ), 53 mg For oral or supplementary tube feeding in children >1 year and
phosphorus, 2.8 mmol potassium, 2.6 mmol sodium weight >8 kg
Nutrini Energy per 100 mL: 4.1 g protein, 150 kcal (630 kJ), 75 mg Can be combined with energy supplements
phosphorus, 4.2 mmol potassium, 3.9 mmol sodium
PaediaSure Plus per 100 mL: 4.2 g protein, 151 kcal (632 kJ), 80 mg
Nepro HP per 100 mL: 8.1 g protein, 180 kcal (722 kJ), 72 mg Consider micronutrient contribution in younger children
Low electrolyte supplements (not nutritionally complete)
PaediaSure Plus juce per 100 mL: 4.2 g protein, 150 kcal (638 kJ), Can be diluted with water or fizzy drinks
9.5 mg phosphorus, 0.49 mmol potassium, 0.32 mmol sodium
Fortijuce per 100 mL: 4 g protein, 150 kcal (640 kJ), 12 mg
Ensure Plus juce per 100 mL: 4.8 g protein, 150 kcal (638 kJ), 11 mg
Renilon 7.5 per 100 mL: 7.5 g protein, 200 kcal (835 kJ), 3 mg
VitaBite per 25 g bar: 0.06 g protein, 137 kcal (571 kJ), <12.5 mg
phosphorus, 0.63 mmol potassium, <0.1 mmol sodium
(contiued to overleaf)
242 Kidney Diseases
Supplement Suggested use
Low protein milk substitute

Sno‐Pro per 100 mL: 0.16 g protein, 89 kcal (371 kJ), <30 mg Use as a substitute for cow’s milk to reduce protein and phosphate
phosphorus, <1.3 mmol potassium, <3.3 mmol sodium, <20 mg intakes
calcium
ProZero per 100 mL: 0 g protein, 67 kcal (278 kJ), 2.0 mg
phosphorus,0.05 mmol potassium, 1.8 mmol sodium, 0.04 mmol
calcium
Renamil per 100 g: 4.6 g protein, 477 kcal (2003 kJ), 32 mg phosphorus,
0.13 mmol potassium, 1.04 mmol sodium
CKD, chronic kidney disease; AKI, acute kidney injury.

*These contain potassium/phosphate/sodium/calcium.
requirements (Table 13.4). The energy density can be built up [14] demonstrated that at similar blood and dialysate/pre-
to 1.5–2.0 kcal/mL (6–8 kJ/mL). Fat emulsions can be given filtered replacement fluid flow rates, there is an equivalent
as a prescribed medicine during the day. urea clearance with haemofiltration and haemofiltration
A few children develop insulin resistance and hypergly- with dialysis. A negative nitrogen balance occurred in chil-
caemia can occur. If managed on PD, this can be exacerbated dren with AKI on PN containing 1.5 g/kg/day of protein
by the absorption of glucose from the PD fluid together with and an energy intake 20%–30% above resting energy
the intake of high CHO supplements. Insulin infusions need expenditure. An 11%–12% loss of dietary amino acids was
to be considered to control blood glucose levels before the found on both modalities. A significant daily accumulative
reduction of dietary CHO. glutamine loss may potentiate nitrogen imbalance. A dose
adjustment of amino acid formulation may be needed to
overcome negative nitrogen balance in children with AKI
Protein
on CRRT. An adult study by Scheinkestel et al. [15] showed
In children with AKI who are being managed conservatively, that a protein intake of 2.5 g/kg/day and meeting energy
protein should be limited to the reference nutrient intake (RNI) requirements increased the likelihood of achieving a posi-
[11] level to minimise uraemic symptoms. Kidney Disease tive nitrogen balance and improving survival. However,
Improving Global Outcomes (KDIGO) guidelines recommend another adult study recommends a protein intake between
avoiding restriction of protein intake as a way to delay RRT 1.5–1.8 g/kg/day and an energy allowance of 25–35 kcal
and recommend starting RRT early [1]. Protein intake needs to (105–145 kJ)/kg/day [16].
be gradually increased as tolerated if RRT is started, with its Nutrition therapy in AKI remains an area of many unan-
associated increased solute removal and possible protein swered questions, especially for those managed on CRRT; Li
losses. The RNI for protein is not always appropriate for the et al. illustrate this in their review of AKI studies in adults
child with AKI on RRT, and requirements should be individu- [17]. A review article in paediatric intensive care patients [8]
ally determined [11]. The age and weight of the child, the serum reinforces the high risk of underfeeding the critically ill
biochemistry and RRT modality, when implemented, all need child, with the presence of AKI further increasing the risk of
to be considered. Inadequate energy intake can exacerbate high protein–energy debt. Further paediatric studies are needed
urea levels; therefore, it is beneficial to maximise energy intake. to investigate nutritional support adequacy, nutritional sta-
Once RRT is established, the following increments can be tus and clinical outcomes [8].
used as a guide to increase protein intake to the RNI Nutritional supplements, using an NGT, are frequently
(Table 1.9). If dialysis is prolonged, an increase in protein used to meet protein and energy requirements in the initial
intake above the RNI may be required: stages of treatment. For infants standard whey‐based for-
mulas (which are already low in electrolytes and phosphate)
• Exclude protein if the serum urea is ≥40 mmol/L
are recommended. These can be modified as required.
• Introduce 0.5 g protein/kg if the serum urea is ≥30 and
Kindergen and Renastart – renal specific low phosphate,
<40 mmol/L
low potassium infant formulas (Table 13.4) – can be benefi-
• Give 1.0 g protein/kg if the serum urea is ≥20 and
cial for infants not receiving RTT or receiving IHD when
<30 mmol/L
serum biochemistry levels are unstable. Nutritionally com-
• Give the RNI for height age (infants) or chronological
plete, energy‐dense infant formulas (Infatrini, Similac High
age (children) if the serum urea is <20 mmol/L
Energy, SMA High Energy) can be useful if blood biochem-
CRRT offers haemodynamic stability while maintaining istry allows when on RTT. The phosphate content of these
excellent control of solutes in extracellular fluid and allows feeds is higher than in standard infant whey‐based formu-
nutritional support in highly catabolic states, but contrib- las, so serum phosphate levels should be regularly reviewed.
utes to nitrogen loss through the filtration of free amino For the older child a number of nutritionally complete
acids and small peptides across haemofilters. Maxvold et al. supplements are available. These can be used solely or in
Acute Kidney Injury 243
combinations with their protein, phosphate and potassium Electrolytes and minerals

contents being assessed prior to use (Table 13.4). If protein
The intake of electrolytes, especially potassium, is likely to
hydrolysate formulas are indicated (in particular when the
be restricted in conservative management. Serum levels and
diarrhoeal phase is prolonged in HUS), they should be
the use of RRT will dictate requirements thereafter. Any
modified with respect to biochemical parameters as well as
dietary restrictions should be minimised to avoid compro-
to meet individual nutritional requirements. Introduction
mising nutritional intake.
should be gradual and delivery is usually by the nasogastric
Potassium‐rich foods including citrus fruits, fruit juices,
(NG) route. Once the child’s appetite improves and protein
bananas, potato crisps and chocolate are commonly brought
intake is met through eating, energy supplemented drinks
into hospital by relatives. All caregivers should be advised
can replace nutritionally complete formulas or protein
about choosing foods with a low potassium content when
supplements.
serum potassium levels are elevated so that rich food sources
are withdrawn (Table 13.5).
Once serum phosphate levels are above the reference ranges,
Fluid
the intake of phosphate‐rich foods should be moderated. A
The volume of fluid prescribed during conservative treat- lower phosphate intake can partly be achieved when protein
ment is based on insensible fluid requirements of 400 mL/m2 intake, particularly that of dairy products, is modified
body surface area (BSA)/day or approximately 20 mL/kg (Table 13.6). Cow’s milk is generally restricted or eliminated
body weight/day, with a 12% increase for each degree from the diet during the acute phase because of its high pro-
Celsius above normal body temperature and a reduction if tein, phosphate and potassium content. Avoidance of cow’s
the child is ventilated. Insensible losses should be added to milk also reduces the potential cow’s milk protein or lactose
the previous day’s urine output to give the total daily fluid intolerance, which can follow the diarrhoeal prodrome in
allowance. Body surface area may be calculated using the patients with HUS. If the milk restriction proves difficult, a low
formula √[(weight kg × height cm)/3600]. protein milk substitute, such as Sno‐Pro or Renamil (Table 13.4),
On RRT, the fluid prescription is determined by monitor- can be advised. Phosphate binders may also be useful (p. 253).
ing the volume of fluid removed by ultrafiltration plus Reduction in sodium intake can aid compliance when
insensible losses. Ideally fluid removal on RRT should be fluid intake is restricted by reducing thirst. This can be
flexibly managed to allow the maximum space for increased achieved by the avoidance of salted snacks and a reduced or
nutritional fluids. Maximal nutrient intakes using supple- ‘no added salt’ diet (Table 13.7). Practical advice for families
ments should be provided within the fluid allowance and is given in Table 13.24.
divided as evenly as possible throughout the day. A pre- The level of the above restrictions depends on each indi-
scription plan should be provided for the ward nurses and vidual child and their clinical condition. They should be fre-
families. quently monitored to avoid unnecessary restrictions when
Table 13.5 Potassium‐rich foods and suggested alternatives.
Potassium‐rich foods* Suggested alternatives
Banana, apricots, kiwi fruit, grapes, avocado, citrus fruits, e.g. orange, Apple, pear, satsuma, blueberries, tinned fruit in syrup
grapefruit; dried fruit, e.g. raisins; tinned fruit in fruit juice; melon,
plums, rhubarb, blackcurrants
Hi juice squash, fruit juices including orange, apple and tomato Squash, cordials, Lucozade, lemonade and fizzy drinks, tea
Instant coffee and coffee essence
Malted drinks
Cocoa, drinking chocolate
Potato crisps and potato containing snacks, nuts, peanut butter, salt Corn or rice snacks (without added potassium chloride and take
substitutes, meat extract, yeast extract account of sodium content), sweetened popcorn, jam, honey,
marmalade, syrup
Jacket potatoes, chips (oven and frozen), roast potatoes Rice (boiled or fried), spaghetti, pasta, noodles, bread, chapatti, naan,
crackers
Mushrooms, spinach, tomatoes, spaghetti in tomato sauce, baked Carrots, cauliflower, swede, broccoli, cabbage
beans, pulses and hummus, tinned and packet soups
Chocolate and all foods containing it, toffee, fudge, marzipan, liquorice Boiled sweets, jellies, mints, marshmallows
Chocolate biscuits Biscuits: plain, sandwich, jam filled, wafer
Chocolate cake, fruit cake Cake: plain sponge filled with cream and/or
jam Jam tarts, apple pie, doughnuts, plain scones
Milk, yoghurt, evaporated and condensed milk Low protein milk substitutes, e.g. Sno‐Pro, Renamil, ProZero
*Allowance will depend on individual assessment.

244 Kidney Diseases
Table 13.6 Phosphate‐rich foods and suggested alternatives.
Phosphate‐rich foods* Suggested alternatives
Cow’s milk (full cream, semi‐skimmed, skimmed) Infants

Dried milk powder and other milk products Whey‐based infant formulas, e.g., Cow & Gate 1, SMA PRO 1, Aptamil Pro
Futura 1 for at least 1–2 years
Children
Reduced intake; consider low protein milk substitute (Table 13.4)
Large portions of meat, poultry and fish Reduced portion sizes
Processed meats containing phosphate additives
Yoghurt, fromage frais, mousse, ice cream, milk puddings including Reduce intake
custard Custard made with milk substitute
Evaporated milk, condensed milk, single cream Double cream†
Cheese, e.g. Cheddar, Edam, processed cheese and cheese spread Limit intake and/or encourage use of cottage cheese or full‐fat cream
cheese
Egg yolk Meringues
Cocoa, chocolate and chocolate‐containing foods, toffee, fudge Boiled sweets, mints, dolly mixtures
Sardines, pilchards, tuna White fish
Baked beans, pulses Vegetables
Nuts, peanut butter, marzipan and seeds Jam, honey, marmalade, syrup
Cola drinks and any others containing phosphoric acid Squash, cordials, lemonade, Lucozade
Convenience and processed foods with phosphorus‐containing Foods with no phosphorus‐containing food additives
additives (Table 13.14)
*Allowance will depend on individual assessment.

†
Caution: vitamin A content (p. 262).
Table 13.7 Sodium‐rich foods and suggested alternatives.
Sodium‐rich foods Suggested alternatives
Salted crisps, nuts and savoury snacks Unsalted crisps, unsalted nuts, rice cakes, unsalted popcorn
Tinned and packet soups Home‐made soups
Pot savouries/noodles Sweet snacks instead of savoury
Tinned foods with added salt *Reduced salt products, e.g. reduced salt baked beans
Bacon, sausages and other processed meats and fish Fresh meats and fish
Cheese and cheese products Cottage cheese, ricotta and cream cheese
Stock cubes, meat and vegetable extracts Halve the amounts used or use reduced salt varieties; add herbs and spices
in their place, use gravy powder and meat juices to make gravy
Pickles, sauces and chutneys Reduced salt alternatives
Ready‐made meals and takeaway meals Home‐made meals using fresh ingredients
See also Table 13.24.

*Many processed/manufactured foods contain high amounts of salt and even lower salt varieties can have a high salt content. A reduced salt or ‘no
added salt’ diet, avoiding the sodium‐rich foods in the table above, provides approximately 3 mmol sodium/kg body weight, assuming the child eats
average food portion sizes.
their appetite is typically poor and their nutrition is easily t ablets. Iron supplementation may be indicated in some chil-
compromised. dren during the recovery phase, particularly in those who
had a poor diet history prior to the onset of AKI.
When on CRRT water‐soluble vitamins, especially folic
Micronutrients
acid, thiamin and vitamin C are lost. Requirements when on
Vitamin supplementation should be considered if dialysis this treatment are unknown and a minimum of the RNI [18]
treatment is prolonged. A general paediatric vitamin supple- should be given. Patients receiving CRRT also lose magne-
ment of water‐soluble vitamins should be adequate for the sium and calcium; this often leads to negative balances
majority of children as appetite improves, e.g. Ketovite requiring additional supplementation. Zinc is also
Chronic Kidney Disease 245
abnormally lost, but serum levels do not generally fall [19, National Kidney Foundation Kidney Disease Outcome
20]. Additionally Wiesen et al. [16] recommend selenium Quality Initiative (NKF KDOQI) classification of CKD into
supplementation. five stages (Table 13.8) [22]. This staging does not apply to
children below 2 years of age where ongoing renal matura-
tion is seen. UK data published in 2015 reveals an incidence
Recovery phase
of established renal failure under the age of 16 years of 10.2
per million age‐related population [23]. Children from
As renal function improves and urine output increases, the
minority ethnic groups displayed higher RRT prevalence
need for RRT is reduced and stopped. Dietary restrictions,
rates when compared with white children, with South Asian
where instigated, can gradually be relaxed. Serum electro-
children exhibiting the highest rates. The causes of CKD in
lytes and dietary intake should be monitored closely as
the registry data are shown in Table 13.9 [23]. Regardless of
major losses, especially of potassium, during the diuretic
the underlying cause, CKD is characterised by progressive
phase can occur.
scarring that ultimately affects all structures of the kidney
Prior to discharge, advice should be given on returning to
[24]. Despite the diverse causes, once CKD develops, the
a normal diet as renal function continues to improve. The
subsequent response of the failing kidney is similar. Initially,
opportunity to educate the child and family about the prin-
the kidney adapts to damage by increasing the filtration rate
ciples of a well‐balanced diet can also be taken if poor eating
in the remaining nephrons, a process called adaptive hyper-
patterns were highlighted during the admission. Where
filtration. Additional homeostatic mechanisms permit the
appetite is slow to improve, some children may need to
serum concentrations of sodium, calcium, phosphate, potas-
continue energy and vitamin supplements for a short time,
sium and total body water to remain within the reference
with monitoring of their progress in clinic.
range, particularly among those with mild to moderate
stages of CKD. Adaptive hyperfiltration, although initially
Outcome of AKI beneficial, appears to result in long‐term damage to the glo-
meruli of the remaining nephrons. This irreversibility is
The prognosis and outcome for children with AKI depends responsible for the development of ESRD [25].
on the underlying cause. Factors associated with a poor out-
come include multi‐organ failure and the need for RRT and
these children need secondary or tertiary follow‐up.
Table 13.8 Stages of renal failure.
Learning points: acute kidney injury GFR (mL/

Stage Description min/1.73 m2)
• Progression of the degree of AKI is based on monitoring
1 Kidney damage with normal or >90
creatinine levels, with or without urine output increased GFR
• Dietary prescription varies with clinical management and
2 Kidney damage with mild decrease in 60–89
stage of the illness GFR
• Nutritional support aims to provide sufficient energy to avoid
3 Moderate decrease in GFR 30–59
catabolism as well as controlling metabolic abnormalities
• Nutritional intervention depends on clinical management, 4 Severe decrease in GFR 15–29
blood biochemistry levels, cause of AKI, gastrointestinal 5 Kidney failure <15 or dialysis
function, growth parameters and dietary intake
• Achieving energy requirements may be difficult during GFR, glomerular filtration rate.
acute treatment; it is important to try to provide the maxi-
mum energy within the prescribed fluid allowance Table 13.9 Causes of chronic kidney disease in childhood in the UK.
• Protein should be limited to the RNI to minimise uraemic
symptoms; however unnecessary protein restriction must Cause Percentage
be avoided
Renal dysplasia ± reflux 34.7
Obstructive uropathy 18.9
Glomerular disease 11.4
Chronic kidney disease Congenital nephrotic syndrome 10
Tubulo‐interstitial disease 6.6
CKD is characterised by an irreversible deterioration of renal
function that can progressively decline to end‐stage renal Renovascular disease 4.8
disease (ESRD) [21], evidenced by structural or functional Polycystic disease 4.3
kidney abnormalities. Renal dysfunction is defined as a con- Metabolic disease 3.8
tinuum from mild to severe. The National Institute for
Malignancy and associated disease 2.2
Health and Care Excellence (NICE) has adopted the US
246 Kidney Diseases
Management of CKD with CKD [27]. The aetiology of growth delay and cachexia
in children with CKD is multifactorial with inadequate
Childhood CKD presents clinical features that are specific energy intake, uraemic toxicity, anaemia, increased inflam-
to paediatrics such as the impact of the disease on growth, matory response and metabolic and endocrine abnormalities
not only influencing the health of the patient through among the foremost causes. The dietitian plays an essential
childhood but also having an impact on the life of the adult role in optimising the management of these causes and
that the child will become. Therefore, the care of this vul- needs to ensure that individualised dietary prescriptions are
nerable population requires the collaborative efforts of a practical and flexible to aid adherence.
multidisciplinary team (MDT). The aim is to optimise the
quality of life of the child and family while treating Growth
the complications of the disease, delaying or slowing the
progression of the disease and preparing for RRT or pre‐ Achieving optimal growth is the most challenging problem
emptive transplant when the time comes. There needs to for the dietitian in this population. The causes of growth fail-
be an appreciation that the long‐term consequences of ure in children with CKD are multifactorial (Table 13.10)
CKD, e.g. cardiovascular disease (CVD), poor growth and [28]; the two most important factors are the severity of the
bone disease, have a great psychosocial impact on both the CKD and young age at onset.
patient and their family. Parents/caregivers not only fulfil Normal growth in childhood occurs in four phases: foetal,
a parental role but also take on many tasks that are infantile, mid‐childhood and pubertal. Nutrition is impor-
normally the remit of nurses and doctors [26], and they tant in all growth phases, but especially during the infantile
are, therefore, vital members of the MDT. phase when growth is at its most rapid and is less dependent
Irrespective of aetiology, the sequence of events in CKD on growth hormone (GH). There is a slowing of growth
demands attention to the management of nutrition, growth, velocity in the mid‐childhood phase when growth is more
fluid and electrolyte balance, acid–base abnormalities, CKD‐ dependent on the GH/IGF‐1 (insulin‐like growth factor 1)
mineral bone disease, hypertension, slowing the progression axis [28]. At puberty, which is typically delayed in CKD,
of CKD, anaemia, CVD, medication, education and psycho- there is a rapid increase in growth velocity in response to sex
social support. steroids and GH; adequate nutrition is important during this
A good knowledge of biochemical and haematological anabolic phase. A third to a half of total postnatal growth
parameters is essential to identify variations from normal occurs during the first 2 years of life and 20% during the
age‐specific reference ranges when formulating dietary man- pubertal phase.
agement plans. The serum values of particular relevance
include urea, creatinine, sodium, potassium, bicarbonate,
albumin, calcium, phosphate, alkaline phosphatase, parathy-
roid hormone (PTH), glucose, cholesterol and triglycerides.
Table 13.10 Aetiology of growth failure in children with CKD [28].
Haemoglobin, ferritin and percent hypochromic cells (<10%)
can be used to assess iron status in combination with serum Birth‐related factors: Genetic factors:
iron and total iron binding capacity (TIBC) to calculate the Prematurity Height of parents
percent transferrin saturation (TSAT = serum iron × 100 Small for gestational age Sex
divided by TIBC), which should be maintained at >20%. Intensive care Concurrent syndromes
Co‐morbidities
An assessment of the glomerular filtration rate (GFR) pro-
vides an indication of the overall level of renal function. GFR Hormonal disturbances affecting: Metabolic disturbances:
estimation by Cr51 EDTA clearance is used to predict when Somatotropic hormone axis Salt and water balance
PTH and vitamin D metabolism/ Metabolic acidosis
RRT is likely to be required. GFR should not be measured
action CKD‐MBD
before 1 year of age as the kidney function may continue to Gonadotropic hormone axis
mature during the first year of life and even beyond. GFR Gastrointestinal hormones
can be estimated using the Haycock Schwartz formula: Age at onset of CKD Severity of CKD and residual
predicted GFR = 40 × ht (cm)/serum creatinine (μmol/L). Anaemia renal function in those
undergoing dialysis
Nutrition Malnutrition: Protein energy wasting:
Anorexia Uraemic toxins
The adverse effects of poor nutrition in children are mani- Vomiting Infections and inflammation
fested by their influence on the capacity to grow and develop Altered taste sensation Oxidative stress
appropriately. There is a complex interrelationship between Dietary restrictions Inflammatory cytokines
renal dysfunction and nutrition whereby abnormalities or a Nutrients lost to dialysis fluids
decline in renal function frequently leads to changes in Infections and inflammation
Abnormal levels of gastrointestinal
metabolism, as well as a poor nutritional intake complicat-
hormones
ing CKD. Malnutrition is associated with increased mortal-
ity. Early and careful nutritional therapy may improve CKD‐MBD, chronic kidney disease‐mineral and bone disorder; PTH,
growth, development and mortality in all ages of children parathyroid hormone.
As the infantile phase is predominantly dependent on circumference, length, pubertal stage and body mass
nutrition, inadequate intake at this time can have a dramatic index (BMI). Some patients may need to be seen more
influence on growth with irreversible loss of growth poten- frequently in order to prevent the development of malnu-
tial. Nutritional adequacy is complicated by other factors, trition. This will depend on CKD stage and need for enteral
e.g. fluid and electrolyte balance, vomiting, infections, CKD‐ nutrition [30].
mineral bone disorder (CKD‐MBD), acidosis and catabolic In older infants and children, who may have a varied
states. If these factors are adequately controlled, severe diet, a 3‐day dietary diary and 24 hour recalls (for three
stunting can be avoided in the majority of patients (without separate periods in order to account for wide day‐to‐day
untreatable co‐morbidities) [28]. variability) are valuable tools when estimating nutritional
In order to maximise nutritional intake, supplementary intakes and individual baseline requirements [33].
feeding is often used via the enteral route. In a retrospec- Information on prescribed medications, presence or absence
tive analysis of growth in infants and children with of nausea and vomiting, diarrhoea, constipation and energy
severe CKD, catch‐up growth was achieved in the majority levels can be helpful in determining the child’s nutritional
of patients with good metabolic control and enteral and medical needs. Dietary intake should be communi-
feeding [29]. KDOQI advises that early and intensive
cated to members of the MDT, where appropriate, to rein-
nutritional management will benefit nutritional status and force discussions and recommendations made with the
growth [22]. child and family.
In later childhood catch‐up growth is rarely achieved by Height and weight plotted on growth charts are used to
diet alone as the role of the GH/IGF‐1 axis becomes more assess nutritional status. At each clinic visit, accurate meas-
important [30]. Optimising nutrition, however, may still urements of height, or supine length, and weight should be
prevent further growth decline. obtained. Infants with CKD have been shown to be at high
GH resistance is seen in CKD as well as decreased secre- risk of poor head growth [33]. Children <2 years of age
tion when there is metabolic acidosis. This is an important should have regular measurement of their head circumfer-
factor during the peri‐pubertal years and can result in a ence and plotted for chronological age on appropriate
delayed growth spurt [31]. The efficacy and safety of recom- growth charts. Where the child is within normal centile
binant growth hormone (rhGH) has been shown extensively ranges for height (>2nd centile), energy and nutrient
in paediatrics [31]. Pre‐pubertal children (conservatively requirements can be based on recommendations for chil-
managed or on RRT) treated with rhGH demonstrate dren of the same chronological age [13, 19]. For the child
increased height velocity [28]. For children with a height or who falls below the normal centile ranges for height
height velocity for chronological age <–2 SDS, GH therapy (<2nd centile), their height age (age at which the child’s
following the optimisation of nutritional management has height would be on the 50th centile) should be used for
been shown to increase height velocity and final adult comparison with recommended intakes for energy and
height [30]. nutrients [13, 19] and adjusted accordingly thereafter.
IGF‐1 production and sensitivity is also negatively affected Estimated dry weights need to be used in those children
by GH and CKD. The role of IGF‐1 is vital in longitudinal retaining fluid.
growth. Treatment with rhGH stimulates IGF‐1 synthesis Extremes of BMI are associated with increased morbidity
and, therefore, promotes longitudinal growth. and mortality, and children with CKD should avoid becom-
As already described, in the infantile phase, nutrition ing overweight or obese. However, it is difficult to find a
has the greater impact on growth. Two studies have shown measure of body composition that is relevant for children
that infants treated with rhGH showed significantly with CKD. They may not have a normal body composition
greater gain in length than the control groups [27]. Early making a comparison with normal populations inappropri-
rhGH may be beneficial in those infants that, despite ade- ate. CKD may have a disproportionately greater effect on
quate nutrition, show growth failure since it will help spinal growth, and children have been shown to have a low
achieve the body size required for renal transplant without ratio of length of trunk to limb [34]. They also have a rela-
delay [28]. tively high fat mass, low lean mass and increased central
adiposity [35]. BMI should not be used as a measure of fat-
ness for children <2 years of age. It can also be misleading in
Dietary and anthropometric assessment
adolescents with CKD due to delayed sexual maturation and
There is no simple measure of nutritional status for chil- linear growth, which is further confounded by reduced mus-
dren with CKD. Nutritional parameters are complicated cle mass, reduced activity and fluid retention; if BMI is used,
on account of salt and water imbalances together with the it is suggested that it is plotted against the child’s height age
inappropriateness of comparing growth to that of age‐ [36]. Caution should be used when interpreting BMI in this
matched populations. The frequency of nutritional moni- patient group [33].
toring depends on age, stage of CKD and how well the Mid‐upper arm circumference (MUAC) and triceps skin-
child is thriving. Clinical guidelines for growth monitor- fold thickness (TSF) are no longer recommended as part of
ing in children with CKD have been developed in the UK routine assessment, due to concerns of overestimation due to
[32]. The guidelines (Table 13.1) provide recommendations fluid overload and distorted fat and lean distribution in this
for the minimum frequency of reviewing weight, head patient group [22] (Table 13.11).
248 Kidney Diseases
Table 13.11 Growth monitoring guidelines for children with chronic kidney disease.
GFR
ml/min/1.73 m2 CKD stage Measurement Frequency of measurement Action
>90 Stage 1 Normal childhood growth Royal College of Paediatrics and Child Health Measure, document and plot on growth chart
monitoring (RCPCH) guideline
60–89 Stage 2 Length/height and weight Annually Measure, document and plot on growth chart
GFR CKD stage Frequency of assessment

ml/min/1.73 m2 3–5 Measurement (minimum recommended) Action
≤59 All these items for Weight (euvolaemic, i.e. Measure every clinic visit, but for growth Measure, document and plot on growth chart
children with greater normal fluid status) purposes required:
severity CKD, i.e. Every month if aged <6 months
stages 3–5 Every 2 months if 6–12 months
Every 3 months if >1 year
Head circumference Every 2 months if <1 year Measure, document and plot on standard head
Every 3 months if 1–2 years circumference curve on growth chart
Length/height Every 2 months if 0–1 year Measure supine length if <2 years on validated
Every 3 months if >1 year length mat, i.e. rollameter or kiddimeter
Measure standing height if >2 years on wall‐
mounted stadiometer
Document and plot on growth chart
Sitting height, knee height or total leg length
can be used as height proxies
Assess pubertal stage Annually if ≥12 years, i.e. during the older half Consider whether growth and development
of the normal age range of onset of puberty in progress is as expected or whether concern of
girls 8–13 years, boys 9–14 years pubertal delay
Consider using Childhood and Puberty Close
Monitoring (UK CPCM 2–20 years) chart if
concerns
Assess 6 monthly
Body mass index (BMI) Only applicable if >2 years, then do so every Calculate and plot on growth chart (UK 2–18
6 months years) against chronological age
Parental heights As soon after referral as possible if able to do Calculate mid‐parental height using
so information on growth chart
Document in notes and on growth chart
Source: Adapted with kind permission from S. Trace [32].

Learning points: management of chronic kidney disease

Dietary principles in CKD
Nutritional management of children with CKD requires

• Irrespective of aetiology, the sequence of events in CKD
attention to adequacy of energy intake, regulation of protein
demands attention to the management of nutrition, growth,
intake, fluid balance and electrolytes, regulation of calcium
fluid and electrolyte balance, acid–base abnormalities,
and phosphate intakes, correction of acid–base abnormali-
CKD‐MBD, hypertension, anaemia, CVD, medication,
ties and adequacy of micronutrient and iron intakes.
education and psychosocial support
Dietary recommendations depend upon age, stage of
• Early and careful nutritional therapy may improve growth,
CKD, clinical management and nutritional assessment. The
development and mortality in all ages of children with
recommended intakes of energy and protein in conserva-
CKD
tively managed children are given in Table 13.12, based on
• The cause of growth failure is multifactorial, the two most
UK dietary reference values [13, 18]. More recent recom-
important factors being the severity of the CKD and young
mended intakes have been proposed by the Paediatric Renal
age at onset
Nutrition Taskforce (see Guidelines, companion website),
with similar values. Anorexia is a common feature of CKD in
Table 13.12 Nutritional guidelines for the child with chronic kidney disease.
Energy (per kg body weight per day)

Protein (per kg body weight per day)
Age (kcal) (kJ) (g)
Conservative management
Infants
Preterm 110–135 460–560 2.5–3.0
0–2 months 96–120 400–500 2.1
3–12 months 72–96 300–400 1.5–1.6
1–3 years 78–82 325–340 1.1
Children/adolescents
4 years to puberty Minimum of EAR for chronological age (use height age if 1.0–1.1
Pubertal <2nd centile for height) 0.9–1.0
Post‐pubertal 0.8–0.9
Peritoneal dialysis (APD/CAPD)
Infants
Preterm 110–135 460–560 3.0–4.0
0–2 months 96–120 400–500 2.4
3–12 months 72–96 300–400 1.9
1–3 years 78–82 325–340 1.4
4 years to puberty Minimum of EAR for chronological age (use height age if 1.3
Pubertal <2nd centile for height) 1.2
Post‐pubertal 1.0–1.2
Haemodialysis
Infants
Preterm 110–135 460–560 3.0
0–2 months 96–120 400–500 2.2
3–12 months 72–96 300–400 1.7
1–3 years 78–82 325–340 1.2
4 years to puberty Minimum of EAR for chronological age (use height age if 1.1
Pubertal <2nd centile for height) 1.1
Post‐pubertal 1.1
These guidelines are for the initiation of management and require adjustments based on individual nutritional assessment.
Protein intakes reflect the reference nutrient intake (RNI) in the UK [18] plus an increment to achieve positive nitrogen balance including any
transperitoneal losses [22].
EAR, estimated average requirement [13]; APD, automated peritoneal dialysis; CAPD, continuous ambulatory peritoneal dialysis.
250 Kidney Diseases
infants and is a primary reason for growth failure in this depend on the fluid allowance. Powdered glucose polymers
patient group [33]. It can be seen in less severe CKD. Anorexia are useful in children who drink plenty of water or squash.
is caused by a combination of factors including nausea, vom- Each day a target amount to use should be negotiated, and a
iting, gastro‐oesophageal reflux, oral aversion, delayed gas- personalised record chart can aid compliance.
tric emptying, altered taste changes, elevation of cytokine
levels and changes in leptin and ghrelin hormone levels [37].
This will result in suboptimal nutritional intake. In order to Protein
optimise intake and growth, nutritional interventions either
with supplements (Table 13.4) or enteral tube feeding is com- Children, especially infants and young children, have a high
monly required [28]. requirement for protein per kilogram body weight because of
the demands of growth. A systematic review of protein
restriction for children with CKD [38] showed no significant
impact on delaying progression of renal failure, and there is
Energy
an association with inferior growth. The correlation between
dietary protein intake and proteinuria was also insignificant.
The energy requirements for children with CKD are the same
Protein intake should be optimised to allow for the mainte-
as those of healthy children. Energy intakes below the EAR
nance of nitrogen balance and growth, together with the pres-
contribute to growth failure [28]. The provision of adequate
ervation of lean body mass. In CKD, protein must provide at
energy is essential to promote appropriate weight gain and
least 100% of the RNI for age to avoid protein becoming a lim-
linear growth in all children with CKD and to avoid the use
iting factor in growth [27]. The RNI for height age is advised
of lean muscle mass as an energy source. The EAR for energy
when the child is <2nd centile for height. Insufficient protein
for either height age (if the child’s height is <2nd centile) or
will impact on body composition with a predominance of fat
chronological age (if the child falls within the normal centile
rather than lean tissue being laid down. Children achieve rec-
range) is used as baseline guidelines (Table 13.12) [13].
ommended protein intakes more easily than their energy
Raised serum urea levels in combination with increased
requirements, and a protein intake above 3.0 g protein/kg
serum potassium levels can be suggestive of catabolism and
should be avoided because of the associated phosphorus load
the need to increase non‐protein energy intake.
and link with cardiovascular morbidity. Where dairy proteins
have been limited to restrict phosphate intake, and adequate
High energy, low protein foods energy intake has been ensured to promote anabolism, further
protein modification is seldom needed. However, when a
These include sugar, glucose, jam, marmalade, honey and
child’s serum urea remains persistently >20 mmol/L, a grad-
syrup and should be encouraged where possible. The liberal
ual protein reduction based on the child’s 3‐day dietary record
use of polyunsaturated or monounsaturated oils in cooking
should be initiated to lower the urea level to <20 mmol/L,
or margarine spread on bread or toast or added to meals and
aiming not to go below the RNI appropriate for the child.
vegetables can contribute significantly to the child’s energy
Protein of a high biological value should comprise 65%–70%
intake. Special low protein dietary products such as bread
of the total dietary protein intake.
and biscuits are rarely needed.
Should protein supplements be needed, consideration
should be made regarding the phosphate, calcium and
Energy supplements potassium content of these supplements (Table 13.4).
Anorexia, nausea and vomiting are features of CKD and can
be exacerbated by uraemia. These symptoms, together with
Electrolyte and fluid balance
an abnormal sense of taste, contribute to a reduced energy
intake. Energy supplements are helpful in meeting this deficit.
Sodium and fluid balance
A number of supplements are available and enable a flexible
approach (Table 13.4). Combined fat and CHO supplements In several causes of CKD in infancy, including obstructive
or glucose polymer alone, if additional fat is not tolerated, can uropathy and renal dysplasia, there is poor urinary concen-
be successfully added to infant formulas, tube feeds and oral trating capacity and sodium wasting. Sodium depletion
nutritional supplements. The concentrations of CHO and fat results in contraction of the extracellular fluid volume and
should be increased gradually to establish tolerance. further impairment in renal function, as well as impairment
Assuming normal gut function, the following upper limits for of growth [39]. Sodium chloride supplements can be added
CHO and fat can be worked towards: to infant feeds or be given as a medicine. The amount should
be increased until an improvement in growth is seen without
• infants <6 months: 12% CHO and 5% fat
the development of hypertension, peripheral oedema or
• infants >6 months to 1 year: 15% CHO and 6% fat
hypernatraemia. Such infants typically require up to
• toddlers aged 1–2 years: 20% CHO and 7% fat
4–6 mmol sodium/kg/day. These infants are usually polyu-
• older children: 32% CHO and 9% fat
ric and require free access to fluids in the form of supple-
Liquid glucose polymers are useful when diluted with a mented feed and extra water. Their preference of water over
fizzy drink or diluted squash, and the volume used will feed/food can diminish their appetite [33].
In contrast, children with primary renal diseases exhibit- sodium retention until CKD stage 5 and, as such, have little
ing hypertension may benefit from a reduction in sodium effect on blood pressure control; they do not usually need to
intake and advice on a reduced salt or ‘no added salt’ diet be included in an assessment of sodium intake. Dialysis will
(Table 13.7). usually correct acidosis.
As the GFR declines in CKD stages 4 and 5, sodium and In older children a protein intake in excess of require-
fluid retention are commonly seen. This can lead to volume ments, and hence an excess in intake of sulphur containing
overload and hypertension; dietary sodium and fluid restric- amino acids, can increase endogenous acid production.
tion together with diuretics are instigated. Fluid restrictions Protein intake should be modified in such instances.
are only instituted as urine output diminishes or oedema
develops, more usually when the GFR falls below 15 mL/ CKD‐mineral bone disorder
min/1.73 m2. Fluid prescriptions are individualised to take
account of insensible losses and a typical day’s urine output. The pathogenesis of CKD‐MBD is complex. Children with
stage 2 CKD usually have no signs of bone abnormalities,
Potassium but biochemical abnormalities can be evident. There is a fall
in 1,25‐dihydroxyvitamin D3 production; this results in an
The majority of children with CKD stages 1–3 maintain
increase in PTH levels and a drop in serum calcium levels,
potassium homeostasis. If hyperkalaemia occurs, other cor-
further stimulating PTH production. Phosphate retention, as
rectable causes including drugs such as angiotensin‐convert-
a result of reduced GFR, causes hypocalcaemia and a rise in
ing enzyme (ACE) inhibitors, metabolic acidosis and
PTH. Secondary hyperparathyroidism (SHPT) causes bone
catabolism should be excluded before initiating a potassium‐
resorption and a further increase in serum phosphate levels
modified diet (Table 13.5). A haemolysed blood sample will
[21]. In addition to MBD, this process can lead to calcification
show a falsely high serum potassium level. In stage 5 CKD,
in other tissues including blood vessels and muscle tissue as
hyperkalaemia necessitates a potassium‐modified diet; any
well as phosphate acting as a uraemic toxin.
nutritional supplements used must be exchanged for low
Vitamin D deficiency is widely prevalent and often severe
potassium varieties. Foods containing the preservative
in children with chronic kidney disease and contributes to
potassium sorbate should be minimised if hyperkalaemia
abnormalities in calcium, phosphate and PTH homeostasis
persists; 100 g of food containing this additive can add
[41]. The mineral dysregulation seen in CKD directly affects
an additional 1.0–2.5 mmol of potassium to the diet.
bone strength, mineralisation and architecture. CKD‐MBD
Hyperkalaemia is the most dangerous of the electrolyte
in childhood presents multiple obstacles to bone accrual,
disturbances, affecting cardiac function.
resulting in bone pain, deformities, growth retardation and
Hypokalaemia is seen in renal tubular disorders such as
fractures [41].
cystinosis and Bartter syndrome (p. 272, 274). Potassium
Management of CKD‐MBD should be based on serial
supplements are usually indicated together with medication
assessments of phosphate, calcium, PTH and vitamin D lev-
(indometacin) that reduces renal sodium, potassium and
els. Therefore, dietary management is a combination of die-
water losses. Hypokalaemia can be seen in polyuric CKD
tary assessment and manipulation of calcium and phosphate
as well as resulting from the use of some diuretics or with
intake and the treatment of vitamin D deficiency [42].
episodes of diarrhoea and vomiting.
Hyperphosphataemia and hypocalcaemia contribute to the
pathogenesis of SHPT. Optimal control of bone and mineral
Acid–base abnormalities homeostasis is essential for preventing debilitating skeletal
complications, achieving adequate growth and preserving
Acidosis can occur as early as CKD stage 2 in young children long‐term cardiovascular health.
with dysplasia. It is common in all causes of CKD when the
GFR falls below 25 mL/min/1.73 m2. It is more commonly
Phosphate
seen in children due to the consumption of base due to
growth of bone and other tissues [30]. Acidosis can have sub- Bones expend 85% of the body’s phosphorus during skeletal
stantial adverse effects on development, exacerbation of mineralisation [43], making phosphate essential for childhood
bone disease, growth retardation, increased muscle degrada- growth. Organic phosphorus is naturally found in foods that
tion, reduced albumin synthesis, resistance to the effects of are rich in protein. Inorganic phosphorus is the main compo-
insulin and acceleration of the progression of CKD. It is also nent of many preservatives and additive salts found in a vari-
associated with increased mortality [40]. Current recommen- ety of processed foods. The bioavailability of organic and
dations are to maintain serum CO2 at ≥20 mmol/L among inorganic phosphorus varies considerably [44] with 30%–80%
children less than 2 years of age and at ≥22 mmol/L in chil- bioavailability from organic plant, meat and dairy sources [45]
dren aged over 2 years of age [22]. and over 90% from inorganic phosphorus preservatives and
Hyperkalaemia can be exacerbated by acidosis. additives [46]. Bioavailability is lower from plant foods,
Extracellular potassium shifts occur with metabolic acidosis including seeds and legumes, due to the limited gastrointesti-
as bicarbonate is lost through the kidney. Acidosis is cor- nal absorption of phytate‐based phosphorus. Food preserva-
rected with the administration of sodium bicarbonate. tives and additives (Table 13.13) add to the burden of the diet
Sodium bicarbonate supplements do not usually cause and need to be factored into dietary counselling.
252 Kidney Diseases
Table 13.13 Phosphate preservatives and additives.
Food industry
Phosphate additive purpose Examples of food
Phosphoric acid Acid Processed meats, cakes, chocolates, sweets, jams, vegetable fats
and oils, cola drinks, beer
Sodium phosphate Antioxidant Processed meat, processed cheese, powdered milk
Potassium phosphate Antioxidant Cured meats, milk and cream powders, drinking chocolate
Calcium phosphate Anti‐caking agent Self‐raising flour, cake and pancake mixes, powdered milk drinks,
instant pasta and sauces
Magnesium phosphate Anti‐caking agent Salt substitutes, prepared mustard
Diphosphate Emulsifier Processed cheese, instant mashed potatoes, cakes
Triphosphate Emulsifier Fish fingers
Polyphosphate Emulsifier Dried foods and desserts
Distarch phosphate Thickening agent Batters for frozen foods, custards, sauces, mayonnaise, salad
dressings, pies and fillings, dried foods, drinking yoghurt, flavoured
milk, whipped cream, pre‐cooked pasta and noodles, starch‐based
puddings, instant beverages
There is much debate as to when to start dietary phos- dietary allowance. Guidelines for phosphate intake are
phate restriction. In the past phosphate restriction was based on body weight as follows:
started when either serum phosphate or PTH levels were
• infants <10 kg < 400 mg/day
above normal; this is now felt to be too late in relation to
• children 10–20 kg < 600 mg/day
CKD progression, advancement of CKD‐MBD and the
• children 20–40 kg < 800 mg/day
increase in risk of CVD. Consumption of a phosphate‐rich
• children >40 kg < 1000 mg/day
diet in the early stages of CKD releases fibrin growth factor
23 (FGF‐23) from the bones [47, 48]. A study in adults with Care needs to be taken not to compromise protein intake
ESRD proposes that FGF‐23 is the earliest marker of abnor- while restricting dietary phosphate. A guide to the phospho-
mal phosphate metabolism [49] and it has been found to be rus content of different foods per gram of protein is given in
an independent risk factor for CKD progression in chil- Table 13.14. Note this is not appropriate for processed foods
dren [50]. FGF‐23 levels above the normal range have been due to their added phosphate preservative and additive con-
seen as early as CKD stage 3 [51]. Raised serum phosphate tent. Dietary strategies should enable children and their care
levels are not normally seen until CKD stage 4 and signifi- givers to choose foods with less phosphate, but to maintain
cant CKD‐MBD has already occurred by this time [50]. an adequate protein intake. Maintenance of serum phos-
Therefore, reducing dietary phosphate in the early stages phate within the normal reference values for age is desirable.
of CKD has been suggested as a possible strategy to slow During conservative management and when on haemodial-
down the progression of FGF‐23 levels and, thus, delay ysis (HD), phosphate intake will be reduced with protein
disease progression [47, 50] and decrease mortality risk
from CVD [52, 53].
Table 13.14 Guide to the phosphorus content of foods related to their
protein content.
Phosphate restriction
For infants, standard whey‐based infant formulas are used Type of food Phosphorus (mg/g protein)
for at least the first 1–2 years of life due to their lower phos- Poultry, meat and white fish 7–9
phate content. Where hyperphosphataemia persists,
Pulses 12–18
Kindergen or Renastart (Table 13.4), usually in combination
with standard whey‐based infant formula, can be used to Tofu 12
regulate serum phosphate levels. Consideration should be Shell fish, oily fish, offal 15–20
given to their lower calcium and potassium contents (and Egg 16
higher sodium content). In older children, cow’s milk can be
Hard cheese 20
introduced in a controlled amount. Individualised targets
should be given for cow’s milk and cow’s milk products. Milk, yoghurt 28
Phosphate‐rich foods and alternatives also should be tai- Peanuts 15
lored to the individual’s diet (Table 13.6) Where indicated, Almonds 26
nutritional supplements with a lower phosphate content Walnuts 48
(Table 13.4) should be chosen and be included within the
modification. Phosphate binders may be needed in addition Phosphate binders

to dietary phosphate restriction.
Although dietary management can control plasma levels in
early CKD stages, persistent hyperphosphataemia requires
Calcium the addition of oral phosphate binding drugs to block intes-
tinal phosphate absorption (Table 13.15). Compounds use
Childhood and adolescence are critical periods for bone
the anionic nature of phosphate for ionic exchange to form a
mass accrual. Therefore, it has been advised that serum
non‐absorbable compound that is excreted in the faeces [54].
calcium levels be maintained in the age‐appropriate nor-
Aluminium salts, although effective phosphate binders,
mal range in children and adolescents; this recognises the
have been abandoned in children due to their toxicity.
high calcium requirements of the growing skeleton [42].
Calcium‐based binders are the first‐line phosphate binder in
Hypocalcaemia is a feature of CKD secondary to dimin-
children [59] and can be made from calcium carbonate or cal-
ished gastrointestinal uptake of calcium due to vitamin D
cium acetate.
deficiency. Calcium intake is compromised when phos-
Calcium carbonate binders should be chewed and taken
phate is restricted in the diet and may need supplementa-
preferably just before meals/snacks as a lower pH improves
tion. An average of 20%–30% of the calcium in
binding capacity. Alternatively, calcium carbonate solution
calcium‐based phosphate binders is absorbed and, there-
can be added to feed bottles or overnight/daytime bolus
fore, can be factored into calcium intake [54]. It has been
feeds. Calcium carbonate impairs the absorption of iron so
suggested that total daily intake of calcium from both
should be taken separately from oral iron supplements.
binders and dietary sources should be in the range of
Approximately 20%–30% of the calcium contained in a cal-
100%–200% of the dietary reference intake for age and not
cium phosphate binder will be absorbed and can contribute
exceed 1.5 g/day [22, 55]. The Paediatric Renal Nutrition
to hypercalcaemia. Calcium acetate achieves a similar con-
Taskforce has published more recent recommendations
trol of serum phosphate at a lower dose of elemental cal-
for the dietary management of calcium and phosphate
cium. It is taken during meals and swallowed whole (but can
(see Guidelines, companion website).
be crushed and added to drinks if necessary).
Calcium‐based binders can lead to an increase of the Ca × P
Vitamin D and parathyroid hormone ion product and the development of vascular and soft tissue
Vitamin D deficiency is common in CKD. Therefore, it has calcification. Soft tissue calcification has been reported in
been recommended that children with CKD stages 2–5 who 60% of autopsies of children with renal failure [60]. If a series
have a serum 25(OH)D concentration less than 75 nmol/L be of serum calcium measurements shows a trend towards the
supplemented either with vitamin D2 or D3 [41]. A high PTH upper limit of normal, a combination of a calcium‐based
level in children with decreasing GFR can sometimes reflect binder with a non‐calcium‐based phosphate binder, seve-
vitamin D deficiency/insufficiency and not the activity of lamer, could be used having taken into account other causes
renal bone disease [56]. of rising calcium [59]. Sevelamer hydrochloride and seve-
Vitamin D is converted to the activated form 1,25‐dihy- lamer carbonate are calcium‐free synthetic anion exchange
droxyvitamin D3 in the healthy kidney. The decrease in polymers that bind phosphate and cholesterol. Sevelamer
activated vitamin D levels seen in CKD contributes to
binds to bile salts and may interfere with normal fat absorp-
hypocalcaemia (due to decreased absorption in the tion and the absorption of fat‐soluble vitamins. Therefore, it
small intestine), SHPT and the spectrum of CKD‐MBD. is recommended that fat‐soluble vitamin and folic acid levels
Recommendations suggest that children with CKD stages are monitored when sevelamer is prescribed [54]. Sevelamer
2–5 who have persistently increased serum PTH are pre- carbonate reverses the negative effect of sevelamer hydro-
scribed a vitamin D analogue. Supplementation solely with chloride on acid–base balance. If, with a mixture of phos-
native vitamin D may not adequately treat hyperparathy- phate binders, serum calcium rises above the age‐adjusted
roidism [57]. Preparations include calcitriol (a naturally upper limit, a switch to all non‐calcium‐based binders can be
occurring form of active vitamin D), alfacalcidol (1α‐hydrox- considered [59]. It should be noted that sevelamer is con-
ycholecalciferol) and paricalcitol. The dose is based on traindicated in patients who are at risk of small bowel
serum calcium and PTH levels and is reduced or suspended obstruction.
if calcium levels are above or below the normal range [57]. Lanthanum carbonate is another available calcium‐free
The optimal level for PTH in children with CKD is not phosphate binder, but is not currently used in children due
known; modest increases may represent an appropriate to a lack of data on its effect on the growing skeleton.
adaptive response to declining kidney function. KDIGO Sucroferric oxyhydroxide is an iron‐based phosphate binder.
guidelines [42] have been adjusted to reflect this and stress Trials in adults have demonstrated efficacy, tolerability and
the importance of looking at modifiable factors, such as safety, with a reduction in pill burden from sevelamer [58]. It
hyperphosphatemia, hypocalcaemia, high dietary phos- is not currently licensed for children as a phosphate binder.
phate intake and vitamin D deficiency, in patients who have Nicotinamide (vitamin B3) has been trialled in conjunction
PTH levels that are progressively rising or persistently above with a phosphate binder in adults and shown to reduce
the upper normal limit. Higher PTH levels are associated serum phosphate level further. Nicotinamide reduces phos-
with a higher morbidity and mortality. phate absorption by inhibiting intestinal sodium–phosphate
254 Kidney Diseases
Table 13.15 Phosphate binders.
Elemental calcium
mg (mmol) Estimate of potential
per tablet Dose Flavour binding power
Calcium carbonate binders

Setlers Tums tablets (500 mg) 200 (5.0) 1–3 tds Various fruit flavours Approximately 39 mg
phosphorus bound per 1 g
calcium carbonate
Calcium carbonate (20% 400 (10.0) per 5–15 mL tds —
solution) 5 mL
Rennie tablets 272 (6.8) 1 tds Peppermint/spearmint
Digestif/Spearmint (680 mg)
Remegel tablets (800 mg) 320 (8.0) 1–3 tds Mint
Calcichew tablets (1250 mg) 500 (12.6) 1 tds Orange
Adcal (1500 mg) 600 (15.0) 1 tds Fruit flavour
Calcium acetate binders
Phosex tablets (1000 mg) 250 (6.25) 1–3 tds Designed to be swallowed Approximately 45 mg
whole, but can be crushed phosphorus bound per 1 g
Phosex tablets (500 mg) 125 (3.1) 2–4 tds
and mixed with water or calcium acetate
named patient basis
other drink
Renacet* tablets (475 mg) 120 (3.0)
Renacet* tablets (950 mg) 240 (6.0)
Sevelamer binders
Sevelamer hydrochloride
Renagel tablet (800 mg) None 1–3 tds Swallow whole Approximately 26 mg
Sevelamer carbonate phosphorus bound per 1 g
Renvela tablet (800 mg) or None 1–3 tds or 1 Powder in natural or citrus sevelamer (this amount
powder (2.4 g) sachet of flavour varies between 21 and
powder 39 mg) [58]
tds, three times a day.

*Not prescribable for children.
co‐transporter 2b [54]. Additional data on safety and efficacy restriction (Table 13.7), exercise, carefully monitored
are required before widespread use and at the time of writ- weight loss in overweight children and strict fluid control
ing a trial in adults is underway. where appropriate.
Many children readily exceed the adult daily maximum
Calcimimetic agents recommendation for sodium intake of 100 mmol/day (6 g
salt) due to their intake of salted snacks and processed foods.
Cinacalcet is a calcimimetic agent that increases the sensitiv- Dietary advice should take into account current lifestyles
ity of calcium sensing receptors to extracellular calcium ions, and the hidden salt in foods when devising targets to reduce
thereby inhibiting the release of PTH. It is gaining use in salt intake. Advice needs to be given on interpreting food
severe cases of hyperparathyroidism. Promising results have labels and giving ideas for lower salt snacks. Poor compli-
been seen in limited paediatric trials [28, 61, 62]; however, ance with salt restriction is a common observation. The UK
there is still limited experience especially in the first years of Scientific Advisory Committee on Nutrition (SACN) [64]
life [63]. A large multicentre trial was stopped due to a severe gives recommendations on maximum daily salt intake for
serious event (hypocalcaemia) in one patient; caution in the children throughout childhood, which can be used as a
use of this drug is therefore advised [28]. guideline (Table 13.16).
In the absence of fluid overload, hypotensive therapy is
Hypertension started when the child’s systolic or diastolic blood pressures
are repeatedly >90th centile for age. A systematic review in
Hypertension is common in the late stages of CKD and is adults showed a reduction in sodium intake significantly
due to fluid overload and the activation of the renin– reduced resting systolic blood pressure [65]. It would be
angiotensin–aldosterone system [21]. Hyperparathyroidism prudent to avoid excessive sodium intakes in this group of
can also contribute. Management strategies include salt children.
Table 13.16 Recommendations on salt consumption in children. Management aims are to prevent the development of iron
deficiency anaemia and the maintenance of adequate iron
Age range Target daily intake of salt and sodium stores. Haematology results are frequently monitored by the
MDT.
0–6 months <1 g <17 mmol
7–12 months 1 g 17 mmol
1–3 years 2 g 34 mmol Dietary assessment
4–6 years 3 g 50 mmol Foods rich in iron, folic acid and vitamins C and B12 should
7–10 years 5 g 84 mmol be advised to ensure children are achieving recommended
11–14 years 6 g 100 mmol
intakes for age and sex [19]. Sources of haem iron are to be
recommended together with advice about non‐haem iron
Target salt intakes for infants and children have been estimated as an and its potential inhibition by phytates in cereal grains and
increase in the reference nutrient intake (RNI) by a factor of 1.5 [64] and legumes; polyphenols including tannin in tea, coffee and
should be considered the maximum daily intake. cocoa; and calcium in milk and dairy products.
To convert grams of salt to milligrams of sodium: divide the salt figure in
grams by 2.5 and then multiply by 1000, e.g. 6 g
salt ÷ 2.5 = 2.4 × 1000 = 2400 mg sodium = 100 mmol sodium. Oral iron supplements
Oral iron supplements are prescribed when dietary iron
intake is insufficient to maintain adequate iron stores. As the
Preservation of renal function child progresses to stage 5 CKD, intravenous iron therapy is
used.
Control of hypertension and proteinuria continues to be the Iron preparations can be prescribed as liquid, tablet or cap-
strongest independent predictor for progression of renal dis- sule to aid compliance. Vitamin C enhances the absorption of
ease [66]. The ESCAPE study group showed that strict blood non‐haem iron. It is important to avoid over‐supplementa-
pressure control slowed the progression on CKD in children tion. It can be given in two to three divided daily doses [70].
[67]. The same trial also showed the benefits of the use of an Iron is best absorbed in the absence of medications (antacids,
ACE inhibitor on proteinuria. Proteinuria is associated with phosphate binders), food, infant formulas, milk or nutritional
inflammatory factors in the urine, which contribute to renal supplements. Ideally, it should be taken 1 hour before or
disease progression. 2 hours following a feed or meal and be taken with a micro-
There is clear evidence in adults that obesity is associated nutrient supplement where prescribed. Problems with
with increased risk of development and progression in CKD. compliance are common, particularly with the potential side
A similar association is seen in children; however, there is a effects including nausea, vomiting and constipation. The
lack of large and long‐term follow‐up studies in paediatrics ideal prescription can be impractical, and a flexible approach
[66]. There is reluctance to recommend dietary modification that is conducive to the child’s feeding pattern, school and
in an attempt to delay the progression of chronic renal insuf- family should be advised.
ficiency in the early stages of CKD [68]. The lack of signifi-
cant impact from protein restriction in children was
Cardiovascular disease
considered earlier (p. 250). Some paediatric data suggest that
factors such as anaemia, hypoalbuminaemia, hyperphos-
The lifespan of children with advanced CKD remains low
phataemia and hypocalcaemia might be associated with the
compared with the general paediatric population, with
rate of CKD progression; however, further studies are
CVD accounting for the majority of deaths [55].
needed to confirm this [66].
Cardiovascular abnormalities develop early in the course of
CKD and progress as end stage is reached. Recognised risk
Anaemia factors in renal insufficiency include a pro‐atherogenic state
with left ventricular hypertrophy (LVH), hyperlipidaemia,
The anaemia of CKD is associated with substantial morbid- hypoalbuminaemia, hypertension and dysregulated min-
ity, an increased risk of CVD, reduced quality of life, eral metabolism. Hypertension and volume overload are
increased hospitalisations, anorexia, growth retardation, associated with the development of LVH in children. There
cognitive impairment and reduced exercise capacity. is consistent association between the length of time on dial-
Anaemia can be seen as early as CKD stage 2 [69]. The blood ysis and deteriorating measures of vascular function.
film is a normochromic, normocytic anaemia as a conse- Thickening and stiffness of the blood vessel walls have both
quence of inadequate erythropoietin production by the dam- been associated with abnormal levels of calcium, phospho-
aged kidneys. The aetiology of anaemia in CKD is rus and PTH [55]. The lifelong nature of CKD reinforces the
multifactorial with iron and folate deficiency, reduced red importance of dietetic involvement in reducing CVD risks
blood cell survival, hyperparathyroidism‐induced bone in connection with addressing the management of fluid lev-
marrow suppression and gastrointestinal loss. Serum ferritin els, hypertension, obesity and the regulation of CKD‐MBD
is used to assess iron status and should be >100 μg/L. and levels of vitamin D.
256 Kidney Diseases
Education and psychosocial support and Transplant when their GFR falls to approximately
10 mL/min/1.73 m2. Living donor transplantation is becom-
The conservative stage of CKD management is a time for ing the choice for an increasing number of families.
ongoing education and preparation for the child and family Pre‐emptive transplantation is not always possible and is
by all members of the renal team in preparation for stage 5 unsuitable for certain renal diseases or if the child presents
CKD management. Progressive renal failure is disruptive to in established renal failure. European guidelines recom-
a child’s schooling, social life and family life. Parents of chil- mend commencing dialysis when the estimated glomerular
dren with CKD reported moderate health‐related quality of filtration rate (eGFR) is between 15 and 10 mL/min/1.73 m2
life scores, with parents of children undergoing dialysis unless the child is growing well and is asymptomatic [74].
experiencing more limitations in quality of life [71]. To many The indications for starting maintenance dialysis are a
families, nutrition can be one of the more demanding parts combination of clinical and biochemical characteristics. The
of management. An understanding of the psychosocial presence of fluid overload that is resistant to medical man-
effects of feeding such children is as important as the nutri- agement, especially if the resulting fluid restriction makes it
tional advice [72]. Many families travel long distances to difficult to provide adequate nutrition, is a major factor.
their renal unit; regular telephone contact and visits to the Subjective indictors include fatigue, drowsiness and general
home, nursery and school can be invaluable supportive weakness, which decrease quality of life and educational
measures to clinic visits. Good communication is essential attainment and attendance [75].
with other team members to help develop practice, manage- Dialysis in children can be by HD or PD. In the UK, PD is
ment strategies and shared team philosophies, which ulti- the favoured dialysis modality for children. Data from the
mately lead to better patient care. There is emerging 2015 UK Renal Registry showed that 44% of paediatric
evidence regarding a positive relationship between MDT patients started RRT on PD, 33% on HD and 23% had a pre‐
support and clinical outcomes [73]. Adequate dietetic time emptive transplant [23].
is crucial to provide the close and frequent assessments and
support, which is required to optimise nutrition and mini-
mise negative outcomes. These negative outcomes can lead
Chronic dialysis
to significant emotional, physical and financial costs to the
Choice of RRT modality needs to be individualised to fit the
patients and their families [73]. Attendance on ward rounds,
needs of the patient and their family. Factors that need to be
outpatient clinics and psychosocial team meetings are
considered are the patient’s age, lifestyle choice, parental
essential [72].
preference and assessment of whether the patient their fam-
ily can adhere to a dialysis regimen at home [75].
Medication
Peritoneal dialysis
Several of the prescribed medications in CKD are nutrition
related (including phosphate binders, oral iron, sodium sup- PD is the method of choice for initiating RRT in the youngest
plements and vitamins) and should be periodically reviewed age group and has been shown to preserve residual renal
as part of the dietary assessment. Children and their families function [74]. PD has numerous advantages: relaxation of
should be advised on the correct administration and timing dietary restriction; avoidance of vascular access, therefore
of medications to ensure compliance, optimise absorption preserving for future use; ability to provide RRT in the home
and minimise potential side effects. Ongoing discussion setting; less disruptive to home and school life; and the daily
with education and information about each medication ultrafiltrate (UF) allowing a more liberal fluid allowance that
should be routine at each dietetic review. The practicalities of may be necessary to optimise nutrition. However, it is very
taking medications, including at school, should be identi- labour intensive and gives a high level of responsibility for
fied, and regimens adjusted accordingly following medical the family.
and team discussion. Adherence with medication is a signifi- The procedure of PD requires a patent abdominal cavity
cant problem, especially among the adolescent group. and a functioning peritoneal membrane across which solute
and fluid transport can take place. A PD catheter is inserted
into the abdominal wall. PD can be performed intermittently
Management of stage 5 CKD (usually overnight) using an automated cycling machine.
This automated peritoneal dialysis (APD) is the preferred
For many children with established renal failure, treatment option in smaller children, combining 5–10 overnight
can be cyclical between dialysis and transplantation. The exchanges with a long daytime dwell of dialysate.
treatment of choice for all children with established renal Alternatively, the child may have continuous ambulatory
failure is a successful renal transplant with pre‐emptive peritoneal dialysis (CAPD) where the child or caregiver
transplantation occurring before dialysis is required. carries out 3–4 exchanges of dialysate during the day with a
Transplantation provides superior long‐term survival and long overnight dwell.
quality of life. Children are usually activated on the national Peritoneal membrane transport capacity for solutes and
waiting list for cadaveric renal transplantation at NHS Blood ultrafiltration can be estimated using a standardised
Management of Stage 5 CKD 257
peritoneal equilibration test (PET), which is used in a central venous catheter in younger children while an
determining the PD prescription including dialysate dwell a rteriovenous fistula is created in older children once blood
times. A low transporter status in the PET indicates low puri- vessels have developed sufficiently. Central venous cathe-
fication rates and potential issues in achieving creatinine ters pose an infection risk.
clearance, but ultrafiltration is good. A high solute transport Intensified HD, which includes short daily HD, intermit-
rate in the PET implies good purification, but poor UF. The tent nocturnal HD and daily nocturnal HD, has demon-
reason is twofold: firstly, due to the rapid absorption of strated improved control of phosphate, anaemia and blood
glucose, the osmotic gradient is lost, resulting in reduced UF; pressure. There is less dietary restriction and room to
secondly, once the osmotic gradient is lost, the rate of fluid optimise nutrition, leading to improved growth compared
reabsorption is more rapid, leading to a positive fluid balance with conventional HD [75].
[76]. Prescriptions can be individualised based on patients’
needs; the combination of dwell times and fill volumes can
Nutrition and chronic dialysis
optimise dialysis [77]. Newer PD solutions that lessen the
harmful effects caused by the exposure of the peritoneal
Children treated with dialysis require a nutritional prescrip-
membrane to glucose have been shown to improve mem-
tion dependent on their age and treatment modality. This
brane health and viability in adults [76]. There is no strong
prescription requires regular dietetic review and includes all
evidence in children; however, the Renal Association guide-
the points highlighted in the conservative management of
line group’s view [76] is that the principles used in adults of
CKD, together with consideration of the efficiency and
minimising glucose exposure and avoiding obesity should
demands of dialysis. Evidence‐based clinical practice guide-
be applied to the paediatric population. The European
lines for all stages of CKD and related complications are
Society for Paediatric Nephrology (ESPN) notes some
published in the NKF KDOQI [22]. Nutritional guidelines
caution in their use in children due to possible hyponatrae-
for the child with stage 5 CKD based on NKF KDOQI data
mia and risk of rebound hypoglycaemia in the daytime [74].
are given in Table 13.12.
Peritonitis is the single most common complication of PD
The monitoring of dialysis prescriptions (dose of dialysis,
and requires antibiotic therapy. Anorexia can be experienced
solution(s) used, ultrafiltration) and urine output should be
as a result of the pressure effect caused by the dialysate in
carried out by the nephrologist, renal nurse and dietitian
the abdomen, which may decrease appetite and increase
and is used when formulating a nutritional prescription.
vomiting.
Dialysis dose affects growth and nutritional status in chil-
dren. Dialysis adequacy can be monitored by urea kinetic
Haemodialysis modelling, in particular by calculation of Kt/V (normalised
whole‐body urea clearance) and nPCR (normalised protein
HD is chosen as the initial mode of RRT in infants with
catabolic rate). Kt/V is termed as the minimally acceptable
primary oxalosis and those with contraindications for PD
dose of dialysis and refers to the dose of dialysis below
(omphalocele, gastroschisis, diaphragmatic hernia, oblite-
which a significant increase in morbidity and mortality
rated peritoneal cavity, bladder exstrophy) [74]. Conventional
would occur. The target Kt/V for patients on PD is >1.7 [76]
HD has the disadvantage of being a hospital‐based treat-
and on HD is 1.2 [79]. Current guidelines recommend that
ment that disrupts the home routine, but it can relieve the
the delivered daily dose be measured monthly. Kinetic
family of a great responsibility and may be used to give the
modelling software programs can be used to tailor PD pre-
caregiver some respite. A child will transfer to HD if there is
scription to the individual’s characteristics and needs. In
a loss of peritoneal access or function. No comparative stud-
contrast to adult patients, Kt/V is difficult to define in chil-
ies of conventional HD and PD outcomes in children suggest
dren, and scientific data demonstrating that dialysis efficacy
that one procedure is superior to the other [78]. Intensified
can be predictive of morbidity and mortality are lacking
and home HD (HHD) is being recognised as an important
[80]. Adequacy of PD in children is better expressed by the
strategy to improve clinical outcomes [75]. Only two centres
attainment of appropriate fluid balance, good electrolyte
in the UK currently provide HHD.
and acid–base control. The most sensitive measure of appro-
Conventional HD is an intermittent process lasting
priate dialysis in infants is appropriate growth and devel-
4–6 hours typically three times a week; smaller children,
opment [74].
especially anuric patients, frequently require four or more
dialysis sessions a week to ensure adequate fluid removal.
Small molecular weight solutes are removed from the blood Energy
by diffusion through a semipermeable membrane. Small
solute clearance is typically measured by urea clearance and The EAR for energy is used as a guideline for requirements.
is dependent on the clearance characteristics of the dialyser This is corrected for height age if the child’s height is <2nd
and the blood pump flow rate [79]. The dialysis fluid compo- centile (Table 13.12). There is no consistent evidence that
sition takes into account concentrations of sodium, potas- energy requirements on dialysis are different from those for
sium, chloride, bicarbonate, calcium, magnesium and normal children. Some studies suggest that HD stimulates
glucose. HD provides a greater level of small molecule mass the release of cytokines and complement that can have the
transfer than PD. Access to the circulation is usually through direct effect of increasing resting metabolic rate [52].
258 Kidney Diseases
Table 13.17 Glucose absorption from peritoneal dialysate (PD). Dietary protein restriction has led to poor growth in chil-
dren on HD. A small study in adults demonstrated a loss of
Grams of anhydrous 0.2 g amino acid/L filtrate in an HD session [83]. Protein
glucose per
intake in children on HD needs to be sufficient for growth,
PD solution
concentration 1 L 1.5 L 2 L Osmotic effect but moderated in order to minimise large variations in blood
urea levels between dialysis sessions. The aim for pre‐dialysis
1.36% 13.6 20.5 27.2 Weak hypotonic serum urea levels should be <20 mmol/L, provided the child
solution is not catabolic. For children on HD, an added dietary protein
2.27% 22.7 34.1 45.4 Intermediate intake of 0.1 g/kg/day should be appropriate to compensate
3.86% 38.6 57.9 77.2 Strong hypertonic for dialytic losses [22].
solution The protein requirements of children on PD are higher than
when on HD to allow for the greater reported transperitoneal
To calculate the energy obtained from glucose absorbed from PD fluid: losses of protein and amino acids, with the greatest losses
total the grams of glucose from all the exchanges, multiply by 4 kcal being seen in the smaller, younger child (Table 13.12). Daily
(17 kJ)/g and then multiply by 60%–80%.
peritoneal protein losses reduce from an average of 0.28 g/kg
in the first year of life to <0.1 g/kg in adolescents [84]. Dietary
However, other studies have shown a deficit of energy stores protein sources with a high phosphate content, including
in children on HD, which, when adjusted for lean body cow’s milk, dairy foods and foods with phosphate additives
mass, gives a similar resting energy expenditure to matched (Tables 13.13 and 13.14), need to be restricted to reduce the
healthy children [81]. Energy requirements should be calcu- dietary phosphorus load that is implicated in the pathogene-
lated based on the individual needs for growth and dialysis. sis of dialysis‐associated calcifying arteriopathy [22]. Infants
Subsequent adjustments for weight gain/weight loss should and children may require complete nutritional supplements
be made. either as sip or tube feeds (Table 13.4) to meet recommended
During PD glucose is absorbed from the dialysis fluid. It is protein intakes. High protein intake could negatively affect
estimated that glucose absorption from the dialysate can be acid–base status, bone mineralisation and fat‐free mass [85];
10–20 kcal (40–85 kJ)/kg/day [74]. Table 13.17 gives a guide therefore, any alterations to protein intake should always be
to the energy from glucose absorbed from PD fluid. Energy made along with ensuring an adequate energy intake.
intake for children on PD should be reduced when excess Consideration of serum urea, albumin and phosphate levels is
weight gain is seen. For those children on PD requiring addi- essential in tailoring an individual’s protein requirements.
tional energy intake, it is best to consider a nutritionally Hypoalbuminaemia is a marker of cachexia and protein
complete supplement (Table 13.4) in preference to a refined energy wasting (PEW) and has been associated with mortality
CHO supplement in view of the raised triglyceride levels in children initiating dialysis such that each 1 g/L fall in serum
seen in children on PD and the additional source of exoge- albumin level has been shown to relate to a 54% increase in
nous glucose derived from the PD fluid. These children also risk of death [86]. Rapid changes in albumin levels can, how-
have increased protein requirements and, therefore, benefit ever, be attributed to non‐nutritional factors including PD loss
from the protein content of complete supplements. The use of albumin, hydration status, the presence of systemic disease,
of complex CHO foods such as bread, potatoes, rice and liver function and a persistent nephrotic state.
cereals should be encouraged. The replacement of glucose in Protein requirements may be increased in patients with
PD fluid by glucose polymers (7.5% icodextrin) is beneficial proteinuria, as well as during episodes of peritonitis or other
in children with sodium and water overload; in addition the intercurrent infections. Peritonitis has a catabolic effect on
transperitoneal absorption rate is much lower than that of the body, and the permeability of the peritoneum for protein
glucose [80] and so contributes much less energy. The quan- and amino acids can increase by 50%–100%. The main pro-
tity of toxic glucose degradation products is also reduced. tein loss is albumin although other immunoglobulins are
Significantly, increased dialysis with an icodextrin daytime also lost. Serum albumin levels fall in these circumstances.
dwell in children on overnight APD showed no effect on Amino acid‐containing PD solutions have been suggested
albumin homeostasis in the short term [82], but longer‐term to replace transperitoneal losses and to reduce glucose load.
studies are awaited. Excess weight gain is emerging as a The ESPN working group found no evidence to suggest a
problem in children on PD in developed countries, and benefit in children [74].
dietary prescriptions need to be modified accordingly. There are losses of amino acids into the dialysate during
HD. There are limited and small studies on the use of intra-
Protein dialytic parenteral nutrition (IDPN) in children receiving
HD. An early study showed no improvement in amino acid
There are limited data to demonstrate the optimal amounts levels after supplementation; another study showed weight
of protein for children on dialysis, and existing data do not gain in three adolescents with organic illness after 6 weeks of
include all age ranges. Protein intake must be no less than starting IDPN [87]. It has been suggested that in patients
100% RNI for children on dialysis, with an addition to com- who do not respond to enteral supplementation, IDPN could
pensate for the losses of protein and amino acids across the be considered in those who have been losing >10% body
dialysing membrane (Table 13.12) [74]. weight for three consecutive months [87]. The use of IDPN
remains controversial and further clinical trials are needed. Increased dietary intake of energy and protein alone is not
There are potential side effects: hyperglycaemia, cramps and enough to reverse the catabolism associated with inflamma-
long‐term changes to liver function. tion. Adequate dialysis is essential. Current diet therapies in
the early stages of investigation into the PEW of CKD are
omega‐3 fatty acids and soya protein, used for their anti‐
Protein energy wasting
inflammatory properties [92]. A systematic review by Rangel‐
Huerta et al. reports a positive correlation between omega‐3
In patients with CKD, especially those undergoing mainte-
fatty acid supplementation and lowering of plasma bio-
nance dialysis, PEW is the strongest risk factor for adverse
marker levels. However, they conclude that further research
outcomes and death [88]. Younger age, duration of CKD and
is required before specific recommendations can be made
time on dialysis together with the presence of inflammatory
about the routine supplementation of omega‐3 fatty acids in
diseases are increased risk factors. PEW is characterised by
chronic renal disease [93]. A trial by Fanti et al., looking at the
the state of decreased body protein mass and fuel reserves.
dietary effect of soy in adult patients with ESRD, suggests a
The PEW seen in CKD is a slow, progressive process. Initially,
possibility of beneficial effects on inflammatory and nutri-
there is slightly impaired nutrient intake and absorption
tional status of HD patients. They acknowledge that larger
plus an increase in inflammatory markers in seemingly well‐
clinical trials are needed [94]. The treatment of inflammation
nourished children. In the second phase, depletion of tissue
to improve body composition and linear growth in children
levels and body stores occurs with a change in biochemical
with CKD is likely to become a cornerstone in management.
and physiological functions; these changes progress with
time and marked cachexia is seen [89].
PEW is the result of multiple mechanisms characteristic to Nutritional supplements
CKD including undernutrition, systemic inflammation, co‐
morbidities, hormonal derangements, dialysis procedure For infants to meet their energy and protein requirements,
and consequences of uraemic toxicity. PEW may cause infec- protein supplements with a lower phosphate content can be
tion, CVD, frailty and depression; these complications may added to standard whey‐based infant formulas, in combina-
also increase the extent of the PEW [90]. tion with energy supplements (Table 13.4). Alternatively,
Inflammation is an important cause of cachexia and PEW where biochemical parameters allow, infant formulas can be
in patients with CKD. An increase in pro‐inflammatory concentrated progressively to provide an increased balance
cytokines, tumour necrosis factor alpha and interleukin‐6 are of all nutrients or energy‐dense infant formulas can be used
seen [91]. These act through the hypothalamus to affect appe- (Table 1.18). Biochemistry should be frequently monitored,
tite and metabolic rate. In turn, poor protein anabolism particularly with respect to potassium, phosphate, calcium,
results in a reduction in serum albumin and prealbumin. sodium and urea. A combination of Kindergen or Renastart
Levels of albumin, prealbumin and C‐reactive protein (CRP) (renal specific low phosphate and potassium infant formulas)
can be used to assess the degree of inflammation or illness, and a standard whey‐based infant formula is used to design
but should not be used as an indicator of nutritional status. a feed to correct high serum phosphate and potassium levels.
Table 13.18 Case study: A young child with chronic kidney disease with a high serum potassium levels.
A 1‐year‐old girl, diagnosed with renal dysplasia, is running high serum potassium levels 5.6 mmol/L. Her current feed is 800 mL of a
whey‐based infant formula, taken orally. She currently does not take any solids.
Wt = 8.5 kg (25th centile). Ht = 72 cm (0.4th centile).
Energy requirement: 72 kcal (300 kJ)/kg. Protein requirement: 1.2 g/kg.
Feed Energy (kcal (kJ)) Protein (g) Na (mmol) K (mmol) Ca (mmol) PO4 (mmol)
Cow & Gate 1 per 100 mL 66 (278) 1.3 0.74 1.8 1.3 1.0
800 mL provides per kg 62 (262) 1.22 0.7 1.7 1.26 0.9
Her feed is changed to a 50:50 mixture of normal infant formula with renal specific low potassium formula, Renastart, to reduce her potassium
intake. There is a beneficial increase in energy intake. Note changes in protein, Na, Ca and PO4 intakes. Her serum biochemistry results and
growth pattern will determine if further changes to the feed profile are necessary. Excellent communication with the multidisciplinary team,
together with regular monitoring, is essential.
Feed Energy (kcal (kJ)) Protein (g) Na (mmol) K (mmol) Ca (mmol) PO4 (mmol)
½ strength Cow & Gate per 100 mL 33.5 (140) 0.65 0.37 0.9 0.65 0.5
½ strength Renastart per 100 mL 45.5 (207) 0.75 1.05 0.3 0.3 0.3
800 mL provides 632 (2640) 11 11 9.6 7.6 6.4
800 mL provides per kg 74 (310) 1.3 1.3 1.13 0.9 0.75
260 Kidney Diseases
For infants >12 months of age, or whose weight is greater allow space for nutrition and to avoid overconcentration of
than 8 kg, nutritionally complete supplements can be consid- feeds in order to meet nutritional requirements in a small
ered (Table 13.4). Combining feeds and supplements to volume of fluid.
achieve specific intakes of particular nutrients is a common Meticulous attention should be given to fluid manage-
practice to achieve nutritional and biochemical goals. A case ment to avoid the cardiovascular complications of long‐term
study to show how feeds can be modified to control serum fluid overload. Educating children about their fluid restric-
potassium levels is given in Table 13.18. tion should include practical ways of reducing fluid intake
Nutritional supplements may be useful for children and including using tablet rather than liquid medicines; the judi-
adolescents depending on dialysis modality and biochemi- cious use of foods with a high water content such as jelly,
cal parameters. gravy, sauces, yoghurt and milky puddings; and freezing
drinks and sipping the fluid as it melts. In older children
sucking sugar‐free boiled sweets or chewing gum may help
Carnitine along with drinking from small cups/glasses. Thirst preven-
tion techniques, including reducing salt intake and good
Carnitine is an amino acid derivative that has a key role in the mouth care, should be considered. Involving younger
regulation of fatty acid metabolism and adenosine triphos- children in devising fluid record charts can aid compliance.
phate (ATP) formation. Altered carnitine metabolism is seen It is also better, psychologically, to talk about a fluid allow-
in CKD; limited protein intake, impaired carnitine synthesis, ance rather than a fluid restriction. Case studies showing
malnutrition and dialysis all contribute. A low serum free example feeds for children on HD and PD are given in
carnitine concentration can be seen in paediatric dialysis Tables 13.19 and 13.20.
patients [95]. Carnitine supplements have been proposed as a
treatment for symptoms or complications of dialysis includ-
ing intradialytic arrhythmias, skeletal muscle cramps, hyper- Sodium
triglyceridaemia and anaemia. Further research to support Infants and children, especially the polyuric infant, on PD
the routine supplementation of children on dialysis is needed. can become hyponatraemic (serum sodium <130 mmol/L)
In adults, a systematic review and meta‐analysis reported due to the sodium losses into the UF. To maintain sodium
that two out of seven trials showed l‐carnitine supplementa- balance, medicinal salt supplements are prescribed if increas-
tion significantly decreased the percentage of patients who ing enteral sodium intake does not correct levels. Conversely,
experienced dialysis cramping symptoms at the end of an those children on PD who are hypertensive and oedematous
HD session [96]. The authors comment, however, that no require education regarding a ‘no added salt’ diet (Table 13.7).
definitive conclusions should be drawn due to the lack of Hypertension and excess interdialytic weight gain seen in
data available. With regard to the effects of l‐carnitine on children on HD are invariably related to salt and water over-
haemoglobin and erythropoietin dose, the meta‐analysis load. The importance of a sodium‐restricted diet needs to be
failed to confirm previous findings that supported supple- reinforced to reduce both thirst and fluid intake. An intake
mentation. There was no significant decrease in serum LDL between 1 and 3 mmol/kg body weight/day is usually
cholesterol levels with supplementation. acceptable.
Fluid and electrolytes Potassium

A child with a good urine output can cope with a more lib-
Fluid
eral potassium intake. In anuric or anephric infants and chil-
Fluid allowance is prescribed for the individual depending dren, dietary potassium modification is invariably indicated.
on insensible losses, residual urine output and dialysis In adolescents on APD, or those who are having large vol-
modality. Insensible fluid losses are calculated as 400 mL/m2 umes of dialysate with CAPD, a moderate intake of potas-
body surface area per day or approximately 20 mL/kg body sium can usually be allowed. However, advice should be
weight/day. On PD the fluid removed by ultrafiltration is targeted at preventing overindulgence of potassium‐rich
also included in formulating fluid prescriptions. Fluid foods and drinks, e.g. potato crisps may be taken occasion-
weight gain between HD sessions can be problematic espe- ally, but suitable low potassium corn snacks are preferable;
cially if the child is anuric; the fluid allowance is based on squash should be drunk in preference to pure fruit juices.
insensible fluid losses and fluid removal between dialysis Although HD is very effective at clearing potassium,
sessions. Ideally, interdialytic weight gain should not exceed because of the intermittent nature of the treatment (typically
5% of the child’s estimated dry weight. Prolonged fluid three times a week), children on IHD invariably require die-
overload in HD can cause cardiac problems, including car- tary potassium advice to minimise problems with hyper-
diomyopathy. Accurate weighing of patients with careful kalaemia (Table 13.5). Some dialysis units allow potassium
interpretation of the intake and output of fluids can help treats such as crisps or chocolate while receiving HD; these
with the interpretation of fluid balance. should be eaten within the first 30 minutes of HD and be
In children and infants receiving enteral feeds, the fluid given in controlled amounts so that the potassium can be
allowance needs to be negotiated with the medical staff to cleared during the dialysis session.
Table 13.19 Case study: Meeting the nutritional requirements of a child on haemodialysis.
A boy aged 4 years and 1 month, with CKD stage 5 due to non‐recovery of renal function post‐cardiac transplant. He has HD three times a week.
Wt = 13.2 kg (2nd centile). Ht = 0.98 m (9th centile).
Fluid allowance 800 mL/day.
This young boy is on a hydrolysed protein formula as he has always experienced feed intolerance due to poor gut perfusion, a consequence of
his cardiac condition. With his history of poor weight prior to starting HD, the hydrolysate formula was continued. His feed is delivered via a
nasogastric tube (he has been tube fed since his was 2 weeks old). He occasionally picks at food, but has no other oral intake.
Pre‐dialysis blood results: Na 136, K 4.9, Ca 2.44, PO4 1.6, urea 17.
His feed, as shown below, is not complete for all B vitamins. The addition of more Paediatric Seravit to give a greater intake of a range of vitamins
and minerals would increase the phosphate content of the feed further, hence has 1 Ketovite tablet a day to provide extra B vitamins. He also has
a small dose of calcium‐containing phosphate binders that provide some elemental calcium (this has helped keep his serum calcium in the
acceptable range).
Feed recipe Amount Energy (kcal (kJ)) Protein (g) Na (mmol) K (mmol) Ca mmol PO4 mmol
Peptamen Junior 17% 153 g 699 (2922) 21 20.2 24.3 16 13.6

Duocal 14% 126 g 620 (2592) 0 1.1 0.13 0.2 0.2
Paediatric Seravit 0.6% 5.4 g 15 (63) 0 0 0.04 3.2 2.7
+ water to 900 mL
Total per 100 mL 148 (619) 2.3 2.4 2.72 2.1 1.8
Total per 800 mL 1184 (4949) 18.4 19.2 21.76 16.8 14.4
Total per kg 89 (372) 1.4 1.4 1.63 1.3 1.1
CKD, chronic kidney disease; HD, haemodialysis.
Table 13.20 Case study: Meeting the nutritional requirements of a child on peritoneal dialysis.
A boy aged 3 years and 8 months, diagnosed with FSGS, thought to be secondary to tacrolimus toxicity (given as immunosuppression for
previous cardiac transplant). He has a single functioning kidney and is on daily overnight PD.
Wt = 13.2 kg (9th centile). Ht = 0.93 m (2nd centile).
Fluid allowance = 800 mL/day.
Post‐dialysis blood results: Na 146, K 4.5, Ca 2.57, PO4 1.81, urea 13.1.
His feed is delivered via a PEG.
The feed meets the RNI for vitamins except for B6 (95%) and niacin (77%). As a prudent measure he has 1 Ketovite tablet a day. The feed meets
57% RNI for vitamin A, serum level within normal range. The feed does not meet the RNI for Na (70%), but serum level is in the normal range
and he is growing well.
Feed recipe Amount Energy (kcal (kJ)) Protein (g) Na (mmol) K (mmol) Ca (mmol) PO4 (mmol)
Nutrini 75% 750 mL 750 (3135) 21.0 19.5 21.0 11.3 12.0
Duocal 11% 110 g 541 (2261) 0 0.1 0.11 0.1 0.2
ProSource TF 1.5% 15 mL 19 (80) 4.4 0.1 0.06 1.7 1.1
+ water to 1000 mL
Total per 100 mL 131 (548) 2.5 2.1 2.12 1.3 1.3
Total per 740 mL 969 (4052) 18.5 15.5 15.6 9.6 9.6
Total per kg 73 (305) 1.4 1.2 1.19 0.6 0.7
FSGS, focal segmental glomerulosclerosis; PD, peritoneal dialysis; PEG, percutaneous endoscopic gastrostomy; RNI, reference nutrient intake.
Hyperkalaemia can result in fatal cardiac arrhythmias. high serum potassium level to achieve an acceptable base-
When plasma levels are >6.5 mmol/L, there is a prolonga- line level due to the movement of potassium from the intra-
tion of the PR interval and peaking of the T wave on electro- cellular fluid.
cardiogram (ECG). In such instances salbutamol is prescribed Education about potassium intake needs to be tailored to
to enhance cellular potassium uptake. An ion exchange resin each individual. Advice on adapting recipes at home to lower
such as calcium resonium can be used as a crisis manage- potassium content of meals may be helpful. Intake needs
ment strategy. It can take several HD sessions following a to be reviewed at frequent intervals together with blood
262 Kidney Diseases
biochemistry results and dietary analysis. A photographic with uraemia. Vitamin A is also not removed in dialysis.
album of foods rich in potassium and food models can be use- Elevated levels of vitamin A in CKD have been associated
ful educational tools. Older children need to be involved in with hypercalcaemia, anaemia and hyperlipidaemia [102]. A
decision making and the setting of targets when discussing study has shown that those children on exclusive or supple-
serum potassium levels. Having potassium ‘swaps’ can also mental feeding received a higher vitamin A intake and had a
be helpful in this age group, e.g. a 5–10 mmol potassium ‘treat’ serum vitamin A level above the upper limit of normal com-
a day of their choice; this could be an extra piece of fruit or pared with those on diet alone [103]. It was also shown that
vegetable portion, a small portion of chocolate or some crisps. those children on dialysis were more likely to have a higher
vitamin A level relative to their vitamin A intake compared
with those children not on dialysis. An excessive intake of
Phosphate vitamin A should be avoided. An intake close to the RNI is a
sensible practice target [103]; however, this can be difficult to
Phosphate restrictions continue when on dialysis (Table 13.6).
achieve when the vitamin A contribution from feeds and
In adults 800 mg of phosphate is typically removed during
nutritional supplements is also considered.
each HD session and 300–400 mg/day on PD. Removal fig-
Vitamin D has been discussed earlier (p. 253).
ures will be lower in children due to lower flow rates and
Homocysteine is an intermediary of methionine metabo-
volume of dialysate used.
lism that, at raised levels, is a risk factor for CVD.
As with potassium restriction advice needs to be tailored
Hyperhomocysteinaemia is common in adult patients with
to each individual. Education and support around the taking
chronic renal insufficiency and appears to relate to reduced
of phosphate binders is also advisable.
clearance of plasma homocysteine. Supraphysiological
folic acid treatment has been used to normalise homocyst-
Micronutrients eine levels in CKD, but a recent systematic review has
shown that homocysteine lowering based on folic acid does
Little is known about the essential micronutrient require- not reduce cardiovascular events in people with kidney
ments or biochemical status of children with CKD. It is rec- disease and should not be used as such [104]. Increased
ognised that children with CKD on dialysis are at risk of cancer outcomes have been shown for patients on high lev-
vitamin and mineral deficiencies. This may be due to inad- els of folic acid [105].
equate intake, poor absorption and dialysis‐related losses Low serum zinc and copper levels were seen in a study of
[22]. Individual dietary assessment is essential, taking into paediatric patients on dialysis, some of which were sup-
account intakes from diet, infant formulas, oral nutritional plemented [106]. Zinc and copper is cleared by dialysis,
supplements and enteral feeds, the latter often being the which could explain the low levels in this group. Low zinc
sole source of nutrition for many younger patients. Only levels can result in anorexia, impaired would healing and
then can micronutrient supplements be individually and faltering growth. Papers in adult studies discuss the theo-
safely prescribed, where indicated [27]. Dietary assess- retical risk of both deficiency and accumulation of trace ele-
ment has numerous limitations, but can be supported with ments depending on dietary intake, removal by dialysis,
regular measurement of serum levels of vitamins and min- composition of source water and residual kidney function
erals that may guide when to start supplementation and [107]. It is helpful to measure serum levels before starting
what to give. supplementation as these trace elements have impaired
The RNI for healthy children of the same age and sex [18] clearance with reduced renal function. Further studies are
provides guidelines for children with CKD [97] and should needed in order to evaluate the benefit of supplementation
be aimed for in stages 2–5 CKD, with the exception of on clinical outcomes.
calcium, phosphate, magnesium, sodium and potassium,
Infants and children receiving nutritional support from
which may not bear any relation to recommended dietary complete feeds, usually by the enteral tube feeding route, are
reference values. less likely to require extra vitamin and minerals. Older chil-
For children on dialysis a water‐soluble vitamin supple- dren, with an inadequate diet and poor compliance with oral
ment is often prescribed as a prudent measure, although a nutritional supplements, may benefit from micronutrient
recent study measuring serum levels of B vitamins of supplements.
mainly unsupplemented children on dialysis showed nor- Micronutrient intakes can be greater than the RNI when
mal to high levels of these in all children [98]. Adult renal adult renal specific feeds are used solely or in combination
studies have shown that there are potential dialysate losses for children. It needs to be borne in mind that some nutri-
of vitamins C, B6 and folic acid [99]. Published adult rec- ents, including pyridoxine and magnesium, can have toxic
ommendations for these vitamins are likely to be too high effects at high intakes. Dietary intake should be evaluated
for the majority of paediatric patients [100]. Excessive and serum levels measured where intake far exceeds the RNI
intakes of vitamin C should be avoided as elevated oxalate for all vitamin and minerals.
levels can lead to the development of vascular complica- To aid compliance and acceptability, the taste and presen-
tions [101]. tation of micronutrient supplements are important fac-
Vitamin A levels are invariably increased in the serum of tors. Ketovite tablets (dose 1–3 per day) are most widely
children on dialysis as retinol binding protein levels increase prescribed.
Feeding Problems in CKD 263
Encapsulating peritoneal sclerosis feeding, which can result in vomiting and/or refusal of for-
mula or food as well as having a detrimental effect on nor-
Encapsulating peritoneal sclerosis (EPS) is a rare, but serious mal oral feeding behaviour in the long term [114]. Data from
complication of long‐term PD. It involves the formation an the International Pediatric Peritoneal Dialysis Network
inflammatory and later fibrotic ‘cocoon’ surrounding the (IPPN) demonstrated a benefit of gastrostomy over NGT
gastrointestinal tract [84]. The result is abdominal inflamma- feeding. A possible explanation is the increased vomiting
tion and intestinal obstruction. The clinical presentation associated with an NGT, which can act as a stent passing
includes abdominal pain, nausea, vomiting, weight loss, through the gastro‐oesophageal junction [30]. Placement of a
low‐grade fever and ultrafiltration failure [108]. The treat- gastrostomy button or percutaneous endoscopic gastros-
ment is immunosuppression or surgery (partial or complete tomy (PEG) tube in a child already on PD may not be ideal as
enterolysis). Post‐surgery, PN is commenced. The possibility it carries the risk of peritonitis. Ledermann et al. recommend
of refeeding syndrome may need to be considered (p. 63). placement prior to a PD catheter [114], while two other
Enteral feeds are gradually reintroduced. A 10‐year study groups report no statistical difference with gastrostomy
showed a prevalence of 1.5% in paediatrics, and the outcome insertion prior to or after PD catheter insertion [115, 116].
data was significantly better then seen in the adult popula- Vomiting can be an ongoing problem for some infants;
tion [109]. feed prescriptions should be closely monitored and altered
appropriately. Some infants are sensitive to changes in their
fluid balance, and this should be considered in relation to
Feeding problems in CKD vomiting. Persistent vomiting is stressful for families, and
close dietetic and team support is required in the long term
Improved clinical experience in dialysis techniques and [72]. Gastro‐oesophageal reflux (GOR) and disturbances in
renal transplantation has seen increasing numbers of infants gastrointestinal motility are common in infants with CKD
taken onto end‐stage management programmes. The ulti- [117], and investigations to detect and treat appropriately are
mate goal is early transplantation; this is technically more essential. Advice about appropriate positioning of the baby
complex in the very small child. Most units prefer to pro- when feeding should be initially given and a thickened feed
mote the growth of the child to a body weight >10 kg or can be tried (p. 133). Gastroparesis (delayed gastric empty-
length >80 cm before they are eligible for transplantation. ing) can be treated with prokinetic agents such as metoclo-
Optimal nutrition, with or without early dialysis, is essential pramide, erythromycin and domperidone. Due to concerns
in the care of these infants and young children since growth with potential side effects and lack of robust evidence, these
is crucially nutrition dependent during the first 2 years of medications are prescribed with caution. Some medications,
life. Nutrition has been one of the most important factors including calcium channel blockers and calcitonin, can delay
responsible for the improved outcomes and improved gastric emptying and should be reviewed. Persistent GOR
growth seen in this population [110, 111]. Data on growth, can respond to proton pump inhibitors such as omeprazole
without the use of GH, and the dietetic contact necessary to and lansoprazole [118]. In extreme cases a fundoplication
manage and support children and their families receiving may be indicated to manage persistent vomiting [74].
chronic PD and intensive nutrition support illustrates the Caregivers, especially those of infants, need frequent
essential role of paediatric renal dietitians in the manage- reassurance that lack of interest in food and anorexia are
ment of such families [112]. The provision of adequate nutri- symptomatic of renal failure.
tion for growth requires frequent adjustments of nutritional Weaning should be encouraged at the customary recom-
prescriptions in accordance with blood biochemistry, mended age to enable the development of oral feeding expe-
especially in preschool children. riences and the reduction of sensitisation to food. The feeding
Once diagnosis is established, there may be a period of problems seen in infants and young children with CKD are
conservative management to determine if renal function multifactorial. Many of these infants commonly pass large
improves or stabilises. Appetite is poor in the infant with volumes of dilute urine; this creates a thirst and preference
CKD, vomiting is common, and there is usually a reluctance for water rather than formula. The large number and volume
to feed spontaneously. This impacts on both growth and of prescribed medications can contribute to refusal to take
biochemical stability. Supplementary enteral feeding is adequate formula by mouth. Some of these infants have dis-
indicated early to achieve and maintain growth and neu- ordered taste perception and refuse energy‐dense sweetened
rodevelopmental progress when oral feeding is insufficient. foods in preference for salty foods. They often find difficulty
In addition, salt and water should not be restricted in the in swallowing lumpy foods and fail to progress from puréed
salt‐wasting polyuric infant as this will also adversely baby foods to more energy‐dense family foods; in extreme
impact on growth [27]. Initiation of enteral feeds before circumstances even puréed foods may cause choking and
height deficits were noted has been associated with superior retching [119]. Caregivers need reassurance that it is typical
height outcomes compared with initiation after growth had for a child with CKD to only take small amounts of food and
faltered [113]. drink and that the early introduction of enteral feeding is
Tube feeding reduces some of the parental anxieties recommended before growth failure is evident. Positive rein-
associated with oral feeding while assuring nutritional and forcement with the use of dummies (pacifiers) and oral feed-
medication prescriptions are met. It is preferable to force ing while receiving daytime enteral bolus feeds should be
264 Kidney Diseases
encouraged to help minimise feeding issues [120]. A review

• Energy requirements are the same as those of healthy chil-
article summarises some common oral feeding challenges
dren; energy intakes below the EAR contribute to growth
and offers useful strategies and interventions [121].
failure
Enteral feeding regimens that provide a balanced fat and
• Protein restriction shows no significant impact on delaying
CHO profile to meet energy requirements do not enhance
progression of renal failure and there is an association with
the hyperlipidaemia seen in CKD [122].
inferior growth
• Protein intake should be optimised to allow for the mainte-
Nutritional support nance of nitrogen balance and growth, together with the
preservation of lean body mass
Prevention of growth disturbances is a major goal of nutri- • Protein must provide at least 100% of the RNI for age to
tional therapy. The early initiation of enteral nutritional avoid protein becoming a limiting factor in growth
support is considered when the child’s oral intake fails to • When on dialysis additional protein may be needed to com-
meet recommended nutritional requirements and growth pensate for the losses of protein and amino acids across dia-
velocity is affected. Prolonged trials of oral supplements lysing membranes
should be discouraged. Brief intervals of poor growth dur- • Hyperkalaemia can be exacerbated by acidosis – extracellu-
ing infancy can result in significant loss of height potential. lar potassium shifts occur with metabolic acidosis as bicar-
Where oral supplementation is unsuccessful, enteral tube bonate is lost through the kidney; acidosis is corrected with
feeding should be instigated early before significant nutri- administration of sodium bicarbonate
tional deficits and aversive feeding interactions have devel- • Vitamin D deficiency is prevalent and often severe and con-
oped between the child and family. tributes to abnormalities in calcium, phosphate and PTH
There needs to be a discussion with the family and the homeostasis
MDT as to the most appropriate feeding route for each child. • Management of CKD‐MBD should be based on serial
Essentially, a shared team philosophy of early and sustained assessments of phosphate, calcium, PTH and vitamin D
nutritional support is required [123]. Play preparation with levels; dietary management: assessment and manipulation
the use of DVDs, photograph albums, booklets and dolls can of calcium and phosphate intakes, treatment of vitamin D
assist in teaching, while some caregivers find it helpful to deficiency
talk to other families with similar experiences. • Reducing dietary phosphate in the early stages of CKD is a
The delivery of the feeds must be tailored to the individual possible strategy to delay disease progression and decrease
child and their home circumstances. Intermittent enteral mortality risk from CVD
tube feeding can be given as daytime boluses or serve as a • The lifelong nature of CKD reinforces the importance of
top‐up if oral feeds are not completed. These bolus feeds can dietetic involvement in reducing CVD risks: management
be given as gravity feeds or given more slowly through an of fluid levels, hypertension, obesity and regulation of
enteral feeding pump. Initially, slower rates may be required CKD‐MBD and levels of vitamin D
for more concentrated feeds to improve tolerance [112]. • Nutrition can be one of the more demanding parts of man-
A continuous overnight infusion via a pump can be benefi- agement; an understanding of the psychosocial effects of
cial in those infants with more severe GOR and may reduce feeding children is as important as the nutritional advice
vomiting; however, many community healthcare profession-
als will not supervise this feeding method, especially if the
child has an NGT rather than a gastrostomy device in situ. If
poor tolerance of feeds is having a negative effect on growth,
Renal transplantation
jejunal feeding should also be considered.
Renal transplantation is the treatment of choice for children
with stage 5 CKD to restore normal or near‐normal physiol-
ogy and metabolic function without dialysis and minimal
Learning points: nutritional management of chronic dietary restrictions. Survival of children with an allograft is
kidney disease superior compared with those remaining on dialysis. The
donor kidney can come from a living related, living unre-
• Considerations: adequacy of energy and protein intakes; lated or deceased donor. Pre‐emptive transplantation results
fluid and electrolyte balance; regulation of calcium and in improved graft survival and reduced mortality compared
phosphate intakes; correction of acid–base abnormalities; with dialysis followed by transplantation [21]. Children on
adequacy of micronutrient and iron intakes the UK cadaveric transplant waiting list are given priority
• Dietary requirements depend upon age, stage of CKD, clin- over adults, and an average wait is 286 days (2016–2017
ical management and nutritional assessment data) [124]. Living related donor (LRD) transplantation is
• Prevention of growth disturbances is a major goal of nutri- increasing. This has the advantages of shorter waiting times
tional therapy; early initiation of enteral nutritional sup- and improved graft survival. Five‐year paediatric allograft
port is considered when oral intake fails to meet recommended survival is 91% for LRD and 79% for cadaveric transplants
nutritional requirements and growth velocity is affected [21]. Of the 127 transplants in the 2016–2017 data, 72 were
LRD, 3 of these through the paired exchange scheme.
Renal Transplantation 265
Post‐transplantation medications aim to prevent graft rejec- may benefit from a behaviour modification approach [127].
tion and include the calcineurin inhibitors cyclosporin and Although a renewed appetite is positive in the initial
tacrolimus, mycophenolate and steroids. Minimising steroid stages of management, excessive weight gain and obesity in
exposure can improve linear growth and reduce metabolic the long term must be avoided. Both the child and family
disorders. Early steroid withdrawal has been shown to sig- should be reminded of this soon after transplant. The princi-
nificantly help growth at 6 months post‐transplant especially ples of a sensible, healthy eating, well‐balanced diet for all
in pre‐pubertal children [125]; improved lipid and glucose the family is advised prior to discharge from hospital.
metabolism profiles were also seen. Nutritional advice All patients on immunosuppressive therapy need to take
continues to be an important feature of treatment post‐
care with food hygiene and avoid foods that carry a high risk
transplant with the dietitian continuing to be involved with of food poisoning organisms such as Listeria and Salmonella;
the ongoing management. this should be discussed with each child and family prior to
discharge.
Hypertension can present following transplantation and
Initial dietary management antihypertensive therapy is prescribed. Early post‐trans-
plantation systolic hypertension strongly and independently
Immediately after transplantation, the main concerns for the predicts poor long‐term graft survival in paediatric patients
recipient include the complications of rejection and infection. [128]. Arterial wall stiffness has been demonstrated in young
Feeding commences on the return of normal bowel sounds. If adults with ESRD since childhood, with hypertension being
there are no complications, the child usually develops an the main determinant [129]. Weight control and advice
appetite as renal function improves and previous dietary regarding salt intake, as part of the healthy eating recom-
restrictions can be relaxed in line with biochemical results. mendations, should be encouraged.
Fluid balance is dependent on output and is assessed daily Dyslipidaemia is seen in some children following trans-
by medical staff. A high fluid intake is initially encouraged to plantation and requires regular assessment. An evaluation
perfuse the transplanted kidney. Serum phosphate levels 2–3 months after transplantation and annually thereafter is
typically fall below reference ranges due to the large tubular recommended [130]. Studies have identified that 40% of
and urinary losses; dietary advice should encourage phos- deaths in adult renal transplant patients are attributed to
phate‐rich foods and drinks at this stage. Invariably phos- CVD and they occur at a younger age than in the general
phate supplements are prescribed in the early post‐transplant population [131]. There is growing evidence that dyslipidae-
days to match urinary losses. Serum magnesium levels can mia hastens the progression of renal disease itself. Disordered
also fall and require medicinal supplementation. Those chil- lipoprotein metabolism results from complex interactions
dren who experience acute tubular necrosis following a renal among many factors including the primary disease process,
transplant require a period of c onservative management or use of medications such as corticosteroids, the presence of
dialysis therapy, including appropriate dietary modification, malnutrition or obesity and diet [132]. All children with
until adequate renal function is achieved. dyslipidaemia should follow the recommendations for ther-
In infants and children receiving enteral feeds pre‐trans- apeutic lifestyle changes [131]. Dietary modification should
plant, concerns have been raised about a prolonged transi- include advice favouring monounsaturated and polyunsatu-
tion to exclusive oral nutrition [120]. Others have shown that rated fats and oils in preference to saturated fats, together
long‐term enteral tube feeding does not preclude the transi- with encouraging the regular consumption of omega‐3 fatty
tion to normal feeding and the majority of children will eat acids and antioxidants from fruit and vegetable intake.
and drink after a successful renal transplant [110]. Feeding Moderate physical activity is recommended.
dysfunction and impaired oromotor development appear to
be more evident in infants who received NG feeding than in
those who had gastrostomy buttons for feeding [126]. Ongoing dietary management
It is recommended to cease tube feeding, whenever possi-
ble, at the time of renal transplantation in order to stimulate Children still receiving nutritional support post‐transplant
appetite as renal function is restored, especially if higher should be regularly reviewed in the outpatient clinic. A transi-
doses of corticosteroids are prescribed. To do this success- tion period to encourage the oral route of feeding should be
fully, the medical staff, dietitian and team members need to agreed with families. To stimulate the appetite, a reduced vol-
provide ongoing support to families. Most children do well ume of bolus feed should be given during the day. Vitamin and/
and resume normal eating and drinking post‐transplant [110, or trace mineral preparations may be required in those children
126]. There will always be exceptions to this approach with whose micronutrient intakes are poor. Iron status should also be
some children requiring short periods of nutritional support, monitored. Many younger children struggle with fluid targets
particularly in the first few weeks or months post‐transplan- post‐transplant and require bolus top‐ups with water.
tation. In such patients a planned and agreed strategy to Transplantation restores the conditions to promote more typ-
wean off enteral tube feeding must be implemented. Common ical growth. However, (when used) corticosteroids as well as a
experience is that some young children take time to adapt to low GFR in the graft kidney will both have growth suppressive
drinking more fluids. In such cases fluid boluses delivered effects. Steroids suppress growth mainly by interacting with
via the enteral feeding tube are given short term. Severe eat- the GH/IGF‐1 axis and by affecting the growth plate [133]. A
ing difficulties present in a small number of children; these retrospective analysis of longitudinal growth in children who
266 Kidney Diseases
had been weaned off steroids within 6 months of transplant therapy and appropriate dietary advice. Hyperglycaemia is
showed improved height growth [28]. A nutritionally adequate also seen in a small number of children when acute rejection
balanced diet should be established to sustain normal growth episodes are treated with pulses of methylprednisolone; this
while guarding against overnutrition. effect is often transitory.
The prevention of weight gain leading to obesity can be a Chronic rejection of the transplanted kidney will eventu-
difficult problem particularly for adolescents where body ally result in the child returning to dialysis with appropriate
image is important. The patient who was anorexic prior to dietary intervention as for CKD.
transplantation may not engage in discussions to modify food
intake to control body weight. Adolescents who experience
excess weight gain and change of body image can be suscep- Learning points: renal transplantation
tible to crash dieting and possible fasting to lose weight.
Healthy eating and exercise should always be encouraged, • Nutritional advice continues to be important post‐trans-
including information on the health risks of alcohol and smok- plant; weight control and advice regarding salt intake, as
ing. Adolescents need to be included in setting their own die- part of the healthy eating recommendations, should be
tary targets. Paediatric data looking at weight status at encouraged
transplant found that obese recipients were at higher risk of • Studies have identified that 40% of deaths in adult renal
mortality and graft failure compared with normal weight transplant patients are attributed to CVD and they occur
patients. Overweight patients also had greater risk of graft at a younger age than in the general population
failure, acute rejection and delayed graft function. Obese chil- • Overweight patients have a greater risk of graft failure,
dren either pre‐ or post‐transplant experience higher work- acute rejection and delayed graft function; obese children
load within the nephrons that contributes to graft loss [134]. either pre‐ or post‐transplant experience a higher workload
A small number of children develop steroid‐induced within the nephrons that contributes to graft loss
diabetes mellitus post‐transplant, which requires insulin

Nephrotic Syndrome and Congenital Nephrotic Syndrome

Shelley Cleghorn
Nephrotic syndrome Dyslipidaemia results from several underlying complex

mechanisms including increased production of cholesterol,
Nephrotic syndrome (NS) is an umbrella term for a group of triglycerides and lipoproteins in the liver, decreased activity
clinical features: proteinuria (early morning urine protein–cre- of lipoprotein lipase and reduction of the albumin transpor-
atinine ratio >200 mg/mmol), hypoalbuminaemia (<25 g/L), tation of cholesterol in the blood [135].
3+ protein on urine dipstick and oedema with or without NS may be due to an inherited condition or it may be
hyperlipidaemia. The kidneys have a filtration barrier made acquired due to an infection, allergy, neoplasm, drugs or
up of a membrane and cells called podocytes with foot‐like another disease process such as inflammation of the blood
processes and a slit diaphragm. When there is disruption of the vessels (vasculitis). It is not always possible to determine the
foot‐like processes, the filtering membrane does not function exact cause of the NS; hence, it is termed idiopathic nephrotic
properly, resulting in protein leakage into the urine. This syndrome (INS).
results in reduced protein in the blood and lowers the plasma NS can be classified according to:
oncotic pressure. Water then moves from the blood vessels to
• age
the body tissues causing swelling (oedema).
• response to steroids
Proteins have important functions in the blood. They:
• histology
• regulate the amount of water in blood vessels • genetics
• act as carriers for many substances in the blood, such as
Congenital nephrotic syndrome (CNS) is usually diag-
hormones and lipids
nosed in the first 3 months of life (p. 269). Infantile NS
• prevent blood from clotting
presents between 3 months of life and a year of age.
• are important for the growth and development of children
Steroid‐sensitive NS (SSNS) includes frequently relapsing
• and, in the form of antibodies, are an important part of
(FRNS) and steroid‐dependent NS (SDNS). 80%–90% of chil-
the immune system
dren with INS will respond to treatment with steroids within
When a large amount of protein is lost in the urine, the 4 weeks. FRNS is when there are ≥2 relapses in 6 months or
child can become oedematous, be prone to infections, become ≥4 relapses in 1 year. In the case of SDNS, the child relapses
anaemic, suffer poor growth and be prone to blood clots. within 2 weeks of stopping steroids, or while they are still on
Nephrotic Syndrome 267
steroids. Steroid‐resistant NS (SRNS), as the name suggests, Dyslipidaemia and diet

is when the child does not respond to steroids; 10%–20% of
Unfortunately there is very little evidence to guide on the
children with INS have this type of disease.
optimal treatment of dyslipidaemia in patients with NS
NS results from changes in the kidneys. These changes
[137]. Dietary supplements, such as fish oils, have been
include:
poorly studied in NS. Two studies examining omega‐3
• minimal change disease (MCD) – very small changes to fatty acids have shown some positive effects; however, the
the glomeruli that can only be seen under an electron studies have a small number of patients and limited fol-
scanning microscope low‐up [138].
• focal segmental glomerulosclerosis (FSGS) – some of the Other lifestyle changes include weight control in patients
glomeruli are damaged and become scarred who are overweight and increased exercise. These recommen-
• membranoproliferative glomerulonephritis (MPGN) – dations have never been formally studied in patients with NS;
the glomeruli become inflamed however, they seem a sensible lifestyle change together with
the use of monounsaturated and polyunsaturated fats and a
A renal biopsy is usually not necessary at diagnosis as it is
decrease in saturated fats. Care must be taken not to compro-
the responsiveness to steroids that is more predictive of the
mise the energy intake of children who have poor appetites
child’s outcome. Children with MCD tend to respond well to
and growth.
steroid treatment, and the outcome is good with minimal
dietary problems. Conversely, those with FSGS tend to be
less responsive to steroids and may be at more risk for Food allergy
progressive kidney disease and may need more dietary
Over the years there have been numerous reports suggesting
involvement. The finding of the recurrence of protein in the an association between INS and allergies. The mechanism
urine after a renal transplant in a child who has FSGS indi- underlying minimal change disease is unknown, but it is
cates that there are circulating factors that may play a role in believed to be immune mediated. As immunosuppression
the pathogenesis of NS. In this instance, plasma exchange with corticosteroids is the most common treatment in NS, it
may induce remission. is reasonable to think that impairment of the immune system
Genetic testing should be considered if a child has CNS, plays a pathogenic role in the disease development.
SRNS or a family history of NS. Genetic mutations in podo- Relapses have been described after exposure to allergens
cyte structure and function present most often as either CNS and patients with MCD can show increased IgE levels [139].
or SRNS [135]. Children with monogenic SRNS experience There are very small clinical trials and case reports on the
higher rates of resistance to immunosuppression, but lower positive effects of hypoallergenic diets, such as milk‐ or glu-
rates of disease recurrence after renal transplantation [136]. ten‐free diets, although the response to these exclusion diets
Although the classifications shed little light on the under- has been inconsistent as well as the results being confounded
standing of the disease, they do guide management and help by a lack of a control group. Research on diets as a therapeu-
predict long‐term outcome [135]. tic option in NS is limited [139, 140], though a recent case
series describing the effect of a gluten‐free diet on eight
Treatment children with difficult to manage NS showed clinical

improvement, with a reduction or discontinuation of steroid
The first‐line treatment for NS is oral corticosteroids. It dosage [141]. The use of hypoallergenic diets is not currently
induces remission in about 80% of children [135]. Side effects recommended as more research is needed in this area.
of long‐term steroid use in children with NS include growth
impairment and weight gain as well as behavioural changes, Growth
anxiety and depression. Some children may need additional
immunosuppressants including rituximab, cyclosporin, tac- Glucocorticoids (GC) are known for their adverse effects on
rolimus, cyclophosphamide (CYP) or mycophenolate mofetil skeletal health [142] and high dose steroid therapy in
(MMF), the aim of which is to reduce the number of relapses children is known to impair growth and increase body mass
and keep them in remission longer. In the relapse phase salt index (BMI), with these effects proportional to dose and
restriction is essential and a key aspect of the management of duration of the disease and therapy. Steroid‐sparing treat-
oedema. ment strategies may improve linear growth [143, 144] and
have been associated with a lower BMI [145].
Some studies suggest that progression of steroid‐induced
Dyslipidaemia
growth failure can be prevented by administration of rituxi-
Dysregulated lipid metabolism leading to dyslipidaemia is a mab. A study including 51 patients with complicated SDNS or
complication of persistent NS. Whereas adults with NS have FRNS showed mean height z‐scores at 1, 2, 3, 4 and 5 years after
a markedly increased risk of both myocardial infarction and the initial rituximab treatment were not significantly different
coronary death compared with that of healthy individuals, from those at the time of initial rituximab treatment [146].
very few data are available regarding these risks in children In a retrospective study looking at long‐term effects of
[137]. The use of statins for the treatment of children with NS using CYP as a treatment for FRNS and SDNS in 143 chil-
has not been well studied; therefore, it is not current practice dren, it was found that height SDS at last follow‐up was not
to treat with statins. significantly different from height SDS at time of CYP
268 Kidney Diseases
introduction. After using CYP treatment, BMI decreased sig- findings of depressed serum copper. Low serum copper levels,
nificantly [147]. as previously reported, may occur in the early disease phase
A study with 60 patients evaluated the final stature of because of loss of ceruloplasmin in urine. Increased plasma
adults with childhood‐onset steroid‐responsive INS. INS‐ levels likely reflect oxidative stress. Plasma selenium was sig-
related issues did not prevent final stature reaching the nificantly decreased in active NS compared with c ontrols [153].
predicted target height [148]. Zinc is an important antioxidant and aids growth in
children. Low serum zinc levels have been seen in children
Vitamin D in clinical practice with SRNS and CNS. Plasma zinc consti-
tutes only 0.1% of total body zinc stores. Zinc is an important
Many small studies have documented very low total 25(OH)
component of alkaline phosphatase (ALP) and zinc defi-
D levels in NS, attributed to the urinary loss of vitamin D
ciency leads to a decreased serum ALP level. In a systematic
binding protein (DBP) and albumin [149]. Children with NS
review including six randomised controlled trials, zinc sup-
and normal renal function have evidence of abnormal bone
plementation reduced the frequency of relapses in children
metabolism and structure, and vitamin D deficiency may be
with SSNS and SDNS/FRNS; however, the GRADE evidence
an important modifiable risk factor in this population.
generated was of very low quality [154].
However, skeletal outcomes have not been addressed, and
There is very limited literature on the dose of supplemen-
guidelines for management of bone health in this population
tation that is needed when low levels of trace elements are
are lacking [149]. In an incident INS cohort, all children at
found [155]. There are no recommendations for monitoring
diagnosis had 25(OH)D deficiency. Supplemental vitamin D
micronutrient status in NS patients. In CNS or SRNS, if there
decreased the odds of 25(OH)D deficiency at follow‐up, sup-
is concern about a child’s growth or ongoing anaemia, meas-
porting a role for supplementation [150].
uring levels of trace elements and relevant micronutrients
More research is needed to provide guidance about the
would seem acceptable; however, more evidence is needed to
management of vitamin D deficiency in NS.
justify routine measurements of these nutrients in all patients.
Micronutrients
Protein
Trace elements play a significant role in several metabolic
processes and often circulate in the blood bound to protein. Whether a high or low protein intake is necessary in NS is
Anaemia is one of the complications seen in patients with questionable, and there is limited evidence on protein needs
persistent NS and may occur as a result of excessive urinary for children. An old study in nephrotic rats suggested that
losses of iron, transferrin (iron transport protein), erythropoi- augmentation of dietary protein stimulates albumin synthe-
etin, transcobalamin (which binds and transports vitamin sis, but also causes an increase in glomerular permeability so
B12) and/or metals. This leads to a deficiency of substrates that the excess albumin synthesised is lost in the urine [156].
necessary for effective erythropoiesis. Supplementation of In a further study, dietary supplementation with protein had
iron and erythropoietin alone often does not lead to correc- no obvious beneficial effect on the nutritional status of
tion of the anaemia [151]. nephrotic rats [157]. Low protein diets have been shown to
Copper plays a significant role in erythropoiesis, and its decrease albuminuria in rats with NS [158]. In children a low
deficiency is known to be associated with anaemia and other protein diet carries the risk of malnutrition and is, therefore,
haematological abnormalities. Urinary losses of ceruloplas- not recommended.
min, a copper carrier protein in plasma, can lead to copper
deficiency and consequent anaemia in children with NS. If
Oedema
anaemia does not improve with iron and erythropoietin
therapy, copper deficiency could be considered with meas- One of the primary strategies in the management of oedema
urement of serum copper levels [151]. is salt restriction. With severe or symptomatic oedema, fluid
Vitamin B12 (cobalamin) is transported in plasma bound to may need to be restricted with the addition of a loop diuretic
the protein transcobalamin. The role of vitamin B12 in eryth- under close medical supervision [159, 160]. In a nephrotic
ropoiesis is well established, and its deficiency can lead to state, the kidneys retain salt inappropriately in the tubules,
acquired megaloblastic anaemia. How much impact these causing oedema [161]. Filtered proteins send a signal to the
urinary losses have on the development of anaemia in chil- kidney tubules to reabsorb salt into the blood, so it is not
dren with NS is not clear. effectively excreted in the urine, which results in salt and
The reticulocyte count is the best laboratory marker of water retention and oedema.
effective erythropoiesis, and levels are expected to be low in
anaemia due to deficiencies in erythropoietin, iron, vitamin
B12, folate and copper [151]. In a small prospective study,
plasma levels of boron, selenium and zinc were shown to be
Nutritional assessment
significantly lower in 14 children with NS in active phase
compared with 14 healthy children [152]. At diagnosis, the child’s length/height and weight should
A study including 48 children with NS showed elevated be measured. The child is likely to be oedematous, so obtain-
serum copper levels in relapse, contrasting with previous ing a history from the parents/caregivers of previous
Congenital Nephrotic Syndrome 269
weights prior to the onset of disease is important in order to these situations; for the younger child, tube feeding may be
help the medical team estimate the dry weight. Length/ necessary. Hydrolysed feeds (partial or extensive hydro-
height and dry weight should be plotted on a growth chart lysates) can be trialled if diarrhoea is present and malabsorp-
and used to estimate nutritional requirements. A diet history tion is suspected. It is likely that these steroid‐resistant
should be taken. children will progress to end‐stage kidney disease. It is
At follow‐up appointments, the dietitian should obtain important to monitor their renal blood tests, growth param-
details from the medical team about how the child has eters and appetite on a more frequent basis.
responded to steroids, if they are currently in relapse or Monitoring of trace elements and 25(OH)D blood levels
remission and whether they are oedematous. A history of the should be considered in children who are steroid resistant
child’s bowel habit should be taken, especially if they have and in a persistent nephrotic state. There is not any strong
not responded to steroids and are in a persistent nephrotic evidence about dosages to supplement with if the levels are
state; the gut and surrounding tissues may be oedematous low; this can be discussed with the medical teams. For zinc
and there may be consequent malabsorption. A diet history supplementation, dosages in the British National Formulary
should be taken at each appointment. can be used as a guide to correct low levels. Measuring CRP
is advised as levels can be affected if the child is in a state of
Energy and protein inflammation.
A balanced diet adequate in energy and protein, providing

the EAR for energy and RNI for protein for the normal Corticosteroids
healthy population, is usually adequate for most children. Corticosteroids are known to be associated with a high BMI
The child’s chronological age should be used for estimating in children with NS [145, 162, 163]. If a child is on steroids, it
requirements or their height age if their height is less than is likely that their appetite and weight will increase. Early
the 2nd centile. advice on weight management should be given, and weight,
height and BMI should be monitored in the community. An
adequate calcium intake meeting the RNI should be advised
Salt
in children on long‐term corticosteroids.
The main nutritional management for children with NS is a
reduced salt (‘no added salt’) diet (Tables 13.7 and 13.24)
when the child is in an oedematous state. The UK Scientific Learning points: nephrotic syndrome
Advisory Committee on Nutrition (SACN) has published
daily target average salt intakes for children [64] (Table 13.16). • Nephrotic syndrome is an umbrella term for a group of
These do not represent an optimal or ideal consumption clinical features: proteinuria, hypoalbuminaemia, 3+ pro-
level, but a possible achievable goal in reducing the level of tein on urine dipstick and oedema with or without
salt in the diet and can be used as a guide for the dietitian in hyperlipidaemia
advising on a lower salt intake. Taking a detailed diet history • In a nephrotic state, the kidneys retain salt inappropriately in
will help to identify high salt foods that must be avoided and the tubules, causing oedema. The main nutritional manage-
finding suitable alternatives. ment for children with nephrotic syndrome is a reduced salt
Snacks high in salt as well as processed foods need to be (‘no added salt’) diet when the child is in an oedematous state
reduced. Takeaway meals should be strongly discouraged. • If a child is resistant to steroids and is in a persistent
Seventy‐five percent of the salt people eat is already in the food nephrotic state, they are likely to have reduced appetite and
they buy. Education on reading and interpreting labels should may have diarrhoea and malabsorption (due to oedema of
be given to those families where appropriate. Many commer- the gut), so care needs to be taken to ensure the diet is palat-
cial foods have colour‐coded labels indicating their high, able and adequate to meet nutritional needs; sip feeds may
medium or low salt content; this is a useful and simple tool; be useful
however, such labels do not appear on all packaged foods. • Monitoring of trace elements and 25(OH)D blood levels
When the child is in remission and the oedema resolves, should be considered in children who are steroid resistant
the salt restriction can be relaxed. and in a persistent nephrotic state. Supplementation should
be given if levels are low. More research is needed in this
area to guide management
Persistent nephrotic state
If a child is resistant to steroids and is in a persistent nephrotic
state, a reduced salt diet will need to be ongoing to control
the persisting oedema. Children in this chronic state are Congenital nephrotic syndrome
likely to have reduced appetites and may have diarrhoea
and malabsorption (due to oedema of the gut), so care needs CNS is defined by hypoalbuminaemia, heavy proteinuria
to be taken to ensure diets are palatable and adequate to and oedema with or without hyperlipidaemia. CNS is diag-
meet their nutritional needs. Dietary supplements, such as nosed in the first 3 months of life and is more commonly an
sip feeds (oral nutritional supplements), may be needed in autosomal recessive inherited disease or less commonly due
270 Kidney Diseases
to a congenital infection. An increasing number of genetic length and head circumference should be plotted on growth
defects have been identified for their involvement in the charts weekly in hospital to closely monitor growth. It is not
pathogenesis of CNS, including NPHS1, NPHS2, WT1, always easy to estimate the dry weight due to the oedema.
PLCE1 and LAMB2. Mutations in the genes NPHS1 and The level of fluid restriction is determined by the medical
NPHS2 are the most common causes. CNS was initially team. Infants are often restricted to 100–130 mL/kg/day.
referred to as the Finnish‐type nephrotic syndrome due to its However, it is important to discuss with the medical team
high incidence in Finland, with NPHS1 mutations underly- the limit on nutrition (and hence growth) that this fluid
ing most cases [164, 165]. These genes provide instructions restriction imposes; they may be able to change the medical
for producing proteins that are found in cells of the glomeru- management to control the oedema and allow more fluid to
lus (filtering unit). When there is a defect of the gene, the provide better nutrition.
kidney leaks protein in the urine. Infectious causes of CNS A feeding history should be taken as well as a history on
include congenital syphilis, toxoplasmosis and cytomegalo- the frequency of vomiting and stool output. Stools can be
virus (CMV). Treatment with antibiotics or antivirals is loose due to malabsorption resulting from oedema of the gut.
sometimes curative.
Dietetic management
Medical management The dietetic aims are to provide adequate nutrition for growth
and development, to minimise diarrhoea and vomiting and
Initially management includes stabilisation of the child, con-
to support the parents through what is a very difficult time.
trolling oedema, preventing and treating infection and
Feeds will need to be concentrated due to the fluid restric-
thrombosis and optimising nutrition to promote growth.
tion. Exclusive breastfeeding is unlikely to be sufficient to
Daily intravenous albumin in the early weeks or months is
meet nutritional requirements and in the early stages is not
typically required with monitoring of thyroid function and
advised due to strict control of the fluid intake. In more sta-
blood tests for anaemia. This may require infants to remain
ble babies, supplementary comfort breastfeeding may be
in hospital for many months, which can affect family life.
allowed. Mothers are encouraged to express their breast-
Serum creatinine levels are typically normal in the early
milk, and expressed breastmilk (EBM) can be fortified
stages of CNS. Once the infant is stable, medications such as
according to local policies. If there is no EBM, standard
ACE inhibitors can be used to reduce protein loss.
whey‐based infant formulas are used and slowly concen-
Clinical symptoms can vary hugely depending on the
trated depending on tolerance. In practice, infant formulas
phenotype, and there is wide variance in practice [166].
have been concentrated up to 20%–23% depending on the
Some centres advocate regular albumin infusions, with
level of fluid restriction, tolerance and age of the child.
planned unilateral or bilateral nephrectomies to reduce the
Proprietary high energy infant formulas can be used.
huge urinary losses of protein, once a child reaches an appro-
Extensively hydrolysed protein formulas (powdered and
priate dry weight of about 7 kg. Peritoneal dialysis is then
liquid), particularly those with a high medium chain triglyc-
commenced until the child is a suitable size for transplanta-
eride (MCT) content, and amino acid‐based formulas may be
tion (weighing aproximately10 kg). Other centres are mov-
helpful where there is diarrhoea and vomiting and feed
ing away from regular daily albumin, giving it on a clinical
intolerance is preventing growth. Protein powders, glucose
basis as required and allowing the child to progress n aturally
polymers and fat emulsions can be added to feeds to help
towards end‐stage renal disease [166]. If the infant is dis-
meet nutritional requirements.
charged home without albumin infusions, they need close
Infants who cannot meet their nutritional requirements
monitoring with frequent outpatient follow‐up, initially
orally and are not growing adequately will need a placement
weekly, and with telephone support by a clinical nurse
of a nasogastric tube. Feeds in hospital should be given con-
specialist and specialist paediatric renal dietitian.
tinuously at first if the baby is vomiting and slowly moved
The decision to carry out a bilateral nephrectomy and start
to bolus feeding as tolerated. A combination of day bolus
dialysis is dependent on the child’s growth, frequency of
feeds and continuous overnight feeding is a commonly used
infections and kidney function. In the majority of cases,
regimen. It is important to involve the family in the decision
kidney transplantation is the only curative outcome [165].
making. If tube feeding is likely to be long term, gastrostomy
feeding should be discussed with the medical team and the
parents. It is advisable to place the gastrostomy before peri-
toneal dialysis is started. A gastrostomy can be very helpful
post‐kidney transplant in order to give daily immunosup-
Nutritional assessment
pressants and to meet high fluid requirements.
Babies with CNS are at nutritional risk due to large losses of Normal weaning practices are encouraged. Some babies
protein, oedema and fluid restriction, poor oral feeding, vom- struggle to take more than tastes; however, some babies
iting and diarrhoea, increased risk of infections that further wean successfully.
affects feeding and losses of vitamin D and trace elements. There have been reports of improved growth in CNS with
It is important to obtain an estimated dry weight from the aggressive treatment regimens. However, it is unknown
medical team in order to calculate requirements. Dry weight, whether this improvement is related to the high protein intake
Congenital Nephrotic Syndrome 271
(4 g/kg/day) or other components of the regimen such as

Learning points: congenital nephrotic syndrome
albumin infusions [167]. Infants with severe CNS have tradi-
tionally been treated with a high energy (130 kcal (545 kJ)/kg/
• CNS is diagnosed in the first 3 months of life and is more
day) and high protein (3–4 g/kg/day) diet [165, 168].
commonly an autosomal recessive inherited disease or less
Micronutrient requirements are not known, but to aim for at
commonly due to a congenital infection
least the dietary reference values [153] seems appropriate.
• Babies with CNS are at nutritional risk due to large losses
Due to the heavy losses of protein, which include iron
of protein, oedema and fluid restriction, poor oral feeding,
transport proteins, copper carrying proteins, B12‐transport-
vomiting and diarrhoea, increased risk of infections that
ing proteins and the reported losses of other trace elements
further affects feeding and losses of vitamin D and trace
such as zinc and selenium, some renal units have started
elements. Regular dietetic monitoring is paramount
measuring these micronutrient levels in their babies with
• Feeds need to be concentrated due to the fluid restrictions.
CNS. There is, however, very little evidence to guide on the
A large percentage of babies with CNS will need to be tube
level of supplementation needed if the serum levels are
fed to aid growth
found to be low. Once supplementation is started, blood
• Monitoring of trace elements and 25(OH)D blood levels should
levels should be monitored together with CRP 2–3 monthly
be considered. Supplementation should be given if levels are
and doses adjusted accordingly. Research in this area is
low. More research is needed in this area to guide management
needed.
• In the majority of cases of CNS, kidney transplantation is
Renal function declines with time so the dietary manage-
the only curative outcome
ment needs to be modified according to the level of CKD and
blood results. If bilateral nephrectomies are performed and
the child starts peritoneal dialysis or haemodialysis, the
dietary prescription is altered accordingly until they receive A case study to show the management of a baby with
a successful kidney transplant. congenital nephrotic syndrome is given in Table 13.21.
Table 13.21 Case study: A baby with congenital nephrotic syndrome.
A 6‐week‐old term baby girl diagnosed with CNS is fluid restricted to 120 mL/kg.
Birthweight = 3 kg (25th centile).
Current estimated dry weight = 3.5 kg (2nd centile). Length = 54 cm (25th centile). Head circumference = 37 cm (50th centile).
Energy requirements 130 kcal (545 kJ)/kg/day. Protein requirements 3–4 g/kg/day.
Mum is not expressing any breastmilk. Feeds using whey‐based infant formula were gradually increased daily to 20% concentration with 1%
added glucose polymer and 1% added protein powder, as tolerated.
Feed recipe Energy (kcal (kJ)) Protein (g) CHO (g) Fat (g) Na (mmol) Calcium (mg)
20 g SMA PRO 1 102 (427) 1.9 11 6 1.6 65

1 g Vitajoule 3.8 (16) 0 1 0 0 0
1 g Protifar 3.6 (15) 0.9 0 0 0 14
Total per 100 mL 109 (458) 2.8 12 6 1.6 79
Total per 420 mL (120 mL/kg) 458 (1924) 11.8 50.4 25.2 6.7 332
Total per kg 131 (550) 3.4 14.4 7.2 1.91 95
The following week, she became more oedematous and was vomiting frequently, and the doctors request the fluid be further restricted to
110 mL/kg. It is difficult to estimate a dry weight, due to oedema, but the medical team has decided on 3.6 kg. A more concentrated feed was
calculated to provide her nutritional requirements in 110 mL/kg. To try to achieve better feed tolerance, the dietitian changed the base feed to a
high energy extensively hydrolysed liquid infant formula with 5% added glucose polymer.
Feed recipe Energy (kcal (kJ)) Protein (g) CHO (g) Fat (g) Na (mmol) Calcium (mg)
100 mL Infatrini Peptisorb 100 (420) 2.6 10.3 5.4 1.4 80

5 g Vitajoule 19 (80) 0 4.8 0 0 0
Total per 100 mL 119 (500) 2.6 15.1 5.4 1.4 80
Total per 400 mL (110 mL/kg) 476 (2000) 10.4 60.4 21.6 5.6 320
Total per kg 132 (556) 2.9 16.8 6 1.6 89
Her vomiting improved by reducing in frequency; however, she still had occasional vomits 2–3 times a week that the medical team felt was
acceptable. She continued to receive daily albumin infusions and her oedema reduced. For the next couple of weeks, it was felt that her dry
weight was increasing well. Close monitoring by the dietitian and liaison with the medical team continues because as she grows, she will need
either an increase in her fluid allowance or a further increase in the feed concentration to continue to meet her nutritional needs.
272 Kidney Diseases
Renal Tubular Disorders

Louise McAlister
The renal tubules play a central role in fluid, electrolyte and reduction of further losses by appropriate medication. Early
acid–base homeostasis. Urine composition is determined by diagnosis and initiation of therapy can improve growth and
active and passive reabsorption from the glomerular ultrafil- prognosis. Glomerular function is preserved in some disor-
trate (mainly occurring in the proximal tubule) and secretion ders (e.g. GS), but can be severely affected in others (e.g. cys-
into the tubule from the surrounding blood supply. The final tinosis and some Bartter patients), leading to chronic kidney
regulation occurs in the distal tubule and collecting duct disease (CKD). Episodes of dehydration or complications
under the influence of hormones. Defects in tubular function related to the original defect (e.g. renal stones in cystinuria)
may be inherited or acquired and disrupt one or more of can also affect glomerular filtration rate (GFR). Although
these absorptive or secretory processes, leading to potential rare, the long‐term outcome and clinical profile of many of
abnormalities in electrolyte, mineral and water balance that these inherited renal tubular d isorders are now being
can be life threatening. reported [170–175].
Classification of renal tubular disorders is based on the Ensuring a nutritionally adequate diet and achieving
location of the defect in the nephron and whether it is iso- appropriate growth can be challenging. The polyuria, which
lated (e.g. nephrogenic diabetes insipidus), generalised (as is a common feature of many of these conditions, drives
in renal Fanconi syndrome) or secondary to a more wide- thirst and can result in a poor appetite, especially during
spread disease process (such as cystinosis, tyrosinaemia or infancy. The medical treatment and dietary considerations
Lowe syndrome) (Table 13.22). Biochemical analysis of for a few of these conditions are described below.
serum and urine assists differential diagnosis, and genetic
testing can confirm the diagnosis in suspected or familial
cases. Bartter syndrome
Inherited renal tubular disorders may present in the first
year of life with faltering growth, polydipsia and polyuria. Bartter syndrome (BS) is not a single entity, but refers to a
Dehydration can lead to symptoms of constipation, recur- group (types I–V) of rare, predominantly autosomal reces-
rent fevers and vomiting. Bone deformities (rickets) may be sive disorders, characterised by hypokalaemic alkalosis,
part of the clinical picture, suggesting loss of phosphate from hypochloraemia, hyper‐reninaemia and hyperaldosteron-
the proximal tubule. The antenatal history can include poly- ism with normal or low blood pressure. The underlying
hydramnios with infants born premature and with low renal abnormality causes high urinary losses of sodium,
birthweight. A few conditions (such as Gitelman syndrome chloride and potassium. Males and females are affected
[GS] and renal glycosuria) may not present until later in equally.
childhood or adulthood [170, 171]. The BS subtypes correspond to specific defective transport
The initial management for most tubular disorders involves proteins in the thick ascending limb (TAL) of the loop of
correction of dehydration and electrolyte abnormalities and Henle caused by a variety of gene mutations. They share
Table 13.22 Disorders of tubular function.
Renal tubular disease Location of defect Main process affected
Hypophosphataemic rickets Proximal tubule Transport: phosphate

Renal glycosuria Transport: glucose
Aminoacidurias, e.g. cystinuria Transport: amino acid
Proximal renal tubular acidosis (pRTA) Transport: bicarbonate
Renal Fanconi syndrome1 Generalised dysfunction
Bartter syndrome (BS) Ascending loop of Henle Transport: sodium, potassium, chloride
Distal renal tubular acidosis (dRTA) Distal tubule Secretion: proton (H+)
Gitelman syndrome, EAST syndrome2 Transport: sodium, chloride
Pseudohypoaldosteronism Collecting duct Transport: sodium, potassium
Liddle syndrome
Nephrogenic diabetes insipidus Transport: water
Primary or secondary to another disorder (e.g. galactosaemia, nephropathic cystinosis, mitochondrial cytopathies, Lowe syndrome, Wilson’s disease).
1
Epilepsy, ataxia, sensorineural deafness, tubulopathy [169].

2
Bartter Syndrome 273
many of the same physiological derangements, but differ Nutritional management

with regard to the age of onset (antenatal to adulthood), pre-
senting symptoms and size of urinary calcium and potas- Growth retardation, poor weight gain, low appetite and
sium losses. Polyhydramnios and prematurity are common feeding problems are all associated with BS. Walsh [171]
for infants with BS types I, II and IV, together with symp- recently reported long‐term longitudinal data on 45 children
toms of polyuria, dehydration, constipation, poor weight with BS and GS finding that median height was low at pres-
gain and nephrocalcinosis. Episodes of severe fever and entation and growth remained poor during follow‐up with
dehydration may occur during the early weeks of life, and median standard deviation scores (SDS) for height being
hypokalaemia can result in muscle weakness, cramping and −1.6 at presentation and −1.2 at follow‐up. Similarly, Kaur in
fatigue. Type IV BS is a result of mutations of barttin protein, a retrospective review of 34 children from three tertiary UK
which is expressed in the kidney and the cochlea, and paediatric nephrology centres [177] reported that a third of
patients, therefore, also have sensorineural deafness. GS has children had a height below the 2nd centile at 15 years of
considerable clinical overlap with BS type III, so is com- age. The exact aetiology of the short stature is unknown,
monly grouped with BS, as the underlying gene is expressed although growth hormone (GH) therapy has been successful
in both the TAL and the distal convoluted tubule (DCT). for some children [171, 178], especially if BS presents in early
These two conditions usually have a milder clinical picture childhood or after a delayed diagnosis.
than the other subtypes, a later age of onset (school age or Dietetic input is particularly important in the first 2 years
adolescence) and a low urinary calcium level. Asymptomatic of life to ensure optimal weight gain and growth by regular
individuals with GS usually require minimal medical treat- monitoring of food, fluid and nutritional intake. Infants born
ment and monitoring. However, both GS and BS type III with a low birthweight are especially vulnerable to the
patients are at risk of severe life‐threatening electrolyte effects of poor nutrition. Fluid requirements can be greater
abnormalities during episodes of intercurrent illness (e.g. than 200 mL/kg in the first 6 months of life and, if this is not
gastroenteritis). A pseudo‐BS with signs and symptoms sim- achievable orally, may need to be given by a feeding tube,
ilar to BS, but no tubular dysfunction, can be caused by diu- nasogastric (NG) or gastrostomy (G), or intravenously (IV).
retics, severe vomiting, laxative abuse or in young children The fluid requirements per kilogram body weight decrease
cystic fibrosis [176]. with age, depending on the control of polyuria. Kaur [177]
The diagnosis of BS is made in the neonatal period in reported that 26% of their cohort were gastrostomy fed,
about 50% of cases [177], requiring correction of dehydra- which enabled them to achieve adequate fluid and nutrition.
tion and electrolyte abnormalities. Oral potassium sup- Standard infant formula or age‐appropriate paediatric feeds
plementation up to 12 mmol/kg may be necessary, but can be used for enteral feeding to provide normal nutritional
this requirement reduces with age, nearing 1 mmol/kg in requirements for age (or height age if stunted), with addi-
the teenage years [177]. However, despite supplementa- tional water to maintain hydration. These feeds may need
tion, serum potassium usually remains low <2.5 mmol/L the addition of extra energy modules (such as a glucose
[171]. Potassium supplements are available in liquid or polymer or a fat emulsion) if weight gain or growth is poor.
tablet form and are often associated with gastrointestinal Normal weaning onto solids can begin at around 6 months,
(GI) side effects such as abdominal pain and diarrhoea. but some infants progress slowly. For children with poor
Sodium requirements can be very high in the first year (up food intake, the use of oral nutritional supplements (p. 224)
to 13 mmol/kg), but by 15 years only about one quarter of and energy‐dense foods can be helpful to achieve an ade-
individuals require supplements [171]. Other medications quate nutritional intake.
used to manage polyuria include non‐steroidal anti‐ Sodium supplementation is often provided in early child-
inflammatory drugs (NSAID), e.g. indometacin, ibupro- hood, but a high dietary salt intake may be sufficient in
fen or a cyclooxygenase‐2 selective inhibitor (COX‐2 older children [177]. Many patients report intense cravings
inhibitor) such as celecoxib. Indometacin and ibuprofen for high salt foods. As GI tolerance of potassium supple-
should be taken with food or milk because of potential GI ments is poor, encouraging high potassium foods may be
side effects including nausea, vomiting, abdominal pain appropriate. In GS hypomagnesaemia is a more prominent
and peptic ulcers. Individuals experiencing these side component, and magnesium supplementation is routinely
effects may be changed to a COX‐2 inhibitor under spe- required for life. High doses of magnesium can cause diar-
cialist supervision. rhoea, so normal levels of serum magnesium may be diffi-
Reduced GFR and proteinuria are seen in about 60% of cult to achieve. Directing food choices for children with low
patients with BS [171], with a small proportion of these appetites to try to include these electrolytes in sufficient and
progressing to CKD requiring renal replacement therapy. reliable amounts is probably unrealistic. Patient support
The mechanism for this is not clear and is likely to be websites [179, 180] include practical advice on dietary
multifactorial, related to prematurity, recurrent dehydra- sources of potassium and salt (and magnesium if needed),
tion,
secondary to nephrocalcinosis or due to chronic but do acknowledge that apart from salt, this is unlikely to
hypokalaemia. High urinary calcium levels can lead to replace the need for medicinal supplementation.
nephrocalcinosis and calcium‐containing renal stones Careful monitoring of serum urea and creatinine levels
in some BS patients, but calcium restriction is not will identify any decline in kidney function, and dietetic
appropriate. advice would then need to be tailored accordingly (p. 249).
274 Kidney Diseases
polyuria, vomiting, constipation, delayed growth, weakness,

Learning points: Bartter syndrome
rickets and recurrent fevers. The typical biochemical profile
includes hypokalaemia, metabolic acidosis, hypophospha-
• High fluid requirements
taemia, low serum uric acid and carnitine. All racial and
• Wean onto solids at around 6 months of age
ethnic groups are affected; however, the classical child with
• May require nutritional support to achieve adequate weight
cystinosis of Northern European descent is fair‐haired and
gain and growth
blue‐eyed (possibly related to the role of cystinosin in the
• Use standard age‐appropriate feeds (oral or enteral)
regulation of melanin synthesis). A single gene mutation
• Allow liberal salt and potassium (and sometimes magnesium)
(57 kb deletion) accounts for about 50% of all cases of nephro-
• Monitoring of renal specific serum biochemistry (particu-
pathic cystinosis in Northern Europe [183].
larly urea and creatinine) will identify any decline in
A milder form of nephropathic cystinosis (juvenile or late
glomerular function (and onset of CKD)
onset) accounts for 3%–5% of cases and is usually diagnosed
later in childhood or during adolescence, but can present
from the age of 2 years [184].
Cystinosis A third form of cystinosis, non‐nephropathic or ocular, is
rarely diagnosed before adulthood and only represents about
Cystinosis is a rare autosomal recessive inherited lysosomal 1%–2% cases. This is characterised by symptoms related to
storage disorder caused by the failure to transport cystine corneal cystine crystal depositions (including photophobia
(the disulphide of the amino acid cysteine) out of lysosomes and an abnormal contraction or twitch of the eyelids).
into the cytoplasm. This accumulated cystine can increase Treatment for nephropathic cystinosis involves rehydra-
the content of cells by 50–100 times the normal value leading tion, replacement of renal loses of electrolytes, administra-
to cellular and tissue damage. Cystinosis is a systemic dis- tion of bicarbonate, attention to nutrition and provision of
ease as lysosomes are present in all cells, but clinical mani- vitamin D supplements. Maintaining normal hydration can
festations are typically first seen in the kidneys and eyes. be difficult as individuals produce large volumes of dilute
Corneal cystine crystals can be seen in all children from urine and so free access to water (and salt) is essential.
about 12 to 18 months of age and contribute to photophobia. NSAID, such as indometacin, are sometimes given to con-
Mutations in the CTNS gene (located on chromosome 17) are trol the polyuria, but there is no consensus on its routine use
responsible for all forms of cystinosis, as the gene encodes in cystinosis.
for the protein cystinosin, which is the lysosomal transmem- The only specific targeted therapy for cystinosis is the
brane transporter for cystine. cystine‐depleting agent cysteamine (also known as mercap-
There are three clinical forms of cystinosis with the most tamine), which is started at diagnosis. This converts
severe form (infantile or nephropathic) accounting for 90%–95% entrapped cystine to cysteine and cysteine–cysteamine
of cases. Cystine accumulation begins in foetal life, predomi- mixed disulphide, which can then both exit the lysosomes
nantly in the proximal renal tubules, leading to renal Fanconi through an alternative transporter. The most commonly
syndrome in the first year. Cystinosis is the most common used preparation has to be taken every 6 hours orally (or via
inherited cause of paediatric renal Fanconi syndrome. a feeding tube) together with aqueous eye drops (applied
Initially, amino acids and glucose are poorly reabsorbed, but 6–12 times per day) [185]. Oral medications have no influ-
as the damage progresses, electrolytes (sodium, potassium, ence on ocular manifestations as there is no blood supply in
magnesium, calcium and phosphate), low molecular weight the cornea. Cysteamine has a strong taste and smell and
proteins and bicarbonate are lost in the urine. Kidney func- binds to the oral mucosa and dental fillings. It is metabolised
tion progressively declines through childhood, despite treat- to volatile sulphur compounds that can cause bad breath
ment, due to chronic interstitial nephritis, leading to and an unpleasant sweat odour, reducing compliance in
end‐stage CKD by the age of 20 years in 90% of patients. The young people [186]. Other common adverse effects of
use of a cystine‐depleting medication (such as cysteamine) cysteamine are nausea, diarrhoea, vomiting, abdominal pain
substantially delays, but does not prevent, the onset of renal and loss of appetite [14]. These can be reduced if the medica-
failure. Renal transplantation is the preferred treatment for tion is taken with or after food (although this may decrease
kidney failure, but a period on dialysis may be required if a absorption) and by the concurrent use of proton pump
live‐related donor is not available or if kidney function has inhibitors (such as omeprazole or lansoprazole). A delayed‐
declined rapidly. Paediatric cohorts report a better renal release enteric‐coated product (Procysbi) has been devel-
graft survival post‐transplant in cystinosis patients com- oped and can control blood levels for up to 12 hours. This
pared with most other renal diagnoses [181]. Cystinosis does should aid adherence, but is not yet routinely available. The
not recur in the transplanted kidney as these cells do not essential role of cysteamine in delaying the progression to
carry the defect, but cystine continues to accumulate post‐ end‐stage renal disease, improving growth, reducing the
renal transplant in other organs including the eyes, thyroid, severity of the extrarenal complications and improving
pancreas, liver, muscle and gonads [182]. prognosis is now well documented [187].
Infants with nephropathic cystinosis usually have a nor- Routine monitoring in children includes assessment of
mal birthweight and progress in the first 3–4 months of life, growth and weight gain to promptly detect any deteriora-
but then develop poor feeding, excessive thirst, profound tion in growth velocity and weight faltering. Slow growth is
Cystinosis 275
multifactorial being secondary to the renal Fanconi syn- supplements (such as glucose polymers and a fat emulsion)
drome [187], inadequate nutrition, rickets and cystine depo- if necessary. It is usually sufficient to aim for 100% of energy
sition in the bones and thyroid. Early initiation and requirements for age (or height age if stunted) [182]. Within
compliance with cysteamine therapy can help prevent the first year many experience feeding difficulties including
growth retardation by increasing GH release and improving frequent vomiting, poor appetite and oral aversion. Weaning
metabolic status, but cannot induce catch‐up growth [188]. can begin at around 6 months, but progression onto solids
Frequent measurement of trough leucocyte cystine levels are can be slow, with an extended reliance on formula and poor
used to adjust cysteamine dose [189] and can help assess acceptance of a cup rather than a bottle [193]. Extreme thirst
compliance with medication. may be a feature due to the polyuria, along with craving for
Hypophosphataemic rickets can be seen at a young age in high salt foods. A reduction in saliva production can com-
cystinosis due to the large urinary losses of phosphate, cal- promise the ability to chew and swallow [194].
cium and vitamin D binding protein and impaired vitamin Achieving adequate nutrition and fluid intake can be dif-
D metabolism. High doses of phosphate supplements and ficult, and infants and children may require intensive die-
active vitamin D may be required to treat and prevent rick- tetic support. Fluid requirements may be up to twice normal
ets. However, careful monitoring of phosphate and bone for weight. Young children can benefit from an NG or G tube
status (using serum phosphate, parathyroid hormone or ion- to administer nutrition, fluid and medications, resulting in
ised calcium levels) is necessary to detect a reduction in improvements in height and weight parameters [189, 195].
phosphaturia that may occur as CKD progresses. High A questionnaire survey of 70 members of the Cystinosis
serum phosphate levels can trigger increases in serum fibro- Foundation [196] reported that 30% of responders had
blast growth factor‐23 (FGF‐23), which is associated with received gastric/jejunal feedings and 7% had periods on
adverse outcomes including increasing progression of renal parenteral nutrition. Oral nutritional supplements can be
disease and risk of cardiovascular disease and mortality. helpful if a child’s appetite is reduced. Children with poor
Urinary carnitine excretion is high in cystinosis due to the growth, whose medical and nutritional therapy have been
renal Fanconi syndrome, as 97% of free carnitine is normally optimised, may benefit from the use of GH.
reabsorbed by the renal tubules. This leads to low levels in Despite treatment, cystine can accumulate in the oropharyn-
plasma and muscle, although clinical signs of deficiency geal muscles, with many patients reporting choking, gagging
(such as cardiomyopathy or metabolic encephalopathy) and vomiting during mealtimes and poor tolerance of changes
have never been reported. In addition, the cysteamine medi- in food textures [193, 197]. A videofluoroscopy can be helpful to
cation may also inhibit the efficient transport of carnitine assess the nature, severity and aspiration risk associated with
into muscle. these swallowing difficulties. A wide range of GI disturbances
Carnitine levels improve with the onset of CKD and the have been reported in this patient group, including intestinal
reduction in urinary losses. The value of supplementation is dysmotility and delayed gastric emptying [198–200].
debatable as it can take many years to replace muscular As renal function declines, dietary intake may need to be
carnitine and it is unclear if this provides any clinical
manipulated according to serum biochemistry (p. 249).
improvement [190]. However, dietary advice requires a careful balance between
High urinary copper excretion (up to four times normal) compensation for renal losses and the usual dietetic manage-
has been reported in patients with cystinosis [191] together ment of CKD.
with low serum copper and ceruloplasmin levels. Copper is
a cofactor involved in maintaining normal collagen and
bone structure, and so it has been proposed that copper defi- Learning points: cystinosis
ciency may play a role in the connective tissue lesions that
have been reported. Monitoring copper status and the use of • Cystinosis is an inherited systemic disease
oral copper supplements may be important to prevent these, • 95% have the severe form (nephropathic or infantile)
but there is no consensus on whether copper supplements • High fluid requirements
should be given [192]. • Breastfeeding and standard infant formula are usually
appropriate
• May need nutritional support (supplementation or tube feeding)
Nutritional management • Symptoms of extreme thirst and feeding difficulties, espe-
cially in infancy
Infants with cystinosis are asymptomatic at birth with a nor- • Normal weaning from about 6 months of age, but often
mal weight and length, but by 6–12 months may be faltering slow progression onto solids
[183]. Breastfeeding, EBM and infant formula are appropri- • Serum copper levels may be low and could be supplemented
ate feed choices, but energy and nutritional intake should be • Cysteamine medication:
regularly assessed along with anthropometry. If weight gain ⚬⚬ improves prognosis and delays progression of CKD
or growth is poor, the optimal feed will depend on the vol- ⚬⚬ has a strong taste and smell which reduces compliance
umes taken or tolerated. Energy‐dense infant formulas, e.g. • 90% of children with cystinosis have stage 5 CKD by age
Similac High Energy or Infatrini, may be useful or concen- 20 years requiring renal replacement therapy
trating a standard infant formula with the addition of energy
276 Kidney Diseases
Nephrogenic diabetes insipidus kg body weight/day will reduce the amount of urine pro-
duced and can help to achieve feed tolerance by decreasing
Congenital nephrogenic diabetes insipidus (NDI) is a rare polydipsia.
genetic condition characterised by insensitivity of the distal The RSL refers to solutes of dietary and endogenous origin
renal tubule to antidiuretic hormone (arginine vasopressin that need to be excreted in the urine along with water [204].
[AVP]) leading to an inability to concentrate urine. The most These include urea (from dietary protein metabolism), cre-
common manifestations are polyuria, polydipsia and hypos- atinine, sodium, chloride, potassium and phosphate. In
thenuria (urine with an osmolality less than that of plasma) practice, most of the RSL is of dietary origin, and the poten-
with recurrent episodes of dehydration and fever. About tial RSL of a feed can be estimated from the protein content
80% of cases have mutations in the gene affecting the vaso- together with the main electrolytes. Formulas for roughly
pressin V2 receptor (AVPR2) in the collecting duct, an X‐ calculating this are given in the literature using slightly dif-
linked recessive disorder. Mutations in the aquaporin water ferent assumptions regarding contributions of dietary elec-
channel (AQP2) in the collecting duct account for 10% with a trolytes and protein. The formula shown in Table 13.23 was
recessive mode of inheritance (or rarely a dominant inherit- devised generalising that all dietary proteins are metabo-
ance pattern). These genes code for critical compounds for lised to urea (and contribute 4 mmol to the RSL per gram of
the transepithelial water permeability of the collecting duct protein) with the addition of a contribution from electrolytes
[201]. A further 10% of cases of NDI are due to unknown (by multiplying the millimolar amounts of sodium and
mutations. potassium by two to allow for the accompanying anions).
The clinical presentation of NDI may be indistinguishable The medical management of NDI usually includes the
from central (or neurogenic) diabetes insipidus (DI), which administration of a thiazide diuretic, often in combination
is due to insufficient AVP production or release. In both of with a potassium‐sparing diuretic (amiloride) or an NSAID
these conditions, the high urine output leads to an increase (such as indometacin or ibuprofen) or a COX‐2 inhibitor
in serum osmolality and hypernatraemia, accompanied by (celecoxib) to reduce urine output. Potassium supplementa-
an inappropriately low urine osmolality. Urine volume is tion may be indicated if serum potassium levels fall below
often greater than 6 mL/kg/hour in neonates (or 4 mL/kg/ the normal range for age.
hour in children), accompanied by a fluid intake of >2 L/m2 Patients have been reported to have developmental delay,
BSA/day (p. 243). The nephrogenic form of DI is confirmed attention deficit hyperactivity disorder (ADHD) and poor
by administering an artificial form of AVP, 1‐desamino‐8‐d‐ short‐term memory [203], although these may be secondary
arginine vasopressin (DDAVP), either IV or subcutaneously. to the feeling of constantly craving for fluids and needing to
In patients with central DI, DDAVP will concentrate the pass urine.
urine to normalise serum osmolality, whereas in NDI there
will be no response. Genetic testing (if available) can help to
confirm the NDI diagnoses. Nutritional management
Most patients with congenital NDI have non‐specific
symptoms in the first weeks of life, e.g. faltering growth, Infants with NDI are usually fed a controlled volume of a
recurrent vomiting, poor feeding, irritability, hypotonia, low solute whey‐based infant formula calculated to provide
fever and constipation. Birthweight and height have been a RSL <15 mOsm/kg H2O per kg body weight (Table 13.23).
reported as normal, suggesting normal prenatal growth This infant formula may be given as a feed up to 150 mL/kg
[202]. In a recently reported retrospective review of 36 NDI body weight, with additional fluids offered freely as water.
cases [174], 69% were diagnosed in the first year of life with Fluid requirements are high (up to 250 mL/kg), but can
a median age of diagnosis of 7 months. The majority (87%) of reduce substantially when urine output is controlled on
patients are diagnosed in the first 2.5 years of life [203]. medication. To achieve the EAR for energy for age, energy
Median height and weight SDS at presentation a the Dutch supplementation of the formula and also of the free water
cohort [203] was −1.06 (range −4.94 to −1.9) and −2.1 (range may be needed. Glucose polymers (p. 14) can be used to
−8.25 to −2.6), respectively. provide extra energy without further increasing the RSL.
Infants with NDI may need IV fluids to rehydrate and Tolerance and acceptance of glucose polymers varies, but
slowly normalise serum sodium in the first instance. Too between 3 and 10 g of glucose polymer powder can be added
rapid a decrease in serum sodium levels can risk cerebral to 100 mL of the fluids, providing an additional 11–38 kcal
oedema and potentially be fatal. The IV fluids should be 5% (45–160 kJ)/100 mL. A total carbohydrate concentration of
glucose, given at an infusion rate just exceeding urinary 10 g/100 mL can be trialled initially and slowly increased in
output, with careful monitoring of urine and plasma bio- increments of about 2 g/100 mL if required (up to a maxi-
chemistry. Only in the event of circulatory shock should a mum of about 20 g total carbohydrate per 100 mL, i.e. 20%
bolus of 0.9% saline be given. In other situations, the higher concentration). Most infants have a preference for water, so
sodium load from 0.9% saline would worsen the hyper- the formula should be offered first to ensure adequate nutri-
natraemia, exacerbating the polyuria. These IV fluids are tion. An NG tube may needed for those infants who refuse to
carefully managed and monitored by the medical team. take an adequate amount of formula orally. Within the first
Once oral feeding is initiated, achieving an adequate fluid year of life, many infants experience feeding problems that
intake to replace urinary losses can be difficult. Lowering the lead to poor weight gain and growth, so regular monitoring
renal solute load (RSL) of the feed to <15 mOsm/kg H2O per and adjustment of feeds may be necessary.
Nephrogenic Diabetes Insipidus 277
Table 13.23 Case study showing calculation of renal solute load.
RSL (mOsm/kg H2O) = total intake of protein (g) × 4 + 2 × [sodium (mmol) + potassium (mmol)]

Case: A 3‐month‐old boy diagnosed with NDI weighing 5 kg
He is unable to concentrate his urine greater than an osmolality of 70 mOsm/kg H2O
Influence of RSL on fluid intake:
• If given a feed with an RSL of 20 mOsm/kg H2O per kg body weight, he would receive 100 mOsm/day
To excrete this he would need 100/70 × 1000 mL of fluid = 1429 mL (286 mL/kg)
• If given a feed with an RSL of 15 mOsm/kg H2O per kg body weight, he would receive 75 mOsm/day
• If given a feed with an RSL of 13.8 mOsm/kg H2O per kg body weight (see feed below), he would receive 68 mOsm/day
Feeding plan:
He is offered a normal feed volume of 150 mL/kg = 750 mL/day of a reduced RSL feed, given as 150 mL × 4 hourly × 5 feeds
In addition he is offered water freely after feeds, aiming for 40–60 mL/kg = 250 mL/day
Total fluid intake = 1000 mL
Fluid volume required to excrete the RSL = 971 mL
Feed calculation:
12% infant formula (e.g. Cow & Gate 1) + glucose polymer (Vitajoule) added up to 10% total carbohydrate concentration
Energy (kcal (kJ)) Protein (g) Na (mmol) K (mmol)
90 g Cow & Gate 1 435 (1820) 8.7 4.9 12.5

28 g Vitajoule + water up to 750 mL 106 (445) 0.3
Total 541 (2265) 5.2 12.5
Intake per kg body weight 108 (455) 1.8
Renal solute load 8.7 × 4 + 2 (5.2 + 12.5) = 69 mOsm/kg H2O

= 13.8 mOsm/kg H2O per kg body weight
RSL, renal solute load; NDI, nephrogenic diabetes insipidus.
The reduced RSL feed may initially result in a shortfall in a G device inserted [174]. Tube feeding is not usually needed
protein and micronutrient intake, but is essential to stabilise beyond the age of 2 years [174], although children and their
urine output and minimise thirst. Preterm infants are par- families often need a lot of support to achieve a consistent
ticularly vulnerable to the effects of poor nutrition, so it may oral intake and careful weaning off from the tube. A multi-
not be possible to reduce RSL below 15 mOsm/kg H2O per disciplinary approach, including the support of speech and
kg body weight, and a compromise of 18 mOsm/kg H2O language therapists and a specialist feeding team, can be
per kg may be more appropriate. Once an infant is thriving helpful to manage this process.
and medically stable, the feed RSL can be relaxed to improve To reduce urine output, lifelong control of dietary salt
protein and nutrient intake. Plasma sodium concentration intake is required. In infants, initial weaning should be a
and routine monitoring of paired urine and plasma osmolal- low sodium diet, with a gradual relaxation to a reduced salt
ity can guide hydration status, although interpreting these diet (or ‘no added salt diet’) by the age of 2 years. Most tra-
can be difficult [205]. A plasma osmolality >300 mOsm/kg ditional weaning foods are low in sodium including fruit,
H2O and serum sodium >150 mmol/L in an NDI infant sug- vegetables and baby rice and manufactured baby foods
gests hypernatraemic dehydration and medication doses (apart from those with added high salt items such as cheese,
may need adjustment (to reflect an increase in body weight) ham and bacon). A reduced salt diet provides about 3 mmol
or extra fluids given. Urine osmolality in NDI is rarely con- sodium/kg body weight (Table 13.7), which is similar to the
centrated above 70–150 mOsm/kg H2O, even when serum healthy eating guidelines given to the general public. A
osmolality is high. web‐based support group for NDI families gives detailed
The tendency to vomit and experience constipation (due advice on strict adherence to a very low sodium diet irre-
to dehydration) is commonly reported in infants and young spective of age, which is not necessary or achievable.
children with NDI. The regular use of laxatives can be help- Practical advice on achieving a reduced salt intake is given
ful. To control vomiting, careful positioning during feeding, in Table 13.24.
the use of feed thickeners, anti‐emetics and prokinetics can A very strict low salt diet can contribute to growth failure
be tried, but are often unsuccessful. For infants with severe despite adequate energy intake and optimal medical treat-
vomiting and faltering growth, a trial of NG tube feeding to ment [206]. Individual tolerance of salt varies, with parents
allow a slower administration of feed volume (by gravity or reporting higher fluid intakes (with accompanying polyuria
pump) can be helpful. In the cohort review by Sharma, about and bedwetting) if salty foods are taken. For this reason,
a third of infants had required NG feeding, and 24% had had many older children self‐regulate their salt intake to avoid
278 Kidney Diseases
Table 13.24 Practical advice to achieve a reduced salt diet (‘no added salt diet’).
General advice
• Do not add salt to your food at the table or in cooking • Season foods with fresh, frozen or dried herbs, black pepper, garlic, onions,
This includes sea salt, rock salt, garlic salt, natural salt, table salt or chilli, lemon juice, vinegar, spices (check spice mixes for salt)
salt substitutes • Try baking or roasting vegetables to bring out their flavour
• Eat foods high in salt less often and in smaller amounts • It is not usually necessary to avoid cereals, bread and normal butter and
• Check food labels spread
Very high salt foods may have >1.5 g salt/100 g. However, salt
intake from these will depend on the amount eaten and a small
portion may be acceptable
High salt foods Lower salt advice
Cheese
Especially hard and processed cheese (e.g. cheddar cheese and Try using a small amount of a stronger cheese or grating hard cheese to make
cheese slices or strips) it go further. Cream cheese, cheese spread and cottage cheese are lower salt
cheeses
Processed meats/ready meals
Bacon, sausages, hot dogs, frankfurters, ham, corned beef, beef Not all processed meals are high in salt – check food labels for those with
burgers, salami, meat pies, sausage rolls, meat paté or paste ≤0.3 g salt/100 g
Ready meals or dried pot meals (particularly if containing bacon, Replace packaged meals with freshly cooked meat, poultry and fish
ham, cheese or soy sauce) Replace dried pot meals with fresh or dried noodles or pasta; discard
ready‐mixed ‘seasonings’ packets and flavour with a low salt spice mix or
suitable sauce
Burgers can be made at home and chicken strips can be oven baked or fried
in batter or breadcrumbs rather than choosing shop‐bought items
Certain fish products
These include smoked salmon or mackerel, tins or jars of fish Fresh or frozen fish
(including anchovies, sardines and pilchards), fish paté or paste
Tinned foods
Check soups and vegetables Prepare fresh soup or choose suitable lower salt products
Use fresh, frozen or salt‐free tinned vegetables and pulses in place of tinned
vegetables with added salt. If you cannot find salt‐free products, rinse the
can’s contents in a colander under running water to remove excess salt
Ready‐made gravy and sauces
These include tomato ketchup, soy, brown, barbecue, mayonnaise, Use these sauces sparingly or replace with a lower salt brand if available. You
pickles, mustard, tabasco, curry paste and pesto could make a stock and/or gravy from suitable ingredients, rather than using
cubes or granules. Try apple, cranberry or mint sauces
Manufactured jars of tomato‐based sauces are often lower in salt than cheesy
ones or those containing olives, bacon or ham. Alternatively, make a sauce
with fresh ingredients such as tomatoes/tomato purée and garlic
Takeaway foods
Including Chinese, Indian, kebabs, fried chicken, burgers and salted Make pizza at home:
chips Spread a base with salt‐free tinned smooth chopped tomato and add
home‐cooked meat, chicken, red peppers, onions, sweetcorn and mushrooms
Unsalted oven and microwave chips
Go to a local restaurant or takeaway shop that will prepare your foods freshly
with minimal salt, e.g. fresh meat or chicken kebab with pitta bread (not
doner or kofte kebab)
In a takeaway or restaurant choose plain rice, sticky or coconut rice rather
than egg fried or pilau rice
Salty snacks
Avoid most crisps, salted nuts, mini cheddars, salted or flavoured corn Choose salt‐free crisps, some toddler finger food sticks/straws (check the label
snacks, olives, most sun‐dried tomatoes, peanut butter, pickles and for salt content), sesame or sunflower seeds (be aware of the choking hazard
some savoury spreads (including yeast extracts) for a child under 5 years)
Popcorn (unsalted), dried fruit, trail mix
Rice cakes, crumpets, croissants, toast
Biscuits, cakes
Source: Adapted from the advice sheet produced by the nephrology dietetic team at Great Ormond Street Hospital for Children NHS Foundation Trust,
London, UK.
Renal Stones 279
these side effects. Free access to water during the day and at Growth has been reported to be suboptimal in long‐term
night is important, and Sharma noted in their cohort [174] follow‐up studies [203, 208], but near normal in others [174].
that the median fluid intake at the age of 13 years in their In the latter, median z‐scores for weight improved from −2.1
sample was 3800 mL/m2 BSA (range 1600–9200 mL/m2 BSA), at presentation to 0.2 at last follow‐up; median height SDS
the mean BSA at this age being 1.4 m2. Nocturnal enuresis is a remained essentially unchanged −1.06 at presentation to
commonly reported problem related to the high fluid intake, −0.9 at last follow‐up.
resolving at a median age of 11 years [174]. Conversely, the
over‐provision of water can drive urine output and poten-
tially result in water intoxication [207]. The reported feeding Learning points: nephrogenic diabetes insipidus
problems, including vomiting and poor appetite, improve in
early childhood with good adherence to salt control and • Feeding problems are common in infancy (related to poly-
medications. Most children take adequate nutrition orally, dipsia, vomiting and constipation)
but regular dietary assessments through childhood can be • Feed renal solute load in infants should be reduced to
helpful to ensure that the recommended intakes for energy, ≤15 mOsm/kg H2O per kg body weight
protein and micronutrients are still being met. • Allow free access to water
Providing advice on how to manage acute episodes of GI • May need tube feeding support up to 2 years of age
symptoms such as vomiting or diarrhoea is important. To pre- • Wean onto a low sodium diet initially
vent hypernatraemic dehydration, a glucose polymer solution • Expand intake up to a reduced salt diet (‘no added salt’) by
can be offered in place of the usual oral rehydration solutions. the age of 2 years
As a precaution, clear instructions should be given on the • Episodes of diarrhoea and vomiting should be managed by
preparation of a 10% concentration of a glucose polymer (10 g offering a glucose polymer solution (e.g. at 10% concentra-
in 100 mL water) using scoop measurements or pre‐measured tion), rather than a rehydration solution
sachets along with a very small supply of suitable product.
Renal Stones
Urolithiasis (or urinary stone disease) is a heterogeneous urolithiasis in adults, with less acute abdominal pain or hae-
group of conditions where minerals crystallise to form hard maturia. The large UK paediatric cohort [209] reported that
solid stones, or calculi, in the urinary tract. They are typically 36% children presented with a urinary tract infection, 32%
classified by their main chemical component (calcium, uric with abdominal pain and 27% with haematuria (especially in
acid, struvate or cystine) or location, e.g. nephrolithiasis (in children <6 years) and 13% were asymptomatic (some pre-
the kidney). Stones vary in size from less than 3 mm diame- senting with more than one main symptom).
ter to larger stones that can block urinary flow and cause The medical management of children with renal stones
renal damage. Stones are less common in infants and chil- involves alleviating acute pain, prevention of renal damage,
dren than in the adult population. A recent UK single‐centre managing infections or obstruction and facilitating passage
retrospective paediatric cohort of 511 patients over a 22‐year or removal of stones. Diagnosis is confirmed by an ultra-
period [209] reported a median age of presentation of sound, enabling assessment of the size of the stone, location
4.4 years for males and 7.3 years for females, but stones were and degree of urinary obstruction. Kidney stones less than
reported from as young as 1 month of age. Paediatric renal 3 mm (‘gravel’) are likely to pass spontaneously [211]. Many
stone disease is more common in males than females, espe- stones can be cleared by lithotripsy using high energy shock
cially in the first decade. waves directed towards the stone. If the stones are in the
A significant proportion (20%–60%) of paediatric patients middle or lower portion of the ureter, an ureteroscopy can
have an underlying condition that is conducive to stone for- assist in removing the stone. Larger and more complex
mation, e.g. a metabolic disorder, urinary tract abnormality stones (such as staghorn stones) in the upper urinary tract
(especially if leading to urinary stasis or risk of an infection), may require percutaneous lithotomy [212].
tubular damage secondary to medications (e.g. furosemide) The majority of stones in children are composed of cal-
or frequent urinary tract infections [209]. There has been a cium oxalate (≥75%) or calcium phosphate (10%–20%), fol-
shift over the past decades in paediatrics from predomi- lowed by struvite, cystine or uric acid in descending order
nantly infectious to metabolic causes and 30%–40% of [209, 213]. Cystinuric patients often present with larger
children have a family history of stone disease [209, 210]. stones and higher new stone formation rates and are more
The prevalence of paediatric urolithiasis varies between likely to require surgery [214]. Evaluation of the composition
countries, with high rates reported in Turkey, Pakistan and of the stone (if available), together with identification of
Saudi Arabia compared with the UK, the USA and Japan. The underlying metabolic risk factors, guides treatment and
incidence and prevalence in developed countries appears to directs targeted advice to prevent recurrence. Metabolic risk
be increasing, particularly in adolescents [210], although this factors include hypercalciuria, hyperuricosuria, hyperoxalu-
may reflect more sensitive imaging technology. The initial ria, cystinuria, disorders of purine metabolism and hypoci-
presentation in children differs from the classic signs of traturia, in addition to environmental factors such as diet
280 Kidney Diseases
and fluid intake. A metabolic screen on a 24 hour urinary Fluid

sample (or a spot urine sample for younger children) is usu-
ally performed along with microscopy to assess for an infec- Dehydration can contribute to the formation of all forms of
tive aetiology [215]. Most UK laboratories will report stones, and this may be secondary to a low fluid intake, high
paediatric urinary concentrations indexed to creatinine dermal or ileostomy losses or diarrhoea. Children with
(rather than BSA or body weight) and have age and sex refer- stones have been reported to have a lower 24 hour urine
ence intervals for some of these. However, there is little evi- volume than controls [220]. An increase in fluid intake will
dence‐based published data and no universally accepted increase urine output, preventing urine stagnation and
standards, so interpretation of urinary values can be diffi- reducing saturation of some solutes such as uric acid, cal-
cult. Table 13.25 gives a guide to normal urinary reference cium, oxalate and cystine molecules [221]. A minimum
values [215, 216]. urine flow of 1 mL/kg/hour has been shown to reduce the
Stone recurrence can be frequent in children (30%–67%) urinary saturation of calcium oxalate, calcium phosphate
[217, 218] especially if there is an underlying metabolic and uric acid [222]. A very high urine output may be neces-
abnormality, with a mean interval of 3–6 years. The preven- sary for patients with cystinuria as the aim of treatment is to
tion of recurrence focuses on improving the balance between reduce the urine cystine concentration below 1 mmol/L
the crystal‐forming and crystal‐inhibiting substances in the (240 mg/L). A prospective randomised trial in 199 adult cal-
urine [219]. The treatment approaches in c hildren are based cium stone formers [223] confirmed the importance of fluid,
largely on extrapolation of adult studies, single institution an intake of more than 2 L/day delaying and reducing total
cohorts or case series in children. The main pharmacological frequency of stone recurrence during the 5‐year follow‐up.
and dietary treatment options used in relation to paediatric A similar fluid intake (1–2 L) has been recommended for
kidney stones are shown in Table 13.26. children [213, 224], but the optimal fluid intake for different
Table 13.25 Guide to normal urinary reference values.
Refer to country, age and laboratory‐specific reference intervals.
Spot urine [215]

Solute 24 hour excretion [216] (from 2nd morning sample)
Calcium (Ca) <0.1 mmol/kg Ca–creatinine ratio (mmol/mmol)

(<4 mg/kg) <1 year <2.2
1–5 years <1.5
5–17 years <0.8
Magnesium (Mg) >3.6 mmol/1.73 m2 Mg–creatinine ratio (mmol/mmol)
(>88 mg /1.73 m2) <1 year <2.2
1–5 years <1.3
5–17 years <1.0
Phosphate (P) P–creatinine ratio (mmol/mmol)
<1 year <19
1–5 years <14
5–17 years <5
Citrate Citrate–creatinine ratio (mmol/mmol)
Female <0.55
Male <0.33
Oxalate <2 mg/kg Oxalate–creatinine ratio (μmol/mmol)
Infant <98
Child <72
Cystine <60 mg/1.73 m2 Cystine–creatinine ratio (μmol/mmol)
<3 months <35
3 months to 3 years <25
>3 years <20
Uric acid (urate) <815 mg/1.73 m2 Uric acid–creatinine ratio (mmol/mmol)
<35 mg/kg <2 years <1.96
2–6 years <1.35
6–18 years <0.85
Creatinine1 0.1–0.2 mmol/kg
15–25 mg/kg
1
Often measured in a 24 hour urine sample to check adequacy of collection.
Salt 281
Table 13.26 Pharmacological and dietary treatment options for paediatric renal stones.
Type of stone Medications Possible dietary changes
Calcium Potassium citrate High fluid intake

(calcium oxalate or phosphate) (increases urinary citrate) Adequate calcium
Thiazide medication Reduced salt diet
(reduces hypercalciuria) Avoid vitamin C supplements
Uric acid Potassium citrate High fluid intake
Allopurinol (reduces the amount of uric acid Reduced dietary purine (probably
made by the body by blocking xanthine not useful)
oxidase)
Struvate Antibiotics High fluid intake
Cystine Potassium citrate High fluid intake
Penicillamine or mercaptopropionylglycine Reduced salt diet
(helps dissolve urinary cystine)
Hyperoxaluria Potassium citrate High fluid intake
Pyridoxine (in some cases) Low oxalate diet (probably not
useful)
age groups has not been investigated. A suggested intake of hence, risk of stone recurrence. The National Institute for
at least 3 L has been proposed for children with cystinuria, Health and Care Excellence (NICE) is producing guidelines
1 L of fluid for every millimole of cystine excreted [225], but on the assessment and management of renal and ureteric
compliance with this is difficult. Some adult research sug- stones that will include dietary and lifestyle advice [224].
gests that water, milk and fruit juices (except grapefruit, Lack of clinical trial data in children means that adult data is
cranberry or apple juice) are all appropriate fluids [226]. often extrapolated by clinicians to the management in chil-
However, consumption of fructose‐containing drinks been dren. The role of diet in preventing paediatric renal stone
shown to increase oxalate and calcium excretion in adults, recurrence is now discussed.
increasing stone risk [227]. Extra fluids are ideally given as
water, rather than fructose or sugar sweetened drinks, espe-
Salt
cially as a link between stones and obesity has been seen in
adults. Prevention of dehydration is central to management,
High dietary sodium intake decreases proximal tubular
and practical advice should be given on regular drinking
sodium and calcium reabsorption, increasing urinary cal-
both day and night, during sports and exercise, during car
cium excretion [232]. Hypercalciuria is found in approxi-
and airplane journeys and in hot weather. Alcohol is also a
mately 30%–50% of stone‐forming children [233]. For
risk factor causing dehydration, so young people should
individuals at risk of developing renal stones, a reduction in
be cautioned about this (taking extra water alongside if
salt intake is helpful to reduce hypercalciuria [230, 234] and
appropriate).
cystinuria [235], and this also increases urinary citrate [236].
However, the level of sodium restriction required has been
Nutritional management debated.
Following a literature review, Tasian [213] recommended
Dietary interventions may reduce urinary stone formation reducing sodium intake to <2–3 mmol/kg for young c hildren
and recurrence, but there is no conclusive consensus in the and <2.4 g sodium/day (<6 g salt/day) in adolescents with
literature regarding their effectiveness in children [221, 228]. hypercalciuria or calcium‐based stones. The usual practice
Restrictive diets may alter urine concentration of solutes, but in the UK is similar, advising on a reduced salt diet (approxi-
not necessarily translate to decreased stone formation [229]. mately 3 mmol sodium/kg; 2–6 g salt per day depending on
The regulation of urine saturation and crystallisation is com- age), achieved by omitting adding salt to meals and avoid-
plex, and dietary alterations of a single component may be ing high salt foods such as most takeaway foods, processed
too simplistic an approach. An example of this has been the meat, cheese, smoked fish, savoury snacks, ready meals and
previous misconception that limiting oral calcium intake high salt soups and sauces (Table 13.24). Personalised practi-
would reduce hypercalciuria and risk of calcium‐containing cal advice based on a careful diet history will improve com-
stones. Paradoxically, diets low in calcium carry an increased pliance. This should include education on identifying high
risk of renal stones, possibly due to lower binding with die- salt manufactured foods, adaptation of standard recipes and
tary oxalate in the gut leading to increased oxalate absorp- ideas for suitable snacks. Salt taste preferences are depend-
tion [230]. A Cochrane review assessing the effectiveness of ent on the salt level in the diet, so it can take time for a child
diets for adults with renal stones [231] concluded that a low with a high salt intake to become accustomed to a reduced
protein, low salt diet (with a normal calcium content) intake. The degree of salt restriction imposed can be reas-
reduced oxaluria, urinary calcium oxalate saturation and, sessed depending on urinary composition.
282 Kidney Diseases
Calcium being to increase fluid intake, reduce salt, consume

a dequate calcium and avoid high doses of supplemental
Deposition of calcium oxalate may be a result of hypercal- vitamin C [249].
ciuria, hyperoxaluria or hyperuricuria or because of hypoci- Primary hyperoxaluria types 1, 2 and 3 (PH1, PH2, PH3)
traturia. Hypercalciuria is usually defined as a calcium are inherited disorders of oxalate metabolism causing
excretion of more than 0.1 mmol/kg (4 mg/kg/day) or a increased liver oxalate production and higher urinary oxa-
urinary calcium–creatinine ratio above 1.5 mmol/mmol late excretion with risk of nephrocalcinosis and nephrolithi-
[237], but this is age dependent (being highest in younger asis. Pyridoxine supplements (vitamin B6) can reduce the
children) (Table 13.25). urinary excretion of oxalate by over one third in about
Hypercalciuria is not usually due to a high calcium intake, 10%–30% children with PH1. Dietary oxalate does not
so decreasing calcium intake is not advised. A low calcium significantly affect urinary oxalate in PH.
intake actually increases stone risk, and an increase in cal- Some GI conditions are linked to a higher risk of stones as
cium intake decreases risk of stones in adults [232]. Ensuring a consequence of increased oxalate absorption in the gut. This
adequacy of calcium intake should be part of the dietary can happen secondary to cystic fibrosis, biliary tract disease,
management to prevent stone recurrence. inflammatory bowel disease and short bowel s yndrome. In
these situations, malabsorbed free fatty acids and bile salts
may bind to calcium in preference to oxalate, increasing the
Citrate absorption of free oxalate (secondary alimentary hyperoxalu-
ria). The effectiveness of limiting dietary oxalate intake to
Hypocitraturia is a common metabolic alteration seen in
reduce the risk of renal stones in these children has not been
about 60% of children with nephrolithiasis [238]. Low citrate
researched. It is probably more important to reduce the diar-
excretion can also occur secondary to use of a ketogenic diet
rhoea and control the malabsorption if possible.
for epilepsy, renal tubular acidosis and diarrhoea. Citrate
acts as an inhibitor for crystal formation and increases the
solubility of stone‐forming calcium salts. Most international Urate
guidelines recommend the administration of alkaline citrate
medication (usually potassium citrate) to prevent stone Hyperuricosuria is an independent risk factor for calcium
recurrence, and this is also given prophylactically to children stones, as uric acid decreases the solubility of calcium
on ketogenic diets [239]. Citrus (lemons, oranges, grapefruit oxalate. In addition, children can also have uric acid stones
and lime) and non‐citrus (melon) fruit are natural sources of (containing xanthine or 2,8‐dihydroxyadenine) due to dis-
citrate, and there is some low quality evidence that these orders of purine overproduction, renal tubular problems
fruits and/or their juices can increase urine citrate levels in or excessive purine ingestion. Purines are metabolised to
adults [240, 241]. uric acid. The main treatment for preventing uric acid
stones is increased fluid intake, alkalinisation of the urine
and allopurinol medication (if overproduction of uric acid
Oxalate is a problem). Dietary purine restriction has been sug-
gested for adults with hyperuricosuria, but is not thought
The most common paediatric stones are predominantly cal- appropriate for children because of the efficiency of allopu-
cium oxalate, and a high urinary excretion of oxalate is a rinol medication [213].
risk factor. Hyperoxaluria may be secondary to increased
oxalate absorption (often called enteric hyperoxaluria) or
high dietary intake or as a consequence of an inherited Protein
defect in oxalate metabolism (primary hyperoxaluria).
Urinary oxalate is primarily produced from endogenous High protein diets, especially from animal protein, can
metabolism of glycine, glycolate, hydroxyproline and vita- increase urinary calcium, decrease urinary citrate and pH
min C, with estimates varying from 10% to 50% originating and also increase urinary uric acid (being a source of
from diet [242, 243]. Oxalate is mainly consumed as plant purines). However, although low protein diets in adults
and plant products, but their reported content varies widely have been shown to reduce the risk of stone formation [230],
reflecting different analytical techniques, processing, restricting protein intake in growing children is not appro-
cooking methods, soil content and even time of h arvest, priate. For intractable recurrent paediatric stones, a cautious
along with many factors that influence its bioavailability reduction in dietary animal protein intake towards the RNI
[244–246]. Although there is no accepted definitive list, the [18] may be appropriate if a dietary assessment indicates a
following consistently have a high content: spinach, beet- high consumption [250].
root, okra, rhubarb, strawberries, almonds, peanuts,
cashew nuts, chocolate and wheat bran. A randomised clin- Probiotics
ical trial in stone‐forming adults indicated that reducing
dietary oxalate lowered urinary oxalate excretion [247], but Theoretically, probiotics could enhance intestinal oxalate
there is little evidence that reducing intake decreases stone metabolism or decrease gut absorption, reducing urinary
risk [248]. Oxalate restriction is not generally recommended oxalate excretion. However, there is insufficient evidence to
in children at risk from oxalate stones [213], the advice support their use in reducing calcium oxalate stone risk [247].
Idiopathic Infantile Hypercalaemia 283
Struvite stones To maintain cystine solubility, individuals are encouraged

to have a very high fluid intake (e.g. 1.5–2 L/m2 BSA), which
Calculi containing struvite (magnesium ammonium phos- should be distributed throughout the day and night ideally.
phate or triple phosphate stones) result from infections with The aim of treatment is to keep urinary cystine levels below
urea‐splitting bacteria and are usually large, sometimes fill- 1 mmol/L. In addition, as cystine is more soluble in alkaline
ing the entire renal pelvis (known as staghorn calculi). urine (optimal pH between 7 and 7.5), potassium citrate and
Struvite stones have to be removed surgically and can cause bicarbonate are often given to prevent calculi forming. For
serious morbidity, being more likely to result in CKD than some children with a high stone recurrence rate, other medi-
other calculi [209, 251]. In the UK cohort [209], 26% of those cations to increase cystine solubility may be given (e.g.
who ended up with CKD also had an underlying structural thiols). A reduced salt diet (Table 13.24) should be advised as
abnormality, which probably contributed to the develop- this will reduce urinary cystine excretion [235], as sodium
ment of infection. Heilberg [252] concluded that diet has no and cystine transport is coupled in the renal tubule. As cys-
definitive role in the prevention of struvite stones following tine is a non‐essential amino acid synthesised from methio-
a comprehensive literature review. However, a high fluid nine, methionine (or protein) restriction theoretically can
intake is usually advised in the presence of normal glomeru- reduce urinary cystine and increase urinary pH. However,
lar function, but the main medical management is focused limiting protein intake is not appropriate in growing chil-
on preventing further infections. dren. For recurrent intractable stones, it may be helpful to
identify children with a very high protein intake and advise
a reduction to nearer the RNI for age.
Cystine
Cystinuria is an autosomal recessive disorder arising from

Learning points: renal stones
defective reabsorption of four amino acids (cystine, ornith-
ine, arginine and lysine) by their common transporters in
To prevent recurrence (especially for cystine stones):
the proximal tubule of the kidney. Only cystine causes prob-
lems due to its low solubility. Patients with homozygous • increase fluids (2–3 L/day depending on age and diagnosis)
cystinuria may excrete up to 30 times the normal amount of • advise a reduced salt diet
cystine, and heterozygotes up to 10 times. Cystine is poorly • ensure adequate calcium intake
soluble and precipitates to form cystine stones in the kid- • stop vitamin C supplements
neys, ureter and bladder (accounting for about 1% of paedi- • avoid very high protein intake (if very frequent stone
atric renal stones). Half of individuals with cystinuria recurrence)
develop their first stone by the age of 10 years and 25%–40% • minimal benefit from reducing dietary oxalate or purine intake
before 20 years [253].
Hypercalcaemia
Hypercalcaemia is uncommon in children, but can be associ- immobilisation, inherited metabolic disorders or occurring
ated with long‐term morbidity including renal, cardiac and secondary to phosphate depletion (e.g. in premature or low
neurological problems. The usual definition of hypercalcae- birthweight infants) [254]. Congenital anomalies associated
mia is a total (albumin‐corrected) plasma calcium (Ca) with hypercalcaemia include idiopathic infantile hypercal-
>2.6 mmol/L or an ionised Ca >1.3 mmol/L, severe levels caemia (IIH) and Williams syndrome.
being >3.0 and >1.5 mmol/L, respectively [216]. However,
reference ranges vary with different laboratories and are age
dependent, with higher levels in infants compared with Idiopathic infantile hypercalaemia
children.
The management of hypercalcaemia involves identifying IIH is an autosomal recessive disorder resulting in high levels
the underlying cause and initiation of treatment to lower of active vitamin D and hypercalcaemia in infancy, often
serum calcium (including fluids, antiresorptive medications resolving by the age of 2 years. Inadequate 24‐hydroxylase
and potentially surgery). A reduction in calcium intake from enzyme activity results in impaired catabolism of vitamin D,
enteral, parenteral, medicinal and supplemental calcium leading to high intestinal calcium absorption, decreased cal-
(and vitamin D) is often appropriate, particularly when cium excretion and increased osteoclastic activity [255]. Infants
increased intestinal absorption is a possible aetiology. present in the first year with severe vomiting, dehydration,
The causes of hypercalcaemia are diverse and may be constipation, faltering growth, weight loss and lethargy, which
genetic or acquired, including abnormalities of parathyroid can be exacerbated by the administration of supplementary
hormone or vitamin D metabolism, malignancies, vitamin D. Hypercalciuria and nephrocalcinosis may develop
284 Kidney Diseases
and persist into adulthood, increasing the risk of renal more severe restriction [262]. Standard infant formulas or
stones. Treatment may be limited to simple oral hydration, breastfeeding may need to be stopped and replaced with
discontinuation of additional vitamin D supplementation and Locasol, a nutritionally complete formula low in calcium
possibly short‐term dietary calcium restriction. However, and vitamin D. This formula can be given to infants or used
more severe cases reported in the literature have required ster- as a supplementary drink in hypercalcaemic children. When
oid, bisphosphonates and even haemodialysis [255]. If a die- prepared using deionised or distilled water (available in the
tary restriction is imposed, a gradual increase in calcium UK on prescription), Locasol provides <7 mg cal-
intake to normal levels is recommended after 6–12 months to cium/100 mL. The calcium content of tap water in the UK is
reduce risks of rickets and poor dentition [256]. Lifelong available by contacting the relevant water suppliers (www.
avoidance of vitamin D supplements should be advised. water.org.uk); hard water can contribute over 0.3 mmol
(12 mg) calcium per 100 mL. The level of calcium restriction
is determined by blood calcium levels and may need to
Williams syndrome remain low throughout infancy and early childhood, e.g. at
300 mg (7.5 mmol) daily, which is less than the RNI (or popu-
Williams (or Williams–Beuren) syndrome (WS) is a rare auto- lation reference intake) in most countries. However, this
somal dominant multisystem disorder known to be associ- should be relaxed when possible, especially if serum PTH or
ated with hypercalcaemia in infancy. It is characterised by alkaline phosphatase starts to rise. Rickets has been described
cardiovascular abnormalities, distinct facial features (often in infants with WS [263] as a result of inappropriate pro-
referred to as elfin face), low muscle tone and manifestations longed treatment of hypercalcaemia. If serum calcium and
relating to endocrine and nervous system disturbances. urinary calcium–creatinine ratios are in the age‐appropriate
Hypercalcaemia has been reported in 5%–50% patients range, then dietary calcium restriction is not necessary.
with WS, but is often transient and mild [257–259]. The mech- Breastfed infants with WS without hypercalcaemia may
anisms underlying this are not known, but may be due to need additional vitamin D to prevent rickets (along with
hypersensitivity to vitamin D, increased 1,25‐dihydroxyvita- careful monitoring).
min D or defective calcitonin metabolism. Hypercalcaemia is Infants are usually born at term, but often with a low
most likely to be symptomatic in infancy, levels normalising birthweight [90], and gain weight poorly and may continue
between 2 and 4 years of age although recurrence in puberty to have a decreased BMI and percentage body fat up until
has been reported [260]. Hypercalcaemia is clinically rele- early adulthood. Conversely, a longitudinal study [264]
vant if it leads to hypercalciuria and nephrocalcinosis. reported that nearly 60% of their WS patients (median age
Nephrocalcinosis is rare and may improve in time, with a 13.6 years) were overweight or obese and 25.9% and 11%
report from Italy finding no evidence on ultrasound in a patients had impaired glucose tolerance and type 2 diabetes,
cohort of 57 WS patients [258]. Guidelines from the American respectively. The weight gain in WS adults is particularly
Academy of Pediatrics [260] suggest a urinalysis for total cal- related to fat accumulation in the lower extremities, as
cium 2–4 yearly, depending on baseline calcium, with spot assessed by thigh circumference [265]. Growth charts for
urine calcium–creatinine ratios every 2 years. However, oth- British children with WS have been published [266] with
ers suggest symptom‐based testing, triggered by changes in data from 169 children and adults with an established genetic
feeding pattern and behaviour, irritability, nausea and vomit- diagnosis. These allow improvement in growth monitoring
ing and/or signs of dehydration [257]. and picking up growth abnormalities that may require
In infants with WS, hypercalcaemia appears to exacerbate further medical investigation.
colic and cause extreme irritability, poor appetite, mild hypo- Infants with WS may experience feeding problems from
tonia and constipation, but not all infants are symptomatic 2 to 3 months of age including feed refusal, reflux, vomiting,
[258]. The acute management of hypercalcaemia may include a sensitive gag reflex, symptoms of colic, constipation and
IV hydration (particularly in infants), to improve urinary disordered suck or swallowing patterns [256]. Weaning onto
calcium output, and the administration of loop diuretics solid foods may be delayed as they may not readily accept
together with a strict reduction in calcium intake and v itamin change in textures (tactile sensory defensiveness). These
D intake. Vitamin D supplements (including multivitamin feeding difficulties tend to resolve in early childhood,
formulations) should be avoided during the stabilisation although gastro‐oesophageal reflux may continue to be a
period as this will significantly increase calcium absorption. problem. Abnormal dentition including small, widely
If hypercalcaemia and hypercalciuria are present, part of the spaced, crooked or missing teeth and malocclusion are com-
dietetic review should include an assessment of fluids, monly reported [267].
advising an increase if necessary, e.g. to 160–200 mL/kg for For children and weaned infants, a low calcium diet limits
an infant to prevent nephrocalcinosis. high calcium foods such as milk and milk products, tinned
Clinical practice guidelines for WS in the UK [261] suggest fish (where the bones are eaten), tofu and calcium or vitamin
calcium intake may need to be reduced to equal or less than D fortified foods (such as orange juice, breakfast cereals and
half the RNI of the child’s age group [18]. However, for some breads). Table 13.27 gives a guide for low calcium and vitamin
infants, lowering of serum calcium is only achieved after D diet. For a 5‐year‐old, this would achieve a calcium intake
Williams Syndrome 285
Table 13.27 Guide to a low calcium and vitamin D diet.
Refer to country‐specific food composition tables if available.

In the UK it is mandatory to fortify all wheat flour (except self‐raising flour with a calcium content ≥0.2% or wholemeal flour) with calcium carbonate,
according to the Bread and Flour Regulations 1998 (SI 1998/141) (www.legislation.gov.uk/uksi/1998/141/contents/made); this addition will be
declared on the ingredient list of products made from these flours. Flour milled and imported from elsewhere may not be fortified.
The calcium naturally present in wholemeal flour may be less bioavailable, due to the present of phytate.
Foods to avoid Suitable alternatives
Water
Tap or bottled water Purified water (deionised or distilled)
Milk and milk products
Infant formulas Locasol (Nutricia)
Cow’s milk – any fresh or dried (whole, semi‐skimmed, skimmed, evaporated, Unfortified (often organic): coconut, rice, soya drinks. Rice drinks
condensed) are not advised under 4½ years of age
Other mammalian milks (including goat, sheep and buffalo)
Calcium fortified milk substitutes, e.g. soya, oat, almond, hemp, coconut
White or cheese sauce
Yoghurt, fromage frais, rice pudding, ice cream, ready‐made custard, instant Jelly, sorbet, pure ice lollies, meringue
custard powder mix
Cheese, cream, quark, crème fraiche Make custard using custard powder and milk substitute. Non‐
milk, non‐fortified ice cream, e.g. soya and coconut (check labels)
Oils and spreads
Margarines and spreads fortified with vitamin D Butter, cooking fats, oils, lard
Cod liver oil
Meat
If made with fortified flour, cheese or milk, e.g. meat pies, lasagne All are suitable – unless made into a product with fortified flour,
cheese or milk
Fish
Oily fish or fish with edible bones, e.g. whitebait, sardines, pilchards, anchovies, White fish, e.g. cod, haddock, hake, monkfish, halibut, plaice,
salmon, mackerel, herring, anchovies, tinned tuna, trout, kippers, eel sole, skate
Prawns, mussels, oysters, fish paste
Eggs
Particularly egg yolk Egg white
Egg dishes, e.g. omelette, quiche
Flours
Calcium fortified wheat flour or products made with this, e.g. bread, crumpets, 100% wholemeal, granary, rye, rice, cornflour, gram flour
biscuits, muffins, bagels, scones, some pasta*, noodles
Self‐raising flour (white, brown or wholemeal) or products made with this, Wholemeal, granary, rye, oats or wholegrain products not made
e.g. cakes with self‐raising flour e.g. bread, chapattis, pitta bread and biscuits
Soya flour Barley, rice, oats, sago, tapioca
Baking powder
Ordinary baking powder A substitute can be made from cream of tartar and bicarbonate
of soda
Breakfast cereals
Calcium and/or vitamin D fortified breakfast cereals All unfortified cereals are suitable unless they have added
unsuitable nuts, seeds or dried fruit
Nuts and seeds
Almonds, brazil nuts, hazelnuts, pecans, pistachios, walnuts Peanuts and peanut butter
Sesame seeds and sesame seed pastes, e.g. tahini Sunflower seeds
Fortified products (with calcium or vitamin D)
e.g. baby rusks, orange juice, breakfast cereals
Fruits
Dried figs, sultanas, raisins, currants, prunes, apricots All other fruit
Rhubarb, orange
286 Kidney Diseases
Vegetables/pulses
Okra, kale, spinach, broccoli, spring greens, watercress, olives All other vegetables
Tofu – especially if firm Small portions only of broad beans, chickpeas, baked beans,
(often processed with calcium sulphate) kidney beans, hummus
Malted and chocolate drinks, malted milk products
Drinking chocolate, Horlicks, Ovaltine drinks and malted milk drinks Purified water (deionised or distilled)
and biscuits Unfortified fruit juice of allowed fruit, e.g. apple, grape,
pineapple
Fruit squash
Sugary drinks, e.g. lemonade, cola drinks
Confectionery
Chocolate, fudge, toffee, chocolate spread Boiled sweets, lollies, pastilles, peppermints, jam, syrup, honey
*Pasta made from wheat flour milled in the UK is also fortified with calcium; pasta made in other countries may not be.
Source: Adapted from the advice sheet produced by the nephrology dietetic team at Great Ormond Street Hospital for Children NHS Foundation Trust,
London, UK.
of less than 250 mg/day. Locasol can be used as a milk substi- Learning points: hypercalcaemia
tute at any age to ensure nutritional adequacy, but unfortified
(usually organic) rice, oat or other plant‐based drinks can also • Paediatric hypercalcaemia has a diverse aetiology including being
be offered to older children. Once serum calcium is approach- secondary to abnormalities of PTH or vitamin D metabolism or
ing the normal range, the calcium intake can be increased status, phosphate depletion malignancy or immobilisation
gradually (e.g. by about by 120 mg at a time, equivalent to • Williams syndrome (WS) and idiopathic infantile hypercalcae-
100 mL cow’s milk) as indicated by blood biochemistry. To mia (IIH) are inherited disorders, usually presenting in infancy
avoid hypercalcaemia, patients are advised to use sunscreen • WS is a multisystem disorder with hypercalcaemia present
to minimise endogenous vitamin D production. in 5%–50%, which is usually mild and resolves by the age
A high incidence of decreased bone mineral density has of 2–4 years of age
been described in adults with WS [265, 268], which may be a • IIH presentation may be precipitated by the use of vitamin
consequence of a prophylactic low calcium diet, initiated by D supplements
parents or professionals. • Symptoms of hypercalcaemia include nausea, vomiting,
Gastrointestinal problems, including chronic constipa- irritability, poor appetite, polyuria, polydipsia, constipa-
tion and colonic diverticulitis, have been reported more tion, faltering weight and height in infants
frequently in WS compared with the general population • A low calcium and vitamin D diet may be appropriate, but
[269, 270], causing recurrent or acute abdominal pain. This is not usually needed beyond infancy
may not be identified promptly, as WS children have been
reported to have an increased pain tolerance. Acute man-
agement of diverticulitis may involve a reduction in die-
tary fibre, but, once in remission, incorporating adequate
soluble and insoluble fibre (fruit, vegetables, oats, pulses,
wholegrain cereals) and fluids may help to minimise
recurrence.
14
David Hopkins and Luise Marino
Congenital Heart Disease
Introduction CHD [6] but interestingly also highlighted the possibility

of good maternal nutrition, including multivitamin prepa-
Congenital heart disease (CHD) in infancy and childhood rations, in reducing CHD incidence.
refers to structural abnormalities that arise in the four main
chambers of the heart itself and/or the great vessels that lead
Learning points: incidence of CHD
to or from the heart. The type, size and combination of
lesions determine the ability of the heart and lungs to,
• Incidence in the West is between 6 and 8 cases in every
respectively, pump and oxygenate blood. This affects the
1000 births
workload and energy utilisation of these organs and associ-
• Incidence is much higher in children with genetic defects
ated musculature that, in turn, determines the type and
extent of faltering growth seen in CHD.
A glossary is given, describing cardiac anomalies and
corrective procedures (p. 311–313). Screening and diagnosis
Some congenital cardiac anomalies are detected by ultra-

Incidence sound at antenatal screening, others during the postnatal
check‐up, while some may present acutely with cardiogenic
The incidence of clinically relevant moderate to severe
shock and elevated blood lactate levels or, chronically, with
forms of CHD in Western Europe and North America is
faltering growth. Table 14.1 summarises the pathways to
between 6 and 8 in every 1000 live births [1, 2], accounting
diagnosis.
for a third of all congenital abnormalities [3]. In Africa the
incidence is lower at around 2 cases per 1000 births [3], but
this may be due to underdiagnosis. It is highest in Asia, Prevalence of faltering growth in CHD
with incidence in Taiwan at around 13 per 1000 births [4].
Eight lesions make up 80% of cases, the most common of Faltering growth is common in CHD [7–10]. Up to a quarter
which are ventricular septal defect (VSD), persistent duc- of patients have weight for height < −2 SD and mean weight
tus arteriosus (PDA), atrial septal defect (ASD) and tetral- for age < −1 SD, and weight for age may cross down two
ogy of Fallot. Children with genetic defects have a higher centile bands in up to 30% of cases prior to corrective
incidence: 50% in infants with Down’s syndrome, present- surgery [8]. In countries where diagnosis may be delayed, an
ing with ventricular or atrioventricular septal defects, and even higher proportion of patients with uncorrected CHD
80% in Noonan syndrome, presenting mainly with pulmo- present with faltering growth. Okoromah has described
nary stenosis or hypertrophic cardiomyopathy [5]. One wasting (weight for height SD score < −2) in 58% of acyanotic
study has implicated increasing maternal and paternal age cases and stunting (height for age SD score < −2) in 68% of
and antenatal febrile illness with increasing incidence of cyanotic cases [11].

288 Congenital Heart Disease
Table 14.1 Modes of diagnosis of congenital heart disease.
Postnatal signs and symptoms
Antenatal Early Late Confirmation
Antenatal ultrasound Heart murmur 1

Collapse with elevated blood lactate 4
Echocardiography
Absent femoral pulse 2
Faltering growth 1,5
Cardiac catheterisation*
Cyanosis3
1
Ventricular or atrial septal defects (VSD/ASD) and persistent ductus arteriosus (PDA).
2
Coarctation aorta.
3
Cyanotic heart lesions.
4
Coarctation of aorta.
5
Complex heart disease.
* In very rare cases.
Learning points: prevalence of faltering growth
th th th st th .6
6.5
2n th 25 50 75 91 98 99
6
• Faltering growth is common
• Up to a quarter of patients have marked wasting 5.5
• Delayed diagnosis increases the prevalence and severity of 5
99.6th
faltering growth 98th 4.5
91st
75th
4
Pathogenesis of faltering growth in CHD
d
9
50th 3.5 h
4t
25th 0.
3
The extent and type of growth attenuation in CHD depend 9th
on how the different lesions affect different metabolic pro- 2nd 2.5
0.4th
cesses. Not all CHD results in faltering growth. Some lesions, 2
such as transposition of the great arteries (TGA), may be
1.5
diagnosed on antenatal ultrasound scan, while others, such
1 Age in weeks/
as coarctation of the aorta, may present shortly after birth.
Both lesions usually undergo primary surgical repair in the 1 2 3 4 5 6
0.5kg
neonatal period and have negligible impact on long‐term 0 2 4 6 8 10 12 14 16 18 20 22 24 26
growth [12]. Other lesions, such as ASD, do not cause cardio-
pulmonary changes that are large enough to affect energy = repair of tetralogy of Fallot.
expenditure and are repaired in early childhood [13].
Relatively mild forms of lesions that would usually result in Figure 14.1 Growth chart of a breastfeed infant with mild tetralogy of
Fallot.
faltering growth, such as small VSD, may either resolve with
time or undergo repair having had limited effect on growth.
Figure 14.1 shows the growth chart of an infant with mild energy available for tissue accretion, and the level of growth
tetralogy of Fallot who continued to breastfeed with mini- failure depends on the extent to which workload is increased.
mal impact on growth until the defect was repaired (see Examples are moderate to large VSD and atrioventricular
arrow), with slight post‐operative weight loss, after which septal defect (AVSD), and PDA. The effect on faltering
he fed more avidly and weight trajectory improved. growth is exacerbated if the lesion progresses to cause con-
For the healthy infant the average daily total energy gestive heart failure (CHF), in which cardiac output is una-
expenditure (TEE) is between 60 and 70 kcal (250–290 kJ)/ ble to meet the metabolic demands of the body [18].
kg/day [14–16]. Achieving the estimated average require- Improving growth before surgery is considered key to
ment (EAR) of 96–120 kcal (400–500 kJ)/kg/day in early improving longer‐term outcomes among infants with com-
infancy [17] results in 35–60 kcal (145–250 kJ)/kg/day being plex heart lesions [20], especially as a high risk growth pat-
available for growth. However, up to a third of children with tern has been quantified as faltering growth during the first 2
CHD have an energy expenditure 120% of normal [18, 19], years of life with subsequent rapid catch‐up growth between
resulting in less energy available for growth. An understand- the ages of 2 and 15 years [21]. It is hypothesised that increased
ing of the primary cardiac anatomy and the surgery involved adiposity in adults with CHD may increase the risk of meta-
in either repair or palliation helps to identify those who are bolic and cardiovascular disease later in life [22–24].
at most risk of faltering growth. Lesions that increase cardi- Complex CHD is associated with malnutrition and growth
orespiratory workload affect growth by reducing the surplus retardation in both infancy [11, 25–30] and childhood [11, 31].
Pathogenesis of Faltering Growth in CHD 289
The type of congenital cardiac defect impacts on energy

expenditure and, hence, growth and can be divided into two Coarctation of aorta
main types: acyanotic lesions, where oxygen saturation of Persistent ductus
haemoglobin is normal, and cyanotic lesions, which cause arteriosus
low oxygen saturation.
Acyanotic lesions: In the normal circulation the weaker Aorta
right ventricle pumps blood to the lungs at a pressure that
is a third of that of the left ventricle, which pumps blood to Pulmonary
artery
the rest of the body, the systemic circulation. However, the
vascular resistance of the lung is considerably less than that Atrial septal
in the systemic circulation resulting in equal blood flow out defect
of each ventricle. However, cardiac anomalies that cause a
‘hole’ between the left and right sides of the circulation
usually result in a larger than normal volume of blood
being pumped to the lungs by both the right and, the more
powerful, left ventricle: a ‘left‐to‐right shunt’. If blood flow
through the shunt is high and prolonged, the elevated pres- Ventricular septal defect
sure causes pulmonary hypertension [18], resulting in inef-
ficient gas exchange across the capillaries. Adequate tissue Figure 14.3 A cyanotic lesion. Transposition of the great arteries with
oxygenation is then achieved only at the expense of ventricular and atrial septal defects, patent ductus arteriosus and
increased respiratory effort. This elevates the body’s TEE, coarctation of aorta.
resulting in less energy being available for growth. The
elevated pulmonary vascular resistance (PVR) [32] and
TEE seen in patients with severe acyanotic lesions [16, 18,
33] correlate inversely with weight gain. This effect is illus-
trated in Figure 14.2 showing twins, one with a normal cir- Persistent ductus
arteriosus
culation and the other with a VSD. Severe, prolonged
‘left‐to‐right shunts’, resulting in CHF, further increases
energy expenditure [18].
Cyanotic lesions: The presence of cyanosis appears to exert
an independent effect on growth resulting in stunting [11, 26,
34]. The mechanism for this is uncertain, but it appears that Atrial septal
hypoxia is a factor causing suboptimal tissue oxygenation defect
[35]. Cardiac defects that result in both pulmonary hyperten-
sion and cyanosis appear to place patients at greatest nutri-
tional risk, by causing both wasting and stunting [26].
Examples of a cyanotic lesion, an acyanotic lesion and tetral-
ogy of Fallot are shown in Figures 14.3–14.5.
Ventricular septal defect
Figure 14.4 An acyanotic lesion. Atrial and ventricular septal defects

with patent ductus arteriosus.
Table 14.2 shows the potential effect of the different types

of lesion on growth. Table 14.3 summarises the risk that spe-
cific defects pose on growth faltering.
Cardiomyopathy: Paediatric cardiomyopathies are a heter-
ogeneous group of disorders affecting the muscle of the
heart, resulting in significant morbidity and mortality. The
incidence is 1.13–1.24 per 100 000 children 18 years and
younger. Nearly one third of children diagnosed with a car-
diomyopathy during the first year of life will die within
Figure 14.2 Twins, one with a normal circulation and the other with a 1 year of diagnosis, and 40% will require a heart transplant
VSD. Source: David Hopkins (Permission from parent, Bristol Royal within 2 years. Growth failure is common and the promo-
Hospital for Children). tion of adequate nutrition is essential [36].
Learning points: pathogenesis of faltering growth in CHD
• Not all CHD results in faltering growth

• Acyanotic lesions that increase cardiorespiratory workload
tend to cause wasting by reducing energy available for
growth
Overriding aorta
• Lesions that cause cyanosis tend to be associated with
Ventricular stunting
septal defect
Pulmonary
stenosis
Energy expenditure and energy intake in CHD
Energy expenditure
Thickened
Doubly labelled water studies have been used to calculate
right ventricle
the TEE of ‘free‐living’ infants with a variety of cardiac
Figure 14.5 Tetralogy of Fallot illustrating the four aspects of the cardiac lesions [16, 18, 37, 38]. However, indirect calorimetry is the
defect. recommended method of calculating energy expenditure of
Table 14.2 Effect of type of cardiac lesion on metabolic processes affecting somatic growth.
Lesion type Metabolic effect Effect on growth Examples
Acyanotic ↑TEE Wasting + VSD, PDA, AVSD

Acyanotic with CCF ↑↑TEE Wasting ++ Persisting large VSD, AVSD
Cyanotic Poor tissue oxygenation Stunting TOF, TGA, hypoplastic left heart
Cyanotic with pulmonary hypertension ↑↑TEE + poor tissue oxygenation Stunting with wasting Truncus arteriosus
TEE, total energy expenditure; VSD, ventricular septal defect; PDA, patent ductus arteriosus; AVSD, atrioventricular septal defect; CCF, congestive
cardiac failure; TOF, tetralogy of Fallot; TGA, transposition of the great arteries.
Table 14.3 Risk of different congenital cardiac defects affecting long‐term growth.
Low
Repaired soon after presentation Limited effect on growth Variable/moderate High
Coarctation of the aorta Atrial septal defect (ASD) Pulmonary atresia* Aortopulmonary window
Cor triatriatum Tetralogy of Fallot* Atrioventricular septal defect (AVSD)
Patent ductus arteriosus (PDA) (if early closure) Ebstein’s anomaly*
Pulmonary stenosis* Hypoplastic left heart (HLH)*
Total anomalous pulmonary venous drainage Partial anomalous pulmonary venous
(TAPVD)* drainage (PAPVD)*
Transposition of the great arteries (TGA)* Patent ductus arteriosus (PDA)¶
Tricuspid atresia*
Truncus arteriosus*
Ventricular septal defect (VSD),
moderate to large
Double outlet right ventricle (DORV)
* Cyanotic lesions.
¶
If PDA is large and/or if surgery is delayed.
Energy Expenditure and Energy Intake in CHD 291
Table 14.4 Effect on energy expenditure according to congenital heart defect.
Lesion Lesion type Total energy expenditure, TEE (kcal/kg)
Healthy control Pre‐operative Post‐operative
VSD [16, 18, 19, 37, 41] Acyanotic 61 [18] 71–97 [41]
62 [16] 77 [18]
78–157 [37]
84–123 [19]
87 [15]
VSD (with CHF) [18] Acyanotic 61 92 ± 20
ASD [19] Acyanotic 77–168 54–92
AVSD [41] Acyanotic 91 [19]
98 [41]
TOF, TAPVD, complex Cyanotic 60* 73*
CHD [38] 72** 94**
TGA [37] Cyanotic 78
TOF [37] Cyanotic 101–185 [19] 79–105 [19]
104 [37]
Resting energy expenditure, REE (kcal/kg)
Post‐operative
Hypoplastic left heart [44] Cyanotic 43

Mixed CHD [45] Acyanotic 70
Mixed CHD [45] Cyanotic 66
Mixed CHD [45] Requiring bypass 74
* At 2 weeks of age.

** At 3 months of age.
VSD, ventricular septal defect; CHF, congestive heart failure; ASD, atrial septal defect; AVSD, atrioventricular septal defect; TOF, tetralogy of Fallot;
TAPVD, total anomalous pulmonary drainage; CHD, congenital heart disease; TGA, transposition of the great arteries.
ventilated post‐operative patients [39]. One study has is unclear [26, 49]. Children with cardiac defects resulting in
shown that congestive cardiac failure (CCF) may increase both cyanosis and pulmonary hypertension have been
energy expenditure in infants as young as 1 month old [40] reported as having significantly lower energy intakes than
although good diuretic control may negate this effect [41]. those with pulmonary hypertension or cyanosis alone
Malnutrition itself reduces ventricular mass and cardiac [26, 49], and these patients may warrant more frequent nutri-
output, which may exacerbate an already compromised cir- tional review.
culation [42]. The elevated energy expenditure causing Any child with faltering growth whose energy intake is
growth failure in lesions resulting in large ‘left‐to‐right normal or above normal warrants cardiac assessment as part
shunts’ and some cyanotic cases [16, 18, 25, 26, 37, 38, 42, 43] of further clinical investigations. The dietitian’s role may be
is summarised in Table 14.4. key in highlighting suspicion if growth failure continues fol-
lowing optimisation of nutritional intake.
Energy intake
Most studies show pre‐operative energy intakes of patients Learning points: energy expenditure and intake in CHD
with CHD are near normal [16, 18, 30, 38, 46, 47]. In one
study where mean daily intake at 6 months of age was able • Most studies report normal energy intakes in most cases of
to be measured, an average intake of 91.1 ± 38.9 kcal/kg and CHD
2.5 ± 0.9 g/kg protein was similar to that of healthy controls: • Elevated energy expenditure is the cause of faltering growth
89.4 ± 16.9 kcal/kg and 2.2 ± 0.55 g/kg [47]. However, some in most cases
authors report low energy intakes [26] of the order of 80%– • Energy intake may be reduced in infants whose cardiac
90% of that recommended [37, 48, 49], although the method- defects result in both pulmonary hypertension and cyanosis
ology for nutritional data collection in some of these studies
Other factors affecting nutritional intake Digestive

and growth
Nutritionally compromised infants are more susceptible to
Delayed diagnosis and additional investigations infections [54], and if these are frequent, the use of antibiotics
may affect gut flora. Patients who develop infected post‐
Where diagnosis is delayed, nutritional deficits become exac- operative sternal wounds may have antibiotic therapy
erbated, one study showing over 90% of cases having weight resulting in diarrhoea, which may transiently affect absorp-
for age Z score (WAZ) < −2 SD and 60% having WAZ < −3 SD tive capacity.
[11]. Repeated investigations such as cardiac catheterisation Infants with CHD have been found to have delayed gastric
or computed tomography scans, requiring patients to be nil emptying [55]. Vomiting, diarrhoea, bloating, constipation
by mouth, interfere with feeding regimens often with limited and gastro‐oesophageal reflux (GOR) are common [49].
scope to catch up with additional feeds. In addition, beliefs Persisting or increasing vomiting frequency may hamper
around the effect of prostaglandin infusions, indwelling progression to higher energy feeds [32]. Prolonged use of
umbilical catheters and cardiac drugs on the ability to tolerate prostaglandin infusions to keep the ductus arteriosus open
feeds may limit intake [50]. Poor pain control may prolong has been linked to transient pyloric stenosis, resolving when
the catabolic response to surgery, having detrimental effects the infusion is stopped [56]. Table 14.5 summarises the addi-
on healing [51], and may delay progression to oral feeding. tional factors that have potential to impact on growth in CHD.
Endocrine Pre‐surgical nutrition to improve outcomes in

high risk patients
Hypermetabolism is thought to reduce insulin‐like growth
factor 1 (IGF‐1) synthesis in children with VSD, with lower Faltering growth and surgical outcome
serum levels correlating with increasing size of the ‘left‐to‐
right shunt’ and reduced body mass index (BMI) [46]. Several studies have linked measures of malnutrition to
Elevated levels of norepinephrine and renin are also associ- poorer post‐operative outcomes. These are summarised in
ated with increasing respiratory rate in children with acy- Table 14.6. Most importantly malnutrition is associated with
anotic CHD [32]. increased post‐operative mortality risk at 1 month of age
[69], 3 months of age [67, 73] and at 1 year [67].
Metabolic
Pre‐surgical nutrition
Lipid metabolism has been shown to be disturbed in infants
with CHD with those with cyanotic lesions having a Lesions that cause marked ‘left‐to‐right shunts’ and/or cya-
decreased ability to oxidise fatty acids [52]. Cardiopulmonary nosis that require staged repairs carry the highest risk of
bypass (CPB) is known to cause the release of inflammatory growth failure. After diagnosis, stabilisation and/or initial
mediators with the raised levels of catecholamines and corti- palliative surgery, some patients are discharged home to
sol, resulting in a degree of insulin resistance [53]. In the undergo a period of growth prior to correcting the primary
acute post‐operative period amino acids, required for defect or undergoing further palliation. This results in a gap
wound healing, may be obtained from muscle breakdown, of several weeks or months and, in the case of hypoplastic
but replenishment of these is needed to optimise growth in left heart syndrome (HLHS), years before the final operation.
the medium to longer term. Table 14.7 summarises the stages of repair of some lesions.
Table 14.5 Additional factors affecting nutritional intake and growth in CHD.
Procedural Digestive Endocrine Metabolic
Delayed diagnosis [11] Gastro‐oesophageal reflux [32, 57] Insulin resistance [53] Elevated energy expenditure [16, 18, 38]
Prolonged respiratory Pyloric stenosis [56] Reduced insulin‐like growth Hypoxia [26]
support [58] factor [46]
Repeated operations [9] Diarrhoea Elevated norepinephrine [32] Increased inflammatory markers [53]
(antibiotic/infective)
Pain [51] Chylothorax [59] Elevated renin [32] Impaired lipid metabolism [52]
Feeding difficulties [60] Hepatic dysfunction [61] Increased sympathetic nerve Increased haemopoiesis [33]
activity [33]
Vocal cord palsy [62–64] Dysregulated microbiome [65] Pyrexia [33]
Wound healing [51]
Pre‐surgical Nutrition to Improve Outcomes in High Risk Patients 293
The dietitian’s role during this intervening period is to moni- local team with cardiac expertise who are in regular contact
tor nutritional status and where possible to try to correct with the tertiary centre. An initial study considering the
nutritional deficits [74–76]. Nevertheless, one study showed implementation of the consensus‐based pre‐surgical nutri-
delayed or no referral to dietetics services in a fifth of CHD tion pathway (Figure 14.7) demonstrated that growth of
patients with faltering growth prior to their surgery [8]. A infants with CHD was significantly improved at 12 months
consensus‐based pathway providing a structured approach of age, as well as a 10‐day reduction in paediatric intensive
to the nutritional care of infants with CHD awaiting surgical care unit length of stay [78].
palliation or repair may help to achieve timely referral to the If sufficient energy is provided, adequate growth can be
dietitian [77]. Patients are categorised into three nutritional achieved [79–81] even in severe CHD [76]. Studies measur-
risk groups according to cardiac diagnosis, weight gain, feed ing TEE in infants with CHD indicate that energy intakes of
intake and tolerance parameters [77]. High risk patients 30 kcal (125 kJ)/kg/day above the EAR should compensate
require weekly, and medium risk fortnightly follow‐up by for elevated energy expenditure in most cases [16, 18, 38, 41].
the tertiary team, with low risk patients requiring follow‐up A reasonable starting point for an infant with faltering
by their local hospital (Figure 14.6). Figure 14.7 summarises growth would be 120–130 kcal (500–545 kJ)/kg/day.
a proposed nutritional and feeding care plan/intervention However, in the most severe cases, some patient’s energy
based on the nutritional risk of these infants. In some intakes may need to be 150+ kcal (630+
kJ)/kg/day to
medium and high risk cases, follow‐up may be deferred to a achieve consistent weight gain [37, 79]. Plotting weight on
growth charts is essential in monitoring the effectiveness of
Table 14.6 Measures of malnutrition in CHD associated with poorer nutritional interventions.
surgical outcome.
Choice of feed
Measure of malnutrition Effect on outcome
Breastfeeding, or expressed breastmilk (EBM), is the initial
Weight for age <−2 SD Increased infection risk [54, 66]
feed of choice for infants with CHD. The mechanics of breast-
Increased time on ventilator [54, 67]
Increased PICU length of stay [54] feeding may cause less cardiorespiratory stress than bottle
Longer hospital stay [68] feeding, resulting in lower oxygen desaturation episodes
Increased risk of cardiac arrest [54] [82], and has even been attempted following heart transplant
Increased 30‐day mortality [54, 69] [51]. If breastmilk is not available, a suitable infant formula
Increased mortality at 1 year of age [67] should be provided. However, early fortification or supple-
Height for age <−2 SD Increased infection risk [54] mentation with a higher energy infant formula in the first
Increased time on ventilator [54] few weeks of life may be needed to achieve satisfactory
Increased PICU length of stay [54, 70] weight gain and prevent growth faltering. These high energy
Increased risk of cardiac arrest [54]
nutrient‐dense formulas provide a favourable protein–
Increased 30‐day mortality [54]
energy ratio of around 10%. A summary of these feeds and
Lower triceps skinfold Increased PICU length of stay [71] their macronutrient breakdown is shown in Table 1.18.
scores Longer duration of ionotropic support [71]
Some units supplement EBM with up to 6% w/v infant
Increased time on ventilator [71]
Elevated levels of serum B‐type natriuretic formula, giving an energy content close to 100 kcal
peptide (greater myocardial stress) [71] (420 kJ)/100 mL while keeping the osmotic load at around
Low bioimpedance Increased PICU length of stay [72]
400 mOsmol/kg H2O (Dr Graeme O’Connor, personal com-
spectroscopy score munication). However, even with this level of supplementa-
tion, the protein–energy ratio remains at around 8%, and
PICU, paediatric intensive care unit. slower growth may have to be an accepted consequence of
Table 14.7 Cardiac defects requiring staged operations for repair.
Cardiac defect First‐stage operation Second/final stage operation Third and final stage operation
Atrioventricular septal defect Pulmonary artery (PA) band PA band removal and AVSD repair N/A
(AVSD)
Double inlet right ventricle Repair of coarctation of the aorta PA band removal N/A
and arch reconstruction, PA band, Damus–Kaye anastomosis of PA
atrial septostomy with PA plasty
Double outlet right ventricle Modified Blalock–Taussig shunt AVSD and pulmonary valve repair N/A
Hypoplastic left heart Norwood stage 1 Norwood stage 2 (Glenn shunt) Norwood stage 3 (total
cavo‐pulmonary connection)
Ventricular septal defect (VSD) Pulmonary artery band PA band removal and VSD closure N/A
N/A, not applicable.

Step 5 Choosing a nutrition care plan: A, B or C:

At each review using the flow diagram below decide the appropriate care plan outlined in the tables that follow
Plan A: Plan B: Plan C:

An infant will be: An infant will be: An infant will be:
Growing well, e.g. on a growth

chart tracking upwards & not more Not growing well, e.g. between
than 1 centile below birth centile No 1–2 centile below birth centile for No Not growing, e.g. > 2 centile below
for weight/length/HC weight/length/HC birth centile for weight/length/HC
Have a CHD lesion with a higher Have a CHD lesion with a higher
No
nutrition risk but drinks well nutrition risk but no oral feeds
Able to meet nutritional
requirements orally, e.g. bottle No
or breast feeding
Finishes >75% of feeds orally No Requires NGT/NJT for feeding
Fluid intake < 120 ml/kg/day No Fluid intake < 100 ml/kg/day
Continue on Plan A:
Local team to monitor growth/
feeding progress
Continue on Plan B: Continue on Plan C:
Review every 2 weeks Review every week
• Step 2: Growth – using an appropriate chart • Step 2: Growth – using an appropriate chart
• Step 3: How an infant is eating or drinking • Step 3: How an infant is eating or drinking
• Step 4: What and how much is eaten or drunk • Step 4: What and how much is eaten or drunk
Figure 14.6 Choice of nutritional care plan based on nutritional risk. Source: From Marino et al. [77].
this approach. A combination of breastmilk and energy‐dense demonstrated in patients with percutaneous endoscopic
infant formula, adjusting proportions to ensure feed toler- gastrostomies (PEG) [85] and should be considered in
ance, is another way of meeting the required energy and patients requiring long‐term tube feeding; gastrostomy feed-
protein intakes. If weight gain is unsatisfactory on a 1 kcal ing may be less of an impediment to the development of oral
(4.2 kJ)/mL feed and feed volumes cannot be increased feeding skills than NG feeding. Laparoscopic gastro‐jejunal
further, energy density may be increased by adding a fat and feeding tubes have been successfully placed in infants with
carbohydrate supplement or infant formula powder in 1% severe cardiac anomalies and GOR disease weighing as little
w/v daily increments up to a maximum of 4%. At this level of as 2.7 kg and may circumvent protracted vomiting [86].
fortification, a protein–energy ratio between 9% and 10% is However, one study has shown that children with single
maintained with an energy density of about 1.2 kcal (5 kJ)/ ventricle anatomy who have a gastrostomy with or without
mL. As these infants are often at risk of GOR [49, 57], a fine laparoscopic fundoplication have a mortality risk 2.3 times
balance must be made between giving a feed of sufficient that of those fed orally or via NG tube [87]. The authors pos-
energy density to achieve adequate growth while limiting tulated that having a gastrostomy with or without fundopli-
vomiting and malabsorption. A hydrolysed protein formula, cation might be a marker for more severe disease with
such as Infatrini Peptisorb, may be useful where there is a evidence of higher risk of complications (GOR, aspiration,
degree of malabsorption (Table 8.15). If weight gain continues faltering growth), but nevertheless found the increased mor-
to be poor, a detailed nutrition review is required to ensure tality disconcerting.
infants are consuming adequate macro‐ and micronutrients. The timing of weaning off tube feeds to allow for the
A nasogastric (NG) tube and micronutrient supplementation development of independent feeding skills should be
may be required to support adequate intake and growth. addressed for each individual child. Shine et al. have
reviewed mainly NG tube‐fed patients and identified longer
duration of tube feeding, older age and classification of
Tube feeding
being orally averse as factors increasing transition time to
Children with complex congenital heart lesions have been full oral feeding [88]. Dietetic interventions aiding transition
shown to achieve greater energy intakes and weight gain included switching from nutrient‐dense to standard infant
when fed continuously via a feeding tube compared with formula, increasing time between feeds and reducing feed
oral feeding using the same feed [83]. It has been suggested volumes while ensuring adequate hydration [88].
that continuous feeding of high energy formulas may be the Common issues identified by parents such as growth
only way in which target intakes more than 140 kcal (585 kJ)/ before surgery and how to feed your baby have been
kg/day can be met [84]. Improved weight SDS has been described in the literature including information on the
Pre‐surgical Nutrition to Improve Outcomes in High Risk Patients 295
Care Plan Nutritional and feeding care plan

A • Normal energy and protein requirements* 90–100 kcal/kg, protein 1.5/kg (e.g. 2 g protein per 150 ml)
• Normal fluid allowance, e.g. 150 ml/kg or above
• Breastfeeding or standard infant formula on demand
• Complementary food from 17 to 26 weeks if ready – 3 small meals/day. Starches should form the basis of all
meals, including veg/fruit. Offer protein containing meals (chicken/fish/meat/eggs/pulses) at lunch/supper.
• Vitamins supplement to provide up to 10 μg vitamin D
• Review by local team – refer to specialist centre with any concerns
B • Approximately 10% extra energy* 100–110 kcal/kg (protein contributing 9%–12% energy)
• Approximately 30%–50% extra protein* (around 2.5 g/kg protein)
• Breastmilk or standard infant formula in addition to 30%–80% of nutrition requirements from nutrient-dense
infant formula per day
• Complementary food from 17 to 26 weeks of age if ready – 3 small meals/day. Starches should form the basis
of all meals, including veg/fruit. Offer protein containing meals (chicken/fish/meat/eggs/pulses) at lunch/supper.
Around 6 months of age add ½– 1 teaspoon of a nut butter or finely ground nuts to both main meals
• Vitamin supplement daily to provide up to 10 μg vitamin D
• If there are any feeding issues refer to SLT
• Paediatric dietetic review growth in 2 weeks – if poor weight gain review earlier and move to plan C
C • May be fluid restricted

• Approximately 10%–20% extra energy* 120–150 kcal/kg (protein contributing 10%–15% energy)
• Approximately 50%–100% extra protein (up to 4 g/kg protein – check renal function)
• Breastmilk or standard infant formula in addition to a minimum of 50% and up to 100% of nutrition
requirements as energy/nutrient-dense infant formula or as overnight or nasogastric feeds
• Complementary food from 17–26 weeks of age ready – 3 small meals/day. Starches should form the basis
of all meals, including veg/ fruit. Offer protein containing meals (chicken/fish/meat/eggs/pulses) at lunch/supper.
Around 6 months of age add 1–2 teaspoon of a nut butter or finely ground nuts to all meals
• Vitamin supplement daily to provide up to 10 μg vitamin D
• If there are any feeding issues refer to SLT
• Paediatric dietetic review of growth in 1 week
STEP 6: Exit criteria for dietetic and SLT support

Dietetics • Post-operatively it may take 12 weeks or more for sufficient catch-up growth to occur
• Nutrition rehabilitation will have been achieved when there is catch-up growth to 1 centile below birth weight
SLT • Eating and drinking skills are following appropriate stages for infant’s presentation
• Child is able to feed safely and independently and is growing appropriately
• Feeding is an enjoyable experience for child and caregiver
• All intervention advice and programmes are in place. Caregivers are skilled in carrying out recommended advice at
which point infant should be discharged with support and re-referral options in place
*Based on actual weight rather than expected weight
Figure 14.7 Nutrition and feeding care plan based on nutritional risk in infants with congenital heart disease. Source: From Marino et al. [77].
Licensed under CC BY 4.0.
introduction of age‐appropriate complementary feeding

advice. Parents often feel the introduction of weaning foods Learning points: improving outcomes in CHD
is forgotten by health care professionals, in addition to a lack
of information on enriching them to make foods more nutri- • Cardiac lesions requiring a staged repair carry the highest
ent and energy dense. Parents report recommendations such risk of faltering growth
as cream, oil, and butter often made their infants sick and • High energy infant formula +/− breastmilk or fortified
that the use of nut butters was an acceptable alternative. breastmilk may be required to achieve adequate growth
Parental feeding information has been developed as well as • Care plans based on nutritional risk may help to identify a
a recipe book, which can be adapted locally [89] targeted approach to delivering optimal nutritional support
• Feeding advice for infants with congenital heart disease • Nasogastric or gastrostomy feeding should be considered in
• Recipe book – for babies who need to make the most of patients who fail to meet growth targets
every mouthful
The patient in the paediatric intensive care unit within 6–24 hours, once haemodynamic stability is achieved.
The use of umbilical arterial or venous catheters, prostaglan-
Surgical procedures for children with CHD vary in their dins or extracorporeal life support (ECLS) does not preclude
complexity, morbidity and mortality risk. A variety of scor- enteral feeding [96].
ing systems are used to classify surgical risk, one of which is In the first 12–24 hours following cardiac surgery, patients
the Risk Adjusted Cardiac Heart Score (RACHS), where sur- are usually fluid restricted to 2 mL/kg/hour (48 mL/kg/
gery for simple lesions such as a patent ductus arteriosus day) to manage the post‐cardiopulmonary bypass‐associ-
closure is category 1 and the Norwood procedure is category ated fluid overload. This is usually liberalised to 3 and then
6 [90]. Some surgical procedures require the use of CPB, 4 mL/kg/hour (72–96 mL/kg/day) on consecutive post‐
involving aortic cross‐clamp and circulatory arrest. Children operative days depending upon circulatory status and
who undergo bypass usually develop capillary leak, which cumulative fluid balance [97]. Drug infusions are included in
is considered to occur because of the release of inflammatory the daily fluid allowance; it is possible for some drug infu-
mediators acting to disrupt intercellular junctions of capil- sions to be made up to double or quadruple the usual
lary endothelial cells. As a result C‐reactive protein is usu- strength, enabling more of the fluid allowance to be pro-
ally elevated post‐cardiac bypass surgery [91]. vided as feed. Fluid flushes for intravascular arterial and
venous pressure monitoring lines and intravenous drugs are
also included in the total fluid allowance; the remaining vol-
Post‐operative energy expenditure ume is for feeds.
A number of paediatric/cardiac intensive care units
As during the acute phase of critical illness, only resting express fluid allowances as a percentage. This is based on
energy expenditure should be calculated following cardiac 100% equating to 4 mL/kg/hour for the first 10 kg body
surgery [39, 92] (Table 6.7). Indirect calorimetry has shown weight, 2 mL/kg/hour for the second 10 kg and 1 mL/kg/
energy expenditure in infants and young children in the pae- hour for every kilogram thereafter. Once the 100% fluid
diatric intensive care unit (PICU) to be between 60 and allowance has been calculated, this is multiplied by a pro-
70 kcal (250–290 kJ)/kg/day [45, 93]. There is little difference portion of the allowance depending on whether the patient
between metabolic rate of acyanotic and cyanotic patients on has had CPB or not. Table 14.8 illustrates changes in fluid
PICU, 62 kcal (259 kJ) and 59 kcal (247 kJ)/kg/day [45, 93]. allowances following cardiac surgery.
Infants with HLHS in the immediate 3 days following their Worked example: Infant weighing 3.5 kg
first complex Norwood stage 1 operation have been shown 100% fluid allowance provides 4 mL/kg/hour = 4 × 3.5 =
to have even lower energy expenditure, 39–43 kcal (163– 14 mL/hour or 336 mL/day. A 50% fluid allowance gives
180 kJ)/kg/day [44]. Having CPB does, however, appear to 14 mL/hour × 0.5 = 7 mL/hour total fluid allowance from
elevate energy expenditure to around 75 kcal (315 kJ)/kg/ which hourly volumes of intravenous drugs and flushes are
day [37], although further research is required to confirm subtracted to leave the volume for feeds.
this as the phenomenon could be temporary. Enteral feeds are increased gradually every 6–12 hours
Although many predictive energy expenditure equations depending on fluid allowance and clinical observation [98].
have been found to be inadequate in estimating resting energy Most are fed via NG tube for the first few days following
expenditure [45, 94, 95], the use of Schofield (weight) equation cardiac surgery, either as continuous or bolus feeds; there is
has been recommended by all of the major European and no evidence to support one method over the other [39].
American societies in estimating resting energy expenditure Breastmilk is again the feed of choice for all infants.
during the acute phase [39], stable and rehabilitative phases of However, less than a third of children undergoing cardiac
critical illness [92]. Recommendations for the first few days surgery achieve their estimated energy requirement while
post‐operatively are to meet two thirds of resting energy on PICU, contributing to further declines in weight during
expenditure as calculated using Schofield equation [39] (see
Chapter 6). Increased periods of sleep, and sedation, use of
paralysing agents and mechanical ventilation, suppression of Table 14.8 Fluid allowance during admission to the paediatric intensive
thyroid hormones and surgical stress curtailing growth might care unit after cardiac surgery.
all contribute towards conservation of energy expenditure
[19]. The general reductions in observed energy expenditure Day post‐surgery Cardiopulmonary Non‐cardiopulmonary
bypass bypass
go some way ameliorating the energy deficits inevitably
imposed by the fluid restrictions that limit post‐operative feed 1 50% 80%
volumes. If the stay on PICU becomes extended, the experi- 2 60% 90%–100%
ence of one of the authors is that energy intakes as low as
3 70% 120%
70 kcal (230 kJ)/kg/day may be necessary to prevent exces-
sive weight gain in some stable long‐term ventilated infants. 4 80% Free fluids
5 90%
Fluid restrictions and feed delivery 6 100%
7 120%–135%
Early enteral nutrition via the NG route is recommended in 8 150%
cardiac infants following surgery and can be safely started
Other Nutritional Issues 297
inpatient stay [70]. The use of energy‐dense infant feeds • small frequent NG tube bolus feeds
early in the post‐operative PICU stay may reduce this pro- • continuous feeds via an enteral feeding pump with some
portion [99, 100] although a small number of patients may time off to allow gastric pH to return to normal. This
show signs of feed intolerance [100]. These feeds are also must be supervised if via a NG tube
associated with increased production of nitric oxide and do
not require a graded approach to introduction [99, 101].
Changes in energy expenditure and nutritional status
following repair of CHD
Learning points: the patient in PICU TEE, which more accurately reflects energy requirements in
non‐ventilated patients, is marginally elevated, but not sig-
• Indirect calorimetry, if available, and the Schofield equation nificantly so at 3 and 12 months’ post‐surgery [106]. A fur-
are the current options for calculating energy requirements ther study measuring resting energy expenditure showed
• Patients on PICU following cardiac surgery usually have no difference at 3 months of age post‐first‐stage palliation
lower energy requirements than prior to surgery for univentricular physiology or correction of biventricular
• Fluid restrictions often limit adequate delivery of nutrition defect compared with healthy infants [107]. These infants
in the post‐operative period had significantly poorer growth and lower percentage
body fat compared with healthy infants, implying that
lower dietary intakes were the contributory factor, but dif-
Most infants and children are discharged from PICU on ficulties encountered in measuring energy intakes could
day 1 or 2 post‐cardiac surgery. If the patient’s clinical condi- not confirm this.
tion results in ongoing fluid restrictions, their nutritional Weight loss may occur in the immediate period between
intake will need close monitoring. Even with active dietetic surgical repair and discharge home, with this attributed to
involvement on PICU energy and protein intakes at the end poor post‐operative intake [108]. Nevertheless, most infants
of the first post‐surgical week may only be 70% of require- and children demonstrate catch‐up growth following repair
ments, with young infants being the most vulnerable [70]. of their primary cardiac defect, with improvements in weight
The dietitian’s role is to ameliorate the effect of any neces- for age, weight for height and height for age SDS scores,
sary ongoing fluid restrictions affecting feed delivery by most of this occurring in the first year following corrective
seeking to liberalise fluid allowances when clinically appro- surgery [109–112]. However some infants may continue to
priate [102, 103]. exhibit growth failure even after haemodynamic correction
[43], and catch‐up growth may be limited if malnutrition
prior to surgery is marked and prolonged [109, 111].
Nutrition on transfer from PICU to the cardiac ward
Fluid allowances often increase on discharge from PICU to Learning points: patient transfer from PICU to ward
the ward, providing opportunity to increase feed volumes. and discharge home
The type of residual lesion affecting cardiopulmonary func-
tion determines the extent to which energy expenditure is • Immediate post‐operative fluid restrictions are usually lib-
elevated and the requirements for catch‐up growth. Where eralised on transfer to the ward
catch‐up growth is required, the FAO/WHO recommenda- • Various strategies may need to be employed to help transi-
tions for energy and protein intake should be followed, in tion to oral feeding
addition to the provision of enough micronutrients to replete • If growth has been impaired pre‐operatively, it should con-
pre‐ and post‐operative losses. tinue to be monitored after correction of the cardiac defect
If not done so already, attempts should be made to until adequate catch‐up growth has been achieved
establish oral feeds. However, some infants may initially
fail to complete feeds by mouth due to fatigue brought on
by the effort of sucking, anorexia or early satiety. Others
may require short‐term tube feeding to ensure require-
Other nutritional issues
ments are met. Poorer oral feeding capability is associated
with long post‐operative ventilation, poor weight at sur-
Gastro‐oesophageal reflux and vomiting
gery and vocal cord injury [104]. A screening tool may
If GOR develops, positioning and feed thickeners may be
help with early identification of those at risk of dysphagia
used as a first‐line treatment (p. 133). Although H2 antago-
or swallowing difficulties [105], enabling early involve-
nists and proton pump inhibitors may not prevent GOR, the
ment of a speech and language therapist to address oral
reduction in acid enables the infant to feel more comfortable
feeding issues.
and more likely to continue oral feeding, and there are no
If an infant is regularly failing to complete feeds, one of
contraindications to their use in CHD. Other causes of vom-
the following strategies should be employed:
iting, such as cow’s milk protein allergy, should also be con-
• offer smaller, more frequent oral feeds sidered [113]. However, although feeding tolerance for some
• incomplete feeds to be topped up via a NG tube may improve on a milk‐free formula, growth among infants
with CHD and cow’s milk protein allergy is significantly but levels <30 mmol/L have been associated with poor
worse compared with non‐allergic CHD infants [113]. This growth [120].
may be associated with a decline in phosphate levels, par- An infant feeding 150 mL/kg of a standard infant formula
ticularly among infants who are also on anti‐reflux medica- receives 1.0–1.3 mmol Na/kg, depending on the formula,
tion. The impact of medications on absorption and compared with the reference nutrient intake (RNI) for
bioavailability of micronutrients and minerals on growth, as sodium for an infant aged 0–3 months of 1.5 mmol/kg.
well as the choice of infant formula, needs to be considered Infants feeding 150 mL/kg of one of the commercially avail-
in these patients [114]. able energy‐dense formulas will receive 1.4–1.65 mmol
Na/kg. Sodium supplementation of 2–3 mmol/kg may be
appropriate in some depleted individuals.
Electrolyte supplementation of infant feeds
Potassium supplementation associated with diuretic use
is common on PICU. Supplementation providing up to
Where infants with CHD fail to gain weight despite energy
3–4 mmol/kg may be required to keep serum levels within
intakes above 140 kcal (585 kJ)/kg, it is important to consider
the normal range. Enteral and intravenous supplementation
whether nutrients such as sodium, potassium, zinc, magne-
has been shown to be equally effective in increasing serum
sium, phosphorus or iron may be insufficient in the diet to
levels [121, 122] although a small number of patients may
support adequate growth [115]. Loop diuretics are com-
vomit supplements given enterally [122]. If additional potas-
monly used on PICU following surgery to prevent fluid
sium is needed on an ongoing basis and the serum level is
overload, but by nature increase sodium and potassium
stable, it may be added into the infant’s feed. This has the
excretion. Chronic electrolyte depletion may become a
benefit of spreading out the supplementation over 24 hours.
growth limiting factor. Table 14.9 lists commonly used drugs
Some units may prefer to split the dose and add it to each
affecting electrolytes. Use of hypertonic solutions after
individual feed.
bypass surgery has been shown to improve cardiac function
and reduce the need for inotropic support [116]. Patients
with cyanotic lesions have higher fractional excretion of Iron deficiency
sodium compared with healthy individuals and those with
acyanotic lesions and may be at higher risk of depletion In developing countries where diagnosis of CHD may be
[117]. In children who have undergone the total cavo‐pulmo- delayed, parents may commence early weaning with solid
nary connection (TCPC) operation, diuretic use correlates foods either in recognition that breast or formula feeding is
with low levels of serum sodium, resulting in increased risk insufficient to promote adequate growth or that the infant
of rehospitalisation [118]. The gold standard method to tires easily on sucking. If weaning foods are nutritionally
establish sodium intake of individuals is to collect 24 hour inadequate, there is an increased risk of iron deficiency anae-
urine. If growth is poor, this may be due to low sodium mia, particularly in those with acyanotic lesions where wast-
intake and/or low total body sodium [119]. It is however not ing predominates [11]. Children with cyanotic lesions need
practical to collect 24 hour urine in infants as they are usu- to have optimal oxygen delivery to the tissues. Ensuring an
ally not catheterised, and as such a spot urine sodium should adequate haemoglobin concentration is vital to help with tis-
be done to establish urinary sodium levels [120]. There is no sue saturation [123], and maintaining adequate iron status is
consensus regarding defined cut‐offs for sodium depletion, important.
Table 14.9 Medication and impact on electrolyte status.
Role Drug Electrolyte affected Effect on serum level
Diuretic Spironolactone Sodium Reduces

Loop diuretic Furosemide Potassium Reduces ++
Thiazide diuretic Metolazone Potassium Reduces ++
Bendroflumethiazide Potassium Reduces +
Antihypertensive Captopril* Potassium Increases
Antihypertensive Propranolol* Potassium Increases
Arterial dilatation, increases Milrinone Potassium Occasionally reduces
blood flow to heart
Increases force of cardiac Digoxin Potassium May be toxic if serum
contraction potassium is elevated
Anti‐reflux medication Proton pump inhibitor Phosphate Reduces +
* Angiotensin converting enzyme (ACE) inhibitor.

Complications of Congenital Heart Disease Affecting Nutritional Status 299
Zinc deficiency Learning points: other nutritional issues

Increased pulmonary blood flow resulting in pulmonary
• Treatment of GOR is essential in ensuring adequate nutri-
hypertension puts children with CHD at increased risk of
tion in CHD, but an awareness of treatment options impact-
bronchopneumonia. Low serum zinc levels have been
ing on long‐term mineral status needs to be considered
recorded in children with CHD who develop pneumonia
• Dietitians should be aware of how various drugs used in
[124]. Slicker et al. recommend initial intravenous zinc sup-
CHD may affect electrolyte status
plementation between 250 and 400 μg/kg/day for patients
• Sodium, potassium, iron and zinc status may all be affected
with HLHS due to chest drain losses [96]. Oral zinc supple-
in CHD
mentation can be provided in doses of 2 mg/kg/day for up to
• Vomiting and a few foods high in vitamin K may affect clot-
6 months (although more commonly 1–2 months) [115, 125].
ting in anticoagulated patients, but the diet should not be
altered unnecessarily
Thiamin deficiency
Thiamin deficiency has been documented pre‐ and post‐

operatively in a small group of infants with VSD and tetral-
Complications of congenital heart disease
ogy of Fallot before and after surgery, with up to a quarter affecting nutritional status
affected despite adequate dietary intakes [126]. Further work
may be needed to identify a cause and the level of supple- Chylothorax
mentation needed.
Normal transport of chyle
Vitamin and mineral supplementation After digestion in the intestinal lumen, dietary fats are
absorbed into the mucosal cells as glycerol and fatty acids.
Supplementation with a vitamin D containing multivitamin Long chain fatty acids of 12 or more carbon atoms are re‐
from birth should be considered in all infants with CHD. esterified to triglycerides and pass into the thoracic lymph
Low vitamin D levels have been reported in infants with duct as chyle. Sixty to seventy per cent of absorbed dietary
CHD and are associated with greater post‐operative cardio- fat passes through the lymphatic system at a concentration
vascular dysfunction, increased post‐operative fluid of between 5 and 30 g/L. Flow increases markedly after
requirements and longer duration of mechanical ventilation ingestion of a high fat meal with lesser, but definite increases
[127, 128]. Additional micronutrients and trace elements after mixed meals of protein, carbohydrate and fat [134]. The
may be worth considering, particularly if growth is subop- principal function of the thoracic lymph duct is to transport
timal [115, 129]. chyle to where it enters the venous system near the junction
of the left internal jugular and subclavian veins [135], and
these vessels then drain into the superior vena cava.
Anticoagulation and the vitamin K content of feeds
Figure 14.8 shows the anatomy of the thoracic lymph duct.
Chylothorax is caused by a fistula between the thoracic
Children undergoing Blalock–Taussig (BT) and Glenn
lymph duct and the pleural cavity resulting in the accumu-
shunts, TCPC (or Fontan) operation, pulmonary artery
lation of chyle in the pleural cavity itself. Chyle contains
reconstruction and some operations requiring tissue homo-
lymphocytes, immunoglobulin, enzymes, triglycerides,
graft or mechanical valves are given either aspirin or warfa-
cholesterol and fat‐soluble vitamins, the loss of which, if
rin post‐operatively for anticoagulation. Vitamin K has an
unchecked, would invariably lead to serious metabolic
antagonistic effect on some of the anticoagulation drugs and
deficit.
may be given in some instances to counter excessive antico-
agulation. Vitamin K doses of 150–250 μg/day have been
found to affect anticoagulation in adults [130, 131]. Fistulas
If the child has a history of vomiting around feed or meal-
There are three types of fistula:
times, giving the warfarin dose away from these times may
help to achieve more stable anticoagulation. Severe vomiting • Traumatic fistula: the thoracic duct drains into the vessels
has been associated with excessively elevated international close to where some cardiac surgical procedures are car-
normalised ratio (INR) in adults [132]. The level of vitamin K ried out. As the thoracic duct is difficult to see, there is an
in some leafy vegetables may have an antagonistic effect on increased risk of disruption and damage to the duct dur-
anticoagulation, but the bioavailability of various forms of ing surgery, resulting in a traumatic fistula.
vitamin K is uncertain [133]. Curly kale, broccoli, spinach, • Obstructive fistula: results from increased pressure in the
Brussels sprouts and endive have a high vitamin K content. thoracic lymph duct itself, which causes its walls to
If these foods appear to exert an effect, then temporary or become leaky. This may be secondary to increased
permanent withdrawal may be needed to achieve a satisfac- venous pressure due to sluggish blood flow or clots in
tory INR. However, unnecessary manipulation of the nor- the veins distal to where the thoracic duct empties.
mal weaning diet is inappropriate. Patients with right‐sided obstructive cardiac lesions
Right lymph Table 14.10 Conditions requiring Glenn and/or total cavo‐pulmonary
duct connection (TCPC) shunt operations.
Heart defect Operation
Superior Ebstein’s anomaly TCPC*

vena cava Pulmonary atresia with/without intact Glenn shunt and TCPC
ventricular septum
Aorta
Tricuspid atresia TCPC
Thoracic
duct Single ventricle physiology Glenn shunt and TCPC
Oesophagus Hypoplastic left heart Norwood stage 2 and 3†
Azygos
vein
Diaphragm * TCPC is one of a number of surgical options in Ebstein’s anomaly.
†
The second stage of the Norwood procedure may be similar to a Glenn
shunt or TCPC, and the third stage may be a TCPC operation.
Area for
low ligation
triglycerides in chyle is higher than that of plasma, this has
also been used to differentiate chylous pleural effusions
from those of other origin [136].
Cisterna
Intestinal chyli
and lumbar Incidence and duration
branches
The incidence of chylothorax is between 1.34% and 9.2% fol-
Figure 14.8 Anatomy of the thoracic duct. Source: Merrigan et al. lowing cardiac surgery for CHD [137, 139, 141]. Low body
[136]. Reproduced with permission from John Wiley & Sons. weight, longer CPB time and secondary chest closures are all
associated with increased risk of developing chylothorax
require venous to pulmonary artery shunt operations to [141]. A higher incidence of chylothorax has been noted in
achieve longer‐term oxygenation. Examples of these patients undergoing repair of tetralogy of Fallot [139], the
shunts are the Glenn or the TCPC operation (see TCPC procedure and heart transplantation [137].
Figure 14.12) where the venous return is plumbed A duration of 9–15 days is expected before chest drain out-
directly into the pulmonary vasculature. Under these cir- put ceases [137, 141], although up to a quarter of cases have
cumstances the blood flow in the lungs is increased, continued outputs beyond 30 days [137]. The amount of chy-
resulting in ‘back pressure’ into the pulmonary arteries lous drainage varies between 2 and 40 mL/kg in most
and the newly connected systemic veins. As a result, the cases [139, 141, 142] with high outputs >100 mL/kg/day indi-
lymph does not drain well into the veins, and the lym- cating that dietary treatment is likely to be unsuccessful [141].
phatic vessels themselves become engorged and leaky,
with chyle passing into the thoracic cavity. However, it
Treatment options
appears that the increased risk of developing chylotho-
rax only occurs with the larger TCPC shunt [137]. An There is a lack of consensus regarding the optimal manage-
exacerbating factor may be the development of either a ment of chylothorax, with no evidence arising from a ran-
chest infection or a post‐operative pleural effusion, and domised controlled trial [135]. A recent international survey
chylothorax may occur some days after operation. A list showed there was considerable variation in practice with
of cardiac defects that may require these operations is regards to the management of chylothorax [143]. As a result,
shown in Table 14.10. variation of practice is considerable, which may result in many
• Congenital fistula: some children may develop congenital infants and children having dietary fat restriction for longer
chylothorax [138], children with Noonan syndrome than is necessary, affecting weight gain and growth [144].
being at higher risk. Historically chylothorax has been treated conservatively
using a minimal long chain triglyceride (LCT) diet [137, 139,
141, 145] or total parenteral nutrition (TPN) [139]. However,
Diagnosis
some suspected cases of chylothorax may be self‐limiting
As chyle contains fat from the intestinal lacteal system, it has with a median resolution time of 1 week following presenta-
a characteristically milky appearance that often raises suspi- tion [140]. As a result, it has been proposed that any inter-
cion when it appears in post‐surgical pleural chest drains. A vention be delayed following diagnosis, with an expectation
chest drain sample with a triglyceride content of that the chyle drainage will resolve within 7 days [73] and
>1.1 mmol/L, a total cell count >1000/μL with a predomi- the role of limiting dietary LCT has been questioned.
nance of lymphocytes, or the presence of chylomicrons has Depending on the cardiac unit, practice is currently to either
been used to confirm diagnosis [137, 139] although others commence a minimal LCT feed/diet or wait for symptom
use a combination of these [140]. As the concentration of resolution while continuing to provide a normal feed or diet.
A survey of US centres showed the majority using TPN as required for 14 days. Once the pleural drainage has decreased
the main treatment mode [59]. to <5 mL/kg/day, PN can be replaced by the infant’s usual
If after 7 days there is no resolution, a period of parenteral milk if tolerated, or a continuation of a low LCT diet for a
nutrition (PN) for 10–14 days or a 2‐ to 4‐week period of further 2–4 weeks [135]. Surgery should be considered for
minimal LCT diet may be required to reduce the lymph flow patients who fail these initial steps or in whom complica-
and so allow the fistula to heal [135]. Dietary fat is mainly tions such as electrolyte and fluid imbalance, malnutrition or
composed of LCT. Normally medium chain triglycerides immunodeficiency persist [152].
(MCT), with 6–10 carbon atoms in the fatty acid chain, do not
constitute more than a minor proportion of dietary fats. Monogen
However, as they are absorbed directly into the portal vein
as ‘free fatty acids’ bound to albumin, they constitute a use- Monogen is a whey protein‐based infant formula with
ful additional source of energy in a diet that may otherwise low LCT content that has been used as the treatment of
be low in energy. As diets high in MCT are used to promote choice in infants with chylothorax. The fat sources are frac-
weight loss in adults, growth monitoring during the treat- tionated coconut and walnut oil. Monogen contains 0.35 g of
ment period is important [146]. LCT/100 mL formula at standard dilution (17.5%) (Table 14.11).
There have been individual case reports of the hormone, If the infant has previously been tolerating normal or con-
somatostatin or an analogue, octreotide (both of which have centrated feeds prior to the development of chylothorax, it
antisecretory and antidiarrhoeal properties) being used in should be possible to introduce Monogen at full strength
isolation or as an adjunct to a minimal LCT diet or PN to despite its relatively high carbohydrate content (12%) and
treat refractory chylothorax. A dose of 1–4 μg/kg/hour is high content of MCT. If the baby has had limited enteral
recommended [147, 148], although benefit has been noted on nutrition, then, as a precaution, Monogen may be introduced
smaller doses [149]. Despite some promising case reports at half strength, i.e. 9% dilution in the first 12–24 hours.
[147–150], results are inconsistent [139, 140]. Surgical liga- Standard dilution provides 74 kcal (310 kJ)/100 mL. In cases
tion of the thoracic lymph duct is usually reserved for of severe fluid restriction, it has previously been advocated
patients who do not respond to 3–4 weeks of conservative to gradually increase the concentration of the feed to meet
management [139, 151]. requirements. However, the current formulation has a higher
LCT content than previously, so it might be prudent to
increase energy density using either glucose polymer (in 1%
Prognosis daily increments) or MCT emulsion (in 1%–2% daily incre-
The conservative dietary approach has a success rate of ments) up to an energy density of 90 kcal (375 kJ)/100 mL.
between 70% and 80% [137, 144, 145]. A useful algorithm for This allows an increase in energy density while maintaining
the management of chylothorax has been produced by a protein–energy ratio close to 10%. However, this is often
Cormack et al. [145]. Development of chylothorax may poorly tolerated, particularly in younger infants, and a
almost triple hospital length of stay [137]. period of PN may be required. Monogen is a complete infant
formula so supplementation with essential fatty acids (EFA)
should not be needed. However, falls in EFA status have
Dietary treatment been noted following commencement on Monogen feeds
The publication describing treatment of chylothorax with a (Luise Marino, personal communication).
minimal LCT diet is now rather old (Diets for Sick Children, To achieve adequate energy intake to facilitate growth, the
4th edition, 1987, Dorothy Francis) and recommends giving total LCT intake may be greater than the 1 g/year of life rec-
no more than 1 g LCT per year of life up to a maximum of ommendation. If chest drain output is unaffected, then a
4–5 g LCT/day. The efficacy for this practice has not since higher LCT intake should be allowed to continue. If chest
been studied in a randomised controlled trial, and it is often drains are not in situ, then clinical signs such as increased
breached [144], particularly in older infants and younger respiratory effort can be used to monitor tolerance to
children where 1–2 g LCT/day is very difficult to manage.
Achieving this without compromising nutritional intake is Table 14.11 Nutritional content of standard Monogen per 100 mL.
challenging and supplementary PN should be considered
[97]. The use of feeds with a high MCT content is also associ- Energy 74 kcal/310 kJ
ated with significant weight loss compared with the use of a Protein 2.2 g
fat‐free enteral feed with peripheral lipid or TPN, both of Carbohydrate 12 g
which have been shown to significantly reduce chyle drain Fat 1.9 g
output in cases refractory to conventional low LCT feeds
MCT 1.52 g
[144]. If the chylous leak is responsive to a low LCT diet,
pleural losses should be reduced to <10 mL/kg/day by day LCT 0.35 g
7 and cease by the end of the second week of treatment. Energy from C18:2 (%) 1.1
However, if the drain output remains unchanged or output Energy from C18:3 (%) 0.17
increases after the first week, the low LCT diet should be
discontinued and PN should be commenced and is usually MCT, medium chain triglycerides; LCT, long chain triglycerides.
increasing amounts of LCT. A chest X‐ray may confirm reac- Table 14.12 Sample day’s menu for a toddler on a minimal LCT diet.
cumulation of chyle in the pleural cavity. The ‘clock’ for the
duration of the diet should be started when it is initiated and Minimal fat milk (MFM)
not when the pleural drains are removed. 60 g skimmed milk powder Provides 500 kcal (2090 kJ)
35 mL Liquigen 22 g protein
Essential fatty acids 30 g glucose polymer 0.8 g LCT

8 g Paediatric Seravit + water
EFA in phospholipids are important for maintaining to 600 mL
the function and integrity of cellular and subcellular
Use throughout the day for drinks and mixed with appropriate foods
membranes. They also participate in the regulation of cho-
lesterol metabolism, being involved in its transport, break- Breakfast 10 g Rice Krispies + 60 mL MFM
down and ultimate excretion. Long chain polyunsaturated Glass MFM (100 mL)
fatty acids (LCP) are important in the growth and develop- Mid‐morning Glass MFM (100 mL) + 2 MCT biscuits
ment of term infants, and their addition to the diet in Lunch 80 g baked beans + 50 g MCT chips
appropriate quantities is safe [153]. A deficiency state aris-
50 g very low fat fromage frais
ing from an inadequate intake of linoleic acid has been
demonstrated in children [154]. Although a specific defi- Glass fruit squash + glucose polymer
ciency state arising from inadequate dietary α‐linolenic Mid afternoon Glass MFM (100 mL)
acid has not been demonstrated in healthy humans, it Meringue or Rice Krispie cake
is regarded as a dietary essential [154]. It has been
Supper 40 g white fish steak fried in MCT oil
recommended that the neonate requires at least 1% of

energy intake from linoleic acid (C18:2) and at least 0.2% Fat‐free mashed potatoes + 2 teaspoons
Liquigen
of energy from α‐linolenic acid (C18:3) [155]. The current
formulation of Monogen has slightly over the required 40 g carrots
percentage energy from linoleic acid while having slightly 50 g very low fat ice cream
less α‐linolenic acid. Jelly
Bedtime Glass MFM (100 mL)
EFA supplementation of feeds Total LCT intake for the day = 2 g

If EFA need to be added to a feed, this may be done using
LCT, long chain triglycerides.
walnut oil; the fatty acid content provides linoleic and α‐
linolenic acids in an acceptable quantity and ratio. Walnut oil
contains 55 g linoleic and 12 g α‐linolenic acids per 100 mL
A minimal fat milk may replace the minimal LCT formula
(Table 30.4). As the energy content of the feed is increased, it
from 1 year if nutritional intake is not compromised by doing
will be necessary to increase the EFA supplementation
so. This minimal fat milk can be flavoured with Nesquik
proportionately.
powder, fruit Crusha syrups or low fat chocolate flavour top-
ping. It can also be used on breakfast cereals, to make custard
or in cereal‐based puddings. The quantities of the ingredients
Minimal LCT weaning diet
may be varied to taste if needed, to provide 70–90 kcal (230–
The following foods contain minimal LCT and can be intro- 375 kJ)/100 mL. Extra energy can be added to the diet by
duced as weaning solids: increasing the concentration of glucose polymer in the milk
or by using a 10%–15% solution of glucose polymer to make
• puréed vegetables, e.g. potato, carrots, swede, green
up fruit squash. Increased energy intake can be achieved by
beans
the addition of Liquigen (MCT emulsion) to suitable foods
• puréed fruit, e.g. pears, apples, banana, peaches
such as mashed potatoes or other root vegetables.
• puréed boiled rice mixed with minimal fat milk
• baby rice reconstituted with minimal fat milk
• tins and jars of baby foods containing less than 0.2 g LCT Feeding the older child and adolescent with chylothorax
per 100 g may be included in the diet (mainly the fruit‐
There are no randomised controlled trials regarding the opti-
based tins and jars). Other commercial baby foods may
mal intake of LCT fat in children with chylothorax as the
contain too much LCT and need to be avoided
overly restrictive low LCT diet may negatively impact on
Even when solids are introduced into the diet of the infant, nutritional quality, particularly as foods that are higher in LCT
a minimal LCT formula will continue to form a major part of are also usually protein rich. Based on results from a world-
the nutritional intake providing energy, protein, vitamins wide survey, a pragmatic approach may be more suitable,
and minerals and is an essential part of the diet up to 1 year allowing a higher LCT intake of around 20–30 g day; this may
of age. A sample day’s menu for the toddler on a minimal ensure better compliance, in addition to providing a more indi-
LCT diet is given in Table 14.12. vidualised approach (Marino et al., personal communication).
MCT can be used in the diet in the form of MCT oil or 25% 4 weeks, and 40% 6 weeks (Marino et al., personal com-
MCT emulsion. MCT oil allows fried foods to be included, munication). Research is urgently required to determine
such as fried fish, chips and crisps. Both MCT oil and MCT duration of treatment and degree of fat restriction. Cormack
emulsion can be used in baking, cakes, biscuits and pastry; et al. [145] have suggested a return to normal diet 4 weeks
all these foods are valuable sources of energy and can greatly after removal of a pleural drain that has not resulted in recur-
enhance the palatability of the diet to the patient. MCT rence of chylothorax, while others suggest 2–4 weeks’ con-
should be gradually introduced over a period of 7–10 days to tinued treatment following chest drain removal [135]. One
avoid abdominal discomfort. Table 14.13 lists foods contain- further study suggested that patients could be transitioned
ing minimal LCT, which can be used freely in the diet. onto normal infant formula within 1 week with limited risk
The weights and fat contents of foods that can be used to of relapse following use of a ‘long chain fatty acid‐free’ for-
construct a day’s meals containing minimal fat for the child mula with only 1%–2% MCT content [141]. For infants, the
or adolescent with chylothorax are given in Table 14.14. A risk of limiting the supply of EFA during a critical point in
review of some suitable low fat foods indicates that there brain and retinal development should be balanced against
may be up to a threefold variation in fat content of some achieving faster resolution of chylothorax. Following rein-
meat and fish products depending on the brand. To make the troduction of a normal diet, clinical signs usually confirm
diet more manageable, the family can be taught to calculate whether chylothorax has recurred or not, but a chest X‐ray
minimal LCT exchanges as follows: may help clarify.
0.2 g fat exchange

0.2 Learning points: chylothorax
100 g
grams of fat/100 g of food
• The incidence of chylothorax in CHD is highest in right‐
0.5 g fat exchange sided obstructive lesions that require pulmonary artery
0.5 shunt operations
100 g
grams of fat/100 g of food • Current opinion regarding length of treatment period with
a minimal long chain fat diet varies from 2 to 6 weeks
• Chylothorax increases the risk of patients incurring nutri-
Vitamin and mineral supplementation tional deficits, and the diet treatment needs to be carefully
Since a wide range of foods must either be excluded from the tailored to ensure overall adequacy
diet or taken in reduced quantities, it is essential to check the
vitamin and mineral content of the diet, giving supplements
if needed.
If an older child with chylothorax requires tube feeding, a
‘juice’ style oral nutritional supplement, e.g. Ensure Plus
Length of treatment period
Juce, Fortijuce, Fresubin Jucy or PaediaSure Plus Juce, may
Results from a worldwide survey suggest there is consider- be used as the feed base as they do not contain any fat. These
able variation in practice regarding treatment duration with supplements may require additional electrolytes and EFA
a minimal LCT diet: 21% of centres recommend 1–2 weeks, from walnut oil to make them nutritionally complete. They
may be diluted if necessary, should a 1.25–1.5 kcal (5–6 kJ)/
Table 14.13 Free foods for minimal LCT diet. mL feed not be tolerated.
All fruits fresh, tinned or frozen (except olives and avocado pear)
Necrotising enterocolitis
All vegetables, fresh, tinned or frozen
Sugar, honey, golden syrup, treacle, jam, marmalade The overall incidence of necrotising enterocolitis (NEC) in
Jelly and jellied sweets such as Jelly Tots, Jelly Babies, wine gums or infants with congenital heart defects is around 10 times that
fruit pastilles found in healthy term infants. Development of NEC mark-
Boiled sweets, mints (not butter mints) edly increases PICU length of stay and may double hospital
length of stay in patients with HLHS [62]. A review of cases
Fruit sorbets, water ices, ice lollies
of NEC in a large cohort of term and preterm infants with
Meringue, egg white, Rite‐Diet egg replacer CHD (n = 643) demonstrated an incidence of 21 cases (3.3%);
Spices and essences 7 had a gestational age <36 weeks; 6 term infants had devel-
Salt, pepper, vinegar, herbs, tomato ketchup, most chutney, Marmite, oped an episode of poor systemic perfusion or shock [156].
Oxo, Bovril Of the eight remaining term infants who developed NEC all
Fruit juices, fruit squashes, Crusha fruit flavouring syrups, Nesquik fruit had lesions that put them at risk of low blood flow in the
flavouring powder, chocolate flavour topping, bottled fruit sauces systemic circulation. HLHS and truncus arteriosus/aor-
Fizzy drinks, lemonade, cola, Lucozade topulmonary window were identified as defects that
increased the risk of the infant developing NEC [156] with
LCT, long chain triglycerides. up to a quarter of HLHS patients affected in one study [62].
Table 14.14 LCT content of foods suitable for use in minimal LCT diet.
Food LCT (per 100 g) Average portion size (g) LCT per portion (g)
Breakfast cereals
Branflakes 2.0 35 0.7
Cornflakes 0.9 25 0.2
Frosties 0.6 20 0.1
Sugar Puffs 1.6 25 0.4
Special K 1.0 20 0.2
Coco Pops 2.0 20 0.4
Just Right 2.5 40 1.0
Rice Krispies 1.0 25 0.25
Ricicles 0.7 20 0.1
Weetabix 1.9 37.5 (2 biscuits) 0.7
Puffed Wheat 2.5 15 0.4
Frosted Shreddies 1.4 35 0.5
Weetaflakes 1.6 30 0.5
Bread
White, large thin slice 1.6 35 0.4
Granary 1.7 35 0.6
Matzos 1.0 20 0.2
Crumpets (toasted) 1.0 45 (1 crumpet) 0.45
Dairy foods
Reduced fat cottage cheese 1.4 50 0.7
Very low fat fromage frais 0.1 100 0.1
Condensed milk, skimmed sweetened 0.2–1.0 50 0.1–0.5
Very low fat yoghurt (Muller Light) 0.1 200 0.2
Very low fat ice cream 0.4 50 0.2
Fish
White cod fillet, raw 0.1–0.7 100 0.7
White cod steak, raw 0.6 100 0.6
Grilled white haddock fillet 0.6 100 0.6
Steamed whiting 0.9 100 0.9
Steamed smoked haddock 0.9 100 0.9
Fish finger 7.2 25 (1 fish finger) 1.8
Tuna 0.2–0.6 100 0.2–0.6
Shell fish
Prawns (peeled) 0.5–1.7 80 0.4–1.4
Crabsticks 0.1 50 Neg
Crab (canned) 0.9 50 0.4
Crab (white meat only) 0.1 100 0.1
Shrimps (canned) 1.2 50 0.6
Cockles (boiled) 0.3–3 50 0.1–1.5
Mussels 2–3 50 1.0–1.5
Meat, poultry and alternatives
Roast turkey, light meat 1.4 70 1.0
Roast chicken, light meat 4.0 25 1.0
Roast lamb, lean 8.0 25 2.0
Roast beef topside, lean only 4.0 45 1.8
Roast beef silverside, lean only 4.9 40 2.0
Thin sliced packet beef cooked with added water 2.6 30 0.8
Ham 2.3–7.0 40 1.2–2.8
Quorn mince 2.0 50 1.0
Legumes, pasta, rice
Baked beans in tomato sauce 0.5 200 1.0
Tinned spaghetti in tomato sauce 0.1 200 0.2
White rice (boiled) 0.3 150 0.4
White pasta (boiled) 0.8 130 1.0
LCT, long chain triglycerides.

Reversal of blood flow in the mesenteric arteries during Protein‐losing enteropathy

diastole was strongly linked with development of NEC irre-
spective of type of CHD in a further study [157]. However, in Children with a cardiac anatomy that gives them a single
a separate smaller study involving neonates with HLHS, functional ventricle undergo a series of operations in which
none developed NEC despite proven reduced mesenteric the venous return is eventually plumbed directly into the
artery blood flow [158]. arteries of the lungs (TCPC procedure), which has the ben-
In addition, lesions requiring high doses of prostaglandin efit of improving oxygenation and reducing the load on the
(>0.05 μg/kg/minute), to keep the ductus arteriosus open to ventricle. Protein‐losing enteropathy occurs in CHF [45],
ensure adequate blood flow to the lungs, may also place the and there is a growing body of evidence that it occurs in
patient at increased risk of NEC. The use of prostaglandin 10%–25% of patients who have undergone a TCPC proce-
introduces a theoretical risk of blood being ‘stolen’ from the dure [164, 165]. Diagnosis is confirmed by positive stool
systemic circulation to the lungs, resulting in reduced mes- α‐1‐antitrypsin [53]. The condition may resolve as cardiac
enteric blood flow and perfusion of the associated gut tissue. function improves following surgery or heart transplant
Disturbed mesenteric artery blood flow in infants with such [63]. Localised lesions have been treated by partial bowel
systemic to pulmonary circulatory shunts has been demon- resection [164]. There is limited evidence for the dietary
strated [159]. treatment of protein losing enteropathy, but a useful start-
Cases of NEC have also been reported in patients with ing point would be to follow that for intestinal lymphangi-
cyanotic lesions, TGA and pulmonary atresia following car- ectasia (p. 118). The diet should provide 5–10 g fat per day
diac catheterisation [160]. The aetiology of NEC in this group and be high in protein using MCT to improve energy
of patients remains unclear; possibly hypoxia, resulting in intake. High protein intakes of up to 3 g/kg/day have been
splanchnic vasoconstriction along with catecholamine suggested with additional supplementation of fat‐soluble
release due to the stress of cardiac catheterisation, might vitamins [53].
result in reduced blood flow to the gut. As a precaution it is
suggested that feeds might be introduced more cautiously in
these patients following catheterisation. Hepatic dysfunction
Coarctation of the aorta has not been identified as a pre-
disposing factor for NEC despite the reduced systemic blood The TCPC operation is known to cause ‘back pressure’ on the
flow, which theoretically could reduce mesenteric blood liver, predisposing patients to hepatic dysfunction. Some go
flow and intestinal tissue perfusion. These infants may be on to develop moderate to severe liver disease [61].
admitted with a history of taking feeds at near normal vol- Prothrombin time becomes progressively deranged from the
umes with no signs of intolerance. However, if they are time of operation, and it has been proposed that this, along
admitted in clinical shock with an acidotic picture, feeds with the ability to eliminate galactose, is used as a test of liver
might then be withheld temporarily until the infant is more dysfunction in this population [61]. Dietary treatment will
clinically stable. depend on the degree of liver failure and its progression.
It is common practice for infants with HLHS to have feeds
withheld in the first few days after birth before the first staged Vocal cord palsy and feeding difficulties
repair (Norwood stage 1 or Sano procedure) with PN provid-
ing pre‐operative nutritional support. However, del Castillo Vocal cord palsy (VCP) is a well‐documented complication
et al. reported that up to one third of their patients are fed of congenital heart surgery with an incidence of between 2%
pre‐operatively with no apparent increase in NEC, although and 8% [64, 104, 166, 167]. Any surgery close to the aortic
details on quantities and type of feed are lacking [161]. arch (where the left recurrent laryngeal nerve branches off
Post‐operative feeding protocols and algorithms provide the vagus nerve), along with the pulmonary arteries, carries
guidance on the introduction of feeds to try to reduce the an increased risk. Surgery to ligate a PDA has an increased
incidence of NEC in patients with HLHS [161, 162]. probability of development of VCP due to nerve damage.
Introduction of feeds at around seven days post‐operatively Smaller infants are particularly at risk with up to two thirds
using either breastmilk or a hydrolysed protein feed, with a of extremely low birthweight infants developing VCP after
slower increase in volumes, achieving full feeds after a fur- PDA ligation [167]. Up to a third of infants with HLHS
ther 7 days has been proposed [161]. Braudis et al. have sug- may be affected [62], but a recent modification in surgical
gested that an adequate cardiac output is required with low technique connecting the right ventricle directly to the lung
requirement for inotropes and good peripheral perfusion circulation (Sano shunt) has resulted in fewer cases [62].
before considering commencing enteral feeds [162]. The extent of feeding difficulty varies depending on car-
However, once initiated, they propose a rapid increase in diac lesion. Infants with HLHS have a far higher incidence of
feeds, initially at 1 mL/kg/hour, but then increasing by feeding difficulties than patients with TGA (48% vs. 4%),
2 mL/kg/hour every four hours until target volumes are take twice as long to achieve a target energy intake of 100 kcal
met, and report no incidence of NEC. Breastmilk, with its (420 kJ)/kg/day and weigh significantly less at 1 month,
known benefits in preventing NEC in premature infants 6 months and 12 months of age [60].
[163], should remain the feed of choice in cardiac infants at Increased breathlessness and fatigue may cause some
high risk of NEC [161]. infants with CHD to feed repeatedly for short periods of
time. Early satiety, vomiting and anorexia, all of which may Table 14.15 Factors associated with increased risk of readmission [170].
be interlinked, lead to low energy intake. Up to half of infants
admitted for cardiac surgery may have feeding difficulties Factor Odds ratio for readmission
when assessed by a speech and language therapist [8]. Single ventricle physiology 2.39
Having CPB and prolonged ventilatory support are associ-
Pre‐operative arrhythmia 2.59
ated with delays in achieving post‐operative energy intake
targets and oral feeding, particularly in those with cyanotic Long post‐operative hospital stay 2.2
lesions [58]. Feeding difficulties associated with CHD may Nasogastric tube on discharge 2.2
become entrenched, affecting intake into early childhood.
Up to a fifth of patients may continue to show signs of feed- Source: Reproduced with permission from Elsevier.
ing difficulties at 2 years of age [168]. Having repeated oper-
ations is associated with a sixfold increase, and those with
pre‐existing feeding difficulties at operation a 20‐fold Treatment and outcome of patients with specific
increase, in feeding difficulties at 2 years of age [168]. cardiac lesions
Identifying these infants for early intervention and support
may help to reduce ongoing problems. In developing coun- Advances in surgical expertise in recent years has meant that
tries early weaning may indicate breastfeeding difficulties increasing numbers of infants with severe cardiac lesions are
associated with heart failure [11]. surviving and being discharged into the community. The
nutritional status of infants and children with CHD depends
on both the type of lesion and the number of operations that
Learning points: other complications of CHD affecting they require. The more complex the lesion and the greater
nutritional status the number of planned operations, the greater the nutritional
risk to the patient.
• There is increased risk of NEC in CHD, but feeding can be
cautiously commenced in high risk infants once haemody-
namically stable; feeding should stop immediately if signs Atrial septal defects
of NEC develop
• Vocal cord palsy occurs in up to 8% of infants with CHD Because blood flow into and out of the atria is at a consider-
and may take time to resolve; early involvement of a speech ably lower pressure than that in the ventricles, the effect of a
and language therapist may help overcome feeding septal defect between the two chambers on energy expendi-
difficulties ture and subsequent growth should be negligible. As a
• Protein‐losing enteropathy and hepatic dysfunction are late result, growth should not be impaired, and closure of the
complications in CHD and may occur in later childhood ASD at the correct time, between 2 and 4 years of age, is
unlikely to have any bearing on subsequent growth.
Although haemodynamic parameters markedly improve in
all patients following surgery, those referred specifically
Patients with VCP have abnormal swallowing patterns because of poor growth demonstrate no significant catch‐up
and are less able to protect their airways resulting in greater growth [13, 171]. However, children left longer before ASD
risk of aspiration [169]. Low birthweight infants with VCP closure may show signs of faltering growth, which improves
following PDA ligation need longer ventilatory support, following repair [172].
have longer hospital stays and may require long‐term tube
feeding [167]. In one series, 63% of infants required long‐
term gastrostomy feeding to meet their nutritional require-
Hypoplastic left heart syndrome
ments [166]. Infants with hypoplastic left heart who are
HLHS is a condition in which the left ventricle fails to
unable to tolerate oral feeds on discharge may take between
develop fully in utero (Figure 14.9). The patient undergoes a
6 and 10 weeks to recover oral feeding, but some may take
series of palliative operations resulting in the right ventricle
considerably longer [62].
taking over the role of pumping blood to both the pulmo-
nary and systemic circulations. The first‐stage operation,
Factors associated with increased risk known as a Norwood stage 1 operation, at around 5 days of
of readmission age involves connecting the pulmonary artery with the
aorta to create one large arterial vessel. Traditionally, a
Readmission to hospital following surgery is not uncommon smaller head and neck artery is then used to connect to the
with rates of around 10% within 30 days of discharge [170]. pulmonary arteries via a Gore‐Tex tube, allowing the blood
However, children with single ventricle physiology and to be oxygenated, a BT shunt (Figure 14.10). A more recent
those with NG tubes may account for up to 50% of these modification (Sano‐modification) is to connect the right
admissions [170]. It has been suggested that focusing post‐ ventricle directly to the right pulmonary artery using an
operative care on those with four high risk factors may be artificial Gore‐Tex conduit. A second‐stage operation,
helpful in reducing readmission (Table 14.15). known as a Glenn shunt (Figure 14.11), is carried out
Treatment and Outcome of Patients with Specific Cardiac Lesions 307
Thin aorta Patent ductus arteriosus between 4 and 5 months [74], connecting the superior vena
cava directly to the pulmonary circulation, allowing the
venous return from the head to be oxygenated; the initial
shunt is taken down. Inter‐stage mortality is between 8%
and 10% [87, 173], but may be reduced with intensive moni-
toring [74, 174]. The final palliative operation, TCPC or
Fontan (Figure 14.12), is carried out at around 4–8 years and
involves connecting the inferior vena cava to the pulmonary
vasculature. Having good pre‐operative nutritional status is
important, and patients are at risk until their second‐stage
operation.
Feeding and growth from birth to Norwood stage 1

operation
Underdeveloped left ventricle Infants with HLHS have a higher risk of NEC [85] with
reduced superior mesenteric [86] and coeliac artery [175]
Figure 14.9 Hypoplastic left heart syndrome.
blood flow. However, evidence on giving or withholding
enteral feeds before the first Norwood stage 1 operation on
incidence of NEC is limited [96]. Having a prostaglandin
infusion or an umbilical arterial catheter should not be
Blalock–Taussig shunt Anastomosed pulmonary artery and aorta valid reasons for withholding feeds [96, 176]. In Europe it is
more common to give infants with HLHS enteral feeds pre‐
operatively than in the USA [50, 176]. If available, breastmilk
with its benefits in aiding gut maturation and its protective
effects from NEC [177] may be the most suitable feed once
the patient is haemodynamically stable, but close monitor-
ing for feed intolerance is needed [96]. However, in the
absence of breastmilk, it is also possible to use energy‐dense
feeds, particularly if there is a fluid restriction. One retro-
spective cohort study has shown pre‐operative feeding of
20–30 mL/kg results in shorter post‐operative ventilator
duration, better perioperative fluid dynamics and earlier full
oral feeding than in those remaining nil by mouth [178].
Right ventricle pumps blood to both systemic and pulmonary circulations Infants with HLHS tend to be small at birth and continue
to lose weight postnatally [7]. The first critical period, where
Figure 14.10 Stage 1 Norwood procedure: anastomosis of pulmonary
artery and aorta with Blalock–Taussig shunt enabling blood flow to lungs.
these patients are most vulnerable to growth retardation, is
Superior vena cava Right ventricle continues to pump

Superior vena cava delivering venous return
blood to systemic circulation
from the head directly to the pulmonary circulation
Right ventricle continues to pump
blood to systemic circulation
Inferior vena cava (delivering venous return from body) Inferior vena cava delivering blood to pulmonary circulation
Figure 14.11 Stage 2 Norwood procedure: connection of superior vena Figure 14.12 Stage 3 Norwood procedure: total cavo‐pulmonary
cava to left and right branches of pulmonary artery. connection (TCPC or Fontan).
between birth and discharge from their stage 1 palliative demonstrated an almost threefold increase in inter‐operative
operation at around a month of age. Over 90% of patients mortality in patients being fed via NG or nasojejunal tube
suffer a weight loss >−0.5 SDS with over a third experiencing compared with those either fed orally or via gastrostomy
a fall of >−2 SD [7]. Other studies showed median weight [173]. Infants who require NG tube feeding have a greater
remaining static for the duration of admission [9] and 60% of burden of medication [182], and the need for tube feeding
patients do not regain their birthweight by discharge [179]. per se may be an indicator of more severe disease.
Male gender, longer post‐operative mechanical ventilation, Overall outcomes on inter‐operative growth are variable.
longer hospital stays and, interestingly, greater birth weight One study showed growth stabilisation between the first
are all predictors of falls in post‐operative weight SDS [7]. (Norwood) and second (Glenn shunt) operations [7], but
other studies report weight for age falling by up to 1 SDS [68,
184], with admission weights at second operation as low as
Feeding and growth following Norwood stage 1 operation
−2 SD [9]. However, a programme of close cardiovascular
Risk of NEC is unaffected by the type of initial shunt [175], monitoring, feed fortification and, where necessary, tube
but does increase with increasing shunt size that affects feeding with target intakes of ≥110 kcal (460 kJ)/kg/day
blood flow into the descending aorta and mesenteric artery demonstrates that catch‐up growth is possible, with average
[180]. However, as up to a third of patients may not meet weight gains of 26 g/day [174] (Tables 14.16 and 14.17).
normal energy requirements during their stage 1 admission Nevertheless, infants with HLHS can be expected to remain
[179], feeding should commence once they are clinically sta- small with an average weight for age of −1 SD by the time of
ble. A post‐operative enteral feeding algorithm has shown their second operation.
that feeds may be increased quite rapidly towards target
intakes without risk of NEC [162]. Bolus and continuous
feeding are equally as effective in achieving satisfactory Growth following stage 2 operation (Glenn shunt)
weight gain in this group of patients if adequate energy The best time for catch‐up growth to occur is after the stage
intake is achieved [181]. 2 operation (Glenn shunt) has been carried out. Between this
Poor post‐operative oral feeding is common following the operation and 14 months of age, mean weight gain is of the
first‐stage operation with one study showing less than 40% order of +1 SDS [7]. However, care must be taken to ensure
achieving full oral feeding on discharge home [62]. Increased that weight gain does not occur without improvements in
risk factors for poor oral feeding are pre‐operative inability length, which would indicate laying down of excess fat
to feed orally and pre‐operative mechanical ventilation, with (Table 14.18 case study).
recovery of normal oral function taking between 2 and 5
months [62]. Issues with poor oral feeding ability or toler-
ance may only become apparent once the infant is at home. Table 14.16 Factors associated with poor weight gain during admission
In these cases, the support of a local paediatric dietitian, chil- for and after first palliative operation for HLHS [9].
dren’s community nursing team, health visitor and speech
and language therapist with the capacity to identify and During inpatient stay Following discharge home
address feeding issues may help to re‐establish oral feeding.
Longer hospital stay Lower feed energy on discharge
Although oral feeding may be a marker for less severe dis-
ease, those managing oral feeds on discharge do have better Longer PICU stay Worse right ventricular function
inter‐operative growth compared with those with tube or Shorter course of TPN More frequent readmissions
oral/tube feeding [174, 182]. Nevertheless, weight gain High diuretic usage Higher oxygen saturation at discharge
slows earlier in orally fed infants [183], and ongoing moni-
toring is required to ensure initial gains do not falter. HLHS, hypoplastic left heart syndrome; PICU, paediatric intensive care
Options for ongoing nutrition support include NG, nasodu- unit; TPN, total parenteral nutrition.
odenal, nasojejunal and gastrostomy feeding. The option of a Source: Reproduced with permission from John Wiley & Sons.
gastrostomy should be considered in any child still fed via
NG tube after 6 months. The benefits of having less interfer-
ence in the oral cavity may be quite marked, allowing for
rapid improvement in oromotor skills and language develop- Table 14.17 Nutritional targets for discharge in HLHS and criteria
ment (David Hopkins, personal communication). for contacting monitoring team [174].
The benefits of one mode of tube feeding over another in
Prior to discharge Alerts for home monitoring team
this group of patients are contentious. One study showed
gastrostomy feeding having no significant effect on improv- Intake above 110 kcal (460 kJ)/kg/day 1. Intake < 100 mL/kg/day
ing growth [184]. Both NG/nasojejunal [173] and gastros- 2. Weight loss > 30 g in a day
tomy [87] tube feeding have been associated with increased
3. Failure to gain 20 g weight in
mortality. One study has shown no difference in inter‐stage 3 days
mortality between infants fed orally and those fed via NG
tube, but a 2.4‐fold increase in those fed via gastrostomy +/− HLHS, hypoplastic left heart syndrome.
Nissen fundoplication [87]. However, a further study Source: Reproduced with permission from Springer Nature.
Treatment and Outcome of Patients with Specific Cardiac Lesions 309
Table 14.18 Case study: treatment progression and dietetic management of an infant with hypoplastic left heart.
Baby boy born at term. Birth weight = 3.42 kg (25–50th centile), length = 51 cm (50th centile). The first child of parents who speak limited English.
The case study illustrates:
• Mix of breastmilk and energy‐dense formula required to ensure adequate growth.
• Good nutritional status with tube feeding from tertiary centre enabled local team to transition to oral feeding while ensuring adequate nutritional
status.
• The involvement of a local paediatric dietitian with knowledge of paediatric cardiology carrying out home visits enabled treatment options to be
discussed and implemented despite language barriers.
• Involvement of multidisciplinary working with speech and language therapist providing support and reassurance in transition from nasogastric to
oral feeding.
Chronology Medical history/investigations Dietetic interventions
1–4 months old Early surgical intervention with stage To promote growth along birth centiles for length and weight (50th centile) a
1 procedure: Norwood and subsequent mix of 50:50 EBM and Infatrini was provided. During periods of fluid
Stage 2 Glenn procedure restriction 80%–100% Infatrini was provided
4½ months old Transition to district general hospital prior Wt = 7.26 kg (50th centile) Length = 64.5 cm (25–50th centile)
to going home. Local dietitian at district BO 1× day. Vomits 1× day, retches 5–6× day
general hospital contacted by tertiary Feeding 100 mL/kg using a combination of Infatrini and EBM: 115 mL × 4
centre dietitian for handover of care hourly × 6 feeds via NG tube (1 feed of EBM and 5 feeds of Infatrini). Current
post‐op Norwood stage 1 and 2 feed gives 95 mL/kg/day, 90 kcal (375 kJ)/kg/day
operations. History of right diaphragmatic Consultant advises no oral feeding pending SLT review
palsy on PICU – plicated diaphragm. Mum had tried purée weaning solids in tertiary hospital but infant retched
Current drugs: omeprazole, ranitidine, Prior to stage 2 operation mum reports that he had been managing 150 mL
aspirin, spirinolactone, furosemide feed volumes orally with no problems
0.6 mL Abidec Reviewed on ward every 1–2 days: mum not able to provide enough EBM so
alternative standard infant formula given as top up. Vomiting more on Infatrini
Home enteral feeding set up prior to discharge
Day 3 post‐discharge Home visit by local dietitian and CCN Wt = 7.66 kg (↑260 g in 8 days)
BO 3× day. Vomits 1× day mostly associated with moving or changing nappy
Mum reports him as getting upset/inconsolable after some feeds
Feeding: 100 mL Infatrini + 20 mL EBM/infant formula × 6 feeds per day via NG
tube
Advised on upright positioning if possible following feeds
Day 4 post‐discharge SLT review SLT reports patient as becoming hot, sweaty and upset before the end of each
feed. Ruminating towards the end of feeds (indicating possible GOR). On
advice from SLT mum has started him on some purée sweet potato. Managed
3–4 teaspoons
5 months old CCN review. Oxygen saturations in air: Wt = 8.04 kg (>50th centile)
84%–86% Continues feeding 100 mL Infatrini + 20 mL EBM/infant formula via NG tube
Reports managing only 1 teaspoon solids per day
Ongoing weekly telephone calls with local dietitian. Patient continues to
vomit in the early morning on waking
6 months old Telephone discussions with tertiary centre No concerns with current weight. Plan to progress with increasing intake of
Nutrition Team weaning solids while continuing on NG feeds
Change in NG tube reported to be better tolerated. Feed regimen altered to
give 60 mL in the morning when he is more likely to vomit, larger volumes of
120 mL later in the day. Intake: 77 mL/kg/day, 73 kcal (305 kJ)/kg/day
6½ months old Further home visit with CCN Wt = 8.66 kg (50–75th centile). Continues to vomit 2× day associated with
opening bowels. Flexible approach to NG feed volumes discussed, feeding
100–130 mL Infatrini + 20–30 mL infant formula via NG tube. Appears to have
entrenched food aversion requiring oral desensitisation
Further SLT assessment: unable to manage a few millilitres of infant formula
and recommends thickened feeds. Plan for gentle approach, applying
thickened feeds and purée food to lips regularly each day. Mum feels he is
getting hungry
7½ months old Professionals meeting with SLT, Consultant Wt = 8.9 kg (50–75th centile). Mum now trained in passing NG tube
paediatrician with interest in paediatric Combination of 100–110 mL Infatrini + 20 mL infant formula feeds × 5 per day
cardiology, parents, CCN and local gives 75 mL/kg/day, 71 kcal (295 kJ)/kg/day. Starting to replace Infatrini with
dietitian some formula feeds to try to improve appetite
SLT: starting ‘messy play’ allowing patient to suck puree food off a variety of
soft utensils. Therapy support workers involved
(contiued to overleaf)
8 months old Outpatient clinic review with local Wt = 8.98 kg (50–75th centile) Length = 69.2 cm (25th centile)
dietitian No longer vomiting in the morning. Mum concerned about weight, but food
intake has improved from 2 weeks ago, now managing 1 dessert spoon solids
at some meals. Trying some water from a syringe. Plan: offer water from
spouted beaker and offer from a syringe if this does not work, increase to
3 meals per day
9½ months old Telephone call to mother Fewer vomits. Now managing 3 dessertspoons of solids at each meal. Using
meat, potatoes and vegetables as basis of main meals. NG feeds: 130 mL
standard infant formula three times a day and 2 feeds of 95 mL Infatrini mixed
with 35 mL standard formula. Trying small amounts of feed orally
10 months old Outpatient clinic review with local Wt = 9.22 kg (50–75th centile)
dietitian. Ongoing fortnightly telephone Length = 68.9 cm (9th centile)
reviews No gagging or vomits reported
Now managing 2 small baby bowls of cereal and meat with vegetables. Has
started to drink milk again 2 × 30 mL/day, but majority of feeds are still via NG
tube. Having a mix of about ½ Infatrini and ½ standard formula
Plan: All feeds as standard infant formula. Increase volume of feeds gradually
from 140 × 5 to 170 mL × 4 feeds per day and progress with weaning to 3
meals per day including main and dessert items
11½ months old Dietetic outpatient and SLT review Weight = 9.44 kg (50th centile) Length = 72 cm (9th centile)
SLT review shows good progress with both solids and fluid intake. However,
becoming constipated
Aiming for 500–600 mL standard infant formula in a total fluid allowance of
800 mL per day. Formula feeds to be given after meals to encourage food
intake. Encouraging to drink more from a cup. Discussed removing NG tube,
but some medications still needing to be given via tube
1 year old Telephone review CCN visit. Wt = 9.46 kg (<50th centile) Length = 72 cm (2nd–9th centile). NG
tube removed. Managing all food and fluids orally. Encouraging more lumpy
solids
EBM, expressed breastmilk; NG, nasogastric; SLT, speech and language therapist; CCN, children’s community nurse; BO, bowels open; GOR, gastro‐
oesophageal reflux.
Tetralogy of Fallot blood flow, increasing respiratory effort that requires addi-
tional nutritional support. Once stabilised or after recovery
This complex cyanotic defect has four separate aspects: a from the shunt operation, the infant can be discharged home.
VSD, an ‘overriding aorta’ in which the aorta straddles the As this is a cyanotic lesion, breathlessness may affect feed-
two ventricles, obstruction of pulmonary blood flow from ing, and growth may slow prior to having the lesion repaired,
the right ventricle (sub‐pulmonary stenosis) and right ven- usually at about 4–6 months of age. The primary defects are
tricular hypertrophy (Figure 14.5). The presence of a VSD repaired with closure of the VSD, repair of the pulmonary
would usually result in excessive pulmonary blood flow, outflow tract and, if it has been necessary, removal of the BT
the development of pulmonary hypertension and subse- shunt. Improvements in feeding ability may then become
quent faltering growth. However, the pulmonary stenosis apparent with full catch‐up growth occurring within 2 years
protects the lungs from excessive lung blood flow prevent- of repair [185].
ing the development of pulmonary hypertension but
increases the workload of the right ventricle causing hyper-
trophy. Patients who have very little outflow tract obstruc- Transposition of the great arteries
tion may develop high pulmonary blood flow and require
nutritional support. With TGA the two main arteries exit from the opposite ven-
Rarely, if blood flow to the lungs is very restricted and the tricles from which they would normally, the aorta from the
patient is very cyanosed, a BT shunt operation is initially right ventricle and the pulmonary artery from the left. The
performed (Figure 14.10) early in life to try to normalise pul- patient survives because blood mixes through a patent
monary blood flow. Infants who have undergone the BT foramen ovale (PFO) and a PDA. Prostaglandin is almost
shunt operation may however develop excessive pulmonary always given to keep the PDA open. In about 25% of
Glossary 311
patients, the PFO is enlarged, using a cardiac catheter in a studies without the risk of selection bias may help to clarify
procedure called a balloon atrial septostomy, to allow for the timing and type of feeding that is most beneficial.
better mixing of blood. The patient can recover before a fur- Several studies have now identified energy requirements
ther operation is carried out at about one week of age in of patients in intensive care who have undergone specific
which the arteries are switched over to their correct posi- operations. Further evaluation of post‐operative energy
tion, the hole between the atria repaired and the PDA requirements in specific patient groups may enable better
closed. These patients tend to have normal birthweights targeting of nutritional support. Clarification of energy pro-
[34, 43] although the reason for this is uncertain. Repairing vision of optimum mix of carbohydrate and fat in different
this complex defect within the first few weeks of life ena- cardiac conditions is needed, with evidence of improving
bles patients to be discharged, feeding normally, usually cardiac function.
without dietetic intervention, with good prospects for nor- A suitable means of improving breastmilk fortification
mal long‐term growth [12]. without raising the osmotic load such that there is increased
risk of developing NEC is needed. Evidence of improved
vitamin and mineral status from an appropriate supplement
Ventricular septal defect is lacking in this group of patients.
There continues to be uncertainty as to whether chylotho-
In VSD a hole exists between the two ventricles. There are rax is a self‐limiting condition and, therefore, whether a min-
several types. The most common is a peri‐membranous imal LCT diet is required for treatment; evidence‐based
defect in which the hole is located at the ‘top’ of the ventricle outcome data is limited. The use of either TPN or a fat‐free
near to where blood exits. A muscular VSD is located near the feed with peripheral lipid in either speeding recovery or
‘bottom’ or apex of the ventricle. In most cases the VSD tends treating cases who initially fail to respond may need further
to close or become so small as to have an insignificant effect evaluation. There is uncertainty as to whether treatment fail-
on cardiac function as the child grows. However, a moderate ures are due to the current level of LCT in feeds (0.35 g/100 mL)
to large VSD causes increased blood flow into the lungs, not being low enough.
resulting in breathlessness, elevated metabolic rate and the The issue of pre‐operative enteral feeding of patients with
child to feed in short bursts. These defects require closure as HLHS differs in Europe and the USA and has not been fully
they invariably result in faltering growth (Figure 14.2). The resolved. The conflicting outcomes from varying modes of
child may undergo an initial pulmonary artery band opera- nutritional support in these patients demonstrate the need
tion that reduces the blood flow to the lungs, protecting them for further multicentre studies.
from the development of pulmonary hypertension. The
infant needs to grow to a size (approximately 5 kg) that ena-
Glossary
bles surgical closure to be carried out more easily. This
requires a careful balance between increasing the energy con-
Anomalous origin of left coronary artery from pulmonary
tent of the feed to promote growth and trying to limit the
artery (ALCAPA) ALCAPA is a rare condition in which
almost inevitable GOR and vomiting. However, there has
the left coronary artery arises from the pulmonary artery
been a tendency towards early closure of clinically significant
rather than the aorta. As a result, deoxygenated blood is
VSD easing the pressure on the nutritional aspects of treat-
provided to the coronary artery, resulting in myocardial
ment. Late diagnosis of a large VSD is associated with marked
ischaemia. Cases usually arise in the first few months of life
faltering growth with an imperative to operate as soon as
with about half presenting with faltering growth [187].
possible [186]. Following surgery most infants demonstrate
However, following repair of the primary defect, weight can
good catch‐up growth [110] although the same authors
be expected to be regained.
expressed concern that rapid growth following a period of
Aortopulmonary window A hole, or ‘window’, is pre-
growth faltering might lead to insulin resistance, obesity and
sent between the aorta and the pulmonary artery. This results
adult cardiovascular disease later in life [110].
in higher pulmonary blood pressure with more blood than
usual going to the lungs and less to the systemic circulation.
Case studies Atrial septal defect (ASD) A hole between the right
and left atria. There is malformation of the septum between
Case studies illustrating aspects of nutritional management the two chambers. The defect may have anomalous pulmo-
of CHD are given in Tables 14.18 and 14.19. nary drainage associated with it, in which some of the
venous return from the lungs enters the right atrium rather
than the left.
Future research and unanswered questions Blalock–Taussig (BT) shunt A procedure in which the
subclavian artery is connected to the pulmonary artery in
Many studies into the benefits of nutritional support in CHD order to provide adequate blood flow to the lungs. Used
are retrospective and observational so may be subject to when the defect results in no direct connection between the
selection bias, resulting in patients with better prognosis right ventricle and the pulmonary circulation, e.g. pulmo-
being fed earlier and more aggressively [53]. Prospective nary atresia. A modified version of this procedure is to use a
Table 14.19 Case study: treatment of an infant who developed chylothorax and vocal cord palsy following arterial switch operation for transposition
of the great arteries.
Baby boy born at term. Birth weight = 3.75 kg (75th centile). Length obtained at 2½ weeks: 53 cm (75th centile) with weight = 4.07 kg
(50th centile).
The case study illustrates:
• Limiting the treatment period for chylothorax
• Need for regular follow‐up in the initial stages following discharge as the reasons for feeding difficulties may become clearer following
discharge home
• Interaction between local and tertiary centre. Monitoring and observations made by the local team on feeding behaviour informed feeding
decisions made by tertiary team
• Gradual transition from tube to oral feeding as vocal cord palsy resolved
3 weeks old Transferred from tertiary centre to home Feed: Monogen (4‐week treatment period). 75 mL × 3 hourly × 8 feeds via
following repair of TGA. Post‐op development NG tube, 150 mL/kg/day
of chylothorax Discharged, reported to be feeding well orally pre‐operatively but
currently taking minimal volumes by mouth
Handover reported that he throws his head back and screams when
attempts are made to feed orally. Some consideration given to possibility
of cow’s milk protein allergy, but omeprazole has eased symptoms
Local dietitian contacted to arrange home enteral feeding
Drugs: spironolactone, furosemide, propranolol
4 weeks old Local CCN reports Wt = 4.15 kg (25th centile), Current feed volumes: 67 mL × 3 hourly × 8, 130 mL/kg/day, advised by
increase of 80 g since discharge tertiary centre dietitian due to issues with vomiting
Length = 53.5 cm (25th centile) Mum keen to stop NG feeding and revert to bottle feeds. Local dietitian
Patient continuing to cough and vomit feeds suggests Gaviscon Infant to try to resolve vomiting
4½ weeks old Tertiary centre commence patient on Now on 2 hourly feeds of Monogen: 45 mL × 12 feeds to reduce vomiting
omeprazole for GOR. Patient coughing but Local dietitian advises change to 55 mL × 2–3 hourly × 10 feeds if tolerating
coping better with feeds
5 weeks old Wt = 4.4 kg (25–50th centile), increase of Telephone call to mother as she would like information about alternatives
250 g/week to Monogen when treatment stops
6½ weeks old Request from tertiary centre for NG tube to Feeds changed from Monogen to standard infant formula
remain in situ to ensure adequate weight gain
7 weeks old Home visit by CCN and local dietitian Infant is now managing up to 30 mL orally with remaining 65 mL via NG
Weight = 4.68 kg (25th centile) tube. Feeding 95 mL × 3 hourly × 7 feeds with 6 hour break during night
Local dietitian contacts tertiary centre to advise Still struggling with oral feeds, only managing half the volume. Has
of suspicion of vocal cord palsy wheeze on feeding and does not appear to like oral feeding
Local dietitian suspects vocal cord palsy and advises continued NG
feeding to augment oral intake. Advises increase to 100 mL × 7 feeds per
day, 150 mL/kg/day mostly via NG tube
8 weeks old Telephone review by local dietitian Infant is now managing half of feed volume orally with remainder via NG
tube
8–12 weeks old Ongoing home visits by CCN and telephone Gradual transition to full oral feeding of 150 mL/kg/day of standard infant
reviews by local dietitian formula. ENT review scheduled at tertiary centre in 3 months’ time
Weight = 5.6 kg (9–25th centile)
Length = 60.5 cm (25th centile)
4½ months old CCN handover to health visitor for ongoing Dietitian discusses weaning with mum for when baby shows interest in
weight monitoring solids. Provided with open appointment with local dietitian
TGA, transposition of the great arteries; NG, nasogastric; CCN, children’s community nurse; GOR, gastro‐oesophageal reflux; ENT, ear, nose and throat.
Gore‐Tex graft between the subclavian and pulmonary arter- pulses. Surgical repair is either with an end‐to‐end anasto-
ies (modified BT shunt). mosis, with the narrowed section being cut out, or by using
Coarctation of the aorta A narrowing of the aortic arch a flap of subclavian artery.
near to where the ductus arteriosus connects in the foetal cir- Cor triatriatum A membrane divides the inside of the
culation. One of the signs is reduced or absent femoral left atrium interfering with blood flow into the left ventricle.
DiGeorge syndrome (22Q11 microdeletion) Cardiac Shunt The redirection of blood flow from one area of the
defects that affect the pulmonary artery and aorta are associ- circulation to another via a ‘short circuit’. This may be due to
ated with this syndrome. Parathyroid hormone is absent, a physiological defect as in the movement of blood from the
and infants often need calcium supplementation post‐opera- left to right ventricle across a VSD or due to an operation
tively. The thymus is also affected, resulting in poor immune such as a BT shunt in which blood is redirected from the sys-
function and the need for irradiated blood products to be temic to pulmonary circulation (see Blalock–Taussig shunt
given if transfusion is required. above).
Double outlet right ventricle (DORV) Both aorta and Tetralogy of Fallot (Figure 14.3) There are four aspects
pulmonary arteries exit from the right ventricle. A VSD is to this defect: a ventricular septal defect, pulmonary steno-
present, allowing blood to exit from the left ventricle. sis, right ventricular hypertrophy and an overriding aorta in
Ductus arteriosus This is a connecting vessel between which the aorta straddles the two ventricles.
the pulmonary artery and the aorta. Its function is to allow Total anomalous pulmonary venous drainage (TAPVD)
blood to bypass the lungs in the foetal circulation. If it The four pulmonary veins usually return blood to the left
remains open once the infant is born, it is known as a ‘patent atrium. In TAPVD all of these veins empty into a variety of
ductus arteriosus’. This causes excess blood flow to the other locations: the superior vena cava, the inferior vena
lungs. cava, the hepatic vein, hepatic portal vein or the right
Ebstein’s anomaly A deformed tricuspid valve, with atrium.
missing leaflets, arises lower than normal from the wall of Total cavo‐pulmonary connection (TCPC) An opera-
the right ventricle. This results in a small functional right tion in which the inferior vena cava is connected directly to
ventricle with the pulmonary artery exiting from above the the right pulmonary artery. This operation follows on from a
tricuspid valve. Poor pulmonary blood flow results. Glenn shunt and occurs when a child is older. These opera-
Glenn shunt A procedure in which the superior vena tions are used where there are right‐sided obstructive car-
cava is disconnected from where it enters the right atrium diac lesions resulting in deoxygenated blood flowing from
and is attached to the right pulmonary artery. The venous the body directly into the pulmonary circulation without
return from the upper part of the body therefore flows going through the right side of the heart.
directly into the pulmonary arteries. This is used as a means Transposition of the great arteries (TGA) The aorta
of oxygenating blood when there is a non‐functioning right exits from the right ventricle and the pulmonary artery exits
ventricle usually due to stenosis of the pulmonary valve or from the left ventricle. Blood is able to mix due to a patent
atresia of either the tricuspid valve or pulmonary artery. foramen ovale and patent ductus arteriosus. Initially the
Hypoplastic left heart syndrome (HLHS) Due to PFO is enlarged, using a cardiac catheter in a procedure
embryological defects the size of the left ventricle is severely called a balloon atrial septostomy, to allow for better mixing
reduced. The aortic and mitral valves are also defective or of blood. Surgical repair in which the arteries are cut and
absent, and the aorta is reduced in size. switched over is carried out at about 2 weeks of age.
Interrupted aortic arch The aorta exits from the left ven- Tricuspid atresia The tricuspid valve between the
tricle but fails to continue round to form the usual arch. The right atrium and right ventricle fails to from. A PFO or ASD
descending part of the aortic arch remains connected to the along with a VSD ensures that this lesion is compatible
pulmonary circulation via the ductus arteriosus. with life.
Partial anomalous pulmonary venous drainage (PAPVD) Truncus arteriosus A single large vessel exits from above
As for TAPVD, but fewer pulmonary veins are misdirected. the two ventricles due to the pulmonary artery and the aorta
Patent ductus arteriosus (PDA) The hole that exists failing to divide in the embryo. There is only one single valve
between the pulmonary artery and aorta in foetal circulation to this large vessel, having 3–6 leaflets. A VSD is also present
persists postnatally. Some cardiac lesions require this hole to just beneath where the vessel leaves the heart. Truncus arte-
remain open in order to get blood to the lungs and so be riosus is classified into four types depending on where the
compatible with life. Prostaglandin E1 is used to keep the right and left pulmonary arteries arise.
duct patent.
Patent/persisting foramen ovale (PFO) The hole
between the two atria that is normally present in the foetal Acknowledgements
circulation persists postnatally.
Pulmonary atresia The outflow from the pulmonary Dr Alison Hayes, Consultant Paediatric Cardiologist, Bristol
artery is completely restricted either at the site of the pulmo- Royal Hospital for Children for providing Figures 14.3–14.5
nary valve or the artery itself. A VSD may or may not be and 14.9–14.12. Ms Angela Drayton, Mr Tom Wellham and
present, and this will affect the surgical course. Ms Katie Peck, Yeovil District Hospital Library for help with
Pulmonary stenosis The valve of the pulmonary artery database searches and sourcing references. Dr Graeme
is not formed correctly, resulting in reduced blood flow to O’Connor, Specialist Paediatric Dietitian, Great Ormond
the lungs. There are three types with areas of tissue above or Street Hospital for Children for reviewing the chapter
below the valve or the valve itself being affected. text. Mrs Pamela Wright, Paediatric Pharmacist, Yeovil
District Hospital for checking drugs used in CHD.

Dr Kevin Roman, Consultant Paediatric Cardiologist,
Southampton Children’s Hospital for reviewing medical
aspects of the text.
15
Rosan Meyer and Carina Venter
Food Hypersensitivity
Introduction • Some foods may cause unpleasant symptoms, e.g. caf-

feine in coffee and cola, vasoactive amines in cheese and
Many symptoms are correctly or incorrectly attributed to wine and phenylethylamine in chocolate. These effects
food hypersensitivity and as a result can lead to confusion are pharmacological and are non‐allergic (Figure 15.1, D).
when it comes to diagnosis and management. In an effort to • Some food‐induced reactions are non‐immune mediated
improve diagnosis, treatment and general understanding of and of unknown origin. These may include a variety
allergic reactions the Nomenclature Review Committee of of gastrointestinal symptoms related to different foods,
the World Allergy Organization issued a report proposing e.g. abdominal cramping with garlic or wheat fibre
revised nomenclature [1, 2]. This report states that any reac- (Figure 15.1, E).
tion to food that causes objectively reproducible symptoms Over recent years a significant amount of research has been
or signs, even when the food is eaten unknowingly (blind), undertaken in this area. This chapter can only provide an
should be described as food hypersensitivity. If immuno- introduction to food hypersensitivity, and further reading is
logic mechanisms can be demonstrated, then the reaction recommended as new research is constantly produced.
can be described as a food allergy. If immunoglobulin E (IgE) Dietetic principles have been concentrated on, but it is essen-
is involved in the reaction, then the term IgE mediated food tial to understand some of the immunological mechanisms
allergy should be used and the term non‐IgE mediated food involved to ensure dietetic management is optimal.
allergic reactions used for immune‐mediated reactions that
are not mediated by IgE. All other reactions should be
described as non‐allergic food hypersensitivity, as there is no IgE mediated allergy
immunological mechanism involved (Figure 15.1).
IgE is an immunoglobulin normally present at very low lev-
els in the plasma of non‐allergic individuals, but levels are
Important factors concerning food hypersensitivity raised in patients suffering from allergic conditions such as
reactions asthma, atopic dermatitis, allergic rhinitis and food allergy.
When atopic individuals are exposed to a food protein (anti-
• A food hypersensitivity reaction is known as a food gen) via the skin, gastrointestinal tract or lung mucosa, the
allergy where the immune system is involved. These antigen is taken up and transported to local lymph nodes by
reactions may involve the immunoglobulin IgE or may specialist processing cells called antigen‐presenting cells.
involve other immune mechanisms (non‐IgE mediated These cells break down and present the antigen to T and B
food allergy) (Figure 15.1, A and B). cells within specific areas of the lymph node. The type of T
• Some food hypersensitivity occurs as a result of enzyme cell involved in this encounter is important in determining
deficiency such as lactase deficiency or disorders of whether IgE (as opposed to other antibody isotypes, IgA or
amino acid or intermediary metabolism, e.g. phenylke- IgG) is produced. T‐helper 2 (Th2) cells play an important
tonuria. These reactions are non‐allergic hypersensitivi- role in determining IgE production by B cells. These sur-
ties, are well documented and are discussed elsewhere in round the antigen and present the antigen to T‐helper 2
this book (Figure 15.1, C). (Th2) cells. This stimulates B cells to produce IgE‐specific

316 Food Hypersensitivity
Food
hypersensitivity
Non-allergic
Food allergy food
hypersensitivity
Non-IgE
IgE mediated Enzymatic Pharmacological Unknown
mediated
(A) (C) (D) (E)
(B)
Figure 15.1 Classification of food hypersensitivity [1]. Source: Reproduced with permission of Elsevier.
antibodies, which then bind to mast cells or basophils via

Clinical manifestation of IgE mediated food allergy
high affinity receptors. This cascade of immune reactions
then leads to the symptoms associated with an immediate Symptoms generally appear within 0–2 hours after a small
food allergy (Figure 15.2). A variety of cytokines are released, amount of food has been consumed. Immediate symptoms
which may induce the IgE mediated late response. may affect the gut, the skin and/or the lungs, and common
Neutrophils and eosinophils invade the site of response and symptoms are summarised (Table 15.1) [4].
infiltrated cells are activated. These then release a variety of Symptoms of upper airway (laryngeal oedema) and lower
mediators including platelet‐activating factor, peroxidase, airway obstruction (bronchoconstriction), hypotension, car-
eosinophil major basic protein and eosinophil cationic pro- diac arrhythmias and even cardiac failure constitute the
tein, leading to a second phase allergic response that is often most severe and sometimes life‐threatening reactions. The
more severe than the initial response. In the subsequent latter is known as anaphylactic shock (which is rare), and
24–48 hours, lymphocytes and monocytes infiltrate the area although more people are being admitted with this in UK
and establish a more chronic inflammatory picture [3]. hospitals, food‐related fatalities have remained stable at 0.01
Allergen
consumption
Specific IgE
antibody
IL-3, IL-4
Th2
Antigen-
presenting IL-4
cell IL-13
Basophils
Specific IgE
entibody
Figure 15.2 Immunological basis for food allergy using cow’s milk as an example (exposure through the gastrointestinal tract) [3]. Source: Reproduced
with permission of Elsevier.
Introduction 317
Table 15.1 Summary of symptom presentation of IgE and non‐IgE mediated food allergy.
IgE mediated Non‐IgE mediated

(immediate onset) (delayed onset)
Gastrointestinal Angioedema of the lips, tongue and palate Gastro‐oesophageal reflux

Oral pruritus Abdominal pain, bloating
Nausea Vomiting
Vomiting Loose frequent stools
Diarrhoea Colicky abdominal pain
Blood and/or mucus stool
Infantile colitis
Food refusal/aversion
Constipation
Perianal redness
Pallor and tiredness
Faltering growth and one or more of the gastrointestinal
symptoms above (with or without serious atopic eczema)
Cutaneous Acute urticaria Atopic dermatitis
Acute angioedema
Erythema
Pruritus
Atopic dermatitis
Respiratory Upper respiratory tract symptoms (nasal itching,
sneezing, rhinorrhoea)
Lower respiratory tract symptoms (cough, chest
tightness, wheezing, or shortness of breath)
Systemic Anaphylaxis
cases per 100 000 population per annum [5–7]. The presenta- vomiting that in severe cases may lead to hypovolaemic
tion of anaphylaxis is varied, but the major causes of death shock (e.g. FPIES) [10], d
iarrhoea, abdominal pain, falter-
are obstruction to the upper airway or shock, hypotension ing growth, irritability, colic‐like pain, constipation and
and cardiac arrhythmia [7, 8]. The results of double‐blind eczema [13, 14]. Gastrointestinal symptoms are further
placebo‐controlled food challenges (DBPCFC) from several discussed in Chapter 8.
studies in the USA and the UK have shown that the most
common foods to provoke immediate reactions are peanuts,
Mixed IgE and non‐IgE food allergy
tree nuts, milk, egg, soy and wheat, fish and shellfish. Seeds
(e.g. sesame) may also cause this type of reaction [6].
It is now recognised that patients can present with a mixed
picture including both the immediate‐type IgE mediated and
Non‐IgE mediated food allergy the delayed‐type non‐IgE mediated reactions. An example of
this overlap is atopic dermatitis and, in some cases EoE, when
These reactions are immune‐mediated delayed hypersensi- patients also exhibit IgE sensitisation to pollen [15–17]. The
tivity reactions with symptoms usually appearing more than same child may show signs of both IgE mediated allergy, e.g.
2–48 hours after antigen exposure. Although the mechanism to egg, and non‐IgE mediated allergy, e.g. to milk.
of this reaction is not yet fully understood, it is thought that
it involves sensitised T cells reacting with the antigen to pro- Symptoms often associated with both IgE and
duce cytokines, which mobilise non‐sensitised cells to fight
non‐IgE mediated food allergy
the antigen. This causes inflammation, tissue damage and
the formation of epithelioid and giant cells [9].
It is important to recognise additional features that are often
present in children with food allergies, and these may have
Clinical manifestation of non‐IgE mediated food allergy implications in the nutritional management. These include
faltering growth; vitamin D, calcium and iron deficiency;
These reactions to foods may develop slowly after an hour
and feeding difficulties [18].
(e.g. food protein‐induced enterocolitis syndrome [FPIES])
[10] or days (e.g. food protein‐induced proctocolitis [FPIP]
and eosinophilic oesophagitis [EoE]) [11], and the expo- Non‐allergic food hypersensitivity
sure dose evoking a reaction varies from small to larger
amounts [12]. As with immediate symptoms, adverse reac- The most well‐known non‐allergic food hypersensitivity is
tions mainly affect the skin and gastrointestinal tract. lactose intolerance (p. 117). Symptoms arise due to the
Symptoms include chronic diarrhoea, chronic or acute osmotic effects of lactose and fermentation thereof by
intestinal bacteria. This may cause excessive flatus, explo- Table 15.2 High risk components (more likely to lead to anaphylaxis)
sive diarrhoea, perianal excoriation, abdominal distension versus low risk components [25].
and pain [19]. The overlap in symptoms with non‐IgE medi-
Food allergens High risk Low risk
ated gastrointestinal food allergies often causes confusion
with the diagnosis, but is distinctly different due to the Peanut Ara 1,1,3,9 Ara h 8, profilin
absence of an immunological mechanism [20]. Hazelnut Cor 1,8,9,14 Profilin
More controversial problems that may be related to non‐ Walnut Jug r 1,2,3 Profilin
allergic food hypersensitivity are migraine, rheumatoid Soya Gly m 5,6 (4) Profilin
arthritis, migraine with epilepsy, enuresis, autism and atten- Rosacea fruit Pru p 3, Mal d 3 Pru p 1, Mal d 1, profilin
tion deficit hyperactivity disorder (ADHD). Dietary manip- Wheat Tria 14, Tria 19 Profilin
Shrimp Pen a 1 N/A
ulation (elimination and challenge) is the mainstay for
diagnosis and treatment of these conditions [2, 21]. It is N/A, not applicable.
important to consider nutritional adequacy when such a diet Source: Reproduced with permission of Springer.
is considered (p. 328).
Diagnosis of food hypersensitivity which particular allergen or allergens are involved in trig-
gering allergic symptoms. CRD has become extremely u seful
IgE mediated allergy as it has enabled identification of specific clinical pheno-
types, prediction of severity of reactions and identification of
cross‐reactive specific components to other similar allergens
Skin prick tests
from different pollen species or foods (Table 15.2) [25, 26].
The skin prick test (SPT) indicates the presence of allergen CRD is, however, mainly available only in specialist centres,
specific IgE. It can be performed in a medical setting equipped and its use is limited to cases where it makes a difference in
to deal with anaphylaxis and yields an immediate result, the diagnosis or management.
which is very useful for clinicians and parents. Drops of food
extract, positive (histamine) control and negative (saline)
control are applied using lancets. In the past a cut‐off of 3 mm
Intradermal test
or larger was considered positive; however, with the publica- Intradermal tests for food allergy are not recommended in
tion of the LEAP (Learning Early About Peanut Allergy) and either UK [27] or US guidelines [28]. Unacceptably high false
EAT (Enquiring About Tolerance) studies, this cut‐off has positive rates as well as safety concerns, such as systemic
been questioned, and interpretation of SPT should be led by reactions (including fatal anaphylactic responses), are asso-
an allergy‐focused history [22]. It is important to note that the ciated with this allergy skin test [29].
positive predictive accuracy of SPTs is less than 50% when
compared with results from DBPCFC. Negative predictive
Basophil activation test
accuracy is 95% [23, 24]. This means that negative SPT
responses are a worthwhile means of excluding IgE mediated Studies are emerging on basophil activation test (BAT) as a
allergies, but positive SPT responses only indicate an atopic new diagnostic tool for food allergy. This test is based on a
individual with a tendency to react to this food. Exclusion three‐step approach: cell stimulation, cell staining and flow
diets should not be based on these results alone [4]. cytometry. The expression of activation markers is then
measured on the surface of basophils following stimulation
with the allergen and has shown high specificity [30]. It has
Specific IgE test
been described as an oral food challenge (OFC) in a test tube
Specific IgE is an in vitro assay for identifying food‐specific and has already been applied to cow’s milk, egg and peanut.
IgE antibodies from serum. It is more expensive than SPT, However, BAT requires a specialist laboratory setting and at
and the results are not available to the clinician immediately, this stage is mainly limited to research [4].
possibly delaying diagnosis. This test may be preferred when
patients have dermatographism, severe skin disease or lim-
Other diagnostic tests
ited surface area for testing (e.g. in severe atopic dermatitis);
where patients have difficulty discontinuing antihistamines; To date there are no additional diagnostic procedures to
or where patients have exquisite sensitivity to certain foods those described above that can be recommended as useful
[23]. Interpretation of results is as difficult as with SPTs as tests in the diagnosis of IgE and non‐IgE mediated food
there are no universally accepted cut‐offs for each allergen, allergy. IgG testing has received a significant amount of
and interpretation needs to also occur in conjunction with an attention in the lay press for assisting in the ‘diagnosis’ of
allergy‐focused history. SPTs and specific IgE tests provide non‐IgE mediated reactions or food intolerances. The
useful contributory information towards a diagnosis when European Academy of Allergy and Clinical Immunology
added to the clinical history and should be interpreted by (EAACI) [31, 32], the American Academy of Allergy, Asthma
clinicians with appropriate competencies [23]. and Immunology (AAAAI) [33] and the UK National
More recently, component‐resolved diagnostics (CRD) Institute for Health and Care Excellence (NICE) [13] advise
have been used in food allergy, giving information about against the use of this ‘test’ for diagnosing any type of food
Elimination Diets for Diagnosis of Ige and Non‐Ige Mediated Food Allergies 319
allergy or intolerance due poor association with actual aller- For IgE mediated allergies the elimination diet is imple-
gies and the concern that misinterpretation may lead to mented to manage symptoms, and reintroduction of these
nutritionally incomplete diets. Other tests that have also foods into the diet will only occur when there is an indica-
been shown to be of no benefit in the diagnosis of food tion that the allergy may have been outgrown. However, in
hypersensitivity include vega testing, hair analysis, cyto- some cases (particularly for non‐IgE mediated allergy and
toxic test, kinesiology, iridology, electrodermal testing and non‐allergic food hypersensitivity), it may not be clear if par-
sublingual provocative food testing [34]. ticular foods are involved, and, therefore, a diagnostic elimi-
nation diet is recommended. Before this is embarked upon, it
is essential to consider whether the child/parent is suffi-
Non‐IgE mediated allergy
ciently motivated and able to adhere to the diet. The length
of time required on an elimination diet to confirm/refute a
There are currently no validated in vitro or in vivo tests that can
non‐IgE mediated allergy is around 4 weeks [37], but may
identify foods responsible for non‐IgE mediated food allergies
vary between 2 and 6 weeks depending on the following:
[4, 12]. It has been suggested that atopy patch testing could be
used to aid the diagnosis of non‐IgE mediated food allergy; • type of suspected food allergy (more severe symptoms
however, studies have not found the test to be sufficiently may take longer to resolve)
accurate, and, therefore, all current guidelines do not recom- • frequency of symptoms
mend this test to be used for diagnostic purposes in delayed • degree of restriction of diet (i.e. one food versus many
food allergy [4, 35, 36]. Currently, the symptomatic improve- foods)
ment on an allergen exclusion diet [37] followed by a return of • nutritional status of the child
symptoms on allergen reintroduction or a food challenge
For non‐allergic food hypersensitivity, the elimination
remains the gold standard for diagnosing this food allergic
time is also poorly defined, but published data indicates an
condition [4, 14, 38]. Therefore, without the reintroduction of
elimination period of also between 2 and 6 weeks being suf-
the allergen, the diagnostic process is not complete.
ficient [21].
Any improvement of symptoms has to be followed up by
Non‐allergic food hypersensitivity reintroduction or a challenge with the offending foods,
resulting in reproducible deterioration and then recovery on
As for food allergy, there is no proven test (outside of those re‐elimination in order to confirm the presence of a food
for disaccharide malabsorption) for the diagnosis of non‐ allergy. The NICE guidelines recommend that challenges for
allergic food hypersensitivity. Advertised diagnostic meth- IgE mediated allergy should be performed in a clinical
ods such as applied kinesiology, hair tests or electrodermal setting; food reintroduction for delayed symptoms can be
tests were evaluated in a Consumer Association report [39]. performed at home, apart from FPIES that needs to occur in
The verdict was that known allergies in individuals were not a hospital setting [13, 43].
picked up, the services exaggerated the number of allergies, Keeping a food symptom diary before starting a diet may
and this could result in unnecessarily restricted and inade- provide a baseline, but seldom adds any useful information
quate diets. The report suggests that people should not waste about suspect foods that has not been revealed by diet his-
their money on these tests. Vega testing has also been assessed tory; keeping a food diary may increase the burden for fami-
in a double‐blind study and was shown to be unable to accu- lies. The initial diet may exclude one food (e.g. cow’s milk)
rately diagnose food hypersensitivity of any mechanism [40]. or a number of foods (e.g. cow’s milk, soya and eggs). The
choice of diet is a matter of clinical judgement taking into
account age, severity and type of symptoms and whether
Elimination diets for diagnosis of IgE and other elimination diets have already been tried [44]. There
non‐IgE mediated food allergies are three levels of dietary restriction: an empirical diet, a few
foods diet or an elemental diet (Figure 15.3).
An allergy‐focused history is the cornerstone for making a
diagnosis of food allergy and guiding food eliminations.
This includes taking a symptom history to assist in the deci- Empirical diet
sion whether the reaction may be IgE or non‐IgE mediated
[41]. Taking a full diet history is mandatory before embark- An empirical diet is used where food hypersensitivity is
ing on an elimination diet as this may indicate provoking suspected and causative foods are not known. One or sev-
foods and also gives an indication of dietary adequacy. The eral of the most commonly provoking foods are avoided.
accuracy of the diet history needs to be taken into account, as Cow’s milk, hen’s egg, wheat, soy, peanut, tree nut, sesame
it is not uncommon for parents to be mistaken as to which and kiwi are responsible for the majority of IgE mediated
foods affect their child and problems with staple foods eaten food‐induced allergic reactions in young children [44]. Fin
several times a day, such as milk and wheat, often go unno- fish, shellfish, tree nuts and peanut are more common food
ticed [41]. Both the clinical and diet history then provide allergens in older children [44]. In children with atopic der-
guidance on which diagnostic test may be required to guide matitis (mixed IgE and non‐IgE mediated), the offending
the elimination diet and, in the case of non‐IgE mediated foods are similar to those in IgE mediated allergies; how-
allergy, to embark on a diagnostic elimination diet [42]. ever, studies of common allergens in delayed reactions yield
Elimination diet
Empirical diet Few foods diet Elemental diet
Followed by Followed by
Food challenge
or
food reintroduction
Single-blind Double-blind
Open food
placebo- placebo- Reintroduction of
challenge
controlled food controlled food food (at home)*
(hospital)
challenges (hospital) challenges (hospital)
Figure 15.3 Using elimination diets and food challenges/reintroduction to aid diagnosis. *Only if there is no risk of an immediate severe reaction.
anecdotal results. The most common food allergens in the Few foods diet
whole spectrum of non‐IgE mediated gastrointestinal food
allergies are cow’s milk, soy, egg and wheat [4, 12, 45]. A few foods diet consists of a small number of hypoaller-
However, it is important to recognise that there are varia- genic foods. This diet may be useful if there is a perception
tions in common allergens, for example, in FPIES foods like that most foods cause an allergic‐type reaction. Although it
rice, oats and also vegetables such as sweet potato may is often suggested as a dietetic option for establishing food‐
cause reactions [46, 47]. induced hypersensitivity reactions, its use has only been
Milk‐free, soya‐free and milk, egg, wheat and soya‐free extensively studied in patients with atopic eczema [49–51].
diets are given in Tables 8.17–8.19. Diets using one meat, one carbohydrate source, one fruit
Outside of non‐IgE mediated allergies, parents may also and one type of vegetable have been used in the past [52].
report allergic‐type symptoms related to fruit and occasion- Examples of such diets are given in Table 15.3. If no improve-
ally to vegetables. It is important to elicit the type of reaction ment occurs with the first diet, a second diet containing a
and also the time of year these occur. Pollen food syndrome different set of foods can be used. Nutritional adequacy
(PFS) (otherwise known as oral allergy syndrome [OAS]) in should be monitored carefully [18, 44, 53]. In extreme cir-
children may need to be ruled out as new data generated from cumstances, more rarely eaten foods such as rabbit, venison
the UK indicates that this can occur as young as 1.4 years of and sweet potatoes could be included [53]. As these diets are
age (average 4.5 years) [48]. In infants and young children, nutritionally demanding, it is suggested that they should not
citrus and tomato are often blamed for exacerbation of atopic be followed for more than 4 weeks.
dermatitis. Flare‐up of eczema may occur around the mouth/ Since the above diets are extremely rigorous, less restricted
face due to the pH of the fruit and its histamine content, but diets have been used to improve adherence (Table 15.4) [53].
specific research supporting this is absent. Fruit and vegeta- It is much more difficult to find a completely different set of
bles contribute important micronutrients to the diet; it is, foods for a second attempt if the first is not helpful. However,
therefore, important not eliminate these foods from a diagnos- it is possible to monitor progress closely and adjust or fur-
tic exclusion diet without ensuring dietary adequacy. Practical ther restrict the diet during the third or fourth week in an
advice is to cover the area around the mouth with petroleum attempt to achieve eventual success.
jelly (e.g. Vaseline) prior to eating these fruits and vegetables. The acceptability of the few foods diet depends greatly on
Problems can occur with empirical diets when excluded the dietitian’s advice regarding planning menus, giving
foods are inadvertently replaced by others that can cause ideas for meals and providing recipes for cooking with the
adverse reactions, e.g. a child on a milk‐free diet may drink allowed foods. Ideas for packed lunches should be given as
soy milk or orange juice instead, and it is possible to be school canteens cannot be expected to cope with such a
equally reactive to these foods. Failure to respond to an restricted diet. For vegetarians a larger range of vegetables,
empirical diet does not always, therefore, rule out the possi- including pulses, would be allowed. The dietitian should
bility of food hypersensitivity. keep in regular contact with the family to ensure adherence
Table 15.3 Two examples of few foods diets. to factors other than change in diet. Regular medication
should not be changed before or during the diet trial for
A B the same reason. Children on regular medication such
Turkey Lamb as anticonvulsants should remain on these, but be switched
to a colour/preservative‐free version if possible. Attention
Cabbage, sprouts, broccoli, Carrots, parsnips
cauliflower
should be paid to non‐food items that may be consumed by
small children such as toothpaste (a white toothpaste should
Potato, potato flour Rice, rice flour
be used), chalks and play dough [53]. It is critical that after a
Banana Pear maximum of 4 weeks on this diet, the reintroduction of foods
Soya oil Sunflower oil occurs. There is very little guidance on the reintroduction of
Calcium and vitamins (Table 15.4) Calcium and vitamins (Table 15.4) foods following a few foods diet or elemental diet, and prac-
tice varies between allergy centres, depending on the:
Tap water Tap water
Hypoallergenic formula (<2 years) Hypoallergenic formula (<2 years) • type of food allergy and symptoms
• most likely offending foods (which are introduced at the end)
Possible additions: milk‐free margarine, sugar for baking. • nutritional status of the child and nutritional adequacy
Possible variations: bottled water; rabbit instead of above meats; peaches of the existing diet
and apricots, melon or pineapple instead of above fruits. • foods the child misses most
Foods should be reintroduced singly in order to try and
Table 15.4 Less restricted few foods diet. identify trigger foods. Each new food may be tried in a small
test quantity, then given in normal amounts every day for a
This diet should be used for no more than 4 weeks. Children under week and then incorporated into the diet as desired. A guide
2 years require a nutritionally adequate substitute for milk to reintroduction of foods is given in Table 15.5.
Choose two foods from each food group
Meat Lamb, rabbit, turkey, pork Elemental diet
Starchy food Rice, potato, sweet potato
Elemental diets based on amino acid formulas (AAF)
Vegetables Broccoli, cauliflower, cabbage, sprouts
(brassicas) (Table 15.6) can occasionally be justified where there has been
Carrots, parsnips, celery no response to a restricted diet. AAF (elemental diet) are also
Cucumber, marrow, courgettes, melon indicated for children with EoE, and data indicates that remis-
Leeks, onions, asparagus sion is >90% when used as a sole source of nutrition [54, 64].
Fruit Pears, bananas, peaches and apricots, pineapple The use of an elemental diet alone should be carefully consid-
Also included: Sunflower oil, whey‐free margarine ered: for nutritional adequacy; how to maintain oral motor
Plain potato crisps skills, in particular in the young; and whether the feed will be
Small amount of sugar for baking accepted as sole source of nutrition in the long run. In particu-
Tap or bottled water lar older children may find the feed unpalatable, and tube
Juice and jam from allowed fruits feeding may be necessary to achieve adequate nutrition. The
Salt, pepper and herbs in cooking insertion of a feeding tube will involve a hospital admission.
It is important to achieve daily requirements for vitamins and minerals
appropriate for the child’s age and diagnosis. On a few foods diet, if
insufficient breastmilk or suitable formula for the management of food Learning points: elimination diets
allergy is consumed, then vitamin and mineral supplementation is required.
• An individualised elimination diet is essential for the
management of known food allergies
and nutritional adequacy of the diet. The cost of the diet • For non‐IgE mediated allergies and non‐immune‐mediated
may be a problem and should be discussed with the family. food hypersensitivities, an empirical elimination of common
The few foods diet is most difficult to carry out in the culprits may be required to establish a food hypersensitivity
toddler age group, as they may still be very reliant on milk or reaction
formula for their nutrition. Ideally, they should take a suita- • A few foods diet should only be implemented in those
ble hypoallergenic formula, but it may be refused due to its patients where an empirical elimination has not lead to
taste, and in this case an over‐the‐counter plant‐based milk symptom improvement and food is still suspected as the
may be considered, but it is important to note that energy, cause of the reactions
protein and vitamins are much lower than in formulas. The • An elemental feed can be used as either the sole source of nutri-
diet can be altered to suit the individual child and, in some tion (e.g. in EoE) or the main formula/feed in a restricted diet
circumstances, can be made less restricted by including a • Dietary elimination needs to be carefully considered and rein-
larger range of meats, fruits and vegetables. troduction/food challenge should always occur after a trial of
Few foods diets are usually carried out in the home envi- few foods diet and to confirm a diagnosis of a non‐IgE medi-
ronment. It is important that the child’s lifestyle is not ated allergy or a non‐immune‐mediated food hypersensitivity
altered; otherwise changes in symptoms could be attributed
Table 15.5 Open reintroduction of foods.
Each food should be given in normal quantities daily for 4–7 days before being allowed freely in the diet. Smaller doses on the first day of introduction
may be recommended initially [44]. The order of reintroduction depends on the child’s preference and on which foods were avoided initially
Oats Porridge oats, Scottish oatcakes, home‐made flapjacks (if sugar is already allowed)
Corn Sweetcorn, home‐made popcorn, cornflour, maize flour, cornflakes if malt is tolerated
Meats Try meats (including offal) singly, e.g. chicken, beef, pork
Wheat Wholemeal or unbleached white flour for baking, egg‐free pasta, Shredded Wheat, puffed wheat,
Weetabix
Yeast Pitta bread; ordinary bread (this usually also contains soya)
Rye Worth trying if wheat is not tolerated; pure rye crispbread; pumpernickel
Cow’s milk Fresh cow’s milk, cream, butter, plain yoghurt, milk containing foods with tolerated ingredients, e.g.
rice pudding
Try cheese separately later
Cow’s milk substitute If cow’s milk is not tolerated, try substitutes one by one
Infant soya formula (if >6 months) or infant hydrolysate formula
Sheep milk, goat milk for >1 year olds (boiled or pasteurised)
Supermarket liquid soya milk (>2 year olds), supermarket rice milk (>4½ year olds) with additional
calcium
Egg Use one whole fresh egg per day for test period
It may be preferred to begin with small amounts of egg in baking
Fish Fresh or frozen (not smoked, battered, etc.), e.g. cod, herring
If one type is not tolerated, others may be. Try shellfish separately later
Tomatoes Fresh tomatoes, canned and puréed tomatoes, ketchup
Peas/beans These include peas, green beans, kidney beans, lentils, and baked beans in tomato sauce if tomato is
tolerated
Orange Pure orange juice, oranges, satsumas. If oranges are tolerated, all citrus fruit probably are too
Sugar Use ordinary sugar on cereal, in drinks and baking
Some parents comment that small amounts are tolerated, whereas larger amounts are not
Chocolate Try only if sugar is tolerated
If diet is milk‐free, use milk‐free chocolate
Cocoa powder in drinks and cooking
Carob Carob confectionery can be tried if chocolate is not tolerated Check other ingredients – it may
contain milk or soya
Tea/coffee Add milk if this is already in the diet
Peanuts Plain or salted peanuts*
Peanut butter
Other nuts Try singly or mixed*
Malt Malt/malt flavouring is present in most breakfast cereals
Try Rice Krispies if rice is tolerated
Nitrite/nitrate Corned beef if beef is tolerated; ham and bacon if pork is tolerated
Sodium benzoate Supermarket lemonade provided other ingredients are tolerated
Sodium glutamate Stock cubes, gravy mixes, flavoured crisps, provided the other ingredients are tolerated
Sodium metabisulphite Some squashes, sausages provided the other ingredients are tolerated, dried fruit
Vitamins/minerals These may be given if needed to enhance nutritional adequacy and introduced singly to test tolerance
Other foods, e.g. fruit and vegetables, can be introduced gradually as desired. Manufactured foods such as ice cream and biscuits can be introduced
taking into account known sensitivities. Many additives, e.g. colours and flavours, will be introduced as mixtures in manufactured foods such as sweets
and canned/bottled drinks. For children with multiple cereal intolerances, flours such as buckwheat, soya, gram (chickpea) and wheat starch may be
tried. Some of the special dietary products for gluten‐free and low protein diets may be suitable, but other ingredients must be checked (they may not
be prescribed for food hypersensitivity).
*Children under 5 years old must not be given whole nuts as they are a choking hazard.
Table 15.6 Formulas suitable for the management of food allergy [14, 54–56].
Formula Protein source Tested for hypoallergenicity* Osmolality (mOsm/kgH2O) Additional information
Nutramigen LGG 1, 2 EHF casein Yes [57] 1 = 290 Clinically insignificant lactose content
and 3 2 = 420 Nutramigen LGG 1 is suitable form birth
(Mead Johnson) 3 = 300 Nutramigen LGG 2 is suitable from 6 months of age
Nutramigen LGG 3 from 1 year of age
Contains LCP and Lactobacillus rhamnosus GG probiotic
Pregestimil Lipil EHF casein No§, but same peptide 280 Contains 55% fat as MCT
(Mead Johnson) mixture as Nutramigen LGG Clinically insignificant lactose content
For allergy and/or fat malabsorption/maldigestion
Suitable from birth to 12 months**
Similac Alimentum EHF casein Yes [58] 374 Clinically lactose‐free
(Abbott) Suitable from birth to 12 months**
Aptamil Pepti‐Junior EHF whey No, but similar peptide 275 Contains 50% of fat as MCT
(Nutricia) mixture to Aptamil Pepti Clinically insignificant lactose content
For allergy and/or malabsorption/maldigestion
Suitable from birth to 12 months**
Aptamil Pepti 1 and 2 EHF whey Yes [59] 1 = 280 Contains prebiotics
(Nutricia) 2 = 290 Pepti 1 contains 41% CHO as lactose and Pepti 2 36% CHO as lactose
Pepti 1 is suitable from birth
Pepti 2 is suitable from 6 to 12 months of age**
Althera EHF whey Yes [60] 335 Contains 53% CHO as lactose
(SMA Nutrition) Suitable from birth to 12 months of age**
MCT Pepdite EHF pork No 290 Contains 75% fat as MCT
(Nutricia) collagen and Not suitable for patients requiring Halal or Kosher diet
soya Rarely used for CMPA
Suitable from birth to 12 months of age**
MCT Peptide 1+ EHF pork No 460 at 91 kcal Contains 75% fat as MCT
(Nutricia) collagen and (380 kJ)/100 mL Not suitable for patients requiring Halal or Kosher diet
soya 580 at 100 kcal Rarely used for CMPA
(420 kJ)/100 mL Suitable >12 months of age
Infatrini Peptisorb EHF whey No 360 Energy‐dense infant formula
(Nutricia) Suitable for children <1 year of age
Occasionally used in CMPA <1 year of age,
if faltering growth is present
Nutrini Peptisorb EHF whey No 345 Energy‐dense formula
(Nutricia) Suitable for children >1 year of age
Rarely used for CMPA
Table 15.6 (continued )
Formula Protein source Tested for hypoallergenicity* Osmolality (mOsm/kgH2O) Additional information
Neocate LCP AAF Yes [61, 62] 360 Truly hypoallergenic, no CMP ß‐Lactoglobulin
(Nutricia) Lactose‐free
With LCP
Neocate Syneo AAF Yes [63] 360 Truly hypoallergenic, no CMP β‐Lactoglobulin
(Nutricia) Lactose‐free
With LCP
PurAmino AAF Yes 350 Truly hypoallergenic, no CMP β‐Lactoglobulin
(Mead Johnson) Lactose‐free
With LCP
Neocate Junior AAF No 580 (at 21.1% Energy‐dense formula
(Nutricia) concentration) Truly hypoallergenic, no CMP β‐Lactoglobulin
Lactose‐free
With LCP
Suitable for children >1 year of age
Can be mixed at different concentrations
Elemental 028 AAF No Unflavoured powder Truly hypoallergenic, no CMP β‐Lactoglobulin
(Nutricia) 502 (at 20% concentration) Lactose‐free
Flavoured = 637–670 Available in ready‐to‐feed (different flavours) and powder
depending on flavour Suitable from >1 year of age
Can be mixed at different concentrations
LGG, Lactobacillus rhamnosus GG; EHF, extensively hydrolysed formula; MCT, medium chain triglyceride; CHO, carbohydrate; LCP, long chain polyunsaturated fatty acids; CMPA, cow’s milk
protein allergy; AAF, amino acid formula; CMP, cow’s milk protein.
*Tolerated by 90% of children with CMPA with a 95% confidence interval (CI).
§
Studies have been performed using this formula in CMPA; however, these were not set out to establish hypoallergenicity.
**Occasionally dietitians may use these feeds in children older than 1 year of age, if nutritionally indicated.
Food challenges dose, dose increment and final dose may not be that critical, it is
essential that the patient has consumed an adequate amount of
Following improvement on the diagnostic diet, the dietitian will food during the challenge to make a diagnosis accurate [69, 70].
need to either perform a food challenge in hospital, in particular
for IgE mediated symptoms, or a reintroduction plan/prolonged
food challenge at home for the delayed‐type reactions. Single‐blind placebo‐controlled food challenges
During the SBPCFC, both active and placebo challenges are
History taking given. The health professionals involved know which food is
active and which is placebo, but the patient does not.
Prior to considering any food challenge, it is important to
Sufficient masking of the challenge food is very important.
gather all the history relevant to performing the challenge
SBPCFC are particularly useful when performing food chal-
safely. Taking a history will provide important information on:
lenges in children who do not want to ingest a specific food.
• the age of the patient to determine how difficult it may
be to perform the food challenge and to help in identify-
ing the possible food causing the symptoms Double‐blind placebo‐controlled food challenges
• the type of food or foods causing reported symptoms, The gold standard for confirming or refuting food allergy is the
e.g. raw egg versus cooked egg DBPCFC [70, 71], although in practice open challenges are more
• the age of onset of symptoms as well as the frequency common. One of the strengths of the DBPCFC is that neither the
and reproducibility of the reaction patient nor the investigator knows when the active or the pla-
• the time of onset of symptoms in relation to food consump- cebo challenge is performed, therefore ruling out reporting bias
tion; the clinical manifestation and duration of the symptoms from the clinician and any psychological effect from the patient.
• the quantity of food causing symptoms in order to The DBPCFC is mainly used for research purposes and
prevent false negative food challenges can be time consuming and difficult to manage. DBPCFC
• a thorough description of the most recent reaction is also still remains the optimal choice to determine clinical reactiv-
very important in designing challenges; the details of the ity to food, especially where there is a possibility that any
most recent reaction may be more helpful than those of observed reaction could be caused by anxiety, or in diagnos-
more distant reactions ing subjective symptoms such as abdominal pain and nau-
• sometimes, more than one food or factor is needed to sea [68, 70]. DBPCFC are also most commonly used to
elicit a positive challenge outcome (e.g. a combination of determine severity of reactions, threshold doses and efficacy
foods eaten together, exercise‐induced anaphylaxis or of desensitisation protocols [66].
with concomitant drug intake)
• a list of foods that are well tolerated and that could be used
as a placebo or vehicle to mask the challenge food [65] Considerations when performing food challenges
There are many different reasons for performing food chal- Elimination period
lenges including determining tolerance to the food allergen,
Prior to a food challenge, the identified food should be
clinical reactions to foods without any tests being p ositive
excluded from the diet as discussed above.
and severity of reactions, determining threshold doses and,
more recently, establishing the efficacy of desensitisation pro-
tocols [66]. Challenges can be performed as either open food Challenge dose
challenges (OFC), single‐blind placebo‐controlled food
challenges (SBPCFC) or DBPCFC (Figure 15.3) [65]. Guidance on performing food challenges (OFC and DBPCFC)
such as the dosages given and foods used is discussed in the
PRACTALL consensus guidance [71].The PRACTALL recom-
Open food challenges mendations suggest the following doses for food challenges
[71]: 4.334 g of protein divided into 3, 10, 30, 100, 300, 1000 and
During OFC both the clinician and patient (or parent) are
3000 mg doses. In terms of amount of food given, this equates to:
informed of the food being administered, and these challenges
should be sufficient to either confirm or refute most reported • Milk
food hypersensitivity. However, many children are very reluc- 12.428 g of skimmed milk powder (8.3 mg; 27.8 mg; 83.3 mg;
tant to eat a food that they do not remember having eaten before 277.8 mg; 833.3 mg; 2777.8 mg; 8333.3 mg)
or that they have previously been told to avoid. Indeed it is not
• Soya
uncommon for children who have had previous severe reac-
134.6 mL of soya milk (0.1 mL; 0.3 mL; 0.9 mL; 3.0 mL; 9.1 mL;
tions to foods to exhibit some degree of food avoidance. It is,
30.3 mL; 90.9 mL)
therefore, often advisable to provide the challenge in a ‘single
blind’ form (culprit food mixed with another food acceptable to • Egg
the child) simply to ensure that the child consumes it [67, 68]. 9.45 g of egg powder (6.4 mg; 21.3 mg; 63.8 mg; 212.8 mg;
OFC are mainly used in the clinical setting, particularly to 638.3 mg; 2127.7 mg; 6383.0 mg)
determine tolerance to a food, and are useful for the diagnosis of 34.711 g of egg (23.4 mg; 78.1 mg; 234.4
mg; 781.3 mg;
objective symptoms [66, 68]. Although factors such as starting 2343.8 mg; 7812.5 mg; 23 437.5 mg)
• Wheat and placebo challenge. In practice, it is very difficult to per-

5.5538 g of gluten powder (3.8 mg; 12.5 mg; 37.5 mg; 125 mg; form two challenges in a child in 1 day. In the case of delayed
375 mg; 1250 mg; 3750 mg) symptoms, 1 week between the active and placebo challenge
should be allowed [65, 69, 77]. The patient’s history will play
• Peanut
a major role in the final decision.
8.886 g of peanut flour (6 mg; 20 mg; 60 mg; 200 mg; 600 mg;
2000 mg; 6000 mg)
18.5126 g of peanut butter (12.5 mg; 41.7 mg; 125 mg; Masking of the challenge food
416.7 mg; 1250 mg; 4166.7 mg; 12 500 mg) The challenge food should be blinded (masked) in terms of
This amount of food should, however, still be followed up smell, flavour and texture. Ideally, the active and placebo
with an age‐appropriate portion of the food at the end of a challenges should be identical regarding taste, appearance,
negative challenge [71]. The interval between doses can be smell, viscosity, texture, structure and volume; blindness
anything between 15 and 60 minutes, but the timing between should also be assessed by standard tests [70, 78]. Although
each dose should be dependent on the patient’s history and this is paramount in performing food challenges for research
sufficient to allow symptoms to develop. purposes, it may not be necessary when performing DBPCFC
There are currently no specific recommendations regard- for a clinical diagnosis or when doing DBPCFC in young
ing the dose or design to be used when performing food chal- children.
lenges to diagnose delayed symptoms, e.g. atopic dermatitis There are a number of factors that should be taken into
or constipation, apart from that the amount normally known account when choosing a challenge vehicle or placebo:
to cause a reaction should be used, or a normal portion of the • The fat content of the vehicle can influence the challenge
food [70]. This raises practical issues where the patient is a outcome [79]
very vague historian. Another difficult issue is that some • The vehicle must also allow for enough challenge food to
reactions only occur when the causative food is eaten in suf- be used [70]
ficient doses on consecutive days and this must be planned • Cooking, canning and roasting can have different effects
for when designing the food challenge. The advantage of on the allergenicity of different foods [80–82]. The food
these challenges is that the reactions are not life threatening challenge should always conclude with consumption of
so the whole challenge can be completed at home. a normal portion of the food, prepared according to the
history to eliminate this issue [83, 84]
Challenge duration A variety of foods can be used for blinding. It is often
For immediate symptoms, if no reaction has occurred after helpful to use foods that are readily accepted by children
all doses have been consumed, the child can go home (after such as ice cream, yoghurt, milkshake, milky puddings,
1–2 hours) with instructions to incorporate that food gradu- fruit purée, mashed potatoes, soup, chocolate pudding,
ally into the diet. A longer challenge period (1–4 weeks) is fruit juice, cocoa/carob and peppermint [75, 76]. Many
recommended when looking for delayed reactions [71–74]. commercial products such as cakes, biscuits or pastas that
are free of egg, milk and wheat can be used as placebo.
Finding a suitable and acceptable vehicle/placebo is par-
Challenge food used ticularly difficult if children suffer from multiple food
hypersensitivity [76].
Dried, cooked or raw food, as indicated by the history, should be
Capsules are not recommended to be used in DBPCFC as
used in order to mimic the history as close as possible [75, 76].
the challenge food bypasses the mouth. The early oral symp-
toms seen in some food allergic individuals will not occur,
Challenge location which could warn against later serious reactions when the
challenge food hits the gut. Also the symptoms of OAS will
It is recommended to perform a food challenge in hospital if be missed in older children (p. 336).
there is a history of immediate reactions and/or if the patient
is sensitised to the offending food. If there is the slightest
concern that the child may experience an immediate or IgE
Interpretation of food challenges
mediated reaction, the challenge should be performed under
The final and most important part of the challenge is the
professional supervision in experienced hospital units; all
interpretation of the symptoms during the challenge [79, 85].
other challenges can be performed at home [68, 70, 71].
This is not always easy as there are some confounding effects,
such as disease patterns for eczema and chronic urticaria.
Considerations when performing double blind Presence of aeroallergens, particularly during the hay fever
season, may also affect the challenge outcome [48, 86, 87].
placebo controlled food challenges
The outcome of the food challenge should either be docu-
mented on a food challenge chart (hospital challenge) or a
Time between active and placebo challenges
food and symptom diary (home reintroduction). Any symp-
When dealing with immediate symptoms, at least 2 hours, toms at home should be verified by the study clinician if
but ideally 3–4 hours, should be allowed between the active possible [2]. The final outcome of the food challenge should
be decided by the supervising doctor and dietitian involved foods is often a very difficult step for families, especially if sig-
based on the history of the child and the symptoms experi- nificant symptom relief has been experienced.
enced. There are no clear guidelines regarding the point at There is very limited guidance on how reintroduction should
which a challenge should be considered positive, but some occur for non‐allergic food hypersensitivity, but a pragmatic
advice is summarised in the PRACTALL guidance [71]. This approach using the guidance from Table 15.5 may be useful.
is based on clinical expertise rather than substantiated by For non‐IgE mediated allergies, apart from FPIES, reintroduc-
evidence. In addition, Koplin et al. [88] have published tion can take place at home. In the UK, the ladder approach
guidelines on performing OFC in children suspected of IgE (suitable only for non‐IgE mediated allergies) has been well
mediated food allergies. Food challenge involved gradually received following the publication of the MAP (Milk Allergy in
increasing doses on day 1 in the hospital and continued Primary Care) guideline and then the iMAP milk ladder
ingestion of the maximum day 1 dose (one teaspoon of pea- (Figure 15.4) [14, 89]. The principle of the milk ladder is based
nut butter or tahini paste or one whole raw egg white) on on the processing and heating of cow’s milk that has an impact
day 2 to day 7. Different criteria have been set for the out- its allergenicity [90–94]. There is currently no data on its effi-
come of food challenges. The LEAP study in the UK set the cacy; however, it is easy to use at home and thought to increase
following criteria for food challenge outcomes [22]: the quality of life for families [92, 95]. Since the publication of
the milk ladder, the Food Allergy Specialist Group (FASG) of
1. A positive food challenge is defined as: the British Dietetic Association (BDA) has also published
• one or more symptoms from the major criteria egg, wheat and soya ladders for use in non‐IgE mediated
• two or more symptoms from the minor criteria allergies (apart from FPIES). These are available online for

2. An equivocal food challenge is defined by the presence BDA members (https://www.bda.uk.com/specialist-groups-
of one symptom from the minor criteria and-branches/food-allergy-specialist-group/diet-sheets.html).
3. A negative food challenge is defined by the absence of Due to the severity of symptoms that can be experienced
any symptoms listed under major or minor criteria with FPIES, a supervised challenge is recommended for this
non‐IgE mediated food allergy. Current consensus is to
In addition, all symptoms should be of new onset and not administer the challenge food at a dose of 0.06–0.6 g, usually
due to ongoing disease and must present within 2 hours of 0.3 g of the food protein per kilogram of body weight, in
consuming the last dose. three equal doses over 30 minutes. It is recommended not to
Major criteria are: exceed a total of 3 g of protein or 10 g of total food (100 mL of
liquid) for an initial feeding (which aims to approximate a
• confluent erythematous pruritic rash
serving size) and observe the patient for 4–6 hours [43].
• respiratory signs (at least one of the following): wheezing
After food challenge or food reintroduction, the food
or inability to speak or stridor or dysphonia or aphonia
should continue to be consumed if there is no reaction or
• ≥3 urticarial lesions
avoided (maintenance diet) if there is a reaction to the food.
• ≥1 site of angioedema
Despite the clear need for food introduction or challenge,
• hypotension for age not associated with vasovagal
some parents/caregivers may refuse to give a particular
episode
food if the child has improved a great deal when it has been
• evidence of severe abdominal pain (such as abnormal
eliminated. It is important to discuss this with the parents
stillness or doubling over) that persists for ≥3 minutes
and highlight the need for a clear diagnosis and also the
Minor criteria are: possible risk of deficiencies [18].
• vomiting
• diarrhoea Learning points: food challenges
• persistent rubbing of nose or eyes that lasts for ≥3 minutes
• persistent rhinorrhoea that lasts for ≥3 minutes • Food challenges, in particular the DBPCFC, are the gold
• persistent scratching that lasts for ≥3 minutes standard for diagnosis of food allergies
The food challenge result is also considered positive if any • It is important to take a careful history before embarking on
of the above reactions occurred within 2 hours of ingestion a food challenge
of the food on days 2–7 of the challenge at home. • The type of food challenge will depend on the clinical indica-
tion for the challenge and also the available clinical facilities
• There are different types of challenges, including open,
Reintroduction of foods for non‐IgE mediated single blind and the gold standard DBPCFC
allergies, non‐allergic food allergic hypersensivities • PRACTALL dosage guidelines should be used to guide dos-
and supervised challenge for FPIES ages for common allergens, but doses are often too large in
the case of other foods, e.g. fruit and vegetables
In the case of suspected non‐IgE mediated symptoms or non‐ • Challenges at home should ideally only happen for non‐IgE
allergic food hypersensitivity, an elimination diet should be fol- mediated allergies (apart from FPIES)
lowed by the reintroduction of offending foods: to confirm the • It is important that foods are reintroduced to the diet at
food‐related reaction, to expand the variety foods consumed home, if a challenge is successful
and to avoid unnecessary eliminations. The reintroduction of
THE iMAP MILK LADDER

To be used only in children with Mild to Moderate Non-IgE Cow’s Milk Allergy
Under the supervision of a healthcare professional
PLEASE SEE THE ACCOMPANYING RECIPE INFORMATION
STEP
6 Pasteurised milk/suitable infant formula

Amount – start with 100 mL (3.5 fl oz) of pasteurised milk/infant
formula and mix this with current milk replacement. Build up to
200 mL (7 fl oz). If this is tolerated switch all current milk
replacements (bottle and in breakfast cereals) to pasteurised milk
or suitable infant formula. Discuss what is an appropriate amount
of milk/milk products with your healthcare professional. UHT and
sterilised milk will be tolerated as well.
Once your child tolerates yoghurt, butter, spread, chocolate buttons,

fromage frais, petit filous (be careful of the sugar content), you can
introduce softer cheese like cream cheese and camembert/brie –
remember to use pasteurised soft cheese for children
STEP
Yoghurt
5 Amount – 125 mL (4.5 fl oz)
STEP Cheese
4 Amount – 15 g (½ fl oz) (hard cheese e.g. cheddar or
parmesan) Once your child tolerates cheese, you can
introduce 15 g baked cheese on a pizza or baked on other
food as well.
STEP
Pancake
3 Amount – ½ and build up to 1 (see Recipe)
STEP
2 Muffin
Amount – ½ and build up to 1 (see Recipe)
STEP
Cookie/Biscuit
1 Amount – 1 and build up to 3 (see Recipe)
AT EACH OF THE FOLLOWING STEPS

Cookie, muffin, pancake, cheese and yoghurt
It may be advisable in some cases to start with a ¼ or a ½ of that particular food and then over a few days to
gradually build up to a whole portion – Please ask your healthcare professional for guidance on this
THE LOWER STEPS ARE DESIGNED TO BE USED WITH HOME MADE RECIPES. THIS IS TO ENSURE THAT
EACH STEP HAS THE APPROPRIATE MILK INTAKE. THE RECIPES WILL BE PROVIDED BY YOUR HEALTHCARE PROFESSIONAL
Should you wish to consider locally available store-bought alternatives – seek the advice of your healthcare professional Re: availability
Figure 15.4 Milk ladder for reintroduction of cow’s milk at home [14]. Source: Licensed under Creative Commons Attribution 4.0 International License.
Challenges for early introduction of peanut

Nutritional requirements and dietary
Following the results from the LEAP study, challenge proto- management
cols for introduction of peanut at home or in a supervised set-
ting were published by the AAAAI. Challenge doses vary Currently, the only treatment for any food hypersensitivity
between 2.0 and 3.9 g of peanut protein, and practical guidance is dietary avoidance of the causative allergen. Although
on challenge doses using either peanut puffs, peanut butter symptom improvement is significant with such diets, the
powder or peanut butter is given in the publication [96]. nutritional impact must be considered.
Nutritional Requirements and Dietary Management 329
Nutritional requirements [101]. This law specifies that pre‐packed foods should pro-
vide information on the label if any of the following 14 aller-
Although it is well known that faltering growth and, in par- gens are ingredients in any amounts in the food: cereals
ticular, poor length/height growth is common in this popu- containing gluten, such as wheat (including spelt and kho-
lation, especially in association with eczema, and that there rasan wheat), rye, barley and oats; crustaceans, e.g. prawns,
is a higher risk of nutritional deficiencies in children with crab, lobster and crayfish; eggs; fish; peanuts; soybeans;
food allergies [18, 97–99], there is very little research on their milk, including lactose; nuts, e.g. almonds, hazelnuts, pista-
requirements. Many factors specific to the allergic child may chios, pecans, walnuts, Brazil nuts and macadamia nuts;
impact on nutritional requirements, as highlighted in celery, including celeriac; mustard; sesame seed; sulphur

Table 15.7. In the absence of specific guidelines, the prudent dioxide/sulphites, if there are more than 10 mg/kg or
approach would be to ensure that the allergic child achieves 10 mg/L in the finished product; lupin, including lupin
at least the normal requirements for a child of that age (p. 9) seeds and flour; and molluscs, e.g. mussels, oysters, snails
and that any deficiencies should be corrected. and squid. The information is required to be clearly visible in
bold, colour, italics or capital letters.
Loose foods include all items that are not pre‐packed.
Dietary management Foods that are wrapped on the same site as they are sold are
also known as loose foods [101, 102]. Rules for declaring the
The principles of dietary avoidance in children with food 14 allergens in loosely sold foods are the following:
hypersensitivity are:
• Information needs to be provided about the allergens
• which foods need to be avoided used in these foods
• suitable alternatives to these foods • Allergen information should be available in writing or
• practical advice for living on a restricted diet by speaking to staff
• dietary adequacy including optimal vitamin and mineral • Logos or symbols can be used when accompanied by
intake words and numbers on menus
• ensuring that oral motor milestones are achieved with
age‐appropriate taste and texture exposure For loosely sold foods allergen information has to be:
• easily accessible to all consumers
Which foods need to be avoided • accurate, consistent and verifiable
Information on foods that may contain ‘hidden’ allergens, If there is a risk of a pre‐packed food product being
and where these allergens may be found in non‐food items, affected by allergen cross‐contamination during its manu-
is the mainstay of any advice about dietary avoidance. The facture, the label should include one of the following state-
European Union (EU) law on food information for consum- ments: may contain X or not suitable for someone with X
ers (Regulation No 1169/2011) came into full effect in 2016 allergy. Foods with this precautionary allergen labelling
Table 15.7 Factors that may impact on nutritional requirements [18, 100].
Possible nutritional deficiencies
Trace
Factors Explanation Energy Protein Vitamins Minerals elements
Elimination diet Many foods contribute significantly to the child’s diet X X X X X

(e.g. cow’s milk)
Severe eczema Increased itching and possible skin healing may increase X X X
energy/protein requirements
Poor sleeping Disrupted sleep may increase energy requirements X X
pattern
Enteropathy/colitis Diarrhoea and possible malabsorption of nutrients may X X X X X
lead to deficiencies
Vomiting Excessive losses X X X X X
Irritability/pain Reduces food intake X X X X X
Aversive feeding Leads to reduced intake X X X X X
Medication Some medication used for treatment has side effects that X X
may impact on nutritional requirements (e.g.
corticosteroids)
should only be used following a thorough risk assessment. products and review existing products. This task can be
Parent/caregivers should take this warning seriously and made easier by joining a specialist support group where this
the dietitian should discuss the risk with them. The dietitian information is shared. Dietitians should also be aware of
also needs to address cross‐contamination issues [103]. suitable website and phone applications that can help
Many manufacturers and supermarkets produce ‘free‐from’ families with the availability of suitable foods.
lists for their products. These are very useful in managing food Food allergies, in particular cow’s milk allergy, most com-
avoidance diets, and families should be encouraged to use monly occur during the first year of life [56], when breast-
these to identify products that can be included in the diet. milk or infant formula is the sole or main source of nutrition.
It is important for parents/caregivers to be able to identify The young child is particularly vulnerable to nutritional
the sources of allergens in composite foods and to recognise deficiencies and growth failure, so it is important that
the terminology that may be used for each allergen dietitians can advise parents on suitable alternatives [18].
(Table 15.8). The dietitian needs to consider the nutrients
that the offending foods contribute to the diet so that these
Human milk
can be replaced with suitable alternatives.
Breastmilk is the ideal source of nutrition and should be
encouraged in all infants with food allergy, and the WHO
Suitable alternatives
guidelines for breastfeeding should be followed where
It is important for dietitians to familiarise themselves with possible [56, 105]. Occasionally, infants exhibit allergic symp-
suitable alternatives for foods that must be avoided. Advice toms while being exclusively breastfed. It is known that aller-
should be given on available products (e.g. peanut free con- gens, including β‐lactoglobulin (a protein unique to cow’s
fectionery, milk substitutes, egg‐free cakes, wheat‐free pasta) milk), egg and soya allergens, consumed by the mother can
and where to find them. Products and ingredients change appear in breastmilk [106, 107] and breastfed infants with
constantly. It is, therefore, essential that dietitians dealing multiple food allergies have been described [108, 109].
with food allergy continually update themselves with new In these cases, it is not recommended to stop breastfeeding
Table 15.8 Common allergens and their sources and nutrient contribution.
Allergen Sources Terminology Macro‐ and micronutrients
Milk Butter and most fat spreads, cheese, cow’s milk, Casein, caseinates, curd, lactoglobulin, Protein, energy, vitamins A, D and
sheep and goat milk, evaporated and lactose, milk solids, whey, buttermilk, B12, riboflavin, pantothenic acid,
condensed milk, cream, ghee, yoghurt, ice milk sugar, whey sugar, whey syrup calcium, phosphorus
creams, custard, dairy desserts and sweetener
manufactured foods using milk or butter in their
ingredients
Egg Egg white and yolk, cakes, biscuits, speciality Albumin, dried egg, egg powder, egg Protein, vitamins A, D, E and B12,
breads, egg pasta, mayonnaise protein, frozen egg, globulin, lecithin riboflavin, pantothenic acid, biotin,
(E322), livetin, ovalbumin, ovomucin, selenium, iodine, folate
ovovitellin, vitellin, pasteurised egg
Soy Soya sauce, soya products, meat substitutes, Soya beans, soya flour, soya protein, Protein, fibre, thiamin, riboflavin,
breads, vegetarian and vegan foods, processed soya gum, soya starch, texturised (or pyridoxine, folate, calcium,
meat hydrolysed) vegetable protein, soya phosphorus, magnesium, iron, zinc
flavouring, soya lecithin (E322)
Wheat Bread, breakfast cereals, pasta, cakes, biscuits, Bran, cereal filler, farina, starch, wheat, Energy, thiamin, riboflavin, niacin,
crackers, cold cooked meat, pies, batter, flour, durum wheat, semolina, spelt, kamut, iron, folate (if fortified)
semolina, couscous, bottled sauces and gravies wheat bran, wheat gluten, wheat starch,
wheat germ oil, hydrolysed wheat
protein, triticale, bulgur wheat
Nuts Peanuts/tree nuts, nut oil, nut flour, nut butter, Arachis oil and hypogaea (peanut), Protein, vitamin E, niacin,
some sprouts, confectionery, frozen desserts, prunus (almond), juglans (walnut), magnesium, manganese,
Asian dishes, nut snacks, trail mix, some rice corylus (hazelnut), peanut protein, chromium; some nuts may contain
crackers, some cereal bars, some cookies, some groundnut, earth nut, monkey nut a significant amount of essential
brownies, nut toppings on ice cream, vegetarian fatty acids
and vegan foods, satay sauce, some breakfast
cereals, some liquors and sauces
Fish All types of white and fatty fish, anchovy Protein, iodine
(Worcester sauce), aspic, caviar, surimi, Caesar Fish bones: calcium, phosphorus
salad, Gentleman’s Relish, kedgeree, caponata, Fatty fish: omega‐3 fatty acids,
fish sauce, paella, bouillabaisse, gumbo vitamins A and D
Source: Adapted from Venter and Meyer [100, 104].

but to suggest that the mother should avoid all suspected gastrointestinal food allergies, due to the possibility of brush
food allergens (p. 317), which appear to upset the infant when border damage related to inflammation. The European
she eats it [108]. In very rare cases, if symptoms cannot be Society for Paediatric Gastroenterology, Hepatology and
controlled by maternal allergen avoidance and harm to either Nutrition (ESPGHAN) advises that adverse reactions to lac-
the infant (e.g. faltering growth, rickets or other nutritional tose in children with CMPA are not reported and states that
deficiencies) or the mother (excessive weight loss or vitamin/ complete avoidance of lactose may not be needed in the
mineral deficiencies) is done, as a last resort after careful con- majority of cases [38]. A recent small cohort study has also
sideration with the parents, the cessation of breastfeeding found that secondary lactose intolerance in a non‐IgE medi-
may be considered. Breastfeeding mothers on exclusion diets ated population was rare [121]. Formulas suitable for CMPA
should be reviewed by a dietitian to check the adequacy of with lactose may, therefore, be considered for all types of
their diets as they may need supplements, especially of CMPA and may also be of benefit in regard to the gut micro-
calcium, vitamin D and iodine [56, 110, 111]. biota [122].
Much of the literature on the use of these formulas relates
to IgE mediated allergy. As far as non‐IgE mediated gastro-
Formulas suitable for the management of children
intestinal allergies are concerned, both extensively hydro-
with cow’s milk protein allergy
lysed casein and whey formulas have been shown to be
There are currently two definitions widely used in the EU to satisfactory. However, the incidence of intolerance to EHF
define products suitable for management of CMPA. The first seems to be higher (29.7%) in children with this delayed‐
such definition for labelling infant formulas with reduced type food allergy compared with the immediate‐type (IgE
allergenicity is arbitrarily based on a content of <1% immu- mediated) cow’s milk allergy (around 10%) [45, 54, 123].
noreactive protein of total nitrogen, which translates into the Therefore, some infants may react to hydrolysed formulas.
majority of peptides being <1.5 kDa [112]. However, there is Anaphylactic reactions have been described with both casein
no evidence that this threshold would prevent a clinical reac- and whey hydrolysates [54, 58, 124]. However, the majority
tion. There has, therefore, been a drive by official bodies for of cow’s milk allergic infants will tolerate any EHF. Luyt
hypoallergenic formulas to be tested in clinical trial using et al. [56] and Venter et al. [14] provide detailed discussion on
another criterion that stipulates that a formula suitable for cow’s milk allergy and the formulas available in the UK.
management CMPA should be tolerated by at least 90% of
children with a CMPA with a 95% confidence interval [112]. Amino acid‐based formulas
EAACI [31] is currently reviewing these guidelines, and an AAF (Table 15.6) consist of pure synthetic amino acids and
updated publication is expected. have been shown to be tolerated by infants and children with
Only extensively hydrolysed formulas (EHFs) [113], rice both IgE and non‐IgE mediated food hypersensitivity [125–
hydrolysates (currently not available in the UK) and AAF 127]. They are particularly useful for those infants who fail to
fall within either of these definitions, and dietitians should tolerate an EHF and may be useful in some allergic infants as
be aware that partial hydrolysates are not suitable for the first‐line treatment. In 2007, Hill et al. [128] undertook a sys-
treatment of CMPA [14, 38, 55, 56, 114]. In the past it was tematic review of food allergic patients that specifically may
recommended that an EHF should contain a majority of pep- benefit from an AAF. This systematic review has recently
tides <1.5 kDa; however this is based on old in vitro data [115, been updated with a new publication including more recent
116], and studies have shown that the percentage of peptides studies and found that in the following conditions an AAF
below this threshold does not predict tolerance, and, there- may be considered preferable in non‐breastfed children [54]:
fore, more attention should be given to research proving tol-
• failure of symptom resolution with an EHF
erance as per the current EAACI definition [117, 118].
• faltering growth, in particular if multiple systems are
involved, e.g. gastrointestinal tract and skin
Extensively hydrolysed infant formulas
• anaphylaxis
An EHF [113] is often the choice for an infant with immediate
• a diagnosis of EoE
or delayed adverse reactions to cow’s milk (Table 15.6). Casein
hydrolysates have been successfully used for over 60 years; The issue about which top‐up formula to use for cow’s milk
whey hydrolysates were introduced in the 1990s, and hydro- allergic breastfed infants, if needed, remains problematic; β‐
lysates of pork and soya are also available, but rarely used for lactoglobulin is detected in EHF made from cow’s milk (0.84–
CMPA [55, 118]. All EHFs in the UK suitable for CMPA have 14.5 μg/L), a similar level to that in breastmilk, and based on
gone through the necessary testing for growth and also toler- this an AAF would be indicated. However, this is not convinc-
ance, as recommended by EAACI. Over the last 5 years, there ingly supported by studies; in food allergic proctocolitis [129,
has been an increase in the use of rice hydrolysates in Europe 130], which most commonly presents in breastfed infants,
for CMPA. Many of these formulas have now also gone EHFs have been used with great success. Data also indicates
through the required testing [114, 119], and Meyer et al. [120] that FPIES in breastfed children is rare and, therefore, most
found very low inorganic arsenic levels in these formulas, guidelines suggest an EHF as first formula choice.
comparable with those in standard infant formulas. The choice of formula remains a challenge for dietitians
Some question the use of hypoallergenic formulas where the clinical need and the cost of the formula have to be
containing lactose in children with non‐IgE mediated
weighed up. Table 15.9 summarises the current available
Table 15.9 Summary of first‐choice formulas recommended by national and international guidelines.
DRACMA ESPGHAN Australian guidelines BSACI MAP and iMAP

Clinical presentation (2010) [55] (2012) [38] (2008) [131] (2014) [56] (2017) [14, 89]*
Anaphylaxis AAF AAF AAF AAF AAF

Acute urticaria or EHF No specific mention, but EHF EHF if <6 months of age EHF EHF
angioedema in general as first‐line treatment Soya if >6 months of age
Atopic eczema/ EHF No specific mention, but EHF EHF if <6 months of age EHF, but if symptoms while EHF
dermatitis in general as first‐line treatment Soya if >6 months of age exclusively breastfed, then
EHF if >6 months of age if also use AAF
presenting with faltering growth
EoE AAF AAF (for EGID) AAF AAF No recommendation
Gastro‐oesophageal EHF No specific mention but EHF in EHF if <6 months of age EHF (unless faltering EHF
reflux disease general as first‐line treatment Soya if >6 months of age growth, then use AAF)
EHF if >6 months of age if also
Cow’s milk EHF AAF (complicated by growth EHF if <6 months of age EHF (unless faltering growth EHF
protein‐induced faltering) Soya if >6 months of age then use AAF)
enteropathy EHF if >6 months of age if also
FPIES EHF AAF EHF AAF No recommendation
Proctocolitis EHF No specific mention, but EHF EHF if <6 months of age EHF (unless faltering growth EHF
in general as first‐line treatment Soya if >6 months of age then use AAF)
EHF if >6 months of age if also
DRACMA, Diagnosis and Rationale for Action Against Cow’s Milk Allergy; ESPGHAN, European Society for Paediatric Gastroenterology Hepatology and Nutrition; BSACI, British Society for
Allergy and Clinical Immunology; MAP, Milk Allergy in Primary Care; AAF, amino acid formula; EHF, extensively hydrolysed formula; EoE, eosinophilic oesophagitis; FPIES, food protein‐
induced enterocolitis syndrome; EGID, eosinophilic gastrointestinal diseases.
*iMAP guidelines only cover mild to moderate presentations of non‐IgE mediated allergies, therefore excluding guidance on the more severe presentations such as EoE, FPIES and children with
faltering growth.
international guidelines on the use of hypoallergenic formu- formula, therefore, based on goat milk is not suitable for the
las in the diagnosis and management of CMPA if breastmilk treatment of CMPA [55]. Some guidelines also hint towards
is not available. These guidelines, however, do not replace camel, and donkey milk being suitable, however, there is still
the clinical expertise of the dietitian. The problem is that >50% cross‐reactivity with cow’s milk protein. Therefore, the
there are very few randomised controlled studies directly introduction of these milks ideally requires the input of a
comparing two different formulas; the studies are relatively suitable healthcare professional to advise whether it is safe
poor quality; numbers are small; and clinical profiles of the to do and may require an OFC.
infants included in the studies are poorly described. Current
research indicates that the majority of children with CMPA
Practical advice
will improve on an EHF. The guidelines suggest the use of an
AAF as a first option only for more severe presentations of It is important to provide families with practical advice on
CMPA, such as a history of anaphylaxis, Heiner syndrome, how to manage their child’s food allergy. This starts with
EoE, faltering growth, and some of the more severe gastroin- how to support breastfeeding. If breastmilk is not available,
testinal and skin presentations. or a top‐up formula suitable for the management of CMPA is
needed, the following hints may help with the introduction:
Formulas based on whole soy protein isolate
• The formula should be offered when the infant is hungry
Infant formulas based on whole soy protein isolate have
and thirsty
been available without prescription for many years. In the
• It may sometimes be easier if the first bottles are not
past, soy‐based formulas were used widely as an alterna-
given by the main caregiver
tive to cow’s milk formula in those infants with CMPA.
• Mixing hypoallergenic formula with weaning foods may
However, in 2004 the UK Chief Medical Officer advised
help the child to get used to the taste of the formula (e.g.
against the use of soy formula in infants under the age of 6
in porridge)
months unless there is a specific medical indication due to
• If the child is able to hold a bottle (usually over 6 months
their high phytoestrogen content [132]. The Committee on
of age), then a baby beaker with free flow may also be
Toxicity of Chemicals in Food, Consumer Products and the
useful
Environment (COT) is reviewing more recent research in
• Vanilla essence may be helpful to improve the taste, but
this area.
care must be taken as if too much is added it may make
The prevalence of concomitant soy allergy in infants with
the formula taste more bitter
CMPA differs between IgE and non‐IgE mediated diseases.
• Flavourings should be avoided, but if all else fails, a milk
Klemola et al. and Zeiger et al. found that 10% and 14% of
and soy‐free milkshake powder or syrup can be added
infants with IgE mediated CMPA, respectively, have con-
(no honey is advised <1 year of age)
comitant soy allergy, whereas associated soy allergy in non‐
IgE mediated CMPA is much higher (up to 50%), especially Parents also need information on the availability of
in enterocolitis and enteropathy syndromes [133–135]. This products to suit their child’s exclusion (avoidance) diet.
data may, however, vary between countries, which has been Many supermarkets now stock a range of ‘free‐from’ foods,
shown by a review of 40 worldwide studies on IgE mediated which may be useful, and there are two apps that are free
soya allergy, finding a prevalence in allergic children rang- to download that may help in finding products free from
ing from 0% to 12.9% in different countries [136]. the offending allergens: the Food Maestro App (www.
The use of soya formula in the diagnosis and management foodmaestro.me/home.html) and the Spoon Guru App
of CMPA is a highly debated topic, with clear differences (www.spoon.guru/spoon‐guru‐news). The BDA FASG has
between different countries and professional bodies produced diet sheets with ‘free‐from’ foods suitable for all
(Table 15.8). Soya formula can be given for the treatment of types of food allergies, free to be downloaded for BDA
CMPA in infants over the age of 6 months if it has been members.
shown that they do not have soy allergy and they have failed Parents find recipes very useful. Some examples include
to take other hypoallergenic formulas due to the taste prefer- cakes without egg, biscuits and cakes without wheat and
ences of the child or if there are strong parental preferences gravy and sauces without wheat. A general discussion
(e.g. following a vegan diet). Soya‐containing products such about menu planning is helpful. Advice may include ideas
as soya desserts enhance the variety in a cow’s milk‐free diet for weaning foods and packed lunches. Other agencies may
and can be given from 6 months of age [56, 137]. need to be contacted, e.g. school caterers. Parents also
appreciate tips on how to get a child to take a new food.
Other mammalian milks For example, wheat‐free products are often better accepted
The most commonly available other mammalian milks in the initially if given with other flavours, e.g. jam on bread and
UK are sheep and goat milk, which are not suitable for sauce on pasta. A caregiver other than the main caregiver is
infants with CMPA as their proteins can be as sensitising as often able to persuade the child to take the new food. It is
cow’s milk protein. Dean et al. have shown that there is also important to discuss the management of food allergies
strong cross‐reactivity in vitro between allergens in all mam- at nursery or school and when the family travels abroad.
malian milks (except human milk) and DRACMA guidelines The FASG diet sheets contain recipes; these can be freely
summarise further cross‐reaction [55, 138]. An infant downloaded by BDA members.
Dietary supplements The key aspect of monitoring childhood food allergies is

establishing when the child has outgrown their allergies or
Whenever a food is removed from the diet, there is the likeli-
when they have developed tolerance to certain forms of the
hood that the diet will no longer meet nutritional require-
food, e.g. baked milk/egg [142]. Food challenges or reintro-
ments (Table 15.8); the more foods that are eliminated the
duction of food at home forms an important part of this
greater the risk of a deficiency. Infants who consume less
process.
than 600–700 mL of hypoallergenic formula, depending on
The dietary management of food hypersensitivity consists
which formula is used, and all infants who are fully breast-
primarily of educating patients and their families so they can
fed will require a multivitamin preparation containing, in
avoid the causative food while eating tolerated foods and
particular, vitamins A and D [139]. In addition, a calcium
still meeting all nutritional requirements. No dietary
supplement will be required in children with CMPA who do
manipulation is easy, so it is the role of the dietitian to not
not consume sufficient formula or calcium‐containing foods.
only give information on how to avoid the causative food
Family doctors are generally happy to prescribe supple-
but also how to make the resultant diet as palatable and var-
ments, but sometimes an over‐the‐counter supplement may
ied as possible. Before any advice is given, it is essential to
be more readily accepted, especially in older children.
consider how strict the diet needs to be. If a child tolerates a
Vitamins and minerals must be free from the offending aller-
food (even with a positive SPT/specific IgE) without any
gens. Vitamin and mineral supplements are often forgotten
reaction, or if they can tolerated the baked version of the
in infants less than 6 months of age; if dietary consumption
food, it is important not to stop these foods, but to encourage
is suboptimal and maternal dietary intake has not been inad-
them to keep this food in the diet. On the other hand, when
equate or there is a known deficiency during pregnancy and
reactions occur when exposed to tiny doses advice on
lactation, then other vitamins (apart from vitamin D) and
complete avoidance is essential.
minerals may be required. It is also important to consider
iron, zinc and iodine status, in particular if gut inflammation
is present and cow’s milk is avoided; cow’s milk is a primary
Natural progression
source of iodine in the UK diet [110, 140, 141].
A case study to illustrate the management of a child with
Food allergy is most commonly acquired during the first
food allergy is given in Table 15.10.
year of life with a peak incidence between 2.2% and 5.5%
during the first 2 years of life in the UK [143, 144]. The preva-
Learning points: dietary management of food allergy lence falls to 2.3% in teenagers and then plateaus at 1%–2%
through adulthood [145]. These figures may be higher in
• Breastfeeding should be supported as far as possible in chil- patients seen in tertiary centres [146]. The majority of
dren with CMPA reactions to foods in infants and young children are to milk,
• The elimination of foods increases the risk for both growth egg, nuts, soy, fish and wheat [147]; however in adulthood
faltering and vitamin and mineral deficiencies the most common food allergens include hazelnut, apple,
• The presence of co‐morbidities (e.g. eczema) increases the peach and shrimp [148]. Although the tendency to develop
risk in particular for length/height growth failure allergies clearly has a genetic component, it is strongly influ-
• Feeding difficulties are common in children with food enced by environment and lifestyle factors. These include air
allergies pollution, environmental tobacco smoke exposure, maternal
• For children with CMPA, most will improve on an EHF, and infant nutrition, environmental allergen exposure,
but for those with the more severe forms of allergy (includ- family size, infections and hygiene [149].
ing EoE, anaphylaxis, multiple system involvement and It has long been established that most children grow out
faltering growth), an AAF is indicated of their allergies, in particular milk and egg allergy.
• None of the mammalian milks are suitable alternatives for However, recent studies performed in tertiary centres have
children with CMPA shown that some of these allergies are more persistent and
• Parents need to have advice on suitable alternatives and, if children outgrow them later in life than previously thought.
a formula is required, how to get the child to accept it Approximately half of egg allergic children will be tolerant
by the age of 3 years and 66% by 5 years of age [150]. For
milk, about 80%–90% of children may become tolerant
according to population‐based studies [146, 151]. It is com-
Monitoring monly thought that peanut allergy does not resolve
although Skolnick et al. [152] have shown that it may be
It is essential that children following an exclusion diet are outgrown in 21.5% of patients. Tree nut, fish and shellfish
followed up regularly. Children’s diets vary enormously as allergies tend to develop in older children and are unlikely
they get older and nutritional requirements also change. It is to be outgrown.
important to ensure they maintain normal growth. There Although many children grow out of their initial food
may also be advances in knowledge that may affect treat- allergies, it is evident that allergic disorders change and
ment strategies, and it is also important to ensure that as the progress from eczema and food allergy in early childhood to
child gets older, they themselves understand their diet. asthma and rhinitis related to pollen allergy in later
Table 15.10 Case study: management of food allergy in a young child.
Presentation
A 3‐month‐old baby girl presented with chronic diarrhoea and mild to moderate eczema across her body and face.
Weight = 25th centile, Length = 50th centile
She was fed on normal infant formula from birth.
Family history: Mother has asthma and father has hay fever. Born at full term, normal delivery.
The infant was seen by a paediatrician, an allergy nurse and a paediatric allergy dietitian, who provided advice regarding skin care and changed her
formula to an EHF [113], in line with current guidelines. Skin prick tests (SPTs) were not conducted at this stage, based on her current symptoms,
which suggested a non‐IgE mediated allergy. Written and verbal advice was given on the avoidance of cow’s milk and soya, and the introduction of
complementary food was advised from around 6 months of age.
Follow‐up
Returned to the allergy clinic at age 6 months; her diarrhoea had resolved and her eczema had cleared, with only the occasional flare.
On examination, she was found to be well and thriving, with a normal physical examination.
Full blood count, clotting profile and liver function were all within the normal range.
Because she was weaning, SPTs were performed to determine which foods could be safely introduced (see table below). The SPT for milk was positive,
which suggested that hypersensitivity to cow’s milk may have played a role in her eczema flares in the past. Together with her improved symptoms
since changing to EHF, this allowed a diagnosis of CMPA to be made. A second, smaller wheal suggested a potential allergy to egg. In consultation
with the paediatrician and dietitian, the baby’s mother was advised to use milk and egg‐free weaning foods, given recipes and website addresses.
An egg challenge was planned to assess tolerance. It was also recommended that all other allergenic foods should be introduced one at a time, with
the precautionary exclusion of soya, because infants with non‐IgE mediated CMPA commonly also have a soy allergy [45]. In addition, the baby’s
formula was changed to a follow‐on EHF, which contains more calcium and is, therefore, suited to babies >6 months of age.
Skin prick tests: results at ages 6 months and 12 months.
Test Wheal size at 6 months (mm)† Wheal size at 12 months (mm)†
Milk 3 1
Egg 2 1
Wheat 0 0
Soya 0 0
Peanut 0 0
Positive control 3 4
Negative control 0 0
†
SPT are considered positive if the wheal is ≥3 mm larger than the negative control; for further information,
see Skypala [2].
At age 9 months
Thriving. Eczema was under control and the diarrhoea had not returned. She was feeding a follow‐on EHF and solid foods, excluding milk, egg and
soy. An oral challenge with one boiled egg was performed in hospital, with a negative result. Therefore, it was recommended that she should be given
a well‐cooked scrambled egg at home the next morning, returning to the children’s ward if symptoms reappeared.
At age 12 months
Thriving. Eating a varied diet and consuming 450–500 mL EHF per day with additional supplement of vitamins A and D and consuming calcium‐
enriched coconut yoghurt. SPT showed negative results for cow’s milk and soya, so oral challenges with these foods were given. The soya
reintroduction over a period of a week at home was negative. However, the cow’s milk challenge, conducted in hospital, resulted in an immediate
flare of her eczema, with diarrhoea the following morning. It was recommended that soya yoghurts and puddings could be introduced to increase
variety in her diet, but she should continue to avoid all milk products.
2 years
SPT for milk produced a 2 mm wheal. On analysing this toddler’s diet, her nutritional intake was found to be adequate. As a result, it was
recommended that the milk‐free diet was continued and calcium‐enriched soy milk could be introduced.
Four months later, this girl accidentally drank a cup of milk at nursery, without an adverse reaction. Consequently, oral challenge was given in hospital,
which continued at home for a week. As she showed no allergic symptoms, the mother was advised that milk products could be gradually
reintroduced. Subsequently, she occasionally experienced eczematous symptoms, which were treated with emollients, antihistamines and a little
hydrocortisone.
3 years
SPTs were negative for all allergens tested and she was tolerating all foods.
childhood. This phenomenon is referred to as the ‘allergic intervention (named transition coordinators), joint clinics
march’ [153, 154]. The ‘allergic march’ has been well estab- run by paediatric and adult physicians and changes to ser-
lished for IgE mediated allergy, but it is only recently that a vice delivery (separate young adult clinics, out of hours
non‐IgE mediated ‘march’ has been hypothesised. Also start- phone support, enhanced follow‐up). All these interven-
ing with eczema and food allergies and migrating to the tions have been shown to improve care [158].
same atopic diseases with age, there is an increased risk of
developing functional gastrointestinal disorders and extra‐
intestinal manifestations when getting older in the non‐IgE Problems with dietary management in food
mediated ‘march’ [16]. hypersensitivity
The avoidance of any foods/food groups in a child’s diet can

increase the risk of nutritional deficiencies [18]. It is, there-
Pollen food syndrome (oral allergy syndrome)
fore, important to avoid unnecessary food eliminations.
However, there may be parents who feel that diet plays a
OAS describes any oral symptoms following oral exposure
role in their child’s illness, and they should have the oppor-
to an allergen, while PFS (also known as pollen food
tunity to discuss in an unbiased fashion the possibilities of
syndrome) is the clinical entity where symptoms,

dietary treatment and, where appropriate, have the opportu-
predominantly OAS, occur following exposure to plant

nity to trial an exclusion diet. A lack of sympathetic approach
foods (fruit and vegetables) that contain allergens similar to
may lead to self‐imposed diets (likely to be inadequate) or
pollen such as grass and trees. These reactions are occasion-
self‐referral to an unqualified practitioner. Whatever the
ally triggered also by foods cross‐reacting with latex [155].
prejudices of the professionals involved, the question of diet
Such cross‐reactivity does not always indicate that avoid-
must be discussed as the child may be on an inadequate and
ance of all these foods is necessary, with clinical history
inappropriate diet [18]. Although some children may be on
being indicative of the requirement to avoid certain foods.
unhelpful diets, others benefit dramatically from the correct
These mucosal reactions are normally to raw fruit, so advice
exclusion diet. The role of the dietitian is to assist in main-
regarding cooking/microwaving the food or trying tinned
taining helpful diets and broaden the diet as much as possi-
varieties can often result in the child being able to eat the
ble. It is equally important to encourage people to abandon
food. This advice is important in helping the child maintain
exclusion diets where they confer no benefit. An open‐
their fruit/vegetable intake. In the UK, Ludman et al.
minded approach is necessary. Occasionally, parents will not
recently reported a point prevalence for physician diag-
take advice, and in exceptional cases, the dietary restrictions
nosed PFS of 48% in a selected cohort of 54 children with
imposed by the parent on the child may be regarded as a
seasonal allergic rhinitis attending a specialist allergy clinic,
form of child abuse.
the prevalence increasing with age [48].
Controversial elimination diets

Migraine and epilepsy
Although many children will outgrow their allergies, some
will continue to have their allergies into adulthood, and Cheese, chocolate and red wine sometimes provoke
some may develop new food hypersensitivities. The migraine, allegedly owing to the presence of a pharmaco-
transitional stage, starting during teenage years, is the time logically active ingredient, tyramine. Children with severe
when children will have to take responsibility of their own migraine who have failed to benefit from avoidance of
management. It is important to realise that teenagers with cheese and chocolate have been shown to respond to a few
food allergies want to eat the same foods as their peers, foods diet, and the most common provoking foods on food
often leading to risk‐taking behaviour [156].A recent study reintroduction were those that are implicated in food hyper-
by Monks et al. [157] found that the majority of teenagers sensitivity in general [159, 160]. When migraine attacks are
reported eating foods labelled ‘may contain’ an allergen as less than one per week, it is difficult to use a diet approach.
they perceive that the foods are actually very unlikely to If symptoms are infrequent, 3 weeks of a few foods diet
contain an allergen. Many of the teenagers only carried their would not be long enough to assess change in rate of attacks,
self‐injectable adrenaline (required for anaphylactic patients and the reintroduction phase would be very muddled.
who accidentally consume an offending allergen) when However, for children with severe frequent migraine who
they thought they were particularly at risk of a reaction; have not responded to medication, a diet trial is a worth-
some did not know how to treat themselves if a reaction while procedure. Sometimes children with severe migraine
should occur. A recent systematic review looking into strate- have other symptoms and epilepsy may be one of these. A
gies that improve transition between paediatric and adult minority of children with epilepsy who also have migraine
care in children with chronic illness found four broad respond to dietary elimination, whereas children with epi-
categories that improved transition: patient‐directed
lepsy alone do not [161]. As with migraine, the diet approach
intervention (educational programmes, skills training), staff cannot be tried unless seizures are frequent. A trial of diet for
Future Research Needs and Unanswered Questions 337
such children who have not responded to conventional treat- that these foods/chemicals are triggering any reactions. If
ment is worth considering. foods are being eliminated for a longer period of time, a
dietitian should be involved to ensure that the diet is nutri-
tionally adequate and take the individual’s eating habits
Attention deficit hyperactivity disorder into account [21].
The question of diet and ADHD is very controversial.
In 1975 Feingold, an American allergist, claimed that Future research needs and unanswered questions
hyperactive children would benefit from avoiding foods
containing salicylates together with artificial flavours Management of food allergies
and colours. Later, food preservatives were also excluded.
The results of studies aimed at testing Feingold’s hypoth- With an increase of our understanding of how nutrition
esis indicated that only a few hyperactive children impacts on the immune system and tolerance development,
responded to the elimination of food additives from their questions increasingly arise regarding manipulation of the
diets. Problems with methodology and interpretation of gut microbiome; the role of particular nutrients, e.g. omega‐3
these studies have been discussed by Taylor [162]. Five fatty acids; food components such as advanced glycation
studies have looked at the relationship between food end products; and diet diversity to increase tolerance devel-
(not just additives) and behaviour [163]. More recently, opment. There is currently no particularly evidence‐based
McCann et al. [164] performed a double‐blind ran- advice that can be given to patients, but these are certainly
domised controlled study using two additive m ixtures areas of nutrition that provide hope for resolution of food
and found that artificial colours or a sodium benzoate allergies [100].
preservative (or both) in the diet resulted in increased
hyperactivity in 3‐year‐old and 8‐ to 9‐year‐old children
in the g eneral population. At the time of publishing this Food allergy treatment
study, the exact mechanism of worsening ADHD through
food additives was not known. Since then, the same The use of oral immunotherapy, sublingual i mmunotherapy,
group has discussed how food additives can exacerbate epicutaneous immunotherapy and biologics to induce tol-
ADHD symptoms and cause non‐IgE dependent hista- erance to food allergens are currently investigated.
mine release from circulating basophils. The fact that However, even though increased threshold levels are seen,
some children reacted worse than others was found to be sustained unresponsiveness is not guaranteed with any of
related to specific genes influencing the action of hista- these treatment modalities, and a number of side effects
mine, which may explain the inconsistency between (including anaphylaxis) are often seen. Allergists may,
p revious studies [165]. however, implement these in the allergy clinic based on
From a practical dietetic point of view, food colourings their level of expertise and confidence in a particular
and sodium benzoate are found in processed foods, often treatment regimen [166].
with high sugar and salt content. Parents of a child with
ADHD should in the first instance be advised to ensure a
healthy balanced dietary intake. For children with severe Prevention of food allergies
ADHD whose parents wish to explore the dietary approach
(free from colourings and sodium benzoate), they should Prevention strategies for food allergy are discussed in
be given the opportunity to do so with the support of a Chapter 16.
dietitian; otherwise they will be tempted to experiment
with a diet unsupervised, which may lead to nutritional
The gut microbiome and probiotics
deficiencies. Other treatments such as behaviour modifica-
tion or stimulant medication may be more effective than
The microbial diversity and species abundance in children
dietary management, although some children may end up
with food allergies have received significant attention in the
on a combination of these treatments.
last 5 years. Studies have shown there to be a difference
between children sensitised to food allergens [167], those with
clinical CMPA [168], those who remain allergic, and those
Vasoactive amines and intolerance reactions
who develop tolerance [169]. However, we are far from being
Skypala et al. discussed the role of food chemicals in possi- able to define what optimal gut microbial diversity means
ble adverse reactions and concluded that there is limited and identifying which bacterial strains are of particular
and mostly outdated evidence for the removal of food importance in reducing symptom severity and induce
chemicals (either added or natural) in the management of tolerance [169].
suspected adverse reactions to foods, e.g. migraine or A probiotic is defined as “an oral supplement or a food
chronic urticaria. Foods should only be excluded for a lim- product that contains a sufficient number of viable microor-
ited period of time, followed by reintroduction to confirm ganisms to alter the microflora of the host and has the
potential for beneficial health effects” [170]. Two publica- Synbiotics

tions [171, 172] indicated that a probiotic Lactobacillus rham-
nosus GG added to a casein‐based EHF increased the ‘Combining the rationale of pro‐ and prebiotics, the concept
development of tolerance in children with IgE mediated of synbiotics is proposed to characterise some foods with
CMPA at 1 and 2 years of age. Follow‐up of this population interesting nutritional properties that make these com-
has indicated also a reduction of allergic manifestations pounds candidates for classification as health‐enhancing
(eczema and asthma) [173]. Three studies, including the functional food ingredients’ [178].
strains L. rhamnosus GG, L. casei CRL431 and Bifidobacterium Studies have been published using a specific synbiotic
lactis Bb‐12, have similar findings to the studies on IgE medi- blend of fructo‐oligosaccharides and Bifidobacterium breve
ated allergies, with increased cow’s milk tolerance acquisi- M‐16V in an AAF. Burks et al. [63] found that this formula
tion in non‐IgE mediated CMPA [172, 174, 175]. was well tolerated and reduced allergic manifestations in
In terms of other CMPA‐related symptoms, one study the same way as the control AAF and there were no statis-
showed that L. rhamnosus GG added to casein‐based EHF tically significant differences in adverse effects between
reduced the occurrence of severe urticaria and any CMPA‐ groups. This was followed by a study on the microbiota in
related symptoms, but not asthma [172]. Three studies children with non‐IgE mediated CMPA by Candy et al.
reported severity of eczema measured with a SCORAD [125], which found no statistically significant differences
(SCORing Atopic Dermatitis) scale. The differences between in symptom improvement between the children on the
groups were on average small (1–4 points) and are unlikely synbiotic AAF and the standard AAF, but the synbiotic
to be clinically important [174–176]. group had statistically higher counts of bifidobacteria and
lower counts of Clostridium coccoides and Eubacterium rec-
tale. Data regarding tolerance development has not been
Prebiotics published.
‘Prebiotics are non‐digestible food ingredients that benefi-

cially affect the host by selectively stimulating the growth
and/or activity of one or a limited number of bacterial spe-
cies already resident in the colon, and thus attempt to References, further reading, guidelines, support groups
improve host health’ [177]. There is currently no data regard- and other useful links are on the companion website:
ing the use of prebiotics for the treatment of food allergies. www.wiley.com/go/shaw/paediatricdietetics-5e
16
Kate Grimshaw
Prevention of Food Allergy
Introduction determining whether an infant will develop allergic disease

[17–21]. The infant’s immune system first meets food aller-
Allergic diseases, such as asthma, rhinitis, eczema and food gens in utero [17] and continues to be exposed after birth via
allergies, are rising globally [1–4]. Within this increased breastmilk [22] and then again when solids are introduced
prevalence, incidents of food‐related anaphylaxis are also into the diet. It is unclear which, if not all, of these exposure
increasing, adding to the overall public health burden related time points are important in initiating the allergic march.
to food allergy, particularly in urbanised countries [5]. Food This is why prevention strategies tend to focus on pregnancy
allergy, let alone other manifestations of allergy, has signifi- and the first year of life [18].
cant individual, household and societal costs [6, 7]. In the
UK, allergic disease accounts for 6% of general practice con-
sultations and 10% of the prescribing budget [8]. Add to this Allergen avoidance
the impact allergic disease has on quality of life of both
sufferers and caregivers [9–11] and that there is currently no As knowledge in the field of immunology has developed, it
cure, it is natural that attention turns to interventions tar- has become clear that exposure to food allergens early in an
geting disease prevention. infant’s immunological development is important in food
Allergic disorders change over time, progressing from allergy initiation and that this exposure could be in utero or
eczema and food allergy in infancy and early childhood to during breastfeeding, as well as directly from the infant’s
asthma, rhinitis and inhalant allergy in older childhood, diet. Consequently, maternal allergen avoidance during
adolescence and adulthood. This is referred to as the ‘allergic pregnancy and lactation (alongside delayed allergen intro-
march’ (or atopic march) [12] and usually starts with the duction into the child’s diet) became the primary strategy for
development of atopic dermatitis, which peaks in preva- allergy prevention in the 1980s and 1990s. A number of ran-
lence within the first 2 years of life [12]. Of the children who domised controlled trials (RCTs) to investigate this hypoth-
develop atopic dermatitis, many, if not most, develop the esis were carried out [23–26], accompanied by national and
disease within the first 6 months of life [12–14]. The age at regional guidelines supporting the concept [27, 28].
which food allergies present varies depending upon the Early this century, research suggested that acquiring tol-
allergen; allergies to hen’s egg and cow’s milk generally erance to foreign (food) proteins was an active rather than a
develop within the first year of life, whereas allergies to passive process [29, 30]. Therefore, delaying the introduc-
wheat, soy and peanut tend to develop later in childhood tion of allergenic foods into the diet may not protect against
[15]. Within the allergic march, eczema and food allergy may sensitisation or allergic disease [31–33]. This meant that
be outgrown or can persist, resulting in individuals who avoidance as an allergy prevention strategy was ques-
‘collect’ allergic conditions as they age. tioned. Additionally, newer publications from observa-
It is well established that early life factors influence the tional birth cohort studies [34–37] and a subsequent
development of all atopic disease, including food allergy systematic review [38] suggested evidence for recommend-
[16], with research showing that events taking place during ing avoidance strategies in pregnancy and lactation was
pregnancy and foetal development play a key role in lacking and delaying the introduction of solid foods did not

340 Prevention of Food Allergy
appear to protect against food allergy. Consequently, the Formula feeding

latest recommendation for allergy prevention by the
European Academy of Allergy and Clinical Immunology It has long been agreed that feeding with a whole protein
(EAACI) does not support avoidance as an allergy preven- infant formula compared with breastfeeding increases the risk
tion strategy during pregnancy, lactation or complementary of the child developing allergic disease [60]. This is because in
feeding [18]. The American Academy of Pediatrics (AAP) newborns, the mucosal barrier is immature and large quanti-
[39], the Australasian Society of Clinical Immunology and ties of macromolecules cross the epithelium into the systemic
Allergy (ASCIA) [40] and other national bodies [41, 42] have circulation to be encountered by the immune system.
similar views.
Hydrolysed protein infant formulas
Breastfeeding and the development
There have been a number of studies examining the merits of
of allergic disease
hydrolysed protein infant formulas as a primary prevention
for allergic disease. Intervention studies in high risk infants
Breastmilk is thought to play an important role in the devel-
who are not breastfed have compared both partially and
opment of oral tolerance as there are a number of compo-
extensively hydrolysed cow’s milk formulas with formulas
nents in breastmilk that are important in protecting the
based on intact (whole) cow’s milk protein. In two studies, a
infant from microbial/antigen attack [43]. Some of these
protective effect of hydrolysed infant formulas was found
factors initiate the innate immune response, but some are
[61, 62], while in three other studies no difference was seen
closely involved in the development of the infant’s adaptive
[63–65]. The German Infant Nutritional Intervention (GINI)
immune system (p. 315). Immunological factors in breast-
study examined three different hydrolysed infant formulas
milk consist of maternal immunoglobulins, oligosaccha-
and standard infant formula, comparing different allergy
rides, cytokines, glycoproteins, long chain polyunsaturated
outcomes between the groups. Both the extensively hydro-
fatty acids (LCPUFAs), lysozyme, nucleotides and comple-
lysed casein formula and partially hydrolysed whey formula
ment. Many of these are thought to have a role in the devel-
were shown to have a preventative effect on both physician
opment of oral tolerance, in particular transforming growth
diagnosis of allergic manifestation and atopic dermatitis.
factor beta (TGF‐β) [44, 45], interleukin‐12 (IL‐12) [46, 47]
Inexplicably, this was not found for the extensively hydro-
and soluble cluster of differentiation 14 (CD14) [48].
lysed whey formula [66, 67]. Consequently, there is debate as
Additionally, secretory IgA in breastmilk is thought to
to which is the best formula for allergy prevention, as reflected
shield the breastfed infant’s gut‐associated lymphoid tissue
by differing national and professional body recommenda-
from dietary allergens, thereby reducing local immune
tions [18, 38–42] and individual clinicians’ opinions [68, 69].
stimulation and contributing to the establishment of oral
However, a recent systematic review and meta‐analysis,
tolerance [22].
using a rigorous approach, failed to find a beneficial effect of
However, the role of breastmilk in allergy development
hypoallergenic (HA) infant formulas on food allergy [70].
remains unclear with studies showing protection, no effect
The authors highlighted that many studies were at uncertain
and even increased risk. This has been explained by the
or high risk of bias; they also found evidence of publication
fact that the levels of nutritive and bioactive factors in
bias. Since it appears preventive efficacy is highly dependent
breastmilk vary according to the nutritional and atopic sta-
on the specific formula studied, the EAACI guidelines group
tus of the mother [43, 48, 49]. When levels of cytokines in
recommended the use of HA formulas with a documented
the milk are taken into account, then a relationship is seen
preventive effect for high risk children in the first 4 months
[50]. Due to these findings and the fact that a number of
of life only [18]. No studies show a preventive effect in low
RCTs in high risk infants investigating the effect of differ-
risk children. Soya formula should not be used for the pre-
ent dietary allergy prevention programmes during breast-
vention of food allergy [18, 39, 71].
feeding [51, 52] or pregnancy and breastfeeding [26, 53, 54]
found no real benefit, maternal dietary intervention dur-
ing lactation to reduce allergy risk is no longer recom- Early introduction of allergenic foods
mended [18, 39, 55].
Another explanation for the apparently conflicting find- In 2001 WHO advised exclusive breastfeeding for at least 26
ings of the role of breastmilk on allergy development is that weeks of age [72] and this recommendation was supported by
the immunomodulatory effect of breastmilk is only apparent the UK Department of Health in 2003 [73]; prior to this the
when the infant’s immune system is exposed to a food at the advice was for solids to be introduced between 4 and 6
same time as breastmilk [56–58]. This supports the WHO months (but not before 17 weeks) [74]. The necessity for exclu-
recommendation that introduction of solid foods should ide- sive breastfeeding for 26 weeks has been questioned [75].
ally take place alongside continued breastfeeding [59]. The first studies in this field in the 1980s were observa-
Despite these conflicting findings, breastfeeding is recom- tional. Fergusson et al. looked at both the timing and rate of
mended for all infants due to its nutritional, immunological introduction of solids into an infant diet with the later devel-
and psychological benefits, and it should ideally be contin- opment of eczema at 2 years of age [76] and found that solid
ued while allergenic solids are introduced to the infant’s diet food introduction before 4 months of age and the number of
[18, 40, 58]. foods introduced were associated with an increased
Early Introduction of Allergenic Foods 341
incidence of physician‐reported eczema. This association However, when the analysis was adjusted for adherence to
persisted to 10 years of age [77]. Kajosaari and Saarinen com- early introduction, there was a statistically significant reduc-
pared the early introduction of allergenic foods with intro- tion in food allergy in the early introduction group (6.4% vs.
duction after 6 months of age and showed no differences in 2.4%, p = 0.03), suggesting that introduction of sufficient
the prevalence of food allergy, either in the first year of life amounts of allergenic foods into the infant diet from 3 to 6
[78] or at age 5 years [79]. A number of similar studies fol- months alongside continued breastfeeding may be effective
lowed, and a systematic review looking at complementary in food allergy prevention. However, the poor adherence to
feeding before 4 months of age found few data linking early study protocol emphasises the challenges around introduc-
solid feeding and allergic conditions other than an associa- ing solids into the diets of infants under 6 months of age.
tion with early solids introduction and persistent eczema Since the STAR study, further trials into the relationship of
[80]. However, a recent study using data collected from pro- egg introduction and allergy development have reported.
spective food diaries has shown solids introduction before The Hen’s Egg Allergy Prevention (HEAP) study [86] exam-
17 weeks of age to be associated with an increased risk of ined 383 infants aged 4–6 months randomised to receive
food allergy development [58]. freeze‐dried egg white or placebo three times a week until 1
This century, infant feeding data collected as part of birth year of age. At 12 months, egg allergy was found in 2.1% in
cohort studies have been analysed to investigate the relation- the active group and 0.6% in the placebo group (p = 0.35).
ship between solid food introduction and the later develop- Overall, this study failed to find evidence that early egg
ment of atopy [34–37]. No study found any benefit on allergic intake prevents food allergy. Comparable results emerged
outcome by delaying the introduction of solids, and two from the Australian Starting Time of Egg Protein (STEP) trial
found an association between the delayed introduction of [87] that recruited 820 high risk infants who had no allergic
milk [37] and egg [81] and increased incidence of eczema and symptoms and had not previously ingested egg. Infants were
atopic sensitisation. More recently it has been suggested that daily fed 0.9 g pasteurised raw egg (½ egg per week) or pla-
children exposed to cereal grains before 6 months of age (as cebo from 4–6 to 10 months of age. No difference in egg
opposed to after 6 months of age) are protected from the allergy prevalence was found between the groups (7% active
development of wheat‐specific immunoglobulin E (IgE) [35]. vs. 10.3% placebo, p = 0.20). Likewise, the Beating Egg Allergy
All these studies retrospectively collected feeding data, which Trial (BEAT) [88] found no difference in egg allergy preva-
makes the findings vulnerable to both recall bias and reverse lence between the active group and the placebo group (10.5%
causality, and they only demonstrate an association, not cau- vs. 6.2%) of pasteurised egg introduction from 4 to 8 months
sality. Large scale RCTs are required to determine causality, of age in high risk infants. Overall, these findings suggest that
and a number have reported their findings over the past few other factors including genetic features, epigenetic modifica-
years, providing important data to the evidence base. tions, nutrient intake and alterations of intestinal flora may
The first of these studies to report was the STAR (Starting play a pathogenic role in the development of food allergy.
Time for Allergy Reduction) study looking at the introduc- Further RCTs are under way, but those that have reported
tion of egg powder into the diet of 86 high risk infants aged have already led to changes in recommendations for the
4–6 months with moderate/severe eczema [82]. Of the infants introduction of solids made by expert groups. In their report
randomised to receive egg powder, 31% had an allergic reac- on feeding in the first year of life, the Scientific Advisory
tion to the egg powder, leading to the study stopping prema- Committee on Nutrition (SACN) has advised that foods con-
turely. At 12 months of age, there was a trend towards fewer taining peanut and hen’s egg can be introduced from around
infants randomised to the egg ingestion group being diag- 6 months of age and need not be differentiated from other
nosed with IgE mediated food allergy (33% vs. 51%, p = 0.11). solid foods [89]. It adds that families of infants with a history
The next study to report was the LEAP (Learning Early About of early‐onset eczema or suspected food allergy may wish to
Peanut Allergy) study, which enrolled 530 high risk infants seek medical advice before introducing these foods. A joint
with moderate/severe eczema and/or egg allergy aged 4–11 statement from the British Society of Allergy and Clinical
months [83]. They demonstrated that in infants randomised Immunology (BSACI) and the British Dietetic Association
to open‐label peanut consumption, 1.9% had peanut allergy (BDA) builds on this advice, addressing the numerous issues
determined by double‐blind placebo‐controlled challenge at associated with making feeding recommendations for allergy
age 5 years compared with 13.7% in the control group who prevention [90]. Ideally, the statement should be read in its
avoided peanuts (p < 0.001). Mean age of peanut introduction entirety for full understanding of all the relevant issues.
was 7.9 months. A follow‐up to the LEAP study (‘LEAP‐On’ However, its main recommendations are that infants in the
Study) suggested that early introduction of peanut into the general population should be exclusively breastfed for
diet may induce long‐term tolerance [84]. around the first 6 months of life with complementary foods
The EAT (Enquiring About Tolerance) study focused on the (including allergenic foods) introduced in an age‐appropriate
early introduction of 6 common food allergens into the diet of manner from around 6 months, alongside continued breast-
1303 breastfed 3‐month‐old infants recruited from a general feeding. For high risk infants with eczema (particularly early‐
(not high risk) population [85]. In an intention‐to‐treat analy- onset or moderate/severe eczema), egg and peanut can be
sis, 7.1% of the standard introduction group and 5.6% of the introduced from 4 months, but the decision on whether this
early introduction group developed food allergy to one or should be done under the care of the local allergy service
more of the six intervention foods (peanut, egg, cow’s milk, and/or after allergy testing needs to be made on an individ-
sesame, white fish and wheat) up to 3 years of age (p = 0.32). ual basis, considering the local allergy resources available.
342 Prevention of Food Allergy
Dietary micronutrients pregnancy (5 trials), lactation (2 trials) or both (1 trial). The

authors concluded ‘there is limited evidence to support
A different explanation for the observed relationship maternal n‐3 LCPUFA supplementation during pregnancy
between delaying the introduction of allergenic foods and and/or lactation for reducing allergic disease in children’
allergy development is that delayed introduction may lead [108]. Further intervention studies are required to identify
to a nutrient difference in the infant diet that has an effect on protective effects and their persistence, but in the meantime
allergy development. For example, two papers have reported encouraging mothers to eat the recommended two portions
an association between the delayed introduction of egg into of oily fish a week [109] appears sensible.
an infant’s diet and increased allergy risk [81, 91]. This asso-
ciation may not be due to the timing of egg into the diet Vitamins and minerals
per se, but the fact that delaying the introduction of egg may
lead to a diet with lower levels of immunologically active A number of vitamins and minerals are thought to have a
nutrients, namely, vitamins A and D, zinc and selenium. role in the development of allergic disease. The role of vita-
Additionally, there have been reports of an association min D in the development of allergy was first proposed in
between fish introduction into an infant’s diet and allergy 1999 [110]. Since then its role has been strongly debated, and
outcome, with early introduction reducing the risk of aller- while the first papers advocated that increased vitamin D
gic disease [92–94]. Again, this association may not be due to supplementation was the cause of rising allergy prevalence
delaying the introduction of the allergenic food (fish) into [111–113], others have since argued the protective effect of
the diet, but to a reduced intake of LCPUFAs, selenium, zinc vitamin D [114–118]. The VITALITY trial (NCT02112734) is
and vitamin D, all of which have a potential role in the aeti- currently looking at the impact of infant vitamin D supple-
ology of food allergy [95–98]. mentation on food allergy prevalence at 1 year.
Vitamins C and E have also been suggested to have a role
in allergy prevention. A recent review stated that although
Polyunsaturated fatty acids
the studies that had found a positive relationship between
these vitamins and allergy outcome were methodologically
Health concerns regarding the consumption of saturated
weak, the possible relationships warranted further investi-
fats [99] in the latter part of the twentieth century led to
gation [95]. There are studies looking at the relationship
an increase in LCPUFA consumption (particularly n‐6
between folate and allergic disease. Two studies have shown
LCPUFAs), and this increase has been causally linked to the
a positive relationship between increased folate intake and
increase in allergic diseases [100, 101]. This is backed by epi-
subsequent allergic disease [96, 119]. A third study looked at
demiological observations [102–105] and is mechanistically
serum folate and total IgE levels and demonstrated an
explained by the fact that LCPUFAs are precursors for eicos-
inverse association [120]. Since folate supplementation is
anoid inflammatory factors including prostaglandins (PG)
widely advocated for pregnant women to protect against
and leukotrienes (LT). Prostaglandins and leukotrienes such
neural tube defects, further research studies have been
as PGE2 and LTB4, derived from n‐6 LCPUFA (e.g. sunflower
urgently called for to investigate the relationship between
oil) via arachidonic acid (AA), strongly promote inflammatory
maternal folate intake and allergy development [121].
responses and play a role in allergic sensitisation. Conversely,
n‐3 LCPUFAs oppose the actions of n‐6 LCPUFAs, particu-
larly with regard to eicosanoid synthesis, leading to the pro- ‘Healthy’ diet
duction of the less biologically active prostaglandins and
leukotrienes such as PGE3 and LTB5 via eicosapentaenoic A change in diet to one that could be viewed as less healthy
acid (EPA) and docosahexaenoic acid (DHA) [106]. Thus, n‐3 has been hypothesised as a reason for the observed increase
PUFAs may protect against allergic sensitisation and allergic in the prevalence of asthma and allergic disease since the
manifestations. 1970s [99, 122]. Therefore, looking at the whole diet may be a
There have been a number of studies looking at maternal more effective way of establishing relationships between
fish oil supplementation and food allergy/eczema‐related dietary intake and allergic disease. Concerning the maternal
outcomes that showed differing results, perhaps due to differ- diet and allergy outcome, a meta‐analysis [95] concluded
ing doses and types of n‐3 LCPUFA given [106]. Additionally, that there was a (weak) protective effect of fruit and vegeta-
an intervention study of salmon supplementation during ble intake in the development of asthma and allergy and a
pregnancy showed no significant difference between the two weak protective effect of a ‘Mediterranean’ diet for asthma
groups for eczema prevalence or severity, in skin prick test outcome. Additional evidence pointing to the importance
positivity or in various allergic manifestations [107]. While a of a ‘full’ maternal diet in allergy prevention is emerging
meta‐analysis of n‐3 LCPUFA intake during pregnancy iden- [123, 124]. Consequently, recommending a healthy balanced
tified that maternal fish oil supplementation had positive out- maternal diet with sufficient portions of fruit, vegetable and
comes for eczema and sensitisation up to 12 months in the n‐3 fatty acids with no avoidance of any foods seems the sen-
offspring, it concluded that the effect of maternal n‐3 LCPUFA sible way forward. The benefits of a ‘healthy’ diet are also
intake on childhood allergies ‘could not be unequivocally applicable for the infant diet. Evidence suggests that an
confirmed or rejected’. Additionally, a Cochrane review infant diet consisting of high levels of fruits, vegetables and
looked at eight RCTs of n‐3 PUFA supplementation during home‐made foods is associated with less food allergy by the
Recommendations 343
age of 2 years [125]. This inverse association with processed guidance for infant feeding and allergy prevention guidance
foods has been observed elsewhere [126] and may be due to for parents [90].
the higher microbial load of home‐prepared foods compared
to commercially processed foods [127] or that home‐pre- For all infants:
pared fruits and vegetables are good sources of naturally
• Mothers should eat a healthy balanced diet with plenty
occurring prebiotics. Both are thought to modify immune
of fruit and vegetables during pregnancy and lactation.
function [128].
Do not avoid any particular foods, e.g. peanuts
• Omega‐3 fatty acids taken during pregnancy and lacta-
Prebiotics and probiotics tion may help reduce the risk of eczema and allergic sen-
sitisation. (Do not eat more than two portions of oily fish
Intestinal microbiota play an important role in the develop- a week)
ment of the mucosal and systemic immune system [129]. • Ideally, breastfeeding should be the sole source of nutri-
Observational studies show both quantitative and qualitative tion until around the age of 6 months
differences in gut microbiota composition between atopic • Standard cow’s milk formula should not be given for the
and non‐atopic infants, with decreased populations of benefi- first 4–6 months unless the child has other forms of cow’s
cial bacteria (bifidobacteria, bacteroides, lactobacilli) and milk in their diet
higher numbers of coliforms and Staphylococcus aureus [130] • Other infant formulas should not be given unless pre-
in atopic infants; since these differences already exist in the scribed by your GP. They have not consistently shown to
first few weeks of life, a causal relationship is suggested [131– reduce the risk of allergy development
133]. Lower consumption of prebiotics (fibre/indigestible • Weaning should never commence before the age of 17
dietary components) are suggested to lead to less favourable weeks and ideally not before 6 months of age. Once
colonisation patterns, which may be implicated in the loss or weaning has become established with traditional wean-
inability to develop oral tolerance. Neonatal prebiotic supple- ing foods, then the introduction of high allergenic foods
mentation trials have failed to show any effect of prebiotics can begin
on food allergy development, but have shown favourable • Weaning foods should ideally be introduced while an
results on other allergic outcomes such as eczema [134]. infant is still being breastfed
Consequently, manipulating the intestinal microflora of • All babies (including those exclusively breastfed) should
atopic children, using pre‐ and probiotics, towards a more receive a vitamin D supplement containing 8.5–10 μg of
‘non‐atopic flora’ could be a way to prevent allergic diseases. vitamin D
There have been a number of trials to investigate the abil- • By the age of 12 months, all the major allergenic foods,
ity of probiotics to prevent allergic disease in high risk which would normally be suitable for a child of this age,
infants, but these studies have mainly focused on atopic der- should have been introduced into the diet
matitis and not on food allergy and have conflicting results • Delayed weaning, beyond 6 months, could adversely
[135–139]. These findings need to be repeated in similar affect the normal dietary and developmental milestones
studies using more readily available probiotics before moth- essential to establishing a good varied diet and may
ers are advised to take probiotics during pregnancy. The increase the risk of allergy development
most up‐to‐date Cochrane review on the subject states that
further research is needed before probiotic use can be recom- Additionally for babies with moderate to severe eczema:
mended for allergy prevention [140]. However, a World
Allergy Organization (WAO) systematic review has sug- • It may be beneficial to introduce peanut and/or egg into
gested using probiotics in infants at high risk of allergy due the infant’s diet before 6 months. Individual advice
to the ‘likely net benefit’ from the prevention of eczema seen should be sought from a healthcare professional
with their use [141]. The guideline panel did, however, • When allergenic foods such as wheat, egg and milk are
acknowledge that their recommendation was supported by introduced into the diet, each food category*1should be
very low quality evidence, demonstrating a need for high introduced singly, starting with a small amount, e.g. ½
quality intervention trials. There are a number of these ongo- teaspoon (2.5 mL). No more than one new allergenic food
ing that may provide further insight in the future. These group should be introduced at a time
studies will also provide information on which strains may
be the most effective for allergy prevention and what dose is
required as these are important factors to consider and about
which there is currently very little information. * Food category: for example, introduce wheat as one category by
giving pasta, bread and other suitable wheat-based products over
a 2- to 3-day period [90].
Recommendations
Although more research is needed in order to offer definitive

allergy prevention advice, a number of recommendations
can be made from the existing evidence base. The following
recommendations are from the joint BSACI and BDA
17 Ketogenic Diets
Julia Ackrill, Vanessa Appleyard and Victoria Whiteley
Introduction Disorders of brain energy metabolism
The ketogenic diet (KD) is a high fat low carbohydrate diet, with KDT is recommended as the first choice of treatment for two
adequate protein content, which has been used for the treat- disorders of brain energy metabolism: glucose transporter 1
ment of severe medically refractory epilepsy since the 1920s [1]. deficiency syndrome (GLUT1DS) and pyruvate dehydroge-
It was designed to mimic the metabolic effects of starva- nase deficiency (PDHD) [8]. The KD produces ketone bod-
tion, with ketone bodies (acetoacetate and beta‐hydroxybu- ies to bypass the metabolic defect, and they provide an
tyrate) becoming the main fuel source for the brain, following alternative energy source for the brain.
reports of the successful treatment of severe epilepsy by fast-
ing. The diet was widely used during the 1930s but fell out of
favour during the 1940s and 1950s when new anti‐epileptic Glucose transporter 1 deficiency syndrome
drugs (AEDs) became available as the diet was then thought
to be too rigid and difficult compared with medication. Glucose transporter 1 (GLUT1) is a glycoprotein that facili-
However, over the past 15–20 years, the use of the KD has tates transport of glucose across the blood–brain barrier to
expanded considerably worldwide [2] with the increase in the brain. In GLUT1DS this process is impaired, resulting in
clinical evidence of its effectiveness. insufficient glucose supply to the brain [9]. The classic phe-
Approximately 600 000 people in the UK have a diagnosis notype presents in infancy as early onset seizures and is
of epilepsy with the incidence in children being approxi- often associated with a complex movement disorder and
mately 1 in 240 [3]. Around 60% will be controlled on mono- developmental delay [10]. However, GLUT1DS is now rec-
therapy, usually with the first or second AED chosen, with ognised as showing wide phenotypic diversity ranging from
the remaining 30%–40% being difficult to control [4]. Brodie mild impairment to severe disability, with or without epi-
found only 11% of patients with inadequate control on the lepsy [10, 11]. As the condition was only described as recently
first AED later became seizure‐free. Therefore, with approxi- as 1991 [9], the disease course remains unclear. Epilepsy
mately a third of cases not responding to anti‐epileptic medi- appears to diminish, but paroxysmal exertional dyskinesia
cation [5], alternative treatments are required. The 2012 (PED), which responds to KDT, has been described in ado-
National Institute for Health and Care Excellence guidelines lescence and adulthood [12, 13].
[6] state that children and young people with epilepsy whose It is recommended that KDT should be started early [9,
seizures have not responded to appropriate AEDs should be 14–16] as GLUT1DS is a treatable disorder with the majority
referred to a tertiary paediatric epilepsy specialist to be con- of patients treated with KDT showing a significant reduction
sidered for ketogenic diet therapy (KDT). Since then the in seizures (67% achieving seizure freedom) and reducing
number of patients in the UK treated with KDT for epilepsy severity of movement disorder [11, 15], and it is further rec-
has increased considerably. In 2010 there were 28 centres in ommended that the diet should be continued until at least
the UK offering KDT, treating 152 patients. This increased to adolescence to meet the increasing energy demands of the
39 centres, treating 754 patients in 2017, with 267 patients on developing brain [10]. It remains to be seen whether there is
waiting lists to start KDT [7]. benefit in following the diet lifelong. It may be prudent to

Types of Ketogenic Diet 345
avoid caffeine in those affected by GLUT1DS, as it is known anti‐seizure effects of ketone bodies [25, 26]. However,
to down regulate GLUT1 in vitro [17]. whether ketone bodies themselves have a direct effect on sei-
Triheptanoin (C7) is an artificial ester that has been theo- zure control or whether they are merely a marker of a shift in
rised as a treatment for GLUT1DS, but it is currently only metabolism remains unclear.
being used in clinical research [18, 19]. Triheptanoin has an One of the more popular hypotheses for KD action
odd number of fatty acids, so it can provide ketone bodies involves γ‐aminobutyric acid (GABA), the major inhibitory
that cross the blood–brain barrier and also replenish the tri- neurotransmitter in the mammalian brain. Yudkoff et al. pro-
carboxylic acid (TCA) cycle by providing the intermediate posed that ketosis induces major shifts in brain amino acid
substrate pyruvate (a process known as anapleurosis). handling, favouring the production of GABA, which in turn
dampens hyperexcitability throughout the brain [27]. Several
studies support this possibility [28, 29].
Pyruvate dehydrogenase deficiency
Failure to meet energy needs may also contribute to initia-
tion and spread of epileptic activity. Another key feature of
In PDHD pyruvate cannot be metabolised into acetyl‐CoA,
the KD is a relative reduction in glycolysis and an increase in
resulting in a mitochondrial disorder with lactic acidosis,
non‐glucose sources of fuel through the oxidation of fatty
seizures and severe encephalopathy. Ketones bypass the
acids and ketone bodies, which ultimately feed through
enzyme defect providing an alternative source of acetyl‐CoA
the TCA cycle through a process known as anapleurosis.
and thus normalising blood lactate levels. KDT has been
Glycolytic restriction is thought to be an important mecha-
shown to be effective at prolonging life in PDHD and may
nism mediating the anti‐seizure properties of the KD [30].
improve neurodevelopment, especially if initiated early [20,
It would seem that multiple mechanisms including the
21]. However, as PDHD is a degenerative disorder, it is dif-
production of ketone bodies, decrease of glucose and reactive
ficult to monitor effectiveness of KDT, particularly if seizures
oxygen species and increase in adenosine triphosphate, cre-
are absent. Some families may decline KDT, as in this condi-
atinine and GABA levels may contribute to the anti‐convul-
tion KDT may be considered ‘life‐extending, but not improv-
sive effect of the KD [31]. Further studies on the mechanisms
ing quality of life’. The International Ketogenic Diet Study
of action are needed and could help determine which specific
Group supports any parents making this decision for their
seizure types or syndromes respond better to KDT [32].
child [8]. Weber [22] suggests it may be more appropriate to
avoid excessive carbohydrate (CHO) intake in this condi-
tion, rather than following a true KD.
Learning points: mode of action
The principles of introducing and monitoring KDT in both
GLUT1DS and PDHD are the same as in the population
• The mechanism of the KD remains unknown
being treated for epilepsy, but consideration as to the type of
• It would seem multiple mechanisms exist that contribute to
KDT in these conditions may be different and is discussed
anti‐convulsive effect of KDT
later in this chapter.
• More research is needed in this area
Learning points: disorders of brain energy metabolism
• KDT is first‐line treatment for both GLUT1DS and Types of ketogenic diet
PDHD – the ketone bodies produced act as an alternative
energy source by bypassing the metabolic defect Several different forms of the diet have been developed.
• GLUT1DS shows wide phenotypic diversity – seizure There are four specific diet protocols: the traditional classical
control and improvement in PED have been demonstrated ketogenic diet (CKD), the medium chain triglyceride (MCT)
on KDT diet; the low glycaemic index treatment (LGIT) and the mod-
• PDHD is a degenerative disorder and the benefit of KDT is ified Atkins diet (MAD). Increasingly in the UK, modified
not always measurable versions of the KD are being used, but protocols are indi-
vidual to the KD centres.
The CKD is the traditional form of the diet and is largely
unchanged from the original described by Wilder in 1921 [1].
Mode of action of the ketogenic diet It is based on a ratio of fat to protein and CHO, usually in the
range of 2:1 to 4:1, i.e. 2–4 g fat to every 1 g of protein and
Research into the mechanism of the KD has greatly increased; CHO combined. Fat is provided as long chain triglycerides
however despite this, the anti‐epileptic mechanism of KDT (LCTs), protein is adequate for growth and CHO is minimal.
remains an ‘enigma’ [23]. A few hypotheses are outlined Each meal needs to be carefully weighed and calculated.
below. The MCT diet was developed by Huttenlocher et al. in
The anti‐seizure effect of ketone bodies was first demon- 1971 [33]. As MCT fat produces more ketones per gram than
strated by Keith in the 1930s. Acetoacetate was shown to LCT, this allows for a more generous allowance of CHO and
protect against thujone‐induced seizures in rabbits [24]. This protein in the diet. The MCT diet has been shown to be
was followed decades later by two studies showing in vivo equally effective as the CKD [34].
346 Ketogenic Diets
The LGIT was developed by Pfeifer and Thiele in 2005 [35] Table 17.1 Conditions for which ketogenic diet has been reported
following observations that children on the CKD have stable to have 20% above the norm* efficacy rates [8].
blood glucose levels and that this may in part relate to the
Angelman syndrome
mechanism of the diet. The LGIT allows approximately
Complex 1 mitochondrial disorders
40–60 g CHO per day but regulates the type to those with a Dravet syndrome
glycaemic index <50. The LGIT has been shown to be effica- Doose syndrome
cious both as a first dietary treatment and as a way of liber- Glucose transporter 1 deficiency syndrome (GLUT1DS)
alising the KD [36]. It is not widely used in the UK. Febrile infection‐related epilepsy syndrome (FIRES)
The MAD was originally designed and investigated at Solely formula‐fed children or infants
Infantile spasms
Johns Hopkins Hospital and has been shown to be similar in
Ohtahara syndrome
efficacy to the CKD [2]. It was first formally referred to as Pyruvate dehydrogenase deficiency (PDHD)
MAD in 2006 to distinguish it from the Atkins diet used for Super‐refractory status epilepticus
weight loss [37]. While CHO must be measured, fat, protein, Tuberous sclerosis complex
calories and fluids are allowed freely, thus making meal
planning easier and, therefore, more tolerable. * Norm being 40%–50% chance of 50% reduction in seizures.
In the UK a broad spectrum of modified ketogenic diets
(MKD) are increasingly being used in clinical practice, which Table 17.2 Conditions for which ketogenic diet has been reported
lie somewhere between the CKD and the MAD [38]. to be effective, but with no more than 40%–50% responder rates [8].
Adenylosuccinate lyase deficiency (LSD)

Learning points: types of ketogenic diet CDKL5 encephalopathy
Childhood absence epilepsy
• There are four specific KDT protocols: CKD, MCT, LGIT Cortical malformations
Epilepsy of infancy with migrating focal seizures
and MAD
Epileptic encephalopathy with continuous spike and wave during sleep
• Modified ketogenic diets are increasingly being used in the Glycogenosis type V
UK; protocols are individualised Juvenile myoclonic epilepsy
Lafora body disease
Landau–Kleffner syndrome
Lennox–Gastaut syndrome
Efficacy of the ketogenic diet Phosphofructokinase deficiency
Rett syndrome
There is a large clinical database of evidence on the efficacy Subacute sclerosing panencephalitis (SSPE)
of the KD. A 2018 Cochrane review looked at the evidence
for the efficacy of the KD from 11 randomised control trials
(RCTs) [32]. All studies examined the efficacy of the KD in in particular for conditions where at least a 20% improve-
children apart from one [39], which looked at efficacy of the ment in efficacy above the norm has been consistently dem-
MAD KD in adults. onstrated, i.e. 60%–70% responder rates (Table 17.1).
Seizure reduction rates (>50% reduction) ranged from 38% The KD is first‐line treatment for two metabolic disorders:
in children following the CKD and MCT KD in one study GLUT1DS and PDHD (p. 344). Other conditions for which
[34], up to 60% in children following MAD [40] and 85% in the International Ketogenic Diet Study Group reports KD as
children following classical KD in a further study [41]. being effective in, but with no more than 40%–50% responder
Interestingly, one study [42] found no overall difference in rates, are shown in Table 17.2.
seizure reduction rates between those following classical KD
and those following MAD.
Learning points: indications
Seizure freedom rates were found to be as high as 25% in
a study of efficacy of MAD in children [42] and as high as
• The KD should be considered in children with complex epi-
55% in a classical 4:1 KD study [41]. The review highlighted
lepsy that has not responded to two anti‐epileptic
the paucity of evidence for the use of KDT in adults and
medications
infants and recommended that further studies are needed in
• The KD is first‐line treatment for two metabolic disorders:
these groups [32].
GLUT1DS and PDHD
Indications
NICE recommends that the KD should be considered in chil- Contraindications and pre‐diet screening
dren with complex epilepsy that has not responded to two
anti‐epileptic medications [6]. The 2018 International A pre‐diet clinic assessment with a consultant neurologist is
Ketogenic Diet Study Group recommendations [8] suggest essential to establish that a diagnosis of epilepsy has been
that the diet should be used early in the course of treatment, made and if it has been optimally treated to date, including
Nutritional Assessment and Considerations 347
Table 17.3 Disorders where ketogenic diet is contraindicated [8].

Learning point: contraindications
Carnitine deficiency (primary)
Carnitine palmitoyltransferase (CPT) or II deficiency • Pre‐diet screening, including baseline bloods, is essential to
Carnitine translocase deficiency rule out pre‐existing metabolic conditions and to uncover
Beta‐oxidation defects
potential complicating factors
Medium chain acyl dehydrogenase deficiency (MCAD)
Long chain acyl dehydrogenase deficiency (LCAD)
Short chain acyl dehydrogenase deficiency (SCAD)
Long chain 3‐hydroxyacyl‐CoA deficiency Nutritional assessment and considerations
Pyruvate carboxylase deficiency
Porphyria
A detailed nutritional assessment is essential prior to com-
Source: Reproduced with permission of John Wiley & Sons. mencing KDT to assess suitability, nutritional status and
requirements and also to assess which type of KDT is most
appropriate. Table 17.5 shows the factors to consider in pre‐
Table 17.4 Baseline laboratory investigations [8]. diet dietetic assessment.
Complete blood count with platelets
Electrolytes including serum bicarbonate, total protein and calcium Energy requirements
Serum liver and kidney tests including albumin, urea and creatinine
Fasting lipid profile A detailed food diary together with growth history is neces-
Serum acyl carnitine profile sary to estimate energy requirements, particularly for those
Vitamin D on CKD, which may differ from those recommended for
Urine organic acids (if diagnosis unclear)
healthy children of the same age. Energy requirements for
Serum amino acids (if diagnosis unclear)
children with neurological disabilities are disease specific
Source: Reproduced with permission of John Wiley & Sons. and vary with the severity of their disability as well as their
mobility, the presence of feeding difficulties and the degree
of altered metabolism.
consideration of other treatments such as epilepsy surgery Calories have historically been restricted to 80%–90% of
or vagal nerve stimulation. the daily recommendations for age; however, this has not
The KD is contraindicated in several specific disorders been proven to be beneficial, and most centres do not rou-
(Table 17.3). KDT uses fat as the primary fuel source rather tinely calorie restrict [8]. The prescription should be regu-
than CHO. Therefore, if a child with a disorder of fat metab- larly monitored and adjusted based on evaluation of growth,
olism is placed on a KD or fasted, it could result in a devas- changes in level of activity, ketosis and seizure control, e.g. if
tating metabolic crisis. As such, it is essential that these seizure activity decreases mobility may increase and, there-
conditions are screened for prior to starting KDT. fore, energy requirements may increase.
It is important not only to rule out these metabolic con-
ditions but also to screen for other complicating factors, Protein requirements
which may require closer monitoring or consideration.
These include liver disease, severe gastro‐oesophageal reflux Adequate provision of dietary protein, vitamins and minerals
(GOR), familial hyperlipidaemia, review of medications (e.g. is mandatory when dietary intake is modified to obtain the
diuretics or medications that increase the risk of acidosis), desired growth rate [44]. Providing a minimum protein intake
constipation, cardiomyopathy, kidney stones and poor nutri-
tional status. It is also important to optimise clinical manage-
Table 17.5 Factors to consider in pre‐diet dietetic assessment.
ment prior to commencing KDT. For example, constipation
and GOR are common side effects of KDT; therefore, review- 3–4 day food diary/enteral feeding regimen if tube fed
ing management prior to commencing KDT will help to min- Weight, height, BMI and growth history
imise these adverse effects and, thus, optimise KDT. It is Head circumference in infants
particularly important to maintain a regular bowel habit as
Mobility
constipation can cause seizure activity to increase [43].
Food allergy/intolerance
A list of pre‐diet screening investigations is listed in
Table 17.4. Food preferences
The International Ketogenic Study Group recommends Behavioural feeding difficulties
that blood tests should be done every 3 months during the Swallowing difficulties/texture of diet
first year on KD and then every 6–12 months thereafter and Fluid intake/thickened fluids – consider carbohydrate content of
should include at least full blood count with platelets, liver thickeners and swap to suitable alternative where possible
and renal profiles, fasting lipid profile and serum calcium, History of GOR
vitamin D and magnesium levels. Other tests often carried Constipation
out include serum selenium and carnitine profiles and uri-
nary calcium and creatinine. BMI, body mass index; GOR, gastro‐oesophageal reflux.
348 Ketogenic Diets
of 1 g per kg body weight on KD has been shown to maintain important to assess parents’ and caregivers’ commitment to
nitrogen equilibrium and allow for growth [45]. However, the diet and that they are aware from the outset what is
rapidly growing younger children may require higher involved in terms of providing the diet, monitoring, side
amounts, whereas older children may not need as much. effects, length of trial and follow‐up. It is recommended
Protein requirements should be based on safe levels for that children should be reviewed after 1 month on KD and
growth. WHO/FAO/UNU has published minimal safe lev- that the diet should be followed for at least a 3‐month
els of protein intake [46] (Table 28.48). period before considering whether it is efficacious or
whether the diet should be discontinued [8]. If deemed effi-
cacious at the end of the 3 month trial, there should be regu-
Fluid
lar review of benefit, tolerability and side effects at clinic
appointments. At the authors’ centres, patients are reviewed
Historically fluid has been restricted; however, this is no
every 3 months in alternate joint neurologist/dietitian and
longer deemed to be necessary [47]. Normal fluid require-
nurse/dietitian clinics. Consideration of weaning off the
ments should be encouraged, and if intakes are low on pre‐
diet should be given after 2 years on the diet. There are
diet assessment, intake should be increased to help minimise
some conditions where this period may be increased, e.g.
the risk of renal stones developing [47] and also help in the
GLUT1DS and PDHD, or shortened, e.g. infantile spasms.
prevention and management of constipation.
Discontinuation of diet is described on p. 369.
Food allergy and restrictions

Learning points: parental expectations and follow‐up
In the case of food allergy, it is first important to ensure the
correct diagnosis has been made and that the food does
• Parental expectations should be discussed in advance
indeed need to be excluded. The KD can be adjusted to accom-
• KDT should be followed for at least a 3‐month period before
modate dietary restrictions and allergies; however, it needs to
considering whether the diet is efficacious or discontinuing
be assessed case by case as further dietary restriction on top of
the diet
an already restricted diet may make the KD impractical.
• Consideration of weaning off the diet should be given after
2 years on the diet; there are some conditions where this
Feeding difficulties period may be increased or shortened
Behavioural feeding problems such as food refusal, selective

eating and physical feeding difficulties including difficulties
chewing and swallowing, increased aspiration risk and pro-
longed feeding times are commonly found in children with
Setting for initiation of ketogenic diet
neurological disability. In the authors’ experience, it is
The traditional method of initiating the KD involved a
important these issues are identified and the appropriate
period of fasting (12–24 hours), which required hospital
treatment/referral made before the KD is initiated; if enteral
admission for monitoring. However, it is now widely
feeding is required, this should be established before KDT is
accepted that this is no longer necessary [2] and that a
commenced.
gradual initiation has been found to result in better toler-
ance and fewer adverse effects while maintaining the effi-
Learning points: nutritional considerations cacy of the diet [49]. This means KDT can be initiated at
home with the proper support of a dedicated team [2].
• A nutritional assessment is essential prior to commencing Fasting may lead to a quicker onset of seizure reduction
KDT and, therefore, may be advantageous when a more imme-
• Feeding difficulties should be identified, and appropriate diate response is desired, e.g. in refractory status epilepti-
treatment/referral made before initiating KDT cus [8]. It is recommended that infants less than 12 months
• Calorie and fluid restriction is not necessary of age should be hospitalised to initiate KDT using a non‐
• Protein requirements should be based on safe levels for fasting protocol [50].
growth
• The KD prescription should be regularly reviewed
Learning points: setting for initiation of diet
Parental expectations and follow‐up • Fasting is no longer essential, so KDT can be safely initi-
ated at home with the proper support of a dedicated team
Parental expectation should be discussed in advance • Infants less than 12 months of age should be hospitalised to
regarding not only seizure reduction but also possible med- initiate KDT
ication reduction and cognitive improvement [48]. It is
Classical Ketogenic Diet 349
Classical ketogenic diet Meal planning
CKD is the traditional form of the diet with approximately Once the diet prescription has been calculated, some centres
90% calories coming from fat. It is calculated based on a in the UK use food choice lists for fat, protein and CHO
ratio of fat to protein and CHO based on a method first based on UK food composition tables [54] in order to prepare
described more than 90 years ago [45, 51]. Typically, ratios meal plans. However, these are not standardised, but are
range from 2:1 to 4:1, the higher the ratio indicating increased individual to each centre. Once families have been given
intensity of diet, e.g. 4:1 = 4 g fat to every 1 g of protein and training using this method, it has the advantage of giving
CHO combined. The amounts prescribed are based on indi- them greater flexibility and control over meal planning
vidual energy requirements. Fat, CHO and protein are care- rather than relying on their dietitian to calculate menu
fully calculated for each meal, and it is important that the changes. There are also a number of meal planning websites
whole prescription is consumed to optimise effectiveness of available (see Companion website, Useful addresses).
the diet. All meals and snacks must be in the same diet ratio, An example meal plan using a 4:1 ratio is shown in
so the relative proportions of fat, CHO and protein remain Table 17.7.
the same.
Free foods
Dietary units
Some centres provide families with a list of ‘free foods’ con-
A worked example of calculating the diet using the method
taining minimal amounts of CHO, which can be incorpo-
of dietary units as described by Kossoff et al. [52] is shown in
rated into the diet without being included in the CKD
Table 17.6. A dietary unit is calculated based on the calorie
prescription. They can help to make meal planning easier
content of fat being 9 kcal/g and protein and CHO being
and improve tolerability of the diet. However, this is not
4 kcal/g each in the chosen ratio, i.e. a dietary unit on 4:1
standard practice and is individual to KD centre. In addition,
ratio = (4 × 9 kcal) + (1 × 4 kcal) = 40 kcal.
the following foods may be allowed freely:
The diet is usually started at a lower ratio, e.g. 2:1, and
then gradually increased if needed to a 3:1 or 4:1 ratio • water, tea and coffee (without milk); at the authors’ centres,
depending on tolerance, level of ketosis and seizure control. sugar‐free squash is allowed providing it contains <0.7 g
It is not always necessary to increase to 4:1 ratio if good sei- CHO per 100 mL undiluted, and fizzy drinks/flavoured
zure control can be achieved on a lower ratio. waters providing they contain <0.3 g CHO per 100 mL
Table 17.6 Worked example of classical ketogenic diet using dietary units.
8‐year‐old boy in mainstream school, active and enjoys sports. A food diary estimates his intake = 1750 kcal/day. Weight = 25 kg. He has 3 main
meals, a snack after school and supper
Daily requirements Calories = 1750 kcal
Protein RNI = 28 g/day (minimum 1 g/kg/day = 25 g) [46]
Ratio 4:1
Dietary unit – based on ratio of 4:1 (9 kcal × 4) + (4 kcal × 1) = 40 kcal per dietary unit
Divide calorie requirements by number of calories in dietary unit 1750 ÷ 40 = 44 units daily
Fat = number of units × ratio 44 × 4 = 176 g
Protein and carbohydrate = number of units × ratio 44 × 1 = 44 g
Protein = RNI or minimum 1 g/kg 28 g
CHO = number of units minus grams of protein 44 − 28 = 16 g
Daily prescription 176 g fat 28 g protein 16 g CHO = 4:1 ratio
Divide into 3 meals, 1 snack and supper Breakfast, lunch, evening meal
=45 g fat per meal, 6 g protein and 5 g CHO (4:1)

Snack
=16 g fat, 3 g protein, 1 g CHO (4:1)

Supper
=24 g fat, 5 g protein and 1 g CHO (4:1)

Total = 175 g fat, 26 g protein, 17 g CHO = 4:1 ratio 1747 kcal/day
RNI, reference nutrient intake [53]; CHO, carbohydrate.

350 Ketogenic Diets
Table 17.7 Example meal plan using a 4:1 ratio.

Learning points: classical ketogenic diet
CHO
Fat (to nearest Protein • It is based on a ratio of fat to protein and CHO, typically
(to nearest g) 0.5 g) (to nearest g) 2:1 to 4:1
• All meals and snacks must be in the same diet ratio
Breakfast – onion and tomato omelette
• The diet is usually started at a lower ratio and then gradu-
1 egg 5 g – 6 g
ally increased if needed
12 g butter 10 g – –
30 g double cream 16 g 0.5 g –
80 g raw tomatoes – 2.5 g –
25 g raw onion – 2 g – MCT ketogenic diet
14 mL oil 14 g – –
The medium chain triglyceride ketogenic diet (MCT KD) is
Total 45 g 5 g 6 g
an alternative to the classical KD and uses another source of
Lunch – tuna mayo salad fat, MCT, in place of a proportion of LCT. MCT metabolism
20 g tuna canned in oil, 1 g – 5 g produces more ketones per gram than LCT, due to several
drained factors: MCTs enter liver mitochondria faster [55, 56], are
30 g mayonnaise 22 g 0.5 g – metabolised preferentially rather than stored in adipose tis-
30 g cucumber – 0.5 g – sue and are promptly and efficiently oxidated to acetyl‐CoA
via β‐oxidation [57]. MCTs are converted to ketone bodies
32 g raw tomato – 1 g –
within 30 minutes of ingestion, and blood levels remain ele-
Pudding – strawberries and cream vated for up to 4 hours [58, 59], which make them a useful
40 g strawberries – 2.5 g – addition to KDT. These properties mean that less total fat is
41 g double cream 22 g 0.5 g 1 g required to achieve ketosis and a larger proportion of protein
and CHO can be included; this could improve compliance
Total 45 g 5 g 6 g
and palatability [33, 60].
Snack – cheese with cucumber sticks and mayo dip
60 g cucumber – 1 g –
Dietary prescription
16 g mayonnaise 12 g – –
12 g cheddar cheese 4 g – 3 g The original MCT KD provides 60% of total calories from MCT
Total 16 g 1 g 3 g [33], which in practice can lead to poor tolerance and gastroin-
testinal problems. A modified MCT diet was developed, using
Evening meal – minced beef and courgettes
30% of energy from MCT, with an additional 30% from LCT
25 g raw minced beef 4 g – 5 g [61], but poor ketosis was noted. In the 2009 RCT by Neal et al.
41 g oil 41 g – – [34], MCT KD was seen to be as effective as the CKD, using
56 g raw courgette (cut – 1 g 1 g levels of 40%–45% of total calories from MCT. This is now a
into thin strips then fried) common starting point, and MCT can be increased further if
26 g canned tomatoes – 1 g – ketosis is suboptimal and tolerance is good during the fine‐
tuning stage. The dietary prescription for the MCT KD is:
Pudding
70 g cantaloupe melon – 3 g – • 40%–45% calories from MCT
Total 45 g 5 g 6 g • 10% calories from protein (ensuring this meets WHO
lowest safe protein intake [46] (Table 28.48))
Supper – cheese and apple with sugar‐free jelly and Calogen • 10%–15% calories from CHO
12 g cheddar cheese 4 g – 3 g • 30%–40% calories from LCT
8 g apple – 1 g –
The energy content of MCT is uncertain. European Union
Sugar‐free jelly sachet – – 2 g (EU) labelling guidance requires that the value of 9 kcal/g is
40 mL Calogen 20 g – – used on product information, but studies state energy con-
Total 24 g 1 g 5 g tent to be between 7 and 9 kcal/g [62]. Multiple literature
sources suggest a value of 8.3 kcal/g, which is the value used
in common UK practice.
• salt, pepper, herbs and spices may be used to flavour meals Once the dietary prescription has been calculated for the
• some artificial sweeteners contain CHO and, therefore, day, this can be divided into meals and snacks to suit the
may be unsuitable, such as most sugar alcohols (e.g. child’s daily routine. Exchange or choice lists of fat (LCT)
maltitol, polyglycitol) or those containing maltodextrin (Table 17.8), CHO (Table 17.9) and protein (Table 17.10) [54]
• suitable sweeteners include aspartame, saccharine, foods are often used, and education is provided around the
sucralose, stevia, acesulfame K and erythritol MCT products available on prescription that need to be
Modified Atkins Diet 351
included at each meal and snack through the day. Prescribable reduced if the MCT is increased slowly over a period of 7–10
products are given in Table 17.17. A worked example of the days to the goal intake. MCT should be included in all meals
MCT KD is shown in Table 17.11. and snacks, and a supper time drink or snack containing MCT
will help to maintain ketosis overnight. All foods should be
weighed, and parents should be educated in reading labels as
Initiating the MCT KD
they will likely want to include foods not on the choice lists
MCT is known to cause gastrointestinal symptoms including that contain both protein and CHO, e.g. yoghurt and baked
abdominal cramping and discomfort, loose stools and diar- beans. There are several standard recipes provided by the feed
rhoea, nausea and vomiting [63]. These symptoms can be manufacturers who supply specialist food and drink products;
the charity, Matthew’s Friends, is also a source for recipes.
Table 17.8 Fat (LCT) choices. Families should be educated on how to adjust these to meet
their dietary targets. Full vitamin and mineral supplementa-
5 g fat choices tion should be advised to meet age‐related requirements.
Fine‐tuning of the diet is likely to be required as with any
6 g butter
KDT and could involve reducing CHO, increasing LCT or
5 g oil MCT depending on tolerance and ketosis. Some centres have
6 g mayonnaise adapted MCT KDT VW further and do not prescribe an
10 g double cream amount of protein, but advise modest intake, and have found
this works well and report improved compliance, although
efficacy of these modified KDT has not been researched.
Table 17.9 Carbohydrate choices.
1 g carbohydrate choices Learning points: MCT KD
8 g apple, eating, raw 31 g broccoli, raw • MCT is included to provide 40%–45% of total daily energy
7 g blueberries, raw 23 g cauliflower, raw • As MCT is more ketogenic, it allows for more CHO in the
13 g peaches, raw 43 g celeriac, raw diet, which may make the diet more palatable for school‐
aged children
22 g raspberries, raw 56 g courgette, raw
• MCT can cause intestinal discomfort, including diarrhoea
16 g strawberries, raw 6 g garlic, raw
and vomiting, so it needs to be introduced slowly
32 g tomatoes, raw 13 g onion, raw • MCT KD has comparable efficacy to CKD
26 g tomatoes, tinned 8 g tomato puree
5 g carbohydrate choices

Modified Atkins diet
14 g white rice, boiled
23 g spaghetti, boiled In 2003 the Johns Hopkins Hospital published a small case
29 g potatoes, old, boiled series of six children and adults with complex epilepsy who
8 g Ready Brek, raw were treated with a KD which was less restrictive than the
12 g wholemeal bread
CKD as it allowed free protein and calories [64]. This new
version of a KD was based on the well‐known ‘Atkins diet,’
Table 17.10 Protein choices (fat adjusted).
Each choice provides 6 g of protein and has been adjusted to ensure each contains 3 g of fat [54].
Food Amount to give 6 g protein Added fat required
White fish (cod, coley, haddock, plaice) 33 g raw or 29 g cooked (baked, poached, grilled or steamed) 3 g oil or 4 g butter or mayonnaise
Salmon 30 g raw or 29 g cooked (grilled or steamed)
Tuna, canned in oil 22 g
Ham 33 g 2 g oil or 3 g butter or mayonnaise
Bacon rashers, back 37 g raw or 26 g grilled
Cheddar cheese 24 g
Minced beef, lean meat 27 g raw weight or 20 g cooked
Chicken, light meat 25 g 3 g oil or 3 g butter or mayonnaise
Eggs 1 medium (approx. 50 g)
Table 17.11 Worked example for MCT ketogenic diet.
8‐year‐old boy in mainstream school, who enjoys sports, and parents report he is very active. His most recent weight is 25 kg. A food diary
estimates intake at 1750 kcal/day. He has three main meals per day, an after‐school snack and a supper. He enjoys toast and cereal
Dietary calculation
Proportion Amount Translation to dietary choices
MCT 45% 95 g

Protein 10% 44 g 7½ choices including 22.5 g fat
CHO 15% 65 g 65 g
LCT 30% 58 g 35 g (minus fat in protein) 7 × 5 g choices
MCT Protein CHO LCT
Breakfast 25 g 15 g 10 g

Lunch 25 g 3 choices 20 g 5 g
Snack 10 g 1 choice 5 g 5 g
Evening meal 25 g 3 choices 20 g 5 g
Supper 10 g ½ choice 5 g 10 g
Total 95 g 7½ choices 65 g 35 + 22.5 g from protein choices
45 g protein and 22.5 g fat 57.5 g
Menu
Breakfast – cereal MCT Protein CHO LCT
24 g Ready Brek 15 g

125 mL Betaquik 25 g
21 g double cream 10 g
Truvia sweetener –
Lunch – sandwich MCT Protein CHO LCT
48 g wholemeal bread 20 g

66 g ham with 6 g butter 2 choices 6 g
24 g Cheddar cheese 1 choice 3 g
6 g mayonnaise 5 g
50 mL Liquigen in sugar‐free jelly 50 g
Snack – cheese and fruit MCT Protein CHO LCT
24 g Cheddar cheese 1 choice

40 g apple slices 5 g
Milkshake with
50 mL Betaquik 10 g
Sugar‐free Da Vinci syrup
Evening meal – pasta and sauce MCT Protein CHO LCT
25 mL MCT oil 25 g

13 g onion 1 g
3 g garlic ½ g
4 g tomato puree ½ g
62 g minced beef 2 choices 6 g
68 g tomatoes, tinned 3 g
32 g boiled pasta 10 g
24 g Cheddar cheese, grated 1 choice 3 g
80 g strawberries 5 g
Supper – milky drink MCT Protein CHO LCT
50 mL Betaquik 10 g

100 mL semi‐skimmed milk ½ choice 5 g 1.5 g
Chocolate Da Vinci syrup
MCT, medium chain triglyceride; CHO, carbohydrate; LCT, long chain triglyceride.
Modified Atkins Diet 353
devised by Robert Atkins as a weight reduction programme restricted, and there is no initial fasting period, which at
[65]. The Johns Hopkins’ MAD differs from the original the time was often typical on the CKD, and so it became
Atkins diet in several ways, primarily because seizure con- possible to initiate the KD in an outpatient setting. The diet
trol, not weight loss, is the goal. In addition, the induction induces ketosis, although studies are contradictory as to
phase (during which CHO is restricted) is continued indefi- whether the level of ketosis correlates to the degree of effec-
nitely, and fat is encouraged (as opposed to just being tiveness [37, 66, 67].
allowed). This diet was first referred to as ‘modified Atkins A strict CHO limit is important during the first 3 months,
diet’ in a prospective trial, which showed that 65% children but a study by Kossoff et al. [40] suggests that it is possible to
had >50% seizure reduction [37]. A subsequent RCT sup- later ‘relax’ the CHO intake from an initial 10 g to 20 g while
ports the effectiveness and tolerability of MAD but rein- still maintaining seizure control. A ketogenic ‘shake’ drink
forces that although less restrictive, it does still have side given in the first month may also improve outcome [68].
effects and close medical supervision is required [5]. A sample menu plan for a modified Atkins diet is shown
The Johns Hopkins modified Atkins KD protocol restricts in Table 17.12.
CHO to 10 g/day in children aged 2–12 years and 15 g in
adolescents (but this can be increased to an adult intake of
20 g daily if adherence is difficult). CHO can be given
throughout the day or at one meal. Fibre is not counted in Learning points: modified Atkins ketogenic diet
the CHO allowance, but sugar alcohols are. A high fat
intake is mandatory, but unlike the CKD, fat is not counted • Modified Atkins diet is a protocol that specifies CHO intake
and protein is free. A ketogenic ratio is not calculated and (10–20 g/day depending on age) while freely allowing pro-
may, therefore, change from day to day. Examination of tein, and it does not specify fat intake
food diaries estimates an approximate ratio of fat to • It has been shown to be effective at reducing seizures in all
CHO + protein of 0.9:1 with 65% of calories provided by fat, age groups
in comparison with 90% in the CKD [40]. Calories are not
Table 17.12 Sample menu plan for modified Atkins diet.
Menu plan for an 8‐year‐old boy (10 g CHO per day) [54]
g CHO
Protein (excluding fibre) Fat
Breakfast – scrambled egg
2 eggs scrambled with butter Not counted 0 Not counted
40 g mushrooms (fried in oil) Not counted Trace –
Total Not counted Trace Not counted
Lunch – sandwich
2 slices low carbohydrate bread Not counted 6 Not counted
(3 g CHO per slice)
Ham and Cheddar cheese with butter Not counted 0 Not counted
Sugar‐free jelly with 50 mL Calogen Not counted 0 Not counted
Total Not counted 6 Not counted
Snack – cheese and celery
Cheddar cheese Not counted 0 Not counted
Celery (¼ stick) – Trace –
Evening meal – minced beef and courgette
Oil – 0 Not counted
13 g onion Not counted 1 Not counted
Garlic – – Not counted
Minced beef Not counted – Not counted
26 g tomatoes (canned) – 1 –
56 g courgette (cut into thin strips and boiled/fried) Not counted 1 Not counted
Cheddar cheese, grated Not counted – Not counted
16 g strawberries Not counted 1 –
Daily total Not counted 10 Not counted
CHO, carbohydrate.
Source: Courtesy of Royal Society of Chemistry.
354 Ketogenic Diets
Modified ketogenic diets with Angelman’s syndrome that five tolerated the diet well
and reported over 90% reduction in seizures, which is a
In UK practice, a broader spectrum of ‘modified ketogenic potentially higher degree of efficacy than in the general epi-
diets’ (MKD) has been described that refers to a KD, which lepsy population, despite the small study size [74]. In 15
does not use diet ratios (i.e. not CKD), but neither does it fol- patients with tuberous sclerosis complex, a prospective
low the MAD protocol. A survey of UK ketogenic practice in study found 47% of patients had a 50% improvement in sei-
2011 reported the use of ‘an adapted version of the MAD’ in zures [75], and multiple studies highlight that stabilised
seven of eight centres [69]. More recently, 40% of centres in the blood glucose, rather than ketosis, correlates with the
UK report using an MKD with no single definitive protocol improvement in seizures [73]. Ketone bodies may be meas-
[38]. Published studies are at present limited, but there is grow- ured on LGIT, but they are not a goal of LGIT; blood glucose
ing interest in research using MKD. A single‐centre study of is monitored to ensure stability within the normal range.
100 paediatric patients on MKD found 40% of children had a
>50% reduction in seizures with 16% showing a >90% reduc- Dietary prescription
tion in seizures after 3 months on diet [70]. This MKD protocol
did not prescribe calories and counted total CHO (with indi- The dietary prescription for LGIT is:
vidual CHO allowance being determined by ketone levels)
while fat and protein were freely allowed. A study of an MKD • 10% energy from low glycaemic index CHO (GI < 50–55),
in adults with epilepsy showed MKD to be tolerated and feasi- equating to 40–60 g/day
ble with ketosis achieved, but it did not examine effectiveness • 60% energy from fat
on seizure control [71]. This MKD protocol encouraged a fat • 30% energy from protein
intake of up to 70% of total energy and limited CHO to 20 g/ Foods are measured using household measures, and only
day. Protein was not restricted. Another small study in adults general estimates for quantities of fat and protein are given
has demonstrated effectiveness of an MKD on seizure control to families. Food choice lists can be adapted from those used
using 15–50 g net CHO/day [72]. The authors’ personal experi- in other dietary therapies, e.g. 10 g fat choices, which may
ence and feedback from other UK centres confirms the effec- help to give a guide to families on how much fat is required.
tiveness of MKD and their increasing use in clinical practice. It should be advised that fat should always be included in a
meal or snack containing CHO, e.g. fruit and cream, to fur-
Learning points: modified ketogenic diets ther reduce the GI and aim to avoid peaks in blood glucose
level. Education on CHO sources should be given with refer-
• There is no set modified ketogenic diet protocol – the term ence to label reading, considering low CHO products that
refers to any ketogenic diet, which produces ketosis, but may be sourced over the internet, perhaps from the USA.
does not follow the protocols of either the classical ketogenic Full vitamin and mineral supplementation is still required
diet, MCT diet or modified Atkins diet as with other KDT, and regular follow‐up, including blood
• Modified ketogenic diets are used effectively in clinical and urine monitoring and anthropometry, must be provided.
practice in many ketogenic centres in the UK As with other KDs, fine‐tuning may be necessary, and this
could include reduction in CHO or reduction in protein to
allow for a higher fat intake.
LGIT is used more in the USA and India, with only a few cen-
Low glycaemic index treatment
tres offering this KD therapy in the UK. From experience, the
authors have found that a further restriction on the type of CHO,
The LGIT was developed at Massachusetts General Hospital
not just the quantity, has discouraged its use with families.
in 2002 [35] as an alternative to the CKD. The authors theo-
An example meal calculation is given in Table 17.13.
rised that as it has been noted that blood glucose levels are
stable in those following a KD and that there can be increased
seizure activity associated with high CHO loads in this Learning points: LGIT
group, then a more liberalised diet increasing CHO content,
but ensuring that it is all sourced from low glycaemic index • Carbohydrate from low GI sources (<50–55)
(LGI) foods, may have a similar effect to KDT. • 10% energy from LGI carbohydrates
Several studies have documented that LGIT is associated • Use household measures and encourage fat intake
with reduced seizure frequency [35, 36, 73–75]. It has been • Ketosis is not a goal of LGIT
successful in both focal and generalised seizure types, and
the retrospective study in 2005 demonstrated that 73% of
patients had at least 50% improvement in seizures, with a
third becoming seizure‐free [35]. More recent studies [73, 74] Which ketogenic diet to use?
found similar efficacy with 66% and 53% of patients having
at least 50% improvement in seizures. There are four KDTs, which have been described by a pro-
The use of LGIT in some genetic disorders has also showed tocol specifying the quantities of specific macronutrients;
efficacy. Thibert noted in a prospective study of six children these are summarised in Table 17.14. The MKD is not a
Which Ketogenic Diet to Use? 355
Table 17.13 Example meal calculation for low glycaemic index allow flexibility, with modified versions of the KD being
treatment [54]. widely used [38].
8‐year‐old boy with estimated calorie requirements of 1725 kcal/day,
The CKD is, by default, used when liquid tube feeding is
following assessment of 3‐day food diary and growth history required and is generally the first‐line method of feeding in
10% of energy from CHO = 40–50 g low GI foods status epilepticus where rapid seizure control is required
60% energy from fat = 115 g (not routinely measured, but encouraged and a 4:1 starting ratio is often used [84–86]. The MAD has
liberally) been successfully used in a case report of status epilepticus
30% energy from protein = 130 g (not routinely measured) [87]. The CKD is recommended in international guidelines
for infants under 2 years of age [8, 50]. The MAD has suc-
Breakfast
cessfully been used in this age group [88–90]; however, Kim
Omelette – 2 eggs, 2 tablespoons of double cream, 1 teaspoon of butter
and grated cheese
et al. [42] found the CKD more effective in a group of patients
less than 2 years of age with 53% showing a significant
2 rashers of bacon fried in oil
response on the CKD compared with 20% on the MAD.
1 slice of low CHO bread (10 g CHO) with butter
The MAD is considered less restrictive and so may be pre-
Lunch ferred in adolescents and adults in whom it has shown to be
Low CHO wrap (6 g CHO) with grilled chicken breast, 1 tablespoon of effective [91, 92]. It has also been suggested that MAD may
mayonnaise, grated cheese and lettuce
have a role in developing countries with fewer dietetic
5 strawberries (5 g CHO) with mascarpone
resources [93] and remote treatment in adults [94]. For
Evening meal patients who require longer‐term use of KDT (i.e. disorders
Fried steak with mushroom and cream sauce served with 4 tablespoons of brain energy metabolism and in those who are either
of green beans (2.5 g CHO) and 3 tablespoons of carrots (2.5 g CHO) reluctant or unable to wean off the diet after 2 years of treat-
Chopped peach (10 g CHO) with 2 tablespoons of double cream ment), a switch to MAD may be considered if adherence
Supper becomes an issue. It is also hypothesised that MAD may
Hot chocolate made with 100 mL semi‐skimmed milk (5 g CHO) and have milder side effects, but this has not been proven [78].
cocoa powder, sweetened with liquid Hermesetas sweetener and Switching from the MAD to the more prescriptive CKD
topped with double cream may improve seizure control in one third of patients who
Total intake CHO = 41 g have already responded to the MAD (especially for those
children with myoclonic atonic epilepsy). However, if the
CHO, carbohydrate; GI glycaemic index.
child has not responded to the MAD, then there appears to
be no benefit in swapping to the CKD [95]. As calories are
single protocol, but rather a spectrum of KDs. There are few controlled with CKD, it may be preferred for those patients
studies that directly compare the effectiveness of these vari- where weight gain or loss is a concern.
ous diets. Variations in diet protocols make it difficult to Studies have shown it is possible to transition from the
accurately compare outcomes between studies, with differ- CKD or MCT diet to a less restrictive MAD without an
ent ratios or CHO allowances being used, with or without increase in seizures [77, 76, 96].
calorie restriction or an initial fasting period [42, 76]. The In GLUT1DS ketones provide fuel for the developing
efficacy of CKD and MAD when the diet is eaten (rather brain. Cerebral glucose utilisation has been shown to increase
than being delivered by tube feed) seems to be very similar linearly after birth, with the brain of a 4‐year‐old metabolis-
[77–80]. A randomised study by Kim et al. [42] found no ing twice as much glucose as an adult; glucose consumption
significant difference in outcome between groups ran- gradually decreases in adolescence [97]. It is recommended
domised to CKD or (a calorie restricted) MAD, although that in infants and preschool children, the CKD should be
MAD was better tolerated with less side effects. The CKD the first choice of diet, and, if tolerated, it should be main-
and MAD have been described as ‘complementary and not tained as long as possible [50, 98]. The MCT diet has also
competing’ [81]. been reported as successful in a GLUT1DS case study [76]. A
A lower (2.5:1) ketogenic ratio may be just as effective as a survey by Kass et al. [16] found that a similar percentage of
higher (4:1 ratio) in the CKD [82]. A randomised trial by Neal children with GLUT1DS were seizure‐free on CKD/MCT
et al. [34] showed CKD and MCT KDs to be comparable. The compared with MAD/LGIT (74% vs. 63%), and it has also
CKD delivered in liquid form appears to be more effective been shown that seizures can be well controlled with a low
than oral CKD or MAD, which may be expected as there is (2:1) ratio CKD [82]. A clinical benefit has been seen even
less risk of diet miscalculation or indiscretion [67, 83]. There with only mild ketosis in the GLUT1DS population [12, 76].
are no studies directly comparing LGIT or modified versions However, the long‐term effects of GLUT1DS are as yet
of the KD with the other KDTs. unclear, and it may be that seizure control is not the only
The International Ketogenic Diet Study Group concluded marker of disease course, with the relationship between
that ‘the specific ketogenic diet therapy chosen should be ketosis and neurodevelopment still to be established. A less
individualized based on the family and child situation, restrictive KD has also been reported successful in a case
rather than perceived efficacy, together with the expertise of study with PDHD [99]. The LGIT is not recommended for
the ketogenic diet center’ [8]. In UK practice, dietitians are treatment of disorders of brain metabolism as it does not
evolving the KD to suit their patients’ individual needs and provide ketones [98].
356 Ketogenic Diets
Table 17.14 Comparison of four specific ketogenic diet therapy protocols.
Classical ketogenic diet MCT diet Modified Atkins diet Low glycaemic index treatment Modified ketogenic diet
Date first described 1921 [1] 1971 [33] 2003 [64] 2005 [35] 2012 [69]
Ketogenic ratio 2:1 to 4:1 No set ratio (approx. 1.2 to 1.6:1) No set ratio (approx. 1:1) No No
Fats prescribed Yes Yes No No Maybe
Depends on ratio 4:1 approx. 40%–45% total calories from MCT and Depends on individual
90% total calories 30%–40% from LCT centre’s practice
Carbohydrates Yes Yes Yes Yes 40–60 g/day Yes
prescribed Depends on ratio and protein 10%–15% total calories 10–20 g/day depending
requirements on age
Protein prescription Yes Yes No No Maybe
Depends on age requirements Approx. 10% total calories Depends on individual
approx. 1–1.5 g/kg centre’s practice
Ketosis goal Yes Yes Yes No Yes
Type of carbohydrates No No No Yes No
specified GI < 50–55
Initiation setting Historically inpatient Historically inpatient Outpatient Outpatient Outpatient
Multivitamin/mineral Yes Yes Yes Yes Yes
prescribed
Age range All All All All All
Preferred choice in infants May be helpful in adolescents/adults as May allow more May be helpful in adolescents/
<2 years of age it allows increased carbohydrate intake flexibility in adolescents/ adults as it allows increased
adults carbohydrate intake
Use recommended in Yes Yes Yes No Yes
GLUT1DS/PDHD?
MCT, medium chain triglyceride; LCT, long chain triglyceride; GI, glycaemic index; GLUT1DS, glucose transporter 1 deficiency syndrome; PDHD, pyruvate dehydrogenase deficiency.
Management of the Diet 357
to lack of insulin and hyperglycaemia). Symptoms of hyper-

Learning points: which KDT to choose?
ketosis include facial flushing, rapid breathing and increased
heart rate, nausea and vomiting, lethargy and irritability.
• All four main KDT protocols have been shown to be effec-
Many of these symptoms are not specific, and hyperketosis
tive in studies, and choice of diet should consider the indi-
may not always be clearly identifiable as a cause without
vidual patient and experience of the ketogenic centre
capillary monitoring, especially in children who have non‐
• There is currently limited published research into other
verbal communication. Urine ketone testing is not sensitive
modified versions of the ketogenic diet; however, their suc-
enough to accurately identify hyperketosis [105] and cannot
cess in clinical practice in the UK is undisputed
identify hypoglycaemia. Treatment is with a measured
• LGIT is not recommended for disorders of brain metabolism
amount of CHO sufficient to prevent any symptoms of
as it does not produce ketones, which are essential to act as
hyperketosis while avoiding complete loss of ketosis, with
alternative fuel in these disorders
potential risk of seizure recurrence. There is no research to
support the correct amount of CHO to be given in this
instance. The Matthew’s Friends Medical Board [107] advises
Management of the diet 5 g CHO (given as glucose polymer solution or a high CHO
drink such as milk or fruit juice), but practice at ketogenic
Measuring ketones centres varies with 5–10 g CHO being given.
As the KD is extremely low in CHO, hypoglycaemia is
It is controversial whether ketone bodies themselves have a a risk, especially during initiation of the diet or during
direct effect on seizure control or are merely a marker of a illness. There are reports of hypoglycaemia in infants [85,
shift in metabolism, and clinical evidence is contradictory 108–110]. The Matthew’s Friends Medical Board [107] rec-
[100–104]. However, ketone monitoring allows fine‐tuning ommends treating blood glucose <2 mmol/L (or sympto-
of the diet to ensure a ‘therapeutic’ level of ketosis while matic hypoglycaemia) with 5 g rapidly absorbed CHO in
avoiding hyperketosis. Traditionally, urine ketones have children <5 years of age and 10 g CHO in older children.
been used to monitor the KD as they are generally thought This treatment should be repeated if blood levels have not
to be a less invasive method of testing (although urine col- improved within 15 minutes. Ketogenic centres may have
lection is not always without difficulty and urine concentra- different thresholds for when to treat hypoglycaemia (the
tion can be affected by hydration and does not reflect current authors’ centre uses 5 g CHO <1 year of age and 10 g CHO
ketosis [105]). The International Ketogenic Diet Study Group >1 year when blood glucose is ≤2.5 mmol/L), and van der Louw
[8] recommends home monitoring of urine ketones several [50] recommends treatment with 2–4 g CHO (as breastmilk,
times per week, preferably at different times of the day as normal infant formula or 10% glucose solution) if blood
ketone levels have been shown to be lowest in the morning glucose levels drop below 2.0–2.5 mmol/L in infants.
[106]. Ketone bodies can be monitored in the blood in the
form of β‐hydroxybutyrate (BHB), using home blood glu-
Supplements
cose meters (as provided to people with diabetes mellitus),
and in the urine as acetoacetic acid or acetoacetate. The
Vitamins and minerals
International Ketogenic Diet Study Group [8] also suggests
that checking BHB at routine clinic visits may be beneficial The KD lacks vitamins, trace minerals and electrolytes and
as there is evidence to suggest that blood levels correspond needs to be properly supplemented [111]. Osteoporosis is
more closely with seizure control than do urine ketones increasingly recognised in patients with epilepsy, and the
[100, 101]. High urine ketone levels (3–4+ or 8–16 mmol/L) causes are likely multifactorial. Children with intractable
have been shown to correspond to blood ketones of epilepsy are exposed to many factors that can increase the
2 mmol/L, while blood ketones of greater than 3 or even risk of poor bone health including falls, which increase
greater than 4 mmol/L may be most effective at seizure the risk for fractures, and also anti‐epileptic medications,
reduction [100, 101]. Blood BHB monitoring is recom- which may negatively affect nutrient metabolism and
mended in infants on KDT [50]. It is practice at the authors’ bone health [112]. The restricted intakes of foods on
centre to measure blood ketones twice daily (morning and KDT and the acidosis associated with the diet may further
evening) during the 3 month trial (or if dietary changes are increase the risk. It is, therefore, recommended that a
being made), reducing to three or four times per week (at CHO‐free multivitamin and mineral supplement that
different times of day) once established and stable on KDT. provides the recommended daily allowance of vitamin D
If on the LGIT then ketosis is not a goal and so ketones do and calcium should be prescribed [8], e.g. FruitiVits and
not need to be measured. Phlexy‐Vits (p. 362).
There is no agreed definition of hyperketosis on KTD; Serum levels of vitamins A and E have been found to be
van der Louw [50] recommends an ideal ketone range of high on KDT due to its high fat content [113, 114]. Vitamin E
2–5 mmol/L in infants, but ketones up to 6 mmol/L may be toxicity is rare [115]; however, excessive vitamin A has been
considered acceptable in children [107]. Hyperketosis should associated with adverse effects such as skeletal and intracra-
not be confused with the life‐threatening condition diabetic nial abnormalities [116]. At the authors’ centre, levels of vita-
ketoacidosis (where ketone production is uncontrolled due min A and E are monitored routinely.
358 Ketogenic Diets
Selenium deficiency has been reported in children on Medications

KDT [117], which has been linked with impaired myocar-
dial function [118]. A recent study found selenium levels Medications should be reviewed by a neurologist before
declined after 6 and 12 months on a KD and suggested that commencing KDT. Carbohydrate content should be assessed,
patients on KDT need close monitoring of this trace ele- and alternative low CHO formulations prescribed where
ment [119]. However, it remains unclear if additional sele- possible; or the amount of CHO must be included in the KD
nium above that provided in a standard multivitamin is calculations [122]. Often, sugar‐free medications contain
required [8]. sugar alcohols, such as sorbitol, which contribute some CHO
to the diet, and, therefore, alternatives should be recom-
Carnitine mended where possible. Suppositories or tablets are gener-
ally preferred to liquid medications as they tend to have
Carnitine has an essential role in fat metabolism, facilitat- lower CHO content. It is important to liaise with pharmacy
ing the transfer of long chain fatty acids into the mitochon- colleagues for guidance on the most appropriate formula-
dria for oxidation. The high fat content of the KD means tion. Some centres in the UK have a pharmacist as a member
there is an increased need for carnitine, potentially increasing of the KD team.
the risk of depletion of body stores. In addition, carnitine
deficiency has also been linked with long‐term use of the
AED, valproate [120]. Carnitine deficiency can compromise Learning points: management of the diet
ketosis due to impaired ketone synthesis. Tiredness and
muscle weakness can be symptoms of deficiency. However, • Measurement of ketone levels allows fine‐tuning of the diet
carnitine supplementation remains controversial. The to optimise clinical outcome and also to reduce the risk of
International Ketogenic Diet Study Group found the major- side effects secondary to hyperketosis and hypoglycaemia
ity of KD centres only supplement carnitine if levels are • Training in ketone monitoring and identification of abnor-
low or the patient is symptomatic [8]. A starting dose of mal levels and appropriate action to take is an essential part
10 mg/kg is frequently used and gradually increased as of education for KDT
required to avoid potential risk of increased seizures, diar- • Blood or urine monitoring can be used; however, blood lev-
rhoea and poor absorption associated with starting with els appear to be more accurate and are also more helpful in
higher dose supplementation. Most children do not require identifying hyperketosis and hypoglycaemia
more than 50 mg/kg/day [111]. • All medications should be as low in CHO as possible; advice
from a pharmacist regarding the most appropriate formula-
tions is essential
Essential fatty acids
Due to the restrictive nature of the KD, it is important to
ensure adequate essential fatty acid (EFA) intake. This is of
particular importance for children following MCT KD, Ketogenic diet in infants
where a large percentage of their energy requirements come
from MCTs. It may be necessary to supplement the diet with Historically, the KD has been avoided during infancy, with
a small amount (2–3 mL) of omega‐3 oil, e.g. walnut or flax- Freeman et al. [123] cautioning that ‘The ketogenic diet is
seed oil [121]. If EFA supplements are advised, levels of vita- not normally advised for children under one year old’.
mins A and E should be monitored regularly due to the high Reluctance to use the KD in this age group was multifacto-
levels of fat‐soluble vitamins in EFA oils. rial but included concerns about the risk of hypoglycaemia
and the potential impact of a severely restricted diet on neu-
rodevelopment, growth and feeding behaviour at this key
Other supplements
life stage. The absence of a ketogenic infant formula made
There is growing interest in the potential link between gut delivery of the diet difficult until Ketocal 3:1 became com-
microbiota, KD and epilepsy and also the potential use of mercially available in the UK in 2012. Prior to this, the only
exogenous ketone supplements. However, there are no rec- way to provide a ketogenic feed for an infant was either to
ommendations for the empiric use of probiotics or ketone modify Ketocal 4:1, a formula designed for children over 1
esters currently [8]. year of age, or to use a modular feed. There are concerns in
using Ketocal 4:1 in infants due to its high sodium and
potassium content, high calorie density (1.5 kcal/mL) and
Learning points: supplements low calcium/phosphate ratio.
A paucity of clinical research also contributed to the lack
• KDT needs to be properly supplemented of confidence in using a KD in infants, and an RCT by Neal
• A carbohydrate‐free multivitamin and mineral should be et al. [124] excluded children less than 2 years of age. More
prescribed that provides recommended daily allowance of recently, however, there have been several studies demon-
vitamin D and calcium strating efficacy and safety in this age group [108, 110, 125–
128], including case reports of the KD being used successfully
Use of the Ketogenic Diet in Emergency Situations 359
in neonates [109]. The Ketogenic Diet in Infants with The principles of weaning onto solids are the same as for
Epilepsy (KIWE) trial is an RCT multicentre UK study cur- the normal population, i.e. appropriate age, developmental
rently underway assessing outcomes of the KD in compari- stage, food textures and advice about any potential allergies.
son with anti‐epileptic medication in infants aged 3 months A speech and language therapist assessment may be indi-
to 2 years [129]. cated if there are concerns that neurological impairment
International guidelines for the use of the KD in infancy has affected the ability to swallow. When first introducing
were published in 2016 [50], which recommend that infants weaning foods, the CHO content may not be significant due
under the age of 1 year start the diet as an inpatient as they to the small volume consumed. However, it is prudent to
have been shown to be at increased risk of hypoglycaemia still avoid high CHO foods, particularly sweet foods, to
and acidosis. Good growth has been shown to be achievable avoid the infant developing a preference for these foods at
in infants on a KD [108, 130], although it has been proposed the expense of lower CHO choices. As the amount increases,
that shorter diet duration shows better growth outcomes then solid meals will need to be calculated in the diet
with no detrimental effect on seizure recurrence [131]. prescription.
An example of feeding regimen for an infant starting a KD
at a 2:1 ratio is given in Table 17.16.
Feeding the infant
The KD for infants prior to being weaned onto solid foods is, Learning points: KDT in infants
by default, a liquid CKD. Ketocal 3:1 ketogenic formula pro-
vides a 3:1 ratio and at standard dilution provides • KDT can be used safely and effectively in infants
66 kcal/100 mL. It has been demonstrated that it is possible • Breastfeeding (or expressed breastmilk in the case of tube
to provide an infant a KD while still receiving some breastfeeding) on a ketogenic diet is possible; however, the high
milk, either from breastfeeds or expressed breastmilk (EBM), CHO content of breastmilk may make it difficult to achieve
with ketogenic formula top‐ups [132]. However, in order to optimal ketosis in some infants
achieve optimal ketosis, the amount of breastmilk received
may need to be limited since it contains approximately 7 g
lactose per 100 mL [133]. If an infant is breastfed and the
Use of the ketogenic diet in emergency situations
mother wishes to continue, then a measured volume of
Ketocal 3:1 should be given before each breastfeed
KTD is being used increasingly in an intensive care setting
(Table 17.15). This principle assumes that the infant will con-
in the management of super‐refractory status epilepticus
sume expected volumes for age and, therefore, the ketogenic
(SRSE) and febrile infection‐related epilepsy syndrome
infant formula will reduce appetite for breastmilk and so
(FIRES). SRSE is defined as refractory epilepsy that contin-
limit CHO intake. Depending on ketone levels, the amount
ues 24 hours after initiation of general anaesthesia or reap-
of Ketocal 3:1 given can be either increased (thus reducing
pears after the discontinuation of general anaesthesia [135].
breastmilk intake if higher ketones are desired) or decreased
Prior reports demonstrate that outcomes in SRSE and FIRES
(to increase breastmilk intake and consequently, increasing
are poor, with hospital mortality ranging from 30% to 40%
CHO intake if hyperketosis is a concern).
and about 75% of patients experiencing a poor functional
For exclusively formula‐fed infants, if ketones are rou-
outcome at discharge [136, 137], so an effective intervention
tinely too high, then some feeds of normal infant formula can
is essential. Both these conditions have been highlighted as
be included, or, alternatively, glucose polymer can be added
conditions in which KDT should be used early, showing a
to the Ketocal 3:1 feed to lower the ratio. If optimal ketosis is
higher than average efficacy [8, 138]. There is limited research
not achieved on a 3:1 infant formula, then small volumes of
into the use of KDT as the published papers are often case
fat emulsion may be added to the feed to increase the ratio.
reports which could have selection bias.
MCT emulsion may be preferred as MCT is more efficient at
It is likely that in the above scenarios, KDT will be admin-
producing ketones [134]. If extra fat is added, then tolerance
istered via an enteral feeding tube (although parenteral
and weight gain will need to be closely monitored.
nutrition may also be considered), and a CKD ratio should
be selected. Due to the nature of the setting in intensive
Table 17.15 Relative proportions of EBM and ketogenic infant formula
care, a rapid introduction of the diet can be used over 24–48
and ratio provided. hours as closer monitoring is available for blood glucose
and blood ketone management. With a rapid induction,
Percentage EBM Percentage Ketocal 3:1 Ketogenic ratio blood glucose levels may be more likely to drop, so levels
should be checked more frequently. Energy requirements
0 100 3:1
should reflect clinical status, considering the reason for
5 95 2.5:1 admission; pyrexia should be considered, particularly if
15 85 2:1 FIRES is the cause of status epilepticus. All drugs, including
25 75 1.5:1 intravenous (IV) medications and fluids, should be
reviewed with the ward pharmacist to ensure that they are
EBM, expressed breast milk. the lowest CHO formulations [139] and nursing and
360 Ketogenic Diets
Table 17.16 Example of feeding regimen for a 6‐month‐old infant starting ketogenic diet at 2:1 ratio.
A male infant, weight = 8 kg, is receiving all his nutrition as 5 oral feeds per day. He is not yet taking solid foods. Mum is keen to continue to provide
some breastfeeds
Calculation of intake of formula:
Assuming an age appropriate intake of 120 mL/kg/day, expected intake = 120 × 8 = 960 mL/day
Total expected volume per feed = 960/5 = 192 mL
To provide a feed with 2:1 ratio, the feed should contain 15% breastmilk and 85% Ketocal 3:1 (Table 17.15)
85% × 192 mL = 163 mL formula per feed. Top‐up feed given as breastmilk = either 192 – 163 = 29 mL EBM or fed to appetite from breast
Feeding regimen = 163 mL × 5 feeds Ketocal 3:1 per day, with a top‐up feed of breastmilk
The infant is tolerating the feeding regimen, but ketones are <2 mmol/L with no reduction in seizures.
The ratio of the feed can be adjusted to improve ketosis:
The volume of ketogenic infant formula should be increased (from 173 mL × 5 to 180 mL × 5 per day would be a sensible adjustment), and it would be
expected that the volume of breastmilk taken by the infant would spontaneously reduce to correspond to appetite, thus increasing the overall ratio of
the diet.
Feed contains 94% Ketocal 3:1 (180/192 mL) and 6% breastmilk (12/192 mL) providing approximately 2.5:1 ratio (Table 17.15).
Ketones are now in the therapeutic range 2–5 mmol/L, and the infant is gaining weight appropriately. A speech and language therapist has advised
that weaning solids can be introduced.
Calculation of 2.5:1 ketogenic meal prescription:
Calorie intake divided over three meals and 2 bottles per day, continuing the current volume of 180 mL Ketocal 3:1 per bottle with a breastfeed
top‐up to be given afterwards (estimated total intake per feed = 192 mL, including assumed 12 mL from the breastfeed, as per previous calculation)
Dietary exchanges
100 mL Ketocal 3:1 provides 192 mL feed provides (rounded to nearest 0.5 g)
Fat (g) 6.4 12.1 2.5 × 5 g exchanges

CHO (g) 0.68 2.1 2 × 1 g exchanges
Protein (g) 1.5 2.8 3 × 1 g exchanges
Sample 2.5:1 meal plan
Provides: 12.5 g fat, 3 g protein and 1.5 g CHO per meal [54]
Fat Protein CHO

Breakfast – scrambled egg and fruit (rounded to nearest 0.5 g) (to nearest g) (rounded to nearest 0.5 g)
½ egg 2.5 3 –
15 mL Calogen 7.5 – –
3 g butter 2.5 – –
13 g apple (stewed) – – 2.0
Total (2.5:1) 12.5 3 2.0
Fat Protein CHO

Lunch – Cheesy celeriac mash (to nearest 0.5 g) (to nearest g) (rounded to nearest 0.5 g)
12 g Cheddar cheese (grated) 4 3 –

50 g boiled celeriac (mashed) – – 1
15 ml gravy – – 0.5
17 g double cream 8.5 – 0.5
Total (2.5:1) 11.5 3 2.0
Evening meal – salmon in creamy Fat Protein CHO

sauce with broccoli (to nearest 0.5 g) (to nearest g) (rounded to nearest 0.5 g)
12 g steamed salmon 2 3 –

20 g double cream 10.5 – 0.5
43 g broccoli (steamed) – – 1.5
Total (2.5:1) 12.5 3 2.0
medical staff should be made aware that IV fluids and An example calculation of a ketogenic tube feed is given in
medications should not contain CHO. Table 17.18.
The length of time that KDT is used in the above condi-
tions is unclear, and recent research has supported success-
Modular feeds
ful use in shorter time periods compared with the usual 2
years [140, 141]. It may be that if the patient responds to KDT
The Ketocal range of products contains cow’s milk protein.
and is extubated and ultimately discharged back to the ward,
A modular feed is, therefore, necessary in the case of a child
they can be weaned off KDT as they are re‐established onto
with cow’s milk protein allergy or whole protein intoler-
oral feeding, without deterioration of seizure control. This
ance. It is important to consider the CHO content of protein
may be an opportune time to wean back to a normal diet as
modules used in the feed, e.g. Complete Amino Acid Mix
it can be challenging to wean from enteral to oral KD in these
may be required due to the CHO content of hydrolysed pro-
scenarios.
tein modules such as Prosource TF and Hydrolysed Whey
Protein/Maltodextrin Powder (Table 17.17). Consideration
Prescribable items must also be given to ensuring electrolyte, vitamin and min-
eral requirements are also met. Further information on
There is an increasing, but limited, range of prescribable modular feeds can be found in Chapter 8.
products available for use in KDT. It should be noted that,
with the exception of Ketocal 3:1, the prescribable items
in the UK are not approved by Advisory Committee on Learning points: enteral feeding
Borderline Substances (ACBS) for children below 3 years of
age for use in the community, e.g. Ketocare breakfast cereals, • The KD can be provided as an enteral feed
Keyo and FruitiVits. This is due to EU legislation prohibiting • Enteral feeds should be calculated based on the current feed-
sweetener use in foods for infants and young children [142]. ing regimen and growth history
Items available on prescription are given in Table 17.17. • Feeds are usually introduced slowly starting at a low
ketogenic ratio of 1:1 or 2:1 and then gradually increased as
needed
Enteral feeding
• Macronutrient and micronutrient levels should be checked
and supplemented where necessary to meet requirements
The KD can be provided as an enteral feed via nasogastric,
• A modular feed may be necessary for children with cow’s
gastrostomy or jejunostomy feeding tubes. Efficacy in this
milk protein allergy or an intolerance to whole protein feeds
group has been shown to be high. A study by Kossoff [83]
found 59% of children exclusively tube fed to have >90% sei-
zure control at 12 months. Compliance in this group has also
been found to be high [143]. This may be due to the relative
Parenteral nutrition
ease of delivery of this form of the diet and reduced room for
error compared with an oral diet.
Indications
Ketocal is a specially designed nutritionally complete
ketogenic formula available in the UK. It comes in various
Parenteral nutrition is indicated in KDT when enteral intake
ratios and formulations, which are suitable as a sole source
is impaired (inability to absorb nutrients through the gastro-
of nutrition in specific populations (Table 17.17).
intestinal tract), and bowel rest is required [144], and ketosis
Enteral feeds should be calculated based on the child’s
for seizure control must be maintained. It may also be needed
current feeding regimen and growth history (p. 349) and cal-
when KDT is indicated, but enteral application is temporar-
culated in a similar way to an oral CKD. Where possible
ily impossible [145]. In UK practice, ketogenic parenteral
feeds can be administered in a similar way to the child’s
nutrition (kPN) is not used at dietary initiation, and there are
usual regimen.
only a few case reports supporting the use of kPN in the lit-
Feeds are usually introduced slowly starting at a low
erature, which are summarised in Table 17.19.
ketogenic ratio of 1:1 or 2:1 and then gradually increased
according to ketosis/seizure control. The ratio of the feed can
be altered by adding/subtracting CHO/protein modules Calculation and provision of prescription
(Tables 1.19 and 1.21). Macronutrient and micronutrient lev-
els should be checked and supplemented where necessary to The flow chart in Figure 17.1 shows the steps to calculate the
meet requirements [111], e.g. children with particularly low prescription for kPN. Standard bags are not available for
energy requirements, and, hence, low volumes of feed may kPN, so a multidisciplinary approach is key to successful
require extra supplementation of protein and electrolytes. As implementation. There needs to be close working with an
MCT fat is more efficient at producing ketones [134], addi- experienced pharmacist to calculate the kPN script, ensuring
tion of MCT fat may also be useful, particularly in this group, its stability and suitable osmolality. It will also be necessary
in order to optimise ketone levels when protein requirements to work with the nursing and medical team to ensure all IV
do not allow for further increase in the diet ratio. medications, fluids and solutions are CHO‐free to support
362 Ketogenic Diets
Table 17.17 Items available on prescription for ketogenic diet therapy.
Product Company Description Indications
Nutritionally complete
Ketocal 4:1 powder Nutricia Advanced Powdered feed enriched with fibre and LCPs Suitable as a sole source of nutrition, or as
Medical Nutrition available in vanilla and unflavoured varieties. a supplementary feed, in children over 1
The standard feed concentration is 14.3% year. For sip and tube feeding
Ketocal 4:1 LQ Nutricia Advanced Ready to use fibre enriched liquid feed Suitable as a sole source of nutrition in
Medical Nutrition available in vanilla and unflavoured varieties children aged 1–10 years or as a
supplement for those over 10 years and
adults
Ketocal 3:1 powder Nutricia Advanced Powdered feed, fibre‐free, enriched with LCPs, Suitable as a sole source of nutrition in
Medical Nutrition unflavoured. The standard feed concentration infants from birth to 6 years or as a
is 9.5% supplement in those over 6 years
Ketocal 2.5:1 LQ Nutricia Advanced Ready to use fibre‐enriched liquid feed Suitable as a sole source of nutrition in
Medical Nutrition available in vanilla flavour children aged 8 years to adults or as a
supplement
Keyo Vitaflo International Ready to eat semi‐solid food Suitable from 3 years of age onwards.
Ltd. Suitable as a sole source of nutrition up to
10 years of age
Fat modules
Liquigen Nutricia Advanced 50% MCT emulsion Suitable from birth
Medical Nutrition
MCT oil Nutricia Advanced Liquid containing only a mixture of MCT Suitable from birth
Medical Nutrition
Calogen Nutricia Advanced 50% LCT fat emulsion Suitable from birth
Medical Nutrition
Carbzero Vitaflo International Ready to use 20% emulsion of LCT Suitable from 3 years of age
Ltd.
Betaquik Vitaflo International Ready to use 20% emulsion of MCT Suitable from 3 years of age
Ltd.
Protein modules
Protifar Nutricia Advanced Powdered, unflavoured, high protein Suitable from birth
Medical Nutrition supplement
Hydrolysed Whey Nutricia Advanced Powdered, whey protein hydrolysate Suitable from birth
Protein/Maltodextrin Medical Nutrition
Powder
Prosource TF Nutrinovo Ltd. Liquid high protein milk‐free (beef collagen Suitable from 3 years of age
derivative) supplement for tube feeding
MCTprocal Vitaflo International Neutral tasting protein powder supplement Suitable from 3 years of age
Ltd. high in MCT
Complete Amino Nutricia Advanced Powdered mix of essential and non‐essential Suitable from birth
Acid Mix Medical Nutrition amino acids
Carbohydrate modules
Super Soluble Maxijul Nutricia Advanced Powdered unflavoured CHO supplement Suitable from birth
Medical Nutrition
Polycal Powder Nutricia Advanced Powdered unflavoured CHO supplement Suitable from 1 year of age
Medical Nutrition
Vitajoule Vitaflo International Powdered unflavoured CHO supplement Suitable from birth
Ltd.
Vitamin and mineral supplements
Phlexy‐Vits sachets Nutricia Advanced Concentrated powdered vitamin, mineral and Suitable for children over the age of
Medical Nutrition trace element preparation 11 years and adults
Phlexy‐Vits tablets Nutricia Advanced Tablets containing vitamins, trace elements, Suitable for children over the age of 8 years
Medical Nutrition calcium, phosphorous and magnesium and adults
Product Company Description Indications
FruitiVits Vitaflo International Orange flavour vitamin, mineral and trace Suitable from 3 to 10 years of age
Ltd. element supplement
Food products
Ketoclassic bar Ketocare 3:1 ratio, high fibre bar Suitable from 3 years of age
Ketoclassic savoury Ketocare 3:1 ratio, high fibre solid meal Suitable from 3 years of age
Ketoclassic chicken Ketocare 3:1 ratio ready meal Suitable from 3 years of age
Ketoclassic bolognese Ketocare 3:1 ratio ready meal Suitable from 3 years of age
Ketoclassic porridge Ketocare 3:1 ratio, high fibre ready-prepared breakfast Suitable from 3 years of age
meal
Ketoclassic muesli Ketocare 3:1 ratio, high fibre ready-prepared breakfast Suitable from 3 years of age
meal
LCP, long chain polyunsaturated fatty acids; MCT, medium chain triglycerides; LCT, long chain triglycerides
Table 17.18 Example calculation of a ketogenic tube feed.
A 3‐year‐old girl who is completely tube fed

Wt = 14 kg, following appropriate centiles for weight and height
Current feeding regimen is 700 mL/day of 1.5 kcal/mL nutritionally complete whole protein feed:
100 mL bolus × 3 in the day
40 mL/hour × 10 hours overnight
Water flushes of 40 mL are given pre‐ and post‐feeds, plus extra 180 mL water/24 hours as flushes with medications
The feed provides: 1050 kcal, 28.7 g protein. Total fluid = 1200 mL
Plan: to base ketogenic feed on current feed regimen

Initiate at 2:1 ratio using the dietary unit method (p. 349)
Prescription = 96 g fat; minimum 1 g/kg protein = 14 g (RNI = 14.5 g); 33.5 g CHO
100 mL Ketocal 4:1 LQ = 14.8 g fat, 0.61 g CHO, 3.09 g protein
Fat required from Ketocal 4:1 LQ = 96 g fat ÷ 14.8 = 650 mL Ketocal 4:1 LQ
650 mL Ketocal 4:1 LQ provides 3.09 × 6.5 = 20 g protein

0.61 × 6.5 = 4 g CHO
Add in 24 g Maxijul glucose polymer to reduce ratio to 2:1
Provides: 96 g fat, 20 g protein, 28 g CHO, 1056 kcal/day
The feed meets full nutritional requirements in the desired ratio; there is no need to restrict protein to minimum requirements
The ratio can then be gradually increased if required by decreasing the amount of Maxijul depending on ketosis and seizure control
RNI, reference nutrient intake.
ketosis. It is not always possible to provide full calorie Monitoring

requirements with kPN due to the limited capacity for lipid
per day and the infusion rate. This also means that the Daily monitoring of kPN should follow the schedule as out-
ketogenic ratio can be limited, so it is particularly important lined in Chapter 5. If the patient is new to KDT, then they
to eliminate additional CHO sources where possible. kPN should have had standard baseline monitoring as per the
can be built up over 1–2 days, either building up the fat con- International Ketogenic Diet Study Group consensus state-
tent from 3 to 4 g/kg/day or providing half a bag on day 1 ment [8]. In addition to standard PN monitoring, twice
and a full bag on day 2. An example calculation for an ado- daily bedside blood glucose and blood ketone measure-
lescent on kPN is given in Table 17.20. ments should be taken to assess effectiveness of the kPN at
364 Ketogenic Diets
364
Table 17.19 Summary of literature for ketogenic parenteral nutrition.
Ketogenic Diets
Duration Established Ketosis achieved Remained on KD
Sample of kPN KD prior (defined as after kPN
Reference size Reason for kPN (days) to kPN BHB > 2 mmol/L) Efficacious Adverse effects discontinued Conclusions
Kang et al. 10 Bowel rest 4.1 (±1.5 Yes Yes Yes ↑ ALT (n = 1) 9 continued kPN is a safe short‐term
[146] days) ↑ amylase and method of continuing KDT to
lipase (n = 1) maintain seizure control
↑ triglycerides
(n = 1)
Strzelczyk 1 Significant 9.5 No Yes Refractory seizures Non‐reported Yes kPN is safe and feasible
et al. [147] reflux and SRSE resolved
Chiusolo 1 Ileus and 3 No Yes NA Non‐reported No, weaned onto kPN is a temporary bridge for
et al.[148] refractory status enteral KDT but KDT for those with partial or
epilepticus stopped after 8 days total intestinal failure who
due to non‐response need to start KDT
Zupec‐ 1 Not identified 1 No No Yes, once Non‐reported Weaned after 2 Poor ketosis due to
Kania et al. transitioned to months due to poor carbohydrate content of
[139] enteral KDT compliance phenobarbitone infusion and
glycerol content of lipid
infusion, which had not been
accounted for
Lin et al. 1 GI bleed 8 No Yes Yes ↑ triglycerides and Yes Early intravenous initiation of
[149] cholesterol a KD in SRSE is an effective
and safe alternative treatment
Rosenthal 1 Bowel rest for 140 Yes Yes Yes Abnormal LFT Died Relatively safe, effective
et al. [150] intractable Iron deficiency short‐term treatment
diarrhoea anaemia
↑ triglycerides and
cholesterol
Roan et al. 1 Intestinal failure 448 Yes On day 3 of Yes Mild ↑ in Remain on kPN long Well tolerated and safe with
[151] initiation triglycerides, term with minimal close and careful monitoring
cholesterol and LFT enteral input
Dressler 17 Non‐ 1–41 Yes – 13 Yes – 10 Those previously Transient ↑ in 12 continued KDT Ketosis can be maintained
et al. [145] functioning GI days No – 4 No – 7 on KDT maintained triglycerides (n = 3), successfully, and relevant
tract ± status efficacy. Of the 7 cholesterol (n = 5), adverse effects were not noted
epilepticus remaining, only 2 HDL (n = 6), LDL in short‐ or long‐term
responded to the (n = 4) and LFT application (41 days)
diet (n = 4)
All resolved after
stopping kPN
kPN, ketogenic parenteral nutrition; KD, ketogenic diet; BHB, β‐hydroxybutyrate; ALT, alanine transaminase; SRSE, super‐refractory status epilepticus; KDT, ketogenic diet therapy; NA, not
applicable; GI, gastrointestinal; LFT, liver function tests; HDL, high density lipoproteins; LDL, low density lipoproteins.
Fine‐tuning the Ketogenic Diet 365
achieving ketosis. The kPN may need adjustment as a result

Establish fluid requirement or volume available
of these monitoring tests, so working closely with the phar-
macist and ward staff is essential.
Determine daily energy requirements
(see Chapter 5 Parenteral Nutrition) Adverse effects
*caution to avoid overfeeding as this will impact on ketosis [145] and
clinical state
As noted in the cases in Table 17.19, short‐term use of kPN is
not associated with significant adverse effects, with transient
increases in lipids being the most commonly seen response.
Determine daily protein requirements and convert to nitrogen (g) With close monitoring, short‐term kPN can be safe and effec-
(see Chapter 5 Parenteral Nutrition) tive for those patients already established on KDT who
require bowel rest or have a non‐functioning gastrointestinal
tract. Enteral nutrition should be re‐established as soon as
possible as there is little research into long‐term use of kPN.
Determine daily fat requirements (maximum 4g/kg/day with a
maximum infusion rate of 0.25g/kg/hour)
Learning points: ketogenic parenteral nutrition
• kPN can be used for those established on KDT, for short

Determine carbohydrate intake and additional requirements periods of time, if the enteral route cannot be used and keto-
(glycerol backbone from lipid will provide 0.11g carbohydrate per
gram of lipid and should be accounted for [139]) sis needs to be maintained
• Nutritional intake is often impaired due to the limited lipid
infusion rate and volume
• All IV medications and fluids need to be carbohydrate‐free
Determine electrolyte, trace element and vitamin requirements. to support ketosis
(see Chapter 5 Parenteral Nutrition)
Assess carbohydrate content of current IV medications and adjust Fine‐tuning the ketogenic diet
where possible in discussion with the pharmacist [139]
Fine‐tuning is necessary to ensure therapeutic levels of
ketones and as a result, hopefully, to improve seizure con-
Calculate final diet ratio trol. Fine‐tuning is often associated with the initial trial
period but can occur at any stage. Selter et al. [152] showed
Figure 17.1 Calculation of prescription for ketogenic parenteral that fine‐tuning lead to an improvement in seizure control in
nutrition. 18% of patients who had already responded to the KD and
Table 17.20 Example calculation for an adolescent on ketogenic parenteral nutrition.
A 14‐year‐old male is established on a modified ketogenic diet (oral and by nasogastric tube) following super‐refractory status epilepticus at 12 years
of age and is maintaining good ketosis
He is admitted to the paediatric intensive care unit following emergency laparotomy: 25 cm necrotic bowel is resected following obstruction
secondary to adhesions. Bowel rest and parenteral nutrition is advised
Weight = 65.6 kg (91st centile) Height = 179.5 cm (75th–91st centile)
Usual ketogenic diet
Energy 1973 kcal
Protein 65.6 kg = 10.5 g nitrogen/day (lowest safe intake protein = 58.4 g/day)
Fat 228 g (129 g LCT and 99 g MCT) per day
kPN prescription
Fat 3 g/kg/day = 197 g fat per day = 0.13 g/kg/hour, given over 18 hours to avoid overfeeding = 0.17 g/kg/hour
CHO 21.67 g CHO from glycerol (0.11 g per g lipid); all medication given IV and CHO‐free
Micronutrients Standard supplementation meets requirements
Final bag 197 g fat, 10.5 g nitrogen, 21.67 g CHO = 2.25:1 ratio providing 2035 kcal
Ketosis was maintained once kPN was established and the patient was weaned back onto enteral KDT after 7 days
LCT, long chain triglycerides; MCT, medium chain triglycerides; kPN, ketogenic parenteral nutrition; CHO, carbohydrate; IV, intravenous;
KDT, ketogenic diet therapy.
366 Ketogenic Diets
3% achieved seizure freedom. Fine‐tuning is also important infection is a common cause of low ketones, and levels
to help manage side effects and to optimise weight gain and should improve post‐illness. If the level of ketones has low-
growth. Fine‐tuning may also improve palatability and thus ered with no obvious increase in seizures, then there may be
adherence to diet. Common fine‐tuning strategies are sum- no need to alter the diet, so avoiding unnecessary further
marised in Table 17.21. restriction.
If there is a sudden reduction in ketosis, with subsequent If the diet is being given correctly with no obvious indis-
increase in seizures, then thorough investigation is necessary cretions, then to optimise ketosis it may be necessary to
to find the cause. There may have been accidental ingestion increase the ratio of the classical diet (in 0.5:1 increments) or
of excess CHO. A food diary can be helpful to check that the to decrease the CHO (in 1–2 g decrements) if the child is on
diet is being administered correctly. Common errors include MAD. If there is consistent hyperketosis, then the converse
miscalculation of meals and incorrect interpretation of food would apply. Calorie control has not been shown to be effec-
labels, product changes and the use of sugar polyols as tive in improving seizure control on KDT [152, 153]. Carnitine
sweeteners in foods and medications. Non‐adherence or supplementation may be of benefit [152, 154] although the
‘cheating’ by the child is always a possibility and can some- International Ketogenic Diet Study Group recommends that
times be facilitated by a misguided relative or teacher who supplementation should only be given if levels are low [8].
believes that the ‘occasional treat won’t hurt’. Intercurrent The use of MCT as a supplement to the CKD or MAD, rather
than giving MCT as the full MCT KD, can be a fine‐tuning
tool [155]. The authors have found the addition of small
Table 17.21 Fine‐tuning the ketogenic diet. measured amounts (15 g MCT given three times a day) of an
MCT emulsion, e.g. Betaquik or Liquigen, to the diet can
Problem Action boost ketosis and so prevent the need for further reduction
Difficulty If ketones lower than usual, but child still in in CHO allowance, but only when mild to moderate ketosis
establishing ketosis ketosis and no associated increase in seizures: has already been established. If ketones are minimal
or a sudden loss of no immediate action necessary, but be vigilant (<1.5 mmol/L), then the addition of MCT to the diet does not
ketones for possible cause of decreased ketones appear to have an effect. A small pilot study [156] investi-
If seizures increased: check for consumption of gated if intermittent fasting improved outcome in children
extra CHO (e.g. cheating, miscalculation of already established on a KD, whereby the child was fasted
meals or misinterpretation of labels); a detailed for two meals on 2 non‐consecutive days per week. Although
food diary may be helpful there was some seizure improvement, it was not sustained,
If intercurrent illness: temporary reduction in and adherence to this regimen was found to be difficult.
CHO may help, but ketosis should improve as It is suggested that during the initial 3 months on a KD, it
child recovers may be beneficial to follow a stricter diet but that it may be
If no obvious cause for loss ketosis: reduce CHO possible to ‘liberalise’ the KD subsequently with no deterio-
allowance (MAD) or increase diet ratio (CKD); ration in seizure control. Both a randomised crossover com-
consider addition MCT emulsion to diet in small parison of either 10 g or 20 g CHO on MAD [40] and a crossover
volumes
3:1 or 4:1 CKD [41] showed improved seizure control for the
If still struggling to regain ketosis: consider groups on the stricter protocol (i.e. either 10 g CHO or 4:1) at
checking carnitine levels and supplementing
the end of trial period, but outcome was maintained, and
if low
tolerability was improved when crossed over to the less
Hyperketosis If occasional and/or only associated with illness: strict protocol (20 g CHO or 3:1).
treat with 5–10 g liquid CHO
If repeated episodes: first check all the CHO
allowance is being consumed; if not consider Learning points: fine‐tuning the ketogenic diet
using higher CHO foods
If all CHO allowance is being consumed: • Fine‐tuning can help to optimise ketosis, growth and adher-
increase the CHO by 1–2 g (MAD) or reduce the ence and reduce risk of hyperketosis and hypoglycaemia and
ratio by 0.5:1 (CKD) can happen at any stage of KDT
If using MCT emulsion: consider reducing or • It has been suggested that it may be possible to liberalise the
discontinuing, but generally the preference is to diet after the initial 3 month trial period while still main-
increase CHO allowance and thus improve taining effectiveness
palatability/variety diet
Concern that If on CKD: recalculate diet using amended
excessive weight calorie requirements
gain or loss Management of illness
If on MAD: adjust fat intake; if issue is ongoing
consider changing to CKD to enable calorie
prescription
During episodes of intercurrent illness, dietary adjustment
may be required to maintain ketosis and prevent seizure recur-
CHO, carbohydrate; MAD, modified Atkins diet; CKD, classical rence. Closer monitoring is also advisable to identify hyperke-
ketogenic diet; MCT, medium chain triglycerides. tosis or hypoglycaemia as the risk is higher during illness.
Adverse Effects of the Ketogenic Diet 367
As with all children who are unwell, medical advice should be Adverse effects of the ketogenic diet
sought if there are concerns or if the illness is ongoing to ensure
correct treatment is received. Where possible, medications The most commonly seen side effects of KDT are gastrointes-
should be low CHO formulations, but medication should not tinal symptoms, hypercholesterolaemia, kidney stones and
be withheld as the illness needs to be treated. Further informa- slower linear growth. Other potentially more serious side
tion about medications and KTD is given on p. 358. effects are rare but support the requirement for monitoring
Ketones and blood sugars should be checked every on KDT and regular follow‐up by an experienced team. A
4 hours if oral intake is significantly reduced, if the child review by Kang et al. [158] looked at 129 patients following a
is vomiting or if recent levels have required treatment. KD for a mean duration of 12 months (±10.1); early‐onset
Hyperketosis should be treated in the first instance, and if symptoms occurred within the first 4 weeks (Table 17.22). Of
there are repeated episodes, then it may be necessary to tem- the 46.5% that experienced dehydration, 52 were fasted prior
porarily increase the CHO allowance of the diet. Further to starting the KD and maintained on 75% of fluid require-
information about measuring ketones is given on p. 357. ments as part of the initiation protocol, which is not common
If ketones are low then, if possible, the CHO allowance can practice in the UK. Bergqvist et al. [49] highlighted that fast-
be temporarily reduced in the diet to compensate. If the ing is not necessary to achieve ketosis; it is commonly associ-
CHO allowance is already at a minimum, then the addition ated with the adverse effects of hypoglycaemia, acidosis and
of MCT emulsion, e.g. Betaquik or Liquigen, to the diet may dehydration.
help to optimise ketone levels, although if vomiting or In practice the most commonly seen side effects in the
abdominal discomfort is associated with the illness, then short term are constipation and GOR. In the longer term
starting MCT simultaneously is not ideal. there can be impacts on growth, raised cholesterol levels and
If the child has a poor appetite, then higher CHO foods, renal calculi. The diet is generally well tolerated, and nutri-
e.g. juice or glucose polymer, fruits and potato, may be help- tional deficiencies are not commonly seen if the diet is ade-
ful to ensure the CHO allowance is consumed (although it is quately supplemented with vitamins and minerals (p. 357).
preferable to still avoid those foods that are not usually per-
mitted on the diet, such as chocolate or normal bread, to Constipation
avoid confusion for the child upon return to their usual KD
allowance after illness has resolved). If meals are not eaten, As the CHO content of the diet is limited, fibre‐containing
then a meal replacement ‘shake’ drink may be used tempo- foods are also limited. Families should be encouraged to
rarily (Ketocal LQ 4:1 or 2.5:1 with additional glucose poly- regularly include high fibre CHO sources and to optimise
mer if necessary to provide the correct classical ratio or CHO fluid intake; CHO‐free laxatives, e.g. macrogol (Movicol
allowance). Sugar‐free fluids should be given to ensure ade- Paediatric Plain), may be required [159]. Constipation is not
quate hydration. Oral rehydration solutions may be used, only more common with the CKD than the MCT diet [8] but
but the CHO content should be taken into consideration, e.g. is also seen with MAD or MKD. It may be a concern for those
Dioralyte provides 1.8 g glucose per 100 mL. If vomiting or children with swallowing difficulties or learning difficul-
diarrhoea is present, then it may be necessary to temporarily ties where their fluid intake may already be compromised.
reduce fat intake, especially MCT. Sugar‐free jellies or sugar‐free ice pops can be important
If nil by mouth for a surgical procedure, then ketones and sources of fluid to supplement intake.
blood sugars should be checked 4 hourly, and diet reintro-
duced as soon as is feasible after the procedure. If IV fluids
are required, then saline or Plasmalyte is preferred to dex- Table 17.22 Complications experienced on the ketogenic diet [158].
trose (unless treating hyperketosis or hypoglycaemia).
Continuing or late‐onset
Valencia et al. [157] showed that serum glucose remained
Early‐onset complications complications
stable in children on KD who underwent general anaesthe-
sia on CHO‐free IV solutions. However, metabolic acidosis Dehydration 46.5%* Gastrointestinal effects 27.9%
was observed in several patients, so it is recommended that Gastrointestinal effects 38.7% Hypercholesterolaemia 19.4%
serum pH or bicarbonate levels are monitored if undergoing
Hypercholesterolaemia 14.7% Hepatitis 5.4%
prolonged surgical procedures.
Raised urate 26.4% Osteopenia 14.7%
Hypoglycaemia 7% Renal stones 3.1%
Learning points: management of illness
Hypomagnesemia 4.7% Hydronephrosis 0.8%
• Close monitoring is advisable during illness to maintain Hyponatraemia 4.7% Iron deficiency 1.6%
therapeutic ketone levels and also to reduce the risk of Hepatitis 2.3% Carnitine deficiency 1.6%
hyperketosis and hypoglycaemia Acute pancreatitis 0.8% Cardiomyopathy 0.8%
• Temporary modification of the diet may be needed to com- Metabolic acidosis 0.8% Raised urate 10%
pensate for abnormal ketone levels, poor intake or feed intol-
Hypomagnesemia 14%
erance; a ‘shake’ drink can be used as a meal replacement
* Fluid is no longer routinely restricted on dietary introduction.
368 Ketogenic Diets
Gastro‐oesophageal reflux or vomiting Renal stones
GOR is common in this patient group, particularly if tube Risk of renal stones may be higher for those children on the
feeding is necessary. The incidence of epilepsy in cerebral diet for longer periods and for those that are concurrently
palsy (CP) is estimated to be between 15% and 62% [160]. using carbonic anhydrase inhibitors, such as topiramate and
GOR is predicted to affect 50% of patients with CP [161]; in zonisamide [171]. The use of oral citrates (potassium citrate
this patient group their GOR is likely exacerbated by the or Effercitrate) appears to be helpful, but there is no consen-
high fat content of KDT and will need careful management, sus on whether these should be used empirically [8]. Often,
considering proton pump inhibitors [8] and feeding meth- common practice is to introduce them if urine calcium/cre-
ods, e.g. pump‐assisted feeds or jejunal feeding. Input from atinine ratio is raised, and it may be prudent to introduce
the gastroenterology team can help to fully investigate GOR early if they are taking topiramate or zonisamide. Good fluid
and advise regarding optimisation of treatment prior to intake of at least 100% of calculated fluid requirements
dietary initiation. is essential, with some specialists advising up to 120% of
Vomiting is most commonly associated with MCT [34] in requirements if patients are deemed at higher risk of renal
children feeding orally, but this side effect can be avoided by stones. This can be particularly challenging in children with
gradual introduction of MCT over a number of days to GOR or with swallowing difficulties and needs to be consid-
improve tolerance. If vomiting persists, a reduction in the ered. Renal ultrasound scans are not advised as a routine
MCT prescription may be required. baseline investigation unless there is a perceived risk, e.g.
family history [8], but they can be useful for monitoring in
high risk patients.
Growth and bone density
Numerous studies have reported impacts on linear Abnormal lipid profiles

growth with KDT, both with short‐term and long‐term use
[162–166] and that this impact may be greater in younger Hyperlipidaemia has been reported in a number of KDT
children [163]. This does not seem to be related to nutri- studies in children [163, 172–176], but whether this is associ-
tional content of the diet as those with a larger protein ated with atherosclerotic and inflammatory risk is not clear.
intake, following MCT KD, for example, still experienced Cardiovascular risk can be better assessed by looking at
reduced growth velocity [165], although a study looking at lipoprotein fractions: LDL and HDL levels. Raised total cho-
35 patients noted that poor linear growth was only seen lesterol and LDL cholesterol is not an indication to stop the
when protein intake was <1.4 g/100 kcal [167]. Growth diet, but will require continued monitoring, and dietary
needs to be monitored regularly, paying particular attention manipulation could improve levels. This could include
to height and considering alternative measures for non‐ alternative fat sources, e.g. choosing polyunsaturated fats
ambulatory patients if necessary. Following discontinua- and considering the use of some MCT in place of LCT. There
tion of the diet, significant catch‐up growth has been noted may also be a place for giving omega‐3 fatty acids to normal-
in both height and weight after a year [168], despite the sim- ise lipid levels [176].
ilar calorie content of the diets. This suggests that the impact It has been reported in some studies that despite initial
on growth could be related to acidosis, which can be man- hypercholesterolaemia, lipid levels can normalise after
aged if poor growth is identified, but there may also be an 12 months [163, 172] on diet, which could suggest some
effect on insulin‐like growth factor by KDT [169]; further metabolic adaption, but the long‐term impacts of KDT
research is required. and hypercholesterolaemia on cardiovascular health are
In long‐term use of the diet, a higher risk of bone fractures unknown. Studies have shown in the short term, up to 12
[170] has been reported. Many children considered for KDT months, that carotid intima media thickness did not alter
are already at risk for poor bone health due to long‐term use [177], but other studies have shown local and systemic
of AEDs and potential non‐ambulatory status (particularly arterial stiffness associated with KDT and raised choles-
in CP) [8]. The acidosis associated with KDT may increase terol and triglyceride levels [178, 179]; the impact of this is
this risk further. It is essential that calcium and vitamin D not clear.
intakes are supplemented to meet requirements; some cen-
tres over‐supplement, but there is no evidence base to sup-
port this practice. Some centres routinely monitor with
dual‐energy X‐ray absorptiometry (DEXA) scans after 2 Learning points: adverse effects
years on diet, but this is not a consensus, and there are limi-
tations in the use of DEXA dependent on age and practicali- • Common early onset side effects include constipation and
ties. The International Ketogenic Diet Study Group vomiting, which can be managed easily
recommendations [8] include this as an optional test during • Long‐term side effects can include renal stones, dyslipidae-
follow‐up and reported that less than half of centres (12/25) mia, reduced bone density and poor growth, and the risk
advocate using DEXA scans in children to evaluate for and presence of these needs to be monitored closely
osteopenia.
Transition 369
Discontinuing the ketogenic diet and Worden et al. conclude that ‘weeks rather than months
appeared to be safe’ [181]. A study by Kang et al. [131] sug-
Reasons for discontinuing KDT are individual, and the deci- gests that in infantile spasms KDT can be discontinued after
sion to withdraw KDT should always be made after a joint just 8 months, with no increase in seizure recurrence and
discussion between parents, the child if they have the capac- improved growth compared with the more typical 2‐year
ity, dietitian and neurologist. KDT is a medical treatment diet duration.
with risk of side effects and should not be continued if it has, The rate of diet discontinuation should be decided in dis-
unfortunately, been unsuccessful in reducing seizures in a cussion with the child and parent/caregiver, as it will
child. The International Ketogenic Diet Study Group [8] rec- depend on the reason for discontinuation. If the presence of
ommends that KD should be discontinued after 3 months if side effects or the diet being too challenging or unpalatable
unsuccessful. It has been shown that 75% of children who is the reason, then a quicker ‘wean’ may be preferred; in
responded to the diet will respond within 14 days, but some other circumstances families may be more anxious and pre-
can take over 2 months to respond [180]. If a trial of KD has fer to adjust the diet more slowly.
shown no benefit, then it can be discontinued safely over
days [181].
Occasionally, even if seizure control has improved on Learning points: discontinuing KDT
KDT, the decision may be taken to stop the diet if the child
and/or family find it so restrictive or unpalatable that it is • The KD can be discontinued over days if the diet has been
affecting adherence to diet and/or quality of life. If signifi- ineffective after a trial period (usually 3 months)
cant adverse effects have been experienced that have not • If KDT has been successful, then consideration should be
responded to diet manipulation or medical treatment (p. 367), given to discontinuing the diet after 2 years; the majority of
then it may also become necessary to stop diet. Less com- children can safely discontinue KDT without an increase in
monly, KDT may be discontinued after epilepsy surgery has seizure recurrence after 2 years on diet
treated a focal cause for seizures, so the diet is no longer • The risk of recurrence is not associated with speed of ‘wean-
required. In some cases it necessary to withdraw the diet ing’ the diet, although (in the absence of significant side
when there is no access to a ketogenic service when transi- effects) it is prudent to discontinue the diet gradually over
tioning from paediatric to adult healthcare. weeks (as would be done with any anti‐epileptic medication
The KD is not intended to be a lifelong treatment for epi- that was discontinued)
lepsy, and the International Ketogenic Diet Study Group • When to discontinue the diet and how quickly will depend
advises that risks and benefits should be reviewed at every on the individual circumstances and preference and should
clinic appointment, and discontinuation should be consid- be discussed with the patient and parent/caregiver
ered at 2 years’ duration of diet [8]. The Group also states • There is no maximum diet duration, and for disorders of
that ‘Shorter durations may be appropriate for infantile brain metabolism, it is generally recommended that the diet
spasms and status epilepticus, but longer diet durations are should be followed into adolescence, although the benefits of
likely necessary for Glut1DS and PDHD and may also be a lifelong diet are not clear
appropriate based on individual responses for other forms
of intractable epilepsy’. It also recommends that there is no
maximum diet duration and indeed KDT has been contin-
ued safely for more than 20 years [182]. Transition
Seizure recurrence is a potential risk of KDT discontinua-
tion in responders, and the recurrence rate has been esti- Guidance from NICE [6] supports the use of KDT in children
mated as 14%–25% [181, 183, 184]. Factors that have been and young people. Unfortunately, this guidance does not
associated with increased recurrence risk include focal recommend use in adults, as there is limited evidence and an
abnormality on magnetic resonance imaging (MRI), abnor- RCT has not been undertaken in this age group. In contrast
mal electroencephalogram (EEG) on discontinuation and the to earlier guidance, it does recommend further research into
genetic condition tuberous sclerosis [181, 183, 184]. It is the potential applications for KDT in adults, which is ongo-
accepted practice that the diet should be gradually discontin- ing within the UK [71].
ued (a process known as ‘weaning’ from the KD), rather than Despite this there are some adult ketogenic centres in the
stopped abruptly, as would be the case with any anti‐epilep- UK, but they are limited with only 7 out of 39 centres treating
tic medication. Stopping the diet, rather than weaning, is adults [7]. The consequence is that over 80% of paediatric cen-
only relevant in rare situations where the KDT is a major risk tres in the UK do not have access to transition services to
to health, e.g. severe hypertriglyceridemia on kPN. The adult care for KDT; children who are reaching transition age
reverse method to introducing the diet is followed, i.e. a step- may need to be weaned off KDT. A study at Johns Hopkins
wise reduction of ratio on the CKD and increasing CHO on Hospital [185] found that those with seizure reduction on KD
the MAD. Kossoff et al. [8] suggest reducing the ratio by 1:1 experienced recurrence or worsening of seizures with
each month on CKD, e.g. 4:1 to 3:1 to 2:1, until ketosis is lost. attempts to wean off diet for this purpose, concluding that
A faster speed of weaning off the diet has been shown not transition plans need to be in place for adolescents to support
to be associated with an increased risk of seizure recurrence, continued KDT in adult care. It has also been seen that
370 Ketogenic Diets
referrals for older children (over 14 years of age) are avoided that ‘high‐quality evidence on the effects of KDs is currently
to prevent this challenge when they reach transition age [186]. lacking in oncology patients’ [193] with evidence so far lim-
NICE guidance advises that service providers and com- ited to animal models, early phase trials and case study
missioners [187] ensure there are systems in place for young reports, although RCTs are in development [194].
people with epilepsy to have an agreed transition period The diet has also been associated with increased energy
during which their continuing epilepsy care is reviewed supply to skeletal and cardiac muscles in glycogen storage
jointly by paediatric and adult services. Unfortunately, this disease type III with KDT improving cardiomyopathy in
is not the case within KDT services, and more work is case studies [195].
needed nationally to improve service provision for this
older age group.
Learning points: extended use of ketogenic diet therapy
Extended use of ketogenic diet therapy
• KDT is recommended by NICE for the treatment for epi-
in paediatric dietetics
lepsy in paediatrics, and its effectiveness has been proven in
randomised controlled trials
Historically, the KDT has been used exclusively in treatment
• KDT in adults for weight management and treatment of
of epilepsy. There is ‘evidence to suggest that low‐carb diets
type 2 diabetes is gaining acceptance, but its use for these
are safe and effective in the short term for improvements in
conditions in children is not currently recommended
glycaemic control, weight loss and cardiovascular risk in peo-
• There is growing interest in KDT in other adult neurologi-
ple with Type 2 diabetes’, but KDT is discouraged in children
cal conditions and as a potential treatment for gliomas, but
with type 2 diabetes due to concern about growth [188].
more evidence is needed before being used as a mainstream
There is also increasing attention on the role of KDT in a
treatment for these conditions
diverse range of adult neurological conditions, including
Alzheimer’s disease, schizophrenia and Parkinson’s disease
[189–191].
There is interest in KDT as a potential treatment in adult
malignant gliomas by stopping glucose supply to tumour
cells and as a consequence inhibiting tumour growth [192].
Extended use of KDT in oncology is not, at present, main-
stream clinical practice, and a systematic review concluded
18
Evelyn Ward and James Evans
Childhood Cancers
and Immunodeficiency Syndromes
Childhood Cancers
Evelyn Ward
Introduction to maintain healthy growth and development throughout

treatment, which can often span several months if not years,
With advances in the treatment of childhood cancers achiev- is paramount.
ing an overall survival of around 82% in developed coun-
tries [1, 2], the role of nutrition has become essential in terms
Implications relating to nutritional status
of treatment, supportive care and treatment‐related morbid-
ity. Childhood cancers are rare. Currently in the UK 1 in 500
During cancer treatment poor nutritional status is linked to
children under the age of 15 years develops a cancer, equat-
adverse outcomes. Both undernutrition and overnutrition
ing to approximately 1600 newly diagnosed children each
can lead to clinical complications, higher relapse rates,
year [1]. Childhood cancers generally refer up to the age of
reduced well‐being and quality of life [3–9]. Malnutrition
15 years. These cancers are different from cancers affecting
contributes to a reduced tolerance to therapy, altered drug
adults in terms of appearance, location and response to treat-
metabolism, delayed wound healing and decreased immune
ment. There are 21 Children’s Cancer and Leukaemia Group
function leading to increased risk of infection and longer hos-
(CCLG) principal treatment centres (PTC) in the UK with
pital stay [10–16]. However, the existence of malnutrition at
many having dedicated Teenage Cancer Trust Units where
diagnosis or during treatment on overall survival is contro-
adolescents and young adults are treated. Many of the 21
versial and may depend on the disease and its extent [14, 17].
PTCs have shared care facilities with local district general
hospital paediatric departments known as paediatric oncol-
ogy shared care units (POSCU).
Learning points: implications of nutritional status
The use of refined multimodal therapy and combination
chemotherapy, as well as new immunotherapies, continues
• The provision of appropriate and effective nutritional sup-
to result in an ever increasing number of children and young
port and advice for the child undergoing treatment for can-
people being treated and surviving childhood cancers. New
cer is well recognised as an important part of supportive
second and third line treatments for relapsed disease have
care in order to:
also led to an increase in the numbers susceptible to the
⚬⚬ reverse any malnutrition seen at diagnosis
nutritional problems associated with their disease, treatment
⚬⚬ prevent malnutrition associated with treatment
and survivorship. The need for optimal nutritional status to
⚬⚬ enhance therapy and improve tolerance to treatment
deal with the rigours of the disease and treatments as well as

372 Childhood Cancers and Immunodeficiency Syndromes
intensification treatment blocks in children depending on

⚬⚬ promote growth and development
the presence of any minimal residual disease (MRD) detected
⚬⚬ improve immunological status
after induction chemotherapy.
⚬⚬ improve general quality of life
Maintenance chemotherapy is then given for up to 2 years
• Overnutrition and undernutrition are both recognised as
in girls and up to 3 years in boys.
major nutritional concerns in both the short- and long-
Intensive chemotherapy is primarily the treatment for AML,
term [18]
generally given as four blocks of chemotherapy, 3 weeks
• Both can lead to adverse outcomes such as more complica-
apart, but is dependent on neutrophil‐count recovery.
tions, higher relapse rates, reduced well‐being and quality
of life
Lymphomas
Lymphomas account for approximately 10% of all childhood

Types of cancers seen in childhood cancers and can be divided into two main groups:
• Non‐Hodgkin’s lymphomas (NHL) account for 60% of
The types of cancers seen in children can be divided into
lymphomas and are a large group of lymphoid tumours.
three main groups:
Those most commonly seen in children include B‐cell
• leukaemias NHL and T‐cell NHL. The majority of patients present
• lymphomas with asymmetric enlargement of lymph nodes in one or
• solid tumours more peripheral lymph node regions. Those with diffuse
bone marrow disease present with anaemia, neutropenia
Table 18.1 gives information on diagnostic tests, treatment
or thrombocytopenia.
and 5‐year survival rates [1, 2].
• Hodgkin’s lymphoma accounts for 40% of lymphomas.
Presenting symptoms are usually painless cervical and/
Leukaemias or mediastinal adenopathy. Symptoms also usually
include fever, night sweats, weight loss, fatigue and
Leukaemia is the most common malignant disease in infancy anorexia.
and childhood and accounts for 31% of all childhood can-
cers. Acute lymphoblastic leukaemia (ALL) is the most com-
Solid tumours
mon form of the disease. Approximately 80% of ALL in
children is of precursor B‐cell origin, about 15% is T cell, and
Solid tumours account for approximately 45% of all malig-
5% is more mature B‐cell derived [19]. Acute myeloid leu-
nant disease in children. The most common solid tumours
kaemia (AML) is the second most common leukaemia
are as follows:
accounting for 10%–15% of leukaemias, with 15%–20% of
the cases occurring in patients with predisposing conditions • Brain tumours. Brain and spinal CNS tumours are the
that include certain congenital syndromes such as Down’s most common solid tumours with medulloblastoma the
syndrome, Li‐Fraumeni syndrome or DNA instability syn- most common CNS tumour. Signs and symptoms of CNS
dromes such as Fanconi anaemia [20]. Although rare, tumours are generally caused by increased intracranial
accounting for 15% of leukaemias, chronic myeloid leukae- pressure including headaches, vomiting, drowsiness,
mia (CML) can occur in older children. It should be noted irritability, fits and diplopia. Other symptoms may
that prognosis in infants with ALL is poor. include weakness or unsteadiness on walking.
The leukaemias are fatal unless treated and clinical features • Neuroblastoma accounts for 8% of all childhood cancers. It
at presentation include bone marrow failure, anaemia, neutro- arises from the neural crest tissue in the adrenal medulla
penia (fever, malaise), thrombocytopenia (bruising, purpura, and elsewhere in the sympathetic nervous system; there-
bleeding gums, nose bleeds) and organ infiltration, tender fore, it most frequently occurs in one of the adrenal
bones, lymphadenopathy, splenomegaly and hepatomegaly. glands but can also occur alongside the spinal cord in the
Current treatment for ALL includes initial induction neck, chest, abdomen or pelvis. Most children present
chemotherapy aimed at achieving remission. The protocol is with an abdominal mass, loss of appetite, lethargy and
graded as regimen A for those children with standard risk bone pain. At presentation the tumour mass can often be
disease, regimen B for those children with intermediate risk large and complex. The presence of the biological marker
disease and regimen C for those children with high risk dis- MYCN, (known as MYCN amplification) suggests more
ease who have not responded to initial treatment or those aggressive disease, and treatment is more intensive.
with poor cytogenetics: Philadelphia chromosome t (9;22), Treatment and survival depends on the stage of the
near haploidy (<44 chromosomes), iAMP21 t (17;19) and disease.
MLL gene arrangement. All of these are rare. • Wilms’ tumour is a congenital malignant kidney tumour,
Following induction the next phase of treatment is con- which can be bilateral. The majority present with a large
solidation, and central nervous system (CNS) treatment abdominal mass. Other symptoms may include poor
aimed to prevent or treat CNS disease. There are one to two weight gain and loss of appetite, blood in the urine and
Table 18.1 Common age of occurrence, diagnostic tests, treatment and 5-year survival rates for some childhood cancers.
Treatment
Common
Diagnosis age range Diagnostic tests Chemotherapy Surgery Radiotherapy HSCT Other 5-year survival rate
ALL 3–7 years Blood tests Yes May be needed if CNS Yes – if likely to Steroids 87%
Bone marrow aspirate or testicular disease at recur or relapsed
Lumber puncture diagnosis disease
AML 3–7 years Blood tests Yes May be needed if CNS Yes – if likely to 67%
Bone marrow aspirate disease at diagnosis recur or relapsed
Lumber puncture disease
NHL Any age Blood tests Yes Yes – if relapsed Steroids 85%
Biopsy, bone marrow disease Rituximab
aspirate
x‐ray, USS, CT, MRI
scans
Hodgkin’s Adolescents Blood tests Yes Yes – if extended disease Yes – if relapsed Steroids 95%
lymphoma x‐ray, CT, MRI, PET or poor response to disease
scans chemotherapy
Medulloblastoma Any age Biopsy Yes Yes Yes – if over 3 years of Steroids to reduce 80% standard risk
CT, MRI scan age swelling around disease
Biological markers the brain 60% high risk disease
Neuroblastoma ≤5 years Blood tests, x‐ray Yes – unless stage 1 Yes Yes – high risk disease Yes – high risk High risk disease 67%
MIBG, CT, MRI scans and complete disease 1‐cis‐retinoic acid
Urinary catecholamine surgical resection Dinutuximab
Biopsy (ant‐GD2) +/−
Biological markers – to interleukin−2
check if MYCN
amplification
Bone marrow aspirate
Wilms’ tumour ≤5 years Blood tests Yes – unless stage 1 Yes Yes – if poor histology 90%
USS, CT, MRI scans disease
Biopsy
Rhabdomyosarcoma ≤10 years Blood tests Yes Yes Yes – depending on 67%
CT, MRI scans histology
Biopsy
Ewing’s sarcoma/ Adolescents Blood test Yes Yes Yes – if incomplete Yes – if poor 66%
pPNET and older CT, MRI scans surgical resection response
children Biopsy
Osteosarcoma Adolescents Blood tests Yes Yes Yes – if poor response Mifamurtide 60%
and older CT, MRI scans
children Biospy
Retinoblastoma ≤5 years Eye examination Yes In some Cryotherapy, laser 95%
Blood test for RB gene cases – enucleation therapy,
brachytherapy
ALL, acute lymphoblastic leukaemia; CNS, central nervous system; AML, acute myeloid leukaemia; NHL, non‐Hodgkin’s lymphoma; USS ultrasound scan; CT/MRI, computerised tomography/magnetic
resonance imaging; PET, positron emission tomography; MIBG, iodine‐123 meta‐iodobenzylguanidine; pPNET, peripheral primitive neuroectodermal tumour.
Source: Adapted from [1, 2].
high blood pressure. Children with the WT1 gene or Metabolic factors
WT1 syndromes have an increased risk of developing a
Wilms’ tumour. Cancer cachexia is complex and multifactorial involving
• Rhabdomyosarcoma is the most common type of soft tissue involuntary progressive weight loss as a result of skeletal
sarcoma in children that develops from muscle or fibrous muscle mass depletion with or without adipose tissue deple-
tissue. There are two main subgroups: embryonal (80%) tion. It is characterised by systematic inflammation and met-
and alveolar (20%). Rhabdomyosarcoma occurs at a wide abolic changes resulting in a negative protein and energy
variety of primary sites but is most common around the balance leading to progressive functional impairment.
head and neck. Other sites include genito‐urinary and Additional factors to consider in a diagnosis of cancer
occasionally limb, chest or abdominal wall. cachexia are chronic inflammation, anaemia, protein deple-
• Ewing’s sarcoma and peripheral primitive neuroectodermal tion, anorexia and fatigue [26]. Although studies in the 1990s
tumour (pPNET). Ewing’s sarcoma is a type of bone demonstrated changes in the metabolism of fat, carbohy-
tumour. Any bone can be affected, but it is more common drate and protein in the child with cancer [10, 27, 28], a recent
in the pelvis, femur or shin bone. Persistent localised review paper suggested that the presence of cachexia in chil-
bone pain is a characteristic symptom that usually pre- dren could not be confirmed [21]. More robust studies are
cedes the detection of a mass. pPNET is a soft tissue sar- required to determine the presence of the inflammatory pro-
coma of neuroepithelial origin, which can be thought of cess in childhood cancer patients and its impact on nutri-
as being similar to a Ewing’s sarcoma. tional status [21, 23]. Other factors can affect the metabolic
• Osteosarcoma is a high grade bone tumour. It often occurs turnover of a child with cancer such as age, gender, nutri-
at the end of bones where new bone tissue is forming, tional status, body composition, hormones, physical activity,
predominantly in the arms or legs, particularly around energy intake, anti‐cancer treatment, surgical stress and
the knee. Pain and swelling around the affected bone are infections [23].
the most common symptoms.
• Retinoblastoma is the commonest malignant eye tumour
in children, accounting for around 3% of childhood can- Complications of the disease and treatment
cers. All bilateral tumours are thought to be hereditary
due to the RB1 gene in 40% of cases, as are 15% of unilat- In childhood cancer, malnutrition is generally due to an
eral cases. Children of affected families are screened from insufficient intake and absorption of nutrients caused by
birth. gastrointestinal (GI) side effects of treatment [22]. Anorexia,
• Additional information on rarer tumours, e.g. hepato- stomatitis, mucositis, constipation, vomiting, diarrhoea and
blastoma and germ cell tumours, can be obtained from dysgeusia are important contributory factors to the weight
the Children’s Cancer and Leukaemia Group (CCLG) loss seen in children undergoing treatment for cancer [29].
website [1]. Table 18.2 shows the side effects relating to drugs commonly
used in treatment of paediatric malignancies.
Aetiology of malnutrition in children with cancer Psychological factors

The incidence of malnutrition in children at diagnosis differs Learned food aversions, nausea and vomiting associated
partly due to variation in the studies conducted in different with foods consumed close to chemotherapy administration,
types of paediatric malignancies and variation in the nutri- have been demonstrated in children with cancer along with
tional assessment parameters used [14]. A review of studies the phenomenon of anticipatory vomiting [30]. Food is one
concluded an estimated prevalence in developed countries area of treatment that both the child and parent can try to
to be [21]: control resulting in increased tension and anxiety around
• 5%–10% at diagnosis and around 0%–5% during treat- food, which can lead to negative feeding behaviour and eat-
ment for leukaemia ing becoming an unpleasant experience for both the child
• 50% at diagnosis and 20%–50% during treatment for and their family.
neuroblastoma
• 0%–30% at diagnosis and during treatment for other
Identification of nutritional risk and assessment
solid tumour patients
Consensus is that the risk of nutritional morbidity Assessment of nutritional status is a vital component of sup-
is higher in children with advanced disease, metastatic portive care and is essential for monitoring the need for nutri-
solid tumours and higher treatment intensity. The initial tional intervention. Nutritional status indices may be useful
nutritional problems resulting from the tumour are soon prognostic markers of response to therapy or toxicity [31].
compounded by iatrogenic nutritional abnormalities, Despite height and weight measurements being the mainstay
the consequence of the treatment and its complications. of nutritional assessment in children with cancer [32], the
Metabolic and psychological factors also have a role reliability of weight‐related indices is reduced in children
[22–25]. with solid tumours, as outlined in Table 18.3. Assessment at
Nutritional Requirements and Feeding 375
Table 18.2 Side effects relating to treatment seen in paediatric oncology diagnosis may not be the best indicator of overall nutritional
patients. status, indicating the need for ongoing nutritional assess-
ment and intervention throughout treatment [33].
Side effect Causative drug
It is well documented that the nutritional risk of the child
Infection Both chemotherapy and radiotherapy are with cancer is associated with the diagnosis of certain
known immune depressants tumours and stages of the disease, either as a result of the
Diarrhoea Actinomycin, doxorubicin, methotrexate, underlying disease and/or as a result of the anticipated tox-
cytosine, interleukin‐2, irinotcan icity from the current treatment protocol (Table 18.4) [23, 33,
Nausea and vomiting Actinomycin, carboplatin, cisplatin, 34]. Studies highlight that there is no simple method to accu-
cyclophosphamide, doxorubicin, ifosfamide, rately identify poor nutritional status in children treated for
cytosine, etoposide, methotrexate, malignancy, and there is also inconsistency between treat-
procarbazine, thioguanine, interleukin‐2 ment centres [35, 36]. The UK Royal College of Nursing
Stomatitis mucositis Actinomycin, adriamycin, daunorubicin, (RCN) in their guideline Nutrition in children and young people
doxorubicin, epirubicin, bleomycin, with cancer includes a condition specific assessment tool
melphalan, methotrexate based on STAMP (screening tool for the assessment of mal-
Renal damage and Cisplatin, cyclophophamide, ifosfamide nutrition in paediatrics) [37] and the disease criteria in
nutrient loss Table 18.4 [38]. However it has not been audited or validated.
Constipation Vincristine SCAN (nutrition screening tool for childhood cancer) has
been assessed for children and young people with cancer. It
Weight gain and raised Dexamethasone, prednisolone
blood glucose levels is designed to identify those who are at risk of malnutrition
by asking six questions [39]:
Hypoalbuminaemia l‐Asparaginase, dinutuximab
Pancreatitis l‐Asparaginase • Do they have a high risk cancer?
• Are they currently undergoing intensive treatment?
Weight loss α‐Interferon
• Do they have any GI tract symptoms?
Bone morbidity Dexamethasone, prednisolone, • Have they had a poor intake over the past week?
methotrexate, ifosfamide
Vincristine (due to reduced physical activity)
• Any weight loss over the past month?
l‐Asparaginase associated with osteonecrosis
• Do they show any signs of under nutrition?
In practice assessment tends to be a combination of nutri-
tional risk based on diagnosis (Table 18.4), anthropometrics
and questions similar to the SCAN screening tool.
Table 18.3 Anthropometric assessment. Learning points: nutritional risk and assessment
Anthropometric • In children with cancer body weight can be influenced by

assessment Potential limitations tumour mass and hydration given alongside chemotherapy
• Weight • Can be unreliable due to solid tumour • This can mask loss of fat and skeletal muscle
mass/ascites/hyper‐hydration given with • There are no simple measures that accurately identify poor
chemotherapy nutritional status in children with cancer
• Height • Some lack of growth in height is observed • In practice nutritional risk is associated with the diagnosis
in children undergoing treatment for cancer and stage of the disease, age of the child and intensity of the
• Growth charts • A decrease in current centiles for weight treatment
(or height) of two major
centiles – indication for nutritional support
• Percentage • Percentage weight:height ≤90% – can be
weight:height indication for nutritional support
Nutritional requirements and feeding
• BMI • Weight change can be distorted by large • Non‐catabolic, low nutritional risk: aim for estimated
solid tumours therefore not reliable and
average requirement (EAR) for energy and the reference
doesn’t correlate to changes in fat free mass
nutrient intake (RNI) for protein, vitamins and minerals
• Total weight loss ≥5% • Check – some weight loss may be due to [40, 41]
relative to pre‐illness solid tumour shrinkage or post‐surgical
weight resection
• Catabolic children, undernourished children or children
with increased losses due to the GI losses or renal tubular
• Mid upper arm • Useful measurement to do in children with
losses: an estimation of the protein and energy require-
circumference solid tumours as independent of tumour
(MUAC) shrinkage
ments for sick children is given in Table 1.13
• Consideration of requirements and method of nutritional
• Triceps skinfold • Not routinely used in clinical practice
support must take into account the child’s age, weight
thickness (TST)
and clinical condition
Table 18.4 Types of childhood cancers associated with high or low nutritional risk and high risk of fat accumulation [23, 33, 34].
High nutritional risk Low nutritional risk High risk of fat accumulation
Advanced disease during initial ALL regimen A patients ALL patients on corticosteriods
intense treatment
High risk neuroblastoma Non metastatic solid tumours Craniopharyngioma
Stage III and IV Wilms’ tumour Retinoblastoma Other malignancies with large or
prolonged does of corticosteroids
High risk rabdomyosarcoma Hodgkin’s disease Total body or cranial irradiation
Ewing’s sarcoma/pPNET Germ cell tumours
Osteosarcoma Advanced disease in remission
during maintenance treatment
Medulloblastoma/CNS PNET
Diencephalic tumour
Nasopharyngeal tumour
B‐cell NHL
AML
Some ALL
Infants and teenagers
Regimen B and C
Patients relapsed ALL
Bone marrow‐transplant patients
Allogeneic
Autologous
pPNETnet, peripheral primitive neuroectodermal tumour; CNS PNET, central nervous system primitive neuroectodermal tumour;
NHL, non‐Hodgkin’s lymphoma; AML, acute myeloid leukaemia; ALL, acute lymphoblastic leukaemia.
• Energy intake should be regularly reviewed, particularly consume enough food. However, some will require oral
in children at high risk of fat accumulation (Table 18.4) nutritional supplements. In clinical practice their consump-
tion can be limited mainly due to treatment‐related taste
With changes in body composition now well documented
alterations and compliance. The following should be
and highlighting an increase in fat mass and risk of overnu-
considered:
trition in children treated for cancer, requirements for energy
in particular should be regularly reviewed throughout the • Advice on how to modify sip feeds, e.g. adding to nor-
child’s treatment [22, 42]. Although there is an increased mal commercial milkshakes or juice; trying as ice lollies;
awareness to try to improve the physical activity of children using neutral flavoured supplements to add to milk to
undergoing treatment for cancer, for the non‐catabolic child drink, milk for breakfast cereals, soups, puddings
who is inactive energy requirements should be adjusted • Fresh milk‐based supplements are more acceptable [45]
accordingly for low physical activity [43]. • Low volume energy supplements can be more accepta-
ble either taken on their own like a ‘medicine’ or added
to food and drinks
Oral feeding
• Nutritionally complete ‘compact’ supplements should
be considered as less volume needs to be consumed
Advice should be given routinely about:
The aim should be to provide the right food at the right
• the impact of cancer and its treatment on nutritional status
time by taking a flexible approach tailored to the individual
• eating problems related to the side effects of
needs of the child [46]. With this is mind some treatment
treatment [44]
centres have the facility for meals and/or snacks to be pre-
• food safety [44]
pared at ward level to achieve this more flexible approach
• use of high energy foods, food fortification and small
to eating.
frequent meals and snacks [44]
Enteral nutrition
Oral nutritional supplements
Oral feeding is the best method of nutrition support in Children at higher nutritional risk due to their disease
patients with a low nutritional risk if they are able to and/or treatment should be identified early in treatment
Nutritional Requirements and Feeding 377
and enteral nutrition (tube feeding) instigated. Early inter- • A fibre‐containing feed should be used in children at risk
vention can prevent nutritional decline during treatment of constipation due to treatment with vincristine, e.g.
[47]. It is well documented [48–50] that enteral nutrition is ALL, brain/spinal CNS tumours
successful in: • A hydrolysed protein feed is recommended if there is
impaired GI function due to malabsorption, lower gut
• reversing any malnutrition seen at diagnosis
mucositis, radiation enteritis, graft versus host disease
• improving nutritional status and maintaining an ade-
(GvHD) or when weaning off PN
quate nutritional status
• An amino acid‐based formula may be required if a
• improving energy intake and well‐being
hydrolysed protein feed is not tolerated, e.g. with severe
• offering an alternative route for fluid and medication.
lower gut mucositis, grade III GvHD
Children on treatment frequently require additional elec-
• A higher energy feed should be used if there are increased
trolyte supplementation such as potassium, phosphate;
energy requirements or to maximise intake over a shorter
an enteral tube in situ can help with their administration
period of time
and subsequently improve compliance
• A higher energy feed is beneficial if there is a fluid restric-
• helping to reduce both parental and child anxiety related
tion due to, e.g. veno‐occlusive disease (VOD) or fluid
to trying to achieve an adequate oral intake
overload
Enteral nutrition has advantages over parenteral nutrition • A higher energy feed is also used where, due to abdomi-
(PN) [34, 49, 50]. While nasogastric feeding is effective, when nal disease, large feed volumes are not tolerated, e.g.
there is a need for long‐term nutrition support or there are neuroblastoma, hepatoblastoma, Wilms’ tumour
problems such as vomiting, thrombocytopenia, mucositis • A trial of a lactose‐free feed may be necessary if diar-
or dysphagia, a gastrostomy tube is more beneficial. rhoea does not settle post-chemotherapy, or the child has
Gastrostomy feeding is safe, effective and only associated had rotavirus or norovirus infections
with minor complications [51–54]. Table 18.5 gives criteria • A minimal long‐chain triglyceride (LCT) formula is indi-
for gastrostomy tube placement in children with cancer. cated if there is post‐operative chylothorax, e.g.
Jejunal feeding should be considered in children with pro- neuroblastoma
longed vomiting or gastric dysmotility associated with treat-
ment in whom antiemetics and prokinetics have had a The volume and delivery of the feed regimen should be
limited effect. A gastrostomy/jejunostomy feeding tube has determined according to the child’s normal daily routine
proved useful in children with brain tumours who have an and can be provided as a continuous infusion, intermittent
unsafe swallow post operatively and vomit large bolus bolus feeds or a combination of both:
gastrostomy feeds. • Continuous feed regimens are usually better tolerated
The choice of enteral feed depends on the child’s age, GI than intermittent bolus feeding due to the GI side effects
function and, to some degree, their treatment protocol. A of treatment such as nausea and vomiting
wide variety of feeds and formulas are used in paediatric • During periods of intensive treatment or admissions for
oncology: febrile neutropenia, it may be necessary to feed continu-
• Generally an age‐appropriate standard enteral feed is ously 20–24 hours in order to achieve tolerance and max-
tolerated in children with normal GI function imum nutrient intake
• Children prone to vomiting and those with large abdom-
inal masses tolerate continuous feeding with frequent
Table 18.5 Indications for gastrostomy placement.
breaks by feeding in cycles of say 5 hours with 1 hour rest
Indications for gastrostomy placement • In between treatments and when at home, most children
Patients treated on intensive protocols with high emetogenicity or risk of
are able to tolerate bolus feeds or combination of contin-
mucositis uous and bolus feeding
Patients requiring long‐term nutritional support ≥3 months Frequent monitoring is essential to provide effective nutri-
Patients unwilling to accept or tolerate a nasogastric tube tion support as feed tolerance and oral intake can vary due
Adolescent patients should routinely be offered the choice of a to treatment and its side effects. The majority of children will
gastrostomy require enteral feeding throughout their intensive treatment
Nasopharyngeal carcinoma or any other tumour in head and neck area protocol, but once treatment is completed or they go onto
requiring radiotherapy treatment maintenance treatment, an effort should be made to wean off
Brain or CNS tumour with post‐operative swallowing dysfunction
enteral feeding. Maintaining some oral intake while being
tube fed can make this process a lot easier and quicker. Input
Contraindications for gastrostomy placement
from a psychologist is helpful for those with feeding behav-
Poor anaesthetic risk iour problems struggling to get off enteral feeding.
Short‐term feeding <3 months Infants treated for cancer can be more challenging due to
Abdominal disease present (individual assessment) the length of treatment, problems with gut toxicity and sto-
matitis. Starting complementary feeding around 17 weeks of
CNS, central nervous system. age may be considered to establish some oral feeding skills
in between periods of severe oral mucositis; otherwise feed- Careful consideration should be given before commence-
ing development is delayed making it harder for the infant ment of PN; it is of limited nutritional benefit if given for less
to develop normal feeding skills [55]. Input from a speech than 1 week [57]. Metabolic complications of PN are described
and language therapist should be considered. [58] and are not significantly different between children with
malignancies and other children requiring PN. The child’s
clinical condition may also limit the effectiveness of PN. The
Learning points: enteral nutrition majority of children with cancer will have central venous
access. Table 18.6 highlights potential problems and solutions
Adequate enteral feeding support can be provided even in using PN in children treated for cancer and post-HSCT.
in children at risk of mucositis by:
• identifying those at risk early in treatment Nutrition and the child with cancer undergoing
• early tube placement
haemopoietic stem cell transplant
• type of feed – consider hydrolysed protein feed if there is
lower gut toxicity
HSCT is widely used in children with malignancies.
Allogeneic transplant is indicated for patients with high risk
leukaemia or patients with leukaemia who have disease
Parenteral nutrition recurrence. Some children with solid tumours, e.g. high risk
neuroblastoma and Ewing’s sarcoma may undergo autolo-
A Cochrane review highlighted there is limited evidence gous stem cell transplantation.
from individual trials to suggest that PN is more effective The priming chemotherapy causes severe nausea, vomit-
than enteral nutrition in well‐nourished children and young ing, mucositis, diarrhoea and protein‐losing enteropathy.
people with cancer undergoing chemotherapy [56]. PN is Transient intestinal failure is common. Nutrition support is
generally indicated in children with: provided to minimise the morbidity of both the conditioning
regimens and complications resulting from the procedure
• neutropenic enterocolitis such as GvHD or VOD of the liver.
• ileus or bowel obstruction VOD can be life‐threatening and is typically characterised
• typhlitis by hyperbilirubinaemia, hepatomegaly, hypoalbuminaemia,
• severe mucositis increased platelet consumption, rapid weight gain and
• severe GvHD of the gut following haemopoietic stem ascites [59]. Incidence rates of 60% have been reported, how-
cell transplant (HSCT) ever few studies report an incidence above 40% [60].
• chylous ascites post‐surgery when there is no response to PN continues to have a role in children who develop
a minimal LCT diet severe GI toxicity or GvHD. Table 18.6 highlights some of the
Table 18.6 Challenges and solutions in the use of parenteral nutrition in children with cancer and post-HSCT.
PN challenges Potential solution
Fluid restriction due to VOD, fluid overload, drug and Check child has central venous access
blood product volumes Use more concentrated solutions to maximise protein and energy intake
Ascites related to VOD Keep sodium addition to a minimum
Large diarrhoeal losses due to mucositis or GvHD Close monitoring of electrolytes and if safe may require additions above normal
recommended amounts [58]
Renal tubular losses post-cisplatin or ifosfamide Close monitoring of electrolytes and if safe may require additions above normal
chemotherapy recommended amounts [58]
Hypokalaemia due to antifungal amphotericin If safe increase potassium in PN
Consider use of potassium sparing diuretics – amiloride, spironolactone, potassium
canrenoate
Monitor blood potassium levels
Risk of iron overload Parenteral iron is not given routinely due to the majority of patients receiving
frequent blood transfusions
Low blood zinc and selenium levels Routinely monitor trace element levels if on PN for >2 weeks
Hyperglycaemia due to steroids for management of GvHD Consider insulin infusion if a reduction in glucose in PN would compromise
nutritional intake
VOD – hyperbilirubinaemia/abnormal LFTs Consider ω3PUFA and MCT lipid solution, e.g. SMOFlipid
HSCT, haemopoietic stem cell transplant; PN, parenteral nutrition; VOD, veno‐occlusive disease; GvHD, graft vs. host disease; LFT, liver function test;
PUFA, polyunsaturated fatty acid; MCT, medium chain triglyceride.
Late Effects of Treatment 379
potential challenges and solutions to using PN in children lysis. Side effects include an increased appetite and raised
following HSCT. blood glucose levels. Hyperglycaemia is usually only tran-
Adequate nutrition support can be provided enterally sient while the child is receiving the dexamethasone; how-
[61, 62], and during periods of gut toxicity, a hydrolysed ever, in some cases it may be permanent. Children who
protein‐based feed is recommended or an amino acid‐based appear more susceptible to hyperglycaemia include those
formula if this is not tolerated. Some centres use a graded with a family history of diabetes, those overweight at diag-
dietary guideline for children with GvHD consisting of dif- nosis and older children and adolescents.
ferent phases relating to the grade of GvHD. An example is Sliding scale intravenous insulin is given until blood sugar
given below: levels are controlled. Subsequently an alteration in diet may
be all that is necessary to control blood sugar levels; how-
• phase 1 – gut rest and supported with PN (Grade IV
ever, a twice daily injection of premixed analogue and
GvHD)
isophane insulin may be advised, or a basal bolus regimen.
• phase 2 – clear liquid diet and amino acid‐based enteral
Using basal and rapid‐acting analogue insulins allows
feed (Grade III GvHD)
greater flexibility with regard to mealtimes as there is no
• phase 3 – low fat, low fibre, low acid, low irritant, lac-
need to adhere to rigid meals and snacks as a bolus of insulin
tose‐free diet (Grade III–II GvHD)
is injected prior to food. Children treated for ALL can have
• phase 4 – continuation of low fat, low fibre, low acid, low
variable appetites and food intakes, and hence a basal bolus
irritant, lactose‐free diet (Grade II GvHD)
regimen allows for this variation.
• phase 5 – lactose‐free diet (Grade II–I GvHD) [63, 64]
Dietary advice should be simple: the avoidance of rapidly
Children who receive a cord blood stem cell transplant absorbed carbohydrate with suitable alternatives and snack
may have prolonged diarrhoea that is distinct from GvHD, suggestions. Restriction of high fat foods and increased fibre
and if all other causes have been excluded, cord colitis syn- intake may not be appropriate in children who have poor
drome may be considered [65, 66]. Treatment involves a 10‐ appetites and who would be unable to achieve an adequate
to 14‐day course of metronidazole alone or in combination energy intake.
with a fluoroquinolone.
In addition patients undergoing bone marrow transplant
Late effects of treatment
(BMT) are severely neutropenic and need to have a ‘neutro-
penic’ diet to prevent GI infection from food‐borne patho-
The development of curative therapy for the majority of pae-
gens. The provision of a neutropenic diet is described
diatric cancers has resulted in a growing population of child-
elsewhere (p. 49).
hood cancer survivors who are at an increased risk of various
health problems [67, 68].
Learning points: monitoring and follow‐up
Bone morbidity
• Children on nutritional support need frequent monitoring
and review throughout treatment Bone morbidity in children with cancer both during and
• It is often necessary to change the method of nutritional after completion of treatment is increasingly recognised as
support, type of enteral feed and route of delivery depend- both a short‐term and long‐term problem [69, 70]. This is
ing on treatment, nutritional status and tolerance especially the case in children who receive large cumulative
• Once on maintenance treatment or completed treatment doses of glucocorticosteroids and methotrexate for treat-
follow‐up continues until weaned off enteral tube feeding or ment, such as ALL. Risk factors, particularly for children
if still tube feed dependent, care may be transferred to local treated for ALL, are highlighted in Figure 18.1. Other
dietetic services: patients at risk include those treated for Ewing’s sarcoma
⚬⚬ advice on the importance of following a healthy diet and and osteosarcoma who have received methotrexate and
exercise should routinely be given at the end of treat- ifosfamide [67, 74].
ment review with the medical team During treatment the majority of PTCs routinely check
⚬⚬ medical follow‐up, repeat scans and blood tests con- vitamin D status at diagnosis and at regular intervals during
tinue at regular intervals, although they reduce in treatment. Vitamin D supplementation during treatment is
frequency until 5 years off treatment when care will advised in line with current national guidelines [75]
transfer to annual review at the late effects clinic (Table 18.7). As a precaution, some centres are not supple-
menting vitamin D during induction chemotherapy for ALL
due to the potential risk of hyperphosphataemia based on
one small study [76]. Children and young people who are 5
Steroid‐induced diabetes years off treatment and attend long‐term follow‐up clinics
annually will routinely have vitamin D levels measured.
Children treated for ALL regularly receive the corticosteroid Osteonecrosis is a debilitating complication seen both dur-
dexamethasone as part of their treatment. Dexamethasone ing and after treatment for ALL and is an iatrogenic compli-
has potent lymphocytotoxic activity causing lymphoblast cation attributed to the risk factors highlighted in Figure 18.1.
Steroids Chemotherapeutics
(Dexamethasone > Prednisolone) Methotrexate - poorer bone
Higher incidence of skeletal morbidity with Dex OR = formation and increased
2.6 (95%Cl 1.1–5.9, p = 0 .027) [71] bone resorption [72]
Vincristine - ? as a result of
reduced physical activity
L–Asparaginase - ? association
Nutritional problems to osteonecrosis [72]

Skeletal
morbidity
Mineral abnormalities Physical inactivity
Body mass composition

Vitamin D depletion
? Disruption of bone acquisition at Disease process [72]

critical time, i.e. puberty [71]
Figure 18.1 Factors that contribute to skeletal morbidity in patients with ALL. ALL, acute lymphoblastic anaemia; ? = other potential factors.
Table 18.7 Serum 25‐hydroxyvitamin D concentrations, health and disease [75].
Serum 25(OH)D (nmol/L) Vitamin D status Manifestations Management
<25 Deficient Rickets Treat with high dose calciferol

Osteomalacia
25–50 Insufficient Associated with disease Vitamin D supplementation: 400 IU (10 μg)
50–75 Adequate Healthy Lifestyle advice
>75 Optimal Healthy None
Reprinted with permission of BMJ Publishing Group Ltd.
The prevalence is around 5.5% with 38% of patients requir- energy expenditure and energy intake. Lack of physical activ-
ing some form of surgery [77]. ity, high energy intake and metabolic changes following pro-
Correction of bone mineral loss may be possible by cor- longed courses of chemotherapy and steroids may all play a
recting dietary deficiencies including those of calcium and part in altering body composition in ALL survivors [81–84].
vitamin D; however, in some cases bisphosphonates such as Attention is also focusing on the increased risk of obesity
pamidronate or alendronate are given. Advice on improving during treatment (Table 18.4), with a prevalence ranging
diet and physical activity should be recognised as a strategy from 25% to 40% [85]. Studies have identified that significant
for amelioration and prevention [74]. weight gain can occur in ALL patients between diagnosis
and the end of treatment [83–86]. As well as affecting emo-
tional and social health‐related quality of life [8], studies
Obesity suggest it may influence survival rates [4, 7, 87]. The mecha-
nisms for weight‐influencing event‐free survival are unclear.
Another well‐reported effect in childhood cancer survivors Some possibilities include pharmokinetic variations on
is the prevalence of obesity, particularly in children treated chemotherapy, direct influence on adipose tissue on leukae-
for ALL and brain tumours [11, 78, 79]. The majority of stud- mia resistance, differences in protein synthesis and haemat-
ies have looked at ALL survivors where, as well as obesity, opoietic reserves causing reduced target dose delivery or
there is a high prevalence of endocrine and metabolic disor- other yet unidentified causes [4]. Studies vary as to when the
ders such as growth hormone deficiency, hypothyroidism, risk of obesity is highest during treatment for ALL [4, 7, 86]
insulin resistance, hyperlipidaemia and increased cardiovas- so routinely giving advice on ‘healthy eating’ and exercise
cular risk [80, 81]. throughout the different stages of treatment should be con-
The mechanism for the onset of obesity following treatment sidered, with monitoring of weight and BMI to guard against
for ALL may be partly due to a sustained imbalance between overweight and obesity.
Areas Requiring Further Research 381
is taking. A useful information book for families is

Learning points: nutrition related late effects of treatment
Complementary and natural therapies for your child available
from the CCLG website [92].
These include:
• overweight and obesity
• endocrine and metabolic problems Areas requiring further research
• growth hormone deficiency
• hypothyroidism Vitamin supplementation/antioxidants
• insulin resistance
• hyperlipidaemia Certain chemotherapy agents’ mode of action involves the
• bone morbidity generation of free radical oxidants to cause cellular damage
and necrosis/apoptosis of malignant cells. The formation of
As weight gain and obesity are identified as risk factors free radicals, leading to oxidative stress, is one of the main
during treatment for ALL, advice on healthy eating and pathogenic mechanisms for toxicity with toxicity being a
exercise should be given during treatment and reiterated dose limiting factor for treatment. However, there is concern
at the end of treatment. that the formation of reactive oxygen species by antioxidants
during treatment may impair the action of some chemother-
apy drugs [93, 94]. A small study has shown an inadequate
antioxidant intake, especially in children not on any form of
Complementary and alternative diets dietary supplementation [95].
Currently there are very few good quality studies looking
Some families will seek out alternative treatments on the at changes in antioxidant status and oxidative stress in chil-
internet including the role of alternative or complementary dren undergoing treatment for cancer. It is clear that further
nutritional therapies. They seek information on food choices, research is required, and until then the UK Paediatric
dietary supplements and complementary nutritional thera- Oncology Dietitians’ Group advises the following for chil-
pies in a bid to improve quality of life and increase chances dren with cancer:
of survival [88]. The majority of such diets are made up of • Generally children on supplementary enteral feeds or
components that claim to have three major functions: detoxi- nutritionally complete oral nutritional supplements
fication, strengthening of the immune system and specific should not need additional vitamin and mineral
therapies to attack the cancer cell [83]. supplements
Apart from a lack of robust evidence for their use, these • Megadoses of a single vitamin or combination of vita-
diets are not recommended for children being treated for mins should be advised against (with the exception of
cancer [89, 90] as they: prescribed vitamin D)
• usually advocate a strict vegetarian or vegan regimen, • Children not receiving nutritional support who have a
restrict animal products, refined carbohydrates and only limited fruit and vegetable intake may benefit from a
allow small quantities of fat general multivitamin supplement
• can be high fibre, high fruit/fruit juice/juicing and veg- • Advice on how to incorporate more fruit and vegetables
etable‐based diets into the diet should be given
• can involve fasting and use of laxatives and enemas • Due to frequent blood transfusion, it is advisable that
• advise addition of supplements that can be toxic in high they take a supplement that does not contain any iron, or
doses only a small amount (maximum of 15% RNI)
This can result in early satiety and diarrhoea leading to

weight loss [90]. The low energy density and low protein Glutamine
content can lead to malnutrition, which in turn can result in
a reduced immune function, increased toxicity from conven- Many chemotherapy drugs cause structural and functional
tional treatment and, therefore, a poorer response [89]. injuries to the GI tract resulting in mucositis. It is well docu-
High doses of vitamins and minerals may be harmful to mented that glutamine is a major fuel and important nitro-
children and there being a risk of interaction with conven- gen source for enterocytes and plays a key role in maintaining
tional treatment. It is essential that any parent contemplating mucosal cell integrity and gut barrier function [96]. An oral
the use of an alternative diet seeks appropriate advice from dose of up to 0.65 g/kg has been shown to be safe and accept-
their child’s physician or dietitian. Frenkel et al. provide use- able to use in paediatric oncology patients [97]. A significant
ful information on 10 supplements that have the best sug- reduction in the severity and duration of stomatitis using a
gestions for benefit, highlighting the safety and interactions smaller dose of oral glutamine in children has been demon-
of the supplements [91]. Best practice is to discuss any poten- strated [98]. Although no significant difference in oral
tial supplements parents may want to give their child with mucositis was observed, significant reductions in the num-
the hospital pharmacist involved in their care. They will be ber of children requiring PN and duration of PN have been
aware of potential interactions with all medications the child demonstrated in other studies using oral glutamine [99, 100],
perhaps reflecting the role of glutamine in improving lower reducing the incidence and severity of mucositis [113] and
gut mucositis. prevention and treatment of GvHD [114]. A recent feasibility
Evidence for the use of glutamine in PN given to children study in children and adolescents undergoing stem cell
with cancer remains weak. One randomised study in chil- transplantation reported no cases of bacteraemia or unex-
dren following stem cell transplantation found no signifi- pected adverse events related to the probiotics [115].
cant difference in the incidence of mucositis [101]. Currently there are insufficient studies to assess the effects of
Although oral glutamine has been shown to be safe to use probiotics in children with cancer, but there is an increasing
in paediatric oncology, studies to date are not statistically interest for studies to be undertaken.
significantly in terms of mucositis, infection rates and length
of stay [56]. It is not widely used.
Ketogenic diet
Eicosapentaenoic acid Ketogenic diets have gained popularity amongst patients and
researchers, although the efficacy and benefits are still contro-
Eicosapentaenoic acid (EPA) derived from fish oil has been
versial in oncology [116, 117]. The aim of the ketogenic diet for
studied in adult cancer patients with cachexia. EPA may mod-
cancer patients is to reduce energy production of the cancer
ulate aspects of the inflammatory responses implicated in the
cells and therefore decrease tumour cell proliferation [116].
metabolic changes associated with weight loss and muscular
The theory and science behind this notion is due to the
atrophy. EPA may downregulate production of pro‐inflamma-
resurgence of the Warburg effect. Warburg described how
tory cytokines and attenuate progression of the acute phase
cancer cells consume glucose and produce lactic acid
protein response. A Cochrane review looking at EPA supple-
under aerobic conditions, and this glycolysis induces car-
ments in adult studies highlighted insufficient data to define
cinogenesis [118]. However, the discovery of oncogenes
the optimal dose and insufficient evidence that it improved
and tumour suppressor genes, leading to theories that
symptoms associated with cancer cachexia [102].
activated oncogenes or the inhibition of tumour suppres-
There is only one poor quality study in children with
sor resulted in tumourigensis, meant that the Warburg
cancer [103, 104]. While some paediatric enteral feeds have
effect fell out of favour [119].
EPA added, there is still insufficient information to deter-
Recently the cancer metabolism debate and the Warburg
mine the ideal amount of EPA that would be effective in
effect have provoked new interest as it is now thought onco-
children [105]. There are lipid PN emulsions containing
genes and tumour suppressors are linked to altered metabo-
fish oils, e.g. SMOFlipid, Omegaven, and further studies
lism that in turn affects the cancer epigenome [118–120]. Part
are required to determine their safety and benefits for the
of the debate is which is the cause and which is the effect?
child with cancer. Despite concerns regarding interaction
Some propose that tumours switch to aerobic glycolysis
of EPA with ciclosporin and platelet function in HSCT and
through activation of oncogenes or loss of tumour suppres-
cancer patients, there is no strong evidence of this in stud-
sors and that this oncogene driven metabolic reprogram-
ies involving other patient groups [106, 107]. PTCs are
ming is needed to support the cancer cell survival and
using fish oil‐containing lipids if the clinical need arises,
proliferation [120]. Others propose that increased glycolytic
e.g. where there are increasing conjugated bilirubin levels
activation can result in upregulating oncogenic signalling
or increasing abnormal liver function tests, with no adverse
leading to tumour development and growth or that damage
issues being highlighted.
to cell respiration precedes the genomic instability that
results in tumour development [118, 121].
Probiotics It is known that many of the well‐established oncogenes
and tumour suppressors, such as HIF, AKT, MYC, RAS
Current UK dietary advice is for neutropenic cancer patients and p53 have a direct effect on metabolism, particularly
to avoid products containing probiotics [108]. It is important on glucose uptake and glycolysis and have been impli-
to investigate the safety of probiotic use in immunocom- cated in the Warburg effect [122]. The insulin pathway,
promised cancer patients, as case reports have identified including insulin, insulin like growth factor (IGF‐1) and
Lactobacillus strain use in probiotic therapy to be involved the IGF‐receptor IGF‐R1 are involved in cell growth, pro-
with sepsis [109]. Two systematic reviews have highlighted liferation and inhibition of programmed cell death by acti-
that the use of probiotics in people with cancer may reduce vating the AKT signal pathway [123]. This pathway is
the severity and frequency of diarrhoea [110, 111]. Both high- upregulated by carbohydrates:
lighted five case reports of probiotic related bacteraemia/
Higher glucose levels stimulate insulin secretion
fungaemia/positive blood cultures. A third systematic
review, looking specifically in children with cancer, high- ↓
lighted evidence of gut dysbiosis, which potentially may be Drives glucose into the cells to produce energy
improved using prebiotic and probiotic supplements [112].
As well as treatment related diarrhoea, other potential ↓
interest in the use of probiotics in cancer patients includes Synthesis and high rate of cell proliferation
Organs of the Immune System 383
Hence the minimisation of carbohydrates in general or by a Currently there are very few clinical studies, with the
ketogenic diet is one potential way to reduce the energy pro- majority being small samples and in adult patients. Improved
duction for cancer cells and decrease tumour proliferation clinical studies to provide stronger evidence are needed [116,
[116]. This is the main reason why families ask ‘Does sugar 117]. The ketogenic diet is complex and not without side
feed my child’s cancer?’ effects and requires close monitoring and guidance. Due to
The majority of studies investigating the use of a the lack of good clinical trials in children, the ketogenic diet
ketogenic diet have focussed on brain tumours, particu- is currently not recommended by CCLG centres. However, it
larly malignant high grade glioma/glioblastoma, where is imperative that any family contemplating a ketogenic has
recurrence rate is high resulting in decreased survival. a fully informed choice including taking into account the
Ketone bodies can be used as an energy source by neurons, child’s quality of life, especially if their disease is palliative.
glia and other cells; however cancer cells are unable to If they do embark on a ketogenic diet, it must be properly
metabolise them. monitored to prevent nutritional deficiencies.
Immunodeficiency Syndromes
James Evans
Introduction • bacteria (extracellular or intracellular), e.g. Streptococcus

pneumonia
The immune system is composed of a variety of organs, cells • viruses, e.g. cytomegalovirus (CMV)
and proteins, which collaborate to protect the body from dis-
Defects or failures in any part of the immune system may
ease. Each component has its own unique function in recognis-
lead to immune‐pathological reactions and disease, often
ing and reacting against foreign material, and the spread of
because of not being able to mount an immune response
each component throughout the body enables a rapid response
against an antigen, thus allowing it to successfully infiltrate
to infection. This response is typically divided into two broad
and cause harm. Immunodeficiency disorders are catego-
categories: the innate and adaptive immune systems.
rised as either:
The innate, or ‘first line’, immune response occurs rapidly
after the invasion of a pathogen and involves phagocytic • primary – the deficiency is caused by defects in the
cells ready to engulf the pathogen through phagocytosis. immune system itself, which can be hereditary or due to
These cells do not require previous antigen exposure making genetic defects
innate immunity crucial to survival in early infancy. Innate • secondary – the deficiency is caused by other condi-
immunity is important in containing an infection and tions such as chemotherapy or immune suppression
includes complement cascade reactions and phagocytic therapy
cytokine release that induce inflammation. However, it is
non‐specific and does not produce antibodies nor confer life‐
long immunity to a repeated infection. This initial response Organs of the immune system
alerts and triggers the adaptive immune system that can take
several days to fully activate. The immune system is made up of numerous organs known
The adaptive, or ‘second line’, immune response is more collectively as lymphoid organs. These can be primary or
specific enabling the body to recognise and remember secondary depending on the stage of lymphocyte develop-
pathogens and amount a stronger immune response during ment and maturation the organ is involved in.
subsequent exposures. This response involves B cells (B Lymphocytes are formed and mature in primary lym-
lymphocytes), T cells (T lymphocytes) and natural killer phoid organs including the bone marrow and thymus. All
(NK) cells, some of which produce antibodies that can be cells of the immune system are created from haematopoietic
targeted at specific pathogens during future exposures stem cells in the bone marrow. Some lymphocytes mature in
[124]. The adaptive response undergoes rapid maturation the bone marrow forming B cells, whereas others migrate to
during early life as children become exposed to a variety of the thymus and mature into T cells.
infections [125]. An overview of the structure of the immune Secondary lymphoid organs are where the defence cells
system, including cell components, is shown in Figure 18.2. do their work and include the spleen and lymph nodes.
There are four main types of pathogens that should illicit The spleen removes old or damaged erythrocytes and
an immune response: stores and releases various defence cells when needed.
Lymph nodes produce and store different defence cells
• fungi, e.g. Aspergillus fumigatus that trap pathogens and activate the production of
• protozoa (free‐living or parasitic), e.g. Plasmodium falciparum antibodies.
Bone marrow
Haematopoietic stem cell
Myeloid progenitor cell Lymphoid progenitor cell
Red blood cell
Platelet
Neutrophil Natural T Lymphocytes B Lymphocyte

killer cell Helper cells
Eosinophil
Regulatory cells
Basophil Cytotoxic cells Plasma cell
Dendritic
Monocyte cell Antibodies
Innate Macrophage Adaptive
Figure 18.2 Overview of the immune system. Source: adapted with permission from [126].
Cells of the immune system NK cells are important in the defence against viruses. The
name ‘natural killer’ comes from the fact these cells do not
B cells make up the humoral (antibody mediated) immune require the same maturation as T cells.
response, and their main function is to produce antibodies Phagocytes are the cells of the immune system that pro-
(immunoglobulins), namely IgA, IgD, IgE, IgG and IgM vide innate immunity. They include eosinophils, basophils,
[127]. The humoral response protects the extracellular monocytes, macrophages and neutrophils, the latter being
spaces from pathogens, particularly bacteria. There are two the most abundant of all white blood cells. Their main role is
types of B cells: to ingest and destroy bacteria and fungi.
• B1 cells – are polyspecific with low affinity for many

antigens
• B2 cells – are constantly renewed in the bone marrow Learning points: immune system
B2 cells then progress through a further maturation process, • Innate immunity involves a rapid response to an invading
which results in more specific B‐cell subsets [127]: pathogen but does not produce antibodies nor long‐lasting
immunity
• plasma B cells (effector B cells) – already exposed • Adaptive immunity produces antibodies and creates immu-
to antigens, subsequently producing and secreting nological memory after an initial response to a specific
antibodies pathogen
• memory B cells – made from activated B cells specific to • B cells mature in the bone marrow and form the humoral
a previous antigen; they are secreted quickly on encoun- response that involves antibody production
ter with the same antigen for the second time • T cells mature in the thymus and illicit a cell‐mediated
• marginal zone B cells – resident in the spleen response involving phagocyte activation
• follicular B cells – resident in lymphoid tissues • Primary immunodeficiency disorders arise from inherited
or genetic defects leading to a dysfunctional immune
T cells undergo positive/negative selection during matu- system
ration in the thymus. This ensures the resulting T cells
will not over‐ or under‐recognise host ‘self’ antigens.
T cells illicit a cell mediated, intracellular immune
response; therefore, they can help to fight off intracellular
pathogens such as viruses. There are three main catego- Primary immunodeficiency diseases (PIDs)
ries of T cells [127]:
PIDs are a large and growing group of conditions with more
• naïve T cells than 350 recognised by the World Health Organization [128].
• memory T cells The lives of patients with PIDs are profoundly impacted by
• effector T cells their condition that, if not treated, can be chronic, serious or
Primary Immunodeficiency Diseases (PIDs) 385
even fatal [129]. Most are inherited in one of three different Table 18.8 Common primary immunodeficiency diseases and possible
ways [130]: dietetic considerations.
• X‐linked recessive PID Possible dietetic considerations

• autosomal recessive
• autosomal dominant B cell defects
IgA deficiency Malabsorption, coeliac disease [135],
Some PIDs affect a single part of the immune system, gastrointestinal infection
while others can affect multiple components. The defective
IgG subclass deficiency Malabsorption, possible food allergy/
immune system increases susceptibility to infections and, if colitis [136, 137]
poorly regulated, may also start to attack tissues leading to
Common variable Abdominal pain, diarrhoea
autoimmunity and inflammation [131].
immunodeficiency
T‐cell defects
Diagnosis Autoimmune enteropathy Protracted diarrhoea of infancy, severe
faltering growth, often failure of normal
Early diagnosis allows prompt initiation of supportive treat- nutritional interventions [138],
ments including prophylactic antibiotics and immunoglobu- hypoallergenic diet may be required
lin replacement therapy, as required by the specific disorder. Class II MHC deficiency Chronic diarrhoea, severe infections
Early searches can also begin for matched donors for those Combined T and B cell defects
requiring definitive treatment with haematopoietic stem cell
SCID (including X‐SCID, Diarrhoea, malabsorption, vomiting,
transplant (HSCT). These factors mean infants will be more
adenosine deaminase gastro‐oesophageal reflux, infectious
protected from infection and transplanted earlier in a better deficiency SCID and diarrhoea, faltering growth, increased
clinical condition, thus improving the chance of survival [129]. Omenn syndrome) nutritional requirements [139], skin losses,
Laboratory and genetic investigations are necessary to possible fluid/electrolyte imbalance,
determine the presence of PIDs. Clues from the patient’s hydrolysed protein formulas often required
medical history, which typically include recurrent and/or Wiskott–Aldrich syndrome Malabsorption, bloody diarrhoea [127]
chronic infections, and physical examination direct the Phagocyte defects
appropriate choice of investigations. Diagnostic protocols
Chronic granulomatous Diarrhoea, protein‐losing enteropathy,
are available to optimise the speed of diagnosis and referral
disease pancolitis, frequent infections, intolerance
for treatment [132]. of high feed volume, increased nutritional
requirements requiring nutrient dense
enteral feeds [140]
Classification
Leucocyte adhesion Mucosal infection and inflammation
The International Union of Immunological Societies (IUIS) deficiency
currently classifies PIDs into numerous groups depending
PID, primary immunodeficiency disease; IgA, immunoglobulin A;
on the part(s) of the immune system affected [128]. These can IgG, immunoglobulin G; MHC, major histocompatability complex;
be broadly differentiated into disorders of: SCID, severe combined immunodeficiency.
• B cell maturation and/or their ability to produce
antibodies
• low B cell count but deficient B cell subclass, resulting in
• T cell defects
a variable degree deficiency such as low IgA/IgG
• combined T and B cell defects
• normal B cell count but with light‐chain deficiency/
• phagocyte defects
isotype selective IgA deficiency
• complement deficiencies
Over 50% of affected patients have antibody deficiencies
Selective IgA deficiency (SIgAD)
and treatment consists of replacing the missing antibodies
[133]. Cellular lymphocyte defects are more severe requir- SIgAD is the most common of the primary antibody defi-
ing stem cell replacement through HSCT [134]. Common ciencies affecting approximately 1 in 875 people in England
PIDs and their possible dietetic considerations are listed in [141]. Patients may have a deficiency or total absence of IgA,
Table 18.8. but usually have normal levels of other immunoglobulins.
Patients may be asymptomatic with ‘silent IgA deficiency’ or
may require immunoglobulin treatment. IgA acts to protect
B cell defects mucosal surfaces; deficiency, therefore, leads to recurrent or
chronic infections such as sinusitis, pneumonia, bronchitis
B cell defects can range in type and severity. They may
and gastrointestinal infections. There is no specific treatment
encompass:
for patients with symptomatic SIgAD, although prophylactic
• absent B cells – severe reduction in all antibodies such as antibiotic therapy along with immunoglobulin replacement
X‐linked agammaglobulinemia (XLA) could be helpful for patients with a severe phenotype [142].
The prevalence of coeliac disease is up to 30% higher in coeliac disease [138]. However, patients do not respond to
patients with SIgAD than the general population [135]. This dietary modification, including a gluten‐free diet [146].
IgA deficiency persists when following a gluten‐free diet Medical therapy commonly uses corticosteroids, but some
despite the return of normal mucosa [143]. IgA antibodies patients are refractory to this, and immunosuppression may
against both tissue transglutaminase (tTG) and endomysial be required to control the disease. If these conventional ther-
antibodies (EMA) are relied upon for serum screening of apies fail, HSCT can be a successful treatment [148].
coeliac disease; therefore, patients with IgA deficiency will Intense nutritional management is a crucial component of
not have a reliable tTG/EMA serum level and should have care as poor nutritional status can worsen mucosal integrity.
IgG, tTG and EMA testing when available [144]. IgA plays a A trial of oral nutritional supplementation may be successful
vital role in mucosal integrity and so is also associated with [147] though for many patients parenteral nutrition (PN) is
the onset of food allergy [142]. required [147, 149]. Nutritional management of patients
undergoing HSCT for AIE is similar to that in graft versus
host disease (GvHD) in that post‐transplant, patients are
IgG and IgG subclass deficiency
usually maintained on a milk, egg, wheat and soya‐free diet
Children may have deficiencies in one or more of the IgG for up to 2 years. Extreme caution should be applied when
subclass (IgG1–4). Clinical presentation depends on the challenging with new feeds or foods.
severity and combination of the deficiency, with some indi-
viduals being asymptomatic. Most commonly children may
DiGeorge syndrome (DGS)
present with recurrent infections, usually of the upper air-
ways, food allergy or food allergic colitis [136]. However, DGS is caused by abnormal migration and development of
food allergy testing involving IgG is not recommended [137]. certain cells and tissues during foetal development. As part
The outlook for patients with selective IgG subclass defi- of the developmental defect, the thymus gland may be
ciency is generally good with low IgG subclass levels in chil- affected consequently impairing T cell production, which
dren very likely to improve with age and return to normal by results in low T cell numbers and frequent infections. DGS
around 10–12 years of age [145]. If necessary treatment with athymia, known as complete DGS (cDGS), occurs in
requires only occasional use of antibiotics to clear infections around 1.5% of children with DGS [150].
as they occur. For patients with a persistent deficiency and Two approaches have been used to correct cDGS. The first
significant documented infections, immunoglobulin replace- is HSCT, but because of the absence of the thymus, this
ment therapy may be used to prevent serious infections and approach can only achieve engraftment of post‐thymic T
complications. cells, and the quality of immune reconstitution achieved is
poor [151]. The alternative approach is to use thymus trans-
plantation that aims for a more complete reconstitution. A
T cell defects
recent study on 12 children undergoing thymus transplant
for cDGS concluded this should be the corrective treatment
T cell defects range in type and severity, for example:
of choice [152]. It offers the possibility of immune reconstitu-
• complete insufficiency of T cell/T cell function, with/ tion that will produce a quality of life not limited by infec-
without concurrent B cell defect such as severe com- tion susceptibility, and, despite the significant risk of
bined immunodeficiency syndrome (SCID), including autoimmune complications for survivors, these can often be
Omenn syndrome and major histocompatability com- managed.
plex (MHC) class II deficiency
• partial or complete insufficiency of T cell function such
Phagocyte defects
as DiGeorge syndrome (often associated with absent thy-
mus) or Wiskott‐Aldridge syndrome
Phagocytic cells are important in host defence against
• T cell dysregulation, i.e. autoimmune enteropathy
pyogenic bacteria and other intracellular organisms. These
cells leave the bone marrow and migrate to peripheral
Autoimmune enteropathy (AIE) tissues, particularly to sites of infection or inflammation.
Phagocytes ingest pathogens and degrade them. Therefore,
AIE is a rare disease resulting in immune mediated damage
phagocyte defects can lead to severe infections and as a
to the intestinal mucosa. The immune dysfunction may vary
result may be fatal [4]. Some patients may present with
in nature including activation of mucosal T cells causing per-
gastrointestinal complications similar to those of inflamma-
sistent damage to the gut mucosa or by autoantibodies pre-
tory bowel disease [140].
sent on the gut mucosa [146]. This condition most commonly
affects infants in the first 6 months of life who commonly
present with intractable diarrhoea, malabsorption and ano-
Chronic granulomatous disease (CGD)
rexia leading to severe weight loss [147]. Severe inflamma-
tion, villous atrophy with crypt hyperplasia, and increased In CGD phagocytes are unable to produce microbial oxygen
mitosis may be seen on small intestinal biopsy. These changes metabolites so cannot degrade pathogens after ingestion.
in the small intestinal mucosa may resemble those found in This leads to recurrent, often life‐threatening, bacterial and
Dietetic Management of Infants with SCID 387
fungal infections that are difficult to cure. These frequent accumulation of metabolic substrate precursors that are toxic
infections increase nutritional requirements and decrease to lymphocytes [155].
the appetite for food and tolerance of adequate volumes of Data from newborn screening programmes in the USA
oral feeds. It is, therefore, often necessary to initiate enteral estimate the incidence of SCID to be approximately 1 in
feeding as soon as an acute episode begins to prevent exces- 58 000 live births [156]. Infants with SCID are unable to fight
sive weight loss. Diarrhoea is usually common due to inten- infections until they have restored immune function. Siblings
sive antibiotic therapy, but despite this, children are often diagnosed at birth, following testing due to a positive family
able to tolerate a whole protein, energy‐dense feed. Recent history, have an overall survival rate above 90% compared
HSCT outcomes have produced excellent results suggesting with 40% in the first presenting family member [157].
all children should undergo HSCT if a matched donor is Otherwise most infants present between 3 and 6 months of
available [153]. age with recurrent infections after the protective effects of
maternal immunoglobulins have worn off [158]. When diag-
nosis is delayed, the onset of infections leads to end‐organ
Leucocyte adhesion deficiency (LAD) damage, meaning a significant number of infants die in the
LAD is characterised by impaired migration of neutrophils first year of life before definitive treatment with HSCT can
from the intravascular space to the site of infection. It usually be undertaken [158]. Even those who make it to HSCT with
presents in early infancy with deep tissue infections, ongoing infections or organ damage have a poorer outcome
impaired pus formation and delayed wound healing. [159]. The key to improving the outcome for SCID is early
diagnosis and treatment so that severe infections can be pre-
vented [157].
Haemophagocytic lymphohistiocytosis (HLH)
HLH is characterised by the early onset of fever and hepato- Newborn screening
splenomegaly associated with pancytopenia, hypertriglyc-
eridaemia and haemophagocytosis in the bone marrow. The Newborn screening for SCID can now be performed by
pathogenesis has been associated with uncontrolled T cell detecting biomarkers of healthy T cell development: T cell
activation leading to increased inflammatory cytokine lev- receptor excision circle (TREC) in DNA extracted from blood
els. The condition is fatal if not treated with HSCT, which spot on routine Guthrie cards in the first days of life [160].
gives an overall 3‐year survival of 64% [153]. Veno‐occlusive Results from recently established screening programmes in
disease (VOD) is the major toxicity associated with HSCT in the USA have demonstrated improved outcomes [156].
HLH and reduced intensity conditioning may be a preferen- Despite this, screening for SCID is not currently available in
tial option. the UK. However, in December 2017 the UK National
Screening Committee recommended that screening for SCID
should be trialled in the National Health Service (NHS).
Combined immunodeficiencies
Wiskott–Aldrich syndrome (WAS) Dietetic management of infants with SCID

WAS is an X‐linked disorder characterised by thrombocyto- Infants diagnosed with SCID often face a nutritional chal-
penia with small platelets, early infantile eczema and pro- lenge. They may suffer from persistent diarrhoea, malab-
gressive immunodeficiency leading to numerous chronic sorption, oral thrush, recurrent or opportunistic infections
infections. These children often bleed easily, including [158], vomiting and gastro‐oesophageal reflux [161] and/or
bloody diarrhoea, and many are given amino acid‐based faltering growth, despite a seemingly adequate oral intake.
feeds from diagnosis. Without HSCT children with WAS One study has shown infants with SCID have increased
have a poor prognosis with the main causes of death being nutritional requirements due to hypermetabolism; 100% of
infection, bleeding and lymphoproliferative disease [153]. the infants presenting with diarrhoea, independent of pneu-
Outcomes for WAS patients undergoing HSCT between 1980 monia, were at risk of hypermetabolism and subsequent fal-
and 2009 have shown overall survival of 84% [154]. tering growth [139]. Infants diagnosed between 3 and 12
months of age were at greatest risk.
Severe combined immunodeficiency (SCID) Due to the increased risk of cytomegalovirus (CMV) trans-
mission through breastmilk, breastfeeding is discouraged
SCID arises from a variety of genetic defects that lead to an until the mother’s and infant’s CMV status is known [162]. If
absence of lymphocyte development and function. Most breastfeeding is commenced, an energy‐dense formula, e.g.
forms of SCID have absent T cells but are further divided by 0.9 kcal (3.8 kJ)/mL or 1 kcal (4 kJ)/mL, may need to be given
the presence or absence of B and NK cells leading to various in addition. Hydrolysed protein feeds are generally better
immunophenotypes including X‐SCID, recombinase‐acti- tolerated, particularly in Omenn syndrome with marked gut
vating gene (RAG) deficiency and adenosine deaminase inflammation, as they are better absorbed [158]. Feeds can be
(ADA) deficiency. The latter is the most common form and given either orally and/or via a nasogastric tube, as com-
results from a deficiency of the ADA enzyme causing monly indicated, to optimise nutritional intake. A nasojejunal
tube can be considered in infants where ongoing gastro‐ Treatment for SCID

oesophageal reflux or delayed gastric emptying is preventing
the establishment of oral or nasogastric feeding. Conservative management is centred on reducing infection
Parenteral hydration and nutrition may be necessary and associated end‐organ damage prior to definitive treat-
where an infant requires stabilisation pre‐ or post‐diagnosis. ment with HSCT. Most infants remain in hospital between
Some infants with very high requirements may need PN diagnosis and HSCT and during this time will be isolated in
alongside enteral and/or oral feeds. It may not be possible to individual high‐efficiency particulate air (HEPA) filtered
meet full requirements with PN alone. Sodium status (uri- rooms to reduce exposure to pathogens. Conservative man-
nary and serum) can be a useful tool to ensure adequate agement will involve replacement immunoglobulins given
sodium levels for growth [163]. In practice, a urinary sodium 2–3 times weekly and regular surveillance for viruses, res-
level <20 mmol/L may indicate poor sodium status (despite piratory and stool organisms.
normal serum sodium), and sodium supplements may be Enzyme replacement in the form of polyethylene glycol‐
necessary or the sodium content of PN increased in incre- adenosine deaminase (PEG‐ADA) is used in the treatment of
ments of 1 mmol/kg/day. Urinary sodium levels should ADA deficiency SCID. This is administered 1–2 times weekly
then be monitored weekly or biweekly until a level by intramuscular injection causing cellular immune recon-
>20 mmol/L is maintained. There is limited evidence for this stitution, which reduces the toxic accumulation of metabo-
practice, but clinically this can be effective, especially for lites. However, the extent of immune recovery is variable,
infants with chronic diarrhoea who may have high sodium and over time patients show a decline in T cell numbers, loss
losses. Where full PN is given (except at times of complete of thymic function and remain lymphopenic [164].
gut rest), trophic feeds should be given to help maintain the Possibly the greatest advance over recent decades in the
integrity of the gut mucosa. treatment of PIDs has been the development of gene therapy.
This uses autologous gene‐corrected HSCT and has become a
novel treatment option for patients with ADA deficiency SCID
Reintroduction of feeds following period of gut rest and X‐SCID. The use of autologous cells precludes the risk of
GvHD, there is no requirement for immunosuppressive
At all times reintroduction of enteral feeds should be con- prophylaxis, and much lower doses of conditioning agents can
sidered a priority and started as soon as the infant is medi- be used than in those regimens used for allogenic HSCT; thus
cally stable. Oral rehydration solution may be given first. If there is a reduction in organ toxicity [165]. So far over 50
this is tolerated, then a suitable formula can be introduced. patients worldwide with ADA deficiency SCID have been
Reintroduction of feeds should be done slowly. Continuous treated by gene therapy. Encouraging results have been shown
feeding over 20–24 hours is recommended to begin with, suggesting this may offer a viable treatment option for patients
often starting at slow rates of 5 mL/hour and increasing in where there is no well‐matched donor for HSCT [158].
5–10 mL/hour increments daily, as tolerated. Rather than
whole protein feeds, extensively hydrolysed protein or
amino acid‐based formulas are likely to be better tolerated. Learning points: SCID
These formulas have a higher osmolality than standard for-
mulas; therefore, it may be beneficial to start with half • SCID is characterised by absent T cells combined with the
standard concentration, building up gradually in 1%–2% presence or absence of B and NK cells
increments per day, as tolerated. Once standard concentra- • Early diagnosis optimises survival through avoiding severe
tion is achieved and tolerated, it is often necessary to infections and allowing prompt work up for HSCT
increase the concentration further to achieve higher energy • Gene therapy is an emerging treatment option for ADA
and nutrient density. This should be done with caution, deficiency and X‐SCID
increasing by 1% at a time, usually not exceeding a concen- • Newborn screening is now being trialled in the NHS
tration of 1 kcal/mL (4 kJ/mL). It is often possible to offer • Diarrhoea, infections, vomiting, gastro‐oesophageal reflux
the infant a proportion of their feed (however small) orally. and faltering growth pose dietetic challenges
This will help to promote oromotor skills, avoid oral sensi- • Many require nasogastric tube feeding with extensively
tisation and can also be a valuable input to the infant’s care hydrolysed protein feeds
by the parent(s). • Some may need PN in place of, or alongside, enteral feeds
In older children or infants of weaning age, food can be • Reintroduction of feeds following gut rest should be done
introduced as early as tolerated. Initially the diet may be cautiously, often starting with continuous half strength
milk, egg, wheat and soya free. This is usually necessary feeds
following HSCT for autoimmune enteropathy and in
patients who have developed gut GvHD post‐transplant.
In addition, foods may be kept ‘bland’ with the introduc-
tion of one new food at a time. Once immune function has Haematopoietic stem cell transplant
stabilised following transplant, and in the absence of gas-
trointestinal symptoms, restricted foods can be added in HSCT remains the primary treatment for SCID, as well
one by one. as many other PIDs. The procedure begins with the child
Treatment for SCID 389
receiving various conditioning chemotherapy regimens for Continuous low volume enteral formulas can be initiated
7–10 days prior to transplant. The purpose of conditioning is once stool frequency has decreased. Again extensively
to destroy the existing bone marrow and make space for hydrolysed protein or amino acid, rather than whole protein,
donor stem cells to engraft and undergo normal haemat- formulas are usually better tolerated from observations in
opoiesis. Such regimens are typically categorised as highly clinical practice, despite a lack of published evidence. In
toxic myeloablative conditioning (MAC), or less toxic severe cases it may be necessary to start with half‐strength
reduced intensity conditioning (RIC). MAC generally leads feeds to reduce osmotic load. Some patients tolerate feed or
to the highest levels of donor engraftment, but at the risk of food better than others, with no known explanation. The
significant morbidity. RIC results in less chemotherapy‐ first foods offered should be low in fat and fibre [170], and
induced organ damage allowing more unwell children, who some patients may tolerate a simple ‘few foods’ diet very
would previously have been deemed not fit for chemother- well, e.g. plain chicken with potato or rice. For those suffer-
apy, to undergo transplant [158]. ing from more severe gut GvHD, a milk, egg, wheat and
After conditioning the child receives their transplant, soya‐free diet may be required, with reintroduction of these
commonly referred to as ‘day 0’ (the preceding days referred foods sequentially once the child is medically stable.
to as day −1, −2 etc. and proceeding days as day +1, +2 etc.). VOD is a condition where the tiny blood veins in the liver
Sources of donor stem cells include bone marrow and become blocked due to chemotherapy given during condi-
peripheral blood from related or unrelated donors, or umbil- tioning, particularly busulfan, high dose melphalan and/or
ical cord blood from unrelated newborns. The donor type is total body irradiation. If VOD is suspected, fluid restriction
a major factor influencing outcome. European data from is indicated and lipid‐free PN may be necessary. The evi-
children undergoing HSCT for SCID over the past 30 years dence base for this practice is lacking. It will be difficult to
have shown over 90% survival with a matched sibling donor, meet energy requirements in this situation, and it is impor-
69% with an unrelated donor and 66% with a mismatched tant to monitor and restart lipids as soon as possible.
relative [166]. Supplementation with walnut oil (p. 649) to meet essential
fatty acid requirements should be considered early on, par-
ticularly if lipid‐free PN is used for prolonged periods, or if
Complications post‐HSCT leading to impaired the patient is a young infant.
nutritional status
After conditioning the child enters an extremely vulnerable Dietetic management of children undergoing HSCT
period where their existing bone marrow is destroyed, and
the donor stem cells have not yet engrafted and started to Regardless of diagnosis prior to transplant, maintaining
produce healthy, functioning blood cells. They are, therefore, nutritional status pre‐, peri‐ and post‐transplant is essential
extremely susceptible to infection and will be prescribed a as there are negative associations between malnutrition and
plethora of prophylactic medications and remaining isolated survival, transplant‐related mortality and relapse risk [171].
in HEPA filtered rooms. Energy requirements calculated using Schofield equations
Oral mucositis occurs in most patients treated with to predict basal metabolic rate (BMR) have been shown to
chemotherapy for HSCT. It is characterised by mucosal closely resemble resting energy expenditure (REE) pre‐HSCT
damage ranging from mild inflammation to extensive [172]. However, REE has been shown to reduce to 79% of
ulceration and may affect the oral cavity and other parts of predicted BMR in the early weeks post‐transplant putting
the digestive tract mucosa. This makes eating or passing a children at risk of being overfed [173]. Patients are typically
nasogastric tube painful. The potential breakdown of less active post‐transplant, being kept in isolation, and
mucosal barriers increases the risk of systemic infection receive sedatives for pain relief, both possibly contributing
and, coupled with mucositis associated pain, causes signifi- to reduced REE. Estimates of BMR using equations devel-
cant morbidity and mortality [167]. Mucositis usually oped from healthy children are also likely a poor reflection
occurs between day +6 and +12 with resolution coinciding of the energy expended during recovery following HSCT.
with engraftment. If a child develops severe mucositis, Children are likely to require somewhere between 80% and
most will require pain management, gut rest and PN [168]. 100% requirements predicted using Schofield throughout
Once engraftment has taken place, the child is at risk of admission for HSCT.
GvHD – reactions between the donor stem cells (graft) Almost all children going through HSCT will require
and the host’s own tissues. If GvHD occurs soon after nutritional support beyond oral supplementation. It is rec-
engraftment, it may affect one, or all, of the skin, liver ognised from European guidelines [168] and a Cochrane sys-
and gut. Prophylaxis typically involves ciclosporin and tematic review [174] that enteral nutrition should be
mycophenolate mofetil; if severe GvHD develops, it may provided as first line nutrition support over PN. A proactive
be treated with steroids. Gut GvHD results in profuse approach to enteral tube placement should be encouraged,
watery diarrhoea, exacerbated by feed/food, with a con- and timing of nasogastric tube placement is crucial. If
current rapid decline in oral intake and nutritional status nasogastric tubes are placed during conditioning (approxi-
[169]. Gut rest and PN are recommended if gut GvHD mately days −7 to −2) there is a chance the tube will be dis-
develops [168]. lodged multiple times through vomiting. If placed too late
(approximately after day +7), the procedure may be trau- transplant team will review annually. Reviews will monitor
matic or contraindicated if mucositis is severe, or the child is immune reconstitution (from which duration and intensity
thrombocytopenic. Placing nasogastric tubes between day of antimicrobial prophylaxis can be adjusted), chimerism
−1 and +1 seems to be a good compromise and has been (proportion of the child’s lymphocytes which are native or
shown to be well tolerated and acceptable [175]. Some fami- donor), GvHD and need for immunoglobulin replacement.
lies may even opt for prophylactic gastrostomy placement It is also becoming increasingly recognised that effects on
prior to admission. Although this has potential benefits of mental health, well‐being and quality of life of both the child
avoiding dislodgement due to vomiting and irritation to the and family should be monitored, with counselling offered as
throat when mucositis develops, there is a paucity of studies required [158].
investigating the benefits of this feeding route in HSCT. Growth and development will also need to be monitored
Dietetic management of HSCT is similar to that described closely, and the dietitian has a key role in this. Many patients
for SCID patients. Hydrolysed protein formulas are usually will require enteral nutrition support at home following dis-
better tolerated post‐transplant than whole protein formulas. charge, and advice will be needed regarding weaning off
Patients may initially require a continuous feeding regimen, enteral feeds according to improvements in oral diet, and rein-
building up to an overnight feed, daytime boluses and oral troducing any restricted foods to normalise intake. This will
diet. Infection remains life‐threatening to children having help ease parental anxiety. Close team working and communi-
HSCT, and a ‘neutropenic’ diet (p. 49) is required. Meals may cation between the dietitians within the transplant centre and
be provided by a designated ward or diet kitchen, or main the child’s local hospital, as well as the medical teams within
hospital menus adapted following food safety precautions to each site, will be crucial to facilitating appropriate growth.
reduce the risk of infection from food borne microorganisms. A case study showing the dietetic management of a child
Oral and enteral feeds may be pasteurised as an additional with SCID undergoing HSCT is given in Table 18.9.
precaution. A diet including cow’s milk protein can be given
during this time in the absence of gut GvHD and is usually
tolerated. Some centres may allow commercial bottled water Future research needs and unanswered questions
to be taken orally. However, common practice is to only allow
water that has been boiled, whether tap or bottled water. There is a paucity of literature investigating the effectiveness
Pharmacy grade sterile water can be used, but is often unpal- of nutrition support specifically in PIDs, with most studies
atable. Food safety precautions usually continue for 3–6 combining those having HSCT for PIDs with those having the
months post‐transplant depending on immune reconstitu- same procedure for haematological malignancies and other
tion. Oral intake is often slow to recover to achieve full nutri- disorders. Most of the current paediatric literature comprises
tional requirements. Therefore, many children often require low to moderate quality cohort studies investigating the feasi-
enteral feeds for several months post‐discharge. bility and benefits of early enteral nutrition, with some mak-
ing comparisons to the provision of upfront PN, during HSCT.
There is, therefore, a need for more well‐designed trials
Learning points: HSCT assessing the effectiveness and safety of nutritional support
in children with PIDs during the early stages of diagnosis
• HSCT remains the primary treatment for PIDs and throughout HSCT. The main research recommendations
• Conditioning leads to numerous dietetic challenges includ- from the literature regarding nutrition support during HSCT
ing nausea, vomiting, diarrhoea, anorexia, mucositis, VOD include:
and cytopenia with infection risk
• an urgent need for randomised controlled trials investi-
• Following engraftment there is a risk of GvHD of the skin,
gating the benefits of enteral versus PN
liver and/or gut
• further research investigating the effectiveness and
• Gut GvHD will require a period of gut rest and PN
safety of enteral nutrition interventions including both
• Reintroduction of feeds following gut rest is similar to
the route of nutrition, e.g. comparisons between nasogas-
SCID
tric, gastrostomy and jejunal feeding, and the type of for-
• Food reintroduction in gut GvHD will require restriction of
mula used
milk, egg, wheat and soya, alongside food safety precautions
• the effect of enteral and parenteral glutamine on mucositis,
diarrhoea, infections, GvHD and malignancy relapse rates
From the existing literature a diverse range of clinical out-
Follow‐up and monitoring comes have been reported making it difficult to compare tri-
als. For such future studies listed above, consideration should
Frequency of patient reviews post‐discharge for HSCT will be given to the adoption of standard multicentre clinical out-
vary between centres, but generally children will be moni- comes. Families should be involved in the setting of out-
tored closely by the transplant team, a minimum once to comes that are important to them and could include factors
twice monthly for the first year. Following this care will be such as anthropometry, cost of interventions, complications
shared between the child’s local hospital supported by 6 and quality of life to improve the nutritional and immune
monthly visits to the transplant centre [176]. After 5 years the status of transplanted patients.
Table 18.9 Case study: treatment progression and dietetic management of a child with SCID.
Summary
Anthropometry: Baby boy born at term weighing 2.75 kg (9th centile). Over the first 6 months of life (up to admission for HSCT), weight decline
to 0.4th centile. Over the first month of HSCT, weight continued to decline to <0.4th centile. By discharge the child, now 8 months old, had
increased weight to 0.4–2nd centile. At 1 year of age, he was on the 2nd centile with further increase in weight centile.
Biochemistry: At 4 months old the child was found to have low T and B cells following investigations for an ear infection. Following
conditioning, immune cell counts flattened between day +1 to +7 post‐HSCT. Counts began to reconstitute between day +8 to +20, and had
recovered by day +30.
Clinical: Following an ear infection revealing an opportunistic bacterial pathogen, the child was referred to an immunology team and diagnosed
with RAG1 deficient SCID. He was admitted for a RIC conditioned, matched family donor, HSCT.
Dietary: Following admission a nasogastric tube was placed due to weight loss and reducing oral intake. The child was changed from a standard to
a high energy formula and, shortly after, to an extensively hydrolysed protein and later amino acid‐based formula to aid absorption as mucositis
developed. Despite this, diarrhoea and weight loss persisted and the child was placed on PN. Following engraftment an extensively hydrolysed
formula was gradually reintroduced and titrated against PN until this was eventually stopped. At discharge, the child was beginning to take small
amounts of feed and puréed foods orally, but required ongoing nutrition support as four pump‐assisted day boluses of a high energy formula.
Environment: The baby was a first child of healthy parents. During admission he was isolated in a high‐efficiency particulate air‐filtered room as
standard infection prophylaxis.
Focus: The dietetic aims were to prevent further weight loss following admission, maintain weight during the period of mucositis after
conditioning and, following engraftment, gradual weight gain towards that on admission. To achieve this the aim was to provide 80%–100%
requirements via oral, enteral and/or parenteral nutrition.
1–3 months old Multiple visits to GP with recurrent ear infections Infant not seen by dietitian, but after initially being
requiring antibiotic treatment. The infant also suffered breastfed had been changed to a standard infant
three bouts of diarrhoea each lasting 3–5 days. Weight formula.
initially plateaued and later fell to 0.4th centile.
4 months old Taken to GP with further ear infection, but this time NA
cultures grew Pseudomonas aeruginosa (a bacteria
not typically found in infant ear infections). Full
blood count showed low levels of T and B cells.
Referred to tertiary centre for further management
under an immunology team.
5 months old Admitted to tertiary centre and following genetic Nasogastric tube inserted due to weight loss since birth
tests a diagnosis of RAG1 deficient SCID was made. (currently weight on 0.4th centile), and minimal oral
Infant to remain an inpatient in preparation for HSCT intake. Feed changed to high energy 1 kcal/mL (4 kJ/mL)
with father agreeing to be the donor. whole protein‐based formula to facilitate weight gain.
Feeds offered orally with nasogastric gravity bolus
top‐ups as needed, given 3–4 hours to meet full
nutritional requirements. Once feed plan established
no further weight loss occurred, and weight began to
increase gradually.
6 months old Care transferred to HSCT team. Infant stopped feeding orally, so full nutritional
requirements met entirely via nasogastric feeds.
Occasional vomiting with feeds so delivered via pump
assisted boluses, each feed given over one hour.
Gradual weight gain continued.
Day −7 to −1 pre-HSCT RIC conditioning. Infant suffered from frequent Nasogastric tube displaced twice, promptly replaced
vomiting and diarrhoea. each time without difficulty. Commenced continuous
feeding, given over 20 hours, and changed to
extensively hydrolysed protein formula to facilitate
tolerance and absorption.
Day 0 Infusion of peripheral blood stem cells from matched NA
family donor.
Day +1 to +7 post‐HSCT Immune cell counts flatten. Severe mucositis Feed changed to amino acid‐based formula to facilitate
develops with associated pain, irritation and tolerance and absorption in light of severe mucositis.
worsening of diarrhoea. Volume of feed allowance reduced to 90 mL/kg as
infant required occasional blood products and plentiful
IV medications. Feed concentrated to 1 kcal/mL (4 kJ/mL)
to continue to meet 80%–100% requirements.
Day +8 to +20 Immune cell counts remain low, but starting to Due to weight loss following day 0 (weight now <0.4th
reconstitute. Mucositis and diarrhoea persist. centile) and persistent diarrhoea, PN started and child
placed on gut rest without enteral nutrition.
Day +21 to +30 Immune cell counts recovered. Mucositis and stool While PN continued to provide full nutritional
output improved so enteral feeds reintroduced. Mild requirements, an extensively hydrolysed protein
skin GvHD treated with topical steroids. No formula was reintroduced at 5 mL/hour × 20 hours
evidence of gut GvHD, VOD or infections. continuously via nasogastric tube. Feeds increased by
5 mL/hour/day until approximately 50% of nutritional
requirements were met enterally. After this PN was
gradually reduced over three days, while nasogastric
feeds continued to increase towards providing full
requirements. Oral intake remained minimal during
this time. Weight returned to 0.4th centile.
Day +31 to +40 Medicines converted from IV to oral in preparation PN stopped. Regimen gradually transitioned from
for discharge. continuous to small volume 2‐hourly boluses;
subsequently 3‐ then 4‐hourly boluses of increasing
volume. Boluses given via pump due to semi‐frequent
vomiting. Feed gradually transitioned back to 1 kcal/mL
(4 kJ/mL) whole protein infant formula. Infant started to
take small amounts of feed and pureed foods orally. Pump
training and home enteral feeding arrangements made.
Day +41 NA Infant discharged on four pump assisted day time
boluses via nasogastric tube of 1 kcal/ml (4 kJ/mL)
formula providing 80% requirements. Oral intake of
both feeds and pureed foods slowly increased. Weight
slowly increased to 0.4th‐2nd centile. Handover to
local dietitian for follow‐up.
9–12 months old Ongoing monitoring of immune reconstitution, Oral intake and weaning continued to progress well.
GvHD and infection status. Nil concerns. Bolus feeds gradually reduced and stopped with
nasogastric tube removed at 1 year of age. Weight on
2nd centile and increasing.
SCID, severe combined immunodeficiency; HSCT, haematopoietic stem cell transplant; RAG1 recombinase‐activating gene 1; RIC reduced intensity
conditioning; PN, parenteral nutrition; GP, general practitioner; NA, not applicable; IV intravenous; GvHD, graft versus host disease; VOD, veno‐
occlusive disease.

19 Eating Disorders
Graeme O’Connor and Dasha Nicholls
Introduction adolescence is problematic in that it is also the time when

energy requirements, which are essential for pubertal growth
Eating disorders are a range of mental disorders character- spurt, are at their highest. The combination of high energy
ised by abnormal or disturbed eating habits associated with requirements, nutritional restriction and excessive exercising
significant impairment of function or distress. They occur lends itself to a rapid deterioration in health particularly dur-
across the spectrum of body weight. The three main diagno- ing vulnerable periods of brain development and physical
ses of eating disorders are anorexia nervosa (AN), bulimia growth, resulting in potentially permanent physical and psy-
nervosa (BN) and binge eating disorder (BED). Atypical var- chological consequences [5]. For BN onset is typically a little
iants of these are also specified in diagnostic manuals (other later. Data on BED in young people is sparse, with significant
specified feeding and eating disorders [OSFED]), e.g. atypi- variation between studies. However among overweight or
cal AN, which has all the features of AN except for extreme obese adolescents, binge eating or loss of control eating is
low weight and purging disorder (PD), in which the patient found in around a quarter of adolescents [6].
purges but does not binge eat. Avoidant restrictive food Nutritional intervention is an important component of the
intake disorder (ARFID), which has replaced the diagnosis treatment of eating disorders, and the dietitian is an essential
of feeding disorder of infancy and early childhood, is member of the multidisciplinary team, especially when the
included in the broad category of feeding and eating disor- eating disorder occurs in the presence of other co‐morbidi-
ders but is not normally classified as an eating disorder. ties such as coeliac disease, food allergies and type 1 diabetes
Obesity is not classified as an eating disorder, although a mellitus. Dietitians should not treat patients with eating dis-
subgroup of those who are overweight will have significant orders as sole practitioners and must work within a multi-
eating disorder psychopathology [1]. disciplinary team [7].
Among the eating disorders, AN carries the highest risk [1]
and is most likely to require nutritional as well as psychologi- Screening and diagnosis
cal intervention. AN is defined as maintaining a weight
below a healthy range by restriction of energy intake relative Paediatricians and general practitioners often refer young
to requirements, leading to a significantly low body weight in people with a history of weight loss to the dietitian. It is
the context of age, sex, developmental trajectory and physical therefore not unusual for dietitians to be the first health pro-
health. Additionally AN is commonly linked with other co‐ fessionals to identify or question a possible eating disorder.
morbid psychological conditions including depressive disor-
ders, anxiety disorders, obsessive–compulsive disorder and Anorexia nervosa: clinical features
personality disorders [2]. However, there is a significant mor-
bidity and mortality associated with all eating disorders AN predominately affects females, although at least 1 in 10
regardless of weight status [1], in particular PD [3]. patients will be male (more in the younger age group). AN
The peak onset for AN diagnosis in females in the UK is varies in severity, with extreme nutritional restriction
between 15 and 19 years of age with an incidence rate of 0.2% accompanied by other associated behaviours such as binge
of the population [4]. This timing of the peak onset during eating, self‐induced vomiting, purging, over‐exercising and

394 Eating Disorders
self‐harm [8]. The cognitive distortion associated with AN poor self‐esteem, resulting in extreme competiveness,
results in dieting behaviour and an intense fear of weight asceticism and the need to please; subsequently, young
gain and fatness. Generally, there is no loss of appetite; satis- people with AN tend to be high achievers and can be
faction in feeling ‘empty’ and hungry overrides the need to perceived by peers and family as flourishing.
eat, and weight loss is viewed as an achievement. Thus, suf-
ferers have limited desire to change [9].
Bulimia nervosa: clinical features
Identifying an eating disorder in the early stages is diffi-
cult due to the deceptive nature of the disease, especially
In BN a persistent preoccupation with eating is present, with
when presentation is atypical. Such a lack of awareness that
craving and consequent binges, usually with a feeling of loss
AN can occur in younger children and boys may lead to a
of control. Weight is usually maintained within the normal
delay in referral, diagnosis and treatment [10], although this
range by compensatory exercise, vomiting or purging. A pre-
may be changing. Clinical signs of AN include:
occupation with weight leads to attempts at weight control
• weight loss – leading to significantly low body weight in with characteristic cyclical pattern of missing meals, which
the context of what is minimally expected for age, sex, is not sustained as hunger reinforces a propensity to binge
developmental trajectory and physical health. The World eat, often followed by compensatory behaviours and guilt.
Health Organization (WHO) definition of underweight is There are well‐validated treatments that are effective in
a percentage body mass index (%BMI) below 85% (where over 60% of patients; however, BN is less obvious than AN to
%BMI is BMI/median BMI for age and sex). Cole et al. recognise and may only come to light through suspicion of a
provide cut‐offs for degrees of malnutrition based on family member or friend. Clinical signs of BN include:
international BMI data [11]. For the majority of the popu-
• irregular menses
lation, a healthy %BMI will fall between 95% and 105%
• Russell’s sign – callouses on the knuckles of forefingers
[12, 13]. A consequence of low weight is that pubertal
due to abrasions from self‐induced vomiting
development is halted, resulting in either a delay in reach-
• dental erosion from damage to teeth enamel from
ing menarche or secondary amenorrhoea, which can have
stomach acid
implications on bone health. Physical signs of poor nutri-
• swollen parotid glands
tion and low weight include: sunken cheeks, temporal
• depression/low mood
lobes and eyes; dull and thinning hair; lanugo hair; cold
extremities and feeling cold; and delayed puberty [14].
• avoidance of food – this can occur gradually over time, with Binge eating disorder
subtle restriction of nutritional intake including eliminat-
ing snacks, reducing portion sizes, hiding food and miss- In BED the patient has binge episodes, a sense of loss of con-
ing meals. Furthermore avoidance of food can transfer trol over food intake and a preoccupation of weight and/or
into the social setting; the young person will avoid eating shape but does not utilise compensatory behaviours follow-
out perhaps due to a lack of control over food prepara- ing a binge episode.
tion, or it may interrupt rigid exercise routines or other
‘rules’. Conversely the young person can be overly
Purging disorder
involved with food shopping, meal preparation and bak-
ing but will avoid eating themselves. Young people with
In PD, weight is in the normal range, and the patient purges
eating disorders will often have an extensive knowledge
but does not binge, in order to maintain their weight. Purging
about the calorie content of food, but this is often the limit
includes a variety of methods including, but not limited to,
of their understanding about food and nutrition. It is a
self‐induced vomiting, laxative or diuretic misuse, or the
common misconception that young people with AN have
omission of insulin in those with type 1 diabetes mellitus.
a good comprehension of nutrition, but they are often
PD is classified as an OSFED.
unable to understand information or interpret it correctly,
hence the importance of nutrition education [15].
• morbid preoccupation with weight and/or shape – energy‐
dense foods are avoided through fear of gaining weight Learning points: anorexia nervosa
or a change in body shape that may accompany it. Girls
perceive their stomach and thighs as particularly fat, • Among the eating disorders, AN carries the highest risk
whereas boys may be more concerned about muscula- and is most likely to require dietetic input
ture and are more likely to exercise excessively. • The peak onset for AN is between 15 and 19 years of age but
• poor self‐esteem – feelings of ineffectiveness are extremely can present as young as 7 years old, affecting boys and girls
common and often married with depressive and anxiety • AN is linked with low self‐esteem, anxiety and perfectionism
features, impaired concentration and obsessional symp- • AN is characterised by extreme nutritional restriction accom-
toms. Social interests decline as young people with eat- panied by other associated behaviours such as binge eating,
ing disorders lose weight, and most become socially self‐induced vomiting, purging, over‐exercising and self‐harm
withdrawn. Many of these features reverse with weight • AN can be focused on weight or shape or both weight and shape
gain [14]. Perfectionism is a trait that can converge with
Assessment of Eating Disorders 395
Assessment of eating disorders BMI centile charts and to report BMI centile in young people.
However, for patients below the 0.4th BMI centile, there is a
The mainstay of diagnosis is a clinical interview. For young need to quantify the degree of underweight. Using %BMI
people this would typically include parents or the whole fam- (BMI/median BMI for age and sex) instantly provides infor-
ily in the first instance, although it is important to interview mation about a patient’s nutritional status without the need
the young person on their own too, bearing in mind that all to refer to a chart. Furthermore, young people and parents
young people have a right to confidentiality, and this needs to understand the concept of %BMI.
be balanced against the parents’ right to parent, i.e. to have the Mid‐upper arm circumference (MUAC) is a simple and
necessary information to make decisions in their child’s best effective additional anthropometric measure; its use can
interest, particularly before the child is assumed to have the eliminate some of the methods employed by young people
capacity to do this for themselves at the age of 16 years. with eating disorders to mislead practitioners about their
Areas to explore in an assessment include how everyone true weight, such as water‐loading and attaching weights to
feels about coming to the appointment; the history of the various parts of the body [17].
concern including who is most worried (often justifiably);
ideas the family have about triggers for onset of the eating Nutritional
disorder (providing an opportunity to explain that families
do not cause eating disorders and that triggers are not the Acquiring an accurate diet history from young people with
same as cause or blame); previous experience of eating disor- an eating disorder has the added barrier of intentional over‐
ders or other mental health problems within the young per- and underestimation of intake. Therefore, it is essential to
son or the family; specific questioning about eating disorder have input from families along with a 4‐day food record.
behaviours, including direct questions about vomiting, exer- Nutritional assessment should expand on the history of food
cise, binge eating; other areas of risk (eating disorder behav- restriction and other self‐imposed nutritional ‘rules’ such as
iours, self‐harm and suicidal ideation, anger towards others, exclusion of a food group (fats and/or carbohydrates), veg-
risk of abuse and neglect) and then looking at what the fam- etarianism/veganism, daily calorie limits, ritualistic behav-
ily or young person has tried, what resources they have iours or even a limit to the number of spoonsful of food the
accessed, what resources and strengths they have as a family young person will allow themselves to eat each day.
and what ideas they have about treatment. Thoughts and Additionally, when reviewing young people with binge eat-
feelings about eating, anxiety and mood are best elicited ing tendencies, the dietitian will need to ascertain if there is
with young people on their own, while families often given a specific binge food/food group, specific binge time, cycli-
the clearest narratives about the development of the eating cal pattern to binges and which meals are missed.
disorder and factors that may be important in maintaining it. Exercise routines should form part of the nutritional
assessment and be taken into account when estimating
Medical nutritional requirements. An in‐depth nutritional assess-
ment also allows the dietitian to gauge the extent of the
Although medical investigations may be necessary to rule out young person’s nutritional knowledge.
organic aetiology responsible for weight loss or food avoid-
ance, eating disorders are much more common than most pos- Biochemical
sible differential diagnoses for weight loss: hyperthyroidism,
type 1 diabetes, inflammatory bowel disease (IBD), coeliac The initial consultation should include a detailed laboratory
disease or neoplastic disease (tumour). Amenorrhoea may assessment to rule out any organic cause of weight loss and
result from ovarian or pituitary disease or following use of the to obtain baseline biochemistry. Additional markers that
contraceptive pill. Clinical assessment should focus on deter- should be monitored include vitamin B12, folate, zinc, fat‐sol-
mining the severity of malnutrition as well as possible causes uble vitamins A, D and E, and ferritin [16, 18]. Biochemical
and should include hydration status, temperature, muscle monitoring for patients at risk of refeeding syndrome is
wasting and cardiovascular status with particular attention to given at the end of this chapter.
heart rate and orthostatic blood pressure. The sit up, squat,
stand (SUSS) test is a useful clinical sign to monitor the clinical Learning points: assessment process
status of malnourished patients [16].
• A detailed multidisciplinary assessment is warranted to
Anthropometric elicit the nature of the disordered eating
• All family members who have regular contact with the
The simple use of weight or BMI has limited use in young young person should be part of the assessment
people, owing to the normal changes in weight, height and • A thorough medical and biochemical assessment should be
BMI in childhood and through puberty. Weight and BMI can performed to exclude any organic cause of disordered eating
be used to track changes in an individual, but any compari- • An in‐depth diet history can provide valuable information
son of weight against population norms needs to take about eating habits and rules
account of height, sex and age. It is perfectly correct to use
Management: family‐based treatment Table 19.1 Graded‐up meal plan for a 15‐year‐old female accounting
for hypometabolic state of low weight.
Although inpatient and day patient treatments are generally Estimated energy intake 900 kcal/day (3760 kJ/day)
effective for weight restoration of patients with AN, they are on assessment
disruptive to family, social and educational life. Therefore, Estimated average 2400 kcal/day (10.80 MJ/day)
intensive outpatient treatment using an evidence‐based requirements (EAR) for
treatment approach should be sought by preference if the height age
risks are manageable. Family‐based treatment (FBT) can be Estimated energy 1400 kcal/day (5850 kJ/day)
summarised as an intensive outpatient treatment where par- requirements:
ents play an active and positive role in promoting recovery hypometabolic (BMR)
in their adolescent child with AN or BN and has the strong- Meal plan: 1 1500 kcal/day Day 1–3: halt weight
est evidence base of available therapies. Parents are seen as a (6270 kJ/day) losing trajectory
resource and play an active role in treatment, using their Meal plan: 2 1800 kcal/day Day 3–7: weight gaining
own methods to restore their malnourished adolescent’s (7520 kJ/day)
weight. Families are encouraged to explore how the eating Meal plan: 3 2000 kcal/day Week 2+: continual
disorder and the interactional patterns in the family have (8460 kJ/day) weight gain
become entangled and how this entanglement has made it
Meal plan: 4 2500 kcal/day Week 7+: established
difficult for the family to get back on track with their normal (10.45 MJ/day) energy requirements for
developmental course. However, in some cases, outpatient age and height
treatment is just not an option: presence of overt systemic Energy requirements are driven by % body fat and total body
issues (the young person is at risk in the family environment, weights; therefore, as weight increases, so will energy requirements.
e.g. parents unable to provide the necessary level of care); or If weight stabilises, it may be due to this as opposed to compensatory
AN cognitions and behaviours are too strong or risky. In behaviours.
most cases, the treatment comprises three phases consisting
of 15–20 treatment sessions over 6–12 months. The phases of EAR, estimated average requirements [19]; BMR, basal metabolic rate
(Schofield equation [20]).
treatment in FBT for AN, highlighting the potential role of
Source: Data from [20].
the dietitian at each phase, are described below. In FBT for
BN, the first phase focuses on cessation of binge and purge
episodes rather than weight gain. An in‐depth manual, devising a realistic achievable meal plan, which encourages
Clinical guidelines for dietitians treating young people with ano- the young person to engage with treatment. Once weight
rexia nervosa: family focused approach, has been published by loss has slowed and the patient has been able to adhere to
Great Ormond Street Hospital; it is endorsed by the British the meal plan, then energy intake can be increased to achieve
Dietetic Association (BDA) and is available to BDA members a weight‐gaining meal plan.
at https://www.bda.uk.com/uploads/assets/257c0404-
894c-4c69-b909af56b1da9b70/Clinical-Guidelines-for- Refeeding syndrome
Treating-Young-People-with-Anorexia-Nervosa.pdf.
It is essential to ascertain whether the patient is at risk of the
refeeding syndrome prior to commencing this graded meal
Dietetic management within an FBT framework plan. A detailed assessment and nutritional intervention
schedule for refeeding high risk patients is given at the end
Phase 1: help restore their child’s weight to a healthy of the chapter (p. 400).
range
Physical implications of malnutrition and low weight
Accurately calculate energy requirements
Outlining the physical complications of malnutrition and
Energy requirements vary considerably throughout the course/ low weight to the young person is an important part of the
treatment of AN due to normal increments associated with age/ treatment, and these should be reiterated regularly through-
height, changes in percentage body fat and varying activity lev- out the three phases of therapy.
els. Healthy adolescents have very high energy requirements
because of the demands of pubertal growth phase. However,
Bone health
low‐weight adolescents with AN have reduced energy require-
ments because their depleted body fat stores have led to an Chronic fasting, malnutrition and low weight, along with
increase in cardiac vagal tone, causing bradycardia and hypo- compensatory behaviours, have profound effects on all of the
tension, all of which aid conservation of energy [8, 9]. body’s physiological systems [21]. However, bone health is of
This altered metabolic state observed in low‐weight ado- particular importance in adolescents as it is a time when lin-
lescents with AN supports the need for a graded incremental ear growth and mineralisation is rapid and when bone for-
meal plan, outlined in Table 19.1. Initially, the aim is to stop mation should normally exceed bone reabsorption in order
weight loss and build a relationship with the family by for peak bone mass to be acquired [22]. Impaired linear
Dietetic Management within an FBT Framework 397
growth and possible permanent short stature are significant • anaemia

medical problems in adolescents with AN [23]. Invariably, • constipation
short stature in AN is due to delayed growth, the result of
delayed puberty as a consequence of having a low weight Meal planning
[24]. With a few exceptions patients with AN ultimately reach The overarching aim of FBT is to empower the parents and
their expected height [25]. Furthermore, low levels of insulin‐ build their confidence in feeding their child. Therefore, how
like growth factor‐1 (IGF‐1), as seen in adolescents with AN, confident parents feel will determine how prescriptive the
have been linked with low bone mineral density (BMD) [26]. weight‐gain meal plan needs to be. The majority of families
Other factors associated with the uncoupling of bone turno- may only require guidance on portion sizes of main meals
ver in AN include: low levels of oestrogen (amenorrhoea), and the importance of incorporating snacks and fluids.
testosterone, dehydroepiandrosterone and leptin; and high However, some parents may feel disempowered and require
levels of cortisol, ghrelin and peptide YY. All contribute to a prescriptive meal plan, which minimises the opportunity
low BMD and susceptibility to the development of osteope- for manipulation. Table 19.2 outlines an e xample of a pre-
nia, osteoporosis and increased fracture incidence [27]. scriptive meal plan. Typically meal plans do not include spe-
Emphasis should also be placed on: cific calories if they are to be shared with the young person.
• cardiovascular adaptations – hypotension, bradycardia A recent food diary should give guidance when devising a
and QTc prolongation new meal plan, which should:
• growth and final height (stunting) • be clear, concise and comprehensive
• cognitive functioning • be initially devoid of ‘fear foods’ – these will be
• primary secondary amenorrhoea challenged later
Table 19.2 Example prescriptive meal plan.
Meal Food Portion (household measures) Energy kcal (kJ)
Breakfast Cereal – Shreddies 80 g (3 teacups) 150 (630)

7.30–8.15 Semi‐skimmed milk (SSM) 100 mL (half glass) 50 (210)
Fruit 1 medium‐sized piece 75 (315)
Fruit juice – fresh/concentrate 200 mL (full glass) 100 (420)
Breakfast total 375 (1575)
Mid‐morning snack Cereal bar 45–50 g (large size) 250 (1050)

10.30–11.00 Fruit juice/SSM 200 mL (full glass) 100 (420)
Snack total 350 (1470)
Lunch Large bagel or 2 slices bread (butter optional) 10 cm diameter 250 (1050)
12.30–13.45 Meat/egg 50–60 g 100 (420)
Popcorn/rice cakes 3 cups/3 servings 100 (420)
Low fat yoghurt 150 g (1 pot) 100 (420)
Water 200 mL (full glass) 0
Lunch total 550 (2310)
Mid‐afternoon snack Fruit 1 medium‐sized piece 75 (315)

16.00–16.30 Fruit juice/SSM 200 mL (full glass) 100 (420)
Snack total 175 (735)
Dinner Chicken breast 150 g 200 (835)

18.45–19.30 Steamed broccoli 1 cup 50 (210)
Rice 1 cup 200 (835)
Low fat yoghurt 150 g (1 pot) 100 (420)
Water 200 mL (full glass) 0
Dinner total 550 (2300)
Bedtime snack SSM 200 mL (full glass) 100 (420)

21.30–22.00
Day total 2100 (8810)

• avoid ‘anorexic language’ – discussion of calories and may be drunk from taps, toilets and showers; access to
grams these facilities may need to be restricted. If water‐loading is
• transparent – build trust: calories should not be secretly suspected, then unplanned/spot weighing may be
added to a meal plan warranted.
Assuming the patient is medically stable, weight resto-
As the weeks progress the parents would be expected to lead
ration at a rate of 0.8–1.0 kg per week for inpatients and
on changes to the meal plan with the guidance of the d
ietitian
0.3–0.5 kg in an outpatient setting [7, 16, 18] is safe. Initially,
and therapist, in the context of the family meeting and
weight restoration can usually be achieved by meeting the
guided by weekly weight measurements.
estimated average requirements (EAR) for energy for
height age. However, sometimes this is not adequate, and
Meal supervision daily increments of 200–300 kcal (840–1255 kJ) are required
until sufficient weight gain is achieved.
Meals and snacks should be provided under supervision, It is not uncommon for a member of the psychiatric team
ideally by someone who can demonstrate empathy and to request that the dietitian put a hold on weight gain once
understanding while setting firm boundaries about what is the young person is out of the high risk category (once their
expected, e.g. how much is to be consumed in a set period of %BMI is >85%) to allow for directed therapy around anxiety,
time [28]. It is essential that appropriate observations are in which has resulted from the weight gain.
place at mealtimes, i.e. consideration is given to who is pre- If the young person is still expected to grow, then the use
sent at each snack and mealtime and who has the responsi- of target weights should be avoided as a marker of health,
bility for observation of the food and fluid consumed and but instead, a target %BMI is better used as it accounts for
the time limits set for snacks and meals. Time limits for eat- expected changes in height.
ing, e.g. 15 minutes per snack and 30 minutes per meal, all
need to be agreed. Support and supervision is recommended
for 1 hour after each meal and has been shown to reduce the Learning points: phase 1
need for nasogastric (NG) feeding [28]. Additionally, meal
supervision is a good opportunity to explore and discuss • Accurate calculation of energy requirements is necessary,
normal hunger and feelings of satiety. taking into consideration the hypometabolic state of the
Any actions to be taken if a meal is not completed need to young person and risk of refeeding syndrome
be agreed and documented in advance, e.g. volume of sip • Energy requirements should be regularly recalculated to
feed to be given instead of the incomplete meal. Individual account for normal growth and development, along with an
circumstances will help to dictate the exact needs of the increase in percentage body fat and subsequent increase in
young person and any help that may be needed with respect resting energy expenditure
to helping them eat the required amount of food. • Meal plan prescriptiveness should be devised based on the
level of parental empowerment
• A prescriptive meal plan should be concise and clear to
Sip feeds
avoid any confusion and possibility of manipulation once at
High energy sip feeds (e.g. Fortini Compact Multi Fibre, home
Fortisip Compact, Nutrini Energy, Fortisip 2kcal, Pro‐Cal • Weight gain is an expectation of outpatient treatment
shot) can be invaluable supplements for the young person
who is struggling to consume the large quantity of food that
they need for growth. A top‐up supplement can provide a
nutrient‐rich addition, used as an adjunct to the meal plan, Phase 2: returning control over eating
given after meals or snacks. to the adolescent
This phase of treatment focuses on encouraging parents to

Expected weight gain
help their child to take more control over eating again in an
Weighing in the same way and at the same time each week age‐appropriate manner.
will help to minimise fluctuations in weight from non‐nutri-
tional reasons, e.g. the patient should be weighed on the
Dietetic goals
same scales in the morning before breakfast and after empty-
ing their bladder, in underclothes only (bearing in mind that During this second phase it is important to expand on the
items can be hidden in these). Access to the ward or family importance of a balanced diet with particular focus on
weighing scales may need to be restricted to decrease the bone health. This needs to be age‐appropriate, with cau-
likelihood of frequent weighing by the individual. tion around giving too much nutritional information to
Consideration needs to be given to water‐loading by the younger patients. Furthermore, it should be ascertained
patient in order to effect a gain in weight. This may neces- whether the family and young person understand their
sitate restricted access to fluids, and the team needs to be nutritional needs to optimise catch‐up growth and healthy
aware that other patients’ drinks may be consumed. Water development.
Dietetic Management within an FBT Framework 399
Table 19.3 Example of a young person’s ‘eating and feeling diary’.
Amount served What was suggested addition? What addition was managed?
Sunday
Breakfast Good portion nil
Lunch Good portion nil
Dinner Not enough 2 more roast potatoes 1 roast potato
Monday
Breakfast Good portion
Lunch Not enough 1 pot of yoghurt 1 pot of yoghurt
Dinner Not enough Finish food on plate Left rice: 3 tablespoons
Tuesday
Breakfast Not enough Half cup more of Rice Krispies Half a banana (an
appropriate negotiation)
Lunch Good portion nil
Dinner Good portion nil
Positive signs that eating is becoming easier include compensatory behaviour, i.e. exercise, to counteract the
eating to appetite, serving larger portions and having addition of feared foods, and if there is, it must be ensured
additional snacks not included on the meal plan. Once par- that it is time limited.
ents and the therapy team agree that there is a significant
shift in attitude towards eating, then a ‘food and feeling
diary’ can be trialled. Table 19.3 gives an example of how Activity level
to promote the return of eating to the young person. In the
Exercise and activity levels are a contentious issue in young
example, at breakfast the parents documented that a suffi-
people with AN who have previously used exercise to con-
cient amount of food was served by the young person, and
trol weight or shape. It is important to remember that
therefore, no suggestion or addition was needed. However,
healthy exercising has many benefits; one of note is its
at dinner time the parents felt that an insufficient amount
cathartic value, as well as its antidepressant qualities.
of food was served and therefore suggested another two
Therefore, once the team has deemed exercise to be safe,
roast potatoes; what was actually managed was one roast
based on cardiovascular health, BMD and percentage BMI
potato. The point here is that, if there are consistent short-
>85%, low level activity can be introduced. This may include
falls in expected intake and regular battles, it may be that
walking to and from school (20 minutes per day) or
the young person does not have a grasp of what is expected
partaking in physical education lessons at school. Table 19.4
or is not ready/capable of taking control of their condition.
outlines expected energy expenditure from a variety of dif-
A ‘feeling section’ can be added to the diary, which can
ferent activities with worked examples of how to calculate
be kept private or discussed with family or individual
energy requirements.
therapist.
Once the young person has demonstrated that they can
continue to gain weight while performing low level
Challenging feared/forgotten foods activity and manage additional snacks to account for the
increased energy level, then it is viable to consider starting
It is during this second phase of FBT that challenging the
out of school clubs. However, it is important to avoid
young person’s ‘feared foods’ can start. This can be per-
solitary sports such as running and swimming, which
formed in a number of ways including the reintroduction
inadvertently promote rigidity (counting lengths/laps),
of foods that were most recently excluded, in a sequential
or activities that emphasise body shape, e.g. gymnastics,
manner, gradually increasing the number of foods eaten.
dance and ballet. Team sports, which have a social
Alternatively, a list of feared foods can be formulated,
component, like hockey, football and netball, should be
which is usually completed with the parents in conjunc-
encouraged.
tion with the young person as it is a difficult task for
Suitable snacks for episodes of 20–30 minute exercise
the young person; it is essential to have trust between all
(200 kcal, 840 kJ per portion) are:
parties.
Starting with the least feared food, there is discussion how • cereal bar – nut based
it can be incorporated into a family meal or simply just • banana toasted sandwich with butter or honey
touching or tasting the food. It is important to continue with • 75 g dried fruit
regular exposure to feared foods to help with reducing anxi- • 50 g mixed nuts
ety. There must be observance that there is no increase in • blueberry muffin
Table 19.4 Exercise energy requirements.
Exercise/activity Duration/intensity EER = EAR × (PAL × time spent)
Seated jiggling/swinging legs 4 hours/day EAR × (1.4 × 4/24)

Walking/jogging 2 hours/day EAR × (1.8 × 2/24)
Competitive training (gymnastics/dance/swimming) High intensity 2 hours/day EAR × (2.4 × 2/24)
Worked examples:
A 10‐year‐old girl spends 5 hours seated jiggling per day. EER = 1935 kcal (8090 kJ) × (1.4 × 5/24) = 564 kcal (2360 kJ)
Total daily energy requirements = 1935 kcal (8090 kJ) (EAR) + 564 kcal (2360 kJ) (EER) = 2500 kcal (10.45 MJ)
A 7‐year‐old boy spends 2 hours jogging per day. EER = 1650 kcal (6895 kJ) × (1.8 × 2/24) = 250 kcal (1035 kJ)
Total daily energy requirements = 1650 kcal (6895 kJ) (EAR) + 250 kcal (1045 kJ) (EER) = 1900 kcal (7940 kJ)
A 14‐year‐old girl spends 2 hours swimming per day and 1 hour jogging. EER = 2340 kcal (9780 kJ) × ([2.4 × 2/24] + 2340 kcal
(9780 kJ) × ([1.8 × 1/24]) = 545 kcal (2275 kJ)
Total daily energy requirements = 2340 kcal (9780 kJ) (EAR) + 545 kcal (2275 kJ) = 2885 kcal (12.10 MJ)
Source: Adapted from [29].

EER, exercise energy requirement; EAR, estimated energy requirement for energy; PAL, physical activity level.
These snack portion sizes take into account the raised energy premenarche/male >95% BMI) and focused on establishing
expenditure that occurs after exercise. a healthy age‐appropriate relationship with parents.
Learning points: phase 2 Dietetic goals

This can be the most rewarding phase for the young per-
• There is a focus on a balanced diet with bone health at the
son, their clinicians and family as it is a time when control
forefront of discussion and rationale for maintaining a
of their AN becomes noticeable, and they should be encour-
healthy weight
aged and challenged in a guided manner. It is important
• The most appropriate time to commence exercise should be
not to push too hard even if the young person wants to
decided as a team and considers medical and psychological
move faster.
state
During this phase rigid calorie counting can be challenged
• If exercise is to commence, then so must appropriate snacking
by recommending eating out at new restaurants without
• Team sports with a social aspect are encouraged rather than
calling ahead and checking the menu or advising the young
solitary/rigid‐focused sports
person to buy new products and brands without first check-
ing their calorie content.
There is a focus on untangling normal adolescent behav-
Phase 3: establishing healthy adolescent identity iour and development and their AN. Discussions may need
to be around abuse of alcohol and recreational drugs in rela-
This phase can be initiated once the adolescent is able to tion to low self‐esteem. This can be facilitated within a group
maintain a healthy weight (three regular menses or if session along with other mental health professionals.
Refeeding Syndrome: Young People with Anorexia Nervosa

Introduction insulin concentrations decrease, and glucagon levels rise in
response to depleted glucose levels. Glucagon breaks down
Although infrequent and rarely critical, refeeding syndrome glycogen, forming glucose, which rapidly depletes muscle
is a serious potential complication of commencing feeding in and liver glycogen stores [32]. As glycogen stores are
children and young people who have experienced starvation depleted, gluconeogenesis is activated, utilising lipids and
and should be considered and monitored for in such patients proteins as metabolic substrates to form glucose. However,
[30, 31]. As starvation and malnutrition can occur for a large gluconeogenesis has a limited capacity to support the body’s
number of reasons in childhood and adolescence, it should energy requirements. Therefore, during this period of low
be considered in all children irrespective of underlying con- serum insulin, hormone‐sensitive lipase is activated, which
dition or specialty. breaks down adipose tissue to form fatty acids and glycerol;
Refeeding syndrome is a physiological phenomenon the fatty acids are transported to the liver to be converted to
driven by insulin, resulting in deranged biochemistry, which ketones. Ketones now replace glucose as the body’s major
leads to cardiovascular abnormalities. During starvation, energy source during acute starvation [33, 34].
Management of Refeeding Syndrome 401
Complications manifest with the introduction of carbohy- • An electrocardiogram (ECG) according to the individual,
drates (from diet or intravenous [IV] fluids), triggering a especially where there is pre‐existing cardiac arrhythmia
metabolic sequence of events due to a switch from ketone to (particularly prolonged QTc), should be considered
glucose metabolism. The subsequent insulin surge that • Strict monitoring of fluid balance should be put in place
occurs in response to rising serum glucose levels causes a
rapid intracellular movement of glucose, fluid and electro-
Commencing nutrition
lytes [35, 36].
For most children and young people, the most significant
The refeeding of malnourished patients needs to be gradual
finding will be a fall in serum phosphate levels. When under-
and closely monitored and must increase in controlled
nourished patients are fed, there is an increased requirement
phases in order to avoid further weight loss (underfeeding
for phosphate as the body switches back to carbohydrate
syndrome).
metabolism, which can be potentiated by a background of
Note that although initial feed rates provided below are
relative phosphate depletion in starvation. Phosphate levels
for safe initiation of feeding, children and young people may
in the blood begin to fall, and cardiovascular and neurologi-
well have additional requirements, e.g. for increased losses
cal sequelae may follow [37].
or catch‐up growth, which should be considered and incor-
On the initiation of feeding after a period of starvation, it
porated into feeding plans after the safe commencement of
is of the utmost importance to anticipate and remain vigilant
nutrition, as per the protocols below.
for the biochemical and clinical features of refeeding syn-
Adolescents are at particular risk as their high energy
drome, especially in the first 48 hours, and then the first 5
requirements coupled with restricted nutritional intake lend
days after commencement of feeding. Low phosphate levels
itself to a rapid deterioration in health. Table 19.5 outlines
will usually correct when treated with oral phosphate sup-
the refeeding phases that can be adopted to promote appro-
plements or given intravenously if the enteral supplement is
priate weight gain in a timely and safe manner. A worked
not tolerated.
example of a phased refeeding regimen is given in Table 19.6.
Refeeding syndrome may occur up to 2 weeks after initiat-
ing feeding. While it is important to be vigilant and refeed
safely, ‘underfeeding syndrome’, i.e. weight loss or inade- Table 19.5 Refeeding phases for adolescents at high risk of refeeding
quate weight gain, should also be avoided. syndrome [38].
Refeeding
Management of refeeding syndrome phase Target energy requirements and weight gain
Primary • Commence at 30–40 kcal (125–165 kJ)/kg/day

At risk groups Day 1–2 • Increase by 200 kcal (840 kJ)/day until secondary
refeeding phase reached
Those most at risk of refeeding syndrome are children and • Correct deranged electrolytes; do not stop refeeding
young people who have: • Weight loss/maintenance likely during this primary
refeeding phase
• very low body weight (in particular those <70%–80% • Consider oral thiamine 100–200 mg twice a day,
weight for height/median BMI) [38] continue for 10 days
• acute starvation with rapid weight loss prior to com- Secondary • Basal metabolic rate (BMR) + physical activity level
mencement of nutrition Day 2–4 (PAL)
• prolonged IV fluid therapy devoid of glucose; prolonged • Maintain secondary refeeding phase if adequate
fasting; prolonged periods of nil by mouth weight gain (0.5–1.0 kg/week)
• previous history of refeeding syndrome • Once weight gain reduces, increase by 200–300 kcal
(840–1255 kJ)/day until tertiary refeeding phase
• electrolyte abnormalities prior to starting feeds
reached
• low white blood cell count [38]
Tertiary • Estimated average requirement (EAR) energy for
Day 7–14 height age
• Maintain tertiary phase if adequate weight gain
Important considerations prior (0.5–1.0 kg/week)
to commencing feeding
Progression • If sufficient weight gain not achieved with EAR,
continue to increase energy intake by 200–300 kcal
The following should be undertaken before any feed is (840–1255 kJ) every 4 days until weight increase of
given: 0.5–1 kg/week
• Baseline blood samples should be taken (see Biochemical Maintenance • Once weight is >85% median BMI, weight gain can
monitoring) be slowed or maintained depending upon the
therapeutic plan as discussed with the
• Electrolyte disturbances must be corrected as feeding
multidisciplinary team
commences and prophylactic phosphate supplementa-
tion considered for those who are known to have had BMI, body mass index.
refeeding syndrome before Source: Reproduced with permission of John Wiley & Sons.
Table 19.6 Worked example of a phased refeeding regimen. Table 19.8 Estimated energy requirements per day based on low
physical activity.
14‐year‐old girl with anorexia nervosa, weight = 30 kg. She is restricted
to limited activity on the ward giving her a physical activity level Age (years) Energy males (kcal) Energy females (kcal)
(PAL) = 1.2. Her basal metabolic rate (BMR)* = 1223 kcal (5112 kJ).
1 80 per kg 80 per kg
Day (refeeding phase) Target energy requirements and weight gain
Day 1 and 2 (primary It has not been possible to elicit an accurate 3 65 per kg 60 per kg
phase) reliable diet history
Start a meal plan: at 40 kcal/(165 kJ)/
kg = 1200 kcal (4950 kJ)/day 5 60 per kg 55 per kg
Now, calculate the secondary phase energy 6 1150 1050
intake target:
BMR × 1.2 PAL (restricted to ward) 7 1200 1100
[(17.686 × 30 kg) + 692.6] × 1.2 8 1250 1200
PAL = 1468 kcal (6140 kJ)/day
9 1350 1250
Day 3 and 4 (secondary Increase meal plan by 200 kcal (820 kJ)/day
10 1500 1400
phase energy intake until secondary phase requirements met =
target) 1468 kcal (6140 kJ)/day 11 1600 1500
Weight should increase as a result of 12 1650 1550
hydration and glycogen store replenishment
Now calculate the tertiary phase energy 13 1800 1650
intake target: 14 1950 1700
EAR for energy = 2342 kcal (9836 kJ) [19]
15 2100 1750
Day 7 (tertiary phase Increase meal plan by 200 kcal (820 kJ)/day
16 2200 1800
energy intake target) until tertiary phase energy requirements met
Halt energy increments and monitor weight 17 2300 1850
gain 18 2400 1850
From this point weight gain target:
0.6–1.0 kg/week (0.1 kg/day) Source: Adapted from [19]. Licensed under Open Government License.
If weight gain is <0.6 kg/week, increase
meal plan by 300 kcal (1255 kJ) = 2650 kcal
(11.07 MJ)/day • NG tube insertion should be considered if daily energy
Progression If sufficient weight gain is not achieved, requirement is not met orally with food and/or nutri-
continue to increase energy intake by 300 kcal tional supplements
(1255 kJ) every 4 days until weight gain target • Bolus NG feeds are preferable to continuous as they
of 0.6–1.0 kg/week (0.1 kg/day) is achieved
closely mimic normal physiology and reduce the indi-
Be mindful of compensatory behaviours
(secret exercising/purging) if exceeding
vidual’s preoccupation with energy. However, continu-
3000 kcal (12.54 MJ)/day while bed/ward ous feeds may be considered in those with hypoglycaemia,
bound upper gastrointestinal symptoms or malabsorption
EAR, estimated average requirement for energy.

* Schofield equation for calculating BMR can be found in Table 19.7. Monitoring refeeding syndrome
The characteristic and most common finding in refeeding

Table 19.7 Schofield equations to calculate basal metabolic rate (kcal)
syndrome is hypophosphataemia, which, if untreated, can
for children at risk of refeeding syndrome [20].
lead to cardiovascular and neurological sequelae. Other elec-
Age (years) Male Female trolytes can also be affected including potassium, magne-
sium and sodium.
<3 (59.5 × Wt[kg]) − 30.4 (58.3 × Wt[kg]) − 31.1 Monitoring for clinical features is also important and must
3–10 (22.7 × Wt[kg]) + 504.3 (22.7 × Wt[kg]) + 485.9 be responded to, especially fluid balance. Important clinical
features to look for include an unexplained resting tachycar-
dia, oedema, confusion or conscious level.
Furthermore, Tables 19.7 and 19.8 provide guidance for tar- Daily clinical and biochemical monitoring is required until
get energy requirements, which takes into account the full calories are achieved, and the patient is stable.
reduced activity along with the hypometabolic state associ-
ated related with malnutrition.
Nutritional monitoring
Other considerations when starting nutrition:
• Rehydration should ideally be done as part of the feed- • Monitoring the amount of calories/intake that is actually
ing regimen or corrected before to avoid fluid overload being received, as well as changes in weight/BMI, is an
associated with refeeding essential part of the management of refeeding syndrome
Carbohydrates and Refeeding Syndrome 403
Table 19.9 Normal ranges for electrolytes according to age. • consider oral phosphate supplements for mildly low lev-
els or IV phosphate supplements for significantly low
Age 4–9 years 9–15 years >15 years levels of serum phosphate (e.g. <0.5 mmol/L), poor clini-
Magnesium (mmol/L) 0.66–1.0 0.7–0.95 0.7–1.0 cal status or where oral supplementation is not possible/
tolerable
Age 4–9 years 1–15 years >15 years • involvement and discussion between all relevant staff:
medical consultant, senior nurse, ward nurses, dietitian
Potassium (mmol/L) 3.5–5.5 3.5–5.5 3.6–5.0
and pharmacist
Age 4–9 years 10–15 years >15 years • ensure there is peripheral IV access if no central IV
access, particularly in those considered most at risk
Phosphate (mmol/L) 1.2–1.8 1.1–1.75 0.8–1.45 and those with other medical co‐morbidities. Some
children with mild hypophosphataemia who are other-
to ensure that appropriate nutrition is being given, and wise clinically stable may not automatically need IV,
supplementation can take place but the decision should be based on likely risk and
• Urinary sodium may be useful measure to determine other medical problems and should be decided by the
sodium depletion medical team
• Early weight gain may be secondary to fluid retention • repeat ECG if there is evidence of refeeding syn-
drome – monitor for QT interval prolongation
• phosphate level <0.3 mmol/L is considered severe, and
Clinical monitoring HDU/PICU support may be needed – this should be dis-
cussed with consultant, senior nurse and PICU leads for
• The presence of oedema or confusion should be moni- the shift
tored frequently throughout the day
• In particular, identification and reporting of tachycardia
to members of the medical team is important as this can Treatment of clinical features
be an early sign that refeeding syndrome is developing refeeding syndrome
Biochemical monitoring The clinical features of refeeding syndrome include resting

tachycardia, peripheral oedema and confusion/altered
• Urea, creatinine, sodium, potassium, phosphate, cal- conscious level. If these features are evident, it is recom-
cium, albumin and magnesium levels should be meas- mended to:
ured daily for 5 days (Table 19.9 shows electrolyte levels • reduce the energy intake to starting dosage with no
where normal ranges are age‐dependent) increase in energy until serum phosphate levels are nor-
• As refeeding syndrome can occur for up to 2 weeks after mal, and the patient is clinically stable
commencing feeds, electrolyte levels should be repeated • check full blood count (FBC), urea, creatinine, sodium,
at days 10 and 14 potassium, phosphate, magnesium, calcium, liver func-
• Abnormalities usually occur within the first 72 hours tion tests (LFT), gas‐correct any electrolyte and acid–base
after commencing nutrition abnormalities
• Blood sugar levels should be measured if a patient is • check blood sugar levels
symptomatically hypoglycaemic • start cardiac monitoring
• Measuring urine for osmolality, electrolytes, pH, glucose • observations must include full physical examination,
and protein in the first 5–10 days should be considered in lying/standing blood pressure and neuro‐observations
those patients with blood or clinical signs of refeeding
syndrome; this should be discussed and considered with
the senior medical team responsible for this patient Carbohydrates and refeeding syndrome
Despite low energy intakes in the secondary phase of

Treatment of refeeding hypophosphataemia refeeding, weight gain is often achieved due to the rapid
replenishment of glycogen stores. However, refeeding
The following practice points are advised for the treatment
syndrome is driven by insulin, and therefore, the carbohy-
of the hypophosphataemia seen in refeeding syndrome:
drate intake should not exceed the recommended amount
• no increase in the feed regimen until phosphate levels of 60% of dietary energy [39]. Most oral nutritional sup-
are corrected and normalised plements and enteral feeds contain 42%–46% energy from
• check vitamin D and parathyroid hormone (PTH) levels carbohydrates, regardless of whether they are standard or
to optimise phosphate homeostasis high energy formulas. However, the total energy load
• daily monitoring of urea, creatinine, sodium, potassium, from high energy formulas is higher than that from stand-
phosphate, calcium, magnesium and albumin levels ard formulas, which may have an overall deleterious
until phosphate is normal effect [40].
aware of their professional boundaries when treating these

Learning points: refeeding syndrome
complex patients. It is important to highlight the synergy
between psychological and nutritional factors; without
• Refeeding hypophosphataemia is the commonest symptom
psychological understanding and support, nutritional reha-
of refeeding syndrome, a result of phosphate’s essential role
bilitation is likely to be ineffective. Conversely, malnutrition
and utilisation in glucose metabolism
will impact cognitive function and behaviour, including
• High risk group includes acute onset with rapid weight loss,
increasing preoccupation with food and eating in a way that
significantly affecting %BMI and white blood cell count
mirrors the eating disorder itself.
• Initial meal plans should be based on 30–40 kcal (125–
165 kJ)/kg/day and increased by 200 kcal (840 kJ)/day
• EAR should be achieved within 14 days
Future directions
The recommendations in this chapter are largely drawn from

Overview accumulated consensus opinion and some limited research
evidence. There have been few clinical trials to date in the
FBT is the evidence‐based model for young people with AN areas of refeeding or dietetic involvement in the care of chil-
and BN. Therefore, dietitians should be focusing their dren and young people with eating disorders. Furthermore,
treatment programs to align with FBT. Treatment should be research evidence is needed to support the reintroduction of
personalised to the needs of each specific young person. It is carbohydrates into the diet and the safest refeeding proce-
important to appreciate the changeable energy requirements dure to ensure adequate weight gain without the complica-
and therefore the importance of regularly calculating energy tions associated with refeeding syndrome.
requirements throughout the treatment period. A concise Trials, which evaluate the effectiveness of structured
well‐structured meal plan can provide parents with the nutritional sessions in conjunction with psychological input,
confidence needed to engage with FBT, opening the
would help elucidate the most effective method of working
opportunity to promote weight gain and avoid hospitalisa- with young people with eating disorders from a nutritional
tion. Working in conjunction with the therapy team will guide perspective.
the dietetic treatment, ensuring appropriate challenging of
AN and optimising nutritional intake, while minimising the
long‐term physical complications associated with AN. References, further reading, guidelines, support groups
Dietitians working in eating disorders must have an and other useful links are on the companion website:
understanding of the underlying dynamics [41] and be www.wiley.com/go/shaw/paediatricdietetics-5e
20
Zoe Connor
Autism
Introduction current editions of the American Psychiatric Association

(APA) Diagnostic and Statistical Manual of Mental Disorders
Autism is a common developmental condition that affects (DSM‐5) [9] or the World Health Organization (WHO)
communication and behaviour. It is reported to be the International Classification of Diseases (ICD‐11) [10].
costliest condition in the UK, and autistic adults have high Medical investigations are not necessary for the diagnosis of
early mortality rates, which may be partly attributed to autism; however, genetic testing is recommended if the
nutrition. Typical autism characteristics of rigid thinking, child has learning disabilities or congenital anomalies, and
resistance to change and sensory processing difficulties electroencephalography if there is suspicion of epilepsy [7].
(SPDs) make feeding problems common. Traditional Previous diagnoses of Asperger’s, classic autism and
approaches to dietary behaviour change are often inade- others have been replaced by the single term autism spec-
quate. At least 1% of children and young people (CYP) in trum disorder (ASD) in the most recent diagnostic manual
the UK and worldwide are autistic [1–3]. There are no editions, with the use of various specifiers. Current and pre-
significant differences in prevalence by geographic region vious WHO and APA ASD classifications and criteria are
or ethnic/cultural or socioeconomic factors [3]. Diagnosis summarised in Table 20.1. The umbrella term ASC is some-
in males is four times that of females, partly due to a diffi- times preferred to ASD to highlight its existence as part of a
culty in recognition in females who are more able to mask normal continuum of neurodiversity rather than as a ‘disor-
their differences [4]. der’ [11] and to be inclusive of those diagnoses prior to the
current diagnostic term of ASD [5].
Diagnosis, terminology and common
investigations Causes
Signs of autism can be apparent from the first months of life, Up to 15% of autistic people have 1 of more than 60 identi-
and diagnosis typically occurs between 2 and 5 years old, fied genetic causes such as fragile X syndrome, tuberous
but sometimes later, even into adulthood [5]. Parental or sclerosis and Timothy syndrome [12]. For the remainder
other caregiver concerns around social interaction or the cause is unknown and is likely to be varied and multi-
delayed speech typically lead to an initial screening by a factorial. Twin and family studies have shown that autism
general practitioner or health visitor using a tool such as is strongly heritable, from 50% to 95% [13–15]. Genetic
the validated M‐CHAT (Modified Checklist for Autism in studies have failed to find any single ‘autism gene’; how-
Toddlers) [6]. UK national guidelines for recognition, ever, multiple gene families have been identified that link
screening and diagnosis are the National Institute for Health to autism and other neurodevelopmental and psychiatric
and Care Excellence (NICE) clinical guideline 128 in disorders [16–18]. Methylenetetrahydrofolate reductase

England, Wales and Northern Ireland [7] and the Scottish (MTHFR) gene variants have been found more commonly
Intercollegiate Guidelines Network (SIGN) clinical guide- in autistic CYP [19–22].
line 145 [8]. Diagnosis involves in‐depth expert observa- Neuroimaging has shown brain differences in autistic CYP:
tions and assessments against criteria in either of the most accelerated brain development and higher brain volume

406 Autism
Table 20.1 Comparison of the criteria and classifications for autism spectrum disorder in WHO IDCD‐11 and APA DSM‐5.
DSM‐5 (2013) [9] ICD‐11 (2018) [10]
ASD diagnostic A. Persistent deficits in social communication and social ‘Autism spectrum disorder is characterized by
criteria interaction across multiple contexts, as manifested by all persistent deficits in the ability to initiate and to
of the following: sustain reciprocal social interaction and social
1. Deficits in social‐emotional reciprocity communication, and by a range of restricted,
2. Deficits in nonverbal communicative behaviours used repetitive, and inflexible patterns of behaviour and
for social interaction interests. The onset of the disorder occurs during
3. Deficits in developing, maintaining and understanding the developmental period, typically in early
relationships childhood, but symptoms may not become fully
B. Restricted, repetitive patterns of behaviour, interests or manifest until later when social demands exceed
activities, as manifested by at least two of the following: limited capacities. Deficits are sufficiently severe to
1. Stereotyped or repetitive motor movements, use of cause impairment in personal, family, social,
objects or speech educational, occupational or other important areas
2. Insistence on sameness, inflexible adherence to of functioning and are usually a pervasive feature of
routines or ritualised patterns or nonverbal behaviour the individual’s functioning observable in all
3. Highly restricted, fixated interests that are abnormal in settings, although they may vary according to
intensity or focus social, educational, or another context. Individuals
4. Hyper‐ or hypo‐reactivity to sensory input or unusual along the spectrum exhibit a full range of
interests in sensory aspects of the environment intellectual functioning and language abilities’
C. Symptoms must be present in the early developmental
period
D. Symptoms cause clinically significant impairment in
social, occupational or other critical areas of current
functioning
E. These disturbances are not better explained by intellectual
disability or global developmental delay
ASD specifiers Severity based on social communication impairments and Autism spectrum disorder
restricted, repetitive patterns of behaviour: With/without disorder of intellectual development
Level 3 ‘Requiring very substantial support’ and
Level 2 ‘Requiring substantial support’ with mild or no impairment functional language/
Level 1 ‘Requiring support’ with impaired functional language/with the
With or without accompanying intellectual impairment absence of functional language
New diagnoses Social (pragmatic) communication disorder Developmental language disorder
related to ASD
Terms used for ASD Pervasive developmental disorders, autistic disorder, Autistic disorder, pervasive developmental delay
in previous manuals Asperger’s disorder, Rett’s disorder, childhood disintegrative
that are no longer disorder, pervasive developmental disorder not otherwise
included specified (PDD‐NOS)
(but not head circumference) in infancy and early childhood Outcomes and public health impact
compared with typically developing children [23]. These
changes are associated with altered connectivity both Autism is seen as a lifelong condition; however, 4%–40% of
throughout the brain and in specific regions [24–27]. The children lose their diagnosis as they get older [45–47]. Loss of
underlying cellular mechanisms are poorly understood. diagnosis is more common for those more ‘mildly’ affected or
More than 20 environmental factors linked to increased without other coexisting conditions. Whether these changes
risk of autism have been identified, many of which focus on are due to ‘recovery’ or just a shifting of how much underly-
maternal exposure before and during pregnancy and include ing autistic traits impede ‘normal’ life is not known [48].
both maternal and paternal increasing age, pregnancy spac- Autistic people have an increased risk of many preventa-
ing and use of some medications [28–32]. Taking folic acid ble nutrition‐related conditions including vitamin and
before and after conception is associated with more than a mineral deficiencies, dyslipidaemia, hypertension and type 2
40% reduction in risk for having an autistic child, with diabetes and die on average 18 years younger than the gen-
greater reductions in risk when mothers or children carried eral population (30 years younger for autistic people with
the gene variant MTHFR 677 C > T [22, 33–36]. However, intellectual/learning disabilities) [49, 50]. Autism costs the
other studies do not support these associations [37, 38]. UK £32 billion per year in treatment, lost parental earnings,
Other maternal dietary factors that have been linked to care and support – more than heart disease, cancer and stroke
increased risk of autism are low iron intakes in pregnancy combined [51, 52]. The government has highlighted the need
[39], high polyunsaturated fatty acid (PUFA) intake [40] and to reduce the health gap between autistic people and the
low vitamin D levels [41–44]. general population and increase UK research spend from the
Sensory Processing Difficulties 407
current £4 million per year (£6 per year per autistic person conditions are listed in Table 20.2. Assessment for coexisting
compared with £220 spent per person with cancer) [53–56]. conditions, including feeding and nutrition problems, and
referrals to appropriate professionals (including dietitians)
Co‐morbidities on diagnosis are recommended in UK guidance [7, 8].
Over 95% of autistic CYP have at least one coexisting medi- Sensory processing difficulties
cal, psychiatric or behavioural condition [57]. Autistic CYP
have an increased prevalence of gastrointestinal (GI) condi- Impairment in the perception of sensory stimuli is reported
tions and feeding problems. These conditions further impair in over 90% of autistic people [79, 80] and has been incor-
social and psychological functioning and increase the need porated into the DSM ASD criteria for the first time in the
for medical and dietetic input. Prevalence of a selection of current 5th edition: ‘Hyper‐ or hypo‐reactivity to sensory
Table 20.2 Prevalence of coexisting conditions in autism.
Coexisting condition Prevalence
Learning and behavioural problems

Intellectual/learning disability [58, 59] (IQ < 70) USA: 38% of 3820 aged 8
UK: 55% of 156 aged 9–14
Speech and language delay [48, 60] USA: 87% of 87 aged 3
Sleeping problems [57, 61] USA: 25%–40%, 10 times more insomnia than controls in 3800 aged 7–13; 27% of
783 aged 4; 37% of 1091 aged 8
Attention deficit hyperactivity disorder (ADHD) [57, 62] UK: 28.2% of 112 aged 10–14
USA: 5.5% of 783 aged 4; 26.1% of 1091 aged 8
Pica (eating inedible substances) [63] UK: 60% of 70 autistic adults with learning disabilities vs. 4% of adults with Down’s
syndrome and learning disabilities
Mental health problems

Anxiety disorder [50, 57, 62, 64] USA: 29.1% of 1507 adults vs. 9.1% of 15 070 controls
UK: 29.2% of 112 aged 10–14
USA: 4.8% of 783 aged 4; 11.2% of 1091 aged 8
Depression [65] USA: 25.8% of 109 adults, 2.9 times higher than 56 controls (9.9%)
Mood disorder [57] USA: 56% of 783 aged 4; 75% of 1091 aged 8
Bipolar disorder [50] USA: 10.6% of 1507 adults vs. 1.7% of 15 070 controls
Obsessive–compulsive disorder (OCD) [50] USA: 7.6% of 1507 adults vs. 0.5% of 15 070 controls
Schizophrenic disorders [50] USA: 7.8% of 1507 adults, 22 times higher than in 15 070 controls (0.4%)
Medical problems
Autoimmune disease [50] USA: 13.9% of 1507 adults vs. 10.8% of 15 070 controls
Food allergy [66, 67] USA: 0.9% of 5565 children vs. 0.5% of 27 825 controls (diagnosed); 11.25% of 1868
children vs. 4.25% of 199 520 controls (reported)
Motor coordination problems [68, 69] UK: 79%–89% of 97 children aged 10–14, 1.2 times more prevalent in a meta‐analysis
Epilepsy [50, 70] USA: 8.6% vs. 1.2% of 85 248 aged 2–17; 11.9% in 1507 adults vs. 0.73% in 15 070 controls
Mitochondrial disease [71] 5.0% vs. 0.01%, meta‐analysis of 11 studies of 112 autistic children
Gastrointestinal problems
Gastrointestinal symptoms [50, 72–74] Four times more prevalent in autistic CYP than non-autistic CYP (9% to >70%),
meta‐analysis of 2215 autistic CYP, 15 studies
USA: 34.7% of 1507 adults vs. 27.5% of 15 070 controls
Diarrhoea [73] 3.6 times more prevalent in autistic CYP than non-autistic CYP meta‐analysis of 2215
autistic CYP, 15 studies
Constipation [73, 75] 3.9 times more prevalent in autistic CYP than non-autistic CYP (12 times more
prevalent in nonverbal CYP), meta‐analysis of 2215 autistic CYP, 15 studies
85% of autistic CYP in a clinically validated sample of 121 CYP
Coeliac disease [76–78] Sweden: in 36 714 CYP same prevalence in autistic and non-autistic CYP
Italy: 3.3% of 150 screened CYP three times higher than in non-autistic CYP
408 Autism
Table 20.3 Examples of how sensory processing difficulties could affect food preferences and mealtime behaviour.
Sense Hyper‐reactivity Hypo‐reactivity
Taste (gustatory) Strong preference for bland tasting foods Preference for strong tasting spicy foods
Aversion to spicy foods/many foods Licking objects
Ability to detect tastes that others may not, e.g. attempts Pica
to hide foods or supplements in preferred foods
Smell (olfactory) Distracted or disturbed by food smells Preference for strong scents
Ability to detect odours that others may not, e.g. in
protein‐rich foods
Sight (visual) Distracted by lighting, movement or colours at mealtimes Difficulty making out foods on a plate
Distracted by ‘specks’ in food Preference for contrasting foods and plates
Preference for bland‐coloured foods
Preference for different foods to be presented separately
Disturbed by foods not displayed in the usual way
Aversion to certain coloured foods
Sound (auditory) Dislike of the sound of self or others eating, particularly Preference for foods that make sounds when eaten,
crunchy or noisy foods e.g. crunchy ones
Distracted or disturbed by background sounds, some of
which may not be obvious, e.g. fluorescent light tubes
Touch (tactile) Dislike of mixed textures in the mouth Preference for lumpy or crunchy foods
Dislike of hot or cold foods and drinks May not notice when face gets messy when eating
Dislike of some cutlery in mouth Preference for very hot or very cold foods and
Dislike of tooth brushing drinks (possibility of burning self as hyposensitive
Dislike of busy eating places in case someone bumps to pain)
against them A tendency to frequently put foods and other
Dislike of getting messy objects to the mouth
Pica
Proprioception Alterations can contribute to clumsiness in eating or drinking or being distracted by arm movements during
eating
Vestibular Changes can cause a child to be distracted by moving or not moving self or by body position during a meal
attention
Interoception Alterations may create a lack of or excessive experience of hunger and thirst and might affect the ability to
know when to defaecate and urinate or indeed a dislike of these sensations
input or unusual interests in sensory aspects of the environ- spinning, rocking or hand flapping are often forms of self‐stim-
ment’ [9]. The reasons for these sensory processing difficul- ulation when hypo‐reactive to external stimulation; aversions
ties are not understood. to touch, light, smell, taste, sound or certain movements may
SPDs can fluctuate between hyper‐ and hypo‐reactivity in be due to hyper‐reactivity. Table 20.3 gives examples of sensory
each sense and can have marked negative impacts on a issues that could affect food intake and mealtimes.
child’s functioning in daily activities including eating [81].
SPDs not only relate to sight, sound, smell, touch and taste
but also to proprioception, sensations from muscles and Learning points: features of autism
joints that give a sense of where the body is in space; vestibu-
lar, sense of head movement in space that relates to balance; • Autism is a complex, common and costly condition
and interoception, the sensations associated with the physi- • It is characterised by a range of social difficulties with
ological and physical condition of the body such as the sense unpredictable outcomes and trajectories
of thirst, hunger and body temperature. • Causation is likely a complex interplay between multiple
SPDs impact on a child in many ways. Firstly, they may genes and mostly unavoidable environmental stressors
directly impact the way they experience the world around • Vitamin D and folate supplements peri‐conception may
them, impairing (or sometimes enhancing) their understand- play a role in development of autism
ing of objects and experiences, including food and mealtimes. • Autistic people often have numerous coexisting conditions
Secondly, they can affect their alertness: hypo‐responders may that can impair quality of life and affect mealtimes and
be understimulated and not alert enough to take part in a eating
learning activity, for example, or too busy self‐stimulating • Sensory processing difficulties are often a major contribu-
(‘stimming’) to concentrate; hyper‐responders may be over- tor to eating problems
stimulated by a learning activity and overwhelmed. Thirdly, • High premature mortality rates are of great concern and are
coping behaviours may be directly related to sensory an increasing public health priority
processing difficulties: common behaviours such as fidgeting,
Management of Autism 409
Future research needs/unanswered questions

Management of sensory processing problems
Help for sensory processing problems may include changes to

• the role of maternal nutrition
the environment to avoid stimuli that are upsetting where pos-
• the role of nutrition in the prevention of premature mortality
sible, e.g. reducing bright lighting and noise, wearing ear
in adults
defenders or coloured lenses or increasing the stimulation
• the role of nutrition in the treatment and prevention of
when someone seems hypo‐responsive, e.g. by having spicier
coexisting conditions
food or brighter lighting. To manage alertness and arousal lev-
els throughout the day and maximise learning, a ‘sensory diet’
may be used, which incorporates lots of sensory activities that
Management of autism are either calming or arousing for the individual. Activities that
involve high proprioceptive input (massage, squeezing, heavy
The challenges (and talents) of autistic CYP vary widely. lifting) are generally calming, and vestibular activities such as
Management should be individualised, with the aim of swinging and spinning may have a calming or arousing effect
managing comorbidities, and maximising their skills and their depending on the intensity. Vestibular and proprioceptive
quality of life. Some individuals who were very challenged as input can also dampen down sensory information from other
children can, with the right support, have a great quality of senses so that environments that are usually overwhelming can
life, find work, have a family and live independently, whereas sometimes be better tolerated. Specialist assessment and advice
many still need much support in adulthood [48]. are available from sensory integration trained occupational
therapists, speech and language therapists and music thera-
pists, although access to these varies. Practical and straightfor-
Medical management ward help like wearing specially designed weighted clothing,
having a discrete object to fiddle with, changing lighting or
Pharmaceutical interventions are limited to treating coexist-
reducing noise can sometimes have very significant effects on
ing conditions, for example, risperidone or aripiprazole for
concentration and reduction in undesirable behaviours.
irritability and agitation (with common side effects of weight
gain) and methylphenidate, atomoxetine and guanfacine for
ADHD (with common side effects of appetite suppression) Management of stress and anxiety
[82]. Other coexisting conditions are generally treated as
they would be for autistic CYP. The world can be a very stressful place for autistic individuals.
The cumulative effects of sensory difficulties, communication
Management of social communication and social barriers and a dislike of the unpredictable can lead to high
anxiety levels day to day. Anxiety can heighten or supress
interaction issues
appetite and make it difficult for autistic CYP to feel in a
relaxed enough state to tackle difficult situations like explor-
There are many education and behaviour interventions to
ing new foods. The following may help to reduce anxiety:
teach CYP (or to help parents to teach their child) effective
communication and appropriate responses to social situa- • effective management of sensory processing difficulties
tions. These include approaches such as PECS (Picture and other coexisting conditions
Exchange Communication System), TEACCH (Treatment of • a ‘sensory diet’
Autistic and Communication Handicapped Children), ABA • establishing daily routines to give predictability that
(Applied Behavioural Analysis), social stories and speech allows the individual to make sense of the world around
and language therapy. Physical activity is proven to help them and forewarning of any changes
not only with general fitness and motor skills, but social • using visual timetables and visual prompts to aid under-
functioning too [83]. standing of situations
• help with challenging social interaction, e.g. allowing to
sit alone sometimes and social stories to explain how to
Pathological demand avoidance deal with tricky situations
• help to express, e.g. using stress scales, phone apps or col-
Pathological demand avoidance (PDA) is accepted by some oured wristbands that enable them to let someone know
as incorporated within the spectrum of ASC [84, 85]. CYP if he or she is very stressed and unable to verbalise it
with PDA become very anxious when feeling that they are • relaxation and mindfulness
losing control when others put demands on them; this can • sleep and exercise
result in extreme behaviours including being very with- • time spent engaging in preferred special interests
drawn or volatile. CYP with PDA often have good levels of
social interaction and communication, and their behaviour
can be very challenging for parents, carers and professionals. Transition to adult care
Strategies for communication and behaviour change need to
be modified with CYP with high demand avoidance, e.g. The NICE [87] and SIGN [8] guidelines have recommenda-
avoiding rewards and use of more tentative language [86]. tions on the transition to adult services. Preparation for
410 Autism
transition should include all the family and be considered as CD to be three times more common in autistic CYP and,
early as possible, being particularly mindful that autistic therefore, recommended routine screening for CD in autistic
young people may find change incredibly hard. CYP however, a large Swedish study of biopsy registers did
not find a higher prevalence in autism, but instead found a
strong link between autism and CD serology in the absence
Learning points: management
of histologically normal intestinal mucosa [76–78].
An expert US multidisciplinary group consensus statement
• Autistic CYP often need tailored education and behavioural
recommends that ‘individuals with autism who present with
support
gastrointestinal symptoms warrant a thorough evaluation,
• Pharmacological treatment is primarily for coexisting
as would be undertaken for individuals without autism who
conditions
have the same symptoms or signs’ [120]. Markers of abdominal
• Management of stress, anxiety and sensory processing
pain or discomfort include irritability, agitation, aggression,
difficulties can help with overall functioning and eating
constant eating, pica, unusual posturing and unexplained
problems
repetitive behaviours, aggression and sensitivity.
Autistic CYP are significantly more likely to be at risk for
developing nutrient deficiencies [121, 122] and have a
Dietary and nutritional issues significantly lower consumption of calcium, protein and vita-
mins B12 and D [121–123], and a third have intakes below the
Prevalence lower reference nutrient intake (LRNI) for iron, zinc, calcium
and vitamins A, B2 and B12 [89]. Bone mineral density of young
Feeding problems such as extremely fussy eating are up to autistic children has been found to be significantly lower
five times more common in autistic CYP than in non-autistic than the reference for their age [124–131]. Serum 25‐hydroxy-
CYP, affecting up to 90% of children [88–91], and were recog- vitamin D levels are significantly lower than in peers [132];
nised even in the earliest descriptions of autism by Leo rates of iron deficiency range from 8% to 24% [133–137]; and
Kanner in 1943 [92]. Mealtimes for parents of autistic CYP biochemical markers of biotin, folate and vitamins B5, B12 and
and feeding problems can be ‘one of the most stressful times E are lower than in controls [138]. There are many published
of the day’, absent of enjoyment, horrible and even ‘hell on case reports of severe nutritional deficiencies including scurvy
earth’ [93]. A lack of support from professionals is commonly presenting as rash and/or muscle atrophy [139–152], concur-
reported [94–96]. rent vitamin A and D deficiency presenting as a limp and
Compared with typically developing controls, autistic periorbital swelling [153], vitamin B12 deficiency presenting as
children have more severe eating problems that include not partially reversible optic neuropathy [154], vitamin A defi-
staying seated, not eating with their families, ‘food jags’ ciency presenting as vision loss [155–160] and other multiple
(persistently wanting the same foods), narrower food reper- deficiencies leading to severe malnutrition [161–166].
toires, restrictions by food category, texture and the way they It is unclear whether rates of underweight, overweight
are presented [88, 97–99]. Eating habits can be extremely and obesity in autistic CYP are higher than or comparable to
rigid, e.g. only eating two or three foods, preference for food rates in the general population [167–176].
that is only ‘dry’ or ‘wet’, a particular colour or shape or from
a specific brand packaging [89]. Feeding problems are not
associated with the autism ‘severity’ [99–102]. Many autistic Assessment and management of dietary
CYP with eating problems may meet the criteria for the new and nutritional issues
DSM‐5 feeding and eating disorder diagnosis of avoidant
and restrictive food intake disorder (ARFID), but prevalence There is no evidence that autistic CYP have different nutrient
is yet to be studied [103]. Pica, packing or pocketing food in requirements to the general population. In the main, dietary
their cheeks, rumination and regurgitation and other abnor- and nutritional management of coexisting conditions, GI
mal feeding practices are also common, particularly in those conditions and nutritional problems should be as per the
with intellectual/learning disability [63, 104–106]. general population, taking an individualised approach to
The prevalence of autism in adults and young people with each child.
anorexia nervosa (AN) is estimated to be 23% (4%–53%), Having a good understanding of the core and coexisting
although accurate ascertainment of levels is problematic due challenges facing autistic CYP and their families is essential
to individuals acutely ill with AN displaying high levels of in providing assessment and treatment that is accessible and
symptoms characteristic of autism [107–110]. Screening for appropriate. 74% of respondents in a large survey of parents
autism in AN has been recommended as autistic CYP may of autistic CYP and professionals felt that autistic people
require significant treatment adaptations [108]. receive ‘worse’ or ‘much worse’ healthcare than non-autistic
Food hypersensitivities, GI problems, constipation, diar- people [177]. In another survey, the lowest satisfaction
rhoea and abdominal pain, disordered gut microbiota and with the National Health Service (NHS) was with those
increased intestinal gut permeability are more common than related to feeding, nutrition and diet with 24% unable to
controls (see Table 20.2) [67, 68, 74, 111–120]. Coeliac disease access support; 77% of those who did have support did not
(CD) can present as autism, and a prospective study found find it helpful [178].
Dietary and Nutritional Issues 411
Reasonable adjustments of feeding problems but also may lead or contribute to

feeding therapy.
The UK 2010 Equality Act and the 2008 Health and Social There is no clear consensus on the effective management
Care Act require that all health providers make ‘reasonable of feeding problems in autism due to a lack of quality evi-
adjustments’ to ensure their services are accessible and effec- dence [185]. SIGN guidance is to refer to a dietitian [8]; how-
tive to all, including autistic people [179, 180]. Suggested ever, NICE gives no advice as to whom should be involved
adjustments that may be appropriate are given in Table 20.4. in the treatment of feeding problems [87]. Various techniques
The National Autistic Society has further guidance for health and terminology used in feeding therapy are described in
professionals at http://www.autism.org.uk/guidance‐health‐ Table 20.7. Pilots of parent education strategies for feeding
professionals. problems in autistic and non-autistic CYP have been encour-
Table 20.5 summarises some possible underlying causes to aging for parent reported factors [90, 186–188].
consider for eating problems in autism. Much of the published evidence of treatment of feeding
When assessing and treating autistic CYP, the author problems (usually food refusal or extreme fussy eating) are
proposes the use of the following framework in addition to case studies using applied behavioural analysis (ABA) tech-
the usual dietetic aspects, adapted from the author’s work niques [189–192]. ABA in autistic CYP is controversial; it has
(Table 20.6) [184]. been associated with post‐traumatic stress disorder (PTSD) in
individuals [193]. The most ‘effective’ ABA techniques for
increased acceptance of foods typically involve escape extinc-
Feeding therapy tion, which is described in a book instructing on and advocat-
ing its use as ‘a difficult and emotionally upsetting intervention
For some autistic CYP, dietary change will be no more diffi- … imagine if someone put something you truly hate directly in
cult than for other CYP. However, most have some element your face and they would not move it. Non‐removal of the
of rigidity around their diets, and so to achieve any change, spoon is probably among the most intrusive ABA interven-
additional support will need feeding therapy. Dietitians are tions that are still considered appropriate … it is no surprise
uniquely qualified to assess and treat the nutritional aspects that the procedure often evokes challenging behavior’ [194].
Table 20.4 Reasonable adjustments for autism.
Area Possible adjustments
Consultation location Consider alternatives to clinic appointments if attendance is stressful: phone, email, video, home visits
Consider lighting and noise levels in consultation location and waiting rooms, provide a quiet area if needed
Consider if the autistic CYP needs to attend the consultation, especially if needing to discuss things that may be upsetting to
them
Consultation timing Allow double time for processing of information
duration Be punctual and warn if this is unlikely to be possible. Consider giving the first appointment or last appointment of the
clinic, or scheduling appointments outside busy times
Consultation Ask in advance what adjustments are needed
preparation Provide visual information to prepare for appointment, e.g. photos of the building entrance, room, dietitian
Provide easy‐read appointment letters
Verbal Simplify, slow down, avoid idioms that could be taken literally (e.g. ‘I’ll be back in a second’, ‘Eating that will put hairs on
communication your chest’), use positive commands rather than negative (e.g. ‘Sit down there’ rather than ‘Don’t stand over there’)
Don’t assume that CYP who cannot communicate verbally cannot understand verbal communication or that those who can
speak well can comprehend easily
Visual supports Use visual supports to complement any verbal instructions, e.g. written information, signing, the use of objects or pictures
Provide easy‐read information leaflets and advice summaries
Training Training in autism awareness is mandatory for all ancillary staff who work in public services, and more in‐depth training is
mandatory for all dietitians. Essential skills and knowledge for dietitians and ancillary staff are set out in the Skills for Health
Learning Disabilities Core Skills Education and Training Framework and Autism Skills and Knowledge Checklists [181, 182]
Assessment Ask direct questions. Allow written answers in advance
Autistic CYP may have symptoms (e.g. constipation, abdominal pain, symptoms of food hypersensitivities) that they are not
able to communicate verbally or distinguish well due to sensory processing difficulties, but may be indicated by different
behaviours, e.g. unusual irritability, food refusal, behavioural outbursts, unusual posturing
See Table 20.5 for possible underlying causes for eating problems in autism
Giving advice Simplify for some, provide detailed science‐backed information for others
Bear in mind that individuals with high IQ may struggle with executive functioning that may make following recipes and
food preparation difficult without simplified directions
Avoid unnecessary dietary rules that may be followed rigidly
Ensure advice is consistent and unambiguous from all that are involved
412 Autism
Table 20.5 Possible underlying reasons for dietary issues in children and young people with autism.
Dietary problem Possible underlying reasons
Pica • Understanding: not understanding the substance is not food

• Pain: eating inedible objects may ease gut pain or gum pain (or cause it in a sensory seeking way)
• Sensory: may be seeking some sensory input and stimulation from the substance
• Attention: the child or young person may enjoy the response they get from their caregivers when eating
the substance
• Anxiety: high anxiety levels may increase sensory seeking behaviour
• Mineral deficiencies: often cited as a reason for pica, but it is not clear if this is a true contributing
factor
Restricted diet/‘fussy’ eating • Behavioural rigidity and understanding: may need food presented in a certain way to be comfortable to
eat it; may need a predictable routine to be comfortable to eat; may not recognise food or may be upset
by foods mixing because they do not recognise the mix as food, may have self‐imposed rigid dietary
rules
• Anxiety: high anxiety levels may adversely affect appetite and increase reliance on only foods seen as
‘safe’
• Sensory: aversion to certain textures, tastes and smells or strong preference for others
• Obsessive–compulsive disorder (OCD): the need for rigidity around food presentation and routines
around food may become compulsive; may fear contamination or dislike perceived contamination of
foods with other foods or from germs, smells or tastes
• Skills: delayed oromotor or motor skills affecting the ability to eat or prepare food, impaired executive
functioning making planning of intake and food preparation challenging (in young people)
Overeating/voracious appetite • Sensory: a strong preference for certain textures, tastes, smells, the feel of being full, etc. (sensory
seeking behaviour); may not know when full or when to stop eating
• Pain: interpretation of gut pain as hunger; eating for comfort in the presence of pain, e.g. dental,
gastrointestinal, headaches
• Anxiety: anxiety can promote hunger or increase reliance on ‘safe’ foods – which may be high calorie
• Understanding: general desire to eat/enjoyment and lack of understanding that eating cannot happen
constantly; lack of understanding about when to eat and when not to eat (e.g. when inadequate
structure to the day, constant access to food), impaired executive functioning making planning of intake
and food preparation challenging (in young people)
• Skills: delayed oromotor or motor skills affecting the ability to eat or prepare food, resulting on reliance
of easier to eat foods, which may be higher calorie
• Medications: that promote hunger such as risperidone
Undereating/low appetite • Anxiety: high anxiety levels may adversely affect appetite and increase reliance on only foods seen as ‘safe’
• Pain: suppressing hunger or causing pain when eating (which could be dental, gastrointestinal,
headaches or anywhere else)
• Constipation: suppresses hunger
• Sensory: may be averse to foods on offer
• Understanding: may not understand the need to eat and drink to feel well; may not understand the
sensations that occur in the body on eating and so may avoid eating to avoid them, impaired executive
functioning making planning of intake and food preparation challenging (in young people), may have
self‐imposed rigid dietary rules
• Medications: that suppress hunger such as methylphenidate
• Skills: delayed oromotor or motor skills affecting the ability to eat or prepare foods
Inspired by an Autism West Midlands family information sheet [183].
The author’s suggested best practice approach is to carry Learning points: dietary issues
out feeding therapy as part of a multidisciplinary team
(MDT), involving as many of the following as possible: par- • Feeding, dietary and GI problems are widespread
ents, teachers, speech therapists, sensory integration trained • All dietitians should be trained in working with autistic
occupational therapists, paediatricians, clinical psycholo- CYP and ensure their practice is autism-friendly
gists, play therapist and portage. Table 20.8 details a prag- • Reasonable adjustments include allowing extra time for
matic stepwise approach to feeding therapy that could consultations, care with communication and consideration
include group or one‐to‐one sessions with parents and/or of consultation location
parents and the child or young person. • An in‐depth understanding of autism is vital in taking a
Two case studies are described in Tables 20.9 and 20.10, full history and designing support and interventions
suggesting approaches to two of the most common issues • There is little consensus in the best way to manage feeding prob-
parents of autistic CYP seek dietetic help for: firstly extremely lems, but there are a number of options and MDT working is ideal
fussy eating and secondly overeating.
Popular Therapeutic Diets and Supplements 413
Table 20.6 The autism 6Ss.
The autism 6Ss Assessment considerations Treatment considerations
1. Self‐esteem Don’t undermine Don’t undermine

2. Sensory Look for patterns in current diet preferences Consider the need for ‘sensory diet’
Work with sensory preferences not against
3. Structure Is there currently a structured: (a) daily routine Advise on a more structured: (a) daily routine and (b) food time routine
and (b) food time routine
4. Supports What are in place? What helps with other issues, Advise on putting these in place, e.g. visual timetables, social stories
e.g. visual timetables, social stories Ensure any dietary information is given consistently and
unambiguously with appropriate visual supports
5. Special (intense) What are they? Many autistic CYP have a very Can they be used to help with dietary change?
interests intense interest in a particular subject, e.g.
commonly Thomas the Tank Engine, or a game.
Sometimes it is their diet, e.g. veganism
6. Stress What coping strategies are in place? Advise on coping strategies, e.g. sleep, exercise, relaxation and
mindfulness
Source: Adapted from Connor and Mealey [184].
Table 20.7 Components of feeding therapy approaches.
Feeding therapy component Examples/explanation
Satter’s division of responsibility in Trust that if a parent provides the what, where and how of offering food, the child will decide whether
feeding to and how much to eat, a ‘no pressure’ approach to feeding all children (and discourages all the other
components in the table as they involve pressure)
Positive reinforcement Praise, compliments, rewards (food or non‐food), distraction
Negative reinforcement Warning, punishing, withholding preferred food until child eats non‐preferred food, selective attention
(looking away when she/he does not eat, paying attention when she/he does), stopping a video if the
child does not eat
Differential reinforcement of alternative An example of negative reinforcement – the child is allowed access to a preferred item or activity, e.g. a
behaviour toy only after eating a non‐preferred food
Escape extinction Non‐removal of the spoon (spoon held in front of the child’s mouth until she/he gives in and takes a
bite), physical guidance (physically opening the child’s mouth and putting in the food)
Systematic approximation Eating‐related activities, such as chewing on a washcloth, sitting in the chair at the table, offering food
and encouraging interacting with it, then touching it, then smelling it, then licking it, etc.
Food chaining/spreading the sets Widening variety of foods eaten by starting with favourite and then offering closely related foods that
are a bit more challenging
Source: Adapted from www.ellynsatterinstitute.org.
Popular therapeutic diets and supplements

Dietary changes could plausibly improve functioning in
• Which interventions are best in managing feeding problems autism. Individual nutrients or diet patterns could directly
while avoiding harm? affect brain cell structure (e.g. omega‐3 fats), neurotransmitter
• Do feeding problems improve with time and age without activity (e.g. B vitamins) or brain cell metabolism (e.g. ketogenic
interventions? diets). Indirectly, nutrient deficiencies, reactions to foods or
• What is the prevalence of nutrient deficiencies? microbiota imbalance could all affect functioning, the ability to
• How can we best screen and test for nutrient deficiencies in concentrate and learn and behaviours by causing pain. Sound
children and young people who are averse to blood tests? evidence to support recommending dietary changes are, how-
• How can we aid compliance in taking supplements? ever, lacking. There are many barriers to carrying out high
• How can we promote general healthy eating and physical quality dietary intervention studies in autism: diverse subject
activity? groups due to autism being a probable group of conditions
• What role does childhood diet and nutrition play in the high with differing aetiologies [204], a lack of consensus of autism‐
early mortality rates in autistic adults? specific target outcomes or tools [205, 206] and the complex
challenges of clinical nutrition research [207–209].
414 Autism
Table 20.8 Suggested stepwise approach to feeding therapy in autistic children and young people.
Step Detail
1 Do nothing: This is an option if there are few nutritional concerns and it is not a priority for parents. Often one of the key things parents
seek from a dietetic consultation is reassurance that their child is growing well and that their problem is not unique
2 Standard fussy eating management: Changes to the environment and feeding relationship in line with the trust model of feeding and
Satter’s division of responsibility in feeding (sDOR) [195–199]. sDOR is reported by proponents to ‘work’ even in severe feeding issues in
ASC, but there is no empirical evidence for this
3 Autism‐specific fussy eating management: Step 2 plus additional strategies for autism (but no pressure to try any new foods in line with
sDOR as above), which may include:
• Visual timetables detailing when and where they will eat and what will be eaten
• Visual schedules with written or picture symbol schedules detailing behaviour expected at mealtimes or foods to be tried at a mealtime
• Very structured routines day to day and before and after meals
• Social stories or social articles (specially written stories or articles explaining how and why to do something) [200]
• Relaxation exercises before meals, e.g. progressive muscle relaxation
• Stress‐reducing strategies during meals, e.g. playing favourite music/video clips
• ‘Sensory diet’ specific to mealtimes, e.g. incorporating calming or alerting activities before a mealtime such as blowing bubbles,
washing hands and face to ‘wake them up’, heavy lifting or swinging before meals, sitting on a large ball during eating, using a weighted
lap tray, adjusted cutlery
4 Home‐based food introduction: Step 3 plus slow desensitisation to new foods via food play outside mealtimes (if tolerated) and/or food
chaining/spreading the sets [201]. Useful motivators to engaging in food exploration include:
• ‘Eat it up’ books. A written list or picture symbol list of foods liked, foods parents want the child to try and the foods the child is going to
try next. Foods can be moved gradually up the lists
• Using ‘special interests’ to motivate. Autistic CYP often have intense interests, e.g. watching the same part of a popular children’s DVD
story. Reserving access to special interest to ‘reward’ times may be an effective motivator
• Modifying a favourite game to include activities to taste new foods, e.g. snakes and ladders – trying a new food to prevent going down a
snake. An example of a clinical use of a specially devised board game is described by Gillis [202]
5 Professional food introduction: Professional intervention working directly with the child on developmentally appropriate food
desensitisation systematic approximation, e.g. the SOS (Sequential Oral Sensory) Approach [203] is an MDT approach to intensive feeding
therapy using a developmentally informed food school or food scientist approach in groups of CYP, alongside parental training to continue
the approach at home
6 More invasive options: Enteral feeding may be necessary to improve nutritional status in the short to medium term while feeding therapy is
provided. There may be a role for ABA approaches if enteral feeding is contraindicated or rejected (e.g. gastrostomy tube pulled out) and
improved nutritional status is urgently needed
NICE guidance advises against using any therapeutic supplementation with omega‐3 fatty acids [219], vitamin B12
diets or supplements for core autism ‘symptoms’ [87]; SIGN [219], levocarnitine [219], digestive enzymes [219], vitamin
guidance found insufficient evidence to draw firm conclu- B6 and magnesium [222] or camel milk [219]. There is
sions and recommended further research [8]. some pilot evidence for supplementation with iron [223],
There are many organisations and complementary and sulphoraphane (from broccoli sprout extract) [224], ubiqui-
alternative medicine (CAM) practitioners (and some main- nol [225], folic acid [38, 226], high dose vitamin C [227], vita-
stream practitioners) who recommend various diets and min A [228], probiotics (Lactobacillus plantarum WCFS1) [229],
supplements for autism, and many companies sell tailored prebiotics [230] and a multiple dietary and supplement
supplements, parent training and books [210–215]. Many intervention [231]. Dimethylglycine (DMG) [232] and N‐ace-
anecdotes on the Internet describe autistic CYP (and adults) tylcysteine (NAC) [233] supplementation showed no signifi-
who have benefitted from one or more dietary changes, cant effects compared with controls. Randomised controlled
sometimes dramatically so. Unsurprisingly then, around a trials (RCTs) of vitamin D supplementation have given con-
third of parents in England have tried exclusion diets for flicting results [234, 235]. A double‐blind RCT of a multivita-
their child, and over a half have tried micronutrient supple- min and mineral supplement in adults (containing high doses
ments [216]. of B vitamins, no iron and a subclinical dose of lithium) showed
Dietary approaches and supplements for autism range in promising results in improved functioning [236].
plausibility, evidence base and safety [217]. A report by the A ketogenic diet has shown promise in mouse models of
Westminster Commission on Autism highlighted particu- autism [237] and in pilots in autistic CYP [238]. Popular
larly dangerous options, e.g. the ‘supplement’ Miracle dietary approaches that have no published evidence include
Mineral Solution (MMS), a 28% sodium chlorite solution the exclusion of phenolic compounds and salicylates, the
equivalent to industrial strength bleach, and found that Specific Carbohydrate Diet (SCD) and the Gut and
ingestion as ‘recommended’ could be lethal [218]. Psychology Syndrome Diet (GAPS). SCD has a history of
Systematic reviews have found inadequate evidence to more than 50 years; it eliminates grains, sucrose and lactose
recommend gluten and casein/milk exclusion [219–221], with the theory that this modifies intestinal bacteria growth
Popular Therapeutic Diets and Supplements 415
Table 20.9 Case study: Gina, an autistic 5-year-old who has a very selective diet.
Assessment
• Anthropometry: no concerns – tracking the 50th centiles
• Biochemistry: none available – aversive to having blood tests
• Clinical/physical: diagnosed with ASD at 3 years of age, bowels open regularly, good energy levels, no other diagnosis
• Dietary: severely limited diet – eats 4–6 times a day, banana sandwiches, in total six slices white bread with four bananas and 600 mL full‐fat milk to
drink plus water. Dietary analysis shows that despite the lack of variety, the RNI is met for most nutrients and the EAR is achieved for all
micronutrients except for vitamin D
• Environmental/behavioural/social: attends mainstream primary school, limited verbal communication, learning to use PECS but not yet proficient
• Focused on parents’ concerns in order of priority: (1) worry about nutritional adequacy and (2) how to widen food range
Plan
Focus 1: Worry about nutritional adequacy
1. Reassure parents of Gina’s growth and relative dietary adequacy
2. Address vitamin D shortfall:
a. Recommend a vitamin D test due to likely low historic intake and high levels of deficiencies in autistic CYP. A finger prick test may be better
accepted
b. Recommend a standard vitamin D supplement until vitamin D levels established
c. Advise on acceptance of supplement:
i. Hiding it in a preferred food is likely to backfire with autistic CYP who often have very sensitive taste detection
ii. Advise it is usually better to introduce it as a medicine and to use social stories, visual supports and explanations that it is a medicine and
is essential
iii. It can be mixed with something of a preferred taste to reduce its likelihood to elicit a disgust response or paired with a spoonful of a
preferred food directly after
iv. Find out from parents how they have managed to accept medicines previously; often they never have
v. Help from teachers, speech therapists, play therapists, etc. can be utilised to make acceptance of the supplement in the short term the
absolute priority
Focus 2: How to widen food range
1. Establish if this falls under remit of the dietetic service or that of other members of the MDT. If the dietetic service has scope and training and
knowledge to provide feeding therapy, continue as below
2. Explore underlying issues:
a. No apparent underlying oromotor or medical issues
b. Feeding problems have been apparent since introduction of solids at 5 months; no identified traumatic experience associated with it starting
(e.g. choking, silent reflux, tube feeding, illness)
c. 6Ss
i. Self‐esteem – No issues identified
ii. Sensory – Gina has help with various sensory integration issues – messy play has helped accepting getting her hands dirty; massage and
body brushing has helped to calm her down when anxious and the parents and school already have a sensory diet plan that they follow
iii. Structure – Gina has a relatively well‐structured day and mealtimes are very structured to her preferences: the same cutlery, place setting,
sat at a table, etc.
iv. Supports – At school they use visual timetables, PECS and a choice board at mealtimes. Gina is still getting used to these
v. Special (intense) interests – Gina loves kittens; using books with kittens has been used effectively with toilet training
vi. Stress – Change in Gina’s routine cause anxiety. Changes to the presentation or any aspect of her food causes extreme anxiety and often
food refusal. Introduction of new foods in her proximity provokes a fear response
3. Explore management options (from steps shown in Table 20.8):
a. Step 1: Do nothing: Give parents permission to do this as there is little evidence whether feeding therapy is effective in autism; incidental
exposure to foods via family mealtimes, school activities and sensory activities may help her to vary her diet with time. If parents opt for this,
they can be advised to seek further help immediately if Gina’s diet reduces in range as she would then need a multivitamin and mineral
supplement to ensure nutritional adequacy
b. Step 2: Standard fussy eating management: Parents have consistently applied this and it hasn’t helped
c. Step 3: ASC‐specific fussy eating management: Gina’s parents have a good understanding of autism and its management. Discussion of why
feeding problems may be more common in autism helps them to see the problem through Gina’s eyes, e.g. sensory issues, behavioural rigidity
and social demands at mealtimes. As Gina becomes more used to visual supports used at school, these may help with mealtimes at home and
with slow introduction of new foods
d. Step 4: Home‐based food introduction: If Gina’s parents want to try to push her on with food acceptance, they could try food chaining at
home making small changes to her preferred foods, e.g. adding a bit of food colouring or changing the way it looks on the plate. The worry
with this with such a restricted range is that she might then reject a core food and they have reported that changing her foods invokes stress.
Parents and school staff may be able to come up with creative ways to motivate her to interact with new foods in a non‐threatening way
outside mealtimes, e.g. using her special interest of kittens; could they play with feeding foods to a toy kitten supported by a home‐made book
about kittens eating different foods?
e. Step 5: Professional food introduction: Gina may be a suitable candidate for group food play sessions aiming for
systematic approximation as in the SOS Approach
RNI, reference nutrient intake; EAR, estimated average requirement; PECS, Picture Exchange Communication System.
416 Autism
Table 20.10 Case study: Rajesh, a 14‐year‐old autistic boy who overeats.
Assessment
• Anthropometry: height tracking 50th centile, weight >99.6th centile and moving further upwards, BMI >99.6th centile and moving further upwards
• Biochemistry: none available
• Clinical/physical: diagnosed with autism at 3 years of age; chronic constipation, no other diagnoses
• Dietary: eats three meals a day, snacks a lot in the evenings, demands food when he wants it. Meal choices not excessive in fat and sugar and
portion sizes, but evening snacks consist of crisps, chocolate, biscuits and sugary drinks and make up at least a third of his energy intake
• Environmental/behavioural/social: attends a special educational needs school, teachers find his behaviour around food challenging – demanding
food off others’ plates, etc. Rajesh has limited verbal communication but makes his desires known via behaviour and PECS. Rajesh does little
physical activity
• Focused on parents’ priorities, unable to ascertain from Rajesh due to communication barriers; parent priorities: (1) reduce behaviours that
challenge around demanding food and (2) reduce the risk of diseases associated with obesity
Plan
Focus 1: Reduce behaviours that challenge around demanding food
1. Establish if this falls under remit of the dietetic service or that of other members of the MDT. If the dietetic service has scope and training and
knowledge to provide support in changing behaviours that challenge, continue as below
2. Explore underlying issues:
a. No apparent oromotor or medical issues apart from constipation
b. Discuss better medical management of constipation and ruling out potential underlying causes such as coeliac disease
c. 6Ss
i. Self‐esteem – Rajesh is very sensitive about having his weight and eating discussed. After an initial brief consultation meeting Rajesh and
establishing with parents and school staff, further advice and assessment is given without Rajesh present. School staff can monitor his
weight prior to each follow‐up appointment to avoid him needing to be involved further unnecessarily
ii. Sensory – Rajesh hasn’t had sensory issues considered previously. He seems to love the crunch of snack foods in the evening – could this
be ‘sensory seeking’ behaviour? If so could other sensory activities help to replace this, e.g. munching on raw vegetables or wearing an
age‐appropriate chew ring
iii. Structure – Rajesh has a structured day at school but free access to food in the evenings. A very set routine around eating and rules about
when and where food can be eaten can be very effective, especially when backed up by social stories, visual supports and even locked
kitchen doors
iv. Supports – At school Rajesh uses visual timetables, PECS and a choice board at mealtimes. At home little is used. Introducing these around
foods and food times is advisable. Visual supports around home food rules will help parents to say ‘no’ consistently to Rajesh’s demands.
Teaching about hunger and satiety levels using a visual hunger scale, supported by social stories to explain this, can sometimes be
effective in helping autistic CYP manage their desires to eat
v. Special (intense) interests – Rajesh loves dinosaurs. Could activities about dinosaurs and what they eat be used to help to learn about
healthier eating and being more active?
vi. Stress – Could Rajesh’s appetite in the evenings be driven by his stress levels? He does very little exercise – could regular evening exercise
serve the double purpose of reducing stress and reducing the time he is able to access snack foods? Could mindfulness and relaxation help?
Focus 2: Reduce the risk of diseases associated with obesity
1. Dietary management
a. Help parents consider keeping tempting foods out of the house or locked away
b. Avoid giving any hard and fast dietary rules or advice that could cause harm if followed rigidly, e.g. ‘avoid fat’, ‘avoid fatty foods’, etc. If giving
prescriptive dietary advice, ensure that it is clear that it is ok to have some days when they don’t follow them, e.g. at celebrations or religious
feast days
c. Ensure verbal advice given directly to Rajesh is accompanied with clear and unambiguous written information that is developmentally
appropriate. Could appropriate materials be given to the parents to discuss with Rajesh at home?
2. Advise on physical activity levels
This is not primarily for weight management, but for overall health and well‐being, lowering of anxiety and possibly a way to keep him busy in the
evenings and away from food. Sensory issues are sometimes a barrier to engaging in some activities, e.g. aversion to the noise in the gym, and
social communication can sometimes make team sports challenging to participate in. Could going to the gym with a parent in the evenings be an
option, or getting a treadmill or exercise bike at home, or going for long walks, runs, bike rides or swims? Could the family get a trampoline for
their garden?
PECS, Picture Exchange Communication System.
and treats various digestive disorders [239]. GAPS is a more A pragmatic approach to therapeutic
recent modification of SCD, with multiple supplements, and diets and supplementation
its author claims it is effective in many different disorders,
including autism [240]. Both GAPS and SCD have extensive Parents of autistic CYP often do not readily disclose their
(differing) lists of foods to be avoided with limited rationale. use of complementary health approaches, including dietary
GAPS has aspects that risk malnutrition, e.g. the advice to approaches and supplements, to professionals and may wish
follow the first stage – a limited range of broths and fer- to pursue them despite their weak evidence base [217, 242,
mented foods – for as long as it takes for diarrhoea to settle 243]. Left unsupported, parents are at risk of putting their
and ‘the gut to heal’, over a year if necessary [241]. child on more and more restricted and imbalanced diets,
A Pragmatic Approach to Therapeutic Diets and Supplementation 417
accompanied by expensive and often excessive supplements. integrative approaches in autism [247]. Vitamin and min-
Dietitians and other professionals should inquire in a non‐ eral supplementation in the absence of a clear biochemical
judgemental manner about all interventions families are or dietary need, and exclusion diets in the absence of visi-
using and considering [217]. A ‘shared decision‐making’ ble effects after a trial, should not be recommended, but
model is recommended to avoid a paternalistic approach are relatively safe when monitored so can be accepted/
that may alienate parents [242, 244, 245]. tolerated. Overly restrictive diets such as SCD and GAPS
Dietitians should not interpret lack of RCT evidence of should be recommended against due to their lack of sound
efficacy as evidence of inefficacy and should recommend rationale, evidence, nutrition risk, cost and inconvenience.
standard dietetic approaches including a healthy lifestyle, However, if parents are determined to continue, careful
vitamin and mineral supplementation and trials of exclusion dietetic monitoring can help to reduce these risks, although
diets when indicated. Table 20.11 compares the ease, sup- this may fall outside the scope of stretched NHS dietetic
porting evidence and potential risk to health when using service provision. Advice on vitamin and mineral supple-
therapeutic diets in autistic CYP. Families should ideally be mentation to meet the reference nutrient intake (RNI) when
advised to introduce one intervention at a time to monitor dietary intake is insufficient is appropriate. Pharmaceutical
effectiveness and side effects [246]. doses for corrections of deficiencies usually fall under
Table 20.12 adapts the classification of approaches that medical rather than dietetic scope, and appropriate refer-
clinicians can recommend, monitor, tolerate or avoid, rals and requests when deficiencies are suspected should
based on their evidence and safety from a review of be made.
Table 20.11 Qualitative comparison of therapeutic diets used in autism.
Difficulty in following
Intervention the intervention Supporting evidence Negative impact on nutrition/health
Exclusion of gluten and/or Moderate* Some Insufficient calcium, iodine, fibre and energy intake
milk possible, but minimised with dietetic support
Other exclusion diets Moderate* None Possible dietary deficiencies, but minimised with
dietetic support
Ketogenic diet High* Some High risk of dietary deficiencies and growth
faltering, but minimised with dietetic support
Individual vitamin and Low* None/some for vitamin B6 Possible side effects at high doses, e.g. neuropathy
mineral supplementation in high dose vitamin B6; a possible antagonistic
effect for other vitamins and minerals
Multivitamin and mineral Low* None (some for supplements with Unlikely (possible side effects of high doses)
supplement (standard levels) high doses of some nutrients)
Fish oil supplements Low* Some Unlikely
Probiotics Low* Some Unlikely
Digestive enzymes Low* Very little Unlikely
Improvement when on dietary modifications may mask underlying disorders (e.g. coeliac disease, metabolic disorders, epilepsy); therefore continued
communication with the patient’s doctor is vital.
*Ease of intervention is significantly decreased if the child is resistant to changes in diet/resistant to taking supplements.
Table 20.12 When to recommend, monitor, tolerate or avoid a dietary therapy for autism.
Safe
Yes No
Yes (generally accepted Recommend: Monitor:

dietetic practice or Healthy eating, supplementation to meet dietary deficits Exclusion diets – recommend a time‐limited
evidence from two RCTs) (including omega‐3 fatty acids) or correct deficiencies, trial when hypersensitivities suspected, e.g.
probiotics, physical activity and general healthy lifestyle gastrointestinal, skin or behavioural symptoms
Effective
No or not established in Tolerate and monitor: Avoid:

two or more RCTs Single or multivitamin and mineral supplementation, SCD and GAPS diet, high dose vitamin A
digestive enzymes, amino acid supplementation supplementation, dangerous ‘supplements’
Exclusion diets in the absence of evidence of them resolving such as MMS, self‐directed ketogenic diet
food hypersensitivities or gastrointestinal disturbances
RCT, randomised controlled trial; SCD, Specific Carbohydrate Diet; GAPS, Gut and Psychology Syndrome Diet; MMS, Miracle Mineral Solution.
Source: Adapted from Klein and Kemper [247]. Reproduced with permission of Elsevier.
418 Autism
Learning points: therapeutic diets Summary
• Therapeutic diets and nutritional supplements are popular Autism is complex, costly and under‐researched. Dietary
with parents of autistic CYP but lack a quality evidence base issues are common and further study into effective manage-
• Dietitians should directly ask parents about interventions ment is needed. Research into the role of diet and nutrition
they are using or considering as spontaneous disclosure is in reducing comorbidities in autistic CYP continues to
not usual emerge, but the quality remains weak partly due to inherent
• Care is needed to guide parents away from harmful interventions barriers to quality research in this area. All dietitians must
• Support in following interventions that are low risk should ensure they are adequately trained to best support autistic
be offered to reduce any risk of harm CYP and address poor satisfaction with existing care.
Dietitians should ensure that commissioners and service
managers are aware of the additional resources needed to
provide a service with the reasonable adjustments that are
essential to ensure optimal care.
• Are there subsets of autistic CYP who would benefit from

different therapeutic diets or supplements?
• What role does an individualised approach to testing and
correcting metabolic differences in autistic CYP play, and References, further reading, guidelines, support groups
what role can dietitians take in this? and other useful links are on the companion website:
21
Jennifer Douglas
Feeding Children
with Neurodisabilities
Introduction with CP, are small as part of their condition. With the evolution
of enteral feeding, it has become evident that children with
Neurodisability is a term used to describe conditions affect- neurodisability have the potential to grow if adequate nutri-
ing the brain and central nervous system (CNS) and includes tion is provided [9].
muscular, developmental, motor, sensory, learning and neu-
ropsychiatric disorders. CNS damage can be due to disease, Cerebral palsy
genetics, oxygen deprivation or acquired brain injury and
can occur at any stage in a child’s life. The majority of CP is defined as ‘a group of permanent disorders of the
research is on children with motor disorders and cerebral development of movement and posture, causing activity
palsy (CP), which are the two most common causes of limitation, that are attributed to non‐progressive distur-
neurodisability [1]. These children often have neurological bances that occurred in the developing fetal or infant brain’.
involvement of other body systems as part of their condition The motor disorders of CP are often accompanied by distur-
[2]. In the past 10 years, there has been a steady increase in bances of sensation, perception, cognition, communication
the number of children with severe disability due to and behaviour, by epilepsy and by secondary musculoskel-
increased survival of preterm infants and better survival etal problems [10]. There is currently no test before birth to
outcomes for children with brain injury. In 2016 there were identify CP. The incidence in the UK is currently 1 in 400
54 143 infants born before 37 weeks’ gestation in England children and 2.1 per 1000 live births [11].
and Wales [3]. Survival rates have improved dramatically in CP is a condition where there may be abnormal brain
the UK, but neurological impairment is seen in 45% infants development or brain injury during development. This can
born at 22–23 weeks, 30% at 24 weeks, 25% at 25 weeks and occur before, during or after birth, and even during early
20% infants born at 26 weeks’ gestation [4]. childhood. It is not unusual for children to be diagnosed at a
Many children with neurodisability have difficulties with later stage when the child’s motor development is almost
eating and drinking, and they are likely to have nutritional complete. Even before diagnosis is established, children may
concerns that need to be addressed [1, 5]. Oromotor dys- already be experiencing oromotor problems.
function is associated with poor health and nutritional out- Causes of CP may be complex with no obvious single
comes, affecting up to 98% of children with moderate to cause. However, there are certain risk factors that may con-
severe CP [6]. Those with motor, physical or sensory impair- tribute: premature birth, placental abnormalities, birth
ments are more likely to struggle, and the more severe the defects, low birthweight, meconium aspiration, instrumen-
disability, the more likely the child is to be at nutritional risk tal/emergency caesarean delivery, birth asphyxia, neonatal
[1, 7]. The ability of infants, children and adolescents to seizures, respiratory distress syndrome, hypoglycaemia and
achieve their potential for growth and development neonatal infections [12].
depends on the intervention provided at critical time peri- There are four main types of CP, which correspond to inju-
ods. Many children with neurological impairment would ries to different parts of the brain [13]. Children may have:
benefit from individual nutritional assessment and manage-
ment as part of their overall care [8]. It has been accepted in • spastic CP – the most common form of CP causing hyper-
the past that children with neurodisability, especially those tonia, or increased muscle tone, giving movements that

420 Feeding Children with Neurodisabilities
are stiff or jerky. This form is caused by damage to the WHO standard growth charts and other anthropometric
motor cortex either during or after birth measurements of nutritional status [5].
• dyskinetic CP – involves involuntary movements caus- Low micronutrient intake and low micronutrient serum
ing slow twisting or repetitive movements or abnormal concentrations are common in children with CP and can
sustained postures. This form is caused by damage to the also occur in those who are tube fed [18, 19]. Nutritional
basal ganglia status should be assessed frequently to ensure that micro-
• ataxic CP – the least common form of CP causing shaky nutrient requirements are met [5]. Tube feeding and the use
movements, clumsiness, imprecision or instability when of nutritional supplements are associated with higher
walking or picking up objects. This form is caused by micronutrient concentrations [19]. It is important to take
damage to the cerebellum into account the type of CP the child is diagnosed with
• mixed‐type CP – a mixture of two or more of the above (including other comorbidities) as this has significant
implications on the chosen nutritional management plan.
The Gross Motor Function Classification System (GMFCS)
Children with spastic quadriplegic CP, hypotonic patients
can be used to classify a child according to their current level
and those having seizures often have significant feeding
of function and gives an idea of what equipment and mobil-
difficulties [20].
ity aids may be needed in the future. The GMFCS defines
The following factors should be taken into consideration
five grades for children between 6 and 12 years of age [13]:
when assessing a child with CP:
• level I: can walk, run, jump at home, school or in the
• type of CP and limb involvement
community, but speed, balance and coordination is
• mobility: including information about locomotion such
limited
as the use of wheelchair or a walker
• level II: can walk in most settings, but may find long dis-
• gastrointestinal problems: gastro‐oesophageal reflux
tances and uneven terrain challenging without mobility
(GOR) and chronic constipation are common in children
aids. They have minimal ability to run or jump
with CP [21]
• level III: can walk indoors with a handheld mobility aid.
• dependence on feeding: ability to self‐feed, dependent or
They need a wheeled mobility aid for longer distances
partially dependent on assistance from caregivers
and can self‐propel their wheelchair
• feeding dysfunction: detailed information regarding
• level IV: uses mobility aids that require physical assis-
how the child manages food textures such as puréed,
tance or powered mobility. They may walk for short dis-
mashed or chopped foods [5, 22]
tances at home with physical assistance or use powered
• feeding skills: should be assessed at regular intervals in
mobility or a body support walker when positioned
order to identify children at nutritional risk. Parents/
• level V: is transported in a manual wheelchair in all
caregivers should be asked about the presence of tongue
settings
thrust, drooling/dribbling causing fluid loss, lack of
Improved nutritional status in children with CP is associ- hand to mouth coordination, poor lip seal causing food
ated with improvements in general health, such as decreased or fluid loss, inability to communicate hunger, prolonged
irritability and spasticity, improved healing of pressure sores feeding times and dysphagia [5, 14]
and improved circulation [1]. In contrast, undernutrition is • environment: environmental factors can have an impact
significantly associated with poor functional status, poor on growth and nutrition, e.g. the child’s living situa-
motor function, reduced communication ability and tion, mealtime environment, lifestyle, involvement in
increased dependence on the caregiver for feeding [14]. The therapy groups, school and respite care arrangements
level of feeding dysfunction can be directly related to the [23]. Information about the family and the child’s expe-
degree of undernutrition, and even those who have mild rience with oral feeding should be sought as this may
feeding dysfunction may have poor growth and limited fat affect decisions about future oral or non‐oral feeding
stores [5, 8]. Therefore, a child requiring any modified con- methods
sistency of food and fluids can be at risk of nutritional com- • other medical conditions and respiratory health: these
promise. It has been documented that 89% of children with children are vulnerable to respiratory morbidity for sev-
CP need help with feeding and 56% regularly choke during eral reasons, so it is important to find out about frequency
mealtimes [1]. Poor growth and nutritional status is common of chest infections and other respiratory problems that
in children with CP and is more prevalent in those with may have an effect on energy requirements [24]
higher GMFCS grading. Prevalence of poor growth in chil- • bone health: there is a higher risk of low bone mineral
dren with CP can range from around 20% to 51% depending density, osteopenia and osteoporosis due to reduced
on which growth chart has been used [15]. CP specific weight‐bearing activity or being bed bound, lack of
growth charts were first developed by Krick [16] and further nutrition, medication limiting vitamin D metabolism
developed by Day [17]; they show similar growth in children and limited sun exposure. DEXA scans may be useful to
with lower GMFCS grade to that in normal children, but determine bone mineral density [5]
substantially different growth in children with moderate to • anthropometry: there is no universally accepted method
severe disability. These growth charts may be a poor predic- for measuring children with CP. Alternatives to measuring
tor of nutritional status and should be used alongside the height are available and are discussed later (p. 423)
Nutritional Requirements for Children with Neurodisability 421
Down’s syndrome Despite an energy intake below the normal requirement,

there is a high prevalence of obesity in children and adults
Down’s syndrome (also called trisomy 21) is the most com- with Down’s syndrome [35, 36]. Causes of obesity in those
mon genetic cause of learning disabilities. The incidence of with Down’s syndrome may be related to increased leptin
Down’s syndrome in England is estimated at approxi- levels, decreased resting energy expenditure, comorbidities,
mately 1 in 990 live births [25]. There were 1698 cases in undesirable food intake and low activity levels [36]. As obe-
England of Down’s syndrome in 2014 with 64% diagnosed sity is prevalent in adolescence and adulthood, it is recom-
prenatally by cytogenetic diagnosis, and only 574 resulting mended that growth charts are used in conjunction with
in a live birth [25]. Median life expectancy for those with body mass index (BMI), using the same cut‐offs for obesity
Down’s syndrome is 58 years, and average life expectancy as are applied to the general paediatric population. With
is 50.1 years [26]. appropriate support around nutrition and exercise, obesity
Many children with Down’s syndrome will have other can be managed successfully [37].
complications such as congenital heart defect (43%), gastro- The general consensus is that the majority of children with
intestinal problems (10%), coeliac disease (5%), recurrent Down syndrome can meet vitamin and mineral requirements
respiratory infections, joint problems, endocrine dysfunc- if they are eating a normal diet, but monitoring may be
tion particularly hypothyroidism, constipation, haemato- needed for those who are unable to eat a healthy balanced
logical cancers and GOR [27, 28]. Regular screening is diet or those requiring tube feeding [5, 38].
recommended for children with Down’s syndrome to ena-
ble early identification of the common comorbidities. Neuromuscular and progressive neurological
Down’s syndrome is associated with anatomical facial
disorders
abnormalities, which can have significant effects on feeding.
Feeding skills should be assessed at regular intervals [5].
There are approximately 60 different types of muscu-
Dysfunction occurs due to poor neuromotor control, dental
lar dystrophy and related neuromuscular conditions.
anomalies, orofacial dysmorphology and hypotonia particu-
Congenital neuromuscular disorders in children include
larly of the tongue and lips. Children with Down’s syndrome
spinal muscular atrophy and muscle disorders such as
are frequently mouth breathers due to narrowing of the nasal
Duchenne muscular dystrophy and congenital muscular
cavity and chronic inflammation of the tonsils as a result of
dystrophies. These conditions are characterised by the loss
an increased incidence of upper respiratory infections. The
of muscle strength as progressive muscle wasting or nerve
palate is often short and narrow, and this underdevelopment
deterioration occurs.
of the maxilla may alter the position of the muscles used for
Progressive neurological disorders are extremely rare con-
chewing. Infants with Down’s syndrome may have difficulty
ditions where deterioration advances over time. There are a
in initiating a suck and have a weak lip seal, poor coordina-
large number of different diagnoses, e.g. Batten’s disease,
tion of the suck/swallow/breathing sequence with early
leukodystrophies, Cockayne syndrome and Rett syndrome.
fatigue and jaw instability [29]. Breastfeeding is possible for
In some conditions there is a steady rate of deterioration; in
infants with Down’s syndrome, but for many it will be more
others it occurs in phases.
difficult to establish due to the associated oromotor difficul-
Due to the vast number of different neuromuscular and
ties. Adequate support is needed to achieve successful breast-
progressive neurological disorders, it is essential to con-
feeding [30]. Down’s syndrome is associated with impaired
duct a literature search at the time of patient review for the
immune function and higher incidence of obesity. Therefore,
most up‐to-date information. Table 21.1 shows some of the
breastfeeding may confer long‐term benefits. Comorbidities
more common disorders referred to the dietitian and some
such as congenital heart disease and gastrointestinal dysmotility
of the nutritional considerations associated with each
may further compromise feeding [31].
disorder.
Parental surveys suggest that due to oromotor difficul-
ties, children may also have increased choking and vomit-
ing with feeding [32]. With adequate feeding support Nutritional requirements for children
children are likely to become independent feeders by early with neurodisability
childhood.
Anthropometric assessment of children with Down’s syn- Energy
drome is complicated because of the associated abnormali-
ties related to growth such as short stature, decreased head Children with disabilities often have lower energy needs
circumference and altered growth patterns. Cronk suggests than healthy children due to reduced activity and lower
that while height in people with Down’s syndrome is muscle tone. Prediction equations and dietary reference val-
significantly lower than the norm, the period in which most ues therefore tend to overestimate requirements [5]. This has
significant growth failure occurs is during the first 5 years of been shown by the Oxford Feeding Study research team,
life [33, 34]. Specific growth charts have been developed for where children with disabilities tended to lay down stores of
children with Down’s syndrome, and they describe typical fat rather than muscle when gastrostomy fed beyond their
growth, not necessarily ideal growth [33]. needs [8, 24]. There is currently no universally accepted
Table 21.1 Neuromuscular and progressive neurological disorders and nutritional considerations.
Common conditions Nutritional considerations Useful websites
Lysosomal storage disease Commonly have short stature, skeletal deformities, muscle weakness or lack of www.ninds.nih.gov
(Tay–Sachs, Fabry, Pompe, control (e.g. ataxia, seizures), neurological failure/decline and/or loss of gained www.sanofigenzyme.com
metachromatic development. Poor swallow may require tube feeding or texture‐modified diet. www.rarediseases.org www.ulf.org
leukodystrophy, Krabbe, Can have both undernutrition and overnutrition. Frequent dietetic monitoring www.hideandseek.org
Canavan, Zellweger) required due to progressive nature of the disease (Chapter 27)
Adrenoleukodystrophy Lorenzo’s oil can be used in children who are asymptomatic, and this may www.ninds.nih.gov
delay onset of symptoms. Symptom control is needed for all other children www.rarediseases.org
[39] (Chapter 27) www.ulf.org
Rett syndrome Growth failure, oromotor dysfunction, gastro‐oesophageal reflux, constipation www.ninds.nih.gov
and low bone density are common. Often need assistance with feeding. May www.rettuk.org
need gastrostomy feeding to improve growth [40] www.reverserett.org.uk
www.rarediseases.org
Duchenne muscular Predominantly affects males. High prevalence of obesity related to lower www.ninds.nih.gov
dystrophy resting energy expenditure, steroid use and reduced physical activity. Muscle www.rarediseases.org
wasting, poor feeding and poor swallow coordination can lead to malnutrition www.muscular‐dystrophy.org
as they get older. Assistance is often needed with oral feeding and texture www.dfsg.org.uk
modification may improve intakes. Tube feeding may be required. Will need
supplementary calcium and vitamin D if they are on steroids as they have high
risk of osteoporosis. Regular dietetic monitoring required [41]
Spinal muscular atrophy Muscle weakness and bulbar dysfunction lead to swallowing difficulties. www.ninds.nih.gov
Respiratory problems are common including aspiration pneumonia. www.jtsma.org.uk
Undernutrition and overnutrition can occur and regular dietetic monitoring is www.smafoundation.org
essential. Gastro‐oesophageal reflux and constipation are common [42] www.actsma.co.uk
www.rarediseases.org
Prader–Willi syndrome At birth the infant typically has low birth weight for gestation, poor muscle www.pwsa.co.uk
tone (‘floppy’), difficulty sucking and may require tube feeding to prevent www.geneticdiseasefoundation.org
faltering growth. Feeding difficulties resolve over time and at 2–5 years of age www.fpwr.ca
hyperphagia sets in and lasts throughout the lifetime, leading to obesity if not www.pwsausa.org
correctly managed (Chapter 25) www.fpwr.org
Cockayne syndrome Premature ageing and short stature. Growth failure and likely to have feeding www.ncbi.nlm.nih.gov
problems especially as an infant. Will need tube feeding to treat faltering www.amyandfriends.org
growth and/or manage poor swallow coordination. Likely to have www.cockayne‐syndrome.net
developmental delay and increased tone/spasticity. Regular dietetic monitoring
needed due to progressive nature of the disease [43]
Batten’s disease A neurodegenerative disease. Feeding becomes more difficult with resulting www.ninds.nih.gov
poor weight gain and frequent symptoms of aspiration or difficulty coordinating www.bdfa‐uk.org.uk
swallowing (due to progressing lack of coordination and progressive poor www.bdsra.org
muscle tone). Most children will eventually need tube feeding. If they manage www.nathansbattle.com
to feed orally, they are likely to need assistance due to abnormal limb www.hideandseek.org
movement and poor muscle strength. Frequent dietetic monitoring is required www.brainfoundation.org.au
to support child at various stages of disease progression [44]
f ormula for predicting energy requirements in children with nutritional requirements [45]. This should then be adjusted
neurodisability; however, the Schofield equation may be a depending on whether weight loss or weight gain is needed.
good starting point to estimate energy requirements [5]. A child entering their pubertal growth spurt will require
Requirements need to be based on individual clinical assess- more energy than one who is not. In practice energy require-
ment, degree of mobility, fat stores and muscle mass. Regular ments are often no more than 75% of the estimated average
reassessment, with any necessary alterations to the esti- requirement (EAR) for height age and are often considerably
mated energy requirement, should be carried out and intake less; a child receiving as little as 20–30 kcal/kg/day (85–
adjusted accordingly. 125 kJ/kg/day) can still gain weight. The exceptions to this
Children with neurodisability are often smaller than an are those children with mixed CP that includes an athetoid
average healthy child, and until further research becomes component; excessive involuntary movements make their
available, dietetic consensus opinion is to use height age energy requirements higher and closer to the EAR for chron-
(a crude estimation of bone age) as a basis to estimate ological age.
Protein height, but all aspects of their health should be considered

[5]. There should be discussion with the multidisciplinary
Protein requirements for those with neurodisability are team (MDT) involved in their care: paediatrician, dietitian,
likely to be similar to those of the healthy paediatric popula- speech and language therapist (SLT), occupational therapist
tion (p. 9). When energy requirements are low, it may be (OT) and psychologist. The use of knee height (KH) or tibial
hard to meet protein requirements, and the use of a high pro- length (TL) should be used regularly to assess linear growth
tein formula or a protein supplement may be necessary [5]. when height cannot be measured.
Micronutrients Weight
Weight should be measured routinely on the most appropri-
Micronutrient deficiencies (calcium, iron, zinc, vitamins C, ate weighing equipment for the individual child. These
D, E and selenium) can occur in those with neurodisability, include standing scales, hoist scales, wheelchair scales and
especially when oral intake is poor or tube feeding vol- sitting scales for the child, as well as the caregiver holding
umes are low [5]. There are no studies showing require- the child on the scales and then their weight being sub-
ments for micronutrients differ from those of healthy tracted. The chosen method should be recorded and used
children. However, when feed volumes are low due to low when subsequently weighed. Personal equipment such as
energy requirements, micronutrient intake may also be splints should be removed before weighing. Weight meas-
low; aiming to provide the lower reference nutrient intake ures should be plotted on growth charts, the frequency
(LRNI) for age, rather than the RNI for micronutrients, depending on local practice and the child’s individual cir-
may be sufficient. cumstances, but should be a minimum of every 6 months for
older children and young adults but more frequently for
Fluid children under the age of 2 years [5].
Actual body weight is used to calculate fluid requirements Height

and can be based on general recommendations (p. 12).
However, it is interesting to note that many children Accurate height measurements are often difficult to obtain in
appear well hydrated on fluid intakes that are lower than children with disabilities and young people, due to scoliosis
those derived by calculation, and 75% of estimated fluid or kyphosis caused by a twisted posture or contractures of
requirements may be adequate to maintain hydration. A the spine. A standing height using a stadiometer is prefera-
fluid balance chart may be useful to measure hydration ble, but where this is not possible, a supine length can be
status. used if they can lie straight. It is important to note, however,
that a supine length will measure longer than a standing
height and serial measurements should not be confused.
Fibre Where a length or height is not possible, there are three
suggested alternatives; upper arm length (UAL), TL and
The Scientific Advisory Committee on Nutrition (SACN) KH all of which have been found to correlate with actual
recommends daily fibre intake for age should be [46]: height and are repeatable [5]. The frequency of measure-
• 2–5 years: 15 g ments will depend on local practice and individual
• 5–11 years: 20 g circumstances. Height should be taken a minimum of

• 11–16 years: 25 g every 6 months for an older child or young adult, with
• 16–18 years: 30 g more frequent measurements for children under 2 years.
Measurements should be plotted on a growth chart for
For those with oromotor dysfunction requiring a texture‐ each measurement.
modified diet, it may be hard to meet these recommenda-
tions as intakes of wholegrains, vegetables and fruit may be
limited, and an additional source of fibre (e.g. Benefiber, Upper arm length
Resource OptiFibre) may be indicated. For those needing to UAL is measured from the acromion to the head of the
be tube fed, a fibre‐containing feed should be the preferred radius (Figure 21.1). It should be measured on the right or
choice. the least affected side. Two measurements are taken and
then averaged. Research suggests it can only be taken
accurately using an anthropometer. The measurement can
Nutritional assessment be converted into a height measure using the following
formula [47]:
Anthropometry
Estimated stature cm 4.35 UAL 21.8
Children with neurological disorders should not have their
nutritional status assessed based solely on weight and The technical error is 1.7 cm
Figure 21.1 Upper arm length.
Tibial length
The TL is measured from the tibia to the sphyrion. It requires
Figure 21.2 Tibial length or lower leg length.
the child to be sitting and is taken on the right side or the least
affected side. This measurement can be taken accurately with
an anthropometer or steel tape measure (Figure 21.2). Two
measurements should be taken and averaged. The measure-
ment can be converted into a height measure using the
following formula [47]:
Estimated stature cm 3.26 TL 30.8
The technical error is 1.4 cm
Knee height
The KH is measured with the child sitting down and the
knee and ankle bent to 90°. Using a sliding caliper the dis-
tance from the heel to the superior surface of the knee
over the femoral condyle is measured on the left side or
least affected side (Figure 21.3). Two measurements
should be taken and averaged. The measurement can be
converted into a height measurement using the following
formula [47]:
Estimated stature cm 2.69 KH 24.2
The technical error is 1.1 cm
When an alternative length measurement is taken, note of

the limb from which the measurement was taken should be
made, and this should be consistently used for all subse-
quent measurements. Estimated height measurements should
be plotted on standard growth charts. Figure 21.3 Knee height.
Body composition show that children with moderate to severe CP lack a signifi-
cant pubertal growth spurt. These charts should not be
Whole‐body dual‐energy X‐ray absorptiometry (DEXA) is used exclusively, but rather in combination with clinical
an accurate method for measuring body composition, but it assessment, UK‐WHO growth charts and anthropometric
is unavailable to most centres. There is some research into measurements.
the use of bioelectrical impedance analysis (BIA), and this
has been found to be effective in estimation of body compo- Biochemistry
sition in children with CP [5]. There is good evidence that
body composition of children with disabilities can be ascer- Serum albumin and prealbumin levels do not reflect nutri-
tained by measuring skinfold thickness with mid-arm cir- tional status in children with neurodisability. Albumin and
cumference (MAC) and this should be done routinely [5]. prealbumin levels are very rarely below normal reference
Triceps and subscapular skinfold thicknesses in particular values and do not correlate with anthropometric measure-
correlate highly with true fat and fat‐free mass. However, in ments or general health [17]. Regular blood monitoring
routine practice, it can be difficult to take accurate skinfold may be useful for children who are at risk of nutritional
thickness measurements, e.g. subscapular skinfold thickness deficiencies, such as those on texture‐modified diets due to
measurement may be impractical due to the need to remove dysphagia, or those with faltering growth due to poor oral
clothing or spinal jackets. In practical terms annual serial intake. The 2017 guidelines from the European Society for
measurements of MAC and triceps skinfold thickness (TSFT) Paediatric Gastroenterology, Hepatology and Nutrition
can be a useful monitoring tool and can be used to estimate (ESPGHAN) suggest that children with neurodisability
mid-arm muscle circumference (MAMC) [48]: should have annual blood monitoring of electrolytes, urea,
creatinine, glucose, full blood count, haemoglobin, ferritin,
MAMC cm MAC cm 0.314 TSF cm
iron, calcium, magnesium, phosphate, albumin, liver
enzymes, vitamins A, B12, D, E and folic acid, parathyroid
Skinfold thicknesses and MAC can be compared with hormone (PTH) and zinc [5]. A study conducted by
the WHO arm circumference and skinfold thickness charts Gonzalez Ballesteros et al. highlighted hypophosphataemia
and tables [48, 49] or Addo and Himes charts [50]. in those fed exclusively on an amino acid (AA)‐based for-
Measurements should be taken a minimum of every mula, and therefore serum phosphorus, calcium and alka-
12 months. Where possible other anthropometric measure- line phosphatase may need regular monitoring if using
ments, such as subscapular skinfold thickness, should be these formulas [55].
taken. Children with CP can have higher levels of central
adiposity, and so waist circumference may be a useful
measurement to do routinely. Clinical
Clinical assessment requires knowledge of the type of neuro-

Subjective global nutritional assessment disability, level of disability and stage of disease (for pro-
gressive disorders). The following indices are useful to make
Subjective global assessment is a method of assessing nutri- an overall assessment of nutritional needs: neurological
tional status based on clinical judgement, and this method function (including seizure activity), respiratory function,
can be useful for children with neurodisability [51, 52]. cardiac function, muscle tone (including limb function), skin
Subjective global nutritional assessment (SGNA) is a ques- integrity, sensory difficulties, gastrointestinal function, uri-
tionnaire relating to nutrition history and physical examina- nary and/or faecal incontinence.
tion, signs of fat, functional ability, muscle wasting and
oedema, while objective assessments of weight, height and
TSFT measurements can also be collected [52].
Dietary assessment
There are three common methods of assessment: food dia-

Growth charts ries, dietary recall and food frequency questionnaires.
Evidence to support one method over another for assessing
The standard UK‐WHO growth chart 0–4 years and UK food intake is poor, and no method gives absolute accurate
growth chart 2–18 years should be used for monitoring information on food intake. Over‐reporting is the main prob-
weight and height centiles for the majority of children with lem and can be as high as 54% more than the child’s actual
disabilities [53]. There are specific charts for children with intake [56].
Down’s syndrome [54], reviewed in 2011, that can be used Dietary feeding assessments are useful for assessing
instead of the standard UK charts compiled in 2009. Growth meal patterns and the types of food offered and eaten, in
charts are available for children with CP aged 2–20 years, relation to the food groups. Observation of a child at a
classifying children into groups according to the severity of mealtime may be useful and can highlight other factors that
their CP. The charts show observed growth patterns in these affect dietary intake such as the child’s posture and the
groups but may not indicate optimal growth [17]. The charts mealtime environment [45].
Social context Multidisciplinary assessment
Children with disabilities are more vulnerable to both physi- Multidisciplinary and multi‐agency working is vital in
cal and emotional abuse, and child protection is a high prior- supporting and safeguarding children with complex needs.
ity. It is important that services work together to ensure there Children with disabilities are classified as in need in the
is a focus on safeguarding children [57, 58]. It is important Children’s Act (2004), and as such it is the duty of care of
that agencies work together to identify children who need every local authority to provide a range of services at the
help early as laid out in the 2018 guide Working Together to level appropriate to these children’s needs [57]. Strong links
Safeguard Children [58]. Specific standards for the health and within the professional team and effective communication
social care of children with disabilities are described in the are essential to ensure each child’s potential is met and main-
National Service Framework for Children, Young People tained [59]. Having an overview of all sources of information
and Maternity Services: Disabled Children and Young People is important to ensure a holistic assessment and allows for
and those with Complex Health Needs [59]. practical interventions to optimise the child’s potential.
The social issues affecting a child with disabilities are far Often these children, with very complex health and social
reaching, and the pressure on parents/caregivers to provide needs, have a large number of professionals and services
for their child is immense as they cope with difficulties in all involved (Figure 21.4). If managed well, this can be a huge
areas of life: housing, transport, finances, education, f amily benefit to those involved and the families themselves.
dynamics and managing medical interventions. Consideration A multidisciplinary approach to nutritional assessment
of all aspects of the child’s life is important when giving for children with neurodisabilities is essential to achieve
recommendations for nutrition intervention. Ideally the die- feeding and lifestyle goals [45, 60, 61], drawing together the
titian should work within an MDT to get an understanding skills and expertise of caregiver and a range of healthcare
of any social factors that could affect the child’s ability to professionals. In the absence of a validated nutrition screen-
achieve nutritional goals. ing tool, nutrition and feeding problems are identified by
Health
visitor Acute
Psychology
trusts
Parent/
Education
carer
Play Speech
specialist therapy
Team
around
Continuing the child
Physio
care
Community
OT
nurses
Paedia-
Dietitian
trician
Social
GP
services
Figure 21.4 Professionals and services involved in the care of the disabled child. GP, general practitioner; OT, occupational therapist.
Nutritional Intervention 427
measuring children, observing mealtimes and questioning • early attachment difficulties, especially with an ill child
caregivers, other MDT members and nursing staff. • marital/family stress, life events, social support, family
networks
• general parenting skills
Speech and language therapist
• parent–child relationship and interaction
• past and present parental mental health
A feeding assessment by an SLT should always be included
• parental level of anxiety and obsessions
in the nutritional assessment of a child with neurodisability
[62]. Assessment of feeding competence provides important
information for identifying children at risk of poor nutri- Nutritional intervention
tional status. Feeding dysfunction is related to nutritional
risk, and it has been shown that even those who have mild Nutritional management of children with neurodisabilities
dysfunction are still lighter and shorter than their peers [7, can be challenging, and there is little supportive research.
63]. The assessment will also highlight any problems with Nutritional care is determined by the individual child’s
drooling or excess salivation, which will need to be factored needs and is often based on observations rather than set
into calculation of fluid requirements. guidelines. Nutrition aims should focus not only on linear
growth but also on functional and physiological improve-
ments [5].
Occupational therapist
The OT takes a particular interest in the child’s position for

Oral nutrition
eating and drinking, their level of independence and any
special equipment that may aid the child. A child will need
Food fortification
to have a secure base and symmetrical position to obtain
optimum trunk, limb, head and oral control. The position This should be based on the same principles as for other chil-
may be either on the caregiver’s lap for infants and small dren whose growth is faltering. The energy content of food
children or in adapted seating. The assessment should also should be increased by using energy‐dense foods and moni-
involve the caregiver’s needs, so they adopt a position toring the outcome. Energy‐dense foods need to be of the
that is comfortable and safe for their back and facilitates correct consistency for the child’s oromotor skills. Caregivers
the techniques necessary to help the child. Sometimes this familiar with prevailing healthy eating messages are often
will require the caregivers experimenting with different concerned about the use of high fat foods for their child, and
positions until they have the best arrangement for them their re‐education is important. Children with neurodisabili-
both. ties often can only eat small portions, and, therefore, adding
The child’s position during mealtimes can affect their abil- fat/sugar to foods can increase energy density without
ity to swallow safely. Young babies are usually fed in a appreciably increasing volume. Caregivers should choose
reclined position. Children should eat and drink in an high fat dairy products, such as whole milk, butter, cream
upright position to ensure a safe swallow. If a degree of tilt is and full fat yoghurt as additions to meals/snacks. Adding
required on their seating system, a reassessment of their abil- oil to foods can also increase energy density. Foods that can
ity to swallow safely should be carried out. quickly be added to instant mashed potato, e.g. grated
There is a wide range of specialised equipment available cheese, cream cheese, mashed tinned fish, corned beef,
to assist with eating and drinking for children with special cooked lentils and avocado, all provide variety without too
needs. A joint assessment between the child’s OT and SLT much preparation time. Protein foods, e.g. eggs, lentils,
(and perhaps also a physiotherapist) is required to ensure meat, nuts and cheese, can be added to meals to increase
the correct equipment is selected. nutritional value as can skimmed milk powder added to
foods or milkshakes. Adding sugar and cream to puddings
and milkshakes will increase the energy content.
Clinical psychologist
The input of a clinical psychologist may be necessary for a Fluids

full feeding assessment. A child’s early feeding experiences
Inadequate consumption or excessive fluid loss is a feature
may impact on how they currently feed, particularly those
common to many children with feeding difficulties. Advice
children who have experienced distress because of early
should be based on assessment of why the child is not able to
feeding practices. This can sometimes result in learned aver-
consume adequate fluids. Children with poor lip seal, and
sive behaviour often mistaken for a dislike of food or a poor
who thus lose fluid from the mouth, will need to be offered
appetite, which can only be resolved with adequate psycho-
drinks more frequently. The OT and SLT can identify the best
logical support. The psychologist will consider factors influ-
drinking method, allowing the child to drink enough fluid
encing feeding including:
safely.
• the environment where the child usually eats For some children thickened fluids can enable more
• parents’ eating history and attitude to food successful drinking. Commercial pre‐thickened drinks are
available (Table 21.2). Other fluids can be thickened using fibre white/wheatmeal breads, given with plenty of fluids,
foods such as thick yoghurts, ice cream, instant powdered are also useful. Other foods high in fibre, such as linseed,
desserts, instant sauce granules and smooth puréed fruit. A psyllium husk, ground seeds and nuts, can be added to
range of proprietary thickening agents is also available on smoothies, porridge or gravies.
prescription (Table 21.2). Many caregivers have fears about If the child is tube fed, it is advisable to change to a fibre‐
offering thick drinks as they perceive these as not as thirst containing formula. The use of prescribed soluble fibre sup-
quenching, and their use should be fully discussed. plements, e.g. Resource OptiFibre or Benefiber, may be
For children who manage food better than fluids offering useful where it is difficult to increase dietary fibre or when
foods with a high water content between meals, e.g. puréed there is no alternative fibre‐containing tube feed. These sup-
fruit, thick yoghurts, fromage frais, ice cream and ice lollies, plements are of benefit for both constipation and diarrhoea.
will increase their fluid intake. Jelly can be useful, but it dis-
solves immediately on entering the mouth, resulting in the
Oral nutritional supplements
same problems as thin fluids.
The following can be noted to monitor an increase in fluid Prescribed oral nutritional supplements, e.g. PaediaSure,
intake: whether there have been more wet nappies, fewer Frebini Energy, Fortini (Table 12.3), may be appropriate for
urinary tract infections, softer or more regular bowel move- some children. The child’s current nutritional intake should
ments. Despite all efforts some children still find it extremely be assessed first to ensure that the supplement with the
difficult to achieve an acceptable fluid intake orally and may desired composition is selected. The use of supplements
require tube feeding to meet fluid requirements. should be reviewed regularly. Supplements can be thickened
as recommended by the SLT by a powdered thickener or can
also be supplied as a ready thickened drink (Table 21.2).
Increasing fibre
Energy modules based on fat and/or carbohydrate, e.g.
Children with neurodisability are at risk of constipation, Duocal, Calogen, Vitajoule, can be used to improve energy
which is very common. Poor fibre intake increases the risk intakes, and these can be added to food or enteral feeds. A
and arises from the use of low fibre foods for puréed or protein supplement, e.g. Protifar, can be added to foods and
mashed meals, enteral feeds with no added fibre and poor drinks to increase protein intake.
fluid intakes. Therefore, increasing dietary fibre and fluid
intake alongside the use of medications is important [64].
Presentation of food and drink
Puréed fruit can be added to breakfast foods, and extra veg-
etables can be incorporated in gravy, mashed potato, casse- Mealtimes need to be enjoyable for the child to eat and drink
roles and thick soups. Wholegrain cereals and breads or high to their best ability. When the child is alert and healthy, they
Table 21.2 Prescribable thickeners and pre‐thickened drinks.
Manufacturer Product Suitable for*
Powdered thickeners Cow & Gate Instant Carobel Infants and small children
Aptamil Feed Thickener Infants and small children
Abbott Multi‐thick Over 1 year
Sutherland Thixo‐D original Over 1 year
Vitaflo Vitaquick Over 1 year
Nestle Resource ThickenUp Clear Over 3 years
Fresenius Kabi Thick and Easy Over 3 years
Fresenius Kabi Thick and Easy Clear Over 3 years
Nutricia Nutilis Powder Over 3 years
Nutricia Nutilis Clear Over 3 years
Slo Drinks Slo Drinks Powder Over 3 years
Thickened drinks Nestle Resource Thickened Drinks Over 1 year
Fresenius Kabi Fresubin Thickened Stage 1 Over 3 years
Fresenius Kabi Fresubin Thickened Stage 2 Over 3 years
Nutricia Nutilis Complete Stage 1 Over 3 years
Hormel Thick and Easy Over 3 years
Thick‐It AquaCare H2O Over 3 years
Semi‐solid desserts Nutricia Nutilis Fruit Stage 3 Over 3 years
Nutricia Forticreme Complete Over 3 years
Fresenius Kabi Fresubin 2 kcal Creme Over 3 years
Abbott Ensure Plus Creme Over 3 years
*Indicated by manufacturer.
Nutritional Intervention 429
will manage a more challenging consistency of food than if time for the child to experience the taste, texture and
they are tired or unwell. The child’s caregiver needs to be temperature of the food
sensitive to their needs on each eating/drinking occasion. • verbal, to promote the awareness of the concepts of eat-
To reduce the risk of aspiration and improve swallow coor- ing; asking the child how they would like to be fed; tell-
dination, a child should be offered a reasonable choice of food ing the child what is going to happen next; explaining
with a texture they can manage. If the child can feed assisted, what is being done as it occurs. Repetitive phrases
this should be encouraged as the hand to mouth action will throughout the meal help the child know what they are
help with anticipation of receiving food into the mouth. doing, e.g. ‘bite’, ‘chew’ and ‘swallow’
The way food is presented to the child is important for • object recognition, such as a spoon being placed in the
success. Food should be given slowly and rhythmically, child’s hand prior to each meal, helps the child to under-
allowing time to finish each mouthful and anticipate the stand and anticipate that a food is on its way
next one. Small mouthfuls are more likely to be successful.
Assessment will inform which combination the child will
For some children the food needs to be heaped towards the
prefer; however, consistency by all helpers is important.
tip of the spoon to provide sensory cues for the lips. The
spoon should normally be presented horizontally from the
front, and, depending on the techniques being practised at Assistance with feeding
the time, it could be centrally or towards the side of the
All people who could possibly be involved with feeding the
mouth when encouraging chewing. Scraping food off the
child should be identified. Total reliance on one main caregiver
spoon with the top teeth should be avoided. The SLT or OT
should be discouraged as this can make the child dependent
can suggest other methods to help the child to learn to take
on one person’s feeding technique and makes changing
food from the bowl of the spoon and achieve lip closure.
caregivers very difficult. Other members of the family, friends,
respite caregivers, social service family support, students and
Communication volunteers can all give support at mealtimes. The caregiver
should be encouraged to let another person help with at least
A child or young person with a severe neurodisability may one meal a week. Training and support should be offered to
not be able to verbalise or signal their wish for food. This the helpers, and they should be involved in the assessment
inability to make their request leads to an increased risk of and review process. Clear details of the programme such as
insufficient nutrition, as they are unable to make the same a ‘mealtime guidance sheet’ must be accessible to all involved
demands as a healthy child. As a child grows older or their with feeding. A model of how the task of feeding is best
condition progresses, oromotor abilities may also change, carried out provides caregiver a clear picture of what is
which can result in new difficulties with managing food and expected. Also, this can increase the empathy of the demon-
drinks. Children with unrecognised feeding difficulties may strator by briefly experiencing the difficulties experienced
be incorrectly interpreted at mealtimes. Often rejection of by the feeder at every meal.
certain textures or consistencies can be mistaken for the child
being fussy, lazy or badly behaved, or disliking the food.
They may even display self‐injurious behaviour or pica as a Special feeding aids and equipment
sign of distress. When a child is reported to be fussy or badly Positioning of the child is important to ensure they can feed
behaved at mealtimes, thorough investigation of exactly safely as even a slight change in the angle of the child’s head
what is happening is needed, as the possibilities of misinter- or body can affect their ability to feed safely [65]. Children
preting intentions are very great. An SLT and OT can help may need their seating adapted to ensure they are in the cor-
with these issues. Special communication aids, also known rect posture and an OT can help with this.
as augmentative and alternative communication (AAC), Special feeding aids and equipment are tailored to improve
may be used such as communication boards, charts, books eating and drinking and promote independence. Examples
or electronic communication aids with voice output to help of these are:
the child communicate their needs.
• eating systems
• special bowls and plate guards
Prompts • cutlery such as spoons with textured, contoured or
curved handles, e.g. angled spoons and good grip spoons
If the child is unable to feed themselves, then the caregiver
• drinking equipment: cups, mugs and bottles with special
will need to use appropriate prompts to ensure the child is
features such as two handles, one‐way valves, weighted
aware that food is coming and what they are eating. Prompts
bases to reduce tipping, cup holders and straws. Specific
can be:
special cups are the Doidy cup (slanted towards the child
• visual, e.g. an environment with other people eating; for easier drinking); the anyway drinking cup (designed
mirrors; seeing, smelling and hearing the food being pre- to reduce spillage); special needs Medela teats, bottles,
pared or arriving at the table cups; Easyflow cups
• physical, such as the smell of food; stroking the lower lip • bibs and aprons to help keep children clean during mealtimes
with the spoon; giving very small amounts so allowing • slip‐resistant tableware such as placemats
Eating with other people Gastrostomy feeding is a longer‐term (more than 6 weeks),

safe and useful method to allow adequate nutritional
Eating with other people is important for children with feed-
intake and prevention of dystrophy in children with
ing difficulties. However, limitations may prevent this from
neurodisability and dysphagia [69, 74]. Gastrostomy
happening, for instance, the special chair may not fit under
placement carries a surgical risk. Tube feeding does not
the family table. Such problems should be identified in an
prevent aspiration of oral secretions or of gastric contents
MDT mealtime assessment. In some cases the caregiver may
unless the tube is placed in the jejunum. Enteral feeding in
find it easier to give the child their meal before everyone
children with neurodisabilities is well tolerated and can
else. Practical ways in which the child can join in with family
improve energy and protein intake, weight gain and
mealtimes need to be identified. A tube‐fed child can have
nutritional status in addition to improving the parent’s/
their tube feed at the same time as the rest of the family have
caregiver’s perceptions of their child’s health and quality
their meal to promote associations between feeling full and
of life [69, 75, 76].
seeing/smelling foods. This may help a child progress to
oral feeding if this is possible in the future. Eating out may
be a problem, and familiarisation with popular commercial
Feeds
menus will provide ideas for the caregiver, e.g. many venues
serve thick shakes which, if transferred to the appropriate Children with neurodisability often have relatively low
cup, can provide a perfect consistency for some children energy expenditure and high body fat content, and, there-
requiring thickened drinks. fore, caution should be taken not to overfeed patients [77].
Many children appear to grow adequately on very low
energy intakes, and it may not be possible to meet their
Enteral nutrition
macronutrient and micronutrient requirements (based on
the child’s height age) if standard 1 kcal/mL (4 kJ/mL)
Children with disabilities form the largest group of chil-
enteral feed volumes are simply reduced to provide less
dren requiring long‐term home enteral tube feeding
energy. In this case a low energy paediatric feed, such as
(HETF) in the UK [66]. A British Artificial Nutrition Survey
Nutrini Low Energy Multi Fibre (0.75 kcal/mL, 3 kJ/mL),
(BANS) report found that 31% of children registered for
may be the best choice (Table 4.2). A vitamin and mineral
HETF in 2010 had a diagnosis relating to the CNS or men-
supplement may be needed to complement any low energy
tal health [67].
feed, e.g. Paediatric Seravit or Phlexy‐Vits; additional
The decision to initiate enteral feeding is an emotive one,
sodium and potassium supplementation may be given
which can have many ethical considerations. The decision
from an oral rehydration solution, e.g. Dioralyte; a protein
must be in the best interests of the child, from a medical
module may be added to the feed if required, e.g. Protifar.
point of view, for quality of life and ensuring dignity is
Feeds designed for older children or adults, including feeds
maintained. Parents are often reluctant to consent to place-
that are complete in 1000–1200 mL (such as Fresubin 1000
ment of a gastrostomy tube for feeding, as it can be perceived
Complete, Nutrison 800 or 1000 Complete Multi Fibre), are
as a failure or start of degeneration of their child’s health
worth considering in smaller volumes for children.
condition. Gastrostomy feeding may present another loss of
However, the micronutrient levels must be checked and
normality and be a sign of disability for some parents [68].
kept within safe intakes. Constipation is often an issue;
Parents should be given all the information they need to
therefore a feed containing fibre should be the preferred
reach an informed decision about the benefits and risks of
choice.
gastrostomy placement and the process should not be rushed
Many families choose to give blended foods down the
[69–73]. An MDT approach to these conversations is benefi-
enteral feeding tube, and the associated risks, such as
cial. It is important to talk through this process with families
blocking the tube and bacterial contamination, will need to
explaining that often oral feeding can continue with advice
be discussed with the family. ESPGHAN advises against
from the SLT.
the practice of giving liquidised food via feeding tubes [78].
Enteral nutrition should be considered in children with:
If families decide to change to a fully blended diet, then it
• malnutrition, or where they are unable to achieve catch‐ should only be given down a gastrostomy tube feeding into
up growth with oral nutrition alone the stomach and not down an NG tube or fed into jejunum.
• unsafe swallow The nutritional content of the diet, using appropriate die-
• severe oral aversion tary analysis software, will need to be determined. It is
• significant stress during mealtimes likely that additional nutritional supplements will be
• inadequate hydration required alongside blended foods. The British Dietetic
• inability to take medications orally Association (BDA) toolkit on liquidised food via gastros-
tomy tube [79] is expected to be updated in 2020 (p. 62).
The choice of nasogastric (NG) versus gastrostomy feed-
Enteral feed choices include:
ing has to be carefully assessed for the child with feeding
difficulties. NG feeding can be used as a short‐term (approx- • breastmilk or standard infant formula
imately 6 weeks) method of feeding; however, this can cause • energy‐dense infant formula (Table 1.18)
oral/facial aversion if used for extended periods of time. • standard paediatric feed with or without fibre (Table 4.3)
Complications 431
• high energy paediatric feed with or without fibre This can be a very difficult problem to rectify and has led to
(Table 4.3) the precaution of underestimating energy requirements
• low energy paediatric feed with fibre (Table 4.3) rather than overestimating these when feeds are initially
• adult feeds for older children/adolescents with energy started. A low energy paediatric feed or a reduced volume of
density 1–2 kcal/mL (4–8 kJ/mL) with varying protein an adult feed can be useful.
content (Table 4.3)
• adult feeds nutritionally complete in 1000–1200 mL vol-
Monitoring and follow‐up
ume (Table 4.3)
• specialised paediatric/adult feeds based on AAs, pep-
Monitoring and follow‐up will depend on the type of neuro-
tides or soya (Tables 8.14–8.16 and 8.20)
disability, stage of progressive disorder and symptom con-
A case study to illustrate enteral tube feeding in a child trol as it arises. Therefore, it is difficult to give guidance on
with neurodisability is given in Table 21.3. frequency or method. There are often limited resources for
regular review of these patients, and dietitians may rely on
other healthcare professionals, parents, or caregivers to
Feeding regimens highlight problems and monitor nutritional parameters for
The feeding regimen should be discussed with the child, these children. Many of the children may be lost to follow‐up
their family and caregivers. due to non‐attendance at reviews. To minimise non‐attend-
Common choices are: ance it is important to choose locations that are convenient
for the child and their parents and caregivers, e.g. home and
• continuous special school.
• bolus via syringe or gravity set Weight gain is a crude guide to assessing whether the
• bolus via pump right amount of nutrition has been prescribed. Often the
The choice of regimen will be affected by whether the subjective opinion of the parent or caregivers on how well
child is still allowed to eat and drink (whether or not they nourished their child appears is sought as a guide. However,
have a safe swallow). The feed may be used merely as a top‐ these children tend to put on weight as fat rather than
up after meals, or it may replace all oral intake. Commonly, muscle and often do not grow taller no matter how much
children who are at risk of aspiration may still be allowed to additional nutrition is provided [80]. Measuring body com-
take small tastes of food for pleasure (as directed by the SLT), position by taking skin fold thickness and mid-arm circum-
and this should be taken into account when calculating ference measurements can help clarify this quandary. The
energy requirements. rate of growth and weight gain can be tracked using the
If the enteral feed is to be the sole or major source of nutri- child’s growth chart. It is usual for many of these children to
tion, it is common to give a small feed via bolus or pump at be tracking below the 0.4th centile for both height and weight
each mealtime to mimic the psychological and physiological and this is acceptable providing they are following the shape
effects of a meal. Overnight feeding can accompany this type of the growth curve.
of regimen if a larger volume is required, but this should be Children receiving tube feeds should be reviewed every
used with caution if the child has an NG tube due to the risk 2–6 months once stable, depending on their age, to monitor
of displacement and aspiration, particularly as children with weight and height, assess clinical indices and alter feeds as
disabilities often have irregular postures when lying down. necessary. These guidelines may be used for children feed-
Overnight gastrostomy feeding can only be offered if the ing orally who are at risk of nutritional deficiencies or prob-
child can maintain a safe sleeping position, propped up to at lems with growth. Monitoring nutritional parameters in
least 30°. The use of a sleep system can help with safe posi- blood tests for high risk children or those on tube feeds
tioning. The choice of feeding regimen may depend on the should be carried out every 6–12 months [5, 56].
child’s tolerance, particularly if GOR is present, and activity
during the day. Complications
Faltering growth
Overweight
Gastrostomy feeding is beneficial for children with neuro- Faltering growth, or low weight for height, has been well
disabilities who have oral or motor dysfunction and clinical documented in children with neurodisabilities [1, 5, 81, 82].
signs of undernutrition. It aids weight gain; however, cau- Nutrition intervention for children with CP has been shown
tion should be taken not to overfeed as it has been shown to produce improvements in growth and nutritional status
that children with CP have significantly higher body fat con- [83, 84]. There are beliefs that it is ‘normal’ for children with
tent and lower lean body mass than the healthy population severe disabilities, particularly children with CP, to have
[77]. Sometimes children become very overweight when poor stature and low weights, which has been ascribed to
enteral feeds have not been carefully monitored or higher their underlying cerebral deficit or physical inactivity rather
volumes (and hence higher energy) have been given to than to chronic malnutrition [16, 81]. Normal parameters for
ensure an adequate supply of protein and micronutrients. identifying faltering growth may not be appropriate in this
Table 21.3 Case study to illustrate enteral tube feeding in a child with neurodisability.
A 2‐year‐old boy with quadriplegic cerebral palsy

Insertion of a gastrostomy tube and Nissen fundoplication procedure done simultaneously at the age of 18 months due to feeding difficulties,
poor weight gain, constipation and severe GOR
Weight prior to gastrostomy placement 8 kg at the age of 17 months (0.4th centile)
Length measurement (using alternative measure) 77 cm (2nd centile)
He was established on full gastrostomy feeds of 800 mL PaediaSure, 1 kcal/mL (4 kJ/mL) given as:
130 mL × 4 boluses through the day (intermittent with feeding pump)
35 mL/hour over 8 hours continuously overnight (via feeding pump)
He was allowed tastes of puréed food 1–2 times per day as recommended by the SLT
He was not reviewed for 6 months post-gastrostomy placement. The dietitian visited at home at age 2 years, and on assessment his weight gain
had been rapid: weight = 11 kg (9th–25th centile)
Clinically he appeared overweight, well hydrated with regular bowel movements, adequate absorption of feeds with no feed loss due to vomiting
Alternative length measurement was taken: tibial length = 15.4 cm
Height estimated at 81 cm using tibial length (2nd centile)
Plan at 2 years of age: Feed changed to 800 mL Nutrini Low Energy Multi Fibre, 0.75 kcal/mL (3 kJ/mL) = 600 kcal (2510 kJ)/day
Although fluid requirement for 11 kg child was 1050 mL/day, he was well hydrated on 800 mL total fluid volume (assessment of bowel
movements, urine output and concentration, alertness and skin turgor)
Follow up at 2 years 3 months of age: Further dietetic assessment undertaken
Weight 11.9 kg (>25th centile for age)
Rate of weight gain had slowed down; however, still too rapid when plotted on UK‐WHO growth chart and CP growth charts. He is not mobile;
therefore, his requirements are much lower than originally estimated. He continued to gain weight on a low energy feed
Plan at 2 years 3 months of age: Volume of Nutrini Low Energy Multi Fibre further reduced to 500 mL providing 375 kcal (1570 kJ)/day: 30% of
EAR energy for actual age, equivalent to 32 kcal (135 kJ)/kg
Additional water flushes of 300 mL to be given to meet his fluid requirement of 800 mL/day. The reduced feed volume does not meet RNI for
micronutrients. Consider the addition of Paediatric Seravit and Dioralyte to improve the nutritional profile:
500 mL Nutrini
Addition of 1∕2 Low Energy
Daily requirements 500 mL Nutrini Addition of sachet Dioralyte MF + 5 g Paediatric
RNI (1–3 years based on 10.9 kg Low Energy 5 g Paediatric (dissolved in Seravit + 1∕2 sachet
Nutrient boy) (using height age) Multi Fibre Seravit 100 mL water) Dioralyte
Energy 95 kcal (400 kJ)/ 1036 kcal (4330 kJ) 375 kcal (1570 kJ) 14 kcal – 389 kcal (1625 kJ)
kg/day (EAR) (58 kJ) 36 kcal (150 kJ)/kg
Protein 1.1 g/kg/day 12 g 10.5 g – – 10.5 g (1 g/kg/day)
Sodium 1.7 mmol/kg/day 15.5 mmol 13 mmol 0.05 mmol 10.2 mmol 23.25 mmol
(2.1 mmol/kg)
Potassium 1.6 mmol/kg/day 17.4 mmol 17 mmol 0.04 mmol 3.85 mmol 20.9 mmol
(1.9 mmol/kg)
Calcium 350 mg/day 350 mg 300 mg 129 mg – 429 mg
Iron 6.9 mg/day 6.9 mg 5 mg 3.50 mg – 8.5 mg
Vitamin A 300 μg/day 300 μg/day 205 μg 210 μg – 415 μg
Vitamin D 7 μg/day 7 μg/day 5 μg 2.80 μg – 7.8 μg
Vitamin E 3.2 mg/day 3.2 mg/day 6.5 mg 1.10 mg – 7.6 mg
Thiamin 0.36 mg/day 0.36 mg/day 0.75 mg 0.16 mg – 0.91 mg
Riboflavin 0.5 mg/day 0.5 mg/day 0.8 mg 0.22 mg – 1.02 mg
Vitamin B6 0.7 mg/day 0.7 mg/day 0.6 mg 0.17 mg – 0.77 mg
The addition of 1∕2 sachet of Dioralyte in 100 mL water and 5 g of Paediatric Seravit makes up the requirements for vitamins and minerals. The GP and
paediatrician were notified of the patient’s feed plan, and a request was made to monitor his bloods annually to ensure nutritional adequacy of the feed
with electrolyte supplementation.
GOR, gastro‐oesophageal reflux; EAR, estimated average requirement; RNI, reference nutrient intake; GP, general practitioner.
Complications 433
population, and a variety of methods may be needed to wrap [88]. Often a gastrostomy tube is placed at the same
assess nutritional status [5]. Many patients with neurodisa- time. Complications such as dumping syndrome, gas bloat-
bilities have malnutrition and growth failure as the result of ing and retching can occur (p. 155). If underlying oesopha-
inadequate energy intake [85]. There is evidence that the geal dysmotility still remains and if retching or attempted
severity of feeding problems in children with neurodisabil- vomiting are not controlled by continuing drug therapy,
ity is directly related to the degree of faltering growth [7]. slippage or unwrapping of the fundoplication can occur [88].
Resulting malnutrition is linked to poorer health status and An alternative to fundoplication for children on tube feeds is
reduced ability to participate in normal daily activities [7]. for a change to transpyloric feeding via nasojejunal (NJ)
tube, percutaneous endoscopic jejunostomy (PEJ) or percu-
taneous endoscopic gastrostomy with jejunal tube (PEG‐J).
Gastro‐oesophageal reflux disease The latter two procedures have been shown to improve qual-
ity of life and to show decreases in aspiration pneumonia in
GOR is the passage of stomach contents into the oesopha- children with neurological impairment, with similar rates of
gus. Gastro‐oesophageal reflux disease (GORD) is GOR with mortality [89–91]. However, small amounts of reflux may
secondary complications such as feeding difficulties, respir- still occur with transpyloric feeding [92].
atory problems, faltering growth, abdominal pain and exces-
sive regurgitation [86]. GORD is common in children with
neurodisability and can affect up to 70% of children [5, 87]. Constipation
The most important mechanism of GOR is the prolonged
relaxation of the lower oesophageal sphincter. Other mecha- Constipation is a common problem for children with neu-
nisms are reflux and strain‐induced reflux, when abdominal rodevelopmental disabilities with an estimated prevalence
pressure exceeds the pressure of the lower oesophageal of 26%–70% depending on the definition [60, 93, 94]. There is
sphincter [87]. GOR differs from vomiting, the emetic reflex often a delay in recognising and treating the problem either
following ingested toxins, which acts as a protective because of the inability of the child to communicate effec-
mechanism. tively or because constipation is accepted as inevitable or
Diagnosing GORD involves taking a thorough history and because higher priority has been given to other aspects of the
physical examination, alongside any changes in lifestyle, child’s medical management [64]. There are multiple factors
diet and medications. Endoscopy may identify oesophagitis, predisposing to constipation, both neurological and lifestyle.
eosinophilic oesophagitis, coeliac disease or erosions [88]. Colonic transit times may be prolonged, and some children
Oesophageal pH studies may be used to diagnose GOR and have problems with coordination in anal sphincter and pel-
involves insertion of a microelectrode probe into the lower vic floor muscles [64]. It is generally felt that constipation is
oesophagus for 24 hours and measuring the duration and related to poor ambulatory function with CNS damage being
number of reflux episodes. Oesophageal pH studies will not suggested as an important risk factor [64]. Constipation has
show non‐acid reflux [88]. A barium swallow may be used to also been linked with medications, particularly those known
detect anatomical abnormalities. to slow intestinal motility [94].
Treatment for GORD depends on the age of the child and Dietary fibre and fluid intakes in these children are often
the severity of GORD. Offering smaller more frequent meals poor and can be exacerbated with drooling and poor oromo-
and/or feeds with thickener may help manage symptoms in tor function [5]. Dietary intake is often high in fat, moderate
those with mild symptoms [5]. In older children diet modifi- in protein and low in carbohydrates, all of which contributes
cation, weight loss (if overweight) and other lifestyle changes to a lower fibre intake [85]. Additional fluid and fibre may
may help to improve reflux. Elevating the cot or bedhead help for long‐term management of constipation, but initial
when a child is sleeping may help. For those with severe management involves disimpaction and laxative use [5, 64].
GORD, a 2‐ to 4‐week trial of a hydrolysed protein or AA‐ National Institute for Health and Care Excellence (NICE)
based formula, or elimination of cow’s milk from the mater- guidelines recommend a clear treatment for constipation,
nal diet in a breastfed infant, should be considered before the starting with disimpaction and then maintenance of regular
use of medications [88]. A referral to a paediatric gastroen- and painless defaecation. Laxatives are recommended as
terologist may be helpful to identify underlying causes. first‐line treatment, starting with polyethylene glycol, e.g.
There are various drug therapies used to treat GORD. Acid Movicol, and then moving on to stimulant or osmotic laxa-
suppression medications are most widely used [88]. Proton tives as necessary [95]. There is no set treatment regimen for
pump inhibitors (PPI), e.g. omeprazole and lansoprazole, children with neurodisabilities with constipation, but a con-
are effective acid suppressants and should be first‐line medi- sistent approach with clear instructions for caregivers on
cation treatment for children with GORD and neurodisabil- how and when to adjust medications is recommended
ity [5]. H2 receptor antagonists, e.g. ranitidine, are rarely [5, 94]. A bowel habit diary can be useful in assessing
used as PPI are more effective. Prokinetics agents, e.g. dom- response to treatment.
peridone, may help to accelerate gastric emptying, but there Dietetic assessment and treatment is necessary in order to
is limited evidence for their use [5, 88]. avoid further nutritional compromise, and supplementation
Where drug therapy fails, the child may be offered anti‐ with dietary fibre from food, enteral feeds or commercial
reflux surgery as either a complete fundoplication or partial preparations may help to normalise bowel function [5, 96].
However, often simply increasing the child’s fluid intake can • inability to clear the mouth of food after eating
have the most success. • GORD
• frequent consumption of energy‐dense meals and drinks
• children may be unable to communicate to caregivers
Micronutrient deficiency
that they have dental pain and therefore caries are not
investigated promptly
Micronutrient deficiencies are common in children with
neurodisability due to lower overall food intake and variety, There are some strategies to help prevent dental caries:
poor enteral feed tolerance, vitamin losses through liquidis-
• teeth should be brushed twice daily with a small amount (a
ing foods or long cooking methods and other factors affect-
smear for children <2 years and a pea‐sized amount for
ing oral or enteral intakes [85]. Studies have shown lower
children >2 years) of fluoride toothpaste (1000 ppm ± 10%).
intakes of iron, vitamin D, selenium, folate and calcium [85].
If the child is nil by mouth, a cloth or suction catheter
Nutrient deficiencies can cause neurological changes, which
should be used to wipe away excess toothpaste
may be hard to distinguish from the underlying medical
• chlorhexidine mouthwash can be wiped over the teeth
condition and could be considered a progression of the dis-
and gums using a pink sponge
ease rather than initiating an investigation into deficiency
• teeth should be flossed daily
[85]. Sodium and potassium intakes can be low; however,
• children should be seen by their local dentist biannually;
current opinion is that a level between the RNI and LRNI for
they may advise topical fluoride application as a preven-
height age is acceptable provided urine and blood biochemi-
tative measure
cal parameters are within normal ranges [19].
• children who cannot be treated by their local dentist
should be referred to a specialist community or hospital
Osteopenia dental team; they may also be able to arrange dental
cleaning at hospital with sedation
Children with neurodisabilities are more susceptible to • a dry mouth or decreased saliva production increases the
osteopenia (poor bone density) and increased risk of frac- risk of dental caries; Luborant artificial saliva sprays can
tures because they are often non‐weight‐bearing and have be used for these children
limited exposure to sunlight. Many studies have found defi- • care should be taken when advising on diet and nutri-
ciencies in vitamin D status [5, 18, 85]. Long‐term use of anti- tional supplements for possible cariogenic effect on the
convulsant therapy has been associated with alterations in teeth
vitamin D and calcium metabolism [5]. NICE guidelines • bottle feeding for prolonged periods of time should be
suggest that children should be supplemented with vitamin avoided where possible and alternatives should be
D if they are under 4 years old and/or spend significant peri- advised
ods of time indoors [97]. It is advisable that vitamin D and
calcium intakes meet the reference nutrient intakes (RNI) for
age. The requirement for vitamin D for those older than 4 Oral dysfunction and dysphagia
years to prevent deficiency is 10 μg (400 IU) daily [98]. It is
also important to ensure that there is an adequate calcium Oral dysfunction may result from either structural abnor-
intake to build and maintain bone strength, and a prepara- malities such as high roof of the mouth, cleft, enlarged
tion with calcium and vitamin D may be indicated. Regular tongue, abnormal dentition or motor difficulties such as
blood monitoring every 6–12 months for bone indices should those seen in CP. Children with neurological impairment
be done and supplementation given as indicated. The use of commonly have oromotor difficulties, and around 89% need
DEXA scans to measure bone mineral density is a useful part assistance with feeding, 56% choke with food and 28% have
of nutritional monitoring for children with neurodisability if prolonged feeding times [1].
this is available in their area [5]. There are four stages of swallowing, all of which need to
be functioning correctly for the safe and efficient passage of
fluid or solids to the stomach (Table 21.4).
Dental caries From infancy to childhood, as the CNS matures, certain
reflexes usually disappear. Children with physical disabilities
There is a higher incidence of oral/dental problems in these
may keep some of these, and, when coupled with abnormal
children [5] and are caused by a number of factors:
movement patterns, they can make it difficult to coordinate the
• poor dental hygiene due to hypersensitivity to teeth passage of food and fluids to the mouth. Table 21.5 summa-
cleaning rises the effect of abnormal movement on eating.
• inability to clean teeth oneself and dependent on caregivers
for support
Texture modification
• difficulty accessing oral cavity for children who have
behavioural, structural or muscular conditions In order to ensure a safe swallow and to allow for different
• cariogenic effect of some medications due to sugar con- structural, behavioural or reflexive movements, the SLT may
tent or decreasing saliva production alter food and fluid consistencies to reduce the risk of
Complications 435
Table 21.4 Stages of swallowing.
Stage of swallow What is happening Difficulties that can occur at this stage
Pre‐oral The process of thinking about food, smelling food, seeing food, Lack of coordination to touch food or bring food to mouth
(anticipatory) touching food and bringing food to mouth Blindness
Unable to smell/see food if inside packaging, e.g. pouch food
Oral preparatory The process consists of head and jaw movements including Inability to open the mouth voluntarily
voluntary opening of the mouth, lip closure around the utensil Inadequate lip closure
or biting food, transferring the food around the mouth including Overbite or tonic biting (biting down hard)
chewing, sorting and mixing to form a bolus and holding onto Tongue thrust
this bolus ready for swallowing Oral hypersensitivity indicated by food refusal
Oral This relates to the initiation of the swallow and involves Lack of coordination of tongue movement
elevation of the front of the tongue to seal the mouth, Incomplete nasopharyngeal seal
propulsion of the bolus by the tongue to the back of the mouth
and raising the soft palate to provide a nasopharyngeal seal
Pharyngeal This is an involuntary stage triggered by the movement of food to Ineffective function of peristalsis
the lower part of the pharynx. The nasal passage and airway are Problems with pharyngeal anatomy
closed as the food passes from the pharynx into the oesophagus.
The bolus of food is transported through the oesophagus by
peristalsis. Closure of the vocal fold prevents aspiration
Oesophageal This depends on the peristaltic action of oesophageal muscles to Oesophageal obstruction
propel the bolus of food into the stomach and the contraction of Gastro‐oesophageal reflux
the cricopharyngeus muscle to prevent reflux
Table compiled from information in Matsuo and Palmer [99].

Source: Reproduced with permission of Elsevier.
Table 21.5 Abnormal movements and reflexes affecting eating and drinking.
Name Description Effect on mealtimes
Asymmetrical tonic Caused by turning the head and triggers extension of Posture: The child can be difficult to position
neck reflex the limbs on the side which the head is rotated and Feeding: The child may be unable to look at their hand and bring
an increased flexion of the opposite side their hand to mouth
Swallow: Head turned severely to one side may prevent an effective
swallow
Extensor thrust Voluntary or involuntary strong push back of head Posture: The child can be difficult to position
and trunk Swallow: Chin thrust inhibits effective swallow, may cause choking
Oral: Jaw thrust prevents mouth closure and can obstruct suckling
and chewing
Startle reflex Sudden extension of arms and opening of hands, Posture: The child can be difficult to position for self‐ or assisted
stimulated by sudden noise or unexpected feeding
movements Feeding: The sudden loss of posture may rouse feelings of insecurity
Swallow: Associated with a fast intake of breath, which may
cause choking
Rooting reflex When cheek is touched, the head turns to that side Oral: When head is out of midline, the configuration of the mouth
changes including the jaw and lip positioning
Bite reflex When mouth touched there is a sudden jaw closure Oral: Cannot coordinate jaw movement in order to introduce or
withdraw utensil
Tongue thrust Tongue moves in direction when touched Oral: Difficult to introduce food, retain food and deal with it in
the mouth
aspiration and improve swallow. The International 3 – liquidised food, or moderately thick drink
Dysphagia Diet Standardisation Initiative (IDDSI) has devel- 2 – mildly thick drink
oped descriptors for both food and fluid [100]: 1 – slightly thick drink
0 – thin drink
7 – regular food
6 – soft bite‐sized food This sequence and overlap of textures is shown in Figure 21.5.
5 – minced and moist The required texture should be described to the caregiver,
4 – puréed food, or extremely thick drink giving plenty of examples of ways of achieving the desired
Foods
Regular
7
Easy to chew
Tra
ns
itio
Soft and bite size 6
na
l fo
od
Minced and moist 5
s
Pureed 4 Extremely thick
Liquidised 3 Moderately thick
2 Mildly thick
1 Slightly thick
0 Thin
Drinks
Figure 21.5 Descriptors for foods and drinks. IDDSI framework. https://iddsi.org.
texture. The effect that cooling or warming the food may the rate of bone loss for patients on AED [5, 102]. Children on
have on texture, the effect of stirring the food repeatedly and AED may also have reduced levels of vitamin B12, folate and
how saliva from the spoon will thin the consistency during a vitamin B6, and these nutrients may need monitoring and
prolonged meal need to be discussed. supplementation given [103, 104].
Muscle relaxants, such as baclofen, are commonly used for
children with CP and other neurological conditions. If the
Cleft lip and palate
dose is correct, posture for eating can be improved in chil-
dren with spasticity. However, if the dose is too high, then
Children with neurodisability may also have a cleft lip and/
muscle weakness can lead to feeding difficulties.
or palate. They are at risk of poor growth and nutrition
Food can affect absorption of some medications making
because they may not be able to get an effective suck. Feeding
them more or less effective, e.g. phenytoin, which should be
adaptation may involve using different techniques when
given 2 hours before or after a meal/feed. Medications, espe-
breastfeeding, different shaped teats with enlarged or differ-
cially antibiotics, can also alter the gut microbiota of a child,
ent positioned holes, soft squeezy bottles that may help the
and this may increase risk of gastrointestinal upset, e.g. diar-
flow of milk and temporary maxillary plates, or if the child is
rhoea [105].
unable to safely meet nutritional needs orally, then they may
be tube fed [101]. Surgical repair of the lip and palate can
occur any time from 4 to 12 months of age. Normal feeding
can often resume if the cleft has been completely repaired
[101].
The transition of children to adult care normally takes place
when the child leaves full‐time education, and this could be
Drug and nutrient interactions up to 19 years of age. Children are often very carefully moni-
tored within a paediatric MDT, and care should be taken to
Medications can have an impact on nutritional status by ensure that all relevant information is handed over to all the
causing changes in taste, appetite, weight, alertness and/or adult team such as dietitian, general practitioner, hospital con-
gastrointestinal upset. This can be a problem when a new sultant, allied healthcare team and district nurses (where
drug is being introduced and adjusted. Anti‐epileptic drugs appropriate). There is often a transition period where a child
(AED) may have impact on bone health and are associated will start getting used to day‐care units, and the MDT needs to
with an increased risk of bone fractures and reduced bone support this transition. Parents and caregivers will need
mineralisation relating to lower availability of vitamin D. support as often adult services offer different facilities to chil-
Supplementation with calcium and vitamin D may reduce dren’s services, and they may find the change quite stressful.
Future research needs and unanswered • changes to gut microbiota with medications for children
questions with disability
• prevalence of food allergy or intolerance in children with
The following issues need to be addressed in children with disabilities
neurodisability: • energy and protein requirements and whether the use of
height age is a good estimator of requirements
• long‐term use of adult enteral feeds and the effects of
high micronutrient intakes over prolonged periods of
time and gut microbiota References, further reading, guidelines, support groups
• the need for routine supplementation of vitamin D and and other useful links are on the companion website:
calcium with modern AED www.wiley.com/go/shaw/paediatricdietetics-5e
22
Natalie Yerlett
Epidermolysis Bullosa and Rare
Skin Disorders
Epidermolysis Bullosa
Introduction on extremities. Some patients presenting with the same sub-
type of EB may manifest a wide range of symptom severity.
Epidermolysis bullosa (EB) comprises of a group of rare genet- The intellectual development of these children is normal.
ically determined skin blistering disorders characterised by
extreme fragility of the skin and internal mucous membranes.
Mode of inheritance
Types of epidermolysis bullosa EB is usually inherited either dominantly or recessively; it

may also result from a spontaneous genetic mutation with
The most recent classification [1] separates EB into four main no previous family history [2]. In dominant inheritance, the
types (Table 22.1), which are further divided into major sub- affected parent (who has EB) passes on the affected gene to
types, of which there are many further subtypes not listed their child. There is a one in two chance with each pregnancy
here. The first three types are illustrated in Figure 22.1. that a child will inherit the affected gene. The more severe
The classification of each EB type and subtype is based on forms, where each parent carries the affected gene (but does
mode of transmission and phenotypic, ultrastructural, not have EB), are generally recessively inherited. In each
immune‐histochemical and molecular findings [1]. All types pregnancy with two carrier parents, there is a one in four
result from genetic mutations, which cause a defect in, or a chance of an affected child being conceived.
partial or full absence of a structural protein in the dermal–
epidermal basement membrane zone; or, in the case of
Diagnosis
suprabasal EB simplex (EBS), between adjacent keratino-
cytes. The resultant defective adhesion means that minor
In some cases EB may be suspected at birth. Occasionally, the
knocks or friction can cause the skin to blister. The depth of
severity of skin damage at birth does not correlate with the
these blisters and how they heal differs depending on the EB
severity of the diagnostic subtype; due to this, great care is
subtype. DNA blood tests of the patient (or the parent if they
taken to deliver the diagnosis as quickly as possible while
have the same phenotype of EB) are taken in infancy to
trying to avoid a presumed diagnosis. Parental anxiety is
ascertain subtype. Classification of EB subtypes has changed
often very high while awaiting such results as they have
and been updated many times, and many more genes are yet
likely found out that some forms of EB are fatal. In milder
to be identified. Occasionally, the EB subtype is classified by
cases EB may be diagnosed much later on. To make a diag-
clinical presentation alone if genetic testing fails to identify
nosis, the ‘onion skin’ approach is recommended [1]:
the genetic defect; often the gene has yet to be identified. The
consequences of different EB types vary greatly in their • a full personal and family history and physical examina-
impact ranging from infantile mortality to minor blistering tion is undertaken with presence or absence of cutaneous

Nutrition Support 439
Table 22.1 Classification of epidermolysis bullosa.
Level of skin
cleavage EB type Major subtypes Main group of targeted proteins
Intraepidermal EB Simplex Suprabasal Transglutaminase 5, plakophilin 1,

(EBS) Skin fragility syndromes such as desmoplakin deficiency desmoplakin, plakoglobin
Basal Keratin 5 and 14, plectin, exophilin 5,
EBS localised (previously called Weber‐Cockayne) BP23, KLHL24, kindlin‐1
EBS generalised severe (previously called Dowling‐Meara)
Intralamina Junctional EB JEB generalised severe (previously called Herlitz) Lamini‐332, collagen XVII, α6β4 and α3
lucida (JEB) JEB generalised intermediate (previously called non‐Herlitz) integrin
JEB with pyloric atresia
JEB LOC syndrome
JEB localised Collagen XV11, laminin‐332, α6β4
integrin
Sub‐lamina Dystrophic EB Dominant (DDEB) Collagen VII
densa (DEB) Including bullous dermolysis of the newborn
Recessive (RDEB) Collagen VII
RDEB generalised severe
RDEB localised
RDEB generalised intermediate
Mixed Kindler – Fermitin family homolog 1 (kindlin 1)
or extra‐cutaneous symptoms; the EB major subtype Multidisciplinary management is focused on symptom control,
could be elucidated from this wound dressing, therapeutic input, treatment and prevention
• following this, localised or generalised diagnosis may be of infection, monitoring, pain management, surgery, gastroin-
elucidated with further symptomology and later from testinal (GI) review and optimisation of nutritional status [7].
information related to the mode of transmission Worldwide research efforts are under way to find new ther-
• this may be followed up with a skin biopsy, undergoing apies that provide longer lasting improvement in patients’
microscopy with immunohistochemical techniques conditions and, ultimately, a cure. These include [8]:
(immunofluorescence antigen mapping [IFM] with EB‐
• therapies such as gene therapy, protein therapy, drug
specific monoclonal antibodies)
therapy, molecular and cell therapy
• finally, a genetic mutation analysis [1, 3, 4].
• local therapies that target healing such as grafting with
genetically corrected skin or subcutaneous injections of
Prevalence collagen or fibroblasts
• systemic therapies aimed at whole body healing using
The exact prevalence of EB is difficult to assess as very mild intravenous (IV) injections of bone marrow stem cells
cases may go undiagnosed, while the severely affected may from a donor, mesenchymal stem cells or, in the future,
die before diagnosis. In the UK, it is currently estimated that induced pluripotent stem cells
there are approximately 5000 people living with all subtypes While some interventions aim for temporary improve-
of EB. Prevalence of all types of EB and all ages in late 2010 ment (collagen or fibroblast therapy), others aim for a per-
was estimated at 15 : 1 000 000 [5]. EB affects the sexes equally manent cure (grafting with genetically corrected skin or
and is prevalent in all ethnicities. bone marrow transplant).
Management
Nutrition support
Severe types of EB can be extremely physically disabling cou-
pled with constant severe pain. Many patients will have chroni- Current practice relies on retrospective studies of small
cally compromised nutritional status as outlined in Table 22.2. numbers of children, expert clinical experience and extrapo-
These include those diagnosed with RDEB, JEB and the EBS lation from other conditions affecting the skin such as burns
generalised severe patients, all of whom are likely to require and pressure ulcers. Early proactive intervention has the
nutritional intervention from birth. Despite worldwide research best chance of optimising nutritional status, well‐being and
investment and many advances in treatment, there is currently wound healing in the longer term [9–12].
no cure for any type of EB. Treatment with exclusion diets Breastfeeding should always be encouraged; however,
combined with topical and systemic treatments (the Kozak rooting at the breast may cause or exacerbate facial lesions,
regimen) was disproved in an open evaluation [6]. and suckling may lead to blistering of the mouth, tongue and
440 Epidermolysis Bullosa and Rare Skin Disorders
Keratin 5/14
EBS
Plectin
BP230
Hemidesmosome
a6b4
integrin
Cell membrane
Collagen XVII
JEB
Laminin-332/311
Lamina
densa
Collagen VII
DEB
Interstitial
collagen
fibrils
Figure 22.1 Schematic representation of the dermal‐epidermal basement membrane zone. This shows the position of specific structural proteins
relevant to EB. Source: Image reproduced with permission from Medscape Drugs & Diseases (https://emedicine.medscape.com), Epidermolysis Bullosa,
2018, available at: https://emedicine.medscape.com/article/1062939‐overview
gums. This can be eased by applying petroleum jelly to the vacuum, a ‘Special Needs Feeder’ (www.medela.com) may be
lips and to the nipple to reduce friction. In severe cases breast- useful as no vacuum is needed, and the carer can learn to gently
milk may need to be supplemented to meet high nutritional squeeze the shaft of the feeder to deliver a steady flow of milk.
requirements. Breastmilk can be supplemented with stand- Weaning foods can be offered at the usual time of around
ard infant formula or hydrolysed protein infant formula if 6 months (always after 4 months) of age using a shallow
indicated. These can be either mixed with expressed breast soft plastic spoon with rounded edges. Carers may need
milk (EBM) (p. 13) or given in addition to direct breastfeed- reassurance if progression to solids is slow and babies with
ing. In some cases, topping up with one or two feeds of a high an extremely fragile mouth may feed more confidently
energy, high protein formula may be useful. If fully formula from the carer’s fingertip initially. It is common to make
fed, a concentrated infant formula or a commercial energy good progress then have a short period of painful oral blis-
and protein‐dense formula can be used (Table 1.18). tering that may stop progress all together. Carers can be
Soft silicone teats are generally better tolerated. If needed, reassured that this is common in EB and that, once the
teats can be moistened with cooled, boiled water before feeding blister has healed, steady progress can resume. Reluctance
to avoid the teat sticking to the lips and causing damage when to try new foods maybe exacerbated by gastro‐oesophageal
it is removed. In addition, petroleum jelly or teething gel can be reflux (GOR) [13], a very painful mouth or nasogastric
applied if needed to the teat itself before feeding. Occasionally (NG) tube feeding. Scarring and tongue tethering can cause
a slightly larger teat hole may be beneficial as more milk is an uncoordinated swallow with the risk of aspiration [14].
delivered without as much sucking effort – grading up through There is often early aversion to food composed of mixed
the size of teat hole is helpful to avoid giving too fast a flow. If textures (such as the soft lumps within a more liquid matrix
feeding is very difficult due to pain and inability to form a found in many commercial baby foods), whereas uniform
Table 22.2 Main complications influencing nutritional status and suggested interventions in some of the main types of EB.
EB type Complications Suggested nutritional intervention
RDEB Recurrent severe generalised blistering that heals poorly with Significantly increased requirements for energy and protein
generalised scarring and contractures (causing digits to fuse). Severe Supplementation of certain micronutrients may be indicated
severe growth faltering. Dystrophic or absent nails. Internal mucosal including vitamins C and D, zinc, calcium and iron
membrane scarring and contractures cause microstomia, Gastrostomy tube feeding often indicated
dysphagia and oesophageal strictures. Other complications Specialised formula feeds and exclusion diets may be
include osteoporosis/osteopenia, refractory anaemia, anal considered for severe GI symptoms
fissures, ocular issues, constipation, bowel inflammation/colitis Fibre and laxative management is often required
and pubertal delay. Dental caries often requiring extractions
RDEB Recurrent mild–moderate generalised blistering that heals Slightly increased requirements for energy and protein
generalised poorly with scarring and contractures (causing digits to fuse). Supplementation of certain micronutrients may be indicated
intermediate May have a degree of growth faltering. Dystrophic or absent including vitamins C and D, zinc, calcium and iron
nails. Internal mucosal membrane scarring and contractures Fibre and laxative management is often required
may cause microstomia, dysphagia and oesophageal
strictures. Other complications may include mild anaemia,
anal fissures, mild ocular issues and constipation
DDEB Mild–moderate lesions with minimal scarring. Growth may Intervention is not generally indicated other than advice on
be normal. Anal fissures may cause painful and reluctant healthy eating and age‐appropriate increases in fibre and fluid
defaecation. Constipation is common. Oesophageal strictures intakes if defaecation painful
may be problematic Iron levels should be checked periodically
JEB generalised Recurrent moderate to severe blisters that heal without scarring, Moderately increased requirements for energy and protein
intermediate but often very slowly. May be genito‐urinary involvement. May Supplementation of certain micronutrients may be indicated
have airway narrowing requiring MLB. Other complications including vitamins C and D, zinc, calcium and iron
may include anaemia, ocular issues, enamel hyperplasia and Gastrostomy tube feeding may be indicated
dental caries requiring extractions, scalp abnormalities affecting Specialised formula feeds and exclusion diets may be
hair growth, dystrophic/absent nails considered for severe GI symptoms
Fibre and laxative management may be required
JEB generalised Fatal usually within 1–2 years of age. Recurrent moderate to Maintain hydration, feed to appetite, address deficiencies
severe severe and widespread lesions. Dental pain due to abnormal within terminal care framework
tooth composition. Laryngeal and respiratory complications. Gastrostomy placement not usually recommended as
Initial weight gain usually followed by profound, intractable laryngeal/respiratory issues greatly complicate general
growth failure, possible protein‐losing enteropathy and anaesthesia and healing around stoma may be poor
diarrhoea. Tissue granulation occurs, may effect nostrils NG feeding can be discussed with the family as an option
High energy, hydrolysed protein, MCT feeds may be an
appropriate choice of formula
Weighing can be undertaken to determine best regimen for
pain relief
Emphasis to be placed on quality of life
Advice for weaning onto solids may be needed if
appropriate
JEB with Recurrent severe blisters. May have large areas of absent Depends on severity of phenotype. Early repair of atresia.
pyloric atresia skin. Complex genito‐urinary involvement. May have anal, Significantly increased requirements for energy and protein
duodenal or pyloric atresia. Other complications may (and fluid if large areas of skin missing). Supplementation of
include renal complications, rudimentary ears, anaemia, certain micronutrients likely needed including sodium,
ocular issues, enamel hyperplasia and dental caries requiring vitamins C and D, zinc, calcium and iron
extractions, dystrophic/absent nails. High risk of infant Enteral feeding can be considered if appropriate
mortality in severe cases despite early atresia repair. In milder Specialised formula feeds and exclusion diets may be
cases who survive infancy, blistering can improve with age considered for severe GI symptoms
Fibre and laxative management may be required in later years
EBS Severity of skin involvement at birth also dictates level of As for RDEB generalised severe in early years, but
generalised feeding and growth difficulties in infancy. In severe cases gastrostomy placement is rarely necessary
severe gastro‐oesophageal reflux, malabsorption and oropharyngeal In severe cases, NG feeding is often needed initially and may
blistering may be significant and difficult to manage. lead to oral aversion
Nutritional replacement of sodium, micronutrients and Sodium, protein, fibre, iron, zinc and vitamin
protein may be needed if large areas of skin are absent. supplementation may be indicated
Problems may lessen in late infancy/early childhood. Advice on healthy eating and weight maintenance/reduction
Catch‐up growth often occurs around adolescence. Painful may be indicated later on
hands and feet may reduce ability to take part in activities/
physical education at school and this may lead to becoming
overweight in teenage years. Anal fissures frequently cause
painful defaecation often with constipation
EB type Complications Suggested nutritional intervention
EBS localised Lesions usually confined to hands and feet, especially in hot Intervention is generally not indicated other than advice on
weather, often severely limiting mobility. Frequently painful healthy eating and age‐appropriate increases in fibre and fluid
defaecation with/without constipation intakes if defaecation painful
Due to compromised mobility, advice on weight
maintenance/reduction may be indicated
Kindler Photosensitivity. Thin papery skin with variable tendency to Intervention not generally indicated unless growth falters and/
syndrome develop moderate to severe blisters that predominantly affect or GI complications necessitate relevant management
limbs and fingers (which may fuse). Other complications may Nutritional blood samples should be monitored at least
include oesophageal, laryngeal, urethral and anal mucosa annually
involvement, colitis, gingival fragility and inflammation with
poor dentition. May develop anaemia. Growth faltering not
common. Blistering tendency may lessen around adolescence
EB, epidermolysis bullosa; RDEB, recessive dystrophic EB; DDEB, dominant dystrophic EB; JEB, junctional EB; MLB, microlaryngoscopy and
bronchoscopy; NG, nasogastric; MCT, medium chain triglycerides; GI, gastrointestinal; EBS, EB simplex.
textures tend to be accepted with more confidence. Hard or • not meeting nutritional or fluid requirements
sharp foods such as toast, crisps or baked rusks are unsuitable • gastrostomy placement is considered appropriate, but
as they can damage the fragile mucosa of the mouth and gums evidence of the effects of improved nutrition are needed
in some babies. Some bite‐dissolve weaning snacks may need before surgery can be agreed
vigilance, so they do not get stuck to the lips, which can then
cause a blister – moistening them a little first can help.
Gastrostomy tube feeding
Practical information for carers and community personnel
can be found in the booklets Nutrition for Babies with Epidermolysis
G‐tube placement is often a vital and highly beneficial
Bullosa and Nutrition in Epidermolysis Bullosa for Children over 1
method of improving the nutritional intakes of children and
Year of Age published by the Dystrophic Epidermolysis Bullosa
young adults with EB. Particular benefits are increased fluid
Research Association (DEBRA) and downloadable from www.
intake, increased energy and protein intake, and increased
debra.org.uk/publications. DEBRA’s nutritional guidelines for
adherence to medications, particularly laxatives and micro-
the management of EB are currently being revised and will be a
nutrient supplements. Discussion about G‐tube placement is
valuable resource once published.
often greeted with great concern by families as they may be
The complications of RDEB in particular begin in infancy
worried that it is an extra burden of work and may be com-
and, except in mild cases, progressively increase as the child
plicated by poor skin healing and/or become a source of
gets older [11, 15]. The causes and effects of severe general-
potential infection. Great care and consideration of these
ised RDEB on nutritional intake are shown in Figure 22.2.
emotive issues is needed, and multidisciplinary team (MDT)
Factors such as painful defaecation (with or without consti-
work with expert communication skills are required for
pation), extensive non‐healing lesions, chronic infections,
sometimes long periods to talk with the patient and the fam-
general skin and bone pain, anaemia, malaise and refusal of
ily to ensure the best outcome. Ideally the idea of a G‐tube
oral medications and supplements contribute significantly
should be discussed early for patients suffering with severe
to the potential for profound nutritional compromise.
types of EB, as preventing a severe decline in nutritional sta-
tus may benefit all symptoms and help to establish a positive
Nasogastric tube feeding balance between oral intake and intake via gastrostomy.
Dietetic review is essential to ensure the right balance of
NG feeding maybe required in early infancy in severe cases nutrition is provided by feeds, oral foods are encouraged
and occasionally in some older children. The majority of when able, and weight gain is proportionate to good linear
older children who are considered for gastrostomy (G) place- growth and not just creating central obesity.
ment will have one placed without a period of previous NG In practice, patients and parents are happy with the deci-
feeding. Internal nasal and oesophageal damage may be sion to have a G‐tube placed as it often improves weight
caused by placing the NG tube and securing the tube on the gain, reduces the burden of oral medications, improves
cheek should be done in consultation with an EB clinical bowel function and maintains nutritional status and hydra-
nurse specialist. Advice can be sought on non‐adhesive tion during periods of oesophageal stricturing. A recent sys-
dressings and silicone tapes to minimise trauma tematic review concluded that G‐tube placement, although
Circumstances in which NG feeding may be indicated as a not risk free, is safe and effective for improving nutritional
temporary measure include: status and quality of life (QoL) in children with EB [16].
While G‐tube placement has been associated with minimal
• a baby’s mouth becomes excessively traumatised by complications and improved growth and bowel function, it
suckling has also been previously linked to pain, intractable leakage,
Dental caries and gum disease

Oral, pharyngeal and oesophageal blistering
Microstomia, fixed tongue
Painful swallowing
Oesophageal stricture
GORD
Anal fissures
Constipation
Hand deformity
Severe, chronic pain
Infection
Malnutrition
Postural changes and contractures
Reduced:
• Food/fluid intake
• Energy levels
• Mobility and
weight-bearing
• Sunlight exposure
Growth faltering
Nutrient losses via blisters and wounds
Compromised wound healing
Constipation
Compromised immunity
Anorexia
Increased infection rates
Osteoporosis/osteopenia
Increased nutritional requirements
Fractures
Nutritional deficiencies
Apathy
Pubertal delay
Polymedication
Figure 22.2 Causes and effects of nutritional problems in severe generalised recessive dystrophic epidermolysis bullosa.
infection and excoriation around the G‐tube insertion site, Regular review of the gastrostomy site is essential to make
bloating, colitis, gastro‐oesophageal reflux disease (GORD) sure the fit is right, and over time the position of the G‐tube
and central obesity [16–23]. Improvements in G‐tube place- may need to be changed to ensure it is anatomically in the
ment techniques, aftercare, proactive placement of a G‐tube most beneficial place. G‐tube feeds are generally begun
prior to decline to a severe malnourished state and manage- within 4–6 hours of surgery, initially using sterile water, to
ment of constipation are all factors that may improve out- ensure absence of leakage; discharge from hospital is usually
comes of G‐tube placement. Pro‐inflammatory cytokines are within 48–72 hours depending on progress and local policy.
thought to play a critical role in GI complications and the Parents/carers may need to be trained on feed pump use
central obesity, increased fat mass and poor linear growth and feeding regimens, especially as often a prior period of
seen in some G‐tube fed children with EB [22]. NG feeding has not taken place.
Different methods are preferred for G‐tube placement at In rare cases it may be necessary to place a gastrostomy
the EB centres around the world. A team with experience in with a jejunal extension if GOR or aspiration is severe. As with
EB should ideally create the gastrostomy. Techniques that any other child, this has implications for the rate at which
avoid endoscopy and risk of trauma to the oesophagus are feeds can be given, their volume and composition (Table 4.4).
preferred and may include open surgical gastrostomy, lapa-
roscopically assisted endoscopy, modified laparoscopic gas-
trostomy and non‐endoscopic percutaneous gastrostomy [22,
23]. The G‐tube should have soft silicone securing material Parenteral nutrition
where possible. The type of tube placed and local policy will
dictate if it should be rotated and how often. Some G‐tubes The use of parenteral nutrition (PN) in EB babies and chil-
may not need to be rotated, but just pushed gently in and out dren is rare but can be used for profound malnutrition when
to ensure it does not become buried in the stomach wall. The enteral feeding has failed repeatedly. Intravenous lines pose
tube may be replaced by a low‐profile device 10–12 weeks a risk of septicaemia, so PN should be considered as a last
postoperatively if the patient wishes to change it [23]. resort [18, 24].
Nutritional assessment Despite proactive nutritional intervention, growth retarda-

tion can occur early in the course of severe EB [20, 21]. Standard
Measurements of weight and height velocity are the most growth charts should be always used with the aim that the dis-
practical means of assessing growth in EB. Weight and height parity between weight and height should aim to be no greater
(length), if able, should be measured regularly. Downward than 2 centiles. If high requirements are met, normal growth
deviation from the birthweight centile in the first year is can be achieved even in the severe subtypes of EB. Although
common in infants born with extensive skin loss despite body mass index (BMI) does not differentiate between lean
intensive nutritional interventions. and fat tissue, data from a centre with good outcomes follow-
Weight measurements should ideally be performed ing G‐tube placement suggests it is a reliable means to monitor
directly after or during a dressing change as wound exu- growth and can predict optimal timing for placement [25].
dates in the dressings could lead to overestimation. Although Regular nutritional assessment is important not only to
nude weight is ideal, the skin damage incurred during address ongoing problems but also to try to prevent their
handling usually precludes this. severity. The proforma in Table 22.3 can be used to record
Due to pain and contractures around joints, height measure- relevant information.
ments are impractical in severely affected children. A supine A tool to help identify nutritional compromise (THINC)
stadiometer or measuring mat may provide greater accuracy. (currently not validated) has been developed as a compre-
If neither of these is possible, other anthropometric measure- hensive method of assessing the risk of actual or potential
ments may be attempted if safe to do so, such as ulna length. nutritional compromise in children with EB under and over
Table 22.3 Suggested proforma for recording nutritional intake and other relevant information.
Name DOB Hospital number Date

Weight kg centile Height cm centile
Consistency of food Normal Soft Purée Fluid
Reason(s) Oral blistering Microstomia Fixed tongue
Dental caries Dysphagia Oesophageal stricture
Regurgitation of mucus/pooled secretions Gastro‐oesophageal reflux
Typical bowel habit BO × day × week
Pain Bleeding per rectum Stool consistency
Laxative(s), prebiotic(s), probiotic(s) etc.

Lactulose Movicol Sodium picosulphate Other*
Fibre supplement Other prebiotic* Probiotic*
Typical Breakfast
Snack
Meal Lunch
Snack
Pattern Evening
Bedtime
Time taken over an average meal: minutes Finishes amount offered?
Feeding tube in situ? Type (including make, shaft length)
Nutrient dense/energy dense supplement(s)/gastrostomy feeds
Record name(s), dose, frequency
Other supplement(s) Record name(s), dose, frequency
Iron Zinc Fluoride Calcium Vitamin D3
Other vitamins Selenium Other

Approx. daily intake Protein g ( /kg) Normal DRV = g ( /kg)
Energy kcal ( /kg) Normal DRV = kcal ( /kg)
Comments/action
DRV, dietary reference value for age and sex matched healthy child.
*Record name(s), dose, frequency
18 months of age and forms part of nutrition clinical practice • the degree to which oral, oropharyngeal, oesophageal
guidelines written for EB, currently being updated [26]. It and GI complications limit intake
has been developed to aid, not replace, clinical judgement • the diversity of disease severity of patients even with the
and its scoring charts rate the three key aspects of the child’s same EB type
state: weight and height, gastroenterology and feeding; der- • the variability over time of individual patients’ requirements
matology. The higher the score, the greater is the likelihood • varying mobility levels over time and even within the
of nutritional compromise. According to the total nutritional same type of EB
compromise score, algorithms suggest varying courses of • the difficulties associated with estimating desirable
action. weight gain when height growth is compromised
• the presence of infection that complicates the interpreta-
tion of laboratory results
Biochemistry and haematology • the chronic inflammatory nature of EB characterised
by continued expression of pro‐inflammatory
Interpretation of laboratory results in EB children is difficult cytokines [19]
because of the inflammatory nature of the condition.
Table 22.4 [27] lists investigations that should be carried out
with suggested sampling intervals. Frequency may vary Energy
depending on disease severity.
Energy requirements can be estimated using the following
formula [15]:
Nutritional requirements
weight kg kcal/kg for height age
Every patient with EB has different nutritional requirements 1 sum of 3 additional factors
that may fluctuate. Some milder cases of EB may have close
to normal requirements for energy and protein, whereas
Additional factors:
more severe cases of EB may likely have much greater
requirements for energy, protein, fluid and micronutrients.
1. Ratio of blisters to body surface area (BSA): 20%
The main factors potentially compromising nutritional
BSA = 0.19, 40% BSA = 0.5, 100% BSA = 0.95
status in EB are:
2. Sepsis: mild = 0.2, moderate = 0.4, severe = 0.8
• open skin lesions will likely lose blood, serous fluid, protein, 3. Catch‐up growth: 0.1–0.2
fluids, electrolytes and heat. The body constantly attempting
to heal these wounds can result in a chronic hyper‐catabolic An example calculation using this formula is given in
state. In addition, the risk of infection is high with such Table 22.5. Although this method provides a working figure,
wounds that can increase requirements further the scoring of skin involvement is subjective, and the
Table 22.4 Laboratory investigations.
Investigation Suggested sampling intervals
Urea and electrolytes: 6 monthly unless abnormal

Sodium, potassium, urea, creatinine
Urinary sodium Every 2–3 weeks initially in severely affected newborns until corrected
above 50 mmol/L, then less frequently. Older infants and children with
exudate loss should have this checked approximately 6 monthly
Liver function tests 6 monthly
Total bilirubin, albumin, alkaline phosphatase, alanine
aminotransferase, aspartate aminotransferase
Bone profile 6 monthly
Calcium, phosphate, alkaline phosphatase, vitamin D (total)
Trace elements Annually – unless previous deficiency
Zinc, selenium, copper, vitamin B12, vitamin A, vitamin E, vitamin C,
folic acid/folate, vitamin K
Iron studies: Haemoglobin 6 monthly – may be needed more frequently depending on degree of
Total iron binding capacity anaemia
Serum iron
Ferritin
% transferrin saturation
Full blood count (FBC) 6 monthly – may be needed more frequently depending on degree of
anaemia
Table 22.5 Case study: high energy and protein requirements in a boy with EB.
A 6-year-old boy with RDEB generalised severe

Weight = 13 kg (<0.4th centile), Height = 107 cm (2nd centile), Height age = 4.7 years
He has liquid iron supplements twice a day and suffers from constipation. He has 20% body surface area (BSA) blistered, with mild sepsis. He has
microstomia and after two oesophageal dilatations within a year a gastrostomy was placed. He continues to manage small amounts of food orally.
Daily requirements
Fluid requirement based on actual weight 1150 mL
Energy requirement calculated by applying the formula (p. 445): 13 × 90 × [1 + (0.19 + 0.2 + 0.2)] = 1860 kcal (7.8 MJ) or 143 kcal (595 kJ)/kg
Energy requirement based on 130–180 kcal/kg = 1690–2340 kcal (7.1–9.8 MJ)
Protein requirement based on 2.5–4.0 g protein/kg = 33–52 g
Fibre requirement = 20 g
Gastrostomy feeds
1000 mL high energy paediatric fibre containing formula, e.g. PaediaSure Plus Fibre: 152 kcal (635 kJ), 4.2 g protein and 1.1 g fibre per 100 mL
Energy = 1520 kcal (6.4 MJ) Protein = 42 g Fibre = 11 g
Feeding plan
Building up gradually to 100 mL/hour × 10 hours continuously overnight (or 2 × 200 mL boluses morning and late evening with 60 mL/hour × 10 hours
overnight) depending on tolerance and family’s preference
Continue to offer oral intake of foods with the textures altered accordingly. Soft foods orally with high fibre, protein and energy content should be
encouraged.
Follow‐up
Initially 2–4 weekly to assess feed tolerance and weight gain and then every 3 months
formula is complex. It may be that the skin involvement is it may be beneficial to supplement certain micronutrients in
not always directly observed by the dietitian at hospital EB [32] since deficiencies of specific micronutrients includ-
review, which makes this value harder to estimate. A simpler ing iron, selenium, zinc and vitamins A, B6, B12, C and D have
method is to use 115%–150% of the average energy require- been identified [15, 17, 33]. However, the role of increased
ment for the normal population [28] in order to provide suf- intakes of single or multiple micronutrients is unclear even
ficient energy to promote weight gain and wound healing: in individuals with normal skin, and more work is required
130–180 kcal (545–750 kJ)/kg actual body weight per day. to identify both the clinical conditions and the doses of indi-
Requirements may be as high as 225 kcal (940 kJ)/kg if the vidual micronutrients that actively promote or accelerate
skin is septic or growth failure is profound. healing [34, 35]. Although understanding of drug‐nutrient
interactions are limited, especially when body composition
Protein is altered [36], care should be taken to advise families on the
timings of supplementation to maximise bioavailability of
Protein plays a most important role throughout the entire the nutrient absorption.
wound healing process. Collagen is the protein that is pro-
duced mainly in the healing wound of normal skin; therefore, Vitamins
a lack of protein decreases the synthesis of collagen and the
production of fibroblasts [29]. Protein requirements in EB are It is likely that severely affected children need increased
estimated to be approximately 10%–15% of energy intake, amounts of all vitamins [33]. Babies and older children who
extrapolated from the recommendation of 9% energy intake successfully take concentrated or nutrient‐dense feeds
for catch‐up growth in children with normal skin [30]. Children receive correspondingly increased amounts of all vitamins.
with extensive lesions will require an intake at the higher end In some instances additional iron and other micronutrients
of the range, especially where there is associated sepsis. Protein may still be required so serum monitoring is highly recom-
requirements tend to be 2.5–4.0 g/kg, 115%–200% of the refer- mended (Table 22.4).
ence nutrient intake [31], based on chronological age. Children relying on oral diet alone are likely to require an
age‐appropriate multivitamin and mineral supplement.
Micronutrients Supplements available over the counter that provide a wide
range of nutrients, including iron and zinc, are preferable.
Micronutrients are known to play essential roles in metabo- Vitamin C enhances iron absorption and promotes colla-
lism, wound healing, cellular immunity and antioxidant gen synthesis [37]. It also plays a role in the immune response
activity. Research in burns and pressure ulcers suggests that [29] through its antioxidant properties where it limits tissue
damage and prolonged inflammation [38]. Children with EB as promoting healing, optimising immune status and exerting a
may avoid the more astringent food sources of vitamin C beneficial effect on inflammatory conditions [38, 44]. It has been
due to their tendency to irritate the mouth and pharynx; shown in critically ill burns patients that supplementation with
however, in practice many patients enjoy foods such as cau- glutamine has reduced gram positive bacteraemia and mortal-
liflower or broccoli cheese bake, sweet or white potatoes, ity as the requirements for glutamine increase significantly dur-
avocado, mango, berries and the less acidic fruit juices given ing this time [44]. More studies need to be completed
with a meal (such as apple or mango juice). Fruit puree specifically in EB patients who have chronic wounds looking
mixed with yoghurt or ice cream can also be enjoyed. into the effectiveness of supplementing with these nutrients.
Where dietary intake is markedly low in fruit and vegeta-
ble content, it would be beneficial to ensure an age‐appropriate
Calcium and vitamin D: osteopenia and osteoporosis
multivitamin and mineral supplement is given daily, most of
which will contain vitamin C.
A number of mechanisms are thought to contribute to the
observed low bone mineral density (BMD) for chronological
Zinc
age seen in children with RDEB and JEB [24, 45–47]. These
include reduced mobility, poor nutritional intake, reduced
Zinc is an essential trace element in the human body as it
sunlight exposure (from restricted outdoor activities and
serves as a cofactor in numerous transcription factors and
extensive bandaging), chronic inflammation (pro‐inflamma-
enzyme systems including zinc‐dependent matrix metallo-
tory cytokines increase osteoclastic activity) and pubertal
proteinases that augment auto‐debridement and keratinocyte
delay. In addition, GI complications may affect absorption of
migration during wound repair [39]. Zinc confers antioxidant
relevant nutrients [11].
activity including resistance to epithelial apoptosis, protecting
Annual monitoring of all children with RDEB and JEB
membrane stability, and is important in immune function [39,
from 5 years of age is recommended. Lateral X‐rays of the
40]. Zinc deficiency of hereditary or dietary cause can lead to
lumbar and thoracic spine and ankles are suggested to detect
pathological changes, poor growth and delayed wound heal-
clinically significant osteoporosis and fractures, respectively.
ing. In addition, zinc may be involved in anti‐inflammatory
Dual energy X‐ray absorptiometry (DEXA) scan was previ-
responses with chronic zinc deficiency causing an increase in
ously routinely undertaken; however, current practice may
the production of pro‐inflammatory cytokines [40, 41].
move away from such frequent DEXA scanning unless clini-
Most patients with severe types of EB will likely need
cally indicated, such as to monitor impact of bisphosphonate
long‐term zinc supplementation due to their higher require-
treatment. Annual bone age assessment for adolescents with
ments for chronic wound healing. However, the degree of
pubertal delay can also be undertaken [48].
desirable supplementation is unclear. Generally, evidence
Intravenous pamidronate and oral risedronate have been
has shown supplementation of zinc is safe and non‐toxic;
used to address bone pain associated with osteopenia, osteo-
however, if high levels are given, it is prudent to monitor
porosis and fractures. However, information on their effects
both serum zinc and copper levels to ensure the dose is not
on BMD in this group of patients is lacking. If osteoporosis,
too high as excessive zinc may increase copper levels [42]. In
fractures and/or low serum levels are detected, calcium and
practice, if serum zinc is very low, dosing procedure is fol-
vitamin D should be supplemented and the serum bone pro-
lowed as per local protocol for deficiency and levels moni-
file monitored (p. 445).
tored routinely. Soluble zinc tablets available on prescription
can be taken orally (or via gastrostomy); it is often necessary
to ensure the dose is split and taken with food or feed to Iron and anaemia
reduce nausea or gastric irritation and aid absorption.
Interpretation of serum zinc results can be difficult in EB as Children with severe EB are at high risk of chronic and
the levels are affected by the acute phase response during peri- severe iron deficiency anaemia through reduced dietary
ods of infection or inflammation, both of which are common in intake, high requirements from chronic wound healing,
EB. In addition, a low serum albumin will also effect the serum blood loss and possible reduced GI iron absorption. Patients
zinc level. All of these findings will reduce the serum level of often have chronic inflammation, and iron homeostasis is
zinc [43]. Supplementing with excess zinc at this time may result changed significantly during the acute phase response; iron
in it just being excreted as the cells are saturated with zinc. may accumulate in the hepatocytes instead of being avail-
Iron and zinc have the potential to interact, leading to able for use [49]. Although iron’s participation as a cofactor
potentially reduced absorption of both [29]. Timings of sup- for antioxidants and collagen synthesis has been demon-
plements should be planned carefully to minimise these strated, causal links between iron supplementation and
micronutrient interactions, but not increase the daily burden improved wound healing have not been identified [38].
of poly‐medication. Haemoglobin (Hb) levels correlate very poorly with meas-
ures or markers of iron status in EB. Hepatic mechanisms
respond to inflammation by decreasing intestinal uptake and
Immune‐enhanced formulas release of iron into plasma. In addition, transferrin levels
decrease in response to inflammation, and ferritin levels can
‘Immune‐enhanced’ formulas containing nutrients such as argi- increase. Interpretation of iron status is multifaceted, and cor-
nine, glutamine and essential fatty acids are marketed for adults rection of deficiency is done with care and experience.
Prescribable sodium feredetate syrup is widely used, Carnitine supplementation does not reverse cardiomyopathy,
although compliance is often poor as this can directly cause but it can prevent its progression. Carnitine deficiency should
constipation, which is usually already an issue for most be addressed by giving 50–100 mg/kg/day Carnitor
patients with EB. Iron ionic water supplements, iron liquid Paediatric Solution.
preparation and iron spray supplements are all available
over the counter and can sometimes be much better toler-
Painful defaecation and constipation
ated and more palatable than sodium feredetate, with less GI
side effects; however, these are not always available on
GI complications are present in all types of EB with up to 58%
prescription. IV iron supplementation may be necessary in
of patients presenting with some form of GI complication [53].
children with severe chronic deficiency who are refractory
Painful defaecation, with or without constipation, is one of the
to, or unable to tolerate, oral supplements. IV iron must be
most common of these GI problems and is seen in all major
administered carefully under constant clinical supervision
subtypes, especially RDEB. Constipation results from strain-
due to the risks of anaphylaxis and other potential side
ing to defaecate leading to painful perianal blistering and fis-
effects. It is often a short infusion, so this one‐on‐one nursing
sures, or faecal retention due to pain or fear of defaecation.
can be arranged before admission. An Hb level of <80 g/L or
Restricted food intake or a soft blended diet, due to oral
symptoms such as shortness of breath and extreme fatigue
lesions, dental problems and dysphagia, may be lower in total
are taken as a signal to intervene with an IV blood transfu-
fibre content and, therefore, may worsen constipation. This
sion. This only provides temporary benefit, and some
situation is exacerbated by reduced physical activity [18].
patients may need to have a few transfusions per year to
Measures to normalise bowel habit include increasing
maintain a safe level of circulating Hb. Care needs to be
intake of fluid and fibre in the form of age‐appropriate fibre‐
taken when administering any IV treatment for iron defi-
rich foods and fibre‐containing feeds, and pure fibre supple-
ciency anaemia so that iron overload is avoided [19].
ments such as Optifibre or HyFibre. Stool softeners such as
The limited data on the use of erythropoietin (EPO) or an
polyethylene glycol sachets, e.g. Movicol, Laxido, are very
analogue in EB, either alone or in conjunction with IV iron,
commonly used [54] and show very good success in most
indicate that such treatments result in improvement in Hb
patients. To treat constipation it is optimal to give a regular
levels and general well‐being. However, the need for regular
dose of a smaller amount of stool softener than to give large
injections of EPO and its high cost limits its usefulness in
doses and then none; getting the right dose is trial and error
routine practice for children with EB [19].
as every patient will require a varying amount. In young
patients with mild constipation, a starting dose of ¼ sachet is
appropriate once a day, building up to twice a day, then
Selenium and carnitine: dilated cardiomyopathy
increasing the amount given gradually at these two doses.
UK guidance on the fibre requirements for children now rec-
No clear cause of dilated cardiomyopathy (DC) in children
ommends between 15 and 30 g for 2–18 year olds (with no
with EB has yet been identified [50], but poor global nutri-
specific guidance for <2 years) [55].
tional status, chronic iron overload from repeated transfu-
Fragility of the anal mucosa means that suppositories and
sions [51], low carnitine and selenium levels [51], concomitant
enemas should never be given. If clearance of faecal impac-
viral illness, chronic anaemia, coexistent renal failure and
tion or preoperative bowel preparation is required, an
medications (amitriptyline and cisapride) [52] have been
osmotic agent, given orally or via feeding tube, is preferred
proposed as possible contributors to its development. Most
[24]. In the older child, overflow incontinence can be mis-
reported cases have been fatal, and to date there is no evi-
taken for diarrhoea, and carers often reduce or stop the pre-
dence that the underlying genetic mutations in RDEB have a
scribed laxative therapy, inadvertently exacerbating the
role in the pathogenesis of DC. Annual cardiac assessment
situation. Children with faecal impaction demonstrable on
(echocardiogram and electrocardiogram and referral to a
abdominal radiograph must have their bowel evacuated
cardiologist if either of these is abnormal) should be per-
before the introduction of a further fibre source. If such prep-
formed in all children with severe RDEB and JEB to identify
arations are introduced while the child remains faecally
early changes leading to DC.
loaded, abdominal pain, GOR and vomiting will ensue, and
Serum selenium levels are difficult to interpret due to
compliance will be jeopardised [11].
potential effects of chronic inflammation as this will falsely
Constipation is very common in all types of EB patients.
reduce the serum level of selenium. Fifty‐five percent of
Occasionally, if constipation is severe and a thorough history
children with EB‐related DC did have selenium deficiency;
reveals a suspicion of non‐IgE mediated food allergy, then it
therefore, it is important to monitor closely and supplement
would be worth considering a trial period of an elimination
when appropriate [51]. Selenium supplementation reverses
diet for 8 weeks to rule this out as a cause for the constipation.
cardiomyopathy if started early in the disease p rocess [51].
A liquid formulation of selenium is available on prescrip-
tion, e.g. Selenase oral solution, and provides 500 μg/10 mL. Prebiotics and probiotics
When total plasma carnitine is normal, any decrease in free
carnitine should not be considered as a real deficiency and Food groups that are natural prebiotics and prebiotic formulas
does not represent a risk for the development of DC [17]. and powders are generally considered a safe addition to any
Other Issues 449
child’s diet and may act to potentially improve bowel function pain, itch and improved mobility [58]. A coeliac screen is
by improving overall diversity of the individual’s microbiome. appropriate in all EB patients when displaying symptoms of
Probiotics, such as probiotic yoghurt drinks, natural anaemia, constipation and diarrhoea. More research is
yoghurt or fermented yoghurt such as kefir, are popular needed into dietary restrictions in EB with outcomes and
additions to many EB family’s diets. To date the author has improved QoL weighed against the difficulties of following
no experience of a negative impact on the use of such prod- a restricted diet and the subsequent impact on nutritional
ucts; currently there is not enough evidence to routinely status.
advise giving probiotics to treat constipation [56]. Studies
have shown probiotics to be potentially beneficial in other
Protein‐losing enteropathy
areas of health, such as enhancing immune function, improv-
ing colonic integrity and reducing incidence and duration of
Protein‐losing enteropathy (PLE) and diarrhoea have been
intestinal infections, post‐antibiotic use and improvement in
described in JEB [53], mostly in those with pyloric atresia.
digestion and defaecation – all of which would be very desir-
α‐6‐β‐4 deficiency has been shown in an infant with total
able for children with EB. However, they have also been
GI mucosal separation and intractable diarrhoea [59].
associated with adverse effects such as bacteraemia, sepsis
Hydrolysed protein feeds containing mainly medium‐chain
and endocarditis [11]. It would be prudent to advise probiot-
triglycerides (MCT) as the fat source have been used empiri-
ics only in selected and carefully monitored EB children.
cally. As in the treatment of intestinal lymphangiectasia
(p. 118), the use of a predominantly MCT source of fat
Sodium decreases lymphatic flow, and its use has been suggested to
improve hypoalbuminaemia and to reduce levels of stool
In very severe cases of EB where, at birth, a high percentage α‐1‐antitrypsin in JEB [53].
of skin loss has occurred, the infant may need a period of
admission in the neonatal intensive care unit (NICU).
Gastro‐oesophageal reflux disease
Growth can be difficult to achieve at these times, and often
additional iron, zinc and other micronutrients may be neces-
GORD is very common in many types of EB [53]. GORD may
sary. Urinary sodium concentration should be measured,
start early in infancy and may remain throughout childhood.
and if <20 mmol/L the infant should be supplemented with
Recurrent oesophageal scarring by acidic gastric contents
NaCl at 1 mmol/kg/day until the urinary sodium is main-
may cause shortening of the oesophagus, which may predis-
tained around 50 mmol/L. Low sodium status may have a
pose to GORD and to stiffening of the lower oesophageal
direct impact on the ability to gain weight and should be
sphincter, fixing it in an open position and so worsening the
monitored carefully. If the dose of required NaCl is very
reflux [59]. GORD may be exacerbated by oesophageal dila-
high, it is better to split it throughout the 24 hours to reduce
tation that allows reflux of stomach contents into the oesoph-
the impact of nausea and potential vomiting.
agus, or by the introduction of gastrostomy feeding [24, 60]
When vomiting and poor weight gain are observed,
Other issues GORD should be investigated and managed in accordance
with age and symptoms as in the child without EB (p. 125).
Bowel inflammation (colitis) Nissen fundoplication (p. 152) has been used for refractory
GORD in children with EB, but there was only a temporary
The precise mechanisms responsible for the colitis seen in EB (<1 year) reduction of symptoms [53]. The surgery is believed
are not yet understood, but absence of type VII collagen that to have failed owing to abnormal structure and fragility of
is normally expressed in the colonic mucosa has been impli- the gastric mucosa.
cated. There have been reports of children with RDEB pre-
senting with explosive diarrhoea with their histological
features ranging from absence of abnormality to moderately Oesophageal strictures
severe inflammatory changes. The mechanism underlying
these changes is uncertain, but the defective cell adhesion Oesophageal strictures and dysphagia are common in patients
may result in altered epithelial cell turnover and abnormal with severe types of EB and may also be seen in patients with
mucosal permeability stimulating an inflammatory response DDEB. Every patient’s incidence of stricturing is different,
[53, 57]. Children with suspected or proven inflammatory even within the same type of EB. Lower oesophageal strictures
bowel disease are often treated with steroids and, if appro- are likely to be precipitated or exacerbated by GORD, whereas
priate, an amino acid‐based feed. upper strictures probably arise from blistering related to inges-
Suspicions that colitis is exacerbated by food antigens tion of food. The latter tend to impose ever greater restrictions
have led to regimens excluding milk, egg, wheat and soya on the textures of foods that the child is able to swallow, show-
[53] (Table 8.19). In two RDEB patients (one adult and one ing dysphagia with hard or bulky foods initially, then with
child), exclusion of gluten with concomitant low dose corti- softer foods and eventually with liquids [24].
sone is reported to have reversed compromised renal func- When an oesophageal blister or stricture is suspected,
tion and proteinuria, with a reduction in skin blistering, food consistency should be modified to tolerance with
nutritional supplementation. Moist foods of soft consistency and frequent eating, ineffective use of a toothbrush due to
are often preferred, but, if swallowing problems are more pain, extreme fragility of the oral mucosa and reduced man-
severe, foods should be puréed [15]. Sips of water between ual dexterity, side effects of some medications that cause a dry
mouthfuls are helpful. Reliance on oral nutritional supple- mouth, GORD and carers’ capabilities [19, 62].
ments (ONS) and milky drinks is paramount at this time to Dental reviews should be scheduled according to caries
prevent an acute deterioration in nutritional status. Drinking risk. Caries prevention is the dentist’s approach of choice.
while food is still in the mouth risks gagging and aspiration. This includes [19, 63]:
Oral dexamethasone can be prescribed initially, which can
• dietary changes to modify when high sugar foods and
sometimes be enough to alleviate symptoms and for the
drinks are consumed. These items should ideally be
potential blister to heal. If these measures are insufficient to
restricted to the end of mealtimes where possible and
ensure adequate nutritional intake, oesophageal dilatation
continuous sipping of sugary drinks outside mealtimes
(OD) should be considered as soon as possible.
should be discouraged
Balloon dilatation (which applies mainly radial forces),
• mechanical plaque/substrate control by brushing (using
either endoscopically or fluoroscopically, has been used very
appropriate equipment and techniques), flossing, rinsing
successfully and can often be undertaken as a day case. An
(with alcohol‐free mouth washes)
experienced team with knowledge of EB should undertake the
• adjuvant therapies that include fluoride (in toothpaste or
dilatation. Endoscopic dilatation techniques all carry the inher-
supplement) and chlorhexidine (in mouth washes,
ent risk of oropharyngeal and oesophageal trauma, potentially
swabs, sprays, gels or topical varnish)
resulting in strictures that worsen over time. Fluoroscopic‐
• protective covering of teeth using fissure sealants and
guided balloon dilatation uses larger balloons that can achieve
stainless steel crowns
a greater dilatation diameter. Once children are awake and
alert post‐procedure, they can drink. When they are comforta- Exercises for maintaining mouth opening by using ‘mouth
bly able to swallow (usually within 2–4 hours), a soft diet can expanding devices’ as well as for the tongue to maintain
be given with most resuming a normal diet within 24 hours of mobility for adequate swallowing are mentioned in the lit-
the procedure. One potential disadvantage of this procedure erature, but the author has not seen this in practice, and the
lies in the repeated exposure to radiation. This is particularly evidence for their effectiveness is lacking [64].
significant for children with RDEB who are known to be pre-
disposed to aggressive squamous cell carcinoma of the skin in
late teenage or adulthood [61]. Pubertal delay
When oesophageal strictures are too tight to allow ante-
grade passage of a guide wire, or if oral contractures Malnutrition can affect the entire hormonal system (involv-
severely limit mouth opening, a retrograde approach ing insulin, thyroid hormones, cortisol and growth hormone
through a gastrostomy may be successful. If OD is unavail- [GH] and the hypothalamic–pituitary–gonadal axis) and is a
able or strictures have not responded satisfactorily to this direct cause of pubertal delay [65]. Chronic inflammation
procedure, surgical interventions including colonic interpo- mediated by cytokines causes disturbances in the pathway
sition and the resection of localised oesophageal strictures involving GH and insulin‐like growth factor 1 (GH/IGF‐1)
with end‐to‐end anastomosis (oesophago‐colonoplasty) and the hypothalamic–pituitary–gonadal axis [66, 67].
have been very rarely used. However, these procedures Improving nutrition and growth with the use of G‐tube feed-
involve highly complex surgery and have high rates of mor- ing and OD may facilitate attainment of puberty. However,
bidity and mortality [24]. They, therefore, remain the last the introduction of such measures after adolescence may
resort for those whose nutritional status cannot be main- mean that catch‐up growth is not possible. Attention should
tained by any other means. be paid to the likely increased requirements in puberty, and
oral or G‐tube intake may need to be increased to ensure
there is no a decline in nutritional status [15]. Radiographs of
Oral manifestations the left hand and wrist to evaluate bone age can assess skel-
etal maturation and help to confirm the picture of delay.
Oral manifestations in children with EB vary markedly In girls, a pelvic ultrasound scan may be helpful to assess
depending on the specific EB type. Features include micros- uterine development and ovarian activity. Induction of
tomia (reduced mouth opening), trismus (spasm of the jaw puberty with appropriate hormonal intervention is neces-
muscles), ankyloglossia (fixation of the tongue to the mouth sary from a psychological point of view as well as to opti-
floor), malocclusion, blistering and scarring; all compromise mise peak BMD. This may prove problematic for boys as
mouth opening and the normal cleansing action of the intramuscular testosterone injections may be painful and
tongue. Teeth can be structurally defective, having little or buccal preparations may be difficult to take when microsto-
poor quality enamel that erodes easily, rendering them more mia has led to obliteration of the buccal sulci [68]. It is impor-
prone to decay and gum disease [19]. tant for young adults to attain puberty at around the same as
Other factors contributing to increased dental caries include their peers. Collaboration with an endocrinologist may be
consumption of a diet high in fermentable carbohydrate, slow necessary to achieve timely puberty.
Future Research Needs 451
Reduced mobility families develop coping strategies and deal with the changing
stresses that growing up with EB can involve.
Mobility in severe EB is frequently reduced due to complica-
tions such as fixed flexion contractures, bone and skin pain Transition from paediatric to adult care
and fatigue secondary to anaemia and poor nutritional sta-
tus [19, 69]. When longitudinal growth falters, wheelchair For young people with any severe form of chronic illness,
dependency is more likely. Consequent lack of weight bear- transition to adult services is a major life event involving the
ing compounds low BMD, and possible bone pain and loss of lifelong trusted professional carers [75]. With EB,
fractures leads to further immobility. Maintenance of a
increasing age and transition may be perceived as moving a
balance between mobility, growth and nutritional status is step closer to increasing and worsening of complications, the
challenging [47]. Assessment for bone fractures should be potential development of terminal metastatic squamous cell
undertaken periodically or when symptomatic; however, carcinoma [76] and death [70], highly sensitive issues that
often EB patients have a very high pain threshold and may are openly discussed.
not report the severity of pain you might expect from, say, a Awareness of potential transition‐related problems is par-
spinal fracture. Regular review by an experienced physio- amount, and protocols should be in place to minimise them
therapist with knowledge of EB is crucial from a young age [77]. EB clinical nurse specialists are key in liaising between
to optimise motility. parents, patients and healthcare professionals in the hospital
and community settings, and good communication between
all concerned should ease the transition process.
Psychological and psychosocial issues and QoL
It is important that a comprehensive history is provided
by the paediatric dietitian at the time of transition, such as:
The psychological and psychosocial issues affecting both
children with severe EB and their parents can be significant. • a summary of relevant medical history including oesoph-
Building a rapport over time is essential for establishing a ageal dilatations, bowel pattern, iron, bone, mobility and
relationship where families will accept dietetic advice. Tact dental status
and empathy is needed at all times during dietetic consulta- • a growth chart, ideally from birth, details of supplements
tions due to the significant demands of everyday life for tried and rejected
patients with EB. Growth and eating can often be the one • if G‐tube fed details of brand of device, dimensions, when
thing that families can work to improve, and it is very hard placed/changed, ordering procedure, problems encoun-
for families to accept that, despite their best efforts, occasion- tered, details of current feeds and feeding regimen
ally the demands of EB are so great that extra intervention is • current medication regimen including vitamins and min-
needed. This is particularly evident when discussing the erals, orally or via gastrostomy
need for a gastrostomy or weight management advice in • contact details for general practitioner and any other rel-
older children with EB simplex. Coping with the everyday evant key professionals
regimen of dressing changes, lancing blisters, pain manage- • social details – family dynamics, educational stage,
ment and medication intake can be overwhelming and can career ambitions and hobbies
greatly increase family stresses, interpersonal problems and
likelihood of depression [70].
Practices, such as rewarding the child for painful proce-
Future research needs
dures with sweet treats or compensating for eating difficul-
There are many specialist EB centres worldwide. Establishment
ties by allowing a child to drink milk from a bottle for
of collaborative studies between them greatly facilitates
prolonged years, may be detrimental to dental health and
improved practice in several areas:
appetite. Discussion of issues such as these should always be
done carefully and with understanding of the greater priori- • macro‐ and micronutrient requirements for children with
ties the family may have. severe EB
Multiple factors affect QoL for those with EB and these • appropriate biochemical and haematological monitoring
greatly depend on severity and age. The family burden has in order to implement and evaluate nutrition support
been found to be high independent of EB type or severity [71]. • validation of THINC (p. 444)
There is a validated tool to assess QoL specifically in adults • minimising the adverse effects of the inflammatory pro-
with EB [72], in addition to the family burden score (EBBoD) cess in EB as chronic inflammation impacts on anaemia,
that has been developed for families with children with EB osteoporosis and abnormal body composition
[73]. A study has found that children with severe EB express • role of dietary exclusion regimens in the potential reduc-
five main areas of distress: continually itchy skin, pain, diffi- tion of bowel inflammation
culties in participation with peers, lack of understanding by • role of pre‐ and probiotics in promoting gut health and
others and being different [74]. All these can impact on nutri- immune status in EB
tional intake, either directly or indirectly. Early intervention • techniques to better manage oesophageal disease and
with a psychologist is optimal to help patients and their stricture prevention
Harlequin Ichthyosis
Introduction frequent stages to encourage this where possible.
Breastfeeding is always encouraged and can help to build
Harlequin ichthyosis (HI) is the most severe subtype of all a maternal bond [80].
the autosomal recessive ichthyoses [78]. HI presents with a In clinical practice energy requirements appear to be
severely compromised skin barrier. It is caused by mutations higher than normal; however, there is no data on basal meta-
in the ABCA12 gene leading to defective lipid transport [78]. bolic rate (BMR) or energy requirements in these infants.
Newborn infants present with ectropion (outwardly turned A range of 130–170 kcal (545–710 kJ)/kg/day in the first
eyelids) and eclabium (outwardly turned lips), and the skin 3 months would be an appropriate target.
is formed of dense white scales separated by deep fissures Infants have very high fluid requirements and may require
[79]. Families may find it difficult to bond with the infant 180 mL/kg/day on average, and occasionally this might
due to their appearance. HI often goes undetected prenatally increase to 200–220 mL/kg/day to maintain serum sodium
[78] as the skin changes are only evident in the second levels within the normal range during particularly difficult
trimester and may only show on a 3D scan undertaken by an times. During episodes of infection or vomiting, dehydration
experienced sonographer. can quickly occur, and a low threshold for IV fluids or NG
Historically, HI diagnosis has had a very poor prognosis, feeding (if not already established) should be encouraged.
often families being offered just palliation. However, with Protein requirements are higher than normal; however,
greater awareness of the condition and good multidiscipli- there are no data on the amount needed and will depend on
nary working, including medical, nursing, dietetic, occupa- the severity of the disease at presentation; 4.0–4.5 g/kg/day
tional therapy, physiotherapy, social work and psychology, may be needed. Renal function should be monitored and
long‐term survival rates have significantly improved [79]. The protein intake graded down if indicated.
main medical management consists of treatment with retinoid
therapy (acetretin), which is a synthetic form of vitamin A.
Nasogastric feeding
The main risks to infant survival are severe hypernatrae-
mic dehydration, sepsis, respiratory failure and malnutri-
Placement and securing of NG tubing can be a difficult chal-
tion. Infants with HI need immediate transfer to a level 3
lenge. Due to the frequent application of emollients, some-
NICU where possible and placed into an incubator with
times 2 hourly, it is difficult to get dressings to stick to the
high humidity [79]. Narcotics may be appropriate for pain
cheeks to secure the tube. In addition, the nostril may be nar-
relief [79]. Twice‐daily baths to promote shedding of scales
row or blocked with skin, and this may present further
and frequent application of bland emollients (or wet wraps)
complications.
are essential to stabilise the skin [79]. Antimicrobial tech-
Techniques to secure a feeding tube:
nique is essential when applying any product to the skin:
application with a clean spoon, dispensing cream into a • The ‘lasso’ technique: This involves cutting a 2–3 cm loop
clean bowl each time, wearing sterile gloves, etc. A central band of ‘Tubifast’ or similar dressing. This is then passed
line maybe needed to administer fluids, PN or antibiotics. over the head so it is secure, paying attention to the nasal
The risk of line infection is very high, and close monitoring septum and the soft issue of the ear to ensure it is not
and swabbing are needed with targeted antibiotic treatment rubbing. The NG tube is then passed as usual, and the
as per local policy. external portion can be spiralled around the lasso over
one ear. To keep the tube more secure, a soft hat, with a
hole made for the tube, can worn by the infant if needed.
Nutritional requirements and feeding Close monitoring is necessary to ensure the tube is in the
correct position. This technique should be used with cau-
Trans‐epidermal water loss (TEWL), high skin turnover
tion in mobile babies or older children.
and infection all act to increase nutritional requirements
• The ‘dressing sandwich’ technique: This involves bath-
for energy, protein and fluids. The thickened plaques of
ing the cheek as usual, but not using emollients in the
skin may restrict chest expansion and increase work of
area to be dressed. A dressing such as ‘Duoderm’ is put
breathing too, which in turn can increase energy require-
underneath the tube, then multiple pieces of ‘Duoderm’
ments [79]. Eclabium and restricted jaw movement can
are stuck on over the top of the tube. This dressing will
lead to poor vacuum suckling/sucking, which can pre-
need changing daily if it peels away.
vent breast or bottle feeding initially and can result in tir-
ing on feeding. Due to this orogastric or NG feeding
should be commenced as soon as possible as it may be Gastrostomy placement
very difficult to meet nutritional requirements solely with
oral feeds for several months. Often the mouth will Due to the difficulties in maintaining the position of a NG tube,
improve gradually, and oral feeding should be retried at coupled with the chronically high nutritional requirements, a
Introduction 453
gastrostomy can be considered very early on and has proved • Serum electrolytes need to be monitored closely in the
highly successful. initial period. Hypernatremia can occur quickly if fluid
requirements are not met
• Serum albumin may be chronically low due to protein
Tolerance of feeds
losses via the skin. Stabilisation of the skin will improve
this. The addition of extra protein to feeds may be
The high volume of feeds required can often be difficult to
warranted
tolerate. GORD and vomiting is common and can be treated
• Sodium (Na) losses can occur through the skin and when
with anti‐reflux medications as per local policy. Patients may
serum Na levels are stable it may be appropriate to sup-
present initially with steatorrhoea, together with raised faecal
plement with Na if urinary Na is <20–30 mmol/L as per
calprotectin levels and severe exocrine pancreatic insuffi-
local policy
ciency requiring administration of pancreatic enzyme ther-
• Vitamin D levels can quickly become deficient, and sup-
apy. Measurement of faecal calprotectin and faecal elastase
plementation should be started prophylactically. Levels
could be warranted to rule out malabsorption in early life
should be monitored 3 monthly initially, then annually.
and rechecked at periods throughout infancy and childhood.
Vitamin supplements containing vitamin A should be
Breastfeeding or giving EBM should be encouraged (if toler-
avoided as this can be contraindicated when having
ated) and made a priority. If no malabsorption is suspected or
retinoid treatment
identified and additional energy and protein is required, for-
• Iron levels often need supplementing. Liquid iron
tification of EBM with standard infant formula or the use of
supplementation should start as per local policy
energy‐dense formula is indicated. If additional energy and
• C‐reactive protein (CRP) levels will often be high, and
protein is required and the infant does have malabsorption,
this may artificially show a reduction in serum zinc and
EBM can be fortified with the addition of an extensively
selenium. Careful monitoring is vital and if levels con-
hydrolysed protein formula or amino acid‐based formula;
tinue to fall then supplementation is needed
and/or a liquid high energy, high protein extensively hydro-
lysed formula can be used. If an amino acid-based formula is
required, then the feed concentration will need to be gradu-
Copper transport in ichthyosis
ally increased to provide a higher energy and protein intake.
Prolonged continuous tube feeding is often needed for the
An autosomal recessive disorder of copper metabolism char-
infant to tolerate the high fluid volumes required. Wherever
acterised by mental development delay, enteropathy, deaf-
possible oral feeds should be offered in breaks from continu-
ness, neuropathy, ichthyosis and keratodermia (MEDNIK)
ous feeding to enable maintenance of oral feeding skills.
has been recently described with patients presenting with
Weaning onto solid foods can be started as per normal
significantly low serum copper levels and ichthyosis. A
guidelines and may often be enjoyed as a positive interac-
mutation in the affected gene AP1S1 causes abnormal intra-
tion between the parents and the baby. This may also reduce
cellular copper trafficking, which subsequently affects cop-
the volume of feed needed slightly and can help ameliorate
per‐dependent enzymes leading to the symptoms of
symptoms of GORD.
MEDNIK syndrome [81]. Copper may accumulate in the
Growth may be delayed due to chronic inflammation and
liver and brain tissue causing symptoms of copper overload
high requirements and careful and ongoing dietetic monitor-
despite clinical serum copper deficiency. Liver function tests,
ing can help to optimise growth and nutritional status of
brain MRI and treatment with zinc acetate (to treat copper
patients with HI. Patients can often have their gastrostomies
overload) are suggested starting points for treatment [81, 82].
closed as they get older and are able to meet their require-
Treatment with copper supplements should be avoided until
ments orally.
a full diagnosis is made, and it can be ensured that addi-
tional copper is not going to worsen the symptoms of copper
Nutritional monitoring overload.
It would be good practice to check the serum copper levels
Close attention needs to be paid to monitoring nutritional in all patients with ichthyosis to ensure this condition is not
parameters: missed.
Netherton Syndrome
Introduction allergic manifestations [83]. NS is caused by loss of function
mutations in SPINK5 (serine protease inhibitor of Kazal
Netherton syndrome (NS) is a rare autosomal recessive skin type‐5) encoding LEKTI‐1 (lympho‐epithelial Kazal type‐
disorder, which presents with severe erythroderma, skin related inhibitor type‐5), which regulates skin barrier and
inflammation and scaling, hair shaft abnormalities and immunity [84].
There is a clinical spectrum of severity in NS. Some infants increase requirements and reduce feed tolerance. In severe
may be born with severe NS with approximately 75% of skin cases in early infancy, steatorrhoea, diarrhoea and poor feed
affected. These infants are at very high risk of hypernatraemic tolerance with very high fluid requirements can make die-
dehydration, and there is often great difficulty with establish- tetic management very difficult. Breastfeeding can be estab-
ing feeding and hence optimising their growth. Historically, lished successfully from birth and should be encouraged if
the survival rate for severely affected infants was poor, com- tolerated well. Breastfeeding may transfer important
pounded by a lack of recognition of their condition and being immune complexes to the infant. Breastfeeding or giving
misdiagnosed and, hence, not getting adequate treatment. EBM should be made a priority, and if EBM is used, this can
Some infants with NS may present with a milder phenotype, be fortified as described above (p. 440).
with less than 25% of skin affected. These infants may estab- Fluid requirements are higher than normal due to TEWL
lish feeding more easily, with a good growth projection. They and tend to remain very high throughout life. In infancy, the
may not get diagnosed as early as the severe type and may be volume required to maintain sodium in the normal range
misdiagnosed with atopic dermatitis. may be approximately 200–220 mL/kg/day. To achieve and
The main risks to survival are severe hypernatraemic dehy- tolerate this high volume, an orogastric or NG tube is often
dration, hypoalbuminemia, enteropathy, infection, poor body needed. Older patients often display high thirst levels and
temperature control, sepsis and malnutrition. Nursing or paren- enjoy drinking of large quantities of water, potentially
tal care to ensure twice‐daily baths and frequent application of impacting on appetite and nutritional intake.
bland emollients is essential to stabilise the skin. Antimicrobial During episodes of infection or vomiting at any age, dehy-
technique is vital when applying any product to the skin: appli- dration can quickly occur, and a low threshold for IV fluids
cation with a clean spoon, dispensing cream into a clean bowl or tube feeding (if not already established) should be encour-
each time, wearing sterile gloves, etc. Due to the reduced integ- aged. Adolescent patients who have been stable for many
rity of the skin barrier, topical medications are absorbed very years can become unwell with infection and quickly become
readily, so topical steroids may be contraindicated. severely hypernatraemic, requiring hospitalisation.
Greater awareness of NS and good MDT working has Energy requirements are higher than normal; however, to
improved survival rates significantly. The main difficulties date there is no evidence as to exactly what requirements
and risks to survival present in early infancy; after 1 year of might be. A range of 130–170 kcal (545–710 kJ)/kg/day in the
age the acute nature of the medical and dietetic intervention first 3 months would be an appropriate target. In severe
may stabilise somewhat, although the condition is lifelong cases of NS with extreme faltering growth, supplementary
and requires daily dedication to the skin care regimen. feeding with a high energy, high protein formula is usually
All patients with NS are at high risk of developing IgE indicated. The initial presentation of steatorrhoea, diarrhoea
(immunoglobulin E)‐mediated allergies, which does not or carbohydrate malabsorption secondary to enteropathy
appear to correlate with severity of skin affected. A charac- and/or severe exocrine pancreatic insufficiency, seen in
teristic feature of NS can be an exponentially increasing and severe cases, requires administration of pancreatic enzyme
very high total serum IgE level [85], although this may not replacement therapy. Tests, such as faecal calprotectin, sugar
always present early in infancy. chromatography and faecal elastase, could be warranted to
Infants are often born prematurely between 34 and 37 rule out malabsorption in early life and rechecked at periods
weeks’ gestation with their weight between the 2nd and 50th throughout infancy and childhood. These GI disorders may
centiles. Almost all patients will display faltering growth improve with time, and therapy can be weaned off. Growth
within 3 months of birth, with many faltering until at least may be severely delayed in such cases, and amino acid‐
1 year of age. Patients with severe disease often have chronic based formulas with a high percentage of MCT are likely to
inflammation, which has a negative effect on growth. be required. Refeeding syndrome risk may be high when
Patients with the milder phenotype may display good changing formulas so should be managed carefully.
growth within normal parameters. PN may be necessary in some cases; however, risk of line
Early nutritional intervention and monitoring may pre- infection is very high. It is often difficult to maintain a suffi-
vent poorer growth later on. Some late presenting patients, cient intake due to the increased risk of infection from
although stable, may present with chronic severe faltering bacterial presence on the skin.
growth and in some cases acute protein-energy malnutrition Protein requirements may be higher than normal due to
(PEM) [84]. The number of infections, allergic disease, enter- skin losses, although there is no data on the amount needed,
opathy, use of steroids and endocrine abnormalities may all and will depend on the severity and stabilisation at presen-
impact on growth projection [86]. More research is needed tation. The protein-energy ratio of the diet needs to be main-
into the impacts on growth outcomes in NS patients. tained at an appropriate level and a protein intake of
4.0–4.5 g/kg/day has been needed in some patients. Renal
function should be monitored and protein intake graded
Nutritional requirements down as necessary. Liquid high energy and high protein
extensively hydrolysed formulas can be effective if malab-
TEWL infection and high skin turnover all significantly sorption is identified or suspected. If amino acid‐based feeds
increase nutritional requirements for fluids, energy and pro- are required, then the concentration will need to be increased
tein. Patients are at greater risk of sepsis, which can also to provide a higher energy and protein intake.
GORD and constipation are common from infancy and eczema, rhinitis, urticaria, pruritis (itch), asthma, angi-
throughout life. Anti‐reflux medications can be used as per oedema and anaphylaxis [84, 87]. Patients may have a nor-
local policy. Constipation is likely secondary to difficulty in mal total serum IgE level at birth, often increasing
maintaining a high fluid intake. Increasing fibre intake, using significantly on each sequential measure with total serum
regular stool softeners and increasing fluid intake is often IgE ranging from 300 to 7000 kU/L. Due to the very high
successful in achieving a regular bowel motion. Weaning can total serum IgE levels, specific IgE levels can be hard to
be started as per normal guidelines and may often be enjoyed interpret correctly and may often show false positives [88].
as a positive interaction between the parents and the baby. Symptom history is very important to ensure foods are not
This may also reduce the volume of feed needed slightly and removed from the diet unnecessarily. Skin prick testing is
can help ameliorate symptoms of GORD. often contraindicated due to damaged skin. Antihistamine
Early gastrostomy placement can be life‐saving and essen- medication is often used to reduce itch and patients may
tial to maintain good nutritional status. Most patients have have allergies to a wide range of foods, environmental
been able have the gastrostomy tube removed a few years antigens and animal dander. In the author’s cohort the
after placement when intake has stabilised sufficiently. Some most common proven allergenic foods are nuts, eggs and
patients may benefit from prolonged use of a gastrostomy if fish, but patients have reported many foods to elicit aller-
helpful for optimising fluid intake. gic reactions including milk, wheat, soya, watermelon,
coconut, kiwi fruit, berries and cantaloupe melon. In very
severe cases where an infant is having breastmilk and has
Nutritional monitoring acute faltering growth, dehydration and GI involvement,
the removal of allergens from the maternal diet may be
Close attention needs to be paid to monitoring nutritional indicated to attempt to stabilise the patient’s skin and any
parameters: GI inflammation. There is no literature to support this in
NS. More research is needed to identify if allergen avoid-
• Vitamin D supplementation is essential, and rickets has
ance in early infancy or early introduction of allergens
been observed in older patients with NS. Levels can be
would be helpful to reduce later onset of allergic manifes-
monitored 3 monthly initially, then annually throughout
tations in NS.
childhood
• Iron levels may need supplementing in infancy as per
local policy Acknowledgements
• Zinc, selenium and copper should be monitored annu-
ally. A general multivitamin supplement for children The author wishes to thank Dr Anna Martinez for her
containing iron and zinc may be sufficient to maintain medical expertise and help guiding the writing of this
levels in childhood chapter and to all the remarkable children and young
• Electrolytes need to be monitored closely. Risk of hyper- adults living with EB and rare dermatological condi-
natraemia needs to be balanced with supplementing with tions. Thanks to Rosie Jones and Lynne Hubbard for their
sodium chloride (NaCl) if the urinary Na is <20–30 mmol/L ongoing collaboration and shared passion for this area of
(depending on local policy) to ensure adequate growth dietetics. Thanks also to Lesley Haynes and Melanie
• Serum albumin may be chronically low due to protein Sklar for their dedicated work and previous edition of
losses via the skin, particularly in infancy. Stabilisation of this chapter.
the skin and the addition of protein to the diet or feed
may be beneficial in severe phenotypes
Allergy
Allergic manifestations can show in approximately 75% of
all NS patients due to the diminished skin barrier, with no
correlation to severity of skin involvement. These include: www.wiley.com/go/shaw/paediatricdietetics-5e
23 Burns
Helen McCarthy and Jacqueline Lowdon
Introduction the patient’s hand (including fingers) being approximately

0.8% of the total body surface area (TBSA) [5]. This method
A review of the international Burn Injury Database (iBID) for works well with small injuries, but with increasing wound
England and Wales report estimated that between 2003 and size becomes less accurate. In adults the Wallace ‘rule of
2011 the proportion of children under 16 years of age contrib- nines’ is commonly used, and this has been adapted for
uting to admissions for a burn injury increased from 42.8% children (Table 23.2) [5]. The most common method for deter-
to 48.2%. The majority of these were a result of contact burns mining burn size in children is using the Lund and Browder
or scalds [1]. charts, which have been reproduced in many formats since
originally proposed in 1944 [5–8].
The severity of an injury combines the depth, size and
Assessment of injury other factors. In children severe injury can be classified as:
Thermal injury can be classified in a number of ways but • a major burn, defined as a full thickness injury covering
includes contact, flame, electrical and chemical burns as well an area of >10% TBSA
as scalds [2]. The main causes and types of thermal injury in • a partial thickness burn injury of >20% TBSA
children and adolescents are listed in Table 23.1. The most • burn injuries to the eyes, ears, face, hands or feet or other
common injury reported in children is a scald with contact areas that are likely to result in functional impairment
burns almost as common. Of all admissions for children • burns complicated by another major trauma or inhala-
under the age of 16 years, scalds accounted for 52.9% and tion injury [4]
60.2% (males and females, respectively), while contact burns
accounted for 21.2% and 19.1% (males and females, respec-
tively) [1]. Metabolic response to burn injury
It is well documented that the size and depth of a thermal
injury has a direct impact on morbidity and mortality [3, 4]. Thermal injury results in a marked change in metabolism
Burns are dynamic injuries that are rarely uniform in depth that is reported to last up to 12 months or longer depending
and, therefore, require continual reassessment [2, 5]. on the severity of the original injury [9–12]. Initially there is
Burn depth is generally classified as partial or full thick- a reduction in metabolic rate that lasts 3–5 days. This is the
ness. Partial thickness injuries are further subdivided into ‘ebb phase’. During this period there is evidence that the
superficial, where only the epidermis is affected; superficial requirements of the child fall below the estimated average
dermal, where the injury extends through the epidermis into requirements (EAR) for age [13]. This is then followed by the
the dermis and blistering is observed; and deep dermal, hypermetabolic ‘flow phase’ that is associated with physio-
where the injury extends through the dermis, but does not logical, endocrine and immunological changes [9–12, 14, 15].
infiltrate the subcutaneous tissue [5]. The exact cause of the hypermetabolic response remains
Burn size relates to the surface area affected by the injury. poorly defined; however, catecholamines, corticosteroids
There are a number of ways to assess burn size. The simplest and inflammatory cytokines are primary mediators with
method is the ‘palmar surface’, which is based on the palm of raised levels being observed for an extended period

post‐injury [14]. Hypermetabolism affects glucose, fat and Aim of nutritional support
protein metabolism. Burn‐induced hyperglycaemia can have
significant detrimental effects; elevated triglycerides have The aim of nutritional support in a child with a thermal injury
been associated with poor organ function, and the up‐regu- is to provide appropriate intervention in order to moderate
lation of protein catabolism with associated muscle weak- the hypermetabolic response, promote optimal wound heal-
ness prolongs the need for ventilation and can result in ing and maintain normal growth. It is well documented that
prolonged growth delay [16]. improved nutritional status in the critically ill patient reduces
Modern medical and nursing management has had the the likelihood of complications (e.g. infection, poor wound
effect of moderating the hypermetabolic response to the healing) and length of stay in hospital [22–24].
burn injury [10, 14]. These include early excision and graft-
ing, increased use of artificial skin and other novel wound
coverings, regular analgesia, control of ambient tempera- Nutritional requirements
ture, and nutritional intervention [15, 17, 18]. Nonetheless
the metabolic response remains elevated, and evidence Factors influencing the nutritional requirements of a child
clearly links this to the extent of the injury and, in children, with a thermal injury are listed in Table 23.3. A full assessment
their age and sex [19–21]. of nutritional requirements should be made taking these and
any additional factors, such as surface area used as donor sites
for skin grafts, into consideration. As thermal injuries are
Table 23.1 Causes and types of burn injury. dynamic, regular reassessment and adjustment of regimens is
essential to achieve optimal outcomes for patients.
Type of burn Cause of burn
Water Kettle, teapot, cup, mug, bath, saucepan Energy requirements

Contact Radiator, iron, oven, hot water bottle, hair straighteners
Several researchers have investigated energy requirements
Flame House fire, chip pan, electric/coal fire, barbecue
in children with thermal injuries. Although the gold stand-
Fat Chip pan, oven trays ard method for estimating energy requirements would be to
Chemical Cement, hair dye, cleansing agents, cytotoxic drugs measure them daily using indirect calorimetry and adjusting
Electrical Electrical appliances, overhead and underground cables all nutritional support to meet these figures, this is often
impractical. Calculations have been proposed to estimate
Other Overexposure to radiotherapy, frostbite, animal manure
energy requirements, and, while these are commonly used in
Table 23.2 Methods of quantifying burn surface area.
Wallace ‘rule of nines’ Lund and Browder
Adult Child <1 year 1 year 5 years 10 years 15 years Adult
Head (front and back) 18% 9% 19% 17% 13% 11% 9% 7%

Neck (front and back) 2% 2% 2% 2% 2% 2%
Chest/trunk (front) 18% 18% 13% 13% 13% 13% 13% 13%
Back/trunk (back) 18% 18% 13% 13% 13% 13% 13% 13%
Arm (front and back) 9% 9%
Upper arm (front and back) 4% 4% 4% 4% 4% 4%
Lower arm (front and back) 3% 3% 3% 3% 3% 3%
Hand (front and back) 3% 3% 3% 3% 3% 3%
Perineum 1% 1%
Genitalia 1% 1% 1% 1% 1% 1%
Buttocks (both) 5% 5% 5% 5% 5% 5%
Leg (each) 18% 13.5%
Thigh (front and back) 5.5% 6.5% 8% 9% 9% 9.5%
Lower leg (front and back) 5% 5% 5.5% 6% 6.5% 7%
Foot (top and bottom) 3.5% 3.5% 3.5% 3.5% 3.5% 3.5%
Source: Adapted from Hettiaratchy and Papini [5].

458 Burns
Table 23.3 Factors influencing nutritional requirements. Schofield equation [30] may be the most suitable for chil-
dren, but acknowledge that this is a fixed equation and will
Age
not integrate change over time. With the exception of the
Sex Schofield equation, these formulas require an estimate of
Weight body surface area and burn surface area. There are a number
Height/length of equations to aid with this estimation, but the simplest is
probably the Mosteller formula [36]:
Pre‐injury nutritional status
Current nutritional status T
otal body surface area = weight kg height cm / 3600
Percentage burn surface area
Thickness of burn Any formula is only a guideline and provides a starting
Grafted area point for estimating requirements. As already stated, ther-
mal injuries are dynamic and require frequent reassessment
Extent of healing
and amendment of nutritional requirements.
Comorbidities
Protein requirements
Table 23.4 Formulas for energy requirements. Protein requirements for children with burn injuries remain
unclear, but it is evident that these will be increased above
Hildreth/Galveston equations [28] the recommended nutrient intake (RNI) for age [37]. The
Infants <1 year 2100 kcal (8.8 MJ)/m2 TBSA + 1000 kcal hypermetabolic response to the thermal injury results in an
(4.2 MJ)/m2 BSA up‐regulation of protein turnover with both protein catabo-
Children <12 years 1800 kcal (7.5 MJ)/m2 TBSA + 1300 kcal lism and synthesis being increased. Losses of lean muscle
(5.4 MJ)/m2 BSA mass and negative nitrogen balance have both been recog-
Children >12 years 1500 kcal (6.3 MJ)/m2 TBSA + 1500 kcal nised in studies investigating the nutritional needs of this
(6.3 MJ)/m2 BSA patient group [38, 39]. Cunningham et al. suggest that appro-
Curreri Junior equations [29] priate wound healing is achievable in children receiving
Infants <1 year RDA + 15 kcal (0.063 MJ)/m2 BSA
2–3 g protein/kg/day [32]. It has also been suggested that
higher protein intakes may have beneficial outcomes in ther-
Children 1–3 years RDA + 25 kcal (0.105 MJ)/m2 BSA
mally injured children [38, 40]. However, a recent review by
Children 4–15 years RDA + 40 kcal (0.167 MJ)/m2 BSA Herndon and Tompkins states that protein intakes of 3 g/
Scofield equation [30] kg/day may raise urea production without improvement in
Girls 3–10 years (16.97 × wt) + (161.8 × ht) + 371.2
muscle protein synthesis [10].
Protein synthesis, as well as wound healing, does appear to
Boys 3–10 years (19.6 × wt) + (103.3 × ht) + 414.9
be improved when relatively higher protein provision is made
Girls 10–18 years (8.365 × wt) + (465 × ht) + 200 in combination with anabolic agents such as growth hormone
Boys 10–18 years (16.25 × wt) + (137.2 × ht) + 515.5 and oxandrolone [14, 15, 41]. Studies have reported improve-
ments in lean muscle mass, wound healing and scarring at
TBSA, total body surface area; BSA, burn surface area; RDA, 2 years post‐injury when recombinant human growth hor-
recommended dietary allowance; wt, weight in kg; ht, height in cm.
mone (rhGH) is administered during the hospitalisation,
although its use is not without side effects [15, 16]. Oxandrolone
has similarly been shown to have beneficial effects on lean
clinical practice, there is some evidence to suggest their muscle mass, muscle strength and bone mineral density [41].
accuracy is limited [25, 26]. Several amino acids become conditionally essential
Energy requirements in children with burns rarely rise following trauma, particularly burn injuries, including

above the EAR in the first 24 hours post‐burn injury [13, 27]. glutamine, arginine, histidine and cystine [24]. Most of the
Therefore, it may be reasonable to aim for the EAR for age research into supplementation of specific amino acids has
initially for all injuries, particularly those classified as minor focused on glutamine and arginine [42–44]. Current evi-
or of a small surface area. Commonly used formulas for esti- dence suggests that while there are benefits to supplementa-
mating energy requirements for children are detailed in tion of major burn‐injured patients with glutamine,
Table 23.4. These include the Curreri Junior formula and the supplementation with arginine does not appear to provide
Galveston or Hildreth formula, which have been recom- any benefits despite the role it plays in wound healing [45].
mended for some time [28, 29, 31–33]. There is recognition Recommended levels of supplementation for glutamine
that these formulas can overestimate energy requirements have not been established for children, although deficiency
and provision of excess energy and/or protein has been has been reported and further research is required in this
shown to have detrimental effects on outcomes [34, 35]. area [46]. Currently a large multicentred trial is being under-
Current guidelines from the European Society for Clinical taken to establish the role of glutamine supplementation in
Nutrition and Metabolism (ESPEN) [35] suggest that the burn injuries [34].
Meeting Nutritional Goals 459
Moderate hypoalbuminaemia is common in children with Excessive routine supplementation with a multivitamin and
thermal injuries, and this can be well tolerated. Increasing mineral preparation may result in a nutritional imbalance
protein provision above that recommended in the literature and potential toxicity, as well as interference with the utilisa-
has little impact on this. However, it has been suggested that tion of other nutrients.
if the serum albumin level falls to <25 g/L, then albumin
infusions should be considered [24, 47].
Novel substrates
Novel substrates include immune‐enhancing nutrients such

Vitamin and mineral requirements
as antioxidants, omega‐3 fatty acids, glutamine, arginine
and nucleotides. The limited number of studies has focused
Vitamin and mineral requirements at the varying stages of
on use in adults, and much of the available research has used
recovery from a thermal injury are still very much under
heterogeneous intensive or critical care unit patient groups,
debate and very few studies specifically look at the require-
which include a small number of thermal injury patients
ments for vitamins and minerals in children. Animal models
[58]. As such the current recommendation is that immune
and studies in adults suggest that requirements are increased
nutrition is not used in children [59].
for certain vitamins and minerals due to their role in the
Antioxidant therapy (vitamins A, C, E) has been shown to
metabolic pathways of the body. When assessing the nutri-
reduce burn and burn sepsis mortality in adult burns patients
tional requirements in burns patients, the following should
[60]. Omega‐3 fatty acids may impact on immune response
be considered:
and wound healing, although the anti‐inflammatory proper-
• Deficiency in vitamins A, E and C has been reported [48]. ties have led to confounding results in some studies [58, 61].
This deficiency would appear to respond well to enteral The potential therapeutic benefits of specific amino acids,
supplementation. The benefits of routine supplementa- e.g. glutamine, requires more research to establish appropri-
tion over and above meeting the RNI when deficiency is ate supplementation levels in children [34, 46].
not present has yet to be proven, with the evidence pres- These substrates are usually provided in combination
ently equivocal in this area [49]. rather than individually, and early studies have suggested
• B group vitamins are required proportional to energy some benefits both in terms of the immune‐enhancing nutri-
intake; however, little research has been undertaken so ents included and in the ratio in which they are presented
there are no clear recommendations other than ensuring alongside macronutrients [62, 63].
nutritional adequacy.
• Low levels of serum iron in most cases are not diet related
and may have a protective effect against infection.
Meeting nutritional goals
Supplementation should be closely monitored in relation
Additional factors need to be considered in a child with a
to transfusions and status [50].
thermal injury over and above those for normal healthy
• Both zinc and copper have been shown to be depleted in
children; these are listed in Table 23.5. The size and depth
serum following thermal injury. Copper supplementa-
of the injury will have a direct impact on the hypermeta-
tion can result in increased urinary losses; similarly, the
bolic inflammatory response and therefore the nutritional
role of zinc in the up‐regulated inflammatory processes
requirements of the child. The position and the psychologi-
suggests that redistribution rather than deficiency may
cal impact of the injury, including the cause, can have a sig-
explain low serum levels [50, 51].
nificant effect on compliance with dietary management
In recent years an increased incidence of fractures has strategies.
been reported in children post‐ burns injury raising aware-
ness of vitamin D deficiency in this group. It has been sug-
gested that risk factors for vitamin D deficiency include lack Table 23.5 Factors influencing the achievement of nutritional
of sunlight exposure, reduced intake and poor absorption requirements.
post‐injury, coupled with a pre‐injury insufficiency [52, 53]. Percentage burn surface area
Current evidence suggests that standard supplementation of
Site of injury
vitamin D is not sufficient to correct deficiencies seen in
burn‐injured children; however, the provision of therapeutic Pre‐existing clinical conditions
doses routinely has not been proven [54–56]. Previous nutritional status
While it is generally recommended that multivitamin sup- Special dietary needs
plementation be given as standard, the enteral route has
Gastrointestinal function
limitations as the route of administration and doses required
are unclear for many of the key micronutrients [34, 35, 57]. Pain management and sedation
Before a vitamin and mineral supplement is considered, it is Pyrexia
important to check the nutritional composition and bioavail- Periods of fasting
ability of enteral and/or parenteral nutrition (PN) interven- Psychological distress
tion, in conjunction with the biochemical status of the child.
460 Burns
Minor burns (<10% body surface area) periods related to surgical intervention, dressing changes,
physiotherapy and medications. Several studies within a
A ‘food first’ approach should be taken with minor injuries critical care environment have demonstrated suboptimal pro-
of <10% surface area (not including the face) and if the child vision of nutrition support; therefore, effective communica-
does not have a compromised nutritional status pre‐injury. tion and team working are imperative to the nutritional
The child should be encouraged to start eating and drinking management of children with thermal injuries [74].
as early as possible, and every effort should be made to pro- PN should only be considered when there is prolonged
vide familiar foods in order to promote appetite. Nutritious paralytic ileus or where poor tolerance of enteral feeding
drinks such as milk and milkshakes, in preference to juice or prevents nutritional requirements from being met by this
fizzy drinks, should be encouraged. route alone. Where possible, trophic enteral feeds should
Daily food and fluid intake should be accurately recorded continue to be infused at a very low rate (as little as 2 mL/
by nursing staff. If this highlights difficulties in meeting the hour) to maintain the brush border integrity of the gastroin-
dietary targets, alternative nutritional intervention may be testinal tract [24, 75, 76]. The complications of PN are well
necessary. A multivitamin supplement or an oral nutritional recognised, and as infection risks are already high in burns
supplement (ONS) may be beneficial in this group if accept- patients, special care must be taken when considering PN.
ance of hospital food is limited. Other issues, such as electrolyte imbalances and hypergly-
caemia, also require particularly close monitoring. Further
guidance on enteral and PN support in children may be
Major burns (>10% body surface area) found in Chapters 4 and 5.
In a major thermal injury, an enteral feeding tube should be

passed during the resuscitation period, and also where the
Choice of oral and enteral feeds
injury is complicated by smoke inhalation, the injury is
The choice of feed will vary depending on the age of the
extensively to the face or where additional trauma has been
child, the calculated requirements, any unrelated medical
incurred. Many studies report that early enteral feeding of
condition and the clinical course during admission. There is
burns patients (within the first 6 hours) reduces the inci-
some evidence to suggest that the use of high carbohydrate,
dence of paralytic ileus and may moderate the hypermeta-
high protein, low fat feeds may improve protein synthesis
bolic response [64–66]. However, a Cochrane review on early
and muscle mass accretion, although such feeds are not rou-
versus later initiation of enteral feeding found that the ben-
tinely used in the UK at the present time [10, 77]. A 2012
efits were inconclusive as only three studies met their inclu-
Cochrane review concluded that there were limited ran-
sion criteria [67]. Other benefits of early enteral feeding
domised controlled trials on optimal feed composition and
include maintenance of gut integrity and a reduction in
further research is, therefore, required [78].
bacterial translocation, as well as improvements in immune
As the child’s condition improves, the move from enteral
status and wound healing [64–66].
feeding to oral diet, with or without supplementation,
Current practice in most UK centres is to commence con-
should take place as a managed process. Weaning from
tinuous enteral feeding at a low rate and increase as toler-
enteral feeding is challenging requiring team work and clear
ated, aiming to achieve full requirements within the first
communication between the healthcare professionals, the
24–48 hours post‐injury. This should be done cautiously and
family and the child. Much of the published work on wean-
be guided by the severity of the thermal injury. While pub-
ing from enteral to oral nutrition is related to children with
lished studies have failed to demonstrate irrefutable evidence
long‐standing feeding aversion and not short‐term nutrition
of the benefits of early feeding, there are reports of feed‐
support [79]. Enteral feeds should be reduced gradually to
related intestinal necrosis, and thus for more severe injuries
encourage oral intake, but nutritional requirements should
just trophic feeding in the early phases may be indicated [68].
continue to be met; simply stopping the enteral feed without
Nasogastric feeding is routinely used in many centres, but
adequate oral intake being established increases the risk of
where this is poorly tolerated, as demonstrated by increased
nutritional deficiency and wound breakdown.
gastric aspirates, transpyloric feeding should be considered
Examples of oral nutritional supplements and enteral
[69, 70]. Delayed gastric emptying and gastric aspirates in
feeds are given in Tables 4.3 and 12.5.
excess of the hourly feed rate are closely correlated with
ileus, infection and sepsis [71]. Diarrhoea occurs frequently
in children with burn injuries but appears to be more closely Monitoring and outcomes
related to the use of broad spectrum antibiotics rather than
feed osmolality or volume [72]. It has been suggested that Objectively assessing the success of nutritional support of a
the use of prebiotics and probiotics may have a beneficial burns patient is difficult, as the endpoint is global and incor-
effect on gut flora, thus reducing the incidence of diarrhoea; porates many variables. Commonly used variables include
however, the timing and dose, as well as the most effective body weight, nitrogen balance, lean body mass measure-
strain, remains unclear [73]. ments, biochemistry and measurement of serum proteins.
Optimising nutrient provision via enteral feeding can prove Functional measures, such as exercise tolerance, are also pos-
difficult as feeding regimens must take into account fasting sible measurements.
Monitoring and Outcomes 461
It is important to remember that burn injuries are dynamic levels are depressed acutely and chronically, despite success-
and this patient group has constantly changing nutritional ful nutrition, making it a poor marker [86]. Prealbumin has a
needs related to the healing of their wounds. As the percent- short half‐life of 2 days, which should make it more respon-
age burn surface area changes, so the nutritional require- sive to nutritional changes. However, the level falls quickly
ments need to be reassessed. There is no one method that is after a burn injury and recovers slowly, meaning that it may
universally reliable or applicable for the nutritional monitor- not correlate well with ongoing nutritional status [87].
ing of paediatric burns patients. It is important that the Raised serum levels of C‐reactive protein (CRP) can act as a
overall clinical picture is incorporated into the assessment. predictor of sepsis in children with burns injuries [88].
Body weight Vitamin, mineral and trace element status
Body weight is a common measure of nutritional status as it Vitamin, mineral and trace element status should also be
is easy to obtain and can be related to the general paediatric monitored in extensive burns injuries as evidence of defi-
population; however, it can be very misleading in burns ciency has frequently been reported in the literature [48–54].
patients. The initial fluid resuscitation after severe burn will Guidelines for monitoring blood parameters in burns
increase body weight, and although this will eventually lead patients have been developed by several of the regional burn
to diuresis, the time period is unpredictable [80]. Additional networks and local policy should reflect these.
fluid shifts occur with infections, ventilator support and
hypoproteinaemia, making body weight a very unreliable Imaging techniques
gauge of nutrition in this population. Patients can have
increased total body water for weeks after the burn injury, Although a few imaging techniques are now available for
masking the loss of lean body mass that will have occurred nutritional monitoring, due to availability and cost, they are
[81]. Regular weights (without dressings) should be recorded typically used in research only. Bioelectrical impedance anal-
and plotted on appropriate centile charts. These should be ysis calculates total body water and the body’s fat‐free cell
compared with pre‐admission measurements where available; mass by measuring the body’s resistance to the passage of
asking parents and caregivers for these weights can be help- electrical currents. However, it is unknown how the fluid
ful. Long‐term monitoring of trends in weight are valuable, shifts after a burn injury affects this measurement.
especially during the rehabilitation phase. It is important to
remember that oedema and fluid shifts may mask true Changing clinical condition
weight and any loss of lean tissue early in the clinical course.
Studies in severely burned children found that increasing The clinical condition of the child is constantly changing and
energy intake to maintain weight resulted in increased fat includes aspects such as burn area and healing, temperature,
mass instead of improved lean body mass [51, 82]. infection and sepsis, ventilation issues and rehabilitation pro-
grammes. All of these should be closely monitored and require-
ments recalculated on the basis of these changing factors.
Biochemistry
Routine biochemistry should be monitored. Frequency of Feed intake and tolerance

monitoring will vary depending on the child’s clinical course.
Feed intake and tolerance should be closely monitored.
Prescribed versus actual intakes can vary for a number of rea-
Protein sons and under-delivery of nutrition is a commonly recognised
problem [74]. Aspirate volumes and bowel motions (frequency
Adequate protein intake is extremely important after a burn and consistency) should be recorded accurately. Adjustments
injury. Measurement requires accurate urine collection to to feeding regimens, including rate, type of feed and route of
determine urine urea nitrogen (UUN) as well as documenta- administration, may be beneficial. As the child moves from
tion of dietary nitrogen intake [83]. Nitrogen balance for enteral to oral nutrition, intakes should be recorded accurately
burns patients can be approximated with the following for- to ensure adequate nutritional intake is being achieved.
mula although this has been shown to underestimate nitro-
gen losses [84, 85]: Nutrition post‐discharge
Nitrogen balance = nitrogen intake in
Monitoring of nutritional intake and overall nutritional status
24 hour 1.25 UUN + 4 should continue post‐ discharge. Changes in the medical
management of burns patients have resulted in earlier dis-
In practice the collection of UUN is rarely done with the charge home, with follow‐up being provided within the com-
measurement of serum proteins, such as albumin and preal- munity or at outpatient clinics. The hypermetabolic response
bumin, more commonly used. However, these are not with- has been demonstrated to continue for 12 months or more fol-
out their limitations. After a burn injury, serum albumin lowing a burn injury [9–12, 89], putting these children at risk
462 Burns
of longer‐term nutritional deficiencies and growth failure population. This causes further imbalance in calcium and
[89–92]. It should also be noted that even with adequate nutri- vitamin D levels. Studies of paediatric burns patients have
tional intake, poor growth often continues to be an issue. In found that supplementation with a multivitamin containing
these circumstances, children exhibit increased body fat 400 IU of vitamin D2 did not correct vitamin D insufficiency.
stores, but no significant increase in lean body mass [12, 92]. More research is required to determine benefits of supple-
Specifically, with major burn injuries, bone health should mentation and optimal levels [54, 93, 94]. The use of dual
be reviewed longer term with studies reporting significant X‐ray absorptiometry (DEXA) scanning is another imaging
increases in long bone fractures post‐injury [52]. Paediatric option, which can measure bone density and lean body mass.
burns patients can suffer significant dysfunction of calcium Long term follow‐up and monitoring of nutritional status
and vitamin D homeostasis for a number of reasons including and intake should be integral to the dietetic management of
increased bone resorption, osteoblast apoptosis ( programmed burn injuries, particularly those falling into the major burn
cell death) and urinary calcium wasting. Additionally, burned classification.
skin is not able to manufacture normal quantities of vitamin D3, A case study of a young girl with a mixed thickness scald
the main source of vitamin D for the majority of the is described in Table 23.6.
Table 23.6 Case study: A young girl with a mixed thickness scald.
A girl aged 2 years and 11 months old has sustained a 12% mixed thickness scald (7% full thickness, 5% partial thickness) to the lower legs and feet as
a result of being placed in a bath of hot water.
On admission
Weight = 12.85 kg (25th centile). Estimated height = 92 cm (25th centile)
Blood results are within the normal range, and there is no history of iron deficiency anaemia.
She eats three meals plus supper daily and has no noted dislikes or food intolerance. Usual dietary intake is reported to be ‘children’s food’ such as
chocolate‐based breakfast cereals, ham or cheese sandwiches, chicken nuggets and chips or sausage and mashed potatoes. Reported portion size
appears appropriate for age. Drinks are mainly diluted juice or fizzy drinks. No additional vitamin or mineral supplements are taken.
She is receiving pain medication and is currently sedated.
Nutrition assessment
From the information presented, this child had a reasonable intake of food prior to her injury, although the nutritional quality may not have been
adequate. Anthropometric measurements and biochemical results are all currently in the normal range. Sedation and pain management is likely to
reduce dietary intake in the early stage of management.
Calculating requirements
Total body surface area (TBSA)
weight × height / 3600
2
12.85 92 / 3600 = 0.57 m
Burn surface area (BSA)

=12 % × 0.57 = 0.068 m2
Requirements using the Hildreth/Galveston equation:
Energy: 1800 kcal (7.5 MJ)/m2 TBSA + 1300 kcal (5.4 MJ)/m2 BSA
= 1114 kcal (4.6MJ)
Protein: 2–3 g protein/kg
= 26–39 g protein
Fluid: 1140 mL
Requirements using the Schofield equation: (kcal/day) in infants from 0–3 years
Female BMR = 16.25 × Wt + 1023.2 × Ht − 413.5
= (16.25 × 12.85) + (1023.2 × 0.92) − 413.5
= (208.8 + 941.3) − 413.5
= 737 kcal
BMR, basal metabolic rate; Wt, body weight in kilograms; Ht, length/height in metres.
There is a difference of approximately 400 kcal between the two different equations. While ESPEN [35] recommend the Schofield equation [30], it has
to be remembered that it may underestimate requirements as it calculates BMR and does not account for energy requirements for activities of daily
living or the impact of disease and injury. This, coupled with reduced feeding days due to theatre visits and changes of dressings, could significantly
reduce a patient’s nutritional intake and ability to meet their requirements.
Monitoring and Outcomes 463
Nutritional intake is likely to be inadequate to meet requirements specifically for protein, vitamins and minerals, related to increased nutrient
requirements and poor dietary intake post‐injury, as evidenced by the extent of injury requiring sedation at present, and dietary history indicating
energy dense, nutrient poor dietary intake pre‐injury.
Nutritional intervention
Nutritional prescription is for a nutrient dense intake to meet requirements. Initially this will be met via nasogastric feeding and oral intake. In deciding
the nutritional prescription, the following points should be considered:
• Site of injury – Lower legs, therefore, not likely to directly compromise oral intake.
• Percentage burn area – This is >10% and is, therefore, a major burn.
• There is no previous medical history of note
• Previous nutritional status – reasonable, possibility of vitamin insufficiency, particularly vitamin D.
• No gastrointestinal problems.
• Pain management – As a result of the injury, the child will be in a great deal of pain and will be commenced on pain relief; this should be
considered when planning intervention.
• Pyrexia – none noted yet.
• The child is scared and unsure of what is happening to her.
Method of feeding
An enteral feeding tube should be passed during the resuscitation period. Enteral feeds should commence within 6 hours of admission via this route,
until such time as the child is able to feed orally. Enteral feeds should gradually be replaced by oral intake to meet full nutritional requirements. Good
oral hygiene should be maintained throughout.
Choice of feed
• A fibre containing 1 kcal (4 kJ)/mL paediatric enteral feed. The advantage of this option is a nutritionally complete feed that should meet all nutritional
requirements without modification. A fibre containing feed is recommended from initiation due to the high risk of constipation in patients with burn injuries.
This is due to significant fluid shifts and losses as a result of the injury and high doses of sedatives and opioids frequently required for analgesia [35].
• The final feeding regimen should be planned in conjunction with medical and nursing management taking account of times of dressing changes,
physiotherapy sessions and other interventions.
• If taking anything orally, or as oral intake begins, encourage nutrient dense foods that are familiar and acceptable to the child. Encourage high
protein foods. Avoid diluted juice and fizzy drinks; encourage milk‐based drinks or oral nutritional supplements instead.
Nutrition monitoring and evaluation

Review nutritional requirements weekly; this should take account of the following:
• Dressings are changed twice weekly. The child should be weighed and the degree of healing assessed on each of these occasions. Nutritional
support should be reassessed according to these factors.
• Nutritional biochemical markers should be requested and monitored weekly in the early stages of recovery and then as necessary to ‘fine tune’
dietetic intervention and promote a positive outcome.
• A possible side effect of analgesia is constipation; bowel habits should be monitored closely and fibre‐enriched feeds considered.
• Increasing oral intake should be monitored through dietary intake records.
At the point of discharge the child should be reassessed and a new nutritional care plan put in place. At this time, she is likely to be eating better, but
care needs to be taken in terms of overall energy intake and adequacy of micronutrient intakes, particularly vitamin D. Input should be guided by
progress, but at every appointment with the burns team, a weight and height should be recorded, and dietary intake should be considered. Longer‐
term use of a multivitamin and mineral supplement, particularly if the oral diet is limited, should be recommended.
Learning points: nutrition in burns and thermal injury References, further reading, guidelines, support groups
• Early intervention in the form of enteral feeding within 12 www.wiley.com/go/shaw/paediatricdietetics-5e
hours of injury to maintain gut integrity
• Regular reassessment of nutritional requirements to account
for healing of burn and graft sites and changing oral intake
• Follow‐up post‐discharge should consider body composition
and bone health
24
Lisa Cooke and Julie Lanigan
Faltering Weight
Introduction Defining faltering weight
Growth monitoring is the cornerstone of paediatric care. In infancy and early childhood, faltering weight is identi-
Faltering weight may be a marker of undernutrition or fied by downward centile crossing. The degree of centile
disease, and early recognition allows prompt intervention crossing that would lead to concern depends on birthweight
to protect short‐ and long‐term health. Therefore, regular (Table 24.1).
monitoring is advised throughout infancy and early Weight below the 2nd centile on the UK‐WHO 0–4 years
childhood [1]. and UK 2–18 years growth charts indicates faltering regard-
less of birthweight. Infants and children exhibiting the growth
patterning described in Table 24.1 are at risk of growth falter-
Definitions
ing, and regular monitoring is recommended [6].
Failure to thrive (FTT) is an outdated term previously used
to describe infants and young children who failed to reach
Further measurements
their expected growth [2]. This definition is still used by
some clinicians and researchers. However, ‘faltering growth’
Where there is concern about growth faltering, weight
or ‘faltering weight’ is now the most widely accepted defini-
should be measured and plotted on the relevant growth
tion for infants and children with inadequate weight gain.
chart. Previous measurements should also be plotted to
allow a longitudinal assessment of growth. In addition,
Growth assessment length (in infants and children under 2 years of age) and
height (in older children) should be measured. Where there
Growth charts are used to compare measurements in chil- are concerns regarding a child’s length or height, parents’
dren of the same age and sex. It is recommended that inter- height should be measured, and the mid‐parental height
national growth standards are used, which are based on centile (MPC) calculated. If the child’s length or height is
infants and children growing under optimal conditions in a more than two centile spaces below the MPC, this could
range of settings, i.e. the WHO Child Growth Standards [3]. suggest undernutrition or a growth disorder [7]. Head cir-
The UK‐WHO 0–4 years growth charts combine data from cumference is also a useful indicator of growth in the first
the WHO standards with UK term and preterm data. The 2 years of life.
UK 2–18 years growth charts combine data from the UK 1990 Mid‐upper arm circumference (MUAC) is a useful anthro-
growth reference for 4–18 years with the WHO standards for pometric measure of nutritional status that can be done sim-
2–4 years [4]. Growth is monitored according to progression ply with minimal equipment. Data show that in a
along centiles [1, 3]. The growth of healthy infants and chil- well‐nourished population, there are very few children aged
dren will normally follow an established centile from about 6–60 months with a MUAC less than 115 mm. Those with a
2 weeks of age. However, small deviations are common and MUAC less than 115 mm have a highly elevated risk of death
not always a cause for concern [5]. compared with those who are above this cut‐off [3].

Causes 465
Table 24.1 Centile crossing relative to birthweight. Table 24.2 Factors contributing to faltering weight.
Birthweight centile Fall across weight centiles causing concern • Inability to digest or absorb nutrients
⚬⚬ Coeliac disease
<9th centile One or more centile spaces* ⚬⚬ Cystic fibrosis
• Excessive loss of nutrients
9th–91st centile Two or more centile spaces
⚬⚬ Vomiting
>91st centile Three or more centile spaces ⚬⚬ Chronic diarrhoea
⚬⚬ Protein‐losing enteropathy
*A centile space is the distance between two adjacent centile lines. • Increased nutrient requirements due to underlying disease
⚬⚬ Chronic cardiac or respiratory failure
⚬⚬ Chronic infection
• Inability to fully utilise nutrients
Growth charts are the most reliable tools for identifying
⚬⚬ Metabolic disease
faltering weight. However, the following features are com- • Reduced intake of nutrients
monly reported in association with weight faltering: ⚬⚬ Functional problems
⚬⚬ Suck–swallow incoordination
• muscle wasting, poor skinfold thickness
⚬⚬ Oral hypersensitivity
• thin, wispy hair
• visible or prominent bones (e.g. pointed chin in a baby)
• pale complexion (could suggest iron deficiency)
Table 24.3 Factors contributing to inadequate intake.
• poor sleep pattern
• developmental delay (particularly in communication skills) • Delayed/problematic progression of solids
• emotional and behavioural issues (ranging from with- • Early feeding difficulties, e.g. tube feeding, gastro‐oesophageal reflux
drawn/passive to active/chaotic with poor concentration) • Poor appetite following illness or dental problems
• Parental attitudes to food and feeding, including cultural practices
Research has shown that health professionals do not • Behavioural difficulties, e.g. coercive feeding
always recognise faltering weight. Batchelor and Kerslake • Limited or rigid parenting skills
found that one in three children whose weight had fallen • Parental ill health, e.g. maternal depression
substantially were not identified [8]. There were various rea- • Family characteristics, e.g. chaotic household and lack of routine,
poor facilities, neglect
sons for non‐recognition: lack of awareness of the problem,
well‐cared‐for children with no signs of physical neglect, no
reported feeding difficulties, acceptance of children as small
and underuse of growth charts. Children with neurological dysfunction may have prob-
The prevalence of faltering weight varies between and lems with oromotor development, which can affect the abil-
within populations and is influenced by socio‐economic fac- ity to suck and swallow. They may also suffer from oral
tors. For example, 5% of infants living in deprived inner city hypersensitivity and therefore refuse to feed. Children with
areas are affected, but it occurs across a wide social range [9]. metabolic disorders can present with faltering weight as a
result of poor feeding or inability to utilise energy correctly.
Faltering weight is common in infants born prematurely;
Causes
their special nutritional needs and oromotor problems are
reviewed separately (p. 96).
Historically, the focus has been on differentiating faltering
For children with poor weight gain and no apparent medi-
in weight as ‘organic’ (resulting from an underlying medi-
cal problem, inadequate energy intake is the underlying
cal condition) or ‘non‐organic’ (related to unknown psycho-
cause. Many factors contribute to inadequate intake as dis-
social factors). It is now clear that only 5% of cases of
cussed below (Table 24.3).
faltering weight have an underlying medical problem. The
two categories are not mutually exclusive, and undernutri-
tion is recognised as the primary cause of poor weight gain Early feeding problems
in infancy [10].
During infancy and early childhood, relative energy and For many infants, growth begins to falter around the time of
nutrient requirements are high to support rapid growth. complementary feeding. During complementary feeding the
Infants and young children are at risk of nutritional deficien- diet is expanded to include a wider range of foods aiming to
cies due to feeding difficulties and, in a minority of cases, establish a diet that meets nutritional requirements. As the
food insecurity. For some children, medical conditions may infant’s oromotor skills develop, this allows the introduction
be the underlying cause of growth faltering (Table 24.2) [11]. of new foods with a wider range of tastes and textures.
Despite an apparently adequate intake, gastrointestinal Complementary feeding is a time when infants become
disorders may lead to faltering weight because of malabsorp- accustomed to new foods. If this period of acceptance of new
tion, e.g. coeliac disease. Children with congenital cardiac or foods, in particular those with more ‘lumpy’ textures and
respiratory defects may show poor growth due to breathing bitter tastes, is interrupted, progression through the intro-
problems, anorexia or increased energy requirements caused duction of solid foods can be difficult and may compromise
by their disease. the nutritional adequacy of the diet. Overdependence on
466 Faltering Weight
cow’s milk and fruit juice is common in infants and toddlers. prepared to offer their children [19]. In another study, infants
This may restrict intake of solid foods, leading to insufficient of mothers who were both depressed and deprived showed
energy intake to support normal growth [12, 13]. poorer weight gain [20].
As complementary feeding progresses, infants show
increasing independence and a desire to self‐feed. It is
Poverty
important that infants are given opportunities to develop
self‐feeding skills.
Poverty is not a factor in isolation, and there is little evi-
Infants and young children with faltering weight are
dence to suggest an increased risk of faltering weight in the
reported to experience more feeding problems compared
poorest families [20]. However, it has been suggested that
with those growing normally [14]. In a case–control study,
children from larger families are at increased risk of weight
infants with faltering growth were introduced to solids and
faltering [7].
finger foods later than a control group and were described as
variable eaters with low appetite and poor feeding skills.
While causality could not be defined from this observational Neglect and abuse
study, findings suggest that feeding difficulties may increase
the likelihood of faltering weight [15]. Two population studies found that between 5% and 10% of
Faltering growth is often accompanied by chronic feeding children who had faltering weight were registered with
difficulties [14]. For example, one study found that children social services as having suffered abuse or neglect [15, 21]. It
with faltering weight also had severe feeding difficulties, is suggested that children in abusive or neglecting families
according to parental reports. Parents described stressful are at an increased risk of faltering weight, but these families
mealtimes, children crying, clamping their lips, turning away, only represent a small proportion of all cases.
pushing food away, spitting out food and being sick [16].
Behavioural feeding problems, including food refusal,
Outcomes for children with poor weight gain
can present at an early age, and there are many contributing
factors [17]. One of the earliest forms of infant communica-
Nutrition in the early years of life is a major determinant of
tion occurs during feeding, with the caregiver and infant
growth and development and influences future adult health
responding and reacting to each other. When interactions
[22]. Evidence suggests that poor weight gain from birth to
are appropriate, feeding is termed responsive. However,
6–8 weeks of life is a stronger predictor of developmental
parental feeding interactions may be affected by worry, anx-
delay than poor weight gain over the remainder of the first
iety or concern about a child’s intake and will influence how
year [23]. A meta‐analysis found that infants with early onset
a child reacts to food. Feeding cues relayed by the child, e.g.
faltering weight were likely to be shorter and thinner than
signalling discomfort, might not be appropriately inter-
age‐matched peers. Evidence supporting adverse effects of
preted by the caregiver. For young infants with gastro‐
early faltering on later growth and intellectual development
oesophageal reflux, food might well be associated with
was not strong. However, it was acknowledged that poor
vomiting and pain. Feeding can then be an unpleasant expe-
growth could be an important marker and indicate the need
rience, leading to food refusal. There are many reasons for
for intervention in children where there is neglect, a medical
food refusal including extreme temperatures of food, inap-
condition, developmental problems or feeding issues [24].
propriately sized pieces, insensitive feeding or reluctance of
Early home intervention has been reported as mitigating the
parents to allow the child to feed themselves fearing an
effects of faltering weight [25].
inevitable ‘mess’. If the child has dental caries, then pain
may be a factor. Feeding problems can cause severe distress
and disruption to family life and if unchecked can lead to Assessment of faltering weight
persistent weight faltering.
Health visitors, with appropriate training, are ideally
placed to identify children with faltering weight when they
Family and maternal influences undertake routine child health checks. In the UK, babies are
weighed at birth, 8, 12 and 16 weeks, 1 year and at school
Some studies have focused on psychosocial characteristics of entry. If there is concern, they should be weighed more
the family and the environment of the child with faltering often (p. 2).
weight. Parents’ inability to provide emotional nurturing A holistic assessment, preferably undertaken at home,
may well contribute to the problem. Family conflict before should evaluate a child’s intake, feeding behaviour and fam-
the age of 7 years has been shown to have a strong and sig- ily circumstances. The health visitor can provide a detailed
nificant association with slow growth [18]. picture of family life, where it is not possible for this to be
Maternal attitudes towards food and feeding have been completed by a dietitian. The paediatric dietitian can help to
shown to have an influence on the eating habits of children. clarify any dietary concerns and assess nutritional adequacy.
McCann et al. reported that mothers of children whose Should the child appear to have affected oromotor skills,
weight faltered showed greater dietary restraint, both con- assessment by a speech and language therapist (SLT) may be
cerning what they ate themselves and what they were beneficial. If available, joint consultations with the SLT and
Assessment of Faltering Weight 467
dietitian can not only save time but can also offer reassur- Table 24.4 Poor feeding techniques.
ance and reduce anxiety for the family.
A multidisciplinary team approach has been advocated • Infant fed with a bottle in a semi‐lying position
• Infant fed with a bottle while asleep (‘dream’ feeding)
where the medical and psychosocial aspects are combined
• Anxious parent following the child around with food or forcefully
into a clear focus on food and feeding [26, 27]. A full paediat- feeding a child
ric assessment can be undertaken including medical and • Excessive cleaning of the child with every mouthful of solids
feeding history, dietary intake and psychosocial and devel- • Dummy (pacifier) or infant bottle available at any time
opmental aspects. Potential members of a multidisciplinary • Child discouraged from participating in feeding itself
feeding team include: • Child chastised with threats or punishment for not eating
• paediatrician
• paediatric dietitian Observing a child eating is useful to obtain more informa-
• specialist health visitor tion about:
• clinical psychologist • seating of the child and parent positioning
• nurse/nursery nurse • child’s interest in its own food or food of other family
• SLT members
Joint working enables discussion of individual cases and • quantity, texture and type of food offered and what is
close cooperation between families and professionals. eaten
Clinical investigations only need to be undertaken if there are • child’s desire or ability to feed or drink by themselves
any suggestions of symptoms in order to exclude organic dis- • child’s oromotor function and self‐feeding skills
ease and to reassure anxious parents. The feeding clinic‐style • interaction between the child and parent, including
approach is resource costly, although offers a really good parental response to child’s cues
approach to managing ongoing difficulties. There are very • communication between the child and parent, e.g. verbal
few of these services available, but when in place they offer a encouragement
‘one‐stop shop’ with opportunities for positive outcomes. • atmosphere and emotions at mealtime
If there is a specialist team available, it is possible, with
Dietary assessment parental agreement, to video mealtimes. This is difficult to
do unless home visits for appointments are possible.
It is important to construct a complete picture of all aspects However, most parents have smart phones and may be able
of and influences on the child’s feeding. Early feeding his- to bring short videos of their child feeding into clinic.
tory, together with the start and progression of solids, will Observations of mealtimes can allow parents to see feeding
help to identify if there were problems in the first year of life. from a different perspective. For example, a parent who
Dietary recall with further information on the variety, tex- viewed a feeding session made the following comment:
tures and frequency of foods offered and eaten, mealtime ‘Well I’m not surprised she’s not eating. I didn’t realise I was
routines and drinks taken through the day will all help in the so forceful. If someone tried to feed me like that, I wouldn’t
assessment of the child’s current intake. It is important to eat either’. When parents are able to suggest changes and
understand the family practices and dynamics around food contribute to the management plan, there is a greater chance
as these are important factors that may influence poor intake of success. A mealtime video helps the dietitian to support
in the child. Information on where food is purchased and its the parents with positive adjustments to feeding. Feeding
preparation within the home will also help in understanding observations can also highlight ineffective feeding of an
which strategies will best fit the family and their lifestyle. infant or young child (Table 24.4), allowing issues to be sen-
Discussion with the parent/caregiver will identify how long sitively raised with parents.
mealtimes last and whether they are stressful. Gathering It is important to listen to parental concerns and their view
background information will help to identify any difficulties should be taken into account. It is also useful to know who
experienced by the family. else is involved in the care and feeding of the child. For some
There is little research on the dietary intake of children children, with parental agreement, it is useful to observe the
with faltering weight. One study raised the difficulties in child’s behaviour around food in a setting other than the
collecting dietary information and suggested that only a home, e.g. nursery, children’s centre or school. This can help
minority of children with faltering weight will have dietary identify differences in eating and feeding, adding further
histories that are obviously inadequate, but that wider rang- valuable information to a supportive action plan for the
ing nutritional assessment will be more revealing [28]. family.
A food diary is a useful tool in supporting nutritional
assessments and can provide information on the quality of Assessment of oromotor function
diet and help identify dietary inadequacies [29]. Food dia-
ries that have been validated for use in children are availa- For a small number of children who may have neurodevel-
ble from Nutritools and can be downloaded from their opmental problems or continue to exhibit food refusal and
website [30]. faltering weight, it is important for a SLT to assess oromotor
function. Such assessments, often in conjunction with video- • to improve protein and energy intake
fluoroscopy, will identify those who are unable to coordi- • to promote weight gain enabling catch‐up and allowing
nate their suck–swallow reflex. These children are likely to optimum growth
aspirate feeds and may require nasogastric or gastrostomy • to correct nutritional deficiencies and achieve an ade-
feeding. The SLT will also detect oral hypersensitivity and be quate nutritional intake
able to help with desensitisation programmes. In certain
If a child is underweight for height and failing to gain
areas, occupational therapists (OT) lead on oral desensitisa-
weight at the expected rate, whatever they are consuming is
tion programmes. Joint appointments with the dietitian, SLT
not enough for their needs. Working in partnership with par-
and OT can help with children who have physical issues
ents and engaging them in any decisions on nutritional
with feeding, leading to faltering growth.
intervention is crucial.
In a young breastfed infant where weight is faltering, the
Nutritional management maternal diet needs to be assessed, and its quantity and
quality improved. It is essential that observation of the
Nutritional requirements mother breastfeeding is carried out to make sure the infant is
latched on correctly. Additionally, an understanding of the
A dietary intake that provides energy and protein require- mother’s mental and general health and well‐being is needed
ments for age [31, 32] will usually allow for maintenance of to identify factors that may affect faltering growth [37].
growth along an established centile. Additional protein and Supplementation of breastfeeds may be necessary, but this
energy will be required to allow for rate of weight gain to should be done under dietetic supervision and with caution
improve (catch‐up growth). Guidelines suggest that the per- as it may suppress production of breastmilk. The breastfeed-
centage of energy supplied from protein should be between ing mother will need lots of support around her. A study in
8.9% and 11.5% to provide optimal improvement of lean and formula‐fed infants found greater benefits from using a
fat mass [33]. ready‐to‐feed nutrient‐dense formula (Table 1.18) compared
A formula for predicting energy requirements to improve with adding energy supplements to standard infant formula
weight gain in infants and young children has been sug- [38]. Full‐strength high energy formula has been shown to be
gested [34]: tolerated well by infants under the age of 12 months with
faltering weight, but some may benefit from a gradual intro-
120 ideal weight for height kg duction to avoid increased bowel frequency [39].
kcal kJ /kg In general, young children have high energy requirements
actual weight kg
relative to their size. In cases of poor weight gain, when
catch‐up growth is the aim, requirements are even higher.
This may mean an intake of 1.5–2.0 times, the normal rec- This is difficult to achieve as many children have small appe-
ommended energy requirements for age. Experience and tites and consume small food portions at any one time. There
judgement should be used when advising additional energy are various ways of increasing energy intake:
density, making sure that fortification of the diet does not
displace other foods or is provided at the expense of essen- • regular meals
tial nutrients. Therefore, close monitoring with regular • snacks in between meals
review is essential. • use of energy‐dense foods
Anaemia is common in children with faltering weight, • fortification of foods
and in one study one‐third of a sample had iron deficiency • supplements
anaemia [35]. Often young children who falter in growth are • enteral feeding
high consumers of cow’s milk, which is low in dietary iron Emerging evidence supports that rapid growth in the first
and may inhibit iron absorption. Excessive intake is also year of life can lead to metabolic concerns later in life [40].
associated with gastrointestinal bleeding and iron depletion Therefore, growth faltering should be managed with energy
in infants and young children. There is also evidence that requirements adjusted on an individual basis to allow for
zinc deficiency affects growth [36]. Requirements for vita- healthy catch‐up growth and avoidance of continued rapid
mins, minerals and trace elements are increased during peri- growth once the child’s previously established centile is reached.
ods of rapid growth, and a suitable supplement should be
included if the child’s intake is thought to be inadequate. No
guidelines exist, but intakes should be at least appropriate Provision of regular feeding
for the proposed energy intake.
Children need a routine with regular meals, which include
energy‐ and nutrient‐dense foods. It is advisable to start with
Achieving nutritional requirements small quantities and offer realistic portions of everyday fam-
ily foods, with the opportunity for the child to be given more
Following a detailed feeding assessment, a strategy for if they can manage. Emphasis may need to be removed from
catch‐up growth needs to be planned. The main nutritional mealtimes, and the importance of a balanced intake over the
objectives are: day emphasised.
Summary 469
Frequent snacks (nasogastric or gastrostomy) may be required initially. Full

follow‐up support should be offered to allow for the child
Meals alone will usually not enable the child to catch up. and family to continue to move forward with oral feeding
One study found that when children with faltering weight where appropriate.
were offered a high energy snack, they took more at the next
meal compared with a control group where there were no
concerns about growth [41]. In clinical practice, small regu- Behavioural management
lar snacks as well as meals are advised to encourage interest
in food and improve appetite, so increasing overall energy For the child where there are negative associations with
intake. Excess juice and milk consumption encountered in food, parents should be helped in a sensitive way, offering
many young children should be discouraged, and solid food support and constructive advice, with no blame attached
should be offered before fluids. and no criticism of their parenting. Behavioural manage-
ment includes:
Energy‐dense foods • avoidance of force feeding

• positive reinforcement of good feeding behaviour; aber-
Children need to consume as wide a variety of foods as pos- rant behaviour should be ignored, e.g. by turning the
sible from the four main food groups: bread, other cereals face away from the child
and potatoes; meat, fish and alternatives; full‐fat milk and • a time limit of 20–30 minutes for mealtimes
dairy foods; and fruit and vegetables (Table 2.11) with a • small, frequent meals are a possibility to maximise the
greater emphasis on energy‐dense foods. Foods with a very opportunity for feeding practice and to reduce the pres-
high fibre content are bulky and may have high phytate lev- sure to eat at any one meal
els, compromising both energy intake and the bioavailability Young children with feeding difficulties often benefit from
of micronutrients, and so should be limited. messy play. In a relaxed and fun way, a child is encouraged
to touch, feel, smell and possibly attempt different food
Fortification of foods tastes and textures. The case study in Table 24.5 illustrates
the benefit from play experience, which tackles fears around
Energy‐dense products, such as butter, margarine and food, mess and delayed self‐feeding skills.
cheese, can be added to popular foods. Dried full‐fat milk The Paediatric Specialist Group of the British Dietetic
powder can be used to fortify puddings, soups and milk. If Association offers supportive resources that provide advice
necessary, the iron status of young children can be improved to families on the management of children who are refusing
initially by giving iron supplements and, in the longer term, to eat.
encouraging children to consume iron‐containing foods.
Social care
Supplements
In some families where there has been no improvement or
The use of dietary supplements is not recommended for chil- poor weight gain continues, with evidence of parental ina-
dren with no medical reason for poor weight gain. The use of bility to address the child’s physical, nutritional and emo-
these products can medicalise the problem and give the tional needs, a common assessment framework (CAF) may
impression to parents or caregivers that they do not have a be initiated by a concerned professional. In many cases this
role in helping their child to improve nutritional intake. is the health visitor, but it can be initiated by any healthcare
However, for children who are unable to take an adequate professional who feels this is necessary. A CAF is a shared
intake from food alone, dietary supplements may be neces- assessment and planning framework to identify a child’s
sary and can be prescribed. Carbohydrate, fat or protein sup- additional needs and coordinates the services to meet them.
plements can be used to enrich foods, or ready‐to‐feed If the family still struggles to engage and no progress is
nutrient‐ and energy‐dense drinks (oral nutritional supple- made, a referral to social care services, requesting input from
ments) may be more suitable (Tables 1.19, 1.21, and 12.5). a social worker under the category of a ‘child in need’, is
The principle of frequent feeding, regular meals and snacks, necessary. This will enable a better assessment of the family
use of energy‐dense foods and fortification of solids with dynamics and allows support from a wider range of services.
extra energy still applies. Referral to social services is very important whenever there
A case study of a child with faltering growth is given in are concerns about a child’s care, safety or well‐being [42].
Table 24.5.
Summary
Enteral feeding
To thrive, children need adequate nutrition, appropriate
If the child has severe faltering weight and it is not possible nurturing and supportive parenting. The routine use and
to achieve a reasonable intake orally, enteral feeding correct interpretation of growth charts help the prompt
Table 24.5 Case study: Dietetic management of a child with faltering growth.
Summary
Anthropometry: Baby boy Arlo born at term weighing 3.62 kg. Breastfed for 6 weeks and then started on a standard infant formula. Lives with
mum and has an older sibling aged 5 years. Referred from GP at 2 years of age with faltering growth. Weight = 10.2 kg (9th centile).
Height = 85.5 cm (25th centile).
Clinical: Faltering growth and becoming ill with lots of coughs and colds. Mum reports child is grumpy and not sleeping well, listless and
lethargic, crying a lot. Mum is a single parent, exhausted with older child and struggling with Arlo’s lack of sleep and behaviour.
Dietary: Intake inadequate, drinking lots of milk and very little solid food. Diet very low in fruit and vegetables and iron‐rich foods.
Environment: Mum has few cooking skills and relies on processed food. Family lives in a small flat with only a hob, fridge with freezer box and
microwave oven. Mum receiving benefits and has very little money. Has a small table in the lounge.
Chronology Medical history/assessment Dietetic intervention
1–6 months old Thriving well. No problems when checked

by health visitor
6 months old Started solid foods
Wt = 8 kg (50th centile)
Length = 68 cm (50th centile)
2 years old Frequent coughs and colds and regular visits
to GP
Wt = 10.2 kg (9th centile)
Ht = 85.5 cm (25th centile)
Two centile drop in weight from 6 months of
age so GP referred to dietitian
2 years and 2 months old Wt = 10.3 kg (2nd centile) Advised:
Ht = 86 cm (9th–25th centile) • Eat around the table as a family at set mealtimes
Appointment with dietitian • Keep mealtimes to no longer than 20 minutes
Diet history: • Do not offer alternative food, use finger foods, try and all eat
8 a.m.: 200 mL cow’s milk the same as a family
Mid‐morning: banana • Reduce milk feeds to mid‐afternoon and bedtime only
Lunch: 2–3 tsp. scrambled egg/2–3 tsp. • Add extra, butter/margarine to foods like mashed potato,
beans on ½ slice toast vegetables, pasta, rice
250 mL cow’s milk • Add grated cheese to pasta and potato
Mid‐afternoon: 200 mL cow’s milk • Offer 3 meals and snacks at the table
Tea: 2 tsp. cottage pie/fish pie • Give a multivitamin
1 pot fromage frais • Given written information to back up advice: ‘Help my child
Bedtime: 200 mL cow’s milk won’t eat’ diet sheet*
Dietary assessment: • Written letter to GP for prescription for multivitamin
Total energy = 760 kcal (3175 kJ) of which preparation
555 kcal (2320 kJ) from 850 mL cow’s milk • Review in 4 weeks with a plan to suggest oral nutritional
Total protein = 34 g of which 30 g from supplements instead of cow’s milk if weight not increasing due
850 ml cow’s milk to inadequate intake of food
EAR for energy = 1000 kcal (4180 kJ/day, • Discussed with mum whether she can access a local nursery
82 kcal (345 kJ/kg/day) for Arlo to give her support and some free time
RNI for protein = 14.5 g/day, 1.2 g/kg/day
EAR, estimated average requirement; RNI, reference nutrient intake; GP, general practitioner.
*Available from the British Dietetic Association Paediatric Specialist Group. https://www.bda.uk.com/specialist-groups-and-branches/paediatric-
specialist-group.html
identification of suboptimal weight gain. Regular surveil- dietary intake, oromotor function and feeding; and identifica-
lance, e.g. by the primary care team, and early intervention tion of behavioural difficulties. It is important that parental
are important to help ensure adequate nutritional intake and concerns are acknowledged and there is avoidance of blame.
correct growth faltering. Parenting strengths and difficulties should be acknowledged,
Many factors contribute to poor weight gain, and interven- and support offered to encourage responsive feeding prac-
tions will require a multidisciplinary team approach to tices. A strong working partnership between the care team
enable investigation into possible underlying organic causes and the family is essential for the successful management of
including medical diagnoses and social factors; assessment of growth faltering and should be upheld at all times.
Summary 471
Learning points: faltering weight
• Faltering weight may be a marker of undernutrition or disease • UK‐WHO Neonatal and Infant Close Monitoring Growth
• Regular monitoring is advised throughout infancy and early Charts should be used to assess weight faltering in preterm
childhood infants
• Prompt referral is recommended to investigate possible • Feeding difficulties are common in infants and young
underlying medical causes children and increase risk of nutritional deficiencies
• Timely dietetic intervention is recommended to support • There are many other signs of malnutrition, e.g. wasting, dry
catch‐up growth and prevent further weight faltering skin, thin hair and fatigue, that should also be considered
• UK‐WHO Growth Charts 0–4 years should be used to assess (Table 1.5)
weight faltering in term infants and young children

25
Laura Stewart and Chris Smith
Obesity in Childhood
Obesity
Laura Stewart
Introduction 2–20 years centile charts are available from Harlow Printing
Ltd (see Useful addresses), and all dietitians working in
Obesity is the most common childhood nutritional disorder weight management in the UK with children and adoles-
in the world and is widely acknowledged as being a global cents should use these charts [12, 13].
epidemic [1, 2]. In the UK the importance of implementing In the UK the debate over the most appropriate BMI cen-
effective strategies for the prevention and treatment of child- tile cut‐off points for definition has been long agreed with
hood obesity has national significance with the publication both the National Institute for Health and Care Excellence
of government policy documents [3–5] as well as evidence‐ (NICE) and Scottish Intercollegiate Guideline Network
based guidelines [6–8]. The role of the specialist paediatric (SIGN) clinical guidelines recommending ≥98th centile
weight management dietitian should now be viewed as an (WHO/UK 1990 data) for obesity and ≥91st centile (WHO/
important member of a paediatric or weight management UK 1990 data) for overweight. For epidemiological studies
service. Dietitians may work with children living with obesity ≥95th centile (WHO/UK 1990 data) defines obesity, and
and their families in primary or secondary care, utilising group ≥85th centile (UK 1990 data) defines overweight [6, 7].
or individual sessions [9, 10]. Background information, life- Data on waist circumference centiles for British children
style advice and the use of behaviour change tools that a [14] was previously available on the reverse side of the UK
specialist paediatric dietitian will require to manage childhood BMI centile charts; these have been removed. With no agree-
obesity in any combination of these settings are discussed. ment on the relevant clinical cut‐off points for the waist cir-
cumference centiles, they are not recommended for diagnosis
of childhood obesity [2, 7, 11] although they can prove useful
Definition in monitoring progress.
The definition of childhood overweight and obesity associ-
ates excess body fatness with the clinical relevance of such Aetiology
excess body fat. Body mass index (BMI) is generally recog-
nised as the most appropriate proxy measure for body fat to Obesity is the accumulation of excess body fat associated
define and diagnose childhood obesity and overweight [2, 6, with medical consequences. The aetiology of all o
besity is
11]. BMI in childhood changes with age and differs between both complex and multifactorial [15]. It is well recog-
the sexes; therefore, it must be plotted correctly on age and nised that the development of childhood obesity is an
sex‐specific centile charts (WHO/UK 1990 data). UK BMI interaction between the modern obesogenic environment

Management 473
and family lifestyle choices [16]. Increases in the amount common inherited disorders associated with childhood
of energy‐dense foods eaten combined with large portion besity seen in routine clinical practice are:
o
sizes, more time spent watching television, using computers
• Down’s syndrome
and playing video games (screen time) with a simultaneous
• Prader–Willi syndrome
decrease in the amount of physical activity undertaken by
• Duchenne muscular dystrophy
children have all been mooted as causes of the current
• Fragile X
epidemic [2, 17, 18].
Endocrine causes
Genetics
The endocrine glands produce hormones that are important
The polygenetic theory of obesity suggests that the most in the regulation and maintenance of a stable body environ-
common genetic cause will be found to involve a number of ment. In childhood they are important in ensuring normal
genes that could ‘predispose’ a person to gaining excess fat, growth and puberty. Dysfunction of these hormones can
which in turn would lead to obesity if or when that person is lead to hypothyroidism, growth hormone insufficiency,
then exposed to an environment that encourages the neces- hypopituitarism, hypogonadotropic hypogonadism, hypog-
sary behaviours, i.e. a high energy diet and low levels of onadism, excessive corticosteroid administration, pseudo-
activity [19–21]. It has been suggested that by identifying hypoparathyroidism and craniopharyngioma; all of which
common gene variants that predispose individuals to obe- are associated with rare causes of childhood obesity [26, 27].
sity subgroups of people living with obesity could be targeted Many of these endocrine disorders and the inheritable
for particular interventions such as specific diets, behavioural syndromes present with short stature as a clinical feature
approaches or drugs [22, 23]. The Human Obesity Gene Map [26, 28]. There is strong agreement in clinical guidelines and
is an interesting resource to look for information in this area practice that children with obesity who present with short
[22]. Research into polygenetics and obesity is complex, and stature for their age and weight should be referred to a
it may be some years before any findings can be of use in paediatric endocrinologist for further investigation of pos-
day‐to‐day clinical practice [16, 20]. sible underlying medical reasons for their obesity [2, 6].
Although described as rare, monogenetic causes of obe-
sity in humans have been found [19, 24, 25] with much of Consequences
the research being carried out by the Genetics of Obesity
Study (GOOS) group. The GOOS project recruited children There are a number of consequences of childhood obesity
from across the world who have severe obesity (BMI > 3.0 that are seen both in childhood and adolescence, and indeed
SD), a strong family history of obesity and from consan- later life. Clustering of cardiovascular risk factors has been
guineous families. The GOOS has identified seven monoge- reported in children and adolescents including high blood
netic causes of obesity [21]. Most of these have involved pressure, dyslipidaemia, abnormalities in left ventricular
mutations in leptin production, leptin receptors, propeptide mass and/or function, abnormalities in endothelial function,
pro‐opiomelanocortin (POMC) and the melanocortin 4 hyperinsulinaemia and/or insulin resistance. There is evidence
receptor (MC4R) [19–21]. that these cardiovascular risk factors are seen in adults who
Mutations in MC4R are believed to be found in approxi- were living with obesity as children or adolescents [29, 30].
mately 3%–5% of people with a BMI > 40. Mutations in MC4R Hyperinsulinaemia, the metabolic syndrome and type 2
appear to result in a range of phenotypes ranging from those diabetes are also seen in adolescents [31, 32]. Psychological
showing no obesity to individuals with severe obesity (par- problems, particularly in girls, have been reported in rela-
ticularly at an early age), hyperphagia, increased lean body tion to low self‐esteem and behavioural problems. There are
mass, increased linear growth and hyperinsulinaemia [24]. also long‐term consequences of social and economic effects,
Deficiencies in the hormone leptin are reported to produce particularly in women achieving a lower income [29, 30].
extreme obesity (usually from a young age), increased appe- An important reason why tackling childhood and adoles-
tite, hyperphagia and hypogonadotropic hypogonadism. cent obesity is government policy is the evidence that obe-
Injections of leptin in these individuals have been shown to sity in childhood and adolescence tracks into adulthood.
reverse the hyperphagia and extreme obesity [19]. Individuals Risk factors for persistence into adulthood include:
with POMC mutations are reported as having severe obesity
• parental obesity (high risk if one parent is living with
(from an early age), hyperphagia, altered pigmentation, usu-
obesity and higher if both are living with obesity)
ally red hair and adrenal insufficiency [19, 25].
• level of obesity (increasing risk with increasing level of
obesity)
Inheritable disorders • obesity in adolescence [29, 30]
A number of known inheritable disorders have obesity as a Management

clinical feature of the syndrome. Lobstein et al. [2] noted
around 30 such inherited disorders; most are associated with The role of the dietitian, either as a sole professional or as
learning disabilities and dysmorphic features. The most part of a multidisciplinary team, is to educate the child and
474 Obesity in Childhood
family on the necessary lifestyle changes while facilitating Lifestyle changes

behavioural change [33]. A dietitian should be positive, non‐
judgemental and empathetic while developing a rapport Establishing current lifestyle
with the child and parents [34, 35].
For group sessions it is common practice to include some Asking for a ‘typical day’ scenario or a lifestyle diary, to be
separate child and parent sessions. Practice shows that par- completed after the child’s first appointment, is useful for
ents value the opportunity to discuss situations and solu- establishing current lifestyle and is more child friendly for
tions with other parents without the child being present. developing rapport than an interrogative diet history [34, 35].
For dietitians working with individual children and their
families consideration should also be given to seeing the
parents alone, as information is often revealed by parents Behavioural change tools
that would otherwise not be discussed in front of their
child [9]. Both NICE CG189 and SIGN 115 guidelines concur that
Good practice suggests that different age groups require behavioural change tools in particular stimulus control, goal
different engagements: setting, self‐monitoring, problem solving and use of rewards
should be utilised in the management of childhood obesity
• for preschool and lower primary school‐age children, the [6, 7, 35].
intervention, including ownership and responsibility,
engagement directly with the parent/carer Goal setting
• for upper primary‐aged children, engagement jointly
with the child and parent/carer Goal setting is used to help the child (and parents) to iden-
• for teenagers engagement directly with the adolescent, tify small and reasonable behavioural changes towards the
with the parent in a supporting role long‐term target of positive lifestyle changes. Goal setting
allows the child (and parents) to take responsibility and
ownership for identifying the lifestyle changes they feel able
Assessment to make and subsequently keep to these agreed goals [37,
38]. The dietitian should facilitate goal setting by ensuring
At the first session weight and height should be measured
that the goals are SMART: specific, measurable, achievable,
and plotted on child growth centile charts. BMI should be
recorded and timed [9, 39]. Typically goals are written down
calculated [weight (kg) ÷ height (m)2] and plotted at the cor-
to help with the continuing progress [40].
rect age on the appropriate centile chart for sex (WHO/UK
1990 data). Although used regularly in research in clinical
practice, arm anthropometry such as triceps skinfold meas- Rewards for reaching goals
urement and mid‐upper arm circumference is rarely used.
Taking the waist measurement can be difficult in children Some programmes use ‘rewards’ for achieving the agreed
living with obesity but can be a useful tool in monitoring lifestyle goal as these can be a positive reinforcement to both
progress in weight management. the setting and attainment of goals [38, 41, 42]. Rewards
The assessment of any child within a weight management should be inexpensive, non‐food or screen time items such
service should ensure that a holistic view of the child’s health as a book, football or a family excursion. It should be remem-
and well‐being is taken. An example of a current model in bered that praise can be a very powerful reward and should
taking a health and well‐being holistic viewpoint is the be utilised by the dietitian [40].
Getting it right for every child (GIRFEC) [36] used in Scotland,
which has been underpinned in legislation. An important
and useful aspect of GIRFEC has been the assessment tool Self‐monitoring of lifestyle
known as SHANARRI:
The recording of specific lifestyle elements by the child and/
• Safe or parents is a key component of behavioural change tools
• Healthy that enhances motivation to change lifestyle by increasing
• Achieving self‐awareness [38, 41, 43]. Monitoring the child’s food and
• Nurtured drink intake, physical activity levels and screen time in a
• Active diary/journal helps raise awareness of current lifestyle,
• Respected helps to identify potential goals for changes and then moni-
• Responsible tors progress towards their goals [40].
• Included
These eight aspects are reviewed from the child’s point of Problem solving
view and are a useful concept for ensuring a weight concern
is not seen in isolation of the child’s whole life circumstances Problem solving is used to help the child and their parents to
and well‐being. identify barriers and then to explore ways to overcome these
Screen Time (Sedentary Behaviours) 475
barriers [38, 42]. A patient centred approach would recom- • reducing energy‐dense but nutrient poor foods
mend that the child and/or parent identifies their own solu- • reducing sugar sweetened drinks
tions to barriers and difficult situations [37, 40]. • increasing fruit and vegetable consumption
It is also used in relapse prevention by identifying ‘high • decreasing the overall total energy intake
risk’ situations where keeping to goals could be difficult,
These changes came through programmes that lasted a
e.g. holidays, parties and wet weather, and then exploring
minimum of 3 months, with less intense follow‐up periods
strategies to cope with these situations such as participating
of between 3 and 18 months through face‐to‐face meetings
in an indoor activity during wet weather. Relapse preven-
or via phone/texting. Importantly the systematic review
tion is particularly important at the end of the programme
noted that if these dietary changes were maintained they led
to ensure that the child and family maintain behaviour/life-
to a long‐term decrease in BMI SD scores [46].
style changes in the long term [40, 42].
Children and their families should be encouraged to
reduce the amount of foods and drinks in their diet that are
Stimulus control high in sugar and fat and replace them with foods with
lower energy content such as fruits and vegetables. Very
Environmental/stimulus control involves identifying and importantly the dietitian needs to explore that age‐appropri-
then changing/removing stimuli or cues that encourage or ate portions are being taken by all the family. This can often
sustain the ‘unhealthy behaviour’ and substituting cues that be the main area of education for the child and family. There
support/promote the new necessary lifestyle changes [42]. should also be consideration of:
Examples include parents reducing the purchase of high • the number of takeaway meals taken
sugar/high fat snacks in their shopping or the child avoid- • the amount and types of snacks the child eats
ing walking home from school past a local sweet shop or a • the amount of pocket money the child has
football being left at the front door to encourage physical • school lunches
activity after school [40].
Guidelines also recommend that parents should be It is important to ensure that normal growth occurs when
encouraged to be the role models for the positive behav- dietary intake is restricted and that age‐appropriate quanti-
ioural changes required; i.e. they need to change their eating ties of protein, vitamins and minerals are taken. There are
habits, physical activity and screen time behaviours and let some children who dislike certain foods and do not consume
their child see them undertaking these positive activities. a nutritionally adequate diet, and they may require a supple-
Giving affirming, concrete praise to the child when they ment of vitamins or minerals (particularly iron and calcium).
undertake positive changes is also important to reinforce Some children may, therefore, require regular assessment to
behavioural change [6, 7]. compare their intake with recommended nutrient require-
ments [47]. Regular plotting of weight, height and BMI on
approved growth and BMI centile charts is important.
Implementing lifestyle changes
Physical activity
As discussed, the aetiology of childhood overweight and
obesity is multifactorial and management requires both
NICE and SIGN obesity guidelines recommend that
energy in and energy out to be tackled. A Cochrane review of
overweight and children with obesity undertake at least
the treatment of childhood obesity showed that the most
60 minutes of moderate to vigorous activity per day [6, 7].
effective treatments were those that combined diet and life-
Physical activity guidelines in the UK recommend that
style changes [44]. Therefore, the dietitian must facilitate
children under 5 years who can walk unaided should take
changes in total energy intake, physical activity levels and
up to 180 minutes of activity each day [48].
screen time (sedentary behaviours) while using the behav-
Many children living with overweight or obesity dislike
ioural change tools outlined above.
team sports and physical education (PE) at school. It is,
therefore, important to help the child and family find local
Dietary advice activities that they enjoy and are not embarrassed to take
part in. In practice this can be done by working in partner-
A systematic review concluded that no one particular type of ship with local leisure/physical activity organisations.
dietary manipulation in childhood obesity was more effec- Increasing everyday ‘lifestyle activities’, such as walking
tive than any other [45]. The child (and the whole family) and taking the stairs rather than lifts, has been demonstrated
needs to reduce the total energy intake in their diet while bal- to be effective in controlling weight in the long term [41].
ancing essential nutrients. Collins et al. found that the traffic
light type scheme was the most commonly used [9, 41, 45]. Screen time (sedentary behaviours)
Calorie counting is not normally used with children.
A recent systematic review of the effectiveness of dietary NICE and SIGN guidelines recommend that children reduce
intervention concluded that childhood weight management their screen time (watching television, using computers, playing
interventions could be successful in: video/computer games) to no more than 2 hours daily or an
average of 14 hours over a week [6, 7, 49, 50]. Some countries’ 11‐year‐old boy is given in Table 25.1. Infants, preschool chil-
guidelines, e.g. the USA, Canada and Australia, recommend dren and adolescents may require particular consideration.
that children under 2 years should have no screen time [51].
For some children and parents, this is the most difficult
change to make and there needs to be a discussion how this Infants and preschool children
reduction can be attained over time.
The management outlined above covers all age groups. It is difficult to overfeed a breastfed infant, but bottle fed
A case study to demonstrate weight management in an infants can be persuaded to consume a greater volume than
Table 25.1 Case study: child weight management.
An 11‐year‐old boy referred for weight management advice by his family general practitioner
After triaging by the paediatric weight management team, he was accepted into the structured weight management programme SCOTT [9], which
involves 10 family sessions over 4–5 months, including 2 parent‐only sessions
Anthropometry
Referral weight = 50 kg; height = 1.46 m
BMI = 23.5 (98–99.6th centile) therefore classified as obesity
Assessment weight = 49.6 kg; height = 1.474 m
BMI = 22.9 (98th centile)
Biochemistry
None taken. In clinical practice it is not usual to review biochemistry in childhood weight management unless there is an indication of an underlying
medical cause, e.g. short stature; or indication of a comorbidity, e.g. symptoms of type 2 diabetes
Clinical
Obesity due to BMI being above the 98th centile. No medical history to note
Dietary
From a typical day diet assessment, he appeared to eat well‐balanced meals; however, these appeared to include excessively large portion sizes and
multiple snacking in between meals
Environment
Social history
He lived at home with his mother, father and younger brother. He was in his last year of primary school. There was no involvement of social work or
child and adolescent mental health services (CAMHS)
A SHANARRI assessment indicated that he had:
• A supportive family
• Low self‐esteem and confidence
• His screen time was excessive with very low activity levels
• Making changes might be difficult for him, and he may not be able to take responsibility to make changes outside the home
• He had few friends and was being bullied at school due to his weight
Focus
He and his mother had attended the GP surgery due to mother’s concerns that he had been progressively gaining weight in the preceding 2 years,
including having gained 4 kg in the last month. Both were concerned about his weight but did not feel he had an unhealthy dietary intake. He
appeared at assessment stage to be very sedentary, with excessive use of screen time
Motivation to change
The boy 8/10
His mother 8/10
PASS statement
Problem – childhood obesity
Aetiology – sedentary lifestyle, excessive hunger with snacking on sweets
Signs and symptoms – BMI above 98th centile, bullying
At his second appointment (appointment 3 in the programme) he set goals:
• 30 minutes of activity four times per week
• To have pudding four times a week instead of current seven times
• To reduce portion size
Over the course of 4 months, he made the following changes to his lifestyle:
• Decreased the portion sizes of food at meal times
• Stopped having crisps as snacks
• Increased his physical activity to 30–90 minutes every day
• Changed from bakery foods in the morning for breakfast to Rice Krispies
End of programme weight = 48.3 kg; height = 1.496 m
BMI = 21.6 (91–98th centile) therefore classified overweight, rather than obesity
Prevention 477
they want or require; in addition feeds can be made more minerals and micronutrients to meet the requirements for
concentrated than recommended, or items such as cereal can this age group.
be added to the bottle [52]. In general there should be no Drugs for the treatment of obesity are used in adults,
need to restrict an infant’s diet, but for those gaining weight although these have not been licensed for use in children or
too quickly, or those already living with obesity, specific adolescents in the UK. NICE and SIGN guidelines both rec-
advice on feeding and weaning practices and lifestyle will be ommend that they could be used in adolescents with obesity
necessary. The following advice may be helpful: and comorbidities under strict supervision [6, 7].
• Make sure that parents react appropriately to the infant’s
crying; often crying is perceived as indicating hunger, when Written advice
in fact the baby may be bored, tired or uncomfortable
• Avoid any additions to the infant’s bottle, e.g. sugar or Written information should be provided to support any
cereal advice that has been given. It is usual to record goals and
• Make certain that the feed dilution is correct and that the rewards (if used). The Caroline Walker Trust has very useful
volume is appropriate for age pictorial information on portion sizes. Written information
• Solids should not be introduced before the age of 6 on reading food labelling can be helpful, e.g. that produced
months by the British Heart Foundation.
• Weaning solids should initially have a low energy den-
sity, e.g. vegetables and unsweetened fruits Treatment success criteria
• Reduced fat products can be used in the weaning diet,
e.g. low fat yoghurts and reduced fat cheese Current guidelines agree that the goal of childhood weight
• When a greater variety of foods is being consumed, e.g. management for most children is weight maintenance, with
lean meat, white fish and cereals, then the quantity of height growth leading to a natural decrease in BMI. For some
milk should be decreased older children, and particularly those with very severe and
• Infants should be introduced to a cup or teacher beaker extreme obesity, a weight loss of around 0.5–1.0 kg per month
from about 7–8 months of age and bottles omitted by 1 is acceptable.
year of age; more milk is generally consumed when When reporting outcomes on programmes, it is standard
feeding from a bottle practice to report on BMI SD scores, also known as z‐scores.
• Review if bottles of milk are being given at night particu- There is a limited evidence base on the impact of BMI SD
larly to aid getting to sleep or to enable getting back scores on reducing cardiovascular disease risk factors. The
to sleep during the night; discussion with the parents studies suggest that a reduction of between 0.1 and 0.5 BMI
and seeking help for them from early years workers to SD score after 1–2 year follow‐up is significant enough to
support good sleep practices is important show changes in cardiovascular risk factors [53, 54].
• Semi‐skimmed and skimmed milk should not generally be
used before the ages of 2 and 5 years, respectively; however,
these lower fat milks are a useful way of decreasing energy Prevention
intake in a toddler with overweight; it is important that a
supplement of vitamins A and D are given with these milks Promotion of a healthy lifestyle must start in early childhood
• Drinks of water should be offered with and in between if the present trend in childhood obesity is to be reversed.
meals; if the child is reluctant to drink water, then pure Current government initiatives around healthy eating and
unsweetened fruit juice (well diluted) can be given once increasing physical activities at schools may be helpful in the
or twice daily with meals future. Dietitians, particularly those working in the area of
public health nutrition, have a key role to play in prevention
strategies.
Adolescents Growth in infancy and the early years is an important
period in relation to the risk of obesity later in childhood and
Adolescents present dietitians with their greatest challenge. adulthood. It appears that infants at the upper end of weight
Normal adolescent behaviours and peer pressure for the and BMI for their age, and also those who gain weight rap-
consumption of snack foods dense in fat and sugar can lead idly as infants, are at a higher risk of excess body fat and
to resistance towards lifestyle changes. The lifestyle advice obesity later [55]. The Avon Longitudinal Study of Parents
outlined above should be given, but with careful considera- and Children (ALSPAC) has noted eight particular risk fac-
tion of how to approach the adolescent to ensure that they tors in early childhood that were significantly related to later
feel ownership of goal setting and all stages towards behav- childhood obesity [55]. These are:
ioural change.
• parental obesity
Slimming foods and medications • very early BMI or adiposity rebound
• more than 8 hours watching television per week at age 3
‘Slimming foods’ and drinks as a replacement for a meal are years
not appropriate as they usually contain insufficient protein, • weight at 8 and 18 months
• catch‐up growth
Learning points
• weight gain in the first year
• birthweight
• Obesity is the most common childhood nutritional disorder
• short sleeping duration at age 3 years
worldwide and is an important area for dietitians
Prevention programmes that take place in schools and • A paediatric weight management dietitian should be seen as
also target parents would appear to be an effective route. an important member of the team
Prevention strategies need to focus on the complex issues • WHO/UK 1990 BMI centile charts should be used to
around childhood obesity involving diet, physical activity, diagnosis overweight and obesity and for monitoring
sedentary behaviour, family lifestyle and environment. progress
These interventions must, therefore, engage complex behav- • Interventions should be family based, with at least one of
ioural changes. An example of such an intervention is the the parents involved
school‐based Planet Health project, although this appeared • Changes in diet, physical activity and screen time should be
to be more effective for girls than boys [56]. targeted equally
Without a doubt the role of tackling the obesogenic envi- • Dietitians working in paediatric weight management
ronment [4, 5] is now seen to be fundamental in helping should have training in the use of behavioural change tools
with both the prevention of overweight and obesity and and techniques
with supporting those undertaking weight management.
Promoting this role and indeed working with communities
to co‐produce community‐based healthy weight planning
[57] is certainly a role that dietitians should be taking up.
Prader–Willi Syndrome
Chris Smith
Introduction • varying degrees of developmental delay

• scoliosis
Prader–Willi syndrome (PWS) is a rare genetic disorder in • sleep disturbances
which genes on chromosome 15 are either deleted or unex- • high pain threshold
pressed. The three main molecular mechanisms that result in • speech apraxia/dyspraxia
PWS are the following: paternal deletion, maternal unipa- • infertility
rental disomy (UPD) and imprinting defect. The prevalence • poor/immature emotional and social development
of PWS is difficult to ascertain, but in Europe it has been
The most commonly associated characteristic of the con-
reported between 1 in 8 000 and 1 in 45 000 births [58, 59]
dition, however, is hyperphagia. Children with PWS have an
making it the most common genetic cause of obesity. PWS
insatiable appetite, leading to gross obesity if not controlled.
occurs equally in males and females and affects all ethnic
This is the result of a chronic imbalance between energy
groups. There is no cure for PWS. However, the prevention
intake and energy expenditure due to hyperphagia,
of obesity and complications, as well as quality of life, can be
decreased physical activity and reduced metabolic rate.
significantly improved with an early multidisciplinary
Historically, two distinct phases characterised this syn-
approach including diet, growth hormone treatment, activ-
drome, representing the two extreme ends of nutritional
ity and behaviour modification [60].
status:
Diagnosis is most commonly made through the presenta-
tion of hypotonia in infancy, and it is confirmed with a genet-
1. Faltering growth in infancy. The presence of hypotonia
ics blood test. The main characteristics of the condition
results in significant feeding difficulties and subsequent
include [61]:
faltering growth. Tube feeding is often required during
• hypotonia this period [62], which can be from birth to approxi-
• hyperphagia mately 2 years of age.
• short stature 2. Excess weight gain in childhood. From around age 5
• hypogonadism years onwards weight escalates as a switch from poor
Growth Assessment 479
Table 25.2 Nutritional phases in PWS.
Phase Age Feeding behaviour Dietary intervention Growth pattern
0 Prenatal – birth N/A N/A Lower birth weight than siblings

1a 0–9 months Weak suck Orogastric/nasogastric feeding* Growth failure
Breastfeeding may be difficult Specialist teats Downward centile crossing common
Unlikely to wake or cry for feeds
Progress with texture and
weaning may be slow
1b 9–25 months Improved feeding May no longer require orogastric/ Close monitoring of growth pattern
Vocalises appetite nasogastric support Upward centile improvement
2a 2.1–4.5 years No obvious increased appetite Energy assessment and restriction Weight begins to accelerate
or excess intake Requires consistent and structured Can enter obese phase if unrestricted
approach to food
2b 4.5–8 years Obvious increased appetite and Energy restriction and limited Accelerated growth is common
preoccupation with food portion sizes Height growth remains slow
Requires consistent and structured (improved with GH treatment)
approach to food
3 8 years – Hyperphagia Possibly more significant energy Rapid weight gain possible
adulthood restriction Comorbidities due to obesity common
Requires consistent and structured
approach to food
4 Adulthood Appetite may not be insatiable Continued energy restriction Rapid increase in weight possible with
and can fluctuate increased independence
Many adults may however not Comorbidities due to obesity common
enter this phase
N/A, not applicable; GH, growth hormone.

* Gastrostomy placement is rarely required as improvements in oral development will happen as the infant develops.
Source: Adapted from [63]. Reproduced with permission of John Wiley and Sons.
feeding to hyperphagia occurs, resulting in the establish- short stature. Therefore, sequential plotting on standard
ment of the second phase of obesity. growth charts may make growth interpretation difficult.
PWS specific charts are recommended for evaluating growth
More recently, however, a large USA study has proposed for comparison purposes, monitoring growth patterns,
a more gradual and complex range of phases. In total nutritional assessment and recording responses to growth
seven different nutritional phases are described (five main hormone (GH) therapy. Several PWS specific growth charts
phases and two sub‐phases), each with distinct characteris- have been proposed and produced from groups in Japan
tics (Table 25.2) [63]. [66], Germany [67] and the USA [68], although there are no
Throughout these phases it is recognised that the combi- charts from UK data. Most recently, centile charts for non‐
nation of behavioural and nutritional problems requires a growth hormone‐treated children have been produced by
multidisciplinary team approach [64, 65]. It is important that the USA from birth up to 36 months [69], and from 36 months
dietary intervention and advice are given before the onset of to 18 years [70]. Centile charts for growth hormone‐treated
weight gain, in order that excessive weight gain is curtailed. children from 0 to 18 years are also now published [71].
Consistent dietary advice from all professionals must be There are thought to be no racial differences in growth
given to parents and carers, and the need to adhere to this patterns, but interestingly, on comparison, the data suggests
explained. Gross obesity can occur during adolescence, and the degree of overweightness is milder in Japanese children
behavioural problems encountered during this period can compared with Caucasian, with the same pattern reflected in
add to the difficulties of care. However, obesity should not adults [66].
be considered inevitable, as weight can be controlled with Body composition is also inherently different in people
comprehensive management. with PWS, with lower lean body mass even in very young
infants and toddlers [72]. There is limited reference data, but
Growth assessment assessing body composition using valid techniques, where
resources and skills allow, can be useful in the long‐term
The inherent growth pattern of children with PWS varies monitoring of PWS children. Measurements can highlight
from that of healthy children in that they have early child- good weight gain (lean mass) as a result of GH treatment, or
hood obesity, absent pubertal growth spurt and adolescent a change in diet or physical activity that may be missed by
one dimensional weight or BMI measurements. In addition, patients from different continents: Europe [77] and the USA
the accuracy of determining energy requirements can be [78]. Due to the considerable variation in international eating
improved by taking into account body composition meas- habits and diets, extrapolation of these results to other popu-
urements [73]. lations should be done with caution, and some of the results
from these studies were contradictory. Lindmark et al. [77]
showed iron to be under‐consumed in this group; conversely,
Learning points Rubin et al.’s [78] study showed adequate iron consumption
in all of the PWS patients. Calcium intake was below the refer-
• PWS is a rare condition with no cure. However, lives of ence nutrient intake (RNI) in 18% of the group in Rubin’s
children with PWS can be improved with a multidiscipli- study; Lindmark’s study found calcium was not a nutrient of
nary approach, and paediatric obesity should not be consid- concern. Bone health, however, is an important consideration
ered inevitable in PWS. Younger PWS children have been shown to have no
• Inherent growth difference occurs in PWS children and significant difference in bone mineral density compared with
adolescents controls, but a decline in adolescence is reported in both
females and males [79]. Osteoporosis is common by adult-
hood [80]; therefore, vitamin D and calcium are of particular
importance. A recent Italian study reported vitamin D levels
Nutritional requirements in a group of PWS patients to be similar to a control group
with the prevalence of levels <20 ng/mL in 30% of the PWS
A recent systematic review concluded that absolute total
group [81]. No study to date in this patient group has included
energy expenditure, resting energy expenditure, sleep
the assessment of zinc and selenium intakes. However, these
energy expenditure and activity energy expenditure are all
have been shown to be two of the nutrients that were high-
lower in individuals with PWS than in age, sex and body
lighted as very likely to be below the lower RNI (LRNI) in a
mass index‐matched individuals without the syndrome [73].
UK group of patients [82].
The causes for these differences are multifactorial, including
In addition to awareness of likely low micronutrient
inherent disturbed body composition [74]. Limited studies
intakes, care must also be taken in ensuring balanced macro-
have evaluated energy requirements, and calculating spe-
nutrients and, in particular, fat. Historically, a low fat intake
cific energy requirements for PWS children is controversial.
was the diet of choice for management, but several studies
There is particular uncertainty about energy requirements
have suggested that over‐restriction of fat (<20% of total
for small children.
energy intake) can occur [20, 78]. This is associated with poly-
Consensus appears to suggest the energy needs of chil-
unsaturated fatty acid deficiency, increasing the risk of
dren with PWS are typically 60%–80% of the recommended
associated negative consequences on development.
daily allowance [61]. There are several proposals for basing
energy requirement for preschool‐ and school‐age children
on kcal/cm. These are 10–11 kcal/cm height for weight Dietary treatments
maintenance and 8–9 kcal/cm height for weight loss [75],
and more recently 10–12 kcal/cm height for weight mainte- Evidence‐based dietary approaches in children with PWS are
nance and 6–8 kcal/cm height for weight loss [76]. scarce. Several dietary modifications have been proposed for
As with all children, the precise energy intake required treating adults: simple energy restriction (6–7 kcal/cm height
will depend on many factors and requires close monitoring per day); the ‘red, yellow, green’ diet that limits foods with
of growth as a guide. higher energy density, sugar or fat; and general fat restriction
[83]. A recent paediatric study proposed the p rinciple of
Dietary considerations altering the proportion of energy from macronutrients in the
diet (30% fat, 45% carbohydrates and 25% protein). When
While a significant difference in energy requirements is compared with a simple energy restricted diet, encouraging
required, conversely requirements for micronutrients do not results were shown in both weight and body composition
appear to be different from age‐matched healthy controls. [84]. As yet no one specific strategy can be concluded to work
Therefore, focus on the quality, as well as the quantity, of the best, as successes have been described with each. This in part
diet is paramount. Dietitians must take care to balance the supports the notion that, regardless of the approach, the com-
need for provision of sufficient energy and nutrients for mon element of success is the consistency of that approach.
growth without excess energy intake leading to unwanted As a low energy diet may be lacking in some nutrients, it
weight gain. Prevention of over‐restriction, particularly in the is widely recommended that children have a daily vitamin
younger more vulnerable infant, is of particular importance. and mineral supplement [85]. Interestingly, in the largest
Surprisingly, for a condition with fundamental links to die- and most recent review of PWS diets published [78], only
tary intake, there are very few studies published on the actual 40% of patients supplemented their diet with multivitamins
nutritional intake of people with PWS. Only two studies have (with or without calcium).
specifically investigated and reported micronutrient intakes The balance of fat sources, ensuring sufficient essential
in paediatric PWS patients. These studies were small and took fatty acid intake, is advised. Anecdotally, supplementation
Behaviours 481
with medium‐chain triglycerides (MCT) is increasingly pop- Behaviours

ular. Nutritional supplements such as coenzyme Q10 and
carnitine are also, anecdotally, widely used (and recom- Many behaviours of children with PWS are similar to those
mended in many USA clinics) for their association with seen in autism. Table 25.3 shows the common behaviour
energy metabolism. An investigation using serum sampling characteristics of people with PWS.
found no difference in levels in PWS patients compared with An understanding and appreciation of the psychological
obese controls or sibling control groups [86]. Dosing and use aspects associated with PWS is important. Several common
for both of these remain controversial. behaviours, such as the preference for a rigid and structured
In addition to specific nutrient advice, several practical pattern, can be used to management advantage by establish-
restrictive interventions have been proposed, including lock- ing clear boundaries surrounding food.
ing refrigerators and food cupboards, supervising meals and The majority of the data on food behaviours supports the
food shopping, and monitoring access to spending money. common theme that restricted, but predictable, food availa-
Maintaining strict control of portion sizes through standard- bility is an ideal model. Again utilising the inherent behav-
ised weights or measurements can also be very useful. iours of this group can be to the child’s benefit. PWS children
Undoubtedly strict control over dietary intake and access are preoccupied with thoughts of food and so ensuring food
to food is necessary. However, it is worth noting that the pre- security (such as the use of visual menus) can help to limit
conception that PWS children will eat indiscriminately has some of the more difficult anger and food‐seeking behav-
been challenged by several studies. Joseph et al. conducted a iours. Table 25.4 suggests some behaviour strategies and
small experiment offering PWS children and a control group principles to consider.
of children with obesity the option of a larger quantity of Food scavenging, ingestion of inappropriate foods (such
food delivered after a delay (15, 30 or 60 seconds) or a small as from bins) and stealing food can be common. Frozen
quantity of food delivered immediately. Individuals with
PWS selected the larger food quantity, suggesting perceived
differences in food quantity may be an important determi-
nant of food choice [87]. A recent systematic review on food Table 25.3 Common behaviour characteristics of people with PWS.
preferences concluded that PWS patients have a preference
for sweet‐tasting foods but recognises that the food choices Preference for rigid routine
and behaviours require substantially more work in order for Difficulty coping with change
the mechanisms to be understood [88]. Difficulty coping with emotions
Constipation is common in PWS children, and usual die-
Temper tantrums
tary treatments and prevention strategies can be applied.
Regardless of the type of dietary treatment, it is widely Stubbornness/oppositional behaviours
agreed that proactively starting on a consistent approach to Manipulative behaviours
mealtimes and intake before the child becomes hyperphagic Obsessive–compulsive characteristics
is a key recommendation for the long‐term successful man-
Psychosis (affecting 10%–20% by young adulthood; more frequent in
agement of the PWS child. Communication with other health those with UPD) [60]
professionals is essential to ensure a consistent message and,
therefore, consistent approach to management. Equally UPD, uniparental disomy.
important is the emphasis of communication by the parents
to the extended family. This should include family, friends,
teachers and other caregivers to prevent them from under-
mining established and agreed management principles. Table 25.4 Strategies that may help manage PWS eating behaviours.
Structured daily schedule with activities, including meals, snacks and

exercise. Visual schedules placed somewhere consistent may help
Learning points: dietary treatments Give advanced warning of any changes to the normal routine
Educate the child on healthy eating and appropriate food choices
• Energy requirements are likely to be approximately 60% of
normal requirements for age Single plate rule or concept of ‘my plate’ and ‘your plate’
• Requirements for macronutrients may require restriction Consistent strategies for dealing with constant food requests – these
while requirements for micronutrients should be considered can include distraction and visual menus
to be the same as for healthy children Consider ‘no doubt, no hope, no disappointment’ approach [89]
• Assessments of diet quality as well as the quantity is Ensure consistent approach between all caregivers and family
fundamental members
• Evidence is lacking on the best dietary approach Avoid trying to reason with the child
• The principle of a structured and consistent approach from
Avoid using food as a reward
a young age is most likely to yield the best results
foods and toiletries that resemble or smell like food can also
Learning points: behaviours and activity
be eaten. Attempts should be made to check all potential
sources of food, e.g. from neighbours or friends, in keeping
• Common PWS behaviours associated with the condition
with a strict controlled intake. Offering food as a reward or
can be very challenging but can be utilised to promote
withholding food as a punishment is almost always counter-
successful management
productive and should be avoided.
• Growth hormone and activity are important adjuncts to
treatment for weight control
• Establishing a pattern of regular activity should be
Growth hormone
encouraged and supported
Best practice in early intervention management for PWS
now includes recommendations for GH therapy, which is
supported by the National Institute for Health and Care
Excellence (NICE) [91]. A recent systematic review and
Monitoring
international guideline for the use of GH in PWS provides
There is no current UK national standard recommending
good background on this topic [92]. It is widely recognised
the frequency or specific monitoring or considerations for
that GH will aid height growth, promote leaner body
follow‐up in people with PWS. Monitoring guidelines have
composition, increase energy expenditure, improve weight
been published in the USA [99], which suggest evaluating
management, increase energy and physical activity, and
diet (including adequacy of vitamin and mineral intake),
improve strength, agility endurance and respiratory
growth parameters (height, weight and BMI) and activity:
function [89, 91–95].
A recent 4‐year longitudinal randomised controlled trial • every month in infancy
of 50 PWS children (aged 3.5–14 years) on GH treatment • every 6 months in the first decade of life
suggested it also prevented deterioration in cognition
• at least annually thereafter
function, with the most benefit being seen in those with
The application of this for UK dietitians would appear
the greater deficit [96].
sensible. More recently, specific recommendations for endo-
In another small study GH treatment showed improved
crine monitoring and screening have been published [100].
body composition to be variable and suggested it increases
PWS patients may be followed up in a variety of settings.
total energy and fat intakes (although effects appear to vary
There are several PWS specialist multidisciplinary clinics in
depending on the developmental status of the child). It
the UK and the follow‐up timeframe varies between these.
should also be noted that in this study the children on GH
However, the principle of close monitoring and support is
still had raised BMI, and the authors concluded that the
well recognised and consistent.
treated children should have been on a tighter calorie con-
A case study to show the management of a boy with PWS
trolled intake [97]. Indeed, it should be noted that GH‐treated
is given in Table 25.5.
patients do not show complete normalisation of weight or
BMI. However, a downward shift of these profiles when
compared with non‐GH‐treated PWS individuals is evident Transition
[70]. GH treatment is not without risks, so its initiation and
monitoring should be done by a suitable endocrinologist, Ideally a young person with PWS should be transitioned to
ideally with experience in PWS [92]. an adult service with a dietitian who has an interest and
experience in PWS. In some areas this may come under the
remit of the Learning Disability Dietetic Team. Monitoring in
Activity adult patients is as important as in children. As the child
approaches transition, education and identification of tools
It is very easy for people with PWS to gain weight. This is for adult life should be discussed and recommended. There
due to the combination of the overriding desire to eat cou- are four options for adult patients with PWS:
pled with low muscle tone, making exercise difficult and
• living with parents or other relatives
slow and, therefore, of little enjoyment. However, activity is
• group home placement
a key element of treatment. Increasing energy expenditure
• supported living services
and aiming to increase fat‐free mass should be considered a
• specialised residential services
constant goal, and maximising activity can help this [71].
Some activities are physically difficult for the PWS child Each may require different levels of nutritional and weight
due to poor muscle strength, but walking and swimming monitoring, depending on the level of support. It is widely
can be accomplished by most and should be encouraged. A acknowledged that adults with PWS probably lack capacity
small prospective study in prepubertal PWS children from relating to food choices (when and how much), so there is a
the Netherlands showed daily muscle training increased duty of care to support the individual to manage their food
lean body mass when compared with controls, although it intake appropriately. The issue of mental capacity with
did not normalise lean mass [98]. respect to PWS patients in the UK is important and discussed
Transition 483
Table 25.5 Case study: management of a boy with Prader–Willi syndrome.
Presentation
A 12‐year‐old boy with PWS (growth hormone‐treated) attends clinic for 6 monthly review. Presents with clear and sustained acceleration of weight
gain over the last year. Linear growth is maintained. No signs of puberty. Otherwise well with no new medical issues. Historical strict control and
management of diet and steady controlled weight gain (as evidenced from growth chart)
Assessment
a. Anthropometry
Plots on Boys UK Growth chart 2–18 years reveal accelerated acute weight gain
BMI calculations and comparison show significant increase in the last 12 months
Plots on PWS specific growth charts for growth hormone‐treated child suggest overall pattern within that expected, but with recent acceleration
clear
Body composition measurements compared with his historical data (as there are no standards to compare with) show a notable increase in % body
fat and a reduction in lean body mass
b. Biochemistry and other lab results
Review of blood tests indicated growth hormone is at appropriate dose
Review of nutritional bloods including vitamin D, parathyroid hormone, zinc and iron reveal all in range, but with ferritin and zinc borderline
c. Health and disease state
Scoliosis stable. Behaviour aspects challenging
d. Nutritional and food intake
Diet recall with family reveals consistent nutritional intake from previous reviews
No changes to family management strategy
Detailed 3‐day food diary requested from family
Analysis: intake 65% of estimated average requirement for energy; micronutrient intakes low for many minerals, however achieving reference
nutrient intake when vitamin and mineral supplement included
e. Social circumstances
Recent change to mainstream secondary school, but with education, health and care plan (EHCP) in place
New teachers, new peers and small increase in independence
On discussion with patient it becomes obvious access to food much less controlled in the school environment coupled with a lack of
understanding of diligence required from teaching assistant (1:1 supervision necessary)
Identification of diagnosis
Problem:
Accelerated weight gain. Concern of both long‐ and short‐term consequences of this on the child’s health and quality of life if left unaddressed
Aetiology:
Unprepared new environment (school) where previous well established safety mechanisms to prevent access to food no longer in place. Family/home
environment proven successful in the past; main area of issue is external
Sign and symptoms:

Accelerated weight gain and BMI
Changes in body composition
Discussions with school and 1:1 supervisors
Implementation
Education for key school supervisors on principles of PWS care
Provision of written support documentation for school
Request for evaluation of patient’s access of food/any unsupervised situations in school environment
Diet management and requirement for daily structured activity written into EHCP
Monitor and review

Review situation with school and family
Re‐evaluate patient’s access to food
Weekly weight recommended until weight stable
Evaluation
Patient’s weight gain stabilised
Learning points: case study
• Identification of changes in growth pattern weight gain is key to identify an issue with management
• Changing environments for PWS children require careful planning and evaluation to ensure strategies to control access to food
are minimised
• Accelerated weight patterns should be addressed with urgency as uncontrolled weight gain and subsequently raised BMI and %
body fat can have long‐term impacts on the child’s health and quality of life
in detail in a recent guide written in association with the UK • implanted devices, e.g. vagus nerve stimulation
PWS Association [101]. • medications to address hyperphagia
Ensuring young people with PWS transition to adult ser- • medications to impact behaviour
vices with an acceptable weight/BMI is a key target for pae-
Oxytocin has attracted particular interest in recent years in
diatric dietitians. The development of metabolic syndrome
relation to the behaviours of PWS patients. While many of
and complications in PWS adults is closely associated with
these clinical trials (four of five) showed promising results, a
obesity status. Type 2 diabetes is estimated to affect 25% of
recent review of all of these concluded that due to limitations
adults with PWS [102]. A useful paper describes the common
there is currently no convincing evidence that it improves
issues in adult care [103].
symptoms [105].
Surgical interventions, such as gastric bypass, have been
There is much interest currently in the use of ketogenic
used in adults with PWS, although these are not recom-
diets. However, there are currently no robust good quality
mended as treatments [104]. In addition to not addressing
studies that allow any conclusions to be drawn on this as a
the inherent hyperphagia, they are also associated with high
viable treatment approach.
complication rates.
Summary
Future research
In PWS dietary management presents a tremendous
Clinical trials investigating potential treatments for PWS are
challenge for the child, family, caregivers, and health

ongoing. Work is progressing across five main areas:
professionals. Even so, weight control and even weight
• genetic therapies loss is achievable and is frequently associated with
• use of cognitive therapies, e.g. cognitive behavioural improved behaviour, often due to the establishment of
therapy (CBT) routines and clear rules. In addition, weight control can
importantly be a source of pride and achievement for the Acknowledgements

individual with PWS.
A good multidisciplinary approach, agreed early inter- Jackie Waters (PWSA), Dr Shankar Kanumakala and Dr
ventions and careful appropriate monitoring can improve Anne Livesey.
quality of life greatly for people with PWS and their families.
Good quality nutritional support is essential to ensure PWS
individuals achieve their full potential. References, further reading, guidelines, support groups
Parents and dietitians involved in PWS are encouraged and other useful links are on the companion website:
to join the UK PWS Association charity for support and
information.
26
Eulalee Green
Eating for Children from Minority
Ethnic Groups
Introduction Vegetarian and vegan diets
The UK is the home to a multicultural and multi‐ethnic soci- Vegetarianism and veganism are common dietary practices
ety. Immigration during the late 1950s and early 1960s was in among many religious and ethnic groups. In addition,
response to labour shortages. Since the 1980s conflict in increasing numbers of the indigenous population are
Africa and Europe has led to further immigration, and, restricting their intake of meat and animal products for
together with movement of people from European Union either humanitarian, ethical or health reasons. Table 26.5
countries, the diversity of the UK has increased. As with the gives a classification of vegetarian and vegan diets. Providing
early migrations, ethnic communities have remained near that careful attention is given to ensuring nutritional ade-
large industrialised cities. These ethnic groups have intro- quacy, these diets can support normal growth and develop-
duced a wide variety of cultures, including dietary beliefs ment [4–6]. In general, the greater the degree of dietary
and practices, which have had to fit into their new lifestyles. restriction, the greater is the risk of nutritional deficiency [7].
Achieving nutritionally adequate diets became a challenge The vegan diet is most restricted. Parents who chose a vegan
with people finding themselves in an environment very dif- diet for their children should be supported to ensure that
ferent from their homeland. their children have adequate intake. A recent position paper
The top 25 countries of birth of migrants to the UK from from the European Society for Paediatric Gastroenterology,
July 2017 to June 2018 are shown in Table 26.1. Table 26.2 Hepatology and Nutrition (ESPGHAN) suggests that vegan
shows the percentage of ethnic groups in England and Wales diets in infancy should only be used under medical or die-
from the latest national census report of 2011. tetic supervision and that parents should understand the
It is essential that healthcare professionals understand consequences of failing to follow advice regarding supple-
religious and cultural attitudes towards diet when they are mentation of the diet, such as retarded growth, fat and mus-
initiating any dietary intervention in order to achieve opti- cle wasting, slower psychomotor development and an
mal growth and development in these children. Assessment increased risk of irreversible cognitive impairment [8].
of intake must be accurate, and any advice given must be Table 26.6 gives dietary sources of the nutrients most at risk
relevant to dietary custom so that it is both realistic and in a vegan diet.
achievable.
Children are subject to many outside influences and often
start to develop Westernised dietary ideas. With time, these Infant feeding
ideas are taken home and adopted by other members of the
family. The extent of adoption of dietary practices that differ The current recommendation in the UK is for babies to be
from traditional customs is variable; therefore, all diets must exclusively breastfed for around the first 6 months of life and
be individually assessed. for breastfeeding to continue for at least the first year while
Table 26.3 shows the religions practised in the UK, and solid foods are being introduced; most infants should not
Table 26.4 gives a guide to religious and cultural influences start solids until around 6 months of age [9]. There is a higher
on the diet. proportion of women from minority ethnic groups who

Vegetarian and Vegan Diets 487
Table 26.1 Top 25 countries of birth of all migrants to the UK Some vegetarian families choose to give their babies goat’s
(excluding living in communal establishment), July 2017 to June 2018. milk or ewe’s milk in the belief that these confer health ben-
efits and are preferable to cow’s milk. These milks are con-
Number of
traindicated because of their nutritional inadequacy, high
migrants Percentage of
Ranking Country of birth (thousands) population renal solute load and doubtful microbiological safety [12,
13]. The European Food Safety Authority considers that pro-
1 Poland 889 1.4 tein from goat milk can be suitable as a protein source for
2 India 862 1.3 infant formula provided the formula complies with the com-
3 Pakistan 529 0.8 positional criteria laid down in Directive 2006/141/EC [14].
Providing the maternal diet is adequate, breastmilk will be
4 Romania 410 0.6
nutritionally adequate for the first 6 months of life for most
5 Republic of 380 0.6 infants, with a recommended vitamin D supplement. Specific
Ireland
attention must be paid to the mother’s vitamin D, calcium
6 Germany 309 0.5 and iron intakes. Vegan mothers may require supplementa-
7 Bangladesh 259 0.4 tion with additional vitamin B12 [15]. Vitamin B12 deficiency
8 Italy 237 0.4 resulting in neurological damage, irritability, faltering
growth, apathy, anorexia and developmental regression has
9 South Africa 235 0.4
been reported in breastfed infants of vegan mothers [16].
10 China 210 0.3 Some algae (e.g. spirulina) and seaweeds (e.g. nori) contain
11 Nigeria 205 0.3 natural compounds that are similar to vitamin B12; however,
12 Lithuania 184 0.3 the human body cannot use these nutrients. Furthermore,
13 France 178 0.3
because they are so similar to B12, they compete with it and
can be the cause of B12 deficiency in people who do not eat
14 USA 159 0.2
animal products. Vegetarian sources of iron and vitamin B12
15 Spain 155 0.2 are given in Table 26.9.
16 Philippines 144 0.2
17 Australia 142 0.2
Weaning
18 Sri Lanka 135 0.2
19 Portugal 132 0.2 At around 6 months of age, solids should be gradually intro-
20 Jamaica 124 0.2 duced to the infant’s diet, increasing flavours and textures
21 Kenya 123 0.2 with time. Only a small number of women choose to intro-
duce solids before their child is 4 months old, but only 10%
22 Zimbabwe 116 0.2
of women wait until their child is 6 months old. Table 26.10
23 Ghana 113 0.2 shows the age of introduction of solids by ethnic group.
24 Somalia 104 0.2 Pulses must be thoroughly cooked to destroy toxins such
25 Latvia 96 0.1 as trypsin inhibitors and haemagglutinins, which may cause
diarrhoea and vomiting [13]. Breastfeeding or infant formula
Source: Office of National Statistics [1]. Licensed under Open should be continued until 1 year of age. As the child gets
Governemnt License. older, they should be encouraged to take 500 mL/day full fat
cow’s or approved calcium fortified alternative, or the equiv-
alent in cheese or yoghurt, in order to provide enough cal-
cium. Suitable weaning foods for vegetarian and vegan diets
choose to breastfeed their babies up to 6 months of age [10]
are given in Table 26.11.
(Table 26.7). There is no data about breastfeeding at 6 months
and ethnicity after 2010.
All breastfed infants and infants having less than 500 mL Children
of infant formula should be given a vitamin D supplement,
which should continue throughout childhood (p. 28) [11]. Vegan diets are typically high in fibre and low in fat, so care
Suitable vitamin drops include Healthy Start, Abidec and must be taken to ensure an adequate energy intake to sup-
Dalivit (Table 1.22). port growth. A systematic review of vegetarian and vegan
If the infant is not breastfed, an infant formula must be diets found that growth in children was similar or slightly
given. Table 26.8 shows normal infant formulas, milks and less than their non‐vegetarian peers [18]. To provide optimal
special therapeutic formulas that are suitable for vegetarian nutrition a vegetarian or vegan diet should be well bal-
and vegan families and for those who require a halal or anced, containing two or three helpings of protein foods
kosher formula. Some families will accept ‘unsuitable’ for- daily plus cereals, vegetables, fruits and fats (Table 26.12).
mulas if there is a clinical need and may seek advice and Vegetable and pulse proteins have a lower concentration
assurance from their religious leader. and range of essential amino acids than protein from animal
488 Eating for Children from Minority Ethnic Groups
Table 26.2 Percentage of ethnic groups in England and Wales, 2011.
Percentages
Total population Ethnic population
White White British 80.5

Irish 0.9 4.6
Gypsy or Irish traveller 0.1 0.5
Other white 4.4 22.5
Mixed/multiple ethnic groups White and black Caribbean 0.8 4.1
White and Asian 0.6 3.1
White and black African 0.3 1.5
Other mixed 0.5 2.6
Asian/Asian British Indian 2.5 12.8
Pakistani 2.0 10.3
Bangladeshi 0.8 4.1
Chinese 0.7 3.6
Other Asian 1.5 7.7
Black/African/Caribbean/black British African 1.8 9.2
Caribbean 1.1 5.6
Other black 0.5 2.6
Other ethnic group Arab 0.4 2.1
Any other ethnic group 0.6 3.1
Source: Office of National Statistics [2].
Table 26.3 Percentage of the UK population belonging to a religion, rich in vitamin C is given alongside iron‐containing foods to
April 2011 to March 2012. increase bioavailability. When considering recommenda-
tions for dietary fat, a vegan diet is often regarded as
Religion Population percentage Number (thousands)
‘healthy’. The essential fatty acid, docosahexaenoic acid
Christian 62.0 37 191 (DHA) (22: 6n−3), has been found to be absent from vegan
Islam/Muslim 4.6 2 755
diets [21]. DHA has an important role in growth, the health
of the retina, central nervous system and skin. Vegans
Hindu 1.4 860
should, therefore, use oils with a low linoleic‐α‐linolenic
Sikh 0.6 350 acid ratio such as walnut, rapeseed, flax and linseed oils
Jewish 0.5 287 (Table 26.13). Sources of vitamin D and calcium in the diet
Buddhist 0.4 246 are shown in Tables 26.14 and 26.15.
None or undeclared 29.9 17 927
Fruitarian diets
Source: Office of National Statistics [2].
Fruitarian diets are based on fruit and uncooked fermented
or fish sources. Therefore, careful planning of menus with cereals and seeds. These diets are nutritionally inadequate
pulse and cereal combinations is necessary to provide suffi- for children of any age and can lead to severe protein–energy
cient protein of high biological value. The protein and malnutrition, anaemia and multiple vitamin and mineral
energy content of the diet can be increased by the use of deficiencies.
nuts, beans and oils.
The main micronutrients at risk of deficiency in the vegan
diet are shown in Table 26.5. In addition, vegan children South Asian subcontinent
may require a daily supplement of 1–2 μg vitamin B12 [12].
The increased intake of phytate‐containing legumes and The communities from the South Asian subcontinent include
whole grains may lead to poor bioavailability of zinc [19] those from India, Pakistan, Bangladesh and Sri Lanka and
and iron [20]. It is important to ensure that a food or drink those who came to the UK via East Africa. Migrations to the
Table 26.4 A guide to religious and cultural influences on diet.
Food Buddhist Christian Hindu Jewish Muslim Rastafarian Seventh‐Day Adventist Sikh
Eggs Acceptable to Acceptable Acceptable to some No blood spots Acceptable Acceptable to some Acceptable to most Acceptable
some
Milk, Acceptable Acceptable Acceptable to some Acceptable Acceptable to some Acceptable to some Acceptable to most Acceptable
yoghurt
Cheese Acceptable Acceptable Not with rennet Not with rennet Not with rennet Acceptable to some Acceptable to most Acceptable to some
Pork Acceptable to Acceptable to most Rarely acceptable Not acceptable Not acceptable Not acceptable Not acceptable Rarely acceptable
some
Beef Acceptable to Acceptable Not acceptable Kosher Halal Acceptable to some Acceptable to some Not acceptable
some
Lamb Acceptable to Acceptable Acceptable to some Kosher Halal Acceptable to some Acceptable to some Acceptable
some
Chicken Acceptable to Acceptable Acceptable to some Kosher Halal Acceptable to some Acceptable to some Acceptable to some
some
Fish Acceptable to Acceptable – some only Acceptable – with Acceptable – with fins, Acceptable – with fins Acceptable – with Acceptable – with fins Acceptable to some
some fish with fins and scales fins and scales scales and backbone and scales fins and scales and scales
Shellfish Not acceptable Acceptable to most Acceptable to some Not acceptable Acceptable to some Not acceptable Not acceptable Acceptable to some
Animal Acceptable to Acceptable Acceptable to some Kosher Halal Acceptable to some Not acceptable Acceptable to some
fats some
Alcohol Not acceptable Acceptable to most Not acceptable Acceptable Not acceptable Not usually wine Not acceptable Acceptable
Cocoa, Acceptable Acceptable Acceptable Acceptable Acceptable Not acceptable Decaffeinated are Acceptable
coffee, tea suitable
Fasting Good Friday and Ash 3 days a year or 1–2 Yom Kippur 1 day of Ramadan 1 month
Wednesday for some days every week atonement (no food or fasting (no food or
liquid for 25 hours) liquid during daylight)
Other Most Buddhists Certain foods are Kosher (food fit to eat), Halal, i.e. meat must be Processed, preserved Some are vegetarians Some may be
comments are vegetarians taken during prayers. i.e. meat from animals from animals that have or tinned foods may vegetarians
or vegans, Some Hindus may slaughtered by a been bled to death and be avoided. Most
although some be vegetarians or kosher butcher. the phrase ‘in the name only eat Ital foods,
may not be vegans (Jains) Milk and dairy of God’ is said i.e. in a whole and
products are not natural state.
consumed within 3 No fruits of the vine,
hours of each other e.g. sultanas, grapes,
currants
Black and Chinese, Afro‐Caribbean, Gujarati, Punjabi, Jews of all nationalities Arab, Bangladeshi, Afro‐Caribbean Afro‐Caribbean Indian
ethnic Vietnamese Chinese, Greek, Greek Indian Pakistani, Gujarati,
minority Cypriot, Ugandan, Somali, Turkish, Turkish
groups Vietnamese, West Cypriot, Ugandan, West
African (e.g. Nigerian African (e.g. Nigerian
and Ghanaian), Indian and Ghanaian), Indian
Source: Adapted from British Dietetic Association [3].

Table 26.5 Classification of vegetarian and vegan diets.
Foods excluded Animal protein source Non‐animal protein source Nutrients at risk of deficiency
Partial vegetarian Red meat Poultry Beans Iron

Offal Fish Lentils Vitamin D
Eggs Nuts
Milk Seeds
Cheese
Yoghurt
Lacto‐ovo-vegetarian Red meat Milk Beans Iron
Offal Cheese Lentils Vitamin D
Poultry Yoghurt Nuts
Fish Seeds
Eggs
Lacto vegetarian Red meat Milk Beans Iron
Offal Cheese Lentils Vitamin D
Poultry Yoghurt Nuts
Fish Seeds
Eggs
Vegan Red meat Beans Protein
Offal Lentils Energy
Fish Nuts Omega‐3 fatty acids (especially DHA)
Poultry Seeds Vitamin D
Eggs Iron
Milk Vitamin B2
Cheese Vitamin B12
Yoghurt Calcium
Zinc
DHA, docosahexaenoic acid.
Table 26.6 Sources of nutrients at risk of deficiency in a vegan diet.
Nutrient at risk of
deficiency Suitable dietary alternative sources
Protein Pulses (soya, tofu, tempeh, beans and lentils), grains (wheat, rice, rye, millet, etc.), seeds, groundnuts*, nuts* and nut
spreads*. Meals should have a combination of grains with seeds or grains with pulses to get the right balance of essential
amino acids to ensure the best use of the available protein
Energy Vegetable oils/margarine, groundnuts, nut spreads
Iron Iron fortified cereals, wholegrain cereals, wholemeal bread, pulses, dried fruit and nuts. Dark leafy green vegetables are not
a suitable source of iron for infants and young children as the portion size is so large (120 g for 2 mg iron). Foods rich in
vitamin C, such as fruits and vegetables, aid the absorption of non‐animal sources of iron
Fat‐soluble vitamins In England, white people will make enough vitamin D for the year from 30 minutes a day of moderate sunlight from April
to October. Black and Asian people living in England will not make enough and must rely on dietary sources or
supplements: vegetable oils/margarines, fortified soya milk and fortified cereals
Essential fatty acids Whole grains, nuts, seeds and seed oils
Vitamin B2 Wheat germ, almonds, green leafy vegetables, yeast extract (e.g. Marmite, Tastex**), avocado, soya beans, fortified soya
milk
Vitamin B12 Fortified yeast extract (e.g. Marmite, Tastex**), fortified cereals, fortified soya milk, tofu
Calcium Fortified soya products (soya milk and yoghurt), seaweed products (kombu, wakame, nori), nuts and seeds. Other sources
(bread, leafy green vegetables, pulses) are not suitable sources of calcium for infants and young children as the portion size
is so large (>120 g for 100 mg calcium)
Zinc Some soya products (flour, miso, cheese and tempeh), nuts, seeds, wheat germ, wholemeal bread, fortified breakfast
cereals, seaweeds and hard cheeses
Iodine Whole grains, seaweeds and vegetables
* Whole nuts should not be given to children under 5 years of age as they are a choking hazard. Nut allergy is discussed on p. 319.
** Yeast extracts should be used with care in children under 2 years of age due to the high salt content.
South Asian Subcontinent 491
Table 26.7 Prevalence of breastfeeding at ages up to 6 months by mother’s ethnicity in Great Britain, 2010.
Total Great Asian or Asian Black or black Chinese or other

Britain (%) White (%) Mixed (%) British (%) British (%) ethnic group (%)
Birth 82 79 87 96 95 96
2 days 77 75 81 88 90 94
3 days 75 73 80 86 90 93
4 days 73 71 80 85 90 93
5 days 72 69 79 84 90 93
6 days 71 68 79 83 90 93
1 week 70 67 79 83 90 92
2 weeks 66 63 79 81 89 87
6 weeks 56 52 75 73 85 82
4 months 43 39 60 58 73 76
6 months 35 32 49 49 61 66
Source: Data.Gov.UK. Infant Feeding Survey – 2010 [10]. Licensed under Open Governement.
Table 26.8 Infant formulas and milks suitable for religious and cultural diets.
Milk‐based feeds Suitable for kosher Suitable for halal Suitable for vegetarians
Abbott PaediaSure √ √ √
Abbott PaediaSure Compact X X √
Abbott PaediaSure Fibre √ √ √
Abbott PaediaSure Plus √ √ √
Abbott PaediaSure Plus Fibre √ √ √
Abbott PaediaSure Plus juce √ √ √
Abbott Similac High Energy √ √ √
Cow & Gate Anti‐Reflux X X X
Cow & Gate Comfort X X X
Cow & Gate First Infant Milk X √ (P) X
Cow & Gate Follow-on Milk X √ (P) X
Cow & Gate Growing‐up 3 X X X
Cow & Gate Growing‐up 4 X √ (P) X
Cow & Gate Hungrier Baby X √ (P) X
Cow & Gate Nutriprem 1 X √ X
Cow & Gate Nutriprem 2 X √ X
Cow & Gate Nutriprem Human Milk Fortifier X X X
Cow & Gate Nutriprem Hydrolysed X √ X
Mead Johnson Enfamil AR √ X X
Mead Johnson Enfamil Human Milk Fortifier √ √ X
Mead Johnson Enfamil Infant √ X X
Mead Johnson Enfamil Premium √ X X
Mead Johnson Enfamil Premium Newborn √ X X
Mead Johnson Enfamil Premature √ √ X
Nestle NAN Comfort 1 X √ X
(continued overleaf )
Nestle NAN Optipro 1 X X X

Nestle NAN Optipro 2 X √ X
Nestle NAN Optipro 3 X √ X
Nestle NAN Supreme 1 X X X
Nestle NAN Supreme 2 X X X
Nestle Resource Junior X X X
Nutricia Aptamil Anti‐Reflux X √ X
Nutricia Aptamil Comfort X √ X
Nutricia Aptamil First X √ X
Nutricia Aptamil Follow‐on Milk X √ X
Nutricia Aptamil Growing‐up 3 X √ X
Nutricia Aptamil Growing‐up 4 X √ X
Nutricia Aptamil Hungry Milk X X X
Nutricia Aptamil Lactose Free X X X
Nutricia Infatrini √ √ X
Nutricia Nutrini √ √ X
Nutricia Nutrini Energy √ √ X
Nutricia Nutrini Energy Multifibre √ √ X
Nutricia Nutrini Low Energy Multifibre √ √ X
SMA Extra Hungry Infant Milk Powder X √ √
SMA First Infant Milk X √ X
SMA Follow‐on Milk Powder X √ X
Peptide‐based feeds
Abbott PaediaSure Peptide X √ √

Abbott Similac Alimentum X X √
Mead Johnson Nutramigen X X X
Mead Johnson Pregestimil X X X
Nestle Peptamen Junior Advance X X X
Nestle Peptamen Junior Liquid X X X
Nestle Peptamen Junior Powder X X X
Nestle SMA Althera X X X
Nutricia Aptamil Pepti 1 X X X
Nutricia Aptamil Pepti 2 X X X
Nutricia Aptamil Pepti-Junior X X X
Nutricia Infatrini Peptisorb √ √ X
Nutricia Nutrini Peptisorb √ √ X
Soya feeds
Mead Johnson Enfamil ProSobee √ X X

Nestle SMA Wysoy X √ √
Mead Johnson PurAmino √ √ X
(continued overleaf )
Amino acid‐based feeds
Nestle SMA Alfamino Infant X X X

Nestle SMA Alfamino Junior X X X
Nutricia Neocate Junior √ √ X
Nutricia Neocate LCP √ √ X
Nutricia Neocate Syneo √ √ X
P, powder only.
This information is correct at the time of writing.
Always check with the manufacturer.
Table 26.9 Sources of iron and vitamin B12 suitable for vegetarians.
Sources Iron (mg) B12 (μg) in the UK [2]. Traditional dietary customs are largely based
on the religious and cultural beliefs of the three main reli-
Infant formula, 200 mL 1.4 0.2
gious groups: Hindus, Muslims and Sikhs. Dietary variance
Milk (all types except UHT), 200 mL 0.4 2
Yoghurt full fat (1 medium pot), 150 g 0.3 0.3 has been observed within these groups, as income and geo-
Cheddar‐type cheese (1 slice), 50 g 0.1 1 graphical area have an influence on the diet.
Fromage frais (1 medium pot), 100 g 0.1 1.4
Soya cheese (1 slice), 40 g 0.4 0.75
Dietary customs of Hindus
Spinach boiled (3 tbsp), 100 g 4 0
Fenugreek (methi) seeds (1 tbsp), 11 g 4 0 Approximately 1.4% of the UK population are Hindu [2].
Watercress (1 bunch), 80 g 2 0
The majority originally came from the Gujarat region of
Broccoli/peas (2–3 tbsp), 80 g 1 0
India, although some are from the Indian Punjab and East
Apricots (6), figs (3) dried, 60 g 2 0 Africa [22, 23].
Raisins/sultanas (1 tbsp), 30 g 1 0
Hindus classify foods into three groups [24]:
Bread wholemeal (2 slices), 60 g 2 0.3
Bread white (2 slices), 60 g 1 0 • sattvik (nutritious foods) such as milk, fruit, vegetables,
Bran flakes (3 tbsp), 25 g 4 0.5 nuts and whole grains
Fortified breakfast cereals, e.g. 3 0.5 • rajasi (foods of strong emotions) such as meat, eggs, fish,
Special K, Cheerios (3 tbsp), 25 g spices, onions, garlic, hot peppers, pickles and other
Weetabix (2 biscuits), 40 g
pungent or spicy foods
Lentils (dhal) green/brown boiled 3 0 • tamsai (leftovers producing negative emotions), i.e.
(½ cup),100 g foods that are stale, overripe, spoilt or imperfect
Black‐eyed beans/kidney beans, chickpeas 2 0
boiled (4 tbsp), 100 g Fasting is common among Hindus to help reinforce con-
Baked beans (1 small can), 200 g 3 0 trol over the senses and to achieve closeness to God. Fasting
Hummus (2 tbsp), 50 g 1 0 occurs for a few days during holy days, new moon days and
Tofu fried (1 average serving), 50 g 2 0
festivals.
Vegeburger soya mince, fortified with B12 2.5 0.2
(1 average burger) 56 g A restriction on eating beef was introduced between 1500
and 500 BC because Hindus regard the cow as sacred. It is
Nuts, e.g. almonds, cashew, brazil 1 0
(1 average serving), 25 g
also unusual for pork to be eaten as the pig is thought to be
Seeds, e.g. melon, pumpkin, sesame 2 0 unclean. Devout Hindus believe in the doctrine of Ahimsa
(1 average serving), 30 g (not killing) and are vegetarian. Some will eat dairy prod-
Curry powder (1 tsp), 3 g 3 0 ucts and eggs, while others refuse eggs because they are
Plain chocolate (1 bar), 50 g 1 0 potential sources of life. A minority of Hindus practise
Yeast extract (spread on 1 slice bread), 1 g 0 0.01 veganism. Wheat is the staple food eaten by Hindus in the
UK. It is used to make chapattis, puris and parathas. Oil
tbsp, tablespoon (15 mL); tsp, teaspoon (5 mL). and ghee (clarified butter), which is believed to sanctify
Source: Adapted from CompEat Pro nutritional database, based on Ref. [17]. food, are used extensively in cooking [22]. Traditional
Hindus fast on 3 days a year to celebrate the birthdays of
UK began in the seventeenth century when the British East the Lords Shiva (March), Rama (April) and Krishna
India Company first began trading with India [22]. Today (August). Orthodox Hindus may also fast once or twice
the Asian community represents 34.9% of the ethnic groups every week (often on Tuesdays and Fridays). Fasting lasts
Table 26.10 Age of introduction of solids by mother’s ethnicity in Great Britain, 2010.
% Asian or % Black or % Chinese or other % Great

% White % Mixed Asian British black British ethnic group Britain total
6 weeks 1 4 2 5 1 2
8 weeks 2 4 3 5 1 2
3 months 5 4 4 9 1 5
4 months 30 24 22 33 19 29
5 months 77 69 62 65 65 75
6 months 95 90 90 90 83 94
9 months 99 99 97 99 x 99
Source: Data.Gov.UK Infant Feeding Survey – 2010 [10]. Licensed under Open Governement.
Table 26.11 Suitable vegetarian and vegan weaning foods. Table 26.13 Vegetarian sources of essential fatty acids.
Age Foods Energy α‐Linolenic Linolenic

(kcal (kJ)) acid (g) acid (g)
Around 6 months Baby rice
Initially foods may need to Cooked fruit and vegetable Nuts and seeds
be pureed or mashed Weetabix
Walnuts 6 nuts (24 g) 165 (681) 2 9
Cooked pulses and lentils with rice
or wheat foods Sunflower seeds 1 57 (238) 0 3
Pudding or custards made with cow’s tablespoon
milk or calcium fortified soya milk Brazil nuts 3 nuts (15 g) 102 (422) 0 4
7–9 months Whole grains Flaxseed 1 tablespoon (13 g) 66 (274) 3 1
Introduce lumps and soft Bread
finger food Pasta and rice Sesame seeds 1 tablespoon 66 (272) 0 3
Cooked pulses or lentils with rice or (11 g)
wheat foods Pumpkin seeds 1 tablespoon 68 (281) 0 3
Finely ground nuts (12 g)
Dried fruits
Peanuts (groundnuts)10 nuts 68 (281) 0 2
Cheese made from cow’s milk or
calcium fortified soya curd Almonds 12 nuts 70 (290) 0 1
Egg Hazelnuts 10 nuts 68 (280) 0 1
Tofu and Quorn
Oils (10 mL)
9–12 months As above
Minced and chopped texture Safflower 90 (370) 0 6
Evening primrose 90 (371) 0 7
Sunflower 90 (370) 0 7
Table 26.12 Sample vegetarian or vegan meal plan for young children.
Soya 90 (370) 1 5
Breakfast Breakfast cereal with milk or milk substitute Walnut 90 (370) 1 6
Wholemeal or white bread, margarine, peanut butter, Corn 90 (370) 0 5
other nut butter or yeast extract
*Egg Flaxseed 98 (363) 5 1
Midday Beans, dhal, lentils, soya, **nut‐based dish, *egg‐based Sesame 90 (369) 0 4
meal dish or *cheese‐based dish Peanut (groundnut) 90 (370) 0 3
Bread, chapattis, pasta, potatoes, rice, couscous or rice
Fruit or fruit‐based dessert Rapeseed 90 (370) 1 2
Evening Alternative choices from above Hazelnut 90 (370) 0 1

meal Palm 90 (370) 0 1
Drinks Dilute orange juice (not orange squash or juice drink) Olive 90 (370) 0 1
*Cow’s milk or recommended milk substitute
Water Source: Nutritics nutritional analysis software.
Snacks Nuts**, dried fruit, toast, fruit
* Not suitable for vegans.

** Whole nuts should not be given to children under 5 years of age as
they are a choking hazard.
from dawn to dusk and varies from avoiding all foods Dietary customs of Muslims
except those considered pure (e.g. rice, fruit and yoghurt)
to total food exclusion [22, 24]. Approximately 4.6% of the UK population are Muslim. With
Jainism has its roots in Hinduism. Jains practise non‐vio- the majority originating from Pakistan and Bangladesh,
lence to all living creatures, and their diet is a form of lacto‐ more recently they have been joined by Muslims from
vegetarianism that includes the avoidance of root vegetables, African countries such as Somalia, Yemen, Sudan, Morocco,
with the exception of ginger and turmeric. Syria and Lebanon [2].
The Koran provides halal guidelines [24]. Acceptable ani-
mal foods are beef, sheep, lamb, goat, deer, poultry and fish
prepared and stored under halal conditions. Unclean foods
Table 26.14 Vegetarian sources of vitamin D.
are carnivores (except fish), pork, birds of prey, reptiles,
Non‐animal foods Vit D Non‐animal foods Vit D
amphibians, rodents, insects and maggots. Wheat, usually in
(1 average portion) (μg) (1 average portion) (μg) the form of chapattis, is the staple cereal eaten by Muslims
from Pakistan, whereas those from Bangladesh eat more
Special K 31 g 1 Bran flakes 25 g 1 rice. Cooking oil is used in preference to ghee.
Ricicles 35 g 2 Sultana Bran 30 g 1 Fasting for Ramadan occurs during the ninth lunar month
Rice Krispies 29 g 2 Coco Pops 40 g 2
of the Islamic year. Muslims fast between sunrise and sunset.
Frosties 23 g 1
All‐Bran 31 g 1 Non‐dairy margarine (for 0.5 m The purpose is to purify oneself both spiritually and physi-
1 sandwich filling) 8 g cally and to share the experiences of the poor and hungry.
Children under the age of 12 years (puberty) and the elderly
Source: Nutritics nutritional analysis software. are exempt from fasting. People who are ill, pregnant,
Table 26.15 Vegetarian sources of calcium.
Milk, cheese, yoghurt and alternatives
Foods Calcium (mg) Foods Calcium (mg)
Milk, all types 200 mL 240 Soya milk, calcium enriched, 200 mL 240
Hard cheeses (1 slice), 40 g 240 Water/orange juice calcium enriched, 200 mL 292
Fruit yoghurt (1 medium pot), 150 g 240 Soya yoghurt, calcium enriched (1 pot), 125 g 150
Whole milk yoghurt (1 medium pot), 150 g 300
Milky pudding, e.g. kheer/rice pudding (1 small serving), 140 g 120
Rice dessert (1 pot), 228 g 196
Bread, cereals and alternatives
Naan bread (1), 170 g 240 Fortified breakfast bar (1 bar), 37 g 180
White or brown bread (2 slices), 60 g 120 Gluten‐free bread (2 slices), 50 g 180
White flour, self‐raising, (2 tbsp) 50 g 180 Swiss‐style muesli (1 average portion), 60 g 60
Meat alternatives
Nuts, e.g. almonds, brazils, pistachios (1 medium packet), 30 g 30 Baked beans (1 small tin), 220 g 120
Sesame and sunflower seeds (1 tbsp), 25 g 60 Bombay mix (1 medium packet), 100 g 60
Fruit and vegetables
Products Calcium (mg) Products Calcium (mg)
Spinach boiled (½ cup), 120 g 192 Dried figs (4), 40 g 92

Okra (½ cup), 92 g 68 Orange (1 medium), 160 g 40
Spring greens (½ cup), 85 g 64 Sultanas (1 portion), 18 g 12

Source: Nutritics nutritional analysis software.
menstruating or on a long journey are also excused, but are avoided during pregnancy and cold ones avoided when
expected to fast later. Unfortunately, many pregnant women breastfeeding [24].
fast with the rest of the family during Ramadan as they find
it more convenient. The Koran also dictates that children
Infant feeding
should be breastfed up to the age of 2 years.
Early studies reported lower breastfeeding rates among Asians
Dietary customs of Sikhs in the UK compared with the Caucasian population [26, 27] and
Asians in the Indian subcontinent [28]. However, high inci-
Approximately 0.6% of the UK population are Sikhs. dences of breastfeeding among Asian mothers (49% at 6
Sikhism is a relatively new religion, originating as a reform- months) compared with white mothers (32% at 6 months) have
ist movement of Hinduism in the Indian Punjab in the six- more recently been reported in the 2010 Infant Feeding Survey
teenth century [2]. [10]. Interestingly, of mothers who were born outside the UK,
Non‐practising Sikhs are not usually vegetarian, but they 30%–40% who bottle fed initially or who stopped breastfeeding
will usually avoid beef, pork and their products. They will to bottle feed reported that they would have fed their babies
also avoid halal meats preferring animals that have been differently had the babies not been born in the UK. Unfortunately,
killed with a single stroke, i.e. the jhatka method. Sikhs who for some bottle feeding is perceived as the Western ideal and,
have undergone the amrit ceremony are usually lacto‐veg- therefore, better for the baby. This problem is compounded by
etarians avoiding meat, fish, eggs and their products [24]. communication difficulties and overcrowded housing [12],
Punjabi food customs include a wide range of milk dishes making it difficult for a mother to breastfeed in privacy.
from cream, white cheese, butter, ghee and yoghurt that
include maize flatbread (roti), spinach, dhal and chickpeas.
Weaning
Common South Asian dietary habits Grains, roots and tubers are the foods first introduced. A sys-
tematic review in 2018 found that early weaning was not
Common dietary patterns across the three main groups uncommon among most Asian families, with about 70%
(Table 26.16) include alcohol abstinence and the hot and cold starting before 3 months and almost all babies being weaned
properties of foods. Many of the Asian people in the UK share by 6 months of age. However, families from Pakistan intro-
dietary customs, despite their varying religious and geo- duce complementary feeding later than other Asian groups:
graphical background. Older members of the Asian commu- 49% by 6 months of age and 15% after 7 months [29].
nity tend to retain traditional dietary customs, while second
and later generations are consuming more Westernised foods, Nutritional problems commonly found in Asian
especially convenience foods. The extent of adoption of these
children
foods is variable, tending to be greater in the younger genera-
tions who were born in the UK and in those who have lived
Faltering growth
in the UK for some time [22], although they may continue to
eat traditional meals in the evening [25]. Dietary intake, family income, housing standards, maternal
The traditional breakfast includes chapattis, parathas, education, psychological distress and morbidity all influ-
bread and, occasionally, hard‐boiled or fried eggs are eaten. ence growth [22, 26]. The incidence of lower birthweights in
The two main meals are based on staples, usually served this population has decreased recently; longer birth inter-
with a vegetable, pulse or nut‐based curry [23]. Most foods, vals, fewer teenage pregnancies and improved nutrition are
including spices, are usually fried before adding to the thought to be contributing factors [22]. Despite lower birth-
curry, which is then served with home‐made chutneys, weights, some studies show that Asian babies and children
side salads of tomatoes and onions and yoghurt. Very little grow as well as other groups [30, 31]. Table 26.17 shows
hard cheese is eaten; paneer, an Indian soft curd cheese, birthweight by ethnic group.
is preferred. Meals are usually served with tea, which is
made with hot milk and sugar, although English tea is
Iron deficiency anaemia
becoming popular. Traditionally, Asians rarely eat snacks,
although Western snack foods are increasing in popularity. Iron deficiency anaemia has been described in Asian infants.
Traditional Asian savoury snacks (usually reserved for Contributing factors include maternal iron deficiency dur-
celebrations only) are high in fat, and the sweets are often ing pregnancy, premature delivery and low birthweight.
very high in refined sugar. Many Asians believe that foods Inadequate dietary intake of iron is commonly related to the
have heating and cooling effects on the body. These hot early introduction and excessive use of unfortified cow’s
and cold foods should be eaten in the correct balance to milk. Prolonged use of a baby bottle and the mother being
achieve a healthy state. Certain hot foods cause symptoms born outside the UK have also been shown to have a nega-
such as constipation, sweating and body fatigue, while cer- tive influence on the iron status of Asian children [33].
tain cold foods lead to strength and happiness. Foods may Families should be advised on the use of foods rich in iron
also be used to treat a condition, e.g. hot foods should be and vitamin C [34].
Table 26.16 Foods commonly eaten by the Asian population in the UK.
Food Nutrient Method of cooking
Cereals Energy Baked, boiled, fried:

Breakfast cereals, wheat, bread, rice, semolina, ground rice, bajri B vitamins chapatti, paratha, poppadom, bhaji, poori,
(millet flour), puffed rice, rice flakes pakora, porridges, samosa, sweetmeats
Tubers Energy Boiled, fried, curries
Arvi/colocasia root, cassava, taro tuber, yam
Vegetables Vitamin A Boiled, fried, curries, chutneys, pickles
Ackee, amaranth (tanjurdo), aubergine (ringun), colocasia leaves, Riboflavin
mustard leaves, radish leaves, cluster beans, mint leaves, fennel Folic acid
leaves, okra, brinjal pepper, cho cho/chayote, fenugreek leaves, Vitamin C
bitter gourd (darela/dudhi/turia/gulka), kantola, patra leaves, Iron
spinach (palak), leeks, tomatoes Calcium
Fibre
Pulses Energy Curries, fried, snack
Peas, beans, balor/valor/urad gram, chickpeas (chana dhal), lentils Protein
(masoor), black‐eyed beans, whole urad dhal (black gram), whole B vitamins
mung dhal, sprouted pulses Iron
Fibre
Seeds and nuts Energy Fresh, fried, snack
Sesame seeds, peanuts, dried coconut, pistachios, almond, Fibre
cashew nuts Iron
Fruits Vitamin A Raw, curries, chutneys
Banana, citrus fruits, unsweetened juices, dates, blackcurrants, Vitamin C
figs, raisins, apricots, prune/prune juice, guava (jamphal), mango, Fibre
sapodilla (sapota/chiku)
Milk products Energy Milk drinks: boiled, fresh
Milk, yoghurt, cheese/paneer Protein Cheese: fresh, fried
Vitamin A
Eggs Protein Fried
Riboflavin
Nicotinic acid
Vitamin D
Fats and oils Energy Frying, spreading
Ghee/clarified butter Essential fatty acids
Vegetable oil
Margarine
Table 26.17 Percentage low birthweight by ethnic group.
Asian Black White
Birthweight Bangladeshi Indian Pakistani African Caribbean White British White other Other Not Stated
Under 2.5 kg 7.3 6.6 6.2 3.2 4.1 2.6 2.3 3.3 3.1
2006
Under 2.5 kg 5.6 5.6 4.7 2.8 4.3 2.4 2.0 3.0 2.7
2015
Source: Office of National Statistics, 2017 [32]. Licensed under Open Government License.
Megaloblastic anaemia Rickets

Megaloblastic anaemia resulting from vitamin B12 deficiency The steady decline in rickets in the UK was halted in the
has been observed in some strict vegetarian and vegan late 1960s and early 1970s when a number of cases appeared
Asians [35, 36]. Education regarding vitamin B12 sources in in immigrant families, mainly of Asian origin [37–39].
the vegetarian diet is required, and supplementation may be There is evidence that the incidence that was once in
needed in the vegan diet. decline is now resurging [40]. The weaning diets of infants
should include foods rich in vitamin D such as fortified Table 26.18 Prevalence of overweight and obesity (%) within ethnic
milk products, eggs, oily fish, liver, fortified breakfast cere- groups in England, 2017/2018.
als and margarine. Vitamin D supplementation is advisa-
Reception year (4‐ and Year 6 (10‐ and
ble for infants, young children and deficient pregnant
5‐year‐old children) 11‐year‐old children)
women to prevent neonatal hypocalcaemia and rickets
[11]. In addition, children should be encouraged to play White 22.5 32.2
outside [41]. Mixed 21.5 36.2
Asian or Asian 18.5 39.6
British
Dental caries
Black or black 29.3 45.0
Traditionally, sugary foods are reserved for celebrations British
and, therefore, do not have a major role in Asian diets. Chinese 18.3 30.1
However, with increasing Westernisation, over consump-
Any other 23.5 39.6
tion of refined sugar leading to a high incidence of dental
ethnicity
caries has been observed in Asian preschool children [42].
Asian mothers often add sugar to babies’ bottles and give Unknown 22.9 35.0
sweetened drinks via the bottle for prolonged periods. These
Source: NHS Digital. [44]. Licensed under Open Governement.
drinks, as well as having high sugar content, are acidic,
which can lead to tooth decay [43]. Education regarding
infant feeding with the restriction of quantity and frequency
of sugar intake, the use of fluoride‐containing drops and
toothpaste and frequent dental visits will help to reduce the Dietary customs
incidence of dental caries.
Most Afro‐Caribbeans are Christians, such as Seventh‐Day
Adventists, Pentecostals, Baptists and Rastafarians. A high
proportion of Afro‐Caribbeans living in the UK has adopted
Obesity and diabetes
the dietary patterns of the wider UK population than other
With the increasing consumption of high sugar and high fat ethnic groups. However, a small group retain traditional
foods, the prevalence of obesity is increasing. The incidence meal patterns.
of obesity and diabetes is higher in Asian children aged Seventh‐Day Adventists and Pentecostals aim to eat foods
10–11 years than in white children (Table 26.18). In addition that are natural and have few dietary restrictions; they abstain
to restricting these foods, advice on acceptable Asian food from eating pork and fish without scales. Alcohol, caffeine
alternatives and appropriate cooking techniques must be and high intakes of sugar and salt are discouraged. Some
given. The dietary fat intake can be reduced by avoiding Seventh‐Day Adventists may also be lacto‐vegetarians.
deep‐fried foods, reducing the amount of oil or ghee used in Rastafarians aim to eat food in their natural states (Ital
cooking and restricting or not adding fat to chapattis. foods). Some avoid meat completely to obey the command-
Avoiding the popular sweet sugary tea and Asian sweet- ment ‘thou shalt not kill’ and follow a lacto‐ovo-vegetarian
meats will reduce dietary sugar. or vegan diet [48]. Vinegar, raisins, grapes and wine are also
avoided by some Rastafarians as the Nazarite law states that
fruits of the vine should not be eaten.
Afro‐Caribbean communities The two main meals are taken at breakfast time and in
the evening [49]. Traditional breakfasts include fried plan-
The earliest migration from the Caribbean to the UK began tain, cornmeal dumplings and fried dumplings. However,
in the eighteenth century with the trade in people. Small many dietary practices have now been adopted from
communities settled around the major British port cities of British culture, with toast and breakfast cereals largely
Bristol, Liverpool and London. In the second wave in the replacing these foods. The evening meal is more likely to
nineteenth century, there was recruitment from the Caribbean contain traditional foods, especially with the younger gen-
for both the Royal and Merchant Navy. The settled commu- eration who seem keen to retain their identification and
nities continued to serve in the First and Second World War. culture. Cereals and tubers such as rice, green banana, yam
The final migration occurred after the Second World War and sweet potato form the main part of the diet [50]. These
when people from former British colonies were invited to starchy foods are served with small amounts of meat or
the UK to support major industries, public services and the fish [49]. The tropical climate in the homeland makes it dif-
NHS [45]. The largest phase of migration from the Caribbean ficult to keep foods fresh, and, therefore, preserved meat,
occurred in the 1940s and 1950s [46, 47]. Most were recruited fish and milk are eaten. Peas, beans, nuts and green leafy
to re‐staff national transport and health services [45]. The vegetables are widely used, often being made into home‐
Afro‐Caribbean community is 1.1% of the UK population made soups and stews, which are well seasoned with herbs
and 5.6% of ethnic minority groups in the UK [2]. and spices [50].
Chinese Communities 499
Infant feeding Rickets

Rickets is common among Afro‐Caribbean children and vita-
Infant feeding is mainly influenced by the place of birth,
min D supplementation is beneficial.
knowledge of traditional practices and advice from relatives.
Over 95% of black or black British women breastfeed their
Lactose intolerance
babies initially, and 61% are still exclusively or mixed breast-
feeding when their child is 6 months old; this is higher than There is a high incidence of lactose intolerance because of
the UK average of 35% [10]. hypolactasia among the Afro‐Caribbean population. A
reduction in, and occasionally the avoidance of, the con-
sumption of milk and other foods containing lactose will
Weaning usually reduce symptoms.
Infants use to be traditionally weaned as early as 1 month of Chinese communities

age with 45% reported to be receiving solid food by 3 months
of age [49, 50]. The 2010 Infant Feeding Survey [10] indicates Today Chinese people represent 0.7% of the UK population
that most black and black British women now delay the and 5.6% ethnic groups in the UK [2], with roots from the
introduction of solids to between 4 and 6 months. Late wean- Caribbean, Hong Kong, Taiwan, China, Malaysia, Vietnam
ing now only occurs in less than 10% of babies from this and Singapore [57]. The common religions include
group. Common weaning solids include high starch foods Buddhism, Confucianism, Taoism and Islam.
with a low nutrient density such as cornmeal, oats or rice
porridge. This practice may lead to energy, protein, vitamin
and mineral deficiencies if continued for a long time [13–16, Dietary customs
18–54]. The common practice of adding thin porridge to bot-
tles should be discouraged as it can lead to a delay in the Dietary habits vary according to the country and region of ori-
weaning process. It is also common for infants to be given gin. Very few foods are avoided, with the exception of the
bush teas (infusions of herbs and leaves) as a cure for minor Chinese Muslim population not eating pork. Eggs are highly
ailments [49]. Care should be taken to ensure that these are valued as they are regarded as food for the brain. Northern
not given instead of milk. By the age of 9 months, most China has a cool climate favouring the growth of wheat,
infants are eating family foods with the diet having both tra- maize, sorghum and millet. These staples are often made into
ditional and Western influences [49]. steamed bread, dumplings, pancakes or noodles [24, 57].
Meals are often based on root vegetables such as sweet potato
and turnip, with very little meat being eaten. In contrast,
Nutritional problems found in Afro‐Caribbean because of its high rainfall, rice is the staple in southern China.
children Fresh vegetables and fruit are also found in abundance [57]. In
the East, because of the long coastline, fish and shellfish are
Obesity and diabetes plentiful. In the West, livestock are reared, and, therefore, the
consumption of meat, milk and cheese is much higher [57].
With the adoption of British dietary customs, there has been
Traditional breakfasts include rice porridge (congee),
an increase in the consumption of high sugar and high fat
served either plain or with liver, meat, salted fish, salted
convenience foods and drinks. This has led to an increased
eggs or Chinese cheese and a soup made from rice and meat
prevalence of obesity and diabetes in Afro‐Caribbean chil-
[24, 57]. These traditional foods are, however, slowly being
dren compared with white children.
replaced by Western alternatives. The midday and evening
meals consist of boiled rice or noodles and a variety of
Iron deficiency anaemia highly seasoned dishes such as fried or steamed meat and
fish and stir‐fried vegetables. Raw food is rarely eaten, as
Iron deficiency anaemia has been observed in Afro‐Caribbean fertiliser in China commonly contains human manure.
children living in the UK. The main causes were thought to Meals are usually served with either China tea or a thin
be prolonged bottle feeding, late weaning onto foods with soup and then followed with fruit. Sweet foods are usually
low iron content and the early introduction and excessive reserved for special occasions [24, 57]. The main health con-
use of cow’s milk [51]. However, late weaning now only cern is the high salt intake associated with many of the pre-
occurs in less than 10% of babies from this group [10]. served foods, seasonings and soya sauce. A high fat and
refined sugar intake associated with the increasing con-
sumption of Western foods, especially by the younger gen-
Megaloblastic anaemia
eration, is also of concern [57]. A high incidence of lactose
There have been reports of megaloblastic anaemia in intolerance, because of hypolactasia, is also becoming
Rastafarian children living in Jamaica [55, 56]. Vegan chil- apparent with the increasing consumption of milk and other
dren may require vitamin B12 supplementation. dairy products [57].
Yin and Yang foods Vietnamese communities

To Chinese people health is perceived as the maintenance of Some 75% of Vietnamese settlers in the UK are ethnic Chinese
a sound body and mental state rather than absence of dis- and, therefore, share many of the Chinese traditions [57].
ease. In traditional Chinese medicine there is a balance Most arrived in the UK during the 1970s. Common religions
between Yin (feminine energy, cold, passive) and Yang (mas- among Vietnamese are Buddhism, Roman Catholicism and
culine energy, hot, aggressive) [24, 57]. In illness the balance Confucianism.
becomes disturbed and the body becomes either too hot or
too cold. Tolerance of Yin and Yang increases with age. Thus,
an adult can eat a much wider variety of foods than can a Dietary customs
child. The classification of foods varies: in general meat,
duck, goose, oily fish, potatoes, coffee, chocolate, sugar, nuts, The Vietnamese diet is typically high in carbohydrate and
herbs, spices, alcohol and fats are regarded as hot foods; low in fat [61]. Vietnam borders the ocean and has an exten-
chicken, milk, rice and some vegetables are neutral foods; sive river system, and, therefore, fish and shellfish are staple
fish, shellfish, soya beans, certain fruits and vegetables and parts of the traditional diet. There are no forbidden foods;
barley water are cold foods. Stewing, deep fat frying, grilling however, certain unfamiliar foods such as lamb, ox liver,
and roasting make foods hotter, steaming neutralises, and tinned or cooked fruit and some root vegetables may be
boiling and stir frying have a cooling effect [24, 57]. The avoided [24]. Rice is the main staple food and is served
Chinese believe that a healthy diet should be three parts either boiled or fried with small amounts of meat or fish.
Yang and two parts Yin. The balance should be changed for Like Chinese food, main dishes are often heavily seasoned,
certain illnesses (e.g. for hyperactivity more Yin foods should and vegetables are lightly steamed or stir‐fried in oil or lard.
be eaten than Yang foods). The resultant high sodium intake is the main health issue.
During pregnancy and after childbirth, the woman’s body Very little fresh milk, butter, margarine and cheese are used
is thought to become cool, and, therefore, cold foods are because of their lack of availability in Vietnam and the high
avoided. Alcohol, ice cream, mutton, beef and fizzy drinks incidence of lactose intolerance. Snacks of roasted nuts,
are also avoided. In addition, if the woman is breastfeeding, sweet potatoes, rice or noodle soup, spring rolls and fresh
green vegetables and fruit are avoided because of concern fruit are frequently eaten. Common beverages include tea,
that they may give the baby diarrhoea. Consequently, breast- coffee and fruit juice, and alcohol is taken on special occa-
feeding mothers often have a high protein intake [57]. sions [24].
With increasing Westernisation, the intake of high sugar
Infant feeding and high fat snack foods is increasing, especially in the
younger generation. This has led to an increase in dental car-
In the UK, Chinese women often return to work soon after ies and obesity in the Vietnamese population, both in the UK
childbirth, which has led to a decrease in the rate and dura- [62] and other countries [63]. Unfortunately, obesity is tradi-
tion of breastfeeding [58, 59]. Soya bean oil, which is a poor tionally seen as a sign of prosperity.
source of essential fatty acids, is a major source of fat in the The Vietnamese people observe hot and cold food princi-
Chinese diet. Because of this, breastmilk has been found to ples, similar to the Chinese. In contrast to the Chinese, how-
have a low concentration of DHA and arachidonic acid (AA) ever, pregnancy is regarded as a hot condition, and, therefore,
[60]. It has, therefore, been suggested that mothers who are women eat less red meat and fish. A traditional stew called
breastfeeding their infants should supplement their diet with Keung Chow, made from pigs’ trotters, boiled eggs, vinegar
a good source of DHA and AA such as fish oil. Because infant and ginger, is given to women after childbirth to help recov-
formula is regarded as hot, bottle‐fed babies are often given ery and to celebrate the birth of the child. After childbirth,
frequent cooling drinks such as water and barley water. women are encouraged to eat hot foods to regain their
Most infants are weaned at 3 months of age. Traditionally, strength [24].
rice‐based porridges were introduced, but commercial baby
foods are being used [57]. A study examining Westernisation
of the nutritional pattern of Chinese children living in France Infant feeding
reported that at 1 year of age, Chinese children mainly con-
sumed a traditional diet. The intake of dairy products and Since their arrival in Westernised countries, including the
fresh fruit was very low and that of soft drinks high, result- UK, Vietnamese mothers have abandoned traditional infant
ing in suboptimal calcium and vitamin C intakes [58]. In feeding practices in favour of more modern bottle feeding
general, infants are thought to have a hot equilibrium, and, methods [63–65]. In addition, many Vietnamese women
therefore, neutralising or cooling foods are considered best believe that breastfeeding will cause their breasts to sag.
for them. It is common practice for children to be given after- Hence, the incidence of breastfeeding is low, and there is a
noon tea consisting of cooling foods such as bread, biscuits, need for culturally sensitive health education programmes
cake, barley water and herb teas to counteract the heating to support breastfeeding in this group. Infants are typically
effect of school meals [57]. given a rice‐based porridge at around 6 months of age;
Jewish Communities 501
minced meat and vegetables are given at 9 months and more Infant feeding
solid food at 1 year.
Almost all women breastfeed, often for 2–3 years. Breastmilk
Iron, calcium and vitamin D is not offered in the first 24 hours when infants may be given
sugar water or fresh cow’s or goat’s milk. Colostrum is
There is an increased risk of iron deficiency in young thought to have a poor nutritional value or to be unhealthy,
Vietnamese children [66]. This is particularly associated with and it often expressed and discarded. A mixture of rice and
a high milk intake and poor body weight. cow’s milk is introduced at 6 months of age, and drinks from
Children are at risk of calcium deficiency, especially if a cup are offered at 6–8 months.
minimal milk and associated products are eaten. The rice
traditionally grown in Vietnam is a good source of cal- Calcium and vitamin D
cium, but is unavailable in Britain. Traditional Vietnamese
fruit and vegetables also contain more calcium than British The traditional Somali diet is low in vitamin D and calcium
varieties [24]. and could give rise to poor bone mineralisation and the
Vitamin D deficiency has been noted in Vietnamese chil- development of osteoporosis [67]. Vitamin D deficiency has
dren; supplementation is beneficial [24]. been reported in 82% of Somalis living in Liverpool [67].
Dietary advice should focus on improving the intake of these
nutrients from dietary sources with additional supplementa-
Somalian communities tion with vitamin D where appropriate.
Somalis first settled in the UK in 1914 when they were Jewish communities
recruited to fight in the First World War. They are now
thought to be the oldest African community in London. The dietary laws of the Jewish community (kashrus) are
Later arrivals included Somalian asylum seekers who fled based around foods fit to eat (kosher) and foods that are for-
the civil unrest in their country and settled around the main bidden (treifah) [68]. The laws of kashrus may be set aside
cities in the UK. Today there are second‐, third‐ and fourth‐ for life‐threatening conditions and only applies to food or
generation Somalis living in the UK. substances that are ingested orally.
Kosher laws prescribe that only certain meat and fowl can
be eaten and all must be slaughtered as humanely as possi-
Dietary customs
ble and prepared in a way that ensures that as much blood
has been removed as possible. Meat and milk products, or
Somalis are of Arab‐African ethnicity and their faith is Islam.
foods containing them, must be stored separately and
Therefore, they share many of the Islamic (Muslim) dietary
cooked using separate utensils. Meat and milk foods cannot
customs. Somalia was formed in 1960 from a British protec-
be eaten in the same meal, and there must be a break of a
torate and an Italian colony. As a result, many southern
minimum of 3 hours before the other food can be eaten. Only
Somalis eat Italian food, and spaghetti is a national dish. The
milk from kosher animals that has been bottled under the
Somalian diet tends to be relatively high in protein.
supervision of a kashrus authority may be drunk.
Breakfast usually consists of 2–3 pieces of injera (fer-
Fish, fruit and vegetables are known as parev (neutral)
mented pancake-like Somali bread made from corn and
because they do not contain meat or milk. These foods can
wheat) with ghee or butter and tea. Lunch is the main meal
be eaten with either meat or milk‐containing foods. All
and usually consists of spaghetti or rice with a meat sauce
fruits and vegetables are kosher; however, care must be
(beef or goat) and mixed vegetables. Food is often flavoured
taken to ensure that they do not contain any insects. With
with aromatic spices (cumin powder, cinnamon, cloves, car-
regard to seafood, only certain species that can clearly be
damom, garlic, cilantro, parsley). Pork is avoided and
recognised as ‘fish’ are kosher. Eels, crabs and shellfish
chicken, fish and eggs are not usually eaten. The evening
are treifah.
meal consists of injera or bread with butter and jam, or a
The Really Jewish Food Guide (www.kosher.org.uk) lists
traditional meal of rice, beans, butter and sugar. Desserts
commercially produced foods that are deemed to be accept-
and snacks are not considered as part of the daily diet.
able for a kosher diet.
Sweets are usually given to children, but are not usually
The prevalence of breastfeeding among Jewish families is
eaten by adults. Children usually drink cow’s or goat’s milk
very high; however, where infant formula is required, it
three times or more each day. From the age of 3 years, sweet-
should be kosher certified (Table 26.8).
ened tea is usually added to the milk. During pregnancy,
Somali women tend to decrease their meals to ensure an
easier delivery. They believe that too much food will make References, further reading, guidelines, support groups
the baby grow too big, and it will be hard to deliver nor- and other useful links are on the companion website:
mally. The diet usually improves during the third trimester,
although most women do not take prenatal vitamins.
27
Fiona J. White
Inherited Metabolic Disorders:
Introduction and Rare Disorders
This chapter provides information on normal metabolic including the catabolic processes to produce energy and
processes and how these are affected in inherited metabolic urea (the detoxification product of the nitrogen moiety of
disorders (IMD). Also discussed are the basics of inheritance amino acids) and anabolic processes to form tissue protein
and how this relates to IMD, newborn screening (NBS), an and energy stores, glycogen and lipids. Together these pro-
overview of dietary treatment modalities for those disorders cesses are known as intermediary metabolism.
treatable with dietary manipulation and, briefly, the role of
transplantation.
Carbohydrate metabolism
The final section covers IMD requiring nutritional support
and management with a ketogenic diet.
Cellular carbohydrate (CHO) metabolism involves both
catabolic (glycolysis, glycogenolysis) and anabolic (glyco-
Metabolism genesis, gluconeogenesis) processes. Carbohydrates, as
monosaccharides (glucose, fructose, galactose), are absorbed
Metabolism describes the chemical processes that occur in the in the intestine and then transported to the liver where
body’s cells to produce energy and other substances needed excess glucose, galactose and fructose are converted to glu-
for normal body functioning. It comprises two elements: cose‐6‐phosphate (G‐6‐PO4). Depending upon energy needs,
G‐6‐PO4 undergoes either catabolism to form energy or
• anabolism – the formation and storage of complex com-
anabolism to form glycogen, the storage form of glucose, in
pounds needed for growth, tissue repair and energy stor-
liver and muscles. To produce energy, G‐6‐PO4 (derived from
age from simpler molecules
monosaccharides from dietary CHO or from glycogen deg-
• catabolism – the breakdown of large complex molecules
radation by glycogenolysis) undergoes glycolysis. A series of
to provide energy for cellular activity and smaller com-
enzyme reactions in the glycolytic pathway convert G‐6‐PO4
pounds, e.g. amino acids, needed for anabolic reactions
to form pyruvate or lactic acid and then to acetyl‐CoA.
or for elimination from the body
Acetyl‐CoA is also produced from fatty acid oxidation and
Commonly the term metabolism defines the digestion and degradation of the carbon skeleton of the glucogenic amino
absorption of food together with how its components (carbo- acids (Table 27.1). Acetyl‐CoA enters the Krebs cycle, also
hydrates, fats and proteins) are transformed into energy via known as the citric acid or tricarboxylic acid (TCA) cycle,
a sequence of chemical reactions (metabolic pathways), within the mitochondria. Within the Krebs cycle acetyl‐CoA,
which are controlled by large numbers of different enzymes. combined with oxaloacetate, undergoes cycles involving
Enzymes themselves are proteins. These biochemical reac- eight enzymes, when reducing equivalents are produced,
tions frequently involve cofactors, often vitamins, which which then enter the electron transfer chain for the produc-
help the specific enzyme function, e.g. vitamin B6 is the tion of energy as adenosine triphosphate (ATP). When cells
cofactor for the enzyme cystathionine β-synthase, which do not require G‐6‐PO4 for energy production, it undergoes
converts the amino acid homocysteine into cystathionine. glycogenesis to be stored as glycogen until required to
Figure 27.1 illustrates the metabolic processes involved in restore blood glucose levels. G‐6‐PO4 can also be produced
the overall metabolism of carbohydrates, lipids and protein via pyruvate from protein catabolism of several glucogenic

Metabolism 503
Proteins Carbohydrates Lipids

Amino acids Glucose, fructose, galactose Fatty acids
glycerol
Glycogenesis
Lipolysis
Nitrogen pool Glycogen Glucose-6-phosphate
Glycogenolysis
Gluconeo Glycolysis Lipogenesis
genesis
Tissue protein Lactic acid Pyruvic acid β-oxidation of

fatty acids
Acetyl-CoA
Ammonia
ADP ADP ADP
CO2 O2
2H+
Urea cycle Krebs (TCA) Electron transport chain
cycle
2e– H2O
ATP ATP ATP
Urea CO2
Figure 27.1 Summary of metabolism of carbohydrates, lipids and protein. TCA, tricarboxylic acid cycle; ADP, adenosine diphosphate; ATP, adenosine
triphosphate.
Table 27.1 Classification of amino acids. initially hydrolysed by lipases into glycerol and free fatty
acids. Glycerol is then oxidised to acetyl‐CoA via pyruvate.
Glucogenic only Ketogenic only Ketogenic and glucogenic Lipid transport is a complex process and is discussed in
Alanine Leucine Isoleucine
Chapter 30. Long chain fatty acids enter the mitochondria
via the carnitine transport cycle (medium chain fatty acids
Arginine Lysine Phenylalanine
enter primarily independent of carnitine) into the β‐oxida-
Asparagine Threonine tion spiral in which fatty acids, via a series of enzymes, pro-
Aspartate Tyrosine duce acetyl‐CoA and electron carriers. Acetyl‐CoA can enter
Cysteine Tryptophan the Krebs cycle or form ketone bodies in the liver. Electron
carriers (flavin adenine dinucleotide, FADH2, and nicotina-
Glutamate
mide adenine dinucleotide, NAD) enter the electron transfer
Glutamine chain to produce ATP. Acetyl‐CoA in excess of requirements
Glycine for energy production via the Krebs cycle is converted via
Histidine lipogenesis to stored lipids in adipocytes.
Methionine
Proline Protein metabolism
Serine
Dietary protein is broken down into 20 individual amino
Valine
acids for absorption. Of these nine are essential or indis-
pensable (histidine, isoleucine, leucine, lysine, methionine,
phenylalanine, threonine, tryptophan, valine) as they can-
not be synthesised by the body. The other 11 (alanine, argi-
amino acids or breakdown of glycerol from lipids, via glyc-
nine, asparagine, aspartic acid, cysteine, glutamic acid,
eraldehyde‐3‐PO4, both within the gluconeogenesis path-
glutamine, glycine, proline, serine, tyrosine) are classified
way (Table 27.1).
as non‐essential amino acids (NEAA), or dispensable, as
they can be produced from the breakdown of essential
Lipid metabolism amino acids (EAA) by transamination. A few of the NEAA
become conditionally essential in certain disorders or at
Dietary fat is present mainly as long chain triglycerides, times of stress. These include arginine, cysteine, glutamine,
comprising a glycerol backbone and fatty acids. Dietary fats, glycine, proline and tyrosine and in such circumstances
and lipids produced endogenously from acetyl‐CoA, are must be provided in the diet.
504 Inherited Metabolic Disorders: Introduction and Rare Disorders
Nitrogen pool
Tissue protein Dietary protein

Plama proteins
Haemoglobin
Glucose
Hormones
Glycogen
Enzymes
Lipids
Antibodies Amino acid pool
Non-protein compounds
Haeme
New amino acids Catabolism
Heterocyclic amines
Carbon dioxide
Water
Urea
Energy
Figure 27.2 Function of the amino acid pool.
Amino acids enter the body’s nitrogen pool (Figure 27.2) • responding to signals from other cells, involving
and are used to form proteins needed for growth and body hormones and growth factors
tissue repair or are catabolised by transamination and deam-
ination. The amine group (nitrogen moiety) undergoes
Influence of hormone regulation
transamination, in which it is transferred to a keto acid pro-
ducing a new amino acid and a new keto acid, and then
Hormones are released according to metabolic status
deamination to produce ammonia, which is detoxified via
including whether in the fed or starved state and stress.
the urea cycle to produce urea, which is then excreted in
Their regulation of metabolic pathways (Table 27.2) plays a
urine. The carbon skeletons of amino acids (organic acids)
crucial role by:
are either glucogenic, ketogenic or both (Table 27.1).
Glucogenic amino acids degrade either: • altering the availability of substrates, e.g. the sympa-
thetic nervous system response during exercise increases
• directly to Krebs cycle intermediates
the mobilisation of glucose from glycogen, fatty acids
• via acetyl‐CoA or acetoacetyl‐CoA to oxaloactetate,
from adipose tissue [1] and insulin being released in
which is either used in the Krebs cycle or can be con-
response to high blood glucose levels and glucagon
verted to phosphoenolpyruvate and used to produce
being released when glucose levels are low
G‐6‐PO4 via gluconeogenesis
• influencing enzyme activity, e.g. adrenaline, a fight and
• to pyruvate, which can either be used to produce G‐6‐
flight hormone, increases phosphofructokinase (PFK)
PO4 via gluconeogenesis or converted irreversibly to
activity, an important enzyme in glycolysis. In addition
acetyl‐CoA by the pyruvate dehydrogenase (PDH)
glucocorticoids and thyroid hormones also affect energy
complex. Acetyl‐CoA can then enter the Krebs cycle
metabolism
Ketogenic amino acids degrade to acetoacetate or acetyl‐
CoA and are used in fatty acid synthesis or ketone body
Inheritance
production (Figure 27.3).
In 1911 Johannsen [2] introduced the theory that genes were
Control and regulation of metabolism responsible for inheritance, and in 1941 Beadle and Tatum
hypothesised the one gene, one enzyme theory [3]. The
To maintain homeostasis within cells, metabolic pathways molecular disease concept in which gene mutations alter
have to be finely balanced (Figure 27.4). This is achieved by protein structure by changing a single amino acid within the
either: protein was introduced by Pauling et al. [4] and Ingram [5]
with their work on sickle cell anaemia.
• flux through pathways increasing or decreasing by intra-
The structure of deoxyribonucleic acid (DNA), from which
cellular self‐regulation of reactions (feedback), by respond-
genes are formed, was described by Watson and Crick in
ing to concentrations of substrates or products, e.g. a low
1953. DNA contains:
concentration of an essential product causes increased
enzyme activity in the metabolic pathway, resulting in • information as a code made up of four chemical (nucleo-
increased product production from the substrate tide) bases: adenine, cytosine, guanine and thymine
Inheritance 505
Cysteine
Glycine
Serine
Leucine
Threonine
Lysine
Tryptophan
Glucose Phenylalanine
Isoleucine Tryptophan
Leucine Tyrosine
Tryptophan
Pyruvate
Phosphoenoylpyruvate
Acetyl CoA Acetoacetyl-CoA

Asparagine Oxaloacetate
Aspartate
Lipogenesis Ketone
Aspartate Citrate Bodies
Fumerate
Phenylalanine
Tyrosine
Succinyl α-ketoglutarate
CoA
Arginine
Isoleucine Glutamate
Methionine Glutamine
Threonine Histidine
Valine Proline
Figure 27.3 Catabolism of amino acids.
Metabolism
Anabolism Catabolism
Glycogen Glucose Glycogen
Protein Amino acids Protein
Triglycerides Fatty acids Triglycerides
Insulin Glucagon
Growth hormone Adrenaline
Thyroxine Cortisol
Figure 27.4 Hormonal regulation of metabolic balance.
ribonucleic acid (mRNA). mRNA carries this infor-

• the sequence of bases provides information for building
mation out of the nucleus into the cytoplasm for
and maintaining body structures
translation
• DNA sequences are made up of exons and introns:
⚬⚬ translation where ribosomes read the sequence of
⚬⚬ exons are coding sequences that contain information
mRNA bases. Three base (codon) sequences code for
to encode for a protein
specific amino acids (AA). Transfer RNA (tRNA) then
⚬⚬ introns, which occur between exons, do not code for
assembles the protein by sequentially adding AA
proteins
until a stop codon (a three‐base sequence that does
• the process of a gene expressing for a protein involves
not code for an AA) is reached
two significant steps:
⚬⚬ transcription, within the cell nucleus, which involves Genetic disorders arise due to mutations (changes) in the
the transfer of information in the DNA to messenger DNA sequence:
Table 27.2 Summary of the action of hormones on metabolic pathways.
Blood levels
Anabolic or Fatty Amino

Hormone catabolic Stimulates Inhibits Glucose acids acids
Insulin Anabolic Uptake of glucose by muscle • Gluconeogenesis

Released in response to: and adipose tissue • Glycogenolysis
• Increased blood glucose • Glycolysis • Lipolysis
• Increased blood amino acids • Glycogenesis • Fatty acid
• Lipogenesis oxidation
Cellular uptake of • Proteolysis
• Amino acids • Ketogenesis
• Protein synthesis
Glucagon Catabolic Glycogen breakdown and • Glycogenesis
Released in response to: formation of glucose • Lipogenesis
• Decreased blood glucose • Glycogenolysis • Protein synthesis
• Decreased blood amino acids • Gluconeogenesis
Fat breakdown by
• Lipolysis
• Fatty acid oxidation
Adrenaline (epinephrine) Catabolic Glucagon and cortisol • Insulin release
Released in response to: release resulting in glycogen
• Exercise breakdown and formation of
• Strss (stimulates sympathetic glucose
nervous system) • Glycogenolysis
• Gluconeogenesis
Fat breakdown:
• Lipolysis
Cortisol Catabolic Decreased glucose, fatty acid
Released due to physiological and and amino acid uptake by all
emotional stress tissues except brain
Supports effects of decreased insulin • Gluconeogenesis
and increased glucagon secretion • Lipolysis
Growth hormone Anabolic Muscle protein synthesis • Glucose uptake
Released in response to Mobilisation of free fatty acids by muscles
• Hypoglycaemia • Lipolysis (glucose sparing)
• Increased plasma amino acid levels Reduced cellular glucose
• Increased metabolism associated uptake
with growth, exercise • Gluconeogenesis
Thyroxine Catabolic Increases ATP production by Indirectly
Slow response to metabolic changes • Glycolysis
Increases sensitivity to epinephrine, • Glycogenolysis
glucagon and growth hormone • Lipolysis
Increases basal metabolic rate • Fatty acid oxidation
ATP, adenosine triphosphate.
• an error in the coding sequence of a gene can result in Further information can be obtained at https://ghr.nlm.
no protein or an abnormal protein or enzyme being nih.gov and www.genomicseducation.hee.nhs.uk/genetics
produced 101/genes.
• many mutations are benign (silent), whereas others lead
to variable severity of defect (Table 27.3) Patterns of inheritance
• gene mutations result in a genotype that predicts residual
enzyme activity Autosomal recessive inheritance
• single genes do not function independently, but interact
with other genes and the individual’s environment, Features of autosomal recessive (AR) inheritance (Figure 27.5)
resulting in the disease phenotype are as follows:
• there is not always an exact genotype–phenotype • two faulty (mutated) copies of the gene have to be inher-
correlation ited for the disease to be expressed
Inheritance 507
Table 27.3 Types of mutations.
Mutation Change in amino acid

type (AA) code Effect
Point Single base pair change Benign unless causes

change in AA code
Missense Single base pair change Substitution of one AA
for another in the protein
chain. Can have serious A a A a
consequences
Nonsense Single base pair change Signals cell to stop
or premature building a protein, thus
termination of AA code producing a shortened
(stop codon) protein that may function
improperly or not at all
Insertion Adds a piece of DNA, Protein product
which changes number produced may not
of DNA bases function correctly A A A a A a a a
Deletion Removes piece of DNA Function of resulting
protein may be altered
Duplication Piece of DNA Resulting protein
abnormally copied function may be altered
once or multiple times from normal
Frameshift Loss or addition of one Usually results in
or more DNA bases non‐functioning protein Normal Carrier Carrier Affected
causing change in
grouping of the triplet Figure 27.5 Autosomal recessive inheritance (http://www.genetics
base pair coding for AA education.nhs.uk).
Deletions, insertions
and duplications can
also result in frameshift
mutations
Splice site Introns (bulk of the Incorrect protein is
mutations DNA within a gene that produced
is not translated) not
spliced from mRNA
• parents are obligate heterozygotes (carriers), but do not

have the disease; they may carry the same or a different
gene fault (mutation) b b B b
• affected offspring are either homozygous with two
copies of the same gene fault (mutation) or compound
heterozygotes with two different gene faults
(mutations)
• there is a 25% (one in four) risk of having an affected
child with each pregnancy
• unaffected children have a 66% (two out of three) chance
of being a carrier b b b b B b B b
• many IMD are inherited in this way including
phenylketonuria (PKU), maple syrup urine disease

(MSUD), galactosaemia, glycogen storage disease (GSD)
Ia and medium chain acyl‐CoA dehydrogenase d eficiency
(MCADD)
Autosomal dominant inheritance Normal Normal Affected Affected
Features of autosomal dominant (AD) inheritance Figure 27.6 Autosomal dominant inheritance (http://www.
(Figure 27.6) are as follows: geneticseducation.nhs.uk).
• it only requires one copy of a faulty (mutated) gene to inherit inactivation (how many of the mutant X chromosomes are
the disorder; this can be inherited from either parent active), females can be symptomatic to a greater or lesser
• there is a 50% risk of occurrence with each pregnancy extent, e.g. in ornithine transcarbamylase (OTC) deficiency,
• Unaffected offspring will have two normal copies of the some carrier females present with hyperammonaemia
gene • males with X‐linked disorders will pass on the faulty
• dominant mutations can occur sporadically (de novo) gene to all of their daughters; sons are unaffected
with both parents having no mutations. This is often seen • examples of X‐linked IMD include adrenoleukodystro-
in Glut 1 deficiency syndrome. Occasionally an AD dis- phy, OTC deficiency and X‐linked phosphorylase b
order can occur as the result of a germ line mutation; this kinase deficiency (GSD type IXa)
is where parents usually have a normal phenotype, but
one of the parents has a mutation occur in some of his/ Mitochondrial inheritance
her sperm/eggs
Features of mitochondrial inheritance are as follows:
• AD conditions can occur in a homozygous state in which
case they can be very severe or lethal • mitochondria contain their own DNA, which originates
• familial homozygous hypercholesterolaemia (FH) is an in the egg and encodes for enzymes involved in electron
AD disorder; heterozygotes are symptomatic, but transport and energy metabolism
homozygotes are more severe and often die from fatal • some mitochondrial encoded polypeptides join with
myocardial infarction in early adult life nuclear originated protein to form a complete enzyme
• individuals with heterozygous AD disorders (only one • Mitochondrial disorders can be inherited in maternal,
copy of the faulty gene) have a 50% chance of passing on recessive, X‐linked or dominant fashion dependent upon
the faulty gene. All children born to individuals with the defective polypeptide
homozygous AD disorders will inherit the disorder • cells contain multiple mitochondria and, therefore, many
alleles for one gene. When some alleles are mutated the
X‐linked inheritance cells contain a mixture of normal and mutated alleles,
known as heteroplasmy. Depending on the number of
Features of X‐linked inheritance (Figure 27.7) are as follows:
mutated mitochondria in the cell or tissue, diseases with
• mutations occur in genes on the X chromosome the same mutation can be expressed differently
• X‐linked recessive single gene defects affect males as • examples of mitochondrial inherited IMD include Leigh
they only have one X chromosome, and if the gene fault/ syndrome, Pearson syndrome and mitochondrial
mutation is passed on from a carrier mother then they encephalomyopathy lactic acidosis and stroke‐like epi-
are affected sodes (MELAS)
• females carry the gene fault/mutation on one of their two
X chromosomes. Depending upon the degree of X Inherited metabolic disorders
Inherited metabolic disorders are genetic biochemical disor-

ders of specific enzymes or proteins causing a block in a nor-
mal metabolic process of protein, CHO or lipid metabolism.
This results in an abnormality in the normal metabolic pro-
cess and accumulation of intermediary metabolites, which
cannot be further metabolised. Garrod described ‘individu-
alities of metabolism’ in 1902 [6] and introduced his concept
X Y X Xc of IMD in 1908, describing such disorders as alkaptonuria,
albinism, pentosuria and cystinuria [7], which are all inher-
ited in an AR trait.
IMD can be categorised in a number of ways. Based on their
pathophysiology they can be considered in three distinct groups:
1. Disorders of intermediary metabolism leading to

intoxication
Xc Y X X X Xc X Y As illustrated in Figure 27.8, these include disorders in
which the enzyme deficiency leads to:
• accumulation of intermediary metabolites proximal
to the block (B)
• formation of alternative products (D) producing
acute or chronic toxic effects that result in disease
Affected son Normal daughter Carrier daughter Normal son manifestations
• possible deficiencies of products downstream of the
Figure 27.7 X‐linked inheritance (http://www.geneticseducation.nhs.uk). block (C)
Management of IMD 509
Phenylalanine hydroxylase • peroxisomal disorders

(i) Protein (A) Phenylalanine (B) Tyrosine (C) • disorders of glycosylation
• disorders of sterol synthesis
• disorders of purine and pyrimidine metabolism
Deficiency of Management of IMD

phenylalanine hydroxylase
Phenylalanine (B) Tyrosine (C) A significant number of IMD are treatable, often by thera-
(ii) Protein (A)
peutic dietary intervention. The main forms of nutritional
therapy in IMD are as follows:
Phenyl ketones (D) Substrate reduction in which the accumulating
metabolite(s), due to the enzyme deficiency, is restricted (if it
Figure 27.8 Metabolism of phenylalanine: normal (i) and in phenylke- is an essential nutrient) or as far as possible removed from the
tonuria (ii). diet. Such a treatment strategy is employed in managing:
Examples of such disorders include: • disorders of amino acid metabolism

• the amino acidopathies (PKU, MSUD, homocystinuria, • disorders of galactose and fructose metabolism
tyrosinaemias, hyperornithinaemia‐gyrate atrophy • lipoprotein disorders
of the choroid and retina) • disorders of fatty acid oxidation
• organic acidaemias • some peroxisomal disorders, e.g. Refsum’s disease
• urea cycle disorders • the lysosomal storage disorder Infant onset lysosomal
• disorders of sugar intolerance (galactosaemia, hered- acid lipase deficiency
itary fructose intolerance) Provision of products normally produced downstream
• metal intoxication disorders (Menkes disease, Wilson of the block which, as a result of the block, are conditionally
disease) essential to prevent deficiency, e.g.
• porphyria
These disorders all have a symptom‐free period after • tyrosine supplementation in PKU
birth and then present with acute (either in the neonatal • arginine in urea cycle disorders
period or a later onset) or chronic signs of ‘intoxication’: • maintaining normoglycaemia by regular feeding and/or
• acute symptoms can be triggered by dietary intake, CHO supplements in:
catabolism, fever, intercurrent illness ◦◦ glycogen storage disorders
• chronic, progressive presentations include develop- ◦◦ disorders of fatty acid oxidation
mental delay, failure to thrive, cardiomyopathy, • cholesterol in Smith–Lemli–Opitz syndrome
hepatomegaly, lens dislocation • mannose in CDG 1b (phosphomannose isomerase
2. Disorders of intermediary metabolism involving deficiency)
energy metabolism Stimulation of residual enzyme activity by the use of
These include disorders in which the enzyme deficiency pharmacological doses of cofactors, often vitamins, e.g.
results in lack of energy production or energy utilisation
• vitamin B12 in methylmalonic acidaemia
within organs including the liver, muscle, brain and
• pyridoxine (vitamin B6) in homocystinuria
myocardium. They can be subdivided into defects of:
• riboflavin (vitamin B2) in multiple acyl‐CoA dehydroge-
• mitochondrial energy metabolism, including disorders
nase deficiency
of fatty acid oxidation, ketone body defects, congeni-
• sapropterin in some forms of biopterin responsive PKU
tal lactic acidaemias and respiratory chain disorders
• cytoplasmic energy metabolism, including disorders Providing alternative substrates
of glycolysis, glycogen metabolism, gluconeogene-
• use of glucose and medium chain triglycerides in long
sis, glucose transport, hyperinsulinism and creatine
chain fatty acid oxidation disorders
metabolism
• use of the ketogenic diet in Glut 1 deficiency syndrome
Symptoms may include hypoglycaemia, lactic acidosis,
to produce ketones as an alternative energy source to
hepatomegaly, cardiomyopathy, myopathy, hypertonia,
glucose for use by the brain
failure to thrive and sudden infant death.
3. Disorders involving complex large molecules In many IMD the promotion of anabolism and avoidance
These are disorders in which complex molecules are of catabolism at all times is vital to prevent metabolic decom-
incompletely catabolised and accumulate in organelles, pensation occurring with the risk of further irreversible dam-
resulting in a variety of symptoms including progressive age, particularly neurological. In such IMD the use of
loss of function of affected body systems, organomegaly emergency dietary regimens during illness or times of stress,
and dysmorphic features. They include: e.g. surgery, is imperative (Chapter 31). Detailed discussion
• disorders of lipoprotein and cholesterol metabolism of dietary treatment approaches is given in the relevant sec-
• lysosomal storage disorders tions of this and the following chapters.
Patients with IMD are invariably complex to treat, and it is many different IMD including all those part of NBS
important they are managed by an experienced metabolic www.bimdg.org.uk/site/temple.asp
team including doctors, specialist dietitians, clinical nurse • Further information on the disorders and treatment is
specialists, biochemists, pharmacists and psychologists in a given in the disorder‐specific sections of Chapters 28–31
metabolic centre. Local professionals and hospital teams also
form an integral part of the care for metabolic patients, and Transplantation for inherited metabolic disorders
liaison between the metabolic centre and local health, educa-
tion and social care is crucial. Solid organ transplants, e.g. liver, kidney and stem cell trans-
plants are used in some IMD:
Nutritional support and ketogenic diet in IMD Liver transplantation
• If the enzyme affected by the IMD is limited to the liver, then
Some IMD require nutritional support for various reasons, liver transplantation would effect a cure. Such disorders
or, on occasions, dietary advice is required to limit the intake include the urea cycle disorders, MSUD and GSD type Ia
of certain nutrients if there are dietary intolerances due to • Transplantation improves the metabolic stability of
drug treatment, e.g. with the use of Miglustat in Gaucher patient, but continued IMD management is required
disease. Infantile Refsum’s disease requires both therapeutic post‐transplant. Includes organic acidaemias, e.g. propi-
diet and nutritional support. Other IMD may be treated with onic acidaemia, methyl malonic acidaemia and GSDIb
a ketogenic diet. Examples of nutritional interventions are
given in Table 27.4. Kidney transplantation
• Renal transplants can be required in methylmalonic aci-
Newborn screening daemia where the toxic effect of methylmalonic acid
causes end‐stage renal failure. IMD management is still
Early detection is important to ensure a good outcome in required post‐transplant
many IMD, starting treatment before significant or any dam- Haematopoietic stem cell transplantation (HSCT)
age is done. NBS aims to detect affected infants before symp- • HSCT is used as a means of cross correction whereby
toms occur to allow early implementation of treatment. Strict engrafted donor white blood cells make and secrete the
criteria have to be met in order to be considered for screen- deficient enzyme in the recipient that can be taken up
ing, with screening tests having a high positive prediction and used by enzyme deficient host cells, thus correcting
value and low numbers of false positive and false negative the enzyme deficiency [12]. HSCT is used in a number of
results (www.gov.uk/government/publications/evidence‐ IMD including MPS I (Hurler disease) and X‐linked
review‐criteria‐national‐screening‐programmes): adrenoleukodystrophy
• PKU was the first IMD to be part of NBS (from the end of There are review papers on IMD and liver transplantation
the 1960s in the UK) [13, 14], kidney [15], liver–kidney [16] and HSCT [12, 17].
• Screening has been expanded in a number of countries to
include a variety of other disorders, depending on local Summary
health policy
• In the UK NBS was expanded to include: There are over 500 different IMD currently identified. A sig-
◦◦ MCADD (2009 England, 2012 all UK) nificant number are treatable, often by therapeutic dietary
◦◦ homocystinuria, isovaleric acidaemia, glutaric aciduria intervention as the sole treatment or in combination with
type 1 and MSUD (2015 in England) pharmacological agents. These are discussed further in
• Further information on NBS can be found at www.gov. Chapters 28–31.
uk/guidance/newborn‐blood‐spot‐screening‐programme‐
overview
• Metabolic Support UK have developed an app for par- Learning points: inherited metabolic disorders
ents receiving a positive NBS result ‘INHERITED
METABOLIC DISORDERS: A Guide for Parents of a • Understanding of normal metabolism and hormonal control is
Child Detected by Screening’, which can be downloaded key to the understanding of IMD of intermediary metabolism
via their website www.metabolicsupportuk.org • IMD are individually very rare, but as a group are not
• Clinical and dietetic management guidelines can be • Therapeutic dietary treatment is the sole or a significant
accessed from www.bimdg.org treatment modality in many IMD
• NHS Newborn Blood Spot Screening Programme – a • Ketogenic diet therapy is a treatment modality for the
laboratory guide to newborn blood spot screening for underlying metabolic defect in some disorders of energy
inherited metabolic diseases. Updated September 2017. production or glucose transport, as well as being used to
Describes the screening and diagnostic pathway for all treat epilepsy in some IMD
screened disorders • Nutritional support is a part of the management of many
• TEMPLE (Tools Enabling Metabolic Parents Learning) is non‐treatable forms of IMD
a resource for health professionals and families, covering
Summary 511
Table 27.4 Nutritional interventions in inherited metabolic disorders.
Disorder Dietary management
Lysosomal storage disorders (LSD) Children with a LSD may require nutritional
A defect in a specific lysosomal enzyme usually results in accumulation of incompletely intervention as:
catabolised substrates. This can result in organomegaly, dysmorphic or other • Nutritional support including enteral tube feeding,
morphological features as well as neurological deficits. Includes: particularly those with neurodegeneration – see
• Mucopolysaccharidoses (MPS) – result from incomplete breakdown of Chapter 4
glycosaminoglycans; include MPS I (Hurler syndrome), MPS II (Hunter syndrome), MPS • Weight management. Some may have growth
III (Sanfilippo syndrome), MPS IV (Morquio syndrome) retardation as a part of the disorder, e.g. those with
• Mucolipidosis (ML) – has features of MPS and sphingolipidoses; includes I‐cell disease MPS IV have short stature
• Oligosaccharidoses – result from incomplete breakdown of carbohydrate side chains • Low disaccharide diet if on Miglustat therapy [8]
from glycoproteins; includes mannosidosis • Ketogenic diet if they have epilepsy, e.g. Batten’s
• Sphingolipidoses – result from incomplete breakdown of ceramide‐containing disease – see Chapter 17
membrane lipids; includes GM gangliosidosis, Fabry disease, Gaucher disease, Krabbe Infant onset lysosomal acid lipase deficiency (Wolman
disease, Niemann–Pick Type A/B, metachromatic leukodystrophy disease) requires specific therapeutic dietary
• Neuronal ceroid lipofuscinosis (NCL), e.g. Batten’s disease management – see Chapter 30
• Lipid storage diseases, e.g. Niemann–Pick type C, Pompe disease (GSD type II),
lysosomal acid lipase deficiency
• Lysosomal transport defects, e.g. cystinosis

Some LSD are treated with enzyme replacement therapy

Some LSD, e.g. Fabry disease, Gaucher disease, Niemann–Pick type C, may be treated with
Miglustat (substrate reduction therapy). This can cause diarrhoea initially due to malabsorption
of disaccharides, particularly sucrose and maltose; lactose to a lesser extent
Defects in energy production Children with defects in energy production may
A number of different disorders that affect cellular energy supply (ATP) require nutritional intervention as:
Mitochondrial disorders – a heterogeneous group of disorders resulting in impaired energy • Enteral nutritional support, including enteral tube
production by the mitochondrial respiratory chain. Many may result in neurological feeding, for poor growth, inadequate oral intake,
deficits, epilepsy, gastrointestinal symptoms and involvement of unrelated organs over time. unsafe swallow – see Chapter 4
Includes: • Parenteral nutrition may be required in MNGIE due to
• Alpers syndrome – progressive neuronal degeneration of childhood with liver disease severe gut dysmotility causing gastrointestinal pain
• Coenzyme Q10 deficiency – multisystem disease with nephropathy, encephalopathy with enteral intake, resulting in severe undernutrition
including seizures, hearing loss and growth failure – see Chapter 5
• Ethylmalonic encephalopathy (EME) • Pearson syndrome may require pancreatic enzyme
• Leigh syndrome (subacute necrotising encephalomyelopathy) replacement therapy – see Chapter 12
• Mitochondrial encephalomyopathy, lactic acidosis and stroke‐like episode (MELAS) • Ketogenic diet may be used for:
• Myoclonus, epilepsy, ragged red fibres (MERFF) ◦◦ Management of epilepsy
• Mitochondrial neurogastrointestinal encephalopathy (MNGIE) ◦◦ Management of milder cases of PDH deficiency
• Pearson syndrome ◦◦ Management of Glut 1 deficiency syndrome – see
Further information in review papers: Chapter 17
Rahman S Gastrointestinal and hepatic manifestations of mitochondrial disorders [9]
Rahman S Mitochondrial disease and epilepsy [10]

Disorders of pyruvate metabolism and Krebs cycle - includes:
Pyruvate dehydrogenase (PDH) deficiency
• PDH complex converts pyruvate to acetyl‐CoA. Deficiency results in increased blood
and cerebrospinal fluid (CSF) concentrations of pyruvate and lactate and lack of
acetyl‐CoA, thus decreasing availability of precursors feeding into the Krebs cycle and
resulting in limitation of mitochondrial energy production.
Pyruvate carboxylase (PC) deficiency
• PC catalyses the conversion of pyruvate to oxaloacetate, a Krebs cycle intermediate,
and is also needed for synthesis of aspartate required to transport reducing equivalents
across the mitochondrial membrane and in the urea cycle.
There are currently no specific medical or dietetic therapies to effectively treat the
underlying defect
Supportive therapies, including nutritional support, may be required in many cases to
manage symptoms resulting from the underlying defect
Disorder of glucose transport affecting brain energy metabolism
Glut 1 deficiency syndrome
• Lack of glucose transporter type 1 prevents normal transport of glucose across the
blood–brain barrier and a consequent lack of glucose for brain energy metabolism.
For a fuller description see Chapter 17
Disorder Dietary management
Peroxisomal disorders Children with peroxisomal disorders may have

A group of inherited heterogeneous disorders that result from either dysfunction of either neurological impairment affecting feeding abilities and
the biosynthesis of peroxisomes or their function. Peroxisomes are involved in β-oxidation require nutritional intervention as:
of very long chain fatty acids, production of plasmalogens (class of phospholipids) and • Enteral nutritional support, including enteral tube
bile acid synthesis. feeding for poor growth, inadequate oral intake,
There are two main categories of peroxisomal disorders: unsafe swallow – see Chapter 4
• Single peroxisomal enzyme deficiency including:
Children with Refsum’s disease and some cases of
◦◦ X‐linked adrenoleukodystrophy (X‐linked ALD)
Infantile Refsum’s disease require a low phytanic
◦◦ Refsum’s disease
acid diet
◦◦ Rhizomelic chondrodysplasia punctate
• Phytanic acid is derived from the breakdown of
• Disorders of peroxisomal biogenesis:
chlorophyll by microbes in ruminant animals
◦◦ Zellweger spectrum disorders including neonatal adrenoleukodystrophy and
• The following foods rich in phytanic acid must to be
Infantile Refsum’s disease
avoided:
◦◦ Rhizomelic chondrodysplasia punctate (type 1)
◦◦ Meat from ruminant animals (beef, calves’ liver and
For most of the peroxisomal disorders, there is no specific treatment other than supportive
kidneys, lamb, duck, goose, rabbit)
care. Exceptions:
◦◦ Dairy products made from cow, sheep or goat milk
• X‐linked ALD – HSCT may be a possible treatment option if diagnosed before the onset
apart from very low fat alternatives, e.g. skimmed
of neurological symptoms
milk, very low fat/fat‐free yoghurts
• Infantile Refsum’s and Refsum’s disease – a low phytanic acid diet
◦◦ Fish, particularly oily types, shellfish, fish oil
Further information on the peroxisomal disorders can be found in Clinical Paediatric
◦◦ Baked products using butter
Dietetics 4th edition [11]
◦◦ Milk chocolate
Further dietary information is available on the Adult
Refsum’s disease website
https://refsumdisease.org/
Sterol biosynthesis disorders Children with SLOS and other sterol biosynthesis
Multisystem disorders resulting from enzyme deficiencies in the biosynthesis of disorders may require nutritional intervention as:
cholesterol and consequently the formation of bile acids, steroid hormones, cell • Enteral nutritional support, including enteral tube
membranes and vitamin D. This results in dysmorphic and skeletal dysplasias that have feeding for poor growth, inadequate oral intake,
antenatal onset. unsafe swallow – see Chapter 4
Includes:
• Smith–Lemli–Opitz syndrome (SLOS)
• Desmosterolosis
• Lathosterolosis
Cholesterol supplementation is used for SLOS and in other sterol disorders where there is
hypocholesterolaemia. In SLOS restoration of normal plasma cholesterol levels restores
adrenal steroid and bile salt production. Cholesterol supplementation increases plasma
cholesterol levels. In turn this provides feedback inhibition of HMG‐CoA reductase, thus
reducing flux through the endogenous cholesterol synthesis pathway with decreased
production of 7‐dehydrocholesterol and its isomer 8‐dehydrocholesterol, which are toxic.
Exogenous cholesterol cannot cross the blood–brain barrier and so cannot treat the
biochemical defect in the brain.
Congenital disorders of glycosylation Children with congenital disorders of glycosylation
A group of disorders resulting from defects in the glycosylation (addition of sugar may require nutritional intervention as:
molecules) of proteins or lipids to form glycoproteins and glycolipids. They affect multiple • Enteral nutritional support, including enteral tube
organs causing a range of symptoms including developmental delay, hypotonia, seizures feeding for poor growth, inadequate oral intake,
in most and commonly gastrointestinal symptoms of diarrhoea and vomiting. unsafe swallow – see Chapter 4
GSD, glycogen storage disease; ATP, adenosine triphosphate; HSCT, haemopoietic stem cell transplantation.

28
Disorders of Amino Acid Metabolism,
Organic Acidaemias and Urea Cycle
Disorders
Marjorie Dixon, Anita MacDonald and Fiona J. White
Protein requirements Amino acid requirements in healthy infants

and children
Proteins provide an essential structural and functional role;
amino acids are the building blocks of all vital organs, mus- For healthy infants up to 6 months of age, the amino acid
cle (including heart muscle), hormones and biological fluids content of breastmilk is considered the best estimate of
such as blood. Maintenance of growth and other physiologi- amino acid requirements. However, for infants with amino
cal functions requires a constant intake of good quality die- acid disorders, breastmilk given ad lib without supplementa-
tary protein as the human body is incapable of maintaining tion with suitable l‐amino acids would provide an intake in
reserves of protein. The body is in a dynamic state. Its pro- excess of their tolerance. The average essential amino acid
teins and other nitrogenous compounds are degraded and (EAA) content of mixed human milk proteins is given in
resynthesised continuously, a process that is not completely Figure 28.1.
efficient (some amino acids are lost by oxidative catabolism) The FAO/WHO/UNU report on Protein and Amino Acid
[1]. The magnitude of daily protein synthesis in adults is Requirements in Human Nutrition used a factorial calcula-
three‐ to fourfold greater than the intake of protein and five‐ tion approach to estimate the amino acid requirements of
to sixfold greater in growing children [2]. children (Table 28.1). These were based on growth rates
Anabolism, including protein synthesis, increases in tissues and protein deposition for children of different age
following food ingestion. Amino acids are used to support groups, the amino acid composition of whole body pro-
anabolism throughout the day, but especially following meal tein and efficiency of dietary protein utilisation [8]. Amino
ingestion (foods containing carbohydrate, fat and protein). The acid requirements are also determined using a stable iso-
form and nature of dietary proteins may influence amino acid topic technique: indicator amino acid oxidation (IAAO)
utilisation within the body. l‐amino acids do not require diges- method [9, 10].
tion and are directly available for absorption by the small intes- In general, the results of the isotopic experimental
tine [3]. This leads to rapid absorption [4, 5] and may cause a method are similar to those derived by the factorial method,
transient imbalance among amino acids in the systemic circula- except for branched chain amino acids (BCAA) [9]. For
tion. Absorption of l‐amino acids is different from that of school‐aged children the estimated requirement for BCAA
whole protein, such as casein. Ingestion leads to a rapid increase (leucine, valine, isoleucine combined) using the factorial
and higher plasma concentrations, but they also decrease more approach is 96 mg/kg/day [8], and by the IAAO technique
quickly compared to whole protein [5]. In addition, nitrogen 147 mg/kg/day [11]. The factorial approach uses adult
retention and weight gain following ingestion of l‐amino acids BCAA requirements plus the additional needs for growth,
is less efficacious than with casein‐rich protein, suggesting a and it assumes that the maintenance requirements for die-
less efficient transfer of amino acids into tissue and plasma pro- tary EAA are the same for children as adults [9]. More stud-
teins [4, 6]. Increased oxidation has also been suggested when ies are required using the IAAO technique to demonstrate
amino acid supplements are taken in large single doses [7]. their reliability [12].

514 Disorders of Amino Acid Metabolism, Organic Acidaemias and Urea Cycle Disorders
Amino acids mg amino acid/g total milk protein Leucine
Lysine
in human milk
Isoleucine
Valine
Phenylalanine Threonine
Histidine
Tryptophan
Methionine
Figure 28.1 Amino acid composition of mixed human milk proteins [8].
Table 28.1 Amino acid requirements of healthy children determined using the factorial approach [8].
Essential amino acid requirements (mg/kg/day)
Age (years) His Ile Leu Lys SAA AAA Thr Trp Val
0.5 22 36 73 64 31 59 34 9.5 49
1–2 15 27 54 45 22 40 23 6.4 36
3–10 12 23 44 35 18 30 18 4.8 29
11–14 12 22 44 35 17 30 18 4.8 29
15–18 11 21 42 33 16 28 17 4.5 28
His, histidine; Ile, isoleucine; Leu, leucine; Lys, lysine; SAA, sulphur amino acids (methionine, cysteine); AAA, aromatic amino acids (phenylalanine,
tyrosine); Thr, threonine; Trp, tryptophan; Val, valine.
Source: Reproduced with permission of WHO.
Total protein requirement in amino acid disorders (referred to as a protein substitute in this text) is essential
to both prevent protein deficiency and optimise metabolic
Most patients with amino acid disorders require severe control. In most patients, it is likely that precursor‐free
restriction of natural protein intake, and the provision protein substitute will supply >75% of the total protein
of a suitable precursor‐free supplement of l‐amino acids intake [13].
Phenylketonuria
Anita MacDonald
Enzyme Phenylalanine hydroxylase (PAH)
Biochemical defect PAH catalyses the hydroxylation of phenylalanine to tyrosine, using tetrahydrobiopterin (BH4) as a cofactor. Deficiency leads to
complete or partial inability to metabolise phenylalanine, causing increased phenylketones, and elevated blood phenylalanine
concentrations that cross the blood–brain barrier and accumulate in the brain. Tyrosine, dopamine, norepinephrine and
serotonin concentrations are lower (Figure 28.2).
High levels of brain phenylalanine are possibly the main cause of neurotoxicity [14] by interfering with cerebral protein
synthesis [15], increasing myelin turnover and inhibiting neurotransmitter synthesis [16].
Phenylketonuria 515
O O
Phenylalanine
O2 hydroxylase H2O
OH OH
NH2 NH2
HO
Phenylalanine Tetrahydrobiopterin Dihydrobiopterin Tyrosine
(BH4) (BH2)
Neurotransmitter
Dihydropteridine synthesis
reductase Melanin
Epinephrine
Thyroxine
Figure 28.2 Hydroxylation of phenylalanine.
Genetics • Autosomal recessive inheritance. The global prevalence in screened populations is approximately 1 in 12 000 births with
an estimated carrier frequency of 1 in 55 [17], but it varies between populations. It is particularly common in Ireland and
Turkey.
• Phenylketonuria (PKU) is caused by mutations in the gene encoding PAH. There are >1000 PAH gene variants and >2500
different genotypes [18]. There is a good correlation between genotype and phenotype [19].
• A small number of patients with so called severe PKU mutations have escaped intellectual disability despite having high
blood phenylalanine concentrations and poor dietary control. They appear to have near normal brain phenylalanine content
although other neurological, psychological and/or behavioural symptoms may occur [20].
Newborn screening • Screening is by measurement of phenylalanine (≥240 μmol/L) in dried blood spots using tandem mass spectrometry. More
information on UK screening, diagnostic and clinical management protocols can be found at www.bimdg.org and www.
gov.uk Newborn blood spot screening: laboratory guide for IMDs (inherited metabolic diseases).
• UK infants are screened at around day 5 of life. European PKU guidelines 2017 [21] recommend the following:
◦◦ Treatment should start by 10 days of age
◦◦ All patients with untreated blood phenylalanine levels >360 μmol/L should be treated
Clinical onset Untreated PKU causes global intellectual disability, significant delays in developmental milestones, hyperactive behaviour with
presentation, autistic features, seizures, movement problems, eczema, musty body odour and light pigmentation (eyes, hair and skin). If
features treatment is started within the first 3 weeks of life, irreversible intellectual disability is prevented.
Classification
There is a broad continuum of PKU phenotypes ranging from severe to milder forms. PKU is generally classified by the severity
of hyperphenylalaninaemia at diagnosis:
• Classical or severe PKU: usually characterised by blood phenylalanine concentrations >1200 μmol/L. Phenylalanine
tolerance may be ≤250 mg/day (5 g/day natural protein) to maintain phenylalanine concentrations <360 μmol/L
• Moderate PKU: classified with diagnostic phenylalanine concentrations of 600–1200 μmol/L. Most patients with moderate/
severe PKU tolerate between 200 and 700 mg/day phenylalanine (4–14 g/day natural protein) while maintaining
phenylalanine concentrations <360 μmol/L
• Persistent hyperphenylalaninaemia or mild PKU: patients present with phenylalanine concentrations between 120 and
600 μmol/L on a normal diet. They are likely to tolerate >750 mg/day phenylalanine (>15 g/day natural protein). European
PKU guidelines 2017 recommend all patients with untreated blood phenylalanine between 360 and 600 μmol/L be treated
during the first 12 years of life [21] and should remain on treatment >12 years if blood levels exceed 600 μmol/L. Any patient
with a blood phenylalanine between 240 and 360 μmol/L should remain in long‐term follow‐up, particularly women due to
later risks of maternal PKU. Young children require blood phenylalanine monitoring, particularly during the first year of life as
levels may still increase in the late weaning period
About 1%–2% of hyperphenylalaninaemia is caused by mutations in genes coding for enzymes involved in tetrahydrobiopterin
(BH4) cofactor biosynthesis or regeneration [22] affecting phenylalanine homeostasis and catecholamine and serotonin
biosynthesis [23]. BH4 deficiencies are treated with neurotransmitters with or without BH4 supplementation (described in
Clinical Paediatric Dietetics 4th edition). A low phenylalanine diet may be prescribed for hyperphenylalaninaemia.
Long‐term Neuropsychological and mental health
complications Children who commence early dietary treatment from newborn screening should be within the broad normal range of general
and outcome ability, attain expected educational standards and lead independent lives as adults. However, outcome is dependent on the
quality of blood phenylalanine control, and even children with good metabolic control have lower IQs (up to 6 points) than
their unaffected siblings and children without PKU [21]. They may have deficits in selective and sustained attention, processing
speed, fine motor skills, perception and visual–spatial abilities. Executive function (working memory, planning, mental
flexibility, organisation and inhibitory control) may be impaired. Mental health problems (anxiety, depression, mood swings)
have been associated with concurrent and historical high blood phenylalanine levels. Seizures, behavioural problems and
movement disorders are reported in patients with long‐term diet discontinuation [24].
Quality of life
An infant diagnosis of PKU may have a significant psychological impact on parents. The knowledge that their actions can affect
the neurocognitive outcome of their child is a heavy responsibility. Dietary management of PKU by parents has a median time
burden of 19 hours per week [25]. Stigmatisation and feeling socially excluded are common issues. Bullying about diet can
affect a child’s relationship with food, leading to disordered eating [26]. Eating away from home is a barrier to adherence.
Growth
Overall children with PKU have comparable growth patterns to healthy controls, although suboptimal growth has been noted,
particularly in early childhood and adolescence [27, 28], with adults underachieving their final height [28]. Head
circumference increase has been shown to align with natural protein intake [29]. Fat‐free mass and improved body
composition is also associated with higher intakes of natural protein intake [30, 31].
Overweight
Adults with PKU have a higher prevalence of overweight, and females are more overweight/obese than the general population
[27, 32, 33]. Although factors associated with overweight in PKU include relaxation of strict diet therapy, a high carbohydrate
intake and low activity levels [34], causes are probably multifactorial.
Bone health
Osteopenia and osteoporosis may occur, with a lower spine bone mineral density [35], but meta‐analysis of early treated patients
shows that while bone mineral density z scores were lower than healthy peers, they were within normal reference range [36].
Poor bone health is associated with amino acid imbalances; inadequate natural protein intake; low calcium, phosphorus,
magnesium, vitamin D, n‐3 polyunsaturated fatty acids intakes; low calcium/protein ratios; poor dietary adherence with
micronutrient supplemented protein substitute; low plasma magnesium, zinc and copper concentrations; elevated blood
phenylalanine concentrations and lack of weight bearing exercise [35–37].
Vitamin B12 deficiency

Vitamin B12 deficiency is mainly reported in adolescents or adult patients who have either relaxed their diet and are less
adherent with protein substitutes or stopped diet but not eating a normal protein intake, particularly animal protein. Symptoms
such as spastic paraparesis, tremor and slurred speech are associated with vitamin B12 deficiency in adults with PKU [38, 39].
Medical treatment • Lifelong treatment with a low phenylalanine diet
• Care should be provided by a specialist multi‐disciplinary team (medical doctor, dietitian, nurse, psychologist).
Psychological support and family and patient education are essential
• Regular monitoring according to European PKU guidelines 2017 [21], assessing blood phenylalanine control, neurocognitive
outcome and overall psychosocial well‐being
• Diet history and growth: weight, length/height, body mass index (BMI) should be monitored at each clinic visit
• Assessment of bone mineral density in late adolescence only, providing adherence with dietary management, is satisfactory,
and nutrient intakes meet requirements
• Optimisation of calcium, vitamin D and natural protein intake and regular exercise for bone health
• Effective transition processes between paediatric and adult services is essential
Other treatment options

New treatment options, either as an adjunct therapy to a low phenylalanine diet or to replace dietary treatment, are available
or in development.
Biopterin‐responsive phenylalanine hydroxylase deficiency

Sapropterin dihydrochloride (Kuvan) is an oral synthetic form of BH4, the natural cofactor of phenylalanine hydroxylase, which
activates residual PAH enzyme activity. Only some mutant PAH enzymes show enhanced activity in the presence of
pharmacological doses of sapropterin, so it is effective only in a subset of patients (around 20%–30%), mainly those with mild
or moderate phenotypes. Sapropterin has been demonstrated to lower blood phenylalanine concentrations and improve
phenylalanine tolerance. It is either given with a relaxed low phenylalanine diet, or it may replace diet therapy depending on
the individual response to the drug [21].
Prior to treatment, responders are identified by evaluating the reduction in blood phenylalanine following treatment with
20 mg/kg/day of sapropterin for up to a 4‐week period. A 30% reduction from baseline in mean phenylalanine blood levels is
considered an effective response. Once responsiveness is established, the dosage may be adjusted within the range 5–20 mg/
kg/day. Details of responsive testing are given by Muntau et al. [40, 41]. It is important to check that patients are prescribed
phenylalanine to their full tolerance prior to sapropterin responsiveness testing and a treatment trial.
This drug is not routinely commissioned by the NHS in England, Scotland, Wales or Northern Ireland.
Pegvaliase (PEGylated recombinant [Anabaena variabilis] phenylalanine ammonia lyase [PAL]) (Palynziq)
An enzyme substitution therapy given by daily subcutaneous injection. PEGPAL converts phenylalanine into low levels of
ammonia and non‐toxic trans‐cinnamic acid by‐products. This allows patients with PKU to metabolise phenylalanine
independently of PAH residual activity. It is approved by the USA Food and Drug Administration, and the European Medicines
Agency has granted marketing authorisation for patients with PKU aged 16 years and over with blood phenylalanine levels
>600 μmol/L. Its use has not yet been appraised in the NHS. Trial data has demonstrated that 61% of patients were able to
achieve blood phenylalanine levels <360 μmol/L at 24 months of treatment [42] with substantially improved natural protein
intake. Side effects include hypersensitivity type reactions including injection site reactions, anaphylactic episodes, headaches,
and joint pain during the initial stages of dosing with the drug.
Other therapies
Those in development include genetically modified bacteria to lower phenylalanine levels [43] and genome‐targeted gene
therapy [44].
Dietary Management of PKU 517
Dietetic • Primary aim – to prevent adverse neurocognitive and psychological outcomes by restricting protein from natural foods to
management maintain blood phenylalanine levels within the target range while providing enough phenylalanine to support protein
synthesis and avoid catabolism
• Secondary aim – to maintain a healthy nutritional status by providing sufficient low phenylalanine/phenylalanine‐free
protein substitute, energy and other nutrients to support physiological protein synthesis, counterbalance catabolism but
without providing excess energy intake. Protein substitute may be from one of two sources: either phenylalanine‐free
l‐amino acids or low phenylalanine glycomacropeptide (GMP) (p. 520)
Monitoring – Blood phenylalanine levels should be measured weekly in the first year, once every 2 weeks from age 1–12 years and monthly
biochemical >12 years of age. Blood phenylalanine levels should be reported within 5 working days from the time of home blood spot
sampling [21].
For children aged 0–12 years, target blood phenylalanine levels are 120–360 μmol/L. For patients above the age of 12 years
(exception pre‐conception and pregnancy), European PKU guidelines 2017 suggest 120–600 μmol/L to be safe throughout
adolescence and adulthood [21].
Parents should be taught by a specialist nurse how to collect heel or thumb prick dried blood spot samples at home. Blood
samples are posted to the hospital and analysed, usually by tandem mass spectrometry (MS/MS), for phenylalanine (+/−
tyrosine). For patients on dietary treatment, the dietitian should promptly inform the parents/patients of blood phenylalanine
results on the same day of availability, discuss their interpretation and give instruction about any necessary dietary change.
Blood phenylalanine levels should be taken at a standard time each day, preferably before the first dose of protein substitute
in the morning when they are at their highest concentration after an overnight fast [45].
Annual measurement of plasma homocysteine and/or methylmalonic acid, haemoglobin, mean corpuscular volume (MCV)
and ferritin [21]. Serum vitamin B12 concentrations within the reference range do not indicate a satisfactory vitamin status [38].
Clinical European PKU guidelines 2017 [21] includes evaluation/monitoring for cognitive and executive function, neurological
management involvement, psychosocial and mental health, biochemical nutritional monitoring and pregnancy.
guidelines
Parent support The National Society for Phenylketonuria (NSPKU) www.nspku.org
groups The European Society for Phenylketonuria (ESPKU) www.espku.org
Dietary management of PKU • Provision of vitamins, minerals and docosahexaenoic

acid to meet dietary requirements; these are usually
There are six key elements: added to the protein substitute or as separate modules.
• In classical PKU, dietary phenylalanine (protein) restric-
tion to 20% or less of normal intakes is necessary to main-
Phenylalanine tolerance
tain blood phenylalanine concentrations within target
The amount of phenylalanine tolerated will vary depending
range. It is best to avoid high protein foods such as meat,
on the severity of the patient’s phenotype (residual enzyme
fish, eggs and cheese in classical PKU as the amounts
activity), age, use of sapropterin, dosage of protein substi-
permitted would be very small. The percentage of phe-
tute and non‐protein energy ratio.
nylalanine in protein found in milk products, cereals,
Natural protein/phenylalanine tolerance is defined as the
vegetables and fruits is given in Table 28.2.
amount that maintains the blood phenylalanine within a tar-
• Daily allocation of dietary phenylalanine from measured
get treatment range. The amount of natural protein/pheny-
quantities of natural protein foods to provide essential
lalanine from infant formula or food should be titrated
phenylalanine requirements is allocated by an exchange
against blood phenylalanine levels until levels are stable and
system: one food can be exchanged or substituted for
within the target treatment range. Phenylalanine require-
another of equivalent phenylalanine content.
ments are highest (mg/kg/day) in early infancy. After the
• Provision of a suitable protein substitute, with added tyros-
age of 6 months, there is a slow and steady decline in toler-
ine in order to meet nitrogen and tyrosine requirements.
ance per kilogram body weight, although the total daily
• Maintenance of a normal energy intake by encouraging
amount may stay the same (Table 28.3). This is in parallel
liberal use of foods naturally low in phenylalanine and
with decreasing growth rate and protein requirements.
special low protein foods such as bread and pasta.
Phenylalanine is an EAA and its excessive restriction should
Table 28.2 Percentage of phenylalanine found in milk products,
be avoided. Deficiency, with very low blood phenylalanine
cereals, vegetables and fruits [46]. levels, could lead to anorexia, alopecia, perineal rash, falter-
ing growth, osteopenia and even death [21, 47, 48].
Protein contributed by Protein contributed Protein contributed
phenylalanine from cereals by phenylalanine by phenylalanine Exchange systems used to allocate dietary
and milk products from vegetables from fruits
phenylalanine (natural protein)
5% 3%–4% 3%
• Systems for allocating phenylalanine vary throughout
Source: Reproduced with permission of Elsevier. Europe [49]. In the UK, phenylalanine is allocated in
Table 28.3 Tolerance of phenylalanine throughout childhood. Table 28.5 Guide to calculating the weight of 1 g protein exchange
(50 mg phenylalanine) from protein food labels.
Age Phenylalanine (mg/kg)
100 ÷ by the amount of protein per 100 g food = 1 protein exchange
0–6 months 25–60*
Breakfast cereal X contains protein 8.3 g/100 g
7–12 months 25–40 To calculate 1 exchange:
Phenylalanine (mg/day) 100 ÷ 8.3 g = 12 g breakfast cereal X
12 g breakfast cereal X = 1 g protein or 1 protein exchange
1–10 years 200–700*
NB: Always use the protein analysis per 100 g of food and not protein
11–16 years 200–700* analysis per stated food portion size. If using this method for estimating
protein exchange from food portion sizes, see Table 28.7.
This does not take into consideration the additional quantities consumed
from low protein free foods and fruits and vegetables allowed without
measurement/calculation in the diet.
* MacDonald A. Unpublished longitudinal clinical data in 100 patients
Challenging phenylalanine tolerance
with classical/moderate PKU over 20 years: maintaining plasma
phenylalanine 120–360 μmol/L in children aged 1–10 years and From the age of 2 years, if blood phenylalanine control is
120–700 μmol/L in adolescents aged 11–16 years (data collected prior stable, phenylalanine tolerance should be re‐examined from
to European PKU guidelines 2017 [21] using target blood phenylalanine time to time, but particularly at times of rapid growth. Some
levels higher than these recommended guidelines for patients aged adolescents and adults with PKU have been reported to tol-
10 years and older).
erate more natural protein than they had been prescribed
[55]. Any challenge with additional phenylalanine should be
conducted carefully, introducing small measured quantities
(equivalent to 0.5–1.0 g/day natural protein) systematically,
50 mg phenylalanine or 1 g protein exchanges. Generally, ensuring stable blood phenylalanine control within target
for all foods except fruit and vegetables, protein analysis limits before further changes are made. A minimum of three
can be used to calculate exchanges as 1 g protein pro- consecutive blood phenylalanine levels within target range
vides 50 mg phenylalanine. Fruit and vegetables gener- should be achieved before further challenge is considered.
ally contain a lower concentration of phenylalanine
(<50 mg/1 g protein) compared with their protein con-
tent, so phenylalanine analysis is used to calculate phe- Low protein foods
nylalanine exchanges from fruits and vegetables.
• Each patient is allocated a total daily amount of natural There are some foods that are naturally very low in protein
protein/phenylalanine; the number of exchanges to that can be eaten in normal portion sizes in the diet without
make up this daily allowance is then calculated measurement (Table 28.9). They are referred to as exchange‐
(Table 28.4) [49]. One food can be exchanged or substi- free foods [51].
tuted for another of equivalent phenylalanine content. The European Commission and Consumers Regulation (EU)
No more than 50% of the natural protein/phenylalanine No. 1169/2011 on the provision of food information for con-
allowance should be given at any one meal. A guide to sumers states that manufacturers need not declare protein con-
calculating the weight of 1 g protein exchange (50 mg tent if manufactured foods contain ≤0.5 g/100 g protein, and so
phenylalanine) from protein food labels is given in foods may be listed as containing 0 g protein even if they have
Table 28.5. A guide to using protein/phenylalanine protein‐containing ingredients. This has contributed to some
exchanges is given in Table 28.6. unclear protein labelling on manufactured foods. However, the
British Inherited Metabolic Disease Group (BIMDG) dietitians
have examined the protein content of manufactured foods and
Table 28.4 Examples of phenylalanine/protein exchange systems have defined for each food group the foods that can be consid-
for PKU. ered exchange‐free in PKU (Table 28.9) [51].
Approximate Examples of number of

Exchange protein daily phenylalanine Energy intake
system equivalent exchanges allocated
It is important that age‐related energy requirements are met
50 mg 1 g 200 mg Phe daily
for optimal dietary protein utilisation. Total energy intakes
phenylalanine 4 × 50 mg exchanges =
4 g protein/4 exchanges
as a percentage of estimated average requirements (EAR) is
similar to children without PKU [56], but from 12 months of
300 mg Phe daily
6 × 50 mg exchanges =
age, children with PKU consume a higher intake of carbohy-
6 g protein/6 exchanges drate (CHO) providing almost 60% of energy requirements,
with 15% from protein equivalent sources. There are concerns
Phe, phenylalanine. that a high CHO diet may impact on body composition
Table 28.6 Guide to using 1 g (50 mg phenylalanine) protein exchange foods.
1. Exchange foods are generally sourced from low biological protein foods such as potatoes, peas, sweetcorn, rice, pasta and breakfast cereals.
Yoghurt or milk are useful protein sources in older infants and toddlers if appetite is poor
2. It is preferable to weigh foods with digital scales rather than using household measurements, which are not accurate
3. Ideally exchanges should be spread evenly throughout the day so that a phenylalanine load is not given at any one time [50]
4. It is useful to teach parents and patients to calculate 1 g protein exchanges directly from food protein labelling on packages. An example on how
to calculate 1 g protein exchanges is given in Table 28.5. ‘Pocket‐size protein calculators’ are helpful and are available from the NSPKU. Their
website also provides a downloadable PKU exchange calculator www.nspku.org
5. If protein exchange amounts are calculated from food portion sizes listed on food labels, then the protein content per item should be rounded up
or down to the nearest 0.5 g protein using the rule for rounding numbers (Table 28.7) [51]
6. All parents/caregivers should be advised to read food label ingredient lists. Occasionally food protein labelling errors occur that can be
detected by checking the list of ingredients. For example, if a food states that it contains protein <0.5 g/100 g but the first or second ingredient
is wheat flour, then the protein label is likely to be incorrect. Patients should be encouraged to report protein labelling errors to their dietitian
and food supplier.
7. For foods such as ice cream, weight rather than volume should be used to calculate the protein exchange amount. The protein value may
be expressed per 100 g or per 100 mL on food labels. The weight of 100 mL ice cream is not the same as 100 g ice cream because of the
difference in density. The density is influenced by the ‘free’ air a manufacturer whips into the ice cream. Ice cream has a minimum density
of approx. 50 g per 100 mL, but brands of ice cream that contain solid ingredients such as chocolate chips will have higher densities (up to
90 g per 100 mL)
8. Fruits and vegetables:
• Fruits and vegetables containing phenylalanine >75 mg/100 g are counted as exchange foods. Phenylalanine content up to 75 mg/100 g are
exchange‐free [21] as they do not significantly elevate plasma phenylalanine concentrations and can be safely given free [52]
• Fruits and vegetables containing phenylalanine 76–99 mg/100 g (e.g. cauliflower, broccoli) use a standard weight of 60 g as one phenylalanine
exchange (Table 28.8)
• Fruits and vegetables containing phenylalanine ≥100 mg/100 g (e.g. peas, sweetcorn) use the actual phenylalanine content per 100 g to calculate
the weight of food to provide one phenylalanine exchange (Table 28.8) [53]
9. Potatoes should be calculated as part of the phenylalanine/protein allowance. They have a higher phenylalanine/protein ratio than most other
fruits and vegetables. If potato products contain additional exchange ingredients, e.g. wheat flour or milk, then the protein analysis on the packet
should always be used to determine their exchange amount
10. Cooked crisps (snacks) made from vegetables such as beetroot or parsnips are concentrated in phenylalanine and should be counted within the
phenylalanine allowance
11. Theoretically any foods can be eaten as exchanges, but high protein foods can only be given in small amounts. Young children do not understand
exchange systems and have difficulty in understanding why they cannot eat more of these foods. It would seem inappropriate to accustom their
palate to high protein foods when they cannot eat adequate quantities to satisfy appetite
NSPKU, National Society for Phenylketonuria.
Table 28.7 Guidance for calculating protein exchange amounts [51] from food portion sizes on food labels.
Protein content per item when calculated

from food label Calculated exchange
0 g protein per food portion Exchange‐free

0.1 g protein per food portion Exchange‐free
0.2 g protein per food portion Exchange‐free (providing total amount consumed does not exceed 0.5 g protein)
0.3 g protein per food portion Exchange‐free (providing total amount consumed does not exceed 0.5 g protein). If a food is 0.3 g/per
food portion, suggest one portion is exchange‐free and two portions is ½ exchange
0.4–0.7 g protein per food portion ½ exchange protein
0.8–1.2 g protein per food portion 1 exchange protein
1.3–1.7 g per food portion 1.5 exchange protein
1.8–2.2 g per food portion 2 exchange protein
2.3–2.7 g per food portion 2.5 exchange protein
2.8–3.2 g per food portion 3 exchange protein
Source: BIMDG. Licensed under CC BY 4.0.

Table 28.8 Basic 50 mg phenylalanine exchanges for infant formula, fruits and vegetables (using phenylalanine analysis) and 1 g protein exchanges
for dairy products.
Amount of food for Amount of food for

50 mg phenylalanine 50 mg phenylalanine
Food exchanges [53, 54] Food exchanges [53, 54]
Breastmilk 90 mL Kale, cooked 35 g

SMA Pro First Infant Milk (from powder) 70 mL Lentils, raw 5 g
Cow & Gate First Infant Milk (from powder) 90 mL Lentils, boiled 12 g
Cow & Gate First Infant Milk – liquid 85 mL Mangetout, raw or cooked 60 g
Aptamil Profutura First Infant Milk (from powder) 90 mL Passion fruit 40 g
Aptamil Profutura First Infant Milk – liquid 85 mL Peas, petit pois (fresh, frozen, tinned), boiled 25 g
Cow’s milk 30 mL Rocket, raw 35 g
Yoghurt (natural/flavoured) 20 g Romanesco, cooked 35 g
Asparagus, boiled 60 g Spinach, boiled 25 g
Baked beans (canned) 20 g Spring greens, boiled 35 g
Bamboo shoots, raw or cooked 60 g Sugar snap peas, cooked 60 g
Beansprouts, raw or cooked 60 g Sweetcorn (canned), cooked 35 g
Broad beans, boiled 20 g Sweetcorn (corn on the cob), cooked 4 cm
Broccoli, boiled 60 g Vine leaves, cooked 30 g
Brussels sprouts, boiled 60 g Whole hearts of palm, cooked 60 g
Cauliflower, boiled 60 g Yam, boiled 60 g
Chestnut (sweet), tinned 40 g Potato, main crop, boiled, jacket, flesh only 80 g
(average value)
Choi Sum, cooked 35 g Roast potatoes 55 g
Figs 60 g Chipped potatoes 45 g
compared with normal diets although data around this topic The provision of protein substitute is essential. Its func-
is too limited to draw conclusions [56]. tions include:
It has long been established that utilisation of dietary pro-
• prevention of protein deficiency
tein is influenced by energy intake [57–59]. Protein synthesis
• supporting growth
and catabolism are energy dependent and thus are sensitive
• provision of tyrosine
to dietary energy deprivation. Insulin is secreted in response
• optimisation of metabolic control by promoting anabo-
to CHO (and protein) promoting cellular uptake and the use
lism and/or ability of individual large neutral amino
of amino acids. Energy and/or glucose depletion will result
acids (LNAA) to alter phenylalanine transport at gut epi-
in phenylalanine breakdown (gluconeogenesis) to meet min-
thelial level [60]
imal glucose requirements, which can ultimately lead to a
• 35%–50% of the total l‐amino acids content is from
loss of blood phenylalanine control. It is not uncommon to
LNAA; these provide competition with phenylalanine
observe this in young children with classical PKU who may
and block its transport across the blood–brain barrier
have poor appetites. Regular monitoring of energy intake is
[61], both decreasing brain phenylalanine and increasing
important.
brain tyrosine and tryptophan
• prevention of micronutrient deficiencies; most protein
Protein substitutes substitutes are supplemented with additional vitamins
and minerals in amounts that meet requirements provid-
Phenylalanine (Phe)‐free or low Phe protein substitute is the ing they are prescribed in adequate dosages
primary source of protein or protein equivalent in a low phe-
nylalanine diet, typically providing between 50% and 80% of
Casein glycomacropeptide
the total protein intake, depending on the severity of PKU. It
is derived from synthetic protein. Traditionally based on CGMP is a low Phe protein source used as an alternative to
Phe‐free l‐amino acids, more recently casein glycomacro- l‐amino acids in the treatment of PKU. Found in cheese whey,
peptide (CGMP) is also being used in products for children it is associated with better taste and improved nitrogen reten-
aged 4 years and above. tion [62]. In PKU mice studies, it has been shown to improve
Table 28.9 Foods that can be allowed without measurement (exchange‐free) in PKU [51].
Food group Examples of suitable exchange‐free foods
Fruits and vegetables • Fruits and vegetables given in Table 28.10 [21, 52, 54]
Fats • Butter, margarine, ghee, vegetable oils
Starches • Cassava flour, arrowroot, cornflour, custard powder, sago, tapioca and tapioca starch providing they contain protein
≤0.5 g/100 g
Vegan products • Some vegan protein free cheeses (e.g. Violife), chicken substitutes (e.g. Violife), shrimp and salmon substitutes (e.g.
Sophie’s Kitchen) containing protein ≤0.5 g/100 g. They are based on vegetable oil and plant starches. Any vegan food
products containing >0.5 g/100 g of protein should be calculated as part of the protein exchange system, e.g. modified
soya‐based cheeses
Sugars • Sugar, glucose, jam, honey, marmalade, golden syrup, maple syrup, icing sugar, buttercream, sweets containing
protein ≤0.5 g/100 g
Drinks • All drinks must be free of aspartame.* Water, squash, lemonade, cola drinks, fruit juice; black tea, fruit tea, mint tea,
green tea, coffee; tonic water, soda water, mineral water
• Plant milks, e.g. rice† or coconut milk, should be counted as part of protein exchange system (unless protein content
provides ≤0.1 g/100 mL)
• Milk shake liquids and powders, e.g. Crusha, Nesquick, containing protein ≤0.5 g/100 g and aspartame‐free
Pickles • All clear pickles in vinegar, e.g. pickled onions, gherkins, red cabbage
Miscellaneous • Vegetarian jelly, agar‐agar, salt, pepper, herbs, spices, seasonings, vinegar, tomato and brown sauce, baking powder,
bicarbonate of soda, cream of tartar, food essences and colouring. The protein content of some foods (e.g. herbs and
spices) is relatively high, but because they are only used in small amounts, they are considered exchange‐free
• Gravy mixes containing protein ≤0.5 g/100 mL when diluted. Tabletop sauces and cook‐in sauces containing protein
≤1.0 g/100 g
• Soya sauces containing protein ≤1.5 g/100 g
Low protein special foods • A selection of low protein (LP) breads, flour mixes, pizza bases, pasta, biscuits, egg replacers and milk replacements
available on (ACBS) are available on prescription (ACBS) in the UK
prescription • Most LP foods are exchange‐free provided their listed ingredients are also exchange‐free. If they do contain exchange
ingredients such as milk, but total phenylalanine content is ≤25 mg/100 g, they are exchange‐free
• Some LP foods contain protein/phenylalanine ingredients. If their phenylalanine content is >25 mg/100 g, e.g. potato‐
based low protein snack pots, burger mixes, milk replacements, these should be calculated as part of the exchange
system
• A list of all low protein prescribable foods is available from the NSPKU website www.nspku.org
• Age‐based guidelines on the number of units of ACBS‐approved low protein foods that can be prescribed each month
are given on the NSPKU website. This is calculated to provide around 50% of daily energy intake
Energy supplements If appetite is poor and energy intake is low, energy supplements such as glucose polymer, fat emulsions or combined
energy/fat supplements may be needed to maintain phenylalanine control
ACBS, Advisory Committee on Borderline Substances.

* Aspartame (E951) is an artificial sweetener derived from a dipeptide composed of phenylalanine and the methyl ester of aspartic acid. It is added to
squashes, fizzy drinks, chewing gums, sweets, desserts, tabletop sweeteners and some savoury snacks, e.g. flavoured crisps. It should be avoided in
PKU. Other artificial sweeteners such as sucralose, saccharin or Acesulfame K are suitable.
†
It is advisable not to give rice milk to less than 4½ years old children less than due to its high arsenic content.
Source: BIMDG. Licensed under CC BY 4.0.
bone health and acts as a probiotic [63]. Unmodified CGMP is phenylalanine levels in well‐treated children with PKU.
low in some EAA or semi‐EAA such arginine, cysteine, histi- Therefore, it is essential CGMP substitutes are systematically
dine, tryptophan, leucine, lysine and tyrosine. When CGMP introduced when replacing Phe‐free l‐amino acids in chil-
is used as a protein substitute in PKU, it is supplemented dren under 12 years of age [64, 65]. Only one dose of CGMP
with deficient amino acids (except phenylalanine). CGMP should replace one dose of Phe‐free l‐amino acids at any one
protein substitutes, usually with added vitamins and min- time, and stability of blood phenylalanine control must be
eral, are available in powdered, liquid and bar presentations established (at least 3–4 serial blood phenylalanine concen-
(Table 28.A.1). Almost all CGMP protein is sourced from one trations within target range) before replacing a second dose.
supplier, and UK CGMP substitutes adapted for PKU mainly CGMP substitutes should not be used in children <4 years of
provide 1.8 mg phenylalanine for each 1 g protein equivalent age as there are no studies examining efficacy in this age
[63]. Taking 60 g/day of protein from CGMP substitutes (the group. Some brands of CGMP substitutes are higher in CHO
average adolescent/adult dose) provides an extra 108 mg/ and fat and provide a high energy intake. It is advisable not
day phenylalanine. It is established that if CGMP supplies the to mix powdered CGMP products with low protein milk,
entire daily dose of protein substitute, it increases blood such as Prozero and SnoPro, as this will add extra energy.
Table 28.10 Fruits and vegetables that are exchange-free in PKU [53, 54].
Fruits
Fresh, frozen or tinned in syrup (phenylalanine ≤75 mg/100 g)
Apples Jack fruit Plums

Apricots Kiwi fruit Pomegranates
Bananas Kumquats Prickly pears
Bilberries Lemons Prunes
Blackberries Limes Quinces
Blackcurrants Loganberries Raisins
Blueberries Raspberries
Clementines Lychees Redcurrants
Cherries Mandarins Rhubarb
Cranberries Mangoes Satsumas
Currants, black, red, white and dried Melons Sharon fruit
Custard apples Medlars Star fruit
Damsons Mulberries Strawberries
Dates Nectarines Sultanas
Dragon fruit Olives Tamarillos
Dried banana chips Oranges Tangerines
Dried fruit (not gogi berries) Papaya Watermelon
Gooseberries Pawpaws Mixed peel
Grapefruit Peaches Angelica
Grapes Pears Glace cherries
Greengages Physalis Ginger
Guava Pineapples
Vegetables
Fresh, frozen or tinned vegetables (phenylalanine ≤75 mg/100 g)
Artichoke Dudhi Parsley

Aubergine Endive Parsnip
Avocado Eddoe Peppers
Baby corn Fennel Plantain
Beans, French, green, runner Garlic Pumpkin
Beetroot Gherkins Radish
Cabbage, white Gourd Samphire
Carrot Herbs, fresh and dried Spring onion
Capers and caperberries Karela Squash, acorn, butternut, spaghetti
Cassava Kohl rabi Swede
Celeriac Lady’s finger (okra) Sweet potato
Celery Leek Tomato
Chayote Lettuce Tomato purée
Chicory Marrow Turnip
Cress Mooli Watercress
Courgette Onion Water chestnut
Cucumber Pak choi

Dosage of protein substitute prebiotics. If an adequate dose is consumed, they should

meet age‐dependent nutritional requirements. If a smaller
Precise requirements of protein substitute are unclear. The
dose is prescribed than usually advocated (e.g. when sap-
European PKU guidelines 2017 recommend that the total
ropterin is prescribed and there is relaxed natural protein
protein intake should supply 40% more than the FAO/
intake), vitamin and mineral intakes from diet and protein
WHO/UNU safe levels of protein intake for age [21], but this
substitute need to be carefully assessed. Protein substitutes
figure is arbitrary and unconfirmed by research. As most of
designed for children aged >3 years commonly have lower
the available protein substitutes are derived from Phe‐free
CHO added; the majority of energy requirements are pro-
l‐amino acid sources, MacDonald et al. recommend a higher
vided by food. The decrease in CHO content is not usually
dose is given to allow for inefficient absorption of natural/
associated with loss of metabolic control [70]. Some products
intact protein mainly derived from low biological value
contain minimal quantities of sodium and potassium, and
(LBV) plant protein, poor utilisation of l‐amino acids or sub-
adequate intake is expected to be provided by the diet. A
optimal energy intake [66]. This is supported by studies
small number of substitutes without added vitamins and
investigating metabolic control on differing dosages of free
minerals require separate supplementation.
l‐amino acids [66, 67]. Also, PKU data from European sur-
The nutritional composition of protein substitutes is given
veys suggest that most clinicians/dietitians recommend a
in Table 28.A.1. Suitable infant amino acid formulas are dis-
higher amount of total protein in their clinical practice than
cussed in the section on feeding and management of newly
the amount being recommended by the European PKU
diagnosed infants (p. 525).
guidelines 2017 [68]. Higher intakes of protein substitute
have been associated with better body composition (lower %
fat mass) [31]. Presentation of protein substitutes
Recommended daily total protein intakes per kilogram
From 6 months of age, there are spoonable semi‐solid pro-
body weight in the UK are given in Table 28.11.
tein substitutes or powders prepared with added water
Body weight, age, growth and the prescribed amount of
available [71]. For children >12 months of age, protein sub-
natural protein/phenylalanine are considered when deter-
stitutes are mainly presented as flavoured/unflavoured
mining the dose of protein substitute. If an individual is
powders (cans, pre‐measured sachets) or liquids. From the
obese, then the protein substitute requirement should be
age of 3 years, ready to drink pouches, powders, bars or
based on ideal body weight.
semi‐solid protein substitutes are available, together with
In one study, long‐term intake of l‐amino acids has been
tablets for older patients. The various presentations of pro-
linked to proteinuria and decreased glomerular filtration
tein substitutes are given in Table 28.12.
rate (GFR) in PKU, although total protein intake was only
0.96 g/kg; 24% of patients were overweight, 13% were obese
and 16% were not on dietary treatment from early infancy Adherence with protein substitute
[13]. This area requires further controlled study [21].
Adherence is an issue mainly associated with the bitter taste
of the substitutes. Failure to take the prescribed amount is
Nutritional composition of protein substitutes coupled with poor metabolic control. However, the improved
range, taste, volume, presentation and availability (through
The composition of l‐amino acid substitutes was originally
home delivery) of protein substitutes for PKU has improved
based on the amino acid profile of breastmilk [69]. The amino
long‐term adherence, particularly in teenagers taking liquid
acid composition of CGMP protein substitutes differs from
protein substitutes [72–74].
conventional l‐amino acid acids as they are naturally higher
in some amino acids, such as threonine and isoleucine. Most
protein substitutes for children aged >6 months contain Timing of protein substitute intake
added vitamins, minerals and long chain polyunsaturated
It is best to give protein substitutes in small frequent doses,
fatty acids (LCPUFA), usually docosahexaenoic acid
3–4 times spread evenly throughout the day rather than once
(DHA) ± eicosapentaenoic acid (EPA). Some also contain
or twice daily. Infrequent administration of large doses
increases nitrogen excretion as well as amino acid oxidative
utilisation, so this practice is not advocated [75]. Ideally, pro-
Table 28.11 Guidelines for total protein requirements for PKU (protein
tein substitute should be taken with natural protein to
intake from protein substitute and natural protein/phenylalanine
exchanges).
improve the balance of amino acids, thereby increasing effi-
ciency of dietary protein utilisation.
Age (years) Total protein (g/kg body weight/day)
0–2 3.0 Administration of protein substitutes

3–10 2.0 • They are hyperosmolar, ranging from 600 to 2700 mOsm/
11–14 1.5 kg H2O (manufacturers’ data), depending on their dilu-
>14 1.0 (maximum 80 g/day)
tion with water. If they are given in a small volume of
water or as a semi‐solid, they may cause abdominal pain,
Table 28.12 Presentation of protein substitutes, based on l‐amino acids.
Type of protein
substitute Advantages Disadvantages
Powdered Phe‐free • Nutritionally similar to standard infant formula except • May not contain novel nutrients like prebiotics
infant formula Phe‐free, tyrosine supplemented and higher in Phe‐free
protein content (approximately 2 g/100 mL formula)
• Contain LCPUFA and may contain novel nutrients such as
prebiotics
• Usually similar preparation instructions to standard infant
formula
Weaning/spoonable • Supplemented with vitamins and minerals ± DHA/EPA • Concentrated so needs to be administered with extra water
protein substitutes from • Proven to be a successful way of administering l‐amino • Low energy so advice regarding adequate energy
6 months of age. acids but need to be introduced in this format early in a provided from solid foods is necessary
Designed to be given child’s life (preferably from 6 months of age) [54, 55] • Poor taste but most infants adapt
as a semi‐solid • Useful to accustom a young child to the taste of l‐amino • Can be difficult to administer during teething and
consistency from a acids in the weaning period intercurrent illness
spoon • Low volume • Some spoonable protein substitutes thicken on standing
• Pre‐measured in a sachet • Should be prepared immediately prior to administration
• Less convenient than readymade protein substitutes; spoon
and water always need to be available for administration
Protein substitutes • Supplemented with vitamins and minerals ± DHA/EPA • Should be administered with additional water as a drink
suitable for children • Flexible as amount of water added can be varied to make • Poor taste
over 1 year of age. a low volume concentrated drink or higher volume more • Can be difficult to administer during teething
These powders are dilute drink • Needs preparation immediately prior to administration;
mainly presented as • Can be flavoured the smell may be stronger if left reconstituted for
flavoured/unflavoured some time
powders (in cans/ • Less convenient; always needs water available for
pre‐measured sachets) preparation
Ready to drink bottles • Supplemented with vitamins and minerals ± DHA/EPA • High volume
for children over 1 year • Ready to use/convenient • Poor taste
• Can be difficult to administer during teething
• More difficult to transport due to weight of liquids
Protein substitute • Supplemented with vitamins and minerals ± DHA/EPA • Poor taste
powders suitable from • Usually available in pre‐measured sachets (convenient • Less convenient; needs water available for preparation
3 to 4 years or older and easy to transport)
• Concentrated in amino acids so low volume
• Flexible as the amount of water added can be adjusted to
prepare a low volume concentrated drink or higher
volume more dilute drink
• Can be flavoured or available in different flavours
Ready to use liquid • Supplemented with vitamins and minerals ± DHA/EPA • Poor taste
pouches suitable from • Pre‐measured doses of protein substitute in low volume • Smaller volume pouches need extra water given due to
3 years of age • Convenient osmolality
• Different flavours available • More difficult to transport due to weight of liquids
• Usually low CHO/low fat/low energy
• Packaging presentation acceptable
Ready to use semi‐solid • Supplemented with vitamins and minerals ± DHA/EPA • Poor taste
protein substitutes • Pre‐measured doses of protein substitute in low volume • Small volume needs extra water given due to osmolality
• Convenient • More difficult to transport due to weight of product
• Usually low CHO/low fat/low energy • Always need a spoon to administer
• Packaging presentation acceptable
Tablets • Only some are supplemented with vitamins and minerals • Large number of tablets required
• Taste of l‐amino acids is masked in tablet format so useful • Needs to be administered with water
for patients who do not like the taste of liquid or • Not suitable for younger children
powdered products
• Low energy
Ready to use semi‐solid • Usually supplemented with vitamins and minerals • Taste fatigue
protein substitute bars • Novel presentation • Large number of bars needed to meet requirements
• Not palatable
Phe, phenylalanine; LCPUFA, long chain polyunsaturated fatty acids; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; CHO, carbohydrate.
Feeding and Management of Newly Diagnosed Infants with PKU 525
Table 28.13 Strategies for encouraging protein substitute in children. of DHA in plasma and membrane phospholipids compared
with controls without additional supplementation.
Caregivers should be patient, calm and encouraging while remaining DHA ± EPA supplements should be given if not already
persistent
added to the protein substitute (Table 28.A.1). The optimal
Establish a routine for protein substitute: always give at the same time dosage of DHA ± EPA in children is not established, but
each day
between 140 and 500 mg daily are provided by protein sub-
Continue to offer protein substitute even when a child refuses or is stitutes for children aged between 2 and 16 years.
unwell. Giving a child a ‘day off’ from protein substitute will adversely
affect their metabolic control and give the wrong message. Stopping a
protein substitute, even for 24 hours, may create difficulties with its Micronutrients
reintroduction, particularly in young children
With young children, if taken with meals, it may be better to offer Vitamins and minerals are added to most protein substitutes,
protein substitute before food while they are hungry so providing an adequate dose is prescribed, no additional
If more than one person administers the protein substitute, ensure that supplementation is necessary. If either a low dose of protein
all caregivers involved apply the same strategies in the same way substitute is taken, or protein substitute does not supply vita-
It is good practice to ensure that no protein substitute is left behind in mins and minerals, additional vitamin and mineral supple-
containers or pouches mentation is essential. Vitamin and mineral deficiencies are
An adult should always supervise the intake of protein substitute at now uncommon in PKU. Suitable supplements that can be
home, nursery or school prescribed are given in Table 28.14. To improve micronutrient
availability, it is best to administer all vitamin and mineral
supplements in two to three equal doses throughout the day.
diarrhoea or constipation. An additional drink of water

Interpreting blood phenylalanine results
should always be given with protein substitutes if they
are diluted with less water than recommended.
Guidelines on interpreting blood phenylalanine results are
• Artificial flavours should not be added to unflavoured
given in Tables 28.15 and 28.16.
protein substitutes before the age of 1 year.
• It is not usually advocated that protein substitute pow-
ders are added to food as this will spoil the taste of the Feeding and management of newly diagnosed
food and it cannot be guaranteed that all the food will be infants with PKU
eaten.
Blood phenylalanine concentrations consistently >360 μmol/L
Useful strategies for parents/caregivers to encourage pro-
are treated [21].
tein substitute are given in Table 28.13.
Initial treatment depends upon the diagnostic phenylala-
nine concentration:
Tyrosine supplementation
• Phenylalanine concentration >1000 μmol/L: The phenylala-
nine source (breastmilk or infant formula) is temporarily
In PKU, tyrosine is an indispensable amino acid because it is
stopped and replaced by a Phe‐free infant formula given
not supplied endogenously via phenylalanine hydroxyla-
at a minimum volume of 150 mL/kg/day. This is to
tion, or only to a limited degree. l‐tyrosine is important for
achieve a rapid fall in plasma phenylalanine concentra-
the biosynthesis of the brain neurotransmitters (epineph-
tions; a decrease of between 300 and 600 μmol/L/day is
rine, norepinephrine and dopamine), and melanin skin pig-
expected. For example, a diagnostic phenylalanine level
ments. Tyrosine is added to all ACBS prescribable protein
>2000 μmol/L may take 2–3 days to fall to 1000 μmol/L.
substitutes (9%–11% of the amino acids), and providing an
• Breastmilk or 50 mg/kg/day phenylalanine from stand-
adequate dose of protein substitute is prescribed, tyrosine
ard infant formula is introduced when phenylalanine
requirements should be met. Additional supplementation
concentrations are approaching 1000 μmol/L or below.
should be unnecessary.
This should be given with a Phe‐free infant formula.
Blood tyrosine concentrations are difficult to interpret
While breastfeeding (BF) is stopped for a minimal time,
with accuracy as there are wide diurnal variations in blood
mothers should be encouraged to regularly express
tyrosine over 24 hours. Fasting tyrosine concentrations may
their breastmilk. Mothers require a breastmilk pump
be low, but then peak immediately following protein substi-
and support from a midwife. Table 28.3 gives guidance
tute intake [76].
on phenylalanine requirements. Table 28.8 shows the
phenylalanine content of infant formulas.
Essential fatty acids and LCPUFA • Phenylalanine concentration 600–1000 μmol/L: It is not neces-
sary to stop the phenylalanine source. Either breastfeeds
A strict low protein diet is low in fat, α‐linolenic acid, arachi- or 50 mg/kg/day phenylalanine from standard infant for-
donic acid and devoid of any sources of EPA and DHA [77]. mula is given with a Phe‐free infant formula. Blood phe-
Children with PKU are likely to have lower concentrations nylalanine should reach target treatment range in 2–3 days.
Table 28.14 Prescribable micronutrient supplements (UK).
Product Company Daily dosage Age Comments
FruitiVits Vitaflo UK 6 g sachet From 3 years Orange‐flavoured powdered vitamin, trace element and mineral
mix. Contains minimal amount of carbohydrate, sodium and
potassium. Mix with water
Paediatric Nutricia Suggested daily dose: 0–14 years Powdered vitamin, trace element and mineral mix containing
Seravit • Age 0–6 months 14 g only trace amounts of sodium and potassium on a carbohydrate
• Age 7–12 months 17 g base; designed for infants and children; unflavoured and
• Age 1–7 years 25 g pineapple flavour. Mix with water or suitable fruit juice
• Age 7–14 years 35 g
Phlexy‐Vits Nutricia 7 g sachet or 5 tablets >11 years Unflavoured comprehensive vitamin and mineral supplement;
does not contain sodium and potassium; available in powder and
tablets. Powder can be mixed with water or fruit juice; better to
consume immediately after mixing
Forceval Alliance Recommended dose by >6 years Effervescent tablet. Contains all vitamins and minerals but
Junior soluble Pharmaceuticals manufacturer only one contains no calcium, phosphorus, sodium, inositol, choline and
tablet Ltd. daily only a small amount of potassium and magnesium.
If no other source of vitamins and minerals, 1 tablet dose is low
in vitamins A, D, folic acid, iron, zinc, selenium and iodine.
Dissolve in 125–200 mL water
Forceval Alliance Recommended dose by >12 years Effervescent tablet. Contains all vitamins and minerals except
soluble tablet Pharmaceuticals manufacturer only one vitamin K, inositol and choline but contains no sodium and only
Ltd. daily a small amount of potassium, calcium, phosphorus and
magnesium. Dissolve tablet in 125–200 mL water.
Table 28.15 Interpretation of blood phenylalanine results: high concentrations.
Cause of high phenylalanine concentrations Action
Fever/infection/trauma (illness management 1. Increase energy intake

guidance for PKU p. 530) 2. Ensure intake of protein substitute
3. Identify and treat source of infection as clinically indicated
4. Antipyretics as clinically indicated
Excess natural protein intake 1. Check understanding/calculation of phenylalanine exchanges, dietary adherence and
hidden sources of natural protein
2. Check that any low protein products are low protein, not gluten‐free products
Inadequate intake of protein substitute 1. Check adherence (at home, nursery, school)
2. Timing of protein substitute administration: should be spread out evenly over 24 hours
3. Check adequate home supplies of protein substitute
4. Recalculate protein substitute and adjust the dosage appropriately
Incorrect protein substitute Check type of protein substitute; occasionally the wrong type of protein substitute may
accidentally be prescribed or delivered
No obvious reason 1. If phenylalanine blood levels are consistently high (≥3 consecutive levels), consider a
reduction in natural protein by approximately 1 g/day protein or exchange equivalent;
total daily natural protein should not be decreased below 3 g/day
2. It is good practice to recheck blood amino acids before reduction in natural protein
• Phenylalanine concentration 360–600 μmol/L: Minimal restric- Breastfeeding

tion of phenylalanine may be all that is necessary but
depends on the individual baby. Initially breast or standard BF (with a Phe‐free infant formula) is associated with satis-
infant formula milk should provide approximately 75 mL/ factory blood phenylalanine control and growth.
kg/day (estimated 50% ‘normal’ requirements); then phe-
• Breastmilk has several advantages for the infant with
nylalanine intake is titrated according to blood levels.
PKU:
Blood phenylalanine levels should initially be monitored ◦◦ It is low in phenylalanine
twice weekly until stable. ◦◦ It contains LCPUFA
Feeding and Management of Newly Diagnosed Infants with PKU 527
Table 28.16 Interpretation of blood phenylalanine results: low concentrations.
Cause of low blood phenylalanine levels Action
Inadequate intake of natural protein 1. Ensure all prescribed intake of natural protein/exchanges are eaten
2. Check understanding of exchange system
Anabolic phase following an intercurrent 1. Ensure all prescribed intake of natural protein/exchanges are eaten and energy intake is adequate
infection 2. Repeat blood phenylalanine level. If level is still low, consider an increase in natural protein by
1 g/day; careful blood phenylalanine monitoring is required as the increase in extra
phenylalanine tolerance may be temporary
Rapid growth spurt such as puberty 1. Ensure all prescribed intake of natural protein/exchanges are eaten and energy intake is adequate
2. Repeat blood phenylalanine level; if level is still low, consider an increase in natural protein by
1 g/day; careful blood phenylalanine monitoring is required during any increase in natural
protein intake
◦◦ It is convenient and reduces the number of bottles • Alternatively, the calculated volume of standard infant
that needs to be given and helps establish good formula and Phe‐free infant formula can be mixed
mother–infant bonding together, but it is then essential that the full volume is
◦◦ It gives the mother some control over the feeding consumed. A disadvantage of mixing the source of phe-
process nylalanine (standard infant formula) with Phe‐free infant
• BF is based on the principle of giving a measured volume formula is that the infant will not easily adapt to the taste
of a Phe‐free infant formula before each breastfeed, so of the Phe‐free infant formula. Therefore, when phenyla-
inhibiting the baby’s appetite and, hence, suckling. This lanine from food exchanges is introduced and the quan-
reduces the amount of breastmilk taken so lowering phe- tity of standard infant formula is reduced, the Phe‐free
nylalanine intake. infant formula may be less acceptable and consequently
• Babies can still feed on demand, with a varying number refused.
of feeds from day to day, provided the Phe‐free infant • Ensuring a minimum volume of Phe‐free infant formula
formula is always given first. The volume given at each is consumed is just as important as ensuring all the phe-
feed changes according to blood phenylalanine concen- nylalanine source is taken (some infants may require the
trations and frequency of breastfeeds, from 30 to 50 mL Phe‐free formula to be given first to ensure the mini-
per feed. Most breastfed infants will take 6–8 feeds of mum volume is consumed). The total volume provided
Phe‐free infant formula daily. by the two formulas should equate to a feed volume of
• Once blood phenylalanine concentrations are stabilised 150–200 mL/kg/day. The Phe‐free infant formula and
within target treatment ranges, if phenylalanine levels source of phenylalanine (standard infant formula)
then increase >360 μmol/L, the Phe‐free infant formula is should be given at the same feed to deliver the correct
increased by 10 mL per feed; the amount of breastmilk balance of all EAA.
decreases accordingly.
The quantity of standard infant formula is adjusted by
• If phenylalanine concentrations are <120 μmol/L, the
25–50 mg phenylalanine/day according to blood phenylala-
Phe‐free infant formula is decreased by 10 mL per feed,
nine concentrations. If blood phenylalanine concentrations
with breastmilk being increased by similar quantities.
are <120 μmol/L, the standard infant formula is increased. If
• Local and international BF practices vary in PKU [78]. The
the blood phenylalanine is >360 μmol/L, the daily dietary
baby should be weighed weekly for the first 6–8 weeks.
phenylalanine is decreased by 25–50 mg providing the infant
BF can continue for as long as the mother and baby desire.
is well, gaining weight and drinking adequate quantities of
Phe‐free infant formula.
An example feeding plan is given in Tables 28.17 and
Bottle feeding
28.18. A case study is given in Table 28.22.
• Once phenylalanine concentrations are <1000 μmol/L,
50 mg/kg/day of phenylalanine from standard infant Introduction of solids
formula should be introduced (Table 28.8). The total
daily amount of calculated infant formula is divided • Solids should be introduced around 17–26 weeks of age
between 6 and 7 feeds. starting with 1–2 teaspoons of natural low protein
• Traditionally, it is recommended standard infant formula exchange‐free foods such as homemade purée fruits and
is given first to ensure the entire phenylalanine source is vegetables, e.g. apple, pear, carrot, butternut squash and
given, followed by the Phe‐free infant formula that can parsnip. A wide variety of homemade weaning foods or
be fed to appetite, with guidance on an acceptable mini- commercial baby foods containing exchange‐free ingre-
mum volume to give. dients only should be encouraged.
Table 28.17 Example of a daily feeding plan for a 4 kg infant with PKU having infant formula.
Aim: To provide 50 mg phenylalanine/kg/day and 3 g total protein equivalent/kg/day (using natural protein and Phe‐free infant formula)
• Total fluid intake = 200 mL/kg/day = 800 mL daily
• 90 mL Cow & Gate First Infant Milk (reconstituted from powder) = 50 mg phenylalanine
• Total number of feeds = 6
Phenylalanine requirement 50 mg/kg/day = 4 × 50 mg = 200 mg phenylalanine/day
• Daily formula intake from Cow & Gate First Infant Milk = 4 × 90 mL = 360 mL daily
• Total fluid requirement = 800 mL
• Fluid from Cow & Gate First Infant Milk = 360 mL
• Deficit = 440 mL (800–360 mL)
Feed deficit made up with Phe‐free infant formula, e.g. PKU Anamix Infant, PKU Start = 440 mL/day
Feeding plan
First feed: 60 mL × 6 feeds of Cow & Gate First Infant Milk
Second feed: 75 mL × 6 feeds of PKU Anamix Infant/PKU Start (more can be given if the infant is hungry)
However, in this calculation, a ‘generous’ intake is already provided, and a variable daily volume of Phe‐free infant formula may lead to an uneven
blood phenylalanine profile
Table 28.18 Nutritional analysis of a daily feeding plan for a 4 kg infant with PKU having infant formula.
Aim: To provide 50 mg phenylalanine/kg/day and total protein equivalent 3 g/kg/day (using natural protein and Phe‐free infant formula)
Energy
Protein Phenylalanine Fluid
kcal kJ equivalent (g) intake (mg/day) Carbohydrate (g) Fat (g) (mL)
360 mL Cow & Gate First Infant Milk (41 g dry weight) 238 990 4.7 191 26.6 12.2 360
450 mL PKU Anamix Infant (68 g dry weight) 311 1292 9 0 33.3 15.8 450
Total 549 2282 13.7 191 59.9 28 810
Intake per kg 137 571 3.4 48 202
% energy intake 10% 2% 41% 46%
• Low protein weaning foods are usually offered after the Phe‐free infant formula.) 1 g natural protein exchange
breast or formula feeds, so it does not alter the volume of should be introduced, gradually replacing all breast or
breastmilk/formula consumed. The intake of Phe‐free formula feeds with the equivalent natural protein source
infant formula should be carefully monitored to ensure from solid food. Foods such as purée potato, peas,
the amount is adequate. At this stage, the low protein yoghurt, ordinary rusks, baby rice or vegetable based
food is mainly offered for the infant to establish a taste weaning foods in jars or tins are useful protein exchange
for solids foods, and they usually accept these without foods. Cheese‐flavoured sauce mixes (given as exchange
difficulty [79]. food) can be introduced from the age of 6 months.
• Many low protein weaning foods have a low energy den- • More textured food should be gradually introduced from
sity, so higher energy weaning foods should be encour- 6 to 8 months with breakfast cereals, e.g. wheat biscuits
aged: low protein rusks mixed with cooled boiled water or oat based cereal, and mashed potato for protein
to a smooth paste; low protein pasta meal as a ‘porridge’ exchanges.
replacement or low protein breakfast cereal; custard • Finger foods can be given from 7 months of age: fingers
made with protein‐free liquid milk replacements, e.g. of low protein toast; soft fruits such as bananas, straw-
Prozero, SnoPro. Weaning foods are gradually increased berries and peaches; soft vegetable sticks; fingers of low
to three times daily. protein cheese; low protein bread sticks; low protein
• Once infants are taking 8–12 teaspoons at a time, natural rusks and biscuits. The Phe‐free infant formula or a pro-
protein exchange foods are given instead of the equiva- tein‐free milk replacement can be introduced from a
lent quantity of infant formula or a breastfeed. (One feeder beaker at 7 months of age.
breastfeed in combination with Phe‐free infant formula • From 9 months, low protein pasta dishes; sandwiches
is likely to provide approximately 1.0–1.5 g natural pro- made with low protein bread; chopped low protein
tein, but this amount is determined by the number of burgers or sausages; finger exchange foods such as mini‐
breastfeeds consumed in 24 hours and the amount of waffles, potato shapes and rice cakes.
Parent/caregiver Approach and Support 529
Introduction of second stage protein substitute Feeding preschool and school children

and young people
As solids are introduced, an infant may be unable to drink
adequate amounts of Phe‐free infant formula and so, from Issues to consider when feeding preschool and school chil-
the age of 5–6 months, will struggle to meet total protein dren and teenagers and during transition to adult services
requirements of 3 g/kg/day. At this stage, it becomes nec- are given in Table 28.20.
essary to introduce a more concentrated, spoonable second
stage/weaning Phe‐free l‐amino acid substitute (e.g. PKU
Anamix First Spoon, PKU Gel, PKU Squeezie, PKU
Parent/caregiver approach and support
Explore). Most are powdered and reconstituted with water
• If more than one person is involved in feeding a child with
(1 g powder to 1 or 1.5 mL water depending on the product)
PKU, there should be a family approach with all parents/
and given as a paste before meals (PKU Squeezie is ready
caregivers applying the same strategies in the same way.
to use).
• Extended family members should help with food prepara-
Spoonable protein substitutes are gradually introduced to
tion, e.g. making low protein bread, cakes and biscuits. It
meet protein equivalent requirements unmet by natural pro-
is best all family members receive education about PKU.
tein and Phe‐free infant formula. Generally, spoonable Phe‐
• Parents should be encouraged to batch cook and freeze
free l‐amino acid substitutes provide 2 g protein for each 5 g
low protein meals, so there are always ‘ready meals’ that
of product. A plan for introducing these products is given in
are suitable to eat.
Table 28.19. The entire Phe‐free infant formula should not
• Parents should be assisted to support each other: swap-
normally be replaced with the second stage Phe‐free l‐amino
ping recipe ideas, cooking tips and management tips on
acid substitute until infants are at least 1 year old as they still
difficult practical issues and organising local events such
require some Phe‐free infant formula to ensure adequate
as toddler groups, cookery workshops, family picnics.
energy intake. If the Phe‐free infant formula is continued
after 1 year, it is usually as a social drink, perhaps given in Good patient and parent education is essential. The
the morning or evening. NSPKU provides basic guidance on PKU management, pic-
Parents need support when transitioning protein substi- ture lists of exchange‐free/exchange fruits and vegetables,
tutes. It is essential that parents maintain a good daytime Christmas and Easter ideas, information packs for new par-
routine and consistency of approach and are persistent when ents, lists of ACBS prescribable low protein foods and book-
administering spoonable protein substitute. Infants usually lets and leaflets about PKU. They also produce a helpful
only exhibit difficulty in accepting it if they are unwell or teaching skills guide ‘Let’s learn about PKU’, designed to
when teething; but at the same time, they are usually refus- aid dietitians and nurse specialists. They also run annual
ing solid food [79]. Spoonable protein substitute is usually and regional conferences that include low protein cookery
given unflavoured <1 year of age. demonstrations.
Table 28.19 Plan for introducing spoonable Phe‐free l‐amino acid substitutes in infants from the age of 5–6 months.
A boy aged 5–12 months with PKU on 4 g natural protein (200 mg phenylalanine) daily and 3 g/kg/day total protein equivalent
Age 5 months 6 months 8 months 12 months
Weight 7 kg 8 kg 9 kg 10 kg
Protein equivalent (g/day)
4 g/day natural protein from 4 × 50 mg 4 4 4 4

phenylalanine exchanges
PKU Anamix Infant/PKU Start daily 12 (from 600 mL amino 12 (from 600 mL amino 12 (from 600 mL amino 8 (from 400 mL amino
acid infant formula) acid infant formula) acid infant formula) acid infant formula)
PKU Anamix First Spoon/PKU gel/PKU 5 (from approximately 8 (from approximately 11 (from approximately 18 (from approximately
Explore 5 12 g of product) 20 g of product) 28 g of product) 45 g of product)
Total protein equivalent 21 24 27 30
Protein equivalent intake kg/body 3 3 3 3
weight/day
If the infant takes less Phe‐free infant formula, then the amount of spoonable protein substitute should increase.
Table 28.20 Issues to consider when feeding different age groups of children with PKU.
Preschool children School children

• Avoid giving bottles with protein substitute after 1 year of age due to risk • School SENCO teachers need basic information about day to day
of dental caries/limiting appetite for solid foods. Intake of sweetened low practical implications of the PKU special diet. A care plan should be
protein drinks should also be controlled developed for each child including suitable drinks, snacks, school/
• Encourage consistent and regular mealtime routines packed lunches, mealtime supervision, school trips, breakfast clubs
• Encourage a variety of low protein foods, but it is not uncommon to find and after‐school care. Guidance should be given on protein
young children with PKU have food neophobia and are suspicious of substitute administration
new foods [80] • If children take a packed lunch to school, guidance on suitable
• Encourage families to eat together and share at least one low protein lunches is necessary, including choices of low protein bread, bread
food item, e.g. low protein vegetable soup, exchange‐free vegetables, rolls, low protein wraps or crackers. Slices of low protein vegan
fruit or sorbet for dessert. They should try to replicate the same food cheese/meat alternatives, small packets of dried fruit and fresh fruit
choices that the rest of the family are eating, e.g. low protein pizza are useful. Hummus, cereal bars, crisps, popcorn are practical
instead of regular pizza exchange foods
• Encourage children to eat with others, particularly at nursery • School children should have some knowledge about PKU. They
• Provide nursery with a care plan, and use different coloured food mats, need ongoing education about the foods they can eat, ‘exchange’
plate and cups for food and drink to help staff identify the child with foods, why they take their protein substitute and the need for blood
PKU. Adjust nursery menus so they are suitable for PKU. Ensure meals, tests. The PKU team should do one‐to‐one teaching or run group
snacks and protein substitute are carefully supervised and a record of teaching sessions. Parents should encourage children to be involved
food intake/protein substitute is kept for parents in their own treatment to help aid future independence
• Young children should be encouraged to help in the kitchen from an • Encourage attendance at weekend holiday camps and other events
early age, e.g. choosing toppings for low protein pizza, making low specifically for PKU so that children socialise with their peers and
protein cakes. This helps to create an interest in food and their diet share and discuss experiences of how they manage PKU
Teenagers Teenage pregnancy
• This is a challenging time. Young people want to be like their peers, and • In maternal PKU, high blood phenylalanine levels during pregnancy
socialising is encumbered by a low phenylalanine diet. It is well have a teratogenic effect on the developing foetus that can result in
established that blood phenylalanine control deteriorates with many foetal intrauterine growth retardation, infant low birth weight, facial
unable to keep blood phenylalanine levels within target range dysmorphism, microcephaly, developmental delay, intellectual
• From the age of 12 years, the process of transition to an adult clinic disabilities and congenital heart disease
begins. Children will attend a transition clinic, they will be expected to • The European PKU guidelines 2017 [21] state that from the age of 12
learn several core skills about managing their condition and they will see years, all females should receive systematic age‐related sex education,
the PKU team independently from their parents and from around the age with professional counselling about the risk of unprotected sexual
of 14 years will be introduced to the adult PKU team. Education about contacts. They should be informed that unplanned pregnancy can
teenage health issues is important occur even during the first menstrual cycle
• Teenage girls should feel comfortable discussing pregnancy and
Core skills contraception issues with their PKU medical teams. It is essential
• Knowledge about PKU that all discussions are conducted with an assurance of
• Understanding of phenylalanine exchange/exchange free foods confidentiality. They may need signposting to local family planning
• Understanding consequences of high phenylalanine levels clinics. GPs should be informed about the risks of maternal PKU
• Basic low protein cooking skills • Encouraging teenage girls to attend female health and pregnancy
• Learning how to take their own blood spots for phenylalanine study courses run by adult PKU clinics is important. It is an
• Learning how to order their protein substitute and low protein food opportunity for them to talk to women with PKU who have
supplies experienced pregnancy
• Apps/phone alarms to remind them to take their protein substitute, count
exchanges and to do blood tests may be helpful
SENCO, special educational needs coordinator; GP, general practitioner.
Management of illness The amounts of phenylalanine in a medicine may be listed

in its Summary of Product Characteristics, available via the
A formal emergency regimen (ER) is not normally necessary Internet.
during illness as acute metabolic decompensation does not
occur in PKU. However, to prevent an excessive rise in blood
substrate amino acid concentrations, it is prudent to encour- Learning points: phenylketonuria
age l‐amino acid substitutes and high CHO drinks during
illness [21]. • In early treated PKU, outcome is dependent on the quality
Factors to consider in the management of illness are given of blood phenylalanine control
in Table 28.21. • Lifelong treatment and follow‐up is recommended
Blood phenylalanine concentrations are likely to rise • Comprehensive European PKU guidelines for the medical
quickly during illness. For the immediate treatment of and dietary management of PKU are available [21]
infections (until a suitable aspartame‐free medication is • The UK NSPKU produces practical resources to help
sourced), it may be better to use aspartame‐containing patients with dietary management
medications rather than leave a child without treatment.
Management of Illness 531
Table 28.21 Factors to consider in the management of illness in PKU.
Factors Guidance
Protein substitute Maintenance of protein substitute intake to support protein synthesis. It may be better for this to be given in smaller,
frequent doses throughout the day. Try to control fever (temperature ≥38 °C) prior to administration to avoid vomiting
High carbohydrate intake Encourage high carbohydrate fruit juices/glucose polymer solution
Natural protein intake There is no need to formally omit natural protein. Catabolism will probably increase blood substrate amino acid
concentrations more than natural protein. However, in practice, a reduced appetite leads to a lower natural protein intake
Fluids Give regular drinks, particularly if there is high temperature, vomiting or diarrhoea. Oral rehydration solutions
(aspartame‐free) are suitable
Medications All treatment specific medication should be continued during illness. Medications should be free of aspartame.
Continue sapropterin if prescribed
Treat precipitating factors For example, antipyretics for fever; antibiotics (aspartame‐free) for infections
Table 28.22 Case study: a newborn screened infant with PKU being breastfed.
A healthy breastfed term infant

Day 5 of life: Newborn screening test taken
Day 9 of life: A presumptive positive screening result, blood phenylalanine level = 1200 μmol/L reported to the PKU team
The family were contacted by a specialist nurse from the PKU centre and general practitioner (GP) to explain the likely implications of this initial
screening result.
The parents were given the ‘PKU is suspected’ leaflet www.bimdg.org.
A repeat blood spot was taken to confirm the diagnosis of PKU by the specialist nurse and returned to the PKU centre immediately so the result would
be available for the hospital consultation with the family.
The parents and baby attended the PKU centre and were seen by a metabolic paediatrician, dietitian and nurse.
The repeat blood phenylalanine concentration = 1710 μmol/L
A blood sample for pterins was also taken to exclude tetrahydrobiopterin deficiencies (this was negative).
The infant weight = 3.2 kg. She was well and breastfed on demand. There were no issues with feeding.
Dietary intervention:
Breastfeeding was stopped for 24 hours only.
The infant was started on a Phe‐free infant formula given on demand.
The mother kept a daily record of all formula taken (the amounts and times) to estimate total feed intake.
The mother was advised to express breastmilk at least 6 times in 24 hours, and her local midwife was contacted to provide support.
Supplies of the specialist formula were organised (with parental consent) through a home delivery company who liaised with the GP.
The infant drank 60–90 mL of Phe‐free infant formula every 2–3 hours.
Twenty‐four hours later, blood phenylalanine had rapidly lowered = 1210 μmol/L.
Breastfeeding was recommenced; 50 mL of Phe‐free infant formula was introduced prior to each breastfeed.
Within a further 48 hours, the blood phenylalanine reduced = 210 μmol/L, the specialist formula was reduced to 40 mL prior to each breastfeed.
The mother was worried the baby was taking too little breastmilk, but with encouragement and reassurance she was happy to continue breastfeeding
in combination with the Phe‐free formula.
The baby was weighed weekly for the first 6 weeks and gained weight satisfactorily.
Blood spot phenylalanine concentrations were measured twice weekly, and within 2 weeks the parents had both learnt how to take blood samples.
The dietitian reported results to the parents on the same day of availability.
During the first 10 weeks of life, there was little variability in the blood phenylalanine concentrations, almost all = 120–360 μmol/L.
Gradually, phenylalanine concentrations increased to >300 μmol/L.
The baby was only taking six breastfeeds in 24 hours and was feeding for a longer duration at each feed. The Phe‐free infant formula was increased to
50 mL and then 60 mL before each breastfeed until almost all phenylalanine concentrations were maintained well within the target treatment range.
The infant was weaned onto solids at 22 weeks.

At 26 weeks the number of breastfeeds was further decreased with phenylalanine from food (50 mg phenylalanine exchanges) replacing breastfeeds at
breakfast, midday and evening meal.
The mother continued to give two to three breast feeds daily until the baby was 10 months old.
Maple Syrup Urine Disease

Anita MacDonald
Enzyme Branched chain 2‐ketoacid dehydrogenase (BCKD) complex that is composed of three catalytic enzymes (Figure 28.3). It is
the second enzyme in the catabolic pathway of the branched chain amino acids (BCAA): leucine, isoleucine, valine.
Biochemical defect The first step of BCAA catabolism is their transamination to form the branched chain keto acids. The second shared step in
the degradation of the branched chain keto acids is irreversible and catalysed by BCKD enzyme. Deficiency results in maple
syrup urine disease (MSUD) with:
• ↑ accumulation of plasma leucine, isoleucine and valine
• ↑ 2‐ketoacids in plasma, urine and cerebrospinal fluid
• l‐alloisoleucine is always present (≥5 μmol/L) and is pathognomic for MSUD
• ketonuria is present without treatment, poor metabolic control or catabolic stress
• ↑ molar ratio of leucine to other amino acids such as alanine, glutamine and tyrosine [81]
On presentation, plasma leucine levels are commonly 1000–5000 μmol/L (normal reference range 65–220 μmol/L).
Non‐classic forms of MSUD have lower presenting concentrations of BCAA.
Genetics Autosomal recessive inheritance
• >260 mutations reported.
• Estimated prevalence is 1 in 150 000 worldwide but is more common in Saudi Arabia, Qatar and Malaysia [82].
Newborn screening • Screening is by measurement of combined concentrations of leucine, isoleucine and alloisoleucine in dried blood spots
using tandem mass spectrometry (MS/MS). More information on UK screening and diagnostic and clinical management
protocols can be found at www.bimdg.org and www.gov.uk Newborn blood spot screening: laboratory guide for IMDs
(inherited metabolic diseases).
• UK infants are screened aged day 5; infants with classic MSUD may be symptomatic before newborn screening (NBS)
results are available
• NBS will detect patients with classic MSUD, but may not detect intermediate or intermittent forms that have a spectrum
of clinical and biochemical severity; milder variant forms of MSUD may have normal leucine levels in the newborn
period
Clinical onset Clinical phenotype can be divided into five types based on clinical presentation and severity; classical, intermediate,
presentation, features intermittent, thiamin‐responsive and E3‐deficient forms. The distinction between classic and intermediate type is not
absolute [83].
Classification
• Classic MSUD: 0%–2% enzyme activity, presents at the age of 2–3 days with ketonuria, intense sweet malty caramel
smell, irritability, poor feeding, vomiting, leading to lethargy, seizures, brain oedema, encephalopathic crisis, coma,
central respiratory failure and even death
• Intermediate MSUD: 3%–30% of normal enzyme activity, may appear healthy as a neonate, but present with anorexia,
developmental delay, faltering growth and metabolic encephalopathy triggered by intercurrent illness or other catabolic
stress
• Intermittent MSUD: 3%–30% enzyme activity, presentation at any age, normal growth and neurological development, but
may present with encephalopathy triggered by catabolic state (e.g. intercurrent illness or increased protein intake),
between episodes plasma BCAA are normal
• Thiamin‐responsive: A cofactor for BCKD complex with 2%–40% enzyme activity; thiamin‐responsive phenotype is
similar to intermediate MSUD
• Dihydrolipoamide dehydrogenase deficiency (E3‐deficiency): 8%–20% enzyme activity, early‐onset neurologic
phenotype: hypotonia, developmental delay, microcephaly, vomiting, hepatomegaly, lethargy, seizures, spasticity, Leigh‐
type encephalopathy and lactic acidosis
In MSUD, acute elevations of leucine and alpha‐ketoisocaproic acid (αKIC) due to trauma, surgery, illness, excess protein
intake and dietary non‐adherence increase the risk of metabolic decompensation, causing acute metabolic encephalopathy
and life‐threatening cerebral oedema.
Long‐term Without early and effective treatment, children develop severe and permanent brain damage, including spasticity, and may
complications and die within the first few months of life. With early diagnosis and diligent dietary management, the outcome is improving.
outcome Children with milder variants of MSUD tend to have better outcomes [84], but all patients are vulnerable to rapid
deterioration associated with catabolic stress. Treated individuals have average low IQs, inattention, hyperactivity,
generalised anxiety, depression and movement disorders. Some attend normal schools and have normal IQ scores.
Intellectual outcome is related to the length of time after birth that plasma leucine concentrations are >1000 μmol/L and
quality of long‐term metabolic control. High leucine levels are associated with psychological comorbidity (particularly long
periods of leucine toxicity and recurrent acute decompensations) [85]. Pancreatitis has been documented during acute
intercurrent illness/leucine intoxication [83].
Maple Syrup Urine Disease 533
Leucine Isoleucine Valine
2-Oxo-isocaproic acid 2-Oxo-3-methylvaleric acid 2-Oxo-3-isovaleric acid

(1) (1) (1)
Isovaleryl-CoA 2-Methylbutyryl-CoA Isobutyryl-CoA
(2)
3-Methylcrotonyl-CoA
(3) 2-Methyl-3-hydroxybutyryl-CoA
3-Methylglutaryl-CoA (6)
2-Methylacetoacetyl-CoA
(4)
3-Hydroxy-3-methylglutaryl-CoA Propionyl-CoA
(5) (5) (7)
Acetoacetate Acetyl-CoA Methylmalonyl-CoA
(8)
1. Maple syrup urine disease Succinyl-CoA
2. Isovaleric acidaemia
3. 3-Methylcrotonyl-CoA carboxylase deficiency
4. 3-Methylglutaconyl-CoA hydratase deficiency
5. 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
6. 2-Methylacetoacetyl-CoA thiolase deficiency
7. Propionic acidaemia
8. Methylmalonic acidaemia
Figure 28.3 Selected inborn errors of the catabolic pathways of branched chain amino acids.
Growth and nutrition

There may be low height for age z‐scores [86]. A higher BMI at the age of 5 and 10 years in children with MSUD compared
with other IMDs treated with low protein diets was observed [87]. Energy intake in the early treatment years was >200% of
predicted basal metabolic rate (BMR), contributing to long‐term increased BMI and % fat mass [87]. Nutritional deficiencies
may occur including valine and isoleucine deficiency [88], n‐3 fatty acids [81], selenium as indicated by erythrocyte
glutathione peroxidase measurements [89]. Chronic deficiency of BCAA may cause anaemia, acrodermatitis, hair loss,
growth failure, arrested head growth, anorexia and lethargy. Low bone mineral density (BMD) is also reported in adolescents
[83]. Bone fractures cause transient leucinosis [83]. Chronic imbalance of plasma BCAA or natural protein over‐restriction
can lead to abnormal brain amino acid uptake with subsequent decreased myelin and neurotransmitter synthesis, causing
brain damage and possibly manifesting as chronic encephalopathy [90].
Medical treatment • In classic MSUD, lifelong dietary treatment with a low BCAA diet is essential (except post‐liver transplantation).
• Metabolic decompensation is a risk post‐diagnosis and is triggered by trauma, surgery, illness and excess leucine intake.
Meticulous treatment using an emergency regimen (ER) (p. 673) is necessary. It is essential to monitor biochemical and
clinical status and prevent catabolism by providing adequate BCAA‐free protein, energy and fluid. On diagnosis, rapid
reduction of toxic metabolites is vital (p. 535).
• Care should be provided by a specialist multidisciplinary team consisting of medical doctor, dietitian, nurse and
psychologist. Good family/patient education is essential.
• Assessment of developmental milestones and neurocognitive and neuropsychological outcome should be done at regular
intervals such as preschool, primary, middle and senior school ages.
• Diet history and growth (weight, length/height, BMI) should be monitored at each clinic visit. Assessment of BMD should
be conducted in adolescence. Calcium, vitamin D and natural protein intake should be optimised, with regular exercise
for bone health.
• Effective transition processes between paediatric and adult services is essential.
• Consideration of liver transplantation. This is associated with an increase in BCKD activity; diet therapy should be
unnecessary although acute metabolic decompensation has occurred in the early period after heterozygous living donor
liver transplantation in a single case study [91]. Some advocate long‐term monitoring of BCAAs, particularly at times of
illness [92], and others recommend an ER during illness [93]. Even though there is no further neurocognitive deterioration
following liver transplantation, any existing dysfunction cannot be reversed.
• In thiamin‐responsive phenotype, pharmacological doses of thiamin may improve metabolic control and BCAA tolerance.
In thiamin‐responsive patients, leucine tolerance may increase, but patients are likely to require a BCAA restricted diet
and ER during illness [94].
• Hepatocyte transplantation has been shown to correct selected neurometabolic abnormalities in MSUD mice [95].
• Sodium phenylbutyrate has been considered as an adjunct therapy increasing enzyme activity of BCKD and decreasing
blood BCAA levels. However, patient data is limited [96, 97].
Dietetic management • The aim is to maintain plasma BCAA concentrations within a target treatment range that is not associated with
neurotoxicity (that can cause encephalopathy and cerebral oedema). Dietary restriction of leucine, valine and isoleucine
is necessary while avoiding their deficiency.
• Dietary principles are similar to PKU. To ensure adequate protein synthesis, energy intake should meet estimated average
requirements for age [98]. Low protein/exchange‐free foods are similar as for PKU (Table 28.9). Generally, any foods
containing protein ≤0.5 g/100 g weight are considered exchange‐free. Suitable fruits and vegetables given without
measurement are listed in Table 28.23.
• Low protein special foods (e.g. bread, pasta, cereals) are an important source of energy, but some contain higher amounts of
leucine (Table 28.24); these should be calculated as part of the leucine exchange allowance.
• If appetite is poor, additional energy supplements such as glucose polymer or fat emulsions may be necessary to minimise
catabolism. Tube feeding may be required in a few cases. Long periods of fasting should be avoided, particularly in young
children as blood leucine increases with fasting.
• In classical MSUD, leucine tolerance is likely to vary from 400 to 700 mg/day in children [87] and is allocated in 50 mg
leucine exchanges (this is equivalent to approximately 0.5 g protein) (Table 28.25).
The diet is supplemented with leucine, valine and isoleucine‐free l‐amino acids, with dosage and distribution similar to a
low phenylalanine diet in PKU (p. 525). Age‐specific MSUD amino acids are available, but the choice is more limited than
for PKU (e.g. MSUD Anamix Infant, MSUD Anamix Junior, MSUD Gel, MSUD Lophlex LQ, MSUD Cooler 10, 15, 20,
MSUD Maxamum). Total daily protein requirements are given in Table 28.26. They are usually supplemented with vitamins
and minerals, and, if an adequate dose is prescribed, dietary reference values of micronutrients should be met. Details of
presentation, composition, age suitability and preparation can be found on the manufacturers’ websites: www.nutricia.co.uk,
www.vitaflo.co.uk. Similar products are available outside the UK: www.abbottnutrition.com, www.meadjohnson.com,
www.metax.org, www.milupa‐metabolics.com. Separate flavour packs are also available.
Additional valine and isoleucine supplements are invariably necessary. Valine supplementation has a low affinity for the
blood–brain barrier LAT1 transporter, and it is especially vulnerable to competitive inhibition by leucine [83]. Failure to
provide adequate isoleucine and/or valine for protein synthesis during acute metabolic decompensation slows the rate at
which blood leucine decreases. In infants and children, a suggested starting dose of 50–100 mg/day of valine and/or
isoleucine should be given if isoleucine and/or valine are below target treatment range. The dose is then titrated according to
plasma valine and isoleucine concentrations.
Separate valine (50 or 1000 mg) and isoleucine (50 or 1000 mg) supplements are available in pre‐measured sachets (www.
vitaflo.co.uk). A small amount of carbohydrate (CHO) (3.8 g/4 g sachet) is added to each 50 mg valine/isoleucine sachet. This
CHO should be calculated in infant and ER feeds (dosage with ER feeds is given on p. 539 and in newly diagnosed infants
on p. 535). Valine and isoleucine supplements should be given in three doses throughout the day and added to the BCAA‐
free amino acid substitute or low protein milk.
Non‐classic MSUD dietetic management

• Intermediate MSUD: leucine restriction +/− branched chain free amino acids and an ER are necessary
• Intermittent MSUD: may only require moderate protein restriction (no branched chain free amino acids) and an ER
• Thiamin‐responsive phenotype: leucine restriction +/− branched chain free amino acids and thiamin supplementation [94]
and an ER; thiamin is required during illness, fasting, infection or surgery [101]
• E3‐deficiency: a BCAA‐restricted diet does not reverse or prevent ongoing symptoms, but can maintain blood BCAA
concentrations within target ranges; ER is necessary
Monitoring • In order to meet leucine requirements for protein synthesis and avoid protein deficiency, recommended target
biochemical leucine concentrations are 100–300 μmol/L [83, 94]. In the UK, current recommended practice is to maintain leucine
at 150–300 μmol/L, although this is challenging. Some recommend maintaining 2–3 hour postprandial leucine
concentrations close to normal concentrations (80–200 μmol/L) [94], but this may result in leucine deficiency
• Recommended target valine and isoleucine concentrations are between 200 and 400 μmol/L
• Parents may be taught how to collect either dried blood spots or liquid blood samples. Different acceptable BCAA
reference ranges may be used for dried blood spots versus plasma samples
• Ideally, following initial stabilisation in infancy, early morning fasting blood spots for BCAA should be taken weekly in the
first 5 years, once every 2 weeks aged 6–12 years and monthly in teenagers
• BCAA results should be promptly reported to parents and interpretation discussed. The guidelines given in Table 28.15 can
be used for adjusting leucine intake in accordance with blood BCAA levels. Principles are similar to PKU. Instead of
increasing/decreasing protein intake by 1 g/day (as described for PKU), leucine intake should be increased/decreased by
50 mg/day (0.5 g/day protein) in response to low or high blood leucine levels. Factors such as illness, growth and dietary
adherence should be taken into account as in PKU (Tables 28.15 and 28.16). If leucine intake is increased or decreased, it
may similarly affect valine and isoleucine blood levels; therefore adjustment of valine and isoleucine supplements may be
necessary
• Annual measurement of quantitative amino acids, plasma homocysteine and/or methylmalonic acid, haemoglobin, MCV
and ferritin, plasma zinc, selenium and vitamin D
Clinical management BIMDG Newborn Screening Guidelines www.bimdg.org.uk including MSUD clinical management guidelines, MSUD
guidelines dietetic management guidelines, MSUD emergency regimen [102].
USA Nutrition management guideline for maple syrup urine disease: an evidence‐ and consensus‐based approach [94].
Parent support Metabolic Support UK www.metabolicsupportuk.org
groups Maple Urine Disease Family Support Group USA. www.msud‐support.org
Management of Infants with MSUD 535
Table 28.23 Fruits and vegetables allowed without measurement target treatment levels. The stimulation of a high rate of pro-
in MSUD [46, 99]. tein synthesis and to minimise catabolism is essential to aid
removal of leucine from the plasma pool.
Fruits
Treatment of the infant with MSUD includes the
Fresh, frozen or tinned in syrup (<1 g protein/100 g or <30 mg following:
leucine/100 g)
• Immediate removal of toxic metabolites by continuous
Apples Guava Oranges venovenous extra corporeal therapies (CECRT) including
Apricots Kiwi fruit Peaches haemodialysis and haemofiltration [103], reducing leu-
Blackberries Lemons Pears
cine to almost 1000 μmol/L or lower within 24 hours irre-
spective of initial leucine concentration in neonates [104].
Blackcurrants Limes Pineapples
• Newborn screening by MS/MS may lead to earlier treat-
Clementines Loganberries Plums ment and prevent the need for CECRT [105] with dietary
Cherries Loquats Pomegranates treatment alone normalising leucine levels within 2–3 days.
Cranberries Lychees Raspberries • BF and infant formula (leucine source) are stopped
temporarily.
Damsons Mandarins Rhubarb
• The rate of decrease of blood leucine concentrations
Fruit salad Mangoes Satsumas should be >750 μmol/L per 24 hours [106]. CECRT is
Gooseberries Melons Starfruit more effective than diet alone in reducing plasma leucine
Grapefruit Mangosteen Strawberries and can usually be stopped around 24–36 hours after
Grapes Nectarines Tangerines commencement.
• Enteral feeding should be commenced early. BCAA‐free
Greengages Olives Watermelon
infant formula (e.g. MSUD Anamix Infant) will stimulate
Vegetables
protein synthesis. 150 mL/kg/day of BCAA‐free infant
formula (providing 2 g/100 mL protein equivalent) will
Fresh, frozen or tinned (<1.5 g protein/100 g or <100 mg provide 3 g/kg/day BCAA‐free protein equivalent. If fluid
leucine/100 g) is restricted, it may be necessary to supplement BCAA‐free
infant formula with additional concentrated BCAA‐free
Artichoke+ Fennel+ Plantain§ amino acid mixes only (MSUD Aid 111 or MSUD Amino 5)
Aubergine Garlic+ Pumpkin to enable provision of 3 g/kg/day BCAA‐free protein
Beans, French, green §
Gherkins# Radish equivalent. A feeding plan is given in Table 28.27.
Beetroot Gourd #
Samphire§ • A high energy formula (120–140 kcal [500–585 kJ]/kg/
day), administered by a continuous tube feed or bolus, is
Cabbage §
Leek* Spring onion
necessary to promote anabolism. Glucose polymer is
Carrot Lettuce §
Squash, butternut# usually added to BCAA‐free infant formula to provide a
Celery Marrow +
Swede total of 10 g CHO/100 mL and 79 kcal (330 kJ)/100 mL.
Chicory Mustard and cress Sweet potato§ Fat emulsion (e.g. Calogen) is added, as necessary.
Chives #
Onions Tomato
• If enteral feeds are not well tolerated, intravenous (IV)
fluids are given – 10% dextrose with additional electro-
Courgette* Parsley +
Tomato purée
lytes and lipid (e.g. Intralipid at 2 g/kg/day). Any hyper-
Cucumber Parsnip§ Turnip glycaemia requires insulin administration. A continuous
Endive +
Peppers Watercress+ feed of BCAA‐free amino acids (+ valine/isoleucine)
may be tolerated (recipes are given at www.bimdg.org.
* No leucine data are available for these fruits and vegetables. uk) and will help plasma leucine decrease.
+
They are included on the free list because they contain <1 g • Plasma leucine will not decrease if isoleucine and/or
protein/100 g or are consumed in small amounts infrequently.
#
No leucine data are available for these vegetables, but they are
valine are deficient (as they become rate limiting for pro-
consumed in small quantities. tein synthesis), and it has been suggested that 60–90 mg/
§
These vegetables contain 50–100 mg leucine/100 g, so it is better to use kg/day (varying between 200 and 400 mg/day) of isole-
them in small quantities in the diet. ucine and valine should be given to support maximal
NB: The protein content of vegetables is 3%–6% leucine (i.e. 30–60 mg rates of protein synthesis. There is little toxicity associ-
for 1 g protein); the protein content of fruits is 5% leucine (50 mg leucine ated with increased plasma concentrations of isoleucine
for 1 g protein) [100].
and valine [105], and plasma levels are likely to fall
quickly with haemodialysis/haemofiltration.
• Individual supplements of valine and isoleucine (50 mg/
Management of infants with MSUD sachet) may be used. The contribution of energy and CHO
(3.8 g/CHO per 4 g sachet) from these supplements
The newly diagnosed infant is likely to be very sick, requir- should be calculated. These can be either added to the
ing admission to intensive care and ventilation. On presenta- feed or mixed with water and given as a medicine, if there
tion in infancy, rapid leucine reduction is required to achieve is a risk the full volume of enteral feed may not be given.
Table 28.24 Leucine content of low protein manufactured foods that should be calculated as part of leucine exchange system.
Amount of leucine
Product Portion size (mg) per portion size 50 mg leucine exchanges
Nutricia Loprofin Drink 200 mL 40 1 exchange/200 mL

Nutricia SnoPro 200 mL 30 0.5 exchange/200 mL
Taranis Dalia Drink 200 mL 28 0.5 exchange/200 mL
Taranis Fish substitute 19 g portion 57 1 exchange per portion
Promin Low Protein Potato Pot, Sausage and Croutons 50 g pot 57 1 exchange per pot
Promin Low Protein Potato Pot, Bacon, Cabbage and Croutons 50 g pot 68 1 exchange per pot
Promin Low Protein Potato Pot, Onion and Croutons 50 g pot 68 1 exchange per pot
This is not a comprehensive list of low protein manufactured foods that should be counted as leucine exchanges. It is possible that the recipes of some
manufactured products may change over time, so it is important to regularly recheck the leucine content of low protein manufactured foods.
Table 28.25 50 mg leucine exchanges for MSUD.
Food Weight Protein* (g) Leucine† (mg) Isoleucine† (mg) Valine† (mg)
Milk
Human milk, mature 40 mL 0.5 50 29 29
SMA Pro First Infant Milk‡ 40 mL 0.5 52 26 29
Cow & Gate First Infant Milk‡ 38 mL 0.5 52 32 29
Cow’s milk 15 mL 0.5 50 27 36
Single cream 20 mL 0.5 48 26 36
Double cream 35 mL 0.6 52 30 38
Yoghurt (natural/flavoured) 10 g 0.4 57 31 34
Custard 15 mL 0.4 57 31 42
Cereals
Rice, raw 10 g 0.7 56 26 39
Rice, boiled 25 g 0.6 47 22 32
Vegetables
Asparagus, boiled as served 65 g 1.9 49
Baked beans, canned 15 g 0.8 51
Broccoli, boiled 45 g 1.5 51
Brussels sprouts, boiled 35 g 1.1 53
Cauliflower, boiled 40 g 0.8 53
Mushrooms, fresh 50 g 0.8 53
Okra, fried in oil 35 g 1.0 52
Peas, boiled 15 g 0.8 45
Petit pois, boiled 15 g 0.8 51
Spinach, boiled 20 g 0.4 54
Spring greens, boiled 25 g 0.5 51
Sweetcorn, canned 15 g 0.4 50
Yam, boiled 45 g 0.7 49
Potato§
Boiled, jacket 60 g 1.3 55
Roast 45 g 1.2 53
Chips 35 g 1.2 46
Fruits (edible portion)
Avocado 45 g 1.0 52
Bananas 55 g 0.7 53
Dried fruits¶ 60 g 1.4 56
Figures for the weight of food are rounded to the nearest 5 g, although many families use electronic scales which are accurate to between 1 and 2 g.
* [99].
†
[46].
‡
Manufacturers’ data for infant formulas.
§
Potato – the leucine content of potato varies between old, new and different varieties; an average figure has been used.
¶
Dried fruits – the leucine content of different dried fruits is similar, so an average figure has been used.
Management of Infants with MSUD 537
• Oral feeding can usually be re‐established once the the volume titrated according to BCAA amino acid concen-
infant is extubated and leucine level is normalised. trations. This process for BF is similar to PKU (p. 526).
Leucine is given from standard infant formula/ There are few reports of BF infants with MSUD [108].
expressed breastmilk (EBM) when plasma leucine is • Plasma BCAA should be monitored frequently, prefera-
<800 μmol/L. Although young infants often tolerate bly daily in the early stages of management. Feeding
between 300 and 400 mg/day of leucine [107], it may be plans are given in Table 28.28 and 28.29.
prudent to start with 200 mg/day (140 mL infant formula)
of leucine (divided equally throughout the daily feeds) Introduction of solids
and increase/titrate intake according to blood concentra-
tions, aiming for blood leucine 150–300 μmol/L. The timing and principles of weaning is similar to PKU
• As leucine intake from infant formula increases, this natu- (p. 527). Start at one meal only with 1–2 teaspoons of home-
ral protein will also provide a source of isoleucine and made purée fruits and vegetables (e.g. apple, pear, carrot,
valine, and so these individual supplements should be butternut squash and parsnip). Commercial baby foods
reduced and adjusted to maintain them within target treat- should contain exchange‐free ingredients only (e.g. low leu-
ment reference ranges. A total protein intake of 3 g/kg/ cine fruits and vegetables without rice or milk). Gradually
day from standard infant formula and BCAA‐free infant increase to 3 times daily and progress from smooth purée to
formula is necessary. Once oral feeding is established, the lumpier foods and suitable low protein finger foods (p. 528).
BCAA‐free infant formula and infant formula should be Many low protein weaning foods have a low energy den-
administered in separate feeding bottles (similar to PKU sity, so higher energy weaning foods should be encouraged:
p. 527). A measured volume of infant formula is given (6–8 low protein rusks mixed with cooled boiled water to a
times/day) followed by BCAA‐free infant formula. smooth paste, low protein pasta meal as a ‘porridge’ replace-
• An infant with MSUD can be breastfed. During initial stabi- ment or low protein breakfast cereal and custard made with
lisation, BCAA‐free infant formula and valine and isoleu- protein‐free/leucine‐free liquid milk replacements, e.g.
cine supplements are given until leucine levels are Prozero (some low protein milk replacements contain
<800 μmol/L, with the mother expressing breastmilk. leucine – Table 28.24).
Infants can then be breastfed on demand, but always with a As the intake of solids increases, gradually reduce the
measured quantity of BCAA‐free infant formula first, with breastmilk/infant formula by 1 × 50 mg leucine exchange
(e.g. 40 mL breastmilk; 38–40 mL infant formula depending
Table 28.26 Guidelines for total protein requirements for MSUD on the brand), and replace with 1 × 50 mg leucine exchange
(protein intake from protein substitute and natural protein/leucine of food (e.g. 40 g cauliflower or 45 g avocado). This process is
exchanges).
continued until all the leucine from breastmilk or infant for-
mula is replaced. The leucine exchanges should be divided
between the three main meals.
0–2 3.0
3–10 2.0 Introduction of second stage protein substitute
11–14 1.5
As solids are introduced, an infant may be unable to drink
adequate BCAA‐free infant formula to meet total protein
Table 28.27 Example of daily feeding plan for an 8‐day‐old 3 kg infant with MSUD.
Newly diagnosed by newborn screening with leucine concentration of 1200 μmol/L
Energy (kcal Protein equivalent CHO Fat Leucine Valine Isoleucine

Ingredients Amount (kJ)/day) (g/day) (g/day) (g/day) (mg/day) (mg/day) (mg/day)
MSUD Anamix Infant 450 mL 311 (1300) 9 33.3 15.8 0 0 0

Valine 50 sachets 16 g 60 (250) 0.2 15.2 0 0 200 0
Isoleucine 50 sachets 16 g 60 (250) 0.2 15.2 0 0 0 200
Total daily intake 431 (1800) 9.4 63.7 15.8 0 200 200
Intake kg/day 144 (600) 3.1 0
Per 100 mL 96 kcal (400 kJ) 2.1 g 14.2 g 3.5 g 0 44 mg 44 mg
Administration: 19 mL/hour over 24 hours via nasogastric feeding tube.

Total CHO concentration of feed is high due to the CHO content of the valine/isoleucine 50 sachets. However, valine/isoleucine supplied by the
supplementary sachets will decrease as natural protein is introduced from breastmilk or standard infant formula (according to tolerance/titrated
according to blood leucine concentrations). This will decrease the overall CHO concentration of the feed.
Table 28.28 Example of daily feeding plan for 18‐day‐old 3.3 kg infant with MSUD.
Feeding 167 mL/kg/day, tolerating 80 mg/kg/day leucine (264 mg/day) and 200 mg/day of valine and isoleucine
Feeding plan
First feed: 25 mL × 3 × 8 feeds of Cow & Gate First Infant Milk
Second feed: 45 mL × 3 × 8 feeds of MSUD Anamix Infant
Energy
Protein Leucine Isoleucine Valine
(kcal) (kJ) equivalent (g) CHO (g) Fat (g) (mg) (mg) (mg)
190 mL Cow & Gate First Infant Milk (26 g powder) 125 523 2.5 13.9 6.5 260 160 145
360 mL MSUD Anamix Infant (54 g powder) 248 1033 7.2 26.6 12.6 0 0 0
Valine 50 sachets (4 g dry weight) 15 63 0.04 3.8 0 0 0 50
Isoleucine 50 sachets (4 g dry weight) 15 63 0.04 3.8 0 0 50 0
Total 403 1682 9.8 48.1 19.1 260 210 195
Per 100 mL 73 306 1.8 8.7 3.5
Per kg 122 510 3.0 14.6 5.8 79 64 59
Valine/isoleucine supplementation is titrated according to blood valine/isoleucine concentrations. One leucine exchange is equivalent to 50 mg.
Table 28.29 Example of daily feeding plan for a 2‐month‐old 4.5 kg infant with MSUD.
Feeding 165 mL/kg/day to provide 400 mg leucine (8 leucine exchanges) and 250 mg/day of both valine and isoleucine
Feeding plan
First feed: 50 mL × 6 feeds of Cow & Gate First Infant Milk
Second feed: 75 mL × 6 feeds of MSUD Anamix Infant
Energy
Protein Leucine Isoleucine Valine
kcal kJ equivalent (g) CHO (g) Fat (g) (mg) (mg) (mg)
300 mL Cow & Gate First (41 g powder) 198 825 3.9 21.9 10.2 410 253 229
450 mL MSUD Anamix Infant (68 g powder) 311 1291 9 33.3 15.8 0 0 0
Total 509 2116 12.9 55 26 410 253 229
Per 100 mL 68 282 1.7 7.3 3.5
Per kg 113 470 2.9 12.2 5.9 91 56 51
Valine/isoleucine supplementation is titrated according to blood valine/isoleucine concentrations. One exchange of leucine is equivalent to 50 mg.
requirements of 3 g/kg/day. From 6 months, and usually at Feeding preschool and school children
the time of introducing leucine exchanges, it is necessary to and young people
gradually introduce a more concentrated spoonable second‐
stage/weaning BCAA‐free l‐amino acid substitute (e.g. Issues to consider when feeding preschool and school chil-
MSUD gel; 5 g powder provides 2 g BCAA‐free protein dren and teenagers and during transition to adult services
equivalent). This is reconstituted with approximately 1–2 mL are given in Table 28.30.
water for each 1 g of product and is given as a paste before
meals (as in PKU p. 529). At 1 year of age, the spoonable
protein substitute may be replaced by a concentrated/low Emergency regimens for management
volume drink, e.g. MSUD Anamix Junior powder (10 g proof intercurrent illness
tein equivalent/29 g powder) and MSUD Anamix Junior LQ
(10 g protein equivalent/200 mL). During intercurrent infections, surgery and injury, plasma
BCAA‐free infant formula should not normally be com- BCAA concentrations may rise rapidly, particularly leucine
pletely replaced by the second stage amino acid substitute due to inadequate energy intake [109] and the direct cata-
until infants are at least 1 year old as the infant still requires bolic effect of the infection [110]. This may cause rapid neu-
some BCAA‐free infant formula to ensure adequate energy rological deterioration, with neurotoxic levels of leucine and
intake. branched chain keto acids being reached within hours [107].
Emergency Regimens for Management of Intercurrent Illness 539
Table 28.30 Issues to consider when feeding different age groups of children with MSUD.
Preschool children School children/teenagers

• Associated with a higher CHO diet, young children with MSUD • School‐aged children with MSUD may be resistant to transitioning from an
may be at greater risk of dental caries causing decay, pain and amino acid substitute for young children (e.g. MSUD gel) to a liquid pouch
distress. Encourage parents to take their child to see a family (which is easier to administer and has an age‐appropriate micronutrient
dentist as soon as their first teeth come through and at the latest profile). Involving schoolteachers with this change may be helpful. Under
by the age of 1 year, so preventative advice can be offered and the supervision of a teacher/teaching assistant, gradually introduce and
children acclimatise to the dental surgery environment increase the volume of an amino acid substitute from a small liquid pouch.
• Young children with MSUD will often eat a very limited diet, This will help children become accustomed to the new taste, flavour and
repeating the same narrow range of foods. It is important to texture of the protein substitute. Only when at least 10 g protein equivalent is
build their confidence when eating. Avoid aversive food supplied by the new product should one daily dose of protein substitute be
experiences. Introduce new foods by a graduated series of small replaced. This usually takes considerable time
changes around a food, beginning in child’s comfort zone and • SENCO teachers will need comprehensive information about MSUD. A care
expanding at a rate they tolerate. Working with a play therapist/ plan should identify dietary needs, necessity for meal and snack time
psychologist is important. Allow plenty of time for mealtimes supervision, protein substitute administration, illness management, signs of
• If a young child requires tube feeding, it is particularly important metabolic decompensation (e.g. irritability, disorientation) and any
that they are still offered low protein foods regularly during the additional educational needs. If a child has a gastrostomy in situ, a care plan
day and experience the social aspects of eating. Children should should include necessary action if this is accidentally dislodged in school.
be involved in cooking and food shopping from an early age The care plan should be reviewed annually and it may need to escalate to an
• Parents may be reluctant to entrust their child’s care to nursery ‘education, health and care plan’, if additional school resources are required
workers. However, children should experience contact with • Children with MSUD become hungrier with age. Due to their rigid eating
other children to assist with learning development. It may be patterns, some children may want more of the foods they are used to,
better to encourage half‐day attendance at nursery for the first particularly leucine‐containing foods such as potato products. Therefore,
few months, so that staff only need administer suitable snacks dietary adherence may be challenging. It is essential that children learn the
and drinks. This will enable parents to build confidence in the basics of their dietary treatment, why they need to control leucine intake and
nursery workers’ ability to manage the condition. A strict care take their protein substitute. Talking to the children (as well as parents)
plan should be in place regularly will help them understand and accept their dietary treatment
• Feeding problems, food refusal and gastro‐oesophageal reflux • Some children may be overweight, associated with their high CHO diet [87].
can be an issue with some children. The use of gastrostomy is Encouraging daily exercise is important (e.g. dance, trampoline, swimming,
essential to prevent high leucine levels due to catabolism. football)
Reflux should be treated with medications. Psychology support • Some young people who are transitioning into adult care will have learning
can help some families to overcome the stresses of food and disabilities. It is important their individual care needs are carefully
amino acid substitute refusal and the anxiety associated with considered in the transition process enabling appropriate care packages to
high leucine levels be in place when they are transferred to adult services
SENCO, special educational needs coordinator.

Also refer to Table 28.20.
Patients may present with symptoms such irritability, vomit- valine and isoleucine supplements, but this may vary.
ing, dehydration and lethargy. Parents need to recognise Valine and isoleucine content of feeds should be titrated
early warning signs. They often report young children can- according to blood BCAA. A 50 mg leucine exchange
not sit up and fall to one side or fall over with walking, cry- from food or infant formula typically provides 25–30 mg
ing, being ‘clingy’ and poor feeding. Rapid neurological isoleucine and 30–40 mg valine (Table 28.25).
decline, including altered mental state (e.g. disorientation, • Daily monitoring of blood BCAA.
speech disturbances, hallucinations), seizures and encepha- • Glucose polymer is added to the BCAA‐free substitute
lopathy, may occur. Ketoacidosis and ketonuria is present. meeting total CHO concentration as recommended for
Any acute metabolic decompensation is considered a medi- standard ER feeds (p. 677); addition of fat emulsion
cal emergency [111]. The principles of ER are described on should be considered for additional energy, if necessary.
p. 673. The ER for MSUD is disorder specific. • BCAA‐free l‐amino acid substitutes made up according
It is essential to start the ER (Table 28.31) at the first sign of to manufacturer’s instructions have a high osmolality.
illness: This needs to be considered when managing illness par-
ticularly if there is diarrhoea. If tolerance is poor, adding
• Aim to provide the child’s usual intake of branched chain
additional water to make them more dilute may help.
free amino acids and at least the normal energy require-
Continuous feeds can help feed tolerance.
ment for age [109]. If oral intake is poor, tube feeding
should commence without delay. With timely introduction of the ER with mild or moderate
• The usual leucine intake should be stopped or substan- illnesses, most patients can be safely managed at home [83].
tially decreased. It is essential to maintain close contact with parents/caregiv-
• Valine and isoleucine supplements should be added to ers during illness management (at least 3 times a day) to
the BCAA‐free substitute. As a starting point, valine and assess if the prescribed ER feed is being achieved. If there is
isoleucine should replace the amount provided by the any feed intolerance and/or progression of clinical symp-
natural protein allowance and in addition to the usual toms, the child should be admitted to hospital without delay.
Table 28.31 Emergency regimens in MSUD.
Diet Essential Guidance
BCAA‐free amino acid Yes Daily dose

substitute to support 0–3 years: 3 g/kg protein equivalent
protein synthesis
4–5 years: 2.5 g/kg protein equivalent
6–10 years: 2 g/kg protein equivalent
11–14 years: 1.5 g/kg protein equivalent
15–16 years: 60 g/day protein equivalent
Valine and isoleucine Yes Valine and isoleucine to replace the amount provided by the natural
intake protein allowance combined with the usual dose of valine and
isoleucine supplements, but this may vary
Glucose polymer Yes CHO concentration and volume as per standard ER for age (p. 677)
intake
Fat source If tolerated A high energy intake is required to promote anabolism. If fat is
tolerated, the fat concentration could be 3–5 g per 100 mL of
emergency feed. This can be added in the form of 50% fat emulsion;
include any fat provided by the amino acid substitute in the calculation
Natural protein intake Stop or reduce by at least 50% (depending
(leucine exchanges) on severity of illness and BCAA results)
Fluid Yes Fluid requirements as per standard ER for age (p. 677) Additional fluids
may be necessary with diarrhoea or fever
Administration Give orally or via a nasogastric or If oral feeds are not tolerated, administer concentrated BCAA‐free
gastrostomy tube continuously over 24 hours. amino acids (with valine/isoleucine) with IV glucose (ER feed recipes of
If there is poor tolerance of nasogastric/ concentrated BCAA‐free amino acids are given at www.bimdg.org.uk)
gastrostomy feeding, consider administration
via a nasojejunal tube
Monitoring Monitor BCAA concentrations to determine Daily during acute illness
metabolic control/reintroduction of leucine
and doses of isoleucine and valine
Urine ketones (p. 540)
Treat precipitating For example, antipyretics for fever; antibiotics As prescribed by medical doctor
factors for infections
Dietary emergency guidelines with examples of age specific ER recipes are given at www.bimdg.org.uk.
BCAA, branched chain amino acids; CHO, carbohydrate; ER, emergency regimen, IV, intravenous.
Urine ketone monitoring Intravenous therapy
Ketonuria is a physiological result of catabolism in late If emergency feeds are not tolerated and the patient’s symp-
infancy, childhood and even adolescence. In MSUD, daily toms are vomiting, diarrhoea or very high temperature,
home monitoring using standard test strips for ketonuria is then IV fluids (at least 10% dextrose) are given. Some
useful in illness [83], and it is a surrogate marker for meta- patients may require higher concentrations of dextrose,
bolic instability but should be used in combination with (and insulin and Intralipid to promote anabolism [112].
not replace) plasma BCAA monitoring. A positive result Accompanying enteral BCAA‐free amino acid acids (e.g.
indicates catabolism, and the energy content of the ER should MSUD Aid 111 or MSUD Amino 5) providing up to a maxi-
be increased, as tolerated. Usually the result is expressed as mum concentration of 8 g/100 mL protein equivalent [113]
negative or positive with a grade of 1–4. Testing should be together with valine and isoleucine supplements adminis-
performed according to manufacturer’s instructions on fresh tered via a continuous tube feed are essential to promote
uncontaminated urine. Urine test reagents deteriorate with protein synthesis. Pure BCAA‐free amino acid acids with-
exposure to air (so should be kept in a tightly sealed con- out additional nutrients may be better tolerated than the
tainer) or if used after expiry date. The use of old or incor- usual BCAA‐free amino acid substitute with added CHO,
rectly stored test reagents may lead to false negative results. fat and micronutrients. If vomiting persists, consideration
Classical Homocystinuria 541
should be given to nasojejunal feeding as, in the UK, there Table 28.32 Introducing dietary leucine post‐illness.
are no BCAA‐free parenteral amino acid solutions availa-
ble. Careful monitoring of hydration, electrolytes and neu- Plasma leucine
concentrations (μmol/L) Amount of dietary leucine to introduce
rological status is necessary to prevent cerebral oedema.
Acute illness resulting in elevated plasma leucine is usually Leucine <800 25% usual leucine intake
well managed without the need for CECRT. However, if the Leucine >400 and <600 50% usual leucine intake
plasma leucine is >1000 μmol/L, CECRT should be consid-
Leucine <400 75% usual intake
ered [103]. If clinically safe, enteral nutrition including
energy, fluid and BCAA‐free amino acids with valine/iso- Repeat leucine <400 Usual leucine intake
leucine supplements should be given in combination with
dialysis [83].
Learning points: maple syrup urine disease
Introduction of natural protein post‐illness
• In early treated MSUD, outcome is dependent on prompt
Studies suggest reintroduction of leucine when plasma leu- and effective control of plasma BCAA levels
cine reaches the upper treatment target range [83]. Others • Lifelong dietary treatment and follow‐up is required
recommend graded reintroduction over 3–4 days when leu- • Supplementation with valine and isoleucine is commonly
cine concentrations are <800 μmol/L (Table 28.32) (www. necessary
expandedscreening.org). Supplements of isoleucine/valine • Prompt and meticulous use of an ER is essential at any
should be adjusted according to dietary intake and plasma time there is a risk of metabolic decompensation
BCAA concentrations.
Classical Homocystinuria
Fiona J. White
Enzyme Cystathionine β‐synthase. Expressed mainly in the liver and kidneys [114]
Biochemical defect Deficiency of the enzyme cystathionine β‐synthase (CBS) in the catabolic pathway of the essential amino acid methionine
(Figure 28.4):
• Methionine is initially converted into the non‐structural amino acid homocysteine by a series of enzyme dependent
steps
• Homocysteine is not a constituent of protein and so not required for protein synthesis. Normally it undergoes either:
◦◦ degradation through the trans‐sulphuration pathway that converts homocysteine via cystathionine, with the addition of
a serine group, to cysteine or
◦◦ recycling back to methionine by the remethylation pathways [114] by either:
i. methionine synthase, vitamin B12 and folic acid or
ii. betaine–homocysteine methyltransferase – occurring in certain tissues, e.g. liver, kidney [115]
The first step in the trans‐sulphuration of homocysteine requires CBS and pyridoxal‐5‐phosphate (vitamin B6) as a cofactor.
Deficiency of CBS results in:
• increased plasma concentrations of methionine, homocysteine and other sulphur‐containing metabolites (mixed
disulphides)
• low levels of plasma cysteine, cystathionine and serine
• homocysteine is present in large amounts in the urine, hence the condition being termed homocystinuria (HCU)
Homocysteine is present in plasma in several forms [116] with:
• 10%–20% present as free, non‐protein bound homocysteine (fHcy) comprising homocysteine (reduced form <2%),
homocystine (disulphide of homocysteine) and mixed disulphide (homocysteine–cysteine)
• 80%–90% present as protein (albumin)‐bound homocysteine
Plasma total homocysteine (tHcy) concentration is the sum of all the different forms. Normally free homocysteine (fHcy)
is undetectable, and tHcy level is 5–15 μmol/L [117]. fHcy only becomes detectable when tHcy exceeds 60 μmol/L [118].
At diagnosis plasma tHcy in HCU patients will be significantly elevated with levels often >200 μmol/L in non‐screened
patients. Additionally, plasma methionine levels are elevated and cysteine levels are low.
Serine Folic acid

Methionine
7 1
Glycine
Tetrahydrofolate
S-Adenosyl
methionine
5,10-Methylene
Vitamin B12 6 2
tetrahydrofolate
S-Adenosyl
homocysteine
8
5-Methyltetra- 3
Homocysteine
hydrofolate
Vitamin B6 4
Cystathionine
5
Cysteine
Figure 28.4 Metabolic pathways of homocysteine metabolism. 1: methionine adenosyl transferase; 2: SAM‐dependent methyltransferase; 3: SAH hydrolase;
4: cystathionine β‐synthase; 5: γ‐cystathionase; 6: methionine synthase; 7: serine hydroxymethyltransferase; 8: methylenetetrahydrofolate reductase.

• Classical HCU was first described in 1962 [119, 120]. At least 160 mutations have been identified, with the majority
being private (i.e. only occurring within that family) [121]
• Prevalence – The worldwide population prevalence varies, ranging from 1 in 1 800 to 1 in 900 000 [122], but there are
large population differences, being highest in populations where there is a high level of consanguinity. In the Republic of
Ireland, the prevalence is at least 1 in 65 000 [123]. DNA screening studies of newborn infants in a number of countries
have shown that the overall prevalence may be as high as 1 in 20 000 [124]
• The highest reported incidence is in Qatar where there is a high carrier frequency (1% population) of a common
mutation, with a prevalence of 1 in 1800 [125]
There are two distinct phenotypes:

• pyridoxine responsive HCU, which is the milder phenotype
• pyridoxine non‐responsive HCU
There are some cases that show a partial pyridoxine responsive phenotype with tHcy levels decreasing to below 80% of
baseline [122].
Newborn screening Many countries undertake newborn screening (NBS) for HCU:
In the UK infants are screened on day 5 of life using a standard screening protocol with quantification of methionine, and
then, if the level is above the cut‐off, second tier testing with quantification of tHcy.
Only pyridoxine non‐responsive HCU were thought likely to be identified on NBS, as those who are pyridoxine responsive
are more likely to have methionine levels below the screening cut‐off at that time. However, unpublished data from the
European Network and Registry for Homocystinurias and Methylation Defects (E‐HOD) shows that if the screening test is
sufficiently sensitive, then pyridoxine responsive cases may be identified [122]. The author is aware of one case of
pyridoxine responsive homocystinuria identified by NBS in England (personal communication).
More details on UK screening and diagnostic protocols can be found at www.gov.uk and www.bimdg.org.uk
Clinical onset • Individuals with HCU are clinically normal at birth.
presentation, features • CBS deficiency results in accumulation of methionine, homocysteine and their S‐adenosyl derivatives (S‐
adenosylmethionine (SAM), S‐adenosylhomocysteine (SAH) and deficiency of cystathionine and cysteine.
• Without early diagnosis and treatment there is progressive onset of the clinical features of HCU, from the
severe childhood onset of multisystem disease to those where symptoms only appear in adulthood [122].
• The pathogenesis is not fully elucidated. In addition to the accumulation of homocysteine, altered concentrations
of other metabolites may play a role in the pathophysiology [122].
The major clinical features involve:

• the ocular system – lens dislocation, iridodonesis, myopia, glaucoma
• skeletal system – osteoporosis, scoliosis, elongation and thinning of the long bones, Marfanoid appearance
• vascular system – thromboembolisms, malar flush
• central nervous system – developmental delay, learning difficulties, electroencephalogram changes, epilepsy, psychiatric
disturbance
Worldwide up to 50% of cases of CBS deficiency HCU are pyridoxine responsive. Pyridoxine responsiveness results in a
decrease in tHcy <50 μmol/L [122] and elimination of homocysteine from urine [123, 126]. There are population
differences with a much smaller percentage showing pyridoxine responsiveness in certain populations, e.g. UK and Ireland.
Classical Homocystinuria 543
Long‐term complications Good long‐term biochemical control in HCU can prevent the onset of complications in early diagnosed individuals and
and outcome can curtail further progression, but not reversal, of the disorder in late diagnosed cases, apart from the eye disease [127]:
• No long‐term data of tHcy levels over time and clinical outcome have yet been published.
• Published outcome data from follow‐up of patients treated over many years show that lifelong median fHcy <11 μmol/L
significantly reduces the probability of developing complications [123] and levels of fHcy <10 μmol/L indicate good
biochemical control [127]. A median fHcy of around 10 μmol/L corresponds with a median tHcy around 120 μmol/L [122].
• Normal IQ has been reported [127, 128] in pyridoxine non-responsive HCU with good treatment adherence since
diagnosis in the neonatal period.
• In a review of 46 patients [129] 65% were diagnosed from NBS (77% of whom had good/moderate control) with
complication rates: 2% for those diagnosed on NBS and under good control; 17% for those diagnosed on NBS, but with
poor control; and 45% for those not identified on NBS. Tertiary education was achieved by 84% of those diagnosed on
NBS compared with 43% who were clinically presenting cases. Ectopia lentis (lens dislocation) is likely to develop where
fHcy >12.3 μmol/L. Cognitive outcome in children is related to exposure to homocysteine and is best where cumulative
exposure up to age 4 years is fHcy <100 μmol/L.
• Vascular events are the most common cause of death with risk of a vascular event at 25% <16 years of age and 50% by
age 30 years in undiagnosed or poorly controlled HCU [130].
• Cardiovascular risk is greater in pyridoxine non‐responsive HCU [126].
• Growth in a pyridoxine non‐responsive HCU cohort has been reported [131]:
◦◦ At 18 years of age cases, late diagnosed with learning disability had greater height and weight than those picked up
through NBS. This appears related to early accelerated growth pre‐diagnosis as rate of growth >10 years age was
comparable. There was no relationship with metabolic control.
◦◦ Compared with the general population, they were heavier and taller, with those diagnosed on NBS being closer to the
general population.
• Osteoporosis, a known risk in HCU, can be prevented if diagnosed early and good biochemical control is maintained on
treatment [122].
• Psychiatric conditions are more prevalent [122, 132].
Treatment • Aimed at reducing homocysteine levels.
• Modality will depend upon factors such as pyridoxine responsive or non‐responsive and age at diagnosis.
• All newly diagnosed patients should initially have a trial with a pharmacological dose of pyridoxine (vitamin B6): 50 mg
twice daily for 7–14 days in those diagnosed on NBS www.bimdg.org.uk; and 10 mg/kg/day (max 500 mg/day) in older
children for 6 weeks [122], together with 5 mg folic acid to assess for pyridoxine responsiveness.
Pyridoxine responsive HCU

• The enzyme CBS requires pyridoxal‐5‐phosphate, formed from pyridoxine, as its cofactor.
• A significant number of CBS deficient individuals show clinical and biochemical response to pharmacological doses of
pyridoxine, up to 500 mg/day [128].
• Pyridoxine supplementation should be kept to the minimum effective dose as doses >900 mg/day have been associated
with peripheral neuropathy [122, 133, 134].
• The defect in pyridoxine responsive cases is still caused by mutations within the CBS protein and is not due to either
deficient pyridoxine status or a disorder of pyridoxine metabolism. Pyridoxine, in this situation, is acting to increase
residual CBS activity.
Pyridoxine non‐responsive HCU

Plasma homocysteine levels do not fall following pharmacological doses of pyridoxine. Treatment strategies aim at
reducing homocysteine levels by:
• decreasing the intake of the substrate methionine by the use of a methionine‐ or protein‐restricted diet to reduce plasma
methionine and therefore homocysteine levels
• giving an additional pharmacological dose of folic acid, 5 mg daily, to ensure adequate supply of folate for the
remethylation pathway; vitamin B12 status should be monitored and, if suboptimal, supplementation given as it is required
for folate metabolism
• utilising alternative pathways to remove homocysteine by giving betaine (a methyl donor) that remethylates
homocysteine back to methionine and so reduces plasma homocysteine levels; if betaine is used, plasma methionine
levels will usually be elevated
The decision on treatment option varies between metabolic centres, depending upon factors including age and mode of
diagnosis, i.e. screened or clinically presenting, and previous treatment experiences. Those diagnosed on NBS are more
likely to be solely diet treated, at least in the early years, than those clinically presenting at a later age.
Dietetic management Principles are based on:
• substrate (methionine) reduction to decrease the load on the affected pathway
• supplementing deficient products beyond the metabolic block (cysteine)
Primary aims of dietary treatment are to correct abnormal biochemistry:
• decrease plasma methionine levels to within or slightly above the normal age‐related reference range (unless on betaine
therapy)
• decrease plasma homocysteine levels to target treatment levels
• increase plasma cysteine levels to within the normal range (Table 28.33).
Further details of dietary management are on p. 545.
Methionine
N,N-Dimethyl
glycine
S-Adenosyl
methionine
Betaine-homocysteine
methyltransferase
S-Adenosyl
homocysteine
Betaine
Homocysteine
Choline
Cystathionine
Cysteine
Figure 28.5 Methyl group donation by betaine.
Medications Vitamin B6 – Pharmacological doses used in pyridoxine responsive or partial responsive cases.
Folic acid – In CBS deficiency folic acid requirements can increase, due to increased flux through the remethylation
pathway. It is recommended that low dose folate supplements are given although sufficient may be included within the
methionine‐free protein substitutes.
Betaine – A methyl donor, derived from choline, promotes the remethylation reaction of homocysteine to methionine via
the enzyme betaine–homocysteine methyltransferase (Figure 28.5). Its use in HCU results in a decrease in plasma
homocysteine and increase in plasma methionine [135]:
• Oral betaine can be useful, as an adjunct to dietary therapy, in improving biochemical control where dietary adherence
is poor, e.g. adolescents, adults and those late diagnosed. However, adherence with betaine is not always good, with
fHcy levels in 13 patients in one study not being significantly altered with betaine (mean 35 μmol/L pre‐treatment and
33 μmol/L on treatment), and it is unlikely to replace dietary therapy [127], although a European survey [136] identified
significant individuals treated with betaine alone.
• Initial dose in children – 100 mg/kg/day divided in two doses and adjusted depending upon response [122] should result
in a decrease in plasma homocysteine levels and will normally result in plasma methionine levels being significantly
increased, although this is not universal [135, 137].
• Pharmacokinetic studies demonstrated that doses of betaine above 200 mg/kg/day in two to three divided doses were of
no additional value in decreasing tHcy levels [138, 139]. Giving betaine twice daily is adequate, with the half‐life of
betaine around 14 hours [139].
• Betaine alone as treatment of pyridoxine non‐responsive HCU rarely achieves target Hcy levels [122]. This is also seen in
CBS‐deficient mice [140]. The response to betaine has been shown to be less efficient if plasma methionine is
>80 μmol/L [141]; thus betaine should be used as an adjunct to a methionine‐restricted diet and not as a sole treatment.
• The significantly raised plasma methionine levels that occur with betaine use do not appear to affect the
pathophysiology of the disease [127]. Methionine levels should be monitored closely, and the dose reduced if levels
exceed 1000 μmol/L as high levels have been associated with cerebral oedema [142, 143].
Monitoring Dietary monitoring
Monitoring the diet by serial measurements of substrate blood amino acid levels is essential to assess metabolic control.
Treatment targets [122] (Table 28.33)

plasma tHcy <100 μmol/L in pyridoxine non‐responsive cases
plasma tHcy <50 μmol/L in pyridoxine responsive cases
If dried blood spots (DBS) are used, the results will be lower than for plasma. Studies in non‐HCU patients show the DBS
method was approximately 40% of the plasma concentration [144, 145]. This may vary in clinical practice with HCU
patients and so locally, by paired samples, the ratio of DBS to plasma levels should be determined. A correction factor can
then be applied to enable results to be compared with target levels.
Methionine – Within the normal range except in cases on betaine where methionine should be maintained <1000 μmol/L.
Excessive restriction of methionine that results in levels below the normal range could impair growth and
neurodevelopmental outcome [122].
Cysteine – Aim for levels within the normal range, but this can be difficult to achieve. Low levels can be a reflection of
poor homocysteine control, and improving this may improve cysteine levels.
Dietary Management of Classical HCU 545
Frequency of testing
Depends on age, severity, treatment adherence, previous complications [122]. Regular blood sample monitoring can be
challenging as blood samples for total homocysteine require centrifugation within 1 hour of collection [146], so blood
samples are usually taken at a local hospital. More recently DBS monitoring has become available in some centres that
enables samples to be taken at home and therefore can be done more frequently as in PKU (p. 517).
Biochemical/haematological monitoring
• Vitamin B12 and folate status should be assessed as low levels of these could cause inadequate response to treatment due
to their intimate roles in homocysteine metabolism
• Annual monitoring of full blood count (FBC), ferritin
• Other vitamins, minerals, trace elements, essential fatty acids as appropriate
Clinical monitoring
• growth – weight, length/height, BMI at each clinic review
• assessment for signs of any vitamin and mineral deficiencies (e.g. skin rashes, sparse hair)
• neurological and neurocognitive assessments
• DEXA (dual‐energy X‐ray) scans from adolescence to monitor bone health as risk of osteoporosis
• dietary assessment at all clinic reviews
• nutritional biochemistry as above
Guidelines Morris et al. Guidelines for the diagnosis and management of cystathionine beta‐synthase deficiency [122].
Parent Support Group Metabolic Support UK www.metabolicsupportuk.org
HCU Network Australia www.hcunetworkaustralia.org.au
Dietary management of classical HCU Table 28.33 Biochemical monitoring in HCU – treatment targets.
Plasma Plasma
Restriction of dietary methionine intake
methionine cysteine Plasma tHcy Plasma fHcy
Methionine is an EAA required for normal growth and body B6 responsive Normal range Normal <50 μmol/L <10 μmol/L
protein synthesis and so cannot be completely excluded range
from the diet. Methionine intake is restricted by restriction of B6 non‐ Normal range Normal <100 μmol/L <10 μmol/L
dietary protein to maintain blood methionine and homocyst- responsive, range
eine levels within treatment targets (Table 28.37). In practice diet alone
this will require the avoidance of high biological value (HBV) B6 non‐ <1000 μmol/L Normal <100 μmol/L <10 μmol/L
protein foods including meat, fish, eggs, cheese and pulses responsive + range
as they contain high amounts of methionine and, thus, the betaine
amounts permitted would be very small.
Table 28.34 Factors affecting substrate amino acid tolerance.
Methionine tolerance
Residual enzyme activity
• Individuals have a daily methionine allowance that
Growth rate
maintains blood Hcy, methionine and cysteine within
target values (Table 28.33). Degree of adherence to methionine (or natural protein) prescription
• Methionine tolerance varies between individuals and is Adequacy of methionine‐free, cysteine‐enriched protein substitute
influenced by a number of factors (Table 28.34). Adequacy of energy intake
In the author’s unit, a historical group (the majority identi- Taking betaine in combination with methionine restricted diet
fied by NBS), monitored using fHcy with target levels Target treatment substrate blood amino acid concentrations
≤10 μmol/L, had a median tolerance of methionine of
230 mg/day (range 160–900 mg/day). Current patients,
diagnosed on NBS, monitored using tHcy, appear to require • Each exchange contains 20 mg methionine equivalent to
a lower methionine intake, around 80–160 mg/day to achieve approximately 1 g protein; where the methionine content
target tHcy <100 μmol/L. is not available, for example, in manufactured foods, the
protein content is used
• Some centres use 1 g protein exchanges only
Exchange system
• Examples of basic 20 mg methionine exchanges are given
in Table 28.35, and 1 g protein exchanges in Table 28.48
To manage an individual’s methionine allowance, an
exchange system is used, predominantly consisting of foods The guides for calculating exchanges in PKU can be
of LBV protein: adapted for use in HCU (Tables 28.5, 28.6 and 28.7).
Table 28.35 Basic 20 mg methionine exchanges for use in HCU foods with <0.5 g protein/100 g can be allowed freely unless
[147, 148]. a large portion is likely to be eaten. This definition may be
used in HCU.
Food Weight/volume
Milk and dairy Fruits and vegetables (Table 28.36)

SMA Pro First Infant Milk# 65 mL • fruits containing <1 g protein/100 g or <15 mg methionine/
Cow & Gate First Infant Milk# 70 mL 100 g
Aptamil Profutura First Infant Milk# 70 mL • vegetables with <1.0 g protein/100 g or <20 mg methionine/
Cow’s milk 20 mL 100 g
Single cream* 30 mL
Double cream* 45 mL Very low protein manufactured foods (Table 28.9)
Yoghurt (natural/fruit/flavoured) 20 g
• These include flour mixes (all purpose, cakes), bread
Custard 20 g
(loaves, rolls), pizza bases, pasta, rice, couscous, break-
Cereal fast cereals and bars, savoury snacks, biscuits/crackers,
Rice, raw 15 g soup sachets, low protein desserts, low protein energy
Rice, boiled 40 g bars and egg replacers
Vegetables • The majority are available on prescription in the UK
Baked beans, canned in tomato sauce 35 g • Manufacturers include Fate Special Foods, First Play
Broad beans, boiled 75 g Dietary Foods, Gluten Free Foods, Juvela, Metax,
Broccoli, boiled 45 g Mevalia, Nutricia, PK Foods, Promin, Taranis and Vitaflo
Brussels sprouts, boiled 75 g • The methionine/protein content of most of these foods is
Cauliflower, boiled 65 g very low, but they should be checked as some may need
Lentils, raw 10 g
to be counted as part of the daily methionine/protein
allowance unless made completely with exchange‐free
Lentils, boiled 30 g
ingredients
Mushrooms, fresh 35 g
• These foods are an important part of the diet to provide
Peas, petit pois (fresh, frozen, tinned), boiled 35 g
energy and variety. Having a choice of low protein prod-
Spinach, boiled 20 g
ucts is important, but cost and quantity should be con-
Spring greens, boiled 100 g
sidered if these are provided on prescription. The NSPKU
Sweetcorn, canned 25 g
have produced age‐based guidelines on the monthly
Yam, boiled 85 g quantities to provide around 50% daily energy require-
Potatoes ments that are applicable to HCU (www.nspku.org)
Main crop, boiled, jacket, flesh only (average value) 70 g • Recipe booklets and online resources are produced by
Roast 45 g manufacturers
Chips 35 g
Energy supplements such as glucose polymers, fat emul-
Fruit sions or combined fat and glucose polymer supplements.
Avocado 30 g
Dried fruits, e.g. raisins, currants, sultanas 75 g‡
Methionine‐free protein substitute
#
Manufacturers’ data cards July 2019.
* There are a many different dairy creams available with variable fat As the natural protein intake provided by the daily methio-
content and therefore protein content. Always check protein content on nine allowance is inadequate to meet overall protein require-
the individual product nutritional analysis label. ments, a methionine‐free, cystine‐enriched protein substitute
‡
This is an average amount for dried fruits.
is required to provide adequate nitrogen for protein synthe-
sis and growth. This is used to make up total daily protein
requirements (Table 28.37):
Low protein foods
• A number of age-specific methionine‐free, cystine‐
Foods that are naturally very low in protein or protein‐free enriched protein substitutes are available; however, the
are considered exchange‐free and can be included in the diet range is less than that available for PKU due to the far
in normal portion sizes without being weighed. They are smaller numbers of people with HCU. Examples
important in ensuring adequate energy intake is achieved include HCU Anamix Infant, HCU Anamix Junior,
from the diet to meet normal energy requirements for age HCU Anamix Junior LQ, HCU Explore, HCU Lophlex
[98], thus supporting growth and preventing protein catabo- LQ, HCU Cooler and HCU Express. The manufacturers’
lism. These include the following: websites provide information on composition and
usage www.nutricia.co.uk and www.vitaflo.co.uk.
Outside the UK similar products are available from
Sugars, fats and some commercial foods (Table 28.9)
other companies, e.g. www.abbottnutrition.com, www.
Work has been undertaken by the BIMDG Dietitians Group meadjohnson.com, www.metax.org and www.milupa‐
to classify exchange‐free commercial foods in PKU. Generally metabolics.com
Dietary Management of Classical HCU 547
Table 28.36 Fruits and vegetables allowed without measurement • The administration and distribution through the day are
in HCU and tyrosinaemia. similar to those in PKU (p. 523)
• Protein substitutes come in a range of presentations
Fruits
including powdered infant formula, spoonable products
Fresh, frozen or tinned in syrup (<15 mg methionine and/or <1 g useful in weaning, powders and liquids (Table 28.12)
protein/100 g) • Strategies are often required by parents/caregivers to
encourage their child to take the protein substitute
Apples Guava Pawpaws (Table 28.13)
Apricots Kiwi fruit Pears
Blackberries Lemons Pineapples Cystine supplementation in HCU
Blackcurrants Limes Plums
Clementines Lychees Pomegranates Cystine is a conditionally indispensable amino acid in HCU
because of the metabolic block preventing the conversion of
Cherries Mandarins Raspberries
cystathionine into cysteine (Figure 28.4). Although all the
Cranberries Mangoes Rhubarb methionine‐free protein substitutes contain added cystine
Damsons Melons Satsumas (30–50 mg/g protein equivalent), plasma cysteine concentra-
Fruit salad Mulberries Strawberries tions are commonly low:
Figs, green, raw Nectarines – contain Tangerines • Cysteine and homocysteine–cysteine is present in plasma
36 mg methionine/100 g in three different forms:
Allow up to 1 nectarine
◦◦ free cysteine
daily only in HCU
◦◦ bound to homocysteine forming a mixed disulphide
Gooseberries Olives Water melon ◦◦ bound to protein
Grapefruit Oranges • With increased concentrations of plasma homocysteine,
Grapes Passionfruit the amount of cysteine present as the mixed disulphide
homocysteine–cysteine increases, and cysteine and pro-
Vegetables tein‐bound cysteine decrease as cysteine is displaced
from albumen by homocysteine [149]
Fresh, frozen or tinned (<20 mg methionine and/or <1 g • Monitoring plasma cysteine is problematic; most labora-
protein/100 g)
tories only measure free cystine, and if the sample is not
Artichoke Fennel Peppers deproteinised quickly, results may be falsely low [149];
ideally total plasma cysteine (free and bound) should
Aubergine Garlic Plantain
also be assessed, but it is difficult to measure [149, 150]
Beans, French, green Gherkins Pumpkin • It has been reported that as biochemical control improves,
Beansprouts Gourd Radish with decreasing homocysteine concentrations, total
Beetroot Fennel Spring onion cysteine levels increase [150]
Cabbage Leek Swede • There are reports that deficiency of cysteine can lead to
poor weight gain and growth despite adequate energy
Carrot Lettuce Sweet potato
intakes [151] although one study did not find any asso-
Celery Marrow Tomato ciation with low cysteine levels and height [131]
Chicory Mustard and cress Tomato purée • Cystine has a poor solubility, so care is required to ensure
Courgette Onion Turnip it does not precipitate on solution when added to water;
it has an unpleasant taste and can also cause gastrointes-
Cucumber Parsley Watercress
tinal (GI) disturbance [131]
Endive Parsnip
• Additional supplementation may not be warranted if
Source: From [123, 124] and Leatherhead Food RA, Randalls Road,
tHcy is well controlled, as well as growth satisfactory;
Leatherhead, Surrey, UK, 1994. however, cysteine is essential for synthesis of glutathione
that is an important antioxidant. Further research is
needed to accurately assess cysteine status and whether
supplementation to achieve normal levels affects out-
Table 28.37 Guidelines for total protein requirements for HCU (protein come, for example, hHcy levels, glutathione status.
equivalent from protein substitute and natural protein/amino acid Accurate monitoring of cysteine status is needed, and, if
exchanges). low, studies of supplementation in well‐controlled
patients and outcomes are needed
0–2 3.0 Micronutrients

3–10 2.0
11–14 1.5 Intakes of vitamins, minerals, trace elements, essential fatty
acids and LCPUFA should be sufficient to meet age‐appro-
priate requirements. Due to the restriction of dietary protein,
supplementation will be required. A number of methionine‐ Formula‐fed infants

free protein substitutes are already supplemented with these
nutrients. Where they are not, separate supplements are For infants with pyridoxine non‐responsive HCU:
required (Table 28.14).
• initially all natural protein (methionine) intake is stopped,
and the infant is fed entirely on a methionine‐free infant
formula, e.g. HCU Anamix Infant, aiming to give approxi-
Dietary management of newly diagnosed infants mately 3 g methionine‐free protein equivalent/kg body
with HCU weight/day and normal energy requirements for age.
(Other methionine‐free formulas are available outside the
Infants with HCU who fail to respond to a pharmacological UK: www.abbottnutrition.com, www.meadjohnson.com,
dose of pyridoxine are commenced on dietary therapy. The www.milupa‐metabolics.com.)
dietary management guidelines pathway developed when • subsequently a measured amount of natural protein, ini-
NBS was introduced in England in 2012 is given in Figure 28.6. tially to provide 120 mg methionine/day (or 30 mg
Pyridoxine unresponsive/partial response Pyridoxine responsive

commence dietary treatment Continue pyridoxine and folic acid
• Methionine-restricted diet No diet
• Continue 50 mg pyridoxine/day 5 mg folic
acid/day if partially responsive
Bottle feeding regimen

Breastfeeding regimen Decrease or temporarily stop normal formula
Restrict breast milk intake to approx 50% by giving according to plasma methionine levels
methionine free formula (approx 75 mL/kg/day) prior Give methionine free formula only depending on
to breast feeds (mature breast milk contains ~18 mg plasma methionine at 1st follow-up visit
methionine/100 mL)
(expect plasma tHc and methionine to decrease to Plasma Methionine free
target treatment range 7–12 days) Methionine- formula only
Review acceptance of methionine free formula bottle restricted μmol/L number of days
feeds - within 24 hours. If not accepting bottle then >1000 4
temporarily stop breast feeds to establish methionine 600–1000 3
free feeds. Follow bottle feeding regimen guidelines. 200–600 2
Support mum to express milk.
Reintroduce whey based infant formula

(contains ~ 29 mg methionine/100 mL)
Limit methionine intake initially to 90–120 mg
methionine/day. (or 30 mg/kg/day if weight
<3 kg)
Supplement with methionine free formula to
give total protein intake 3 g protein/kg/day
Dietetic review ~ 1 week on dietary treatment Plasma target treatment levels:

Monitor plasma methionine and tHc ~ 7 days after
methionine free feeds started (results in 2 working days) Methionine Normal range
Adjust volume of methionine free formula to maintain Total Hcy 60–100 μmol/L
tHc and methionine within biochemical targets.
Breast milk intake/infant formula typically provides Free Hcy ≤10 μmol/L
around 90–120 mg methionine/day. Total cysteine Normal range
Monitor blood levels, weekly initially and adjust feeding regimen to achieve target treatment levels
Inform GP, health visitor, local dietitian, as appropriate, of patient management plan
Homocystinuria (HCU) Dietetic Management Pathway. V1 April. 2015
Figure 28.6 Homocystinuria (pyridoxine non‐responsive) dietary management pathway. Source: www.bimdg.org.uk.
Interpretation of Homocysteine, Methionine and Cysteine Results 549
methionine/kg/day if weight below 3 kg), from stand- approximately 75 mL/kg/day divided into 5–6 feeds and
ard infant formula is reintroduced, depending on initial given prior to breastfeeds.
biochemistry (Figure 28.6): • If initial plasma methionine is <200 μmol/L, breastmilk
◦◦ the standard infant formula is divided equally intake should be decreased by approximately 50%. This
between several feeds (5–6 times daily) and is offered is achieved by giving the infant 75 mL/kg/day of
first followed by HCU Anamix Infant to appetite after methionine‐free infant formula divided into 5–6 feeds
each standard feed and at additional feeds as the and given prior to BF.
infant demands. An example feeding plan is given in • The prescribed quantity of methionine‐free infant for-
Table 28.38 mula would then be increased or decreased according to
◦◦ the quantity of standard infant formula is adjusted blood methionine/homocysteine levels in order to
according to subsequent plasma methionine and manipulate the amount of breastmilk the infant takes.
homocysteine levels, aiming to keep within the desir-
This has been shown to be successful in practice, main-
able limits (Table 28.33)
taining low plasma tHcy as long as adequate intake of
methionine‐free infant formula is taken [152].
Breastfed infants Further dietary progression with the introduction of wean-
ing solids and food exchanges and onto second stage protein
Early diagnosed infants (newborn or at risk screening) with substitute follows the same pattern as in PKU (p. 529).
pyridoxine non‐responsive HCU can be breastfed using the Feeding issues can occur and parents can need support.
principles employed in the management of PKU. The die- Appropriate guidance around these issues is given on p. 529
tary management guidelines for pyridoxine non‐responsive and Table 28.20.
HCU (Figure 28.6) are as follows:
• If initial plasma methionine is >200 μmol/L, breastmilk Interpretation of homocysteine, methionine
should be withheld for 24–48 hours, and the infant fed and cysteine results
solely methionine‐free infant formula. The mother should
be encouraged to express breastmilk regularly, around 6 Regular monitoring of blood levels of homocysteine, methio-
times a day, to maintain supply. Following this, methionine and cysteine should be carried out with samples taken
nine‐free infant formula should be decreased to at home (dried blood spots) or at the local hospital (venous
Table 28.38 Example of a daily feeding plan for a 4 kg infant with homocystinuria.
Aim: 120 mg methionine/day and 3 g total protein/kg

• Total fluid intake 180 mL/kg/day (= 720 mL daily)
• 70 mL Cow & Gate First Infant Milk = 20 mg methionine
• Total number of feeds = 6 daily
Methionine requirement: 120 mg/day = 6 × 70 mL Cow & Gate First Infant Milk = 420 mL daily
• Total fluid requirement = 720 mL
• Fluid from Cow & Gate First Infant Milk = 420 mL
• Deficit = 300 mL (720–420 mL)
Feed deficit made up with methionine‐free protein substitute, e.g. HCU Anamix Infant = 300 mL/day
Feeding plan
6 feeds per day of
70 mL × 6 feeds of Cow & Gate First Infant Milk followed by
50 mL HCU Anamix Infant
Additional feeds of HCU Anamix Infant can be given if hungry
Energy
Protein Fluid
kcal kJ equivalent (g) Carbohydrate (g) Fat (g) (mL)
420 mL Cow & Gate First Infant Milk 277 1155 5.5 30.7 14.3 420
300 mL HCU Anamix Infant 207 861 6.0 22.2 10.5 300
Total 484 2016 11.5 52.9 24.8 720
Intake per kg/day 121 504 2.9 13.2 6.2 180
10% energy 44% energy 46% energy
Energy requirement per kg/day 96 403
samples). Target aims are given in Table 28.33. Depending Table 28.39 Menu plan for an 8‐year‐old boy with HCU.
upon blood results dietary manipulation may be required:
Weight = 27 kg
• If tHcy is towards the lower target range, then an increase 10 × 20 mg methionine exchanges and methionine‐free protein
in methionine/protein intake, by 10–20 mg methionine substitute to provide 2 g protein equivalent/kg
or 0.5–1.0 g protein per day, should be advised
Total protein equivalent requirement = 54 g (10 g from natural protein/
• If tHcy is higher than target ranges, then a decrease in methionine exchanges and 44 g from protein substitute, e.g. 3 × HCU
methionine/protein intake, by 10–20 mg methionine or Cooler 15 or 2.5 HCU Lophlex LQ)
0.5–1.0 g protein per day, should be advised
Breakfast
It is better to consider trends in blood results before Methionine‐free protein substitute, e.g. 1 × HCU Cooler 15 (130 mL) or
increasing/decreasing natural protein intake. It is advisable 1 HCU Lophlex LQ (125 mL)
to adjust methionine/natural protein intake after more than 3 × 20 mg methionine exchange
one blood result is available unless blood concentrations are 105 g baked beans (3 exchanges)
Low protein toast
very low or very high. Factors such as illness, growth rate
Fruit juice
and dietary adherence should be taken into account. During
Mid‐morning
illness, plasma tHcy and methionine increase due to catabo-
Fruit
lism. Tables 28.15 and 28.16 give guidance on interpretation Water
of blood amino acid results.
Midday
3 × 20 mg methionine exchange
Management of illness Low protein pasta salad + 25 g boiled sweetcorn (1 exchange)
Chopped peppers or tomato or cucumber
Low protein bread and margarine
Children with HCU do not have acute metabolic decompen-
1 cereal bar (2 exchanges)
sation with intercurrent illness. A formal ER is not required. 1 pear
It is prudent, though, to try to prevent catabolism and exces- Fruit juice or water
sive rise in blood homocysteine levels by: Mid‐afternoon
• encouraging intake of methionine‐free protein substitute Methionine‐free protein substitute, e.g. 1 × HCU Cooler 15 (130 mL) or
HCU Lophlex LQ (65 mL)
• giving methionine/protein exchanges to appetite
• giving high carbohydrate drinks 1 × 20 mg methionine exchange
1 packet crisps (1 exchange)
• ensuring good fluid intake
Evening meal
Development of acute venous thrombosis is a potential 2 × 20 mg methionine exchange
risk [122] that can be minimised by: Low protein pizza
Free salad vegetables
• avoiding dehydration and immobilisation Low protein garlic bread (with garlic butter)
• giving intravenous fluids if there is intractable vomiting 60 g ice cream (2 exchanges)
Fruit juice or water
Dietary management in later diagnosed cases Bedtime

Methionine‐free protein substitute, e.g. 1 × HCU Cooler 15 (130 mL) or
of HCU 1 HCU Lophlex LQ (125 mL)
1 × 20 mg methionine exchange
Individuals diagnosed late after the onset of clinical symp-
10 g cornflakes (1 exchange)
toms, or because of investigation following a sibling diag- Protein‐free milk replacement, e.g. Prozero, SnoPro
nosed with HCU, are commenced on treatment. Management
depends on the individual’s circumstances and may be by
dietary methionine/protein restriction alone, dietary restric-
Dietary adherence in this group, in some cases, can be dif-
tion with betaine or betaine alone.
ficult to achieve because they are used to a normal unre-
In the author’s unit the practice is to initiate dietary treat-
stricted diet. Most will have learning difficulties, and so
ment in the following way:
understanding the need for such a radical change in diet can
• restricting methionine intake to 200 mg/day. If, from diet be difficult to achieve. Individuals may ‘cheat’ with high pro-
history, the normal dietary protein intake prior to diagno- tein foods, take additional methionine exchanges or refuse
sis has been exceptionally high, a larger methionine allow- the methionine‐free protein substitute. These problems need
ance may be given to be addressed. A positive family attitude and support from
• giving an age‐appropriate methionine‐free protein sub- the multidisciplinary team, including clinical psychologist,
stitute to make up the total protein requirement for age are important if dietary treatment is to succeed.
as in Table 28.37 For some late diagnosed individuals in whom all attempts
• subsequent methionine allowance is adjusted according to give the methionine‐free protein substitute have failed, a
to plasma methionine and homocysteine levels so as to modified low protein diet using the minimum safe level of
achieve acceptable control (Table 28.33) protein intake [153] to minimise protein catabolism and poor
• a sample menu plan is given in Table 28.39 growth is used in conjunction with oral betaine therapy.
Tyrosinaemia Type I (Hepatorenal Tyrosinaemia, HTI) 551
In some cases, management with betaine alone is used. A betaine), 34% on betaine alone and 3% on unmeasured,
European survey [136] of dietary practices in 181 patients moderate protein restriction and betaine. The use of diet
showed wide variety in treatment with 62% on measured alone decreased with age with the converse for use of
methionine/protein restriction (of whom 92% also had betaine only.
Learning points: classical homocystinuria
• Pyridoxine non‐responsive homocystinuria is part of the newborn screening programme in the UK and many other countries
• Dietary treatment (low methionine diet and methionine‐free, cysteine‐enriched protein substitutes) is required lifelong
• With lifelong good biochemical control of fHcy, clinical features of HCU can either be avoided or not worsened
Hereditary Tyrosinaemias
Fiona J. White
Tyrosine is a non‐EAA found in dietary protein and also Tyrosine
endogenously synthesised from the hydroxylation of pheny- Tyrosine
1
aminotransferase
lalanine. It is used for protein synthesis as well as being a pre-
4-Hydroxyphenylpyruvate
cursor for a number of important body chemicals including
dopamine, epinephrine, norepinephrine, melanin and thyrox- 4-Hydroxyphenylpyruvate
3 dioxygenase (site of
ine. Tyrosine is catabolised by a series of enzyme‐dependent action of nitisinone)
reactions to fumaric acid and acetoacetate (Figure 28.7). Homogentisate
There are three inherited disorders of tyrosine catabolism:
hereditary tyrosinaemia types I, II and III.
In addition to these, raised tyrosine levels can also occur in: Maleylacetoacetate
• neonates, particularly preterm infants. This is most com- Succinylacetoacetate

monly transient tyrosinaemia of the newborn probably Fumarylacetoacetate
due to immaturity of the enzyme 4‐hydroxyphenylpyru- Succinylacetone
2 Fumarylacetoacetate
vate dioxygenase (Figure 28.7) [154]. This may respond to hydrolyase
vitamin C supplementation to induce enzyme activity, Fumaric acid Acetoacetate
with rapid normalisation of tyrosine levels
Figure 28.7 Pathways of tyrosine degradation. ➀ Tyrosinaemia type II.
• any severe liver disease where plasma quantitative
➁ Tyrosinaemia type I. ➂ Tyrosinaemia type III 4‐hydroxyphenylpyruvate
amino acids can show raised tyrosine ± methionine dioxygenase (site of action of nitisinone).
• infants fed unmodified goat’s milk that has a high protein
content and can give rise to suspicion of tyrosinaemia type
I, with raised tyrosine and a metabolic acidosis [155, 156]
Tyrosinaemia Type I (hepatorenal tyrosinaemia, HTI)
Enzyme Fumarylacetoacetate hydrolase (FAH)

Biochemical defect FAH catalyses the final step of tyrosine degradation (Figure 28.7). Deficiency results in accumulation in both plasma and urine
of the toxic metabolites:
• Fumarylacetoacetate (FAA) which is further metabolised to produce succinylacetone (SA) and maleylacetoacetate (MAA)
• Presence of SA is pathognomonic for HTI. It inhibits δ‐aminolevulinic acid (δ‐ALA) dehydratase (PBG synthase) resulting in
accumulation of δ‐ALA, which is excreted in high concentrations in urine
• Plasma tyrosine levels are usually only moderately elevated, around 2–4 times the upper limit of normal (30–120 μmol/L), as
the defect occurs in the terminal rather than early steps of tyrosine degradation
• Plasma methionine concentration can also be markedly increased, due to liver dysfunction or secondary inhibition of
S‐adenosylmethionine synthetase [157]
• The main diagnostic metabolite for HTI is SA measured in plasma, dried blood spot (DBS) or urine
• Alpha‐fetoprotein (AFP) levels are normally markedly raised, even in those identified on newborn screening (NBS), but this
is not specific for HTI [158]

• Caused by mutations encoding for FAH. The gene is located on chromosome 15 with over 95 mutations having been
identified [159].
• Prevalence – Certain FAH mutations occur more frequently in particular areas or ethnic groups including Mediterranean
countries, Finns, Turks and Pakistanis, due to founder effects, leading to a higher prevalence within these populations [159,
160]. Whereas the worldwide population prevalence of HTI is approximately 1 in 100 000, it is higher in:
◦◦ Quebec, Canada – around 1 in 1 846 in the French‐Canadian region of Saguenay‐Lac Saint‐Jean (over 90% alleles are the
same mutation) and Quebec overall 1 in 16 000
◦◦ Finland – in particular the Pohjanmaa region 1 in 5000
◦◦ Birmingham, UK – 1 in 20 791 that is associated with South Asian ethnicity and consanguinity
• There is no clear genotype–phenotype correlation [161].
Newborn screening • HTI is not currently part of NBS in the UK, but is being considered www.gov.uk/government/groups/
uk‐national‐screening‐committee‐uk‐nsc
• Because tyrosine can be raised in a number of situations, on its own it is unhelpful as a screening marker for HTI. In areas
where NBS is carried out, this is based on initial detection of high tyrosine with second tier testing for the presence of SA
Clinical onset • Individuals with HTI are clinically normal at birth
presentation, • Most affected infants will present clinically unless:
features ◦◦ born in a region where NBS for HTI is performed
◦◦ had early testing due to an affected sibling
◦◦ identified on NBS with high tyrosine ± phenylalanine/methionine levels and then SA measured
• can present clinically at any age from the neonatal period until adulthood although biochemical abnormalities may be
present soon after birth, including raised SA and AFP levels
• although most infants rarely present with clinical symptoms in the first few days, some neonates can have rapid onset of
symptoms
• can manifest with a variety of clinical symptoms and severity and is usually classified according to age of onset of
symptoms, broadly correlating with severity of disease [158, 162]:
◦◦ acute – the most common form presents before 6 months of age with acute liver failure, the most severe before 2 months
◦◦ subacute – presents between 6 months and 1 year of age with progressive liver failure, hepatosplenomegaly,
coagulopathy, faltering growth and rickets
◦◦ chronic – presents over 1 year of age with chronic liver and renal disease, rickets or porphyria‐like episodes; some may
also have cardiomyopathy or pancreatic cell hypertrophy that can cause hyperinsulinism [163]
• FAA, MAA and SA, possibly through binding to sulphydryl groups and resulting in tissue injury [163], are considered
responsible for the clinical features of:
◦◦ progressive liver failure with increased risk for hepatocellular carcinoma (HCC)
◦◦ renal tubular dysfunction causing a ‘Fanconi picture’ with aminoaciduria, phosphaturia and renal tubular acidosis;
phosphate loss results in hypophosphataemic rickets
• δ‐ALA is responsible for a porphyria‐like syndrome [158, 164]
Management Acute management
If HTI is suspected because of liver disease, then once appropriate investigations (including plasma amino acids, urine organic
acids, investigations for galactosaemia and, if age appropriate, for hereditary fructose intolerance which can both also present
with acute liver failure) are undertaken:
• start nitisinone (suppresses the production of the toxic metabolites)
• a low tyrosine, low phenylalanine diet should also be commenced pending confirmatory results
• while waiting for diagnostic results, galactose and fructose should also be withheld from the diet until galactosaemia and
hereditary fructose intolerance are excluded [158]
Chronic management
HTI is managed with:
• nitisinone
• dietary restriction of tyrosine and phenylalanine
Historically HTI was treated with a low tyrosine, low phenylalanine diet to minimise formation of toxic metabolites.
Methionine intake was also restricted if plasma levels were high. Dietary treatment improved renal tubular dysfunction, growth
and to some extent liver function, in particular prothrombin time, but dietary management could not completely prevent the
production of toxic metabolites or the development of HCC. Most patients diagnosed early in life, pre‐1992 and the
introduction of nitisinone, either died from progressive liver failure or lethal porphyric crises unless they received a liver
transplant that was the only effective treatment.
Treatment of HTI has been revolutionised since the use of nitisinone (2‐(2‐nitro‐4‐trifluoromethyl‐benzoyl)‐1,3‐
cyclohexanedione, NTBC, Orfadin) was described in 1992 [165].
Nitisinone treatment
• inhibits 4‐hydroxyphenylpyruvate dioxygenase, the second enzyme in tyrosine catabolism (the defect in tyrosinaemia type
III), blocking the tyrosine degradation pathway upstream of the enzyme defect (Figure 28.7) that:
◦◦ suppresses the formation of FAA, MAA and SA
◦◦ increases plasma tyrosine as the degradation pathway is blocked earlier
Tyrosinaemia Type I (Hepatorenal Tyrosinaemia, HTI) 553
• in studies on healthy volunteers, given a single dose of nitisinone, plasma tyrosine concentrations increased from around
10 μmol/L at baseline to approximately 1100 μmol/L [166]
• as high plasma tyrosine concentrations are considered the probable cause of the oculocutaneous manifestations in
tyrosinaemia type II and may also be associated with cognitive impairment [167], restriction of dietary tyrosine and
phenylalanine is necessary
• leads to rapid improvement in hepatic and renal function and prevents neurological dysfunction in most patients [168]
• when started early in life, nitisinone markedly reduces the risk of early development of HCC. For patients who start this
treatment late, there remains a considerable risk for liver malignancy [169, 170]
• is established as a very effective alternative to liver transplantation
• treatment must continue without interruption; otherwise serious complications, including acute liver failure, neurological
crisis or malignant liver changes, may occur [158]
• the usual dose of nitisinone is 1 mg/kg/day in two divided doses. Based on the half‐life being 54 hours in healthy adults,
the frequency of dosing has been examined as less frequent could be beneficial in improving adherence and metabolic
control, as compliance issues have been reported [171]. However experience is divided: a single daily dose could
maintain adequate plasma NTBC levels [172]; but detectable levels of SA were found in those on once but not twice daily
dosing [173]
Dietetic Principles are based on:
management • substrate reduction (tyrosine, phenylalanine) to decrease the load on the affected pathway. Phenylalanine has to be
restricted as it is catabolised to tyrosine
The primary aims of dietary treatment are to correct abnormal biochemistry:

• decrease plasma tyrosine to target treatment levels (Table 28.40)
• maintain blood phenylalanine within the normal range. This may require additional l‐phenylalanine supplementation as
described on p. 556
Further details of dietary management are given on p. 554.

Monitoring Dietary monitoring
Monitoring the diet by serial measurements of substrate blood amino acid levels is essential to assess metabolic control.
The European recommendations 2013 [158] are to maintain:
• blood tyrosine levels between 200 and 400 μmol/L
• blood phenylalanine concentration within the normal reference range. However, it is suggested to maintain phenylalanine
concentration >50 μmol/L to compensate for the daily fluctuation in blood phenylalanine level [174]
Very high tyrosine concentrations are risk factors for neurotoxicity and corneal opacities [175]. Eye complications are said to
be rare with tyrosine concentrations <800 μmol/L [158]. However, there is a case report of a nitisinone‐treated HTI patient
with photophobia and ‘burning eyes’, with tyrosine levels around 600 μmol/L. Corneal deposits resembling those seen in
hereditary tyrosinaemia type II were confirmed [176].
Frequency of testing
Regular monitoring of blood or plasma tyrosine and phenylalanine concentrations should be undertaken. Generally DBS are
taken at home and sent in to the laboratory for analysis. The European recommendations 2013 do not give any
recommendations on frequency of monitoring [158]. A guide would be:
• weekly in infants because growth is rapid, or in newly diagnosed patients until stable
• every 1–2 weeks in 1‐ to 4‐year‐olds
• monthly thereafter or more frequently if levels are unstable
Biochemical/haematological monitoring
• regular monitoring of nitisinone levels and SA. Methods for determining nitisinone levels in DBS have been developed that
enable easier monitoring with samples being able to be sent from home
• SA and AFP at clinic reviews
• liver and renal function tests, clotting, bone profile, FBC
• plasma quantitative amino acid profiles
• iron studies
• annual monitoring of other vitamins, minerals, trace elements, essential fatty acids as appropriate [158]
Clinical monitoring
• eye examination especially if high tyrosine levels
• bone mineral density (DEXA), especially if there is renal tubular disease
• nutritional biochemistry as above
Long‐term Prior to nitisinone treatment, survival rates were clearly related to age of onset of symptoms with death from liver failure,
complications and neurological crisis or HCC usually by 10 years of age [162] (Table 28.41).
outcome Nitisinone is now the mainstay of treatment for HTI. A small proportion of patients presenting acutely with liver failure do
not respond after a week of nitisinone. These cases should be referred for liver transplant assessment [158].
Survival and morbidity

Treatment with nitisinone and a low tyrosine/phenylalanine diet have resulted in an over 90% survival rate with normal
growth, improved liver function, prevention of cirrhosis and correction of the renal tubular dysfunction [177] and the absence
of porphyria‐like crisis [171].
Cognition
• Neuropsychological outcome appears affected in nitisinone‐treated HTI [170, 171, 178–180] in particular affecting IQ
scores, especially performance skills, executive functioning and social cognition.
• Outcome studies on 46 French [171], 10 Belgian [178], 19 Dutch [179] and 7 German (>3 years of age) [181] patients
treated with nitisinone and diet show high incidence of educational difficulties and cognitive impairment, in up to:
◦◦ 35% of the French cases of school age
◦◦ 30% of the Belgian cases
◦◦ 32% of the Dutch cases
◦◦ five of the seven German cases
• The cause of the cognitive deficits is unclear, but may be the result of high tyrosine levels due to poor adherence with the
dietary treatment as chronic high tyrosine levels are associated with cognitive difficulties in HTII and most cases of HTIII
[171, 178]. Tyrosine is a precursor for the neurotransmitters dopamine and norepinephrine, and high tyrosine levels may
alter the synthesis of these [178].
• Some patients have low plasma phenylalanine concentrations [178, 182]. There is a known association in PKU between low
phenylalanine levels and low IQ [178] where patients with the lowest IQ had mean phenylalanine <40 μmol/L in the first 2
years of treatment. Phenylalanine and tyrosine are both large neutral amino acids, and they compete for entry at the blood–
brain barrier; thus high tyrosine levels with low phenylalanine concentrations will limit the amount of phenylalanine
transported into the brain, potentially being rate limiting for brain protein synthesis.
• Recent work from the Netherlands [183] looked at plasma and, by calculation, presumptive brain influx of tyrosine and
phenylalanine. Presumptive brain influx of phenylalanine was decreased more than expected from plasma levels but could
be increased with phenylalanine supplementation; however to achieve adequate presumptive brain phenylalanine influx in
HTI plasma phenylalanine levels probably needs to be above the current thresholds for hypophenylalaninaemia of
30–40 μmol/L [184, 185].
Guidelines European 2013 – Recommendations for the management of tyrosinaemia type 1 [158]
US/Canadian 2017 – Diagnosis and treatment of tyrosinaemia type I: a US and Canadian consensus group review and
recommendations [180]
Parent Support Metabolic Support UK www.metabolicsupportuk.org/
Group
Dietary management of HTI Table 28.40 Biochemical monitoring in HTI.
Blood tyrosine Blood phenylalanine

Restriction of dietary protein intake
200–400 μmol/L >50 μmol/L
Tyrosine is present in protein containing foods and produced
from phenylalanine catabolism. Both tyrosine and its precur-
sor phenylalanine have to be restricted to control blood tyros- Table 28.41 One‐ and two‐year survival probability after the onset
ine. Some natural protein is required to cover requirements of symptoms prior to 1992 [162].
for phenylalanine to support growth and body protein syn-
thesis. In the UK information on tyrosine content of foods is Survival rates
not available, so the overall protein content of foods is used.
Age of onset of symptoms 1 year (%) 2 years (%)
Individuals are prescribed a daily natural dietary protein
intake allowance, thereby limiting both tyrosine and pheny- Very early onset <2 months 38 29
lalanine intakes. This is altered on an individual basis accord- Early onset 2–6 months 74 74
ing to blood tyrosine concentrations to maintain levels within
Late onset >6 months 96 96
target treatment ranges (Table 28.40). An exchange system is
used whereby one exchange is equivalent to 1 g protein. Source: Adapted from John Wiley & Sons.
Exchange system value protein contain high amounts of tyrosine and phenyla-
lanine and thus the amounts permitted would be very small.
Foods used to provide daily protein allowance are mainly of Each exchange provides 1 g protein. Examples of basic 1 g
low biological value protein as foods with a high biological protein exchanges are in Table 28.42. A more extensive list is
Dietary Management of HTI 555
Table 28.42 Basic 1 g protein exchanges for tyrosinaemia [54]. Table 28.43 Factors affecting tyrosine tolerance.
1 g protein Residual enzyme activity

Food exchanges Growth spurt/catch‐up growth
SMA Pro First Infant Milk #
80 mL Adequacy of tyrosine‐ and phenylalanine‐free protein substitute
Cow & Gate First Infant Milk# 75 mL Adequacy of energy intake
Aptamil Profutura First Infant Milk #
75 mL Taking nitisinone
Cow’s milk 30 mL Target treatment tyrosine and phenylalanine concentrations
Single cream* 30 mL
Double cream* 60 mL changes little with increasing age, even in the most adherent
Yoghurt (wholemilk natural/flavoured) 25 g patients:
Rice, raw 15 g
• Average natural protein intake per kilogram decreases
Rice, boiled 45 g with age in this cohort, average intakes being at:
Baked beans in tomato sauce, canned 20 g ◦◦ 1–4 years age 0.6 g/kg/day (median 8 g/day)
Broccoli tops, boiled 30 g ◦◦ 5–10 years 0.4 g/kg/day (median 8 g/day)
◦◦ ≥11 years 0.2 g/kg/day (median 14 g/day, the major-
Brussels sprouts, boiled 35 g
ity in this age group always having an intake around
Cauliflower, boiled 50 g this).
Lentils, raw 5 g • There is intra‐individual variation in natural protein tol-
Lentils, boiled 12 g erance, as observed in all disorders of amino acid metab-
Peas, petit pois (fresh, frozen, tinned), boiled 15 g
olism, with intakes varying between 7 and 16 g/day. One
centre has reported that daily natural protein intake
Spinach, boiled 30 g
increased with age in 6 of 11 patients [187]; however,
Spring greens, boiled 55 g median intakes were not dissimilar to the author’s
Sweetcorn kernels 40 g patient group. Tolerance is influenced by a number of
Yam, boiled 60 g factors (Table 28.43).
Potato, old, boiled 55 g
Potato, new, flesh and skin, boiled 55 g Low protein foods
Jacket baked potato, flesh only 45 g
Foods that are naturally very low in protein or protein‐free
Jacket baked potato, flesh and skin 40 g
are considered exchange‐free and can be included in the diet
Roast potato 40 g in normal portion sizes without being weighed. They are
Chips 30 g important to ensure adequate energy intake is achieved from
the diet to meet normal energy requirements for age, thus
#
Manufacturers data cards July 2019, based on protein. supporting growth and preventing protein catabolism.
* There are a many different dairy creams available with variable fat These include:
content and therefore protein content. Always check protein content on
the individual product nutritional analysis label. • sugars and fats
Source: Adapted from Finglas et al. [54]. Licensed under Open • some commercial foods (Table 28.9); generally foods with
Government UK.
<0.5 g protein/100 g can be allowed freely unless a large
portion is likely to be eaten
• some fruits and vegetables (Table 28.10)
• very low protein manufactured foods:
in Table 28.48. The guides for calculating exchanges in PKU
◦◦ these include flour mixes (all purpose, cakes), bread
can be adapted for use in HTI (Tables 28.5, 28.6 and 28.7).
(loaves, rolls), pizza bases, pasta, rice, couscous,
breakfast cereals and bars, savoury snacks, biscuits/
Natural protein tolerance crackers, soup sachets, low protein desserts, low pro-
tein energy bars and egg replacers
The amount of natural protein tolerated varies between ◦◦ the majority are available on prescription in the UK
patients. From a peak of 1.8–2.4 g protein/kg/day at ◦◦ manufacturers include Fate Special Foods, First Play
4–5 months, it decreases to around 1 g protein/kg/day in Dietary Foods, Gluten Free Foods, Juvela, Metax,
late infancy [186]. This high peak of protein intake could be Mevalia, Nutricia, PK Foods, Promin, Taranis and
related to catch‐up growth following diagnosis. Thereafter, Vitaflo
once the patient has stabilised, the total protein intake usu- ◦◦ the protein content of most of these foods is very low,
ally varies little, irrespective of age, except during growth but they should be checked as some need to be
spurts. This scenario is also observed in the author’s centre’s counted as part of the daily protein allowance unless
cohort of HTI patients where natural protein allowance ingredients are completely exchange‐free
◦◦ these foods are an important part of the diet to p

rovide Phenylalanine supplementation in HTI
energy and variety. Having a choice of low protein
products is important, but cost and quantity should Low plasma phenylalanine concentrations have been observed
be considered if these are provided on prescription. in HTI patients on low tyrosine/phenylalanine intakes [182]. If
The NSPKU have produced age‐based guidelines on plasma phenylalanine concentrations remain low, they may
the monthly quantities to provide around 50% daily become rate limiting for protein synthesis, and plasma tyros-
energy requirements that are also applicable in HTI ine levels will remain high. It is important to monitor phenyla-
(www.nspku.org.uk) lanine concentrations and to supplement with additional
◦◦ recipe booklets and online resources are produced by phenylalanine if consistently low. There is significant diurnal
manufacturers variation between morning (highest) and afternoon (lowest)
• pure energy supplements, such as glucose polymers, fat blood phenylalanine concentrations [174, 184]:
emulsions or combined fat and glucose polymer supple-
ments, may be needed if appetite is poor • Supplementation, starting with 50 mg/day of phenylala-
nine, should probably be given if fasting phenylalanine
concentration is consistently (two consecutive tests)
Tyrosine‐ and phenylalanine‐free protein substitute below 50 μmol/L [174]
• Supplementation can be achieved either by increasing
As the natural protein allowance is inadequate to meet natural protein intake by 1 g, if tyrosine concentration
overall daily requirements, a tyrosine‐ and phenylalanine‐ also low (1 g protein contains around 50 mg phenylala-
free protein substitute is given. The combined intake of nine), or by using an l‐phenylalanine powdered supple-
natural protein and protein equivalent from the protein ment, e.g. Phenylalanine 50 (Vitaflo) (50 mg phenylalanine
substitute provides the daily protein requirement shown in in a 4 g sachet)
Table 28.44: • Care needs to be taken as additional phenylalanine from
• A number of age‐specific tyrosine‐ and phenylalanine‐ extra natural protein or pure phenylalanine powder may
free protein substitutes are available; however the increase tyrosine concentrations. Any supplementation
range is less than that available for PKU due to the far should be carefully monitored
smaller numbers of people with HTI. Examples include
Tyr Anamix Infant, Tyr Anamix Junior, Tyr Anamix Micronutrients
Junior LQ, Tyr Explore, Tyr Lophlex LQ, Tyr Cooler
and Tyr Express. The manufacturers’ websites provide Intakes of vitamins, minerals, trace elements, essential fatty
information on composition and usage www.nutricia. acids and LCPUFA should be sufficient to meet age‐appro-
co.uk and www.vitaflo.co.uk. Outside the UK similar priate requirements. Due to the restriction of dietary protein,
products are available from other companies, e.g. www. supplementation will be required. Most tyrosine‐ and phe-
abbottnutrition.com, www.meadjohnson.com, www. nylalanine‐free protein substitutes provide these. If not sepa-
metax.org, www.milupa‐metabolics.com rate supplements are required (Table 28.14).
• The administration and distribution through the day are
similar to those in PKU (p. 523)
Dietary management of newly diagnosed
• Protein substitutes come in a range of presentations
infants with HTI
including powdered infant formula, spoonable products
useful in weaning, powders and liquids (Table 28.12)
Breastfed infants
• In the future it is likely that there will be protein substi-
tutes for HTI based on glycomacropeptide (GMP), which Infants with HTI can be successfully breastfed while main-
is very low in tyrosine and low in phenylalanine (p. 520) taining satisfactory biochemical control [188]. The principles
• Strategies are often required by parents/caregivers to of BF in PKU can be used in HTI. A measured amount of
encourage their child to take the protein substitute tyrosine‐ and phenylalanine‐free infant formula, e.g. Tyr
(Table 28.13) Anamix Infant, is given prior to BF.
A starting point is:
Table 28.44 Guidelines for total protein requirements for HTI (protein

• to provide 1 g protein equivalent/kg/day from Tyr
equivalent from protein substitute and natural protein exchanges). Anamix Infant divided into 5–6 feeds per day
• breastfeed to appetite following the Tyr Anamix Infant feed
Age (years) Total protein (g/kg body weight/day) • additional breastfeeds to appetite can be given if required
0–2 3.0 Tyrosine levels are monitored regularly:
3–10 2.0 • If tyrosine is >400 μmol/L, the volume of Tyr Anamix
11–14 1.5 Infant is increased to suppress breastmilk intake
• If tyrosine is <200 μmol/L, the volume of Tyr Anamix
Infant is decreased to stimulate appetite for breastmilk
Interpretation of Blood Tyrosine and Phenylalanine Results 557
Formula‐fed infants Further dietary progression with the introduction of

weaning solids, food exchanges and onto second stage pro-
Initial management will depend upon plasma tyrosine tein substitute follows the same pattern as for PKU (p. 529).
levels. Feeding issues can occur. Some guidance around this as
Initial plasma tyrosine level is <500 μmol/L: well as how to manage the diet during different stages of
childhood is given in the PKU section (p. 529 and Table 28.20).
• decrease natural protein intake to 1 g/kg/day, divided
into 5–6 feeds
• give Tyr Anamix Infant to appetite after each feed and at Interpretation of blood tyrosine
additional feeds as the infant demands and phenylalanine results
• aim to give a total of 3 g protein equivalent/kg body
weight/day and normal energy requirements for age Regular monitoring of blood levels of tyrosine and phenyla-
lanine should be carried out with samples taken at home
Initial plasma tyrosine levels are >500 μmol/L, which may (DBS). Target aims are given in Table 28.40. Depending on
be the case particularly if nitisinone has been commenced blood results, dietary manipulation may be required:
prior to dietary treatment:
• If phenylalanine levels are low (<50 μmol/L) on two
• All natural protein (tyrosine and phenylalanine) intake is consecutive measurements, supplement initially with
stopped 50 mg/day of phenylalanine (p. 556)
• Give Tyr Anamix Infant to normal fluid requirements, • It is better to consider trends in blood results before
providing around 3 g protein equivalent/kg body increasing/decreasing natural protein intake. Once there
weight/day and a normal energy intake is stability on diet following diagnosis, it is advisable to
• Subsequently, as plasma tyrosine levels fall, a measured adjust natural protein intake after more than one result is
amount of natural protein, initially to provide 1 g pro- available unless blood concentrations of tyrosine or phe-
tein/kg/day as standard infant formula, is reintroduced nylalanine are very low or very high
• An example feeding plan is given in Table 28.45. The • Factors such as illness, growth rate and dietary adher-
quantity of standard infant formula is adjusted accord- ence should be taken into account when assessing and
ing to subsequent plasma tyrosine levels, aiming to keep interpreting blood monitoring results. Guidance on
within target treatment range (Table 28.40) interpretation of tyrosine results is given in Table 28.46
Table 28.45 Example of a daily feeding plan for a 4 kg infant with HTI.
Aim: 1 g natural protein/kg/day and 3 g total protein/kg/day

Total fluid intake 180 mL/kg/day = 720 mL daily
• 80 mL SMA Pro First Infant Milk = 1 g protein
• Total number of feeds = 6 daily
Protein requirement: 1 g/kg/day = 4 × 1 g = 4 g protein/day = 4 × 80 mL SMA Pro First Infant Milk = 320 mL daily
Total fluid requirement = 720 mL
• Fluid from SMA Pro First Infant Milk = 320 mL (55 mL × 6)
• Deficit = 400 mL (720–320 mL) of tyr/phe‐free infant protein substitute (65 mL × 6)
Feeding plan
6 feeds per day of
55 mL × 6 of SMA Pro First Infant Milk followed by
65 mL Tyr Anamix Infant
Additional feeds of Tyr Anamix Infant can be given if hungry
Energy
Protein Fluid
kcal kJ equivalent (g) Carbohydrate (g) Fat (g) (mL)
330 mL SMA Pro First Infant Milk 221 924 4.3 23.4 11.9 330
390 mL Tyr Anamix Infant 269 1119 7.8 28.9 13.7 390
Total 490 2043 12.1 52.3 25.6 720
Intake per kg/day 123 511 3 13.1 6.4 180
10% energy 43% energy 47% energy
Energy requirement per kg/day 96 403
Table 28.46 Manipulation of diet based on blood tyrosine levels. diagnosed with HTI, are commenced on dietary treatment
and nitisinone:
Blood tyrosine level Protein intake
• Initially natural protein intake is decreased to 0.5–1.0 g/
>400–700 μmol/L Decrease intake by 1–2 g protein/day kg body weight/day, and an age‐appropriate tyrosine‐
<200 μmol/L Increase intake by 1 g of protein/day and phenylalanine‐free protein substitute is introduced
to maintain an age‐appropriate total protein intake/kg/
day (Table 28.44)
Management of Illness • Natural protein intake is then adjusted according to
plasma tyrosine results (Table 28.46) to maintain within
Children with HTI do not have acute metabolic decompen- target treatment ranges (Table 28.40)
sation with intercurrent illness. A formal ER is not required.
It is however prudent to try to prevent catabolism and exces-
sive rise in blood tyrosine levels by:
• encouraging intake of the usual tyrosine and phenylala- Learning points: tyrosinaemia type I (hepatorenal
nine protein substitute tyrosinaemia)
• giving protein exchanges to appetite
• giving sugary/high carbohydrate drinks • HTI is a treatable disorder since the introduction of
nitisinone
Dietary management of later diagnosed • Dietary restriction of tyrosine and phenylalanine is required
cases of HTI lifelong
• Long‐term outcome knowledge is still being accrued as
Individuals diagnosed late after the onset of clinical symp- nitisinone has only been available for 27 years
toms, or as a result of investigation following a sibling being
Tyrosinaemia Type II (Richner–Hanhart syndrome, HTII)
Enzyme Tyrosine aminotransferase (TAT)

Biochemical Hepatic tyrosine aminotransferase catalyses the first step of the tyrosine degradation pathway (Figure 28.7); deficiency results in:
defect • gross accumulation of tyrosine with plasma tyrosine concentrations usually >1200 μmol/L (normal reference range
30–120 μmol/L) at presentation
• tyrosine levels also increased in cerebrospinal fluid
• increased excretion of its phenolic derivatives in urine [154]. If the tyrosine concentration is less markedly increased, HTIII
should be considered
• Most cases of HTII have not been confirmed by enzyme or mutation analysis; therefore some cases may actually be HTIII not
HTII [154]
Clinical onset TAT deficiency results in tyrosine accumulation
presentation, • Usually present in the first few months of life with painful hyperkeratotic plaques on soles and hands
features • High concentrations of tyrosine result in tyrosine crystals depositing within cells causing inflammation and leading to some of
the clinical features that may affect the eyes and skin (oculocutaneous tyrosinaemia) and cognitive development [154]:
◦◦ ocular lesions – occur in around 75% cases; corneal damage is due to tyrosine crystals disrupting corneal epithelial cell
function and leading to an inflammatory response
◦◦ skin lesions – occur in around 80% of cases and affect pressure areas, most commonly the palms and soles; this is possibly
caused by excessive intracellular tyrosine causing structural abnormalities of the epidermal keratinisation [189]
• No liver or renal disease as the biochemical defect is early in the tyrosine degradation pathway, so the toxic metabolites found
in HTI are not formed
Long‐term • With dietary treatment, the skin and eye problems usually improve rapidly. Skin and eye symptoms do not generally occur if
complications tyrosine concentrations are <800 μmol/L [154]
and outcome • Neurological complications occur in around 60% cases with varying degrees of developmental delay including seizures,
self‐mutilation and behavioural difficulties [190]
Dietetic Principles of dietetic management used for HTI (p. 554) are also used in HTII:
management • Low tyrosine and phenylalanine‐restricted diet including tyrosine‐ and phenylalanine‐free protein substitute
• Target treatment blood levels: tyrosine 200–400 μmol/L
phenylalanine >50 μmol/L
Tyrosinaemia Type III 559
• The target for tyrosine is lower than that needed to treat the skin and eye lesions to minimise possible risk of high tyrosine
levels contributing to developmental delay [191]
Monitoring Frequency of blood tyrosine and phenylalanine monitoring
Regular monitoring of blood tyrosine and phenylalanine concentrations should be undertaken. Generally DBS are taken at home
and posted to the laboratory for analysis:
Clinical monitoring including

• eye examination especially if high tyrosine levels
• skin examination (fingers/soles of feet especially if high tyrosine levels)
• nutritional biochemistry including plasma quantitative amino acids, FBC, iron studies, annual monitoring of other vitamins,
minerals, trace elements, essential fatty acids as appropriate
Parent Support Metabolic Support UK www.metabolicsupportuk.org/
Group
Learning points: tyrosinaemia type II (Richner–Hanhart Learning points: tyrosinaemia type III
syndrome, HTII)
• HTIII is extremely rare
• HTII is extremely rare • Treatment with a low tyrosine and phenylalanine diet
• Treatment with a low tyrosine and phenylalanine diet with with tyrosine‐ and phenylalanine‐free protein substitute
tyrosine and phenylalanine protein substitute, as in HTI, although needed initially may not be required long term to
will reduce the accumulation of tyrosine crystals achieve target treatment blood levels
• Neurological outcome is compromised in many cases with • Neurological outcome is compromised in most cases
learning difficulties, challenging behaviour and seizures
Tyrosinaemia Type III
Enzyme 4‐Hydroxyphenylpyruvate dioxygenase (4‐HPPD)

Expressed in the liver and kidney
Biochemical 4‐HPPD catalyses the second step in the tyrosine degradation pathway (the step that is inhibited by nitisinone in the treatment of
defect HTI) (Figure 28.7) resulting in:
• elevated plasma tyrosine
• increased excretion of its phenolic derivatives in urine [154]
• Mutations in the enzyme 4‐HPPD gene located on chromosome 12
• Five mutations have been described [154], but without specific genotype–phenotype correlation
• It is a very rare disorder with only 13 cases described in the literature to date
• In some enzymatically diagnosed cases, no mutations have been identified [192]
Clinical onset • Neurological symptoms include developmental delay, ataxia, microcephaly, seizures, increased reflexes [154]
presentation, • Liver and renal function are normal, and there are no reports of the oculocutaneous features seen in HTII [192]
features • Plasma tyrosine levels are usually in the range 300–1000 μmol/L
• Urine organic acids show increased excretion of phenolic compounds
• Diagnosis is possible by enzyme analysis of liver or kidney biopsy or mutation analysis [154]
Long‐term • There are reports that after infancy many patients with HTIII are able to maintain tyrosine levels within the target treatment
complications range without the need for dietary treatment [193]. This has also been observed in the author’s unit
and outcome • Intellectual impairment is the most common long‐term complication reported in 75% of cases [192, 194]
Dietetic Principles of dietetic management used for HTI (p. 554) can be applied to HTIII:
management • low tyrosine and phenylalanine diet
• tyrosine and phenylalanine protein substitute
• target treatment levels: tyrosine 200–400 μmol/L
phenylalanine >50 μmol/L
Monitoring Frequency of blood tyrosine and phenylalanine monitoring
Regular monitoring of blood tyrosine and phenylalanine concentrations should be undertaken. Generally DBS are taken at home
and posted to the laboratory for analysis:
Clinical monitoring including

• eye examination especially if high tyrosine levels, although this has never been described
• nutritional biochemistry including plasma quantitative amino acids, FBC, iron studies, annual monitoring of other vitamins,
minerals, trace elements, essential fatty acids as appropriate
Parent Support Metabolic Support UK www.metabolicsupportuk.org
Group
Organic Acidaemias and Urea Cycle Disorders

Marjorie Dixon
Dietary management: general principles of low nitrogen scavengers in UCD) or to increase excretion of toxic
protein diets intermediates (e.g. carnitine and glycine to excrete isovaleric
acid in IVA) or to replace a deficient product (e.g. arginine in
Introduction UCD). Medical aspects and disorder‐specific dietary treat-
ments are described under each separate condition. Patients
A low protein diet forms an essential part of the manage- with an OAA or UCD are invariably complex to treat, and it
ment of organic acidaemias (OAA), e.g. methylmalonic aci- is essential they are managed at specialist metabolic centres.
daemia (MMA), isovaleric acidaemia (IVA), glutaric aciduria Local professionals and hospital teams should also form an
type 1 (GA1) and the urea cycle disorders (UCD), e.g. citrul- integral part of their care package.
linaemia, ornithine carbamoyl transferase deficiency. These
disorders arise due to enzyme defects in the catabolic path-
ways of certain amino acids (in the case of OAA) and of Protein requirements
waste nitrogen excretion (in the case of UCD). The aim of the
low protein diet is to limit the substrate load (amino acids in Proteins are large complex molecules. Different proteins
OAA and nitrogen in UCD) on the ‘blocked’ metabolic path- work as antibodies, enzymes, messenger proteins such as
way to reduce the production of toxic metabolites that can some types of hormones and structural components and in
cause neurological sequelae and organ damage. As such, transport and storage. The body does not maintain reserves
these are classified as ‘intoxication type disorders’ of inter- of protein; thus a constant supply is needed (p. 513).
mediary metabolism. Low protein diets should provide at least the minimum
This section describes the provision of a low protein diet amount of protein, nitrogen and indispensable (essential)
and acute management, common to these disorders. Dietary amino acids to meet the body’s requirements. ‘Safe level of
treatment is generally combined with pharmacological treat- protein intake’ (Table 28.47) and requirements for indispen-
ment to reduce the substrate load on the pathway (e.g. sable amino acid intake have been set by FAO/WHO/UNU
Dietary Management: General Principles of Low Protein Diets 561
Table 28.47 ‘Safe level of protein intake’ for infants, children recent advances in determining protein and amino acids
and adolescents. requirements in humans is by a stable isotope method: indi-
cator amino acid oxidation [195]. Using this technique, mean
Age Safe level (g protein/kg/day)
and safe protein intake in children aged 6–10 years is
For infants < 6 months of age (months) reported to be 1.3 and 1.55 g/kg/day that is much higher
1 1.77
than current FAO recommendations. However, while experts
continue to debate the accuracy of alternative methodologies
2 1.5
used to determine protein requirements [12, 196, 197], the
3 1.36 FAO guidelines for protein continue to be used to guide low
4 1.24 protein intake prescriptions in OAA and UCD, although
6 1.14 some countries use local reference value guidelines. Ideally
the protein source in low protein diets should be mainly
For weaned infants (sexes combined) (years)
from HBV protein. However, this is not necessarily common
0.5 1.31 practice because a greater variety of foods and a higher
1 1.14 energy intake per gram of protein can be provided from LBV
1.5 1.03 protein foods. Children on low protein diets who frequently
2 0.97 consume a limited range of LBV protein foods (plant foods)
may be at risk of one or more indispensable amino acids
3 0.9
becoming rate limiting for protein synthesis, e.g. lysine in
4 0.86 predominantly cereal‐based diets. It is, therefore, important
5 0.85 that a variety of LBV protein foods (potato, cereals, rice,
6 0.89 pasta, pulses, vegetables) are eaten to ensure an adequate
intake of all indispensable amino acids. If the protein toler-
7 0.91
ance and prescription is generous enough, more HBV pro-
8–9 0.92
teins should be included to improve the protein quality of
10 0.91 the diet. A new method of calculating protein quality was
Girls published by the FAO in 2013 [198]. However, without more
11 0.9 up to date and extensive amino acids analysis of foods, this
is difficult and time consuming to calculate. There are no
12 0.89
publications describing an optimal ratio of HBV to LBV
13 0.88 foods in low protein diets for these disorders. Dietary prac-
14 0.87 tice surveys in UK and Europe report that HBV foods typi-
15 0.85 cally provide at least some of the daily protein allowance in
16 0.84
patients with UCD [199], and the OAA, propionic acidaemia
(PA) [200] and IVA [201].
17 0.83
Protein allowance (g/day) varies depending on the dis-
18 0.82 order, residual enzyme activity of the specific disorder,
Boys growth rate, age and prescribed medicines. During early
11 0.91 infancy, growth is at a maximum, so protein requirements
per kg body weight are greatest at this time. Clinical and
12–13 0.90
biochemical monitoring are essential to help prevent pro-
14 0.89 tein and amino acid deficiencies, which can cause severe
15 0.88 cutaneous lesions (babies and young children are particu-
16 0.87 larly vulnerable), and to guide protein prescription (refer
17 0.86 to specific disorders).
Protein intake may need to be temporarily increased:
18 0.85
Source: Adapted from [8]. • during periods of catch‐up growth

• if the usual daily protein intake is repeatedly interrupted,
e.g. some MMA patients have frequent episodes of meta-
expert committees, most recently in 2007, based on nitrogen bolic decompensation and acidosis and require intrave-
balance studies [8]. Protein intakes (g/kg/day) decrease nous (IV) 10% glucose and ER instead of usual feeds. It is
with age throughout childhood. The ‘safe level of protein important to monitor days off with less than usual or
intake’ has been calculated as the mean requirement +2 zero protein intake
standard deviations (SD), so as to meet or exceed the require- • during episodes of severe pancreatitis (as seen in MMA,
ments of most individuals. However, for some, a protein PA, IVA), when protein catabolism can be substantial in
intake below the safe intake may be adequate for growth, response to severe inflammation, protein requirements
particularly if protein is mainly from HBV sources. More are increased (p. 186)
Provision of a low protein diet provide more choice in a low protein diet. Parents should be
encouraged to spend time looking at different product
Protein choices in the supermarket.
In OAA and UCD a daily protein allowance is prescribed.
Protein intake (g/kg/day) decreases with age, but the total Protein substitutes (l‐amino acid supplements)
intake (g/day) increases (Table 28.47). Protein is provided Precursor‐free l‐amino acid supplements (i.e. disorder‐spe-
from breastmilk or infant formula for infants and food for cific amino acid supplements that do not contain the amino
older children (unless they are tube fed). Protein intake from acids that cannot be metabolised) are used by some centres
LBV protein foods can be measured by an exchange system, in the treatment of some OAA (further discussed under the
where one exchange equals the amount of each food that specific disorders as their role and use varies between disor-
provides 1 g of protein. This system allows greater variety in ders). The use of EAA supplements in UCD is discussed on
the diet as foods can be substituted for each other and still p. 590. Administration of amino acid supplements (termed
provide a similar protein content and the same total daily protein substitutes) for disorders of amino acid metabolism
protein intake. is discussed on p. 523. Although smaller amounts are used in
Table 28.48 provides a list of 1 g protein exchange weights OAA and UCD, the practical aspects are generally still
and energy content for basic foods such as potato, rice, pasta, applicable.
pulses, vegetables and some infant formulas. Protein can
also be provided by manufactured foods such as bread, pitta,
chapatti, breakfast cereals, biscuits, cake, potato‐based foods Energy
and vegetable fingers. The protein content on the nutritional
Energy requirements need to be adjusted for the individual’s
label is expressed as grams of protein/100 g food and some-
needs considering metabolic stability, rate of weight gain
times per portion. Parents should be taught how to interpret
and physical activity. Inadequate energy intake must be
the food label and calculate exchanges. For manufactured
avoided as it causes poor growth and metabolic instability
foods one exchange (1 g protein) is calculated as follows:
with endogenous protein catabolism, leading to an increased
• 100 ÷ (g protein per 100 g of food) production of toxic metabolites, e.g. ammonia in UCD, and
• if more than 1 g protein is desired, this is multiplied by must be avoided. The aim is to provide around normal
that number of exchanges, e.g. cornflakes = 7 g protein energy requirement for age and sex, except for those with
per 100 g physical disability who are likely to have lower energy
• 100 ÷ 7 = 14 g cornflakes = 1 g protein requirements due to reduced mobility, such as children with
• if 2 g of protein is required, then 14 g
× 2 = 28 g MMA who have had a metabolic stroke and, in others who
cornflakes may have increased energy requirements, such as children
with GA1 with severe dystonia.
Ideally the protein intake should be evenly distributed
Dietary energy can be provided by both the protein
between main meals with some allocated for snacks to avoid
exchanges and the following groups of foods that are allowed
giving a protein load at any one meal. Protein food exchanges
without restriction in the diet:
should be weighed using digital scales that weigh in 1 g
increments, at least initially. If parents cannot cope with the • foods naturally low in or free of protein: sugar, fats and a
concept of protein exchanges or weighing, then a set menu few commercial foods (Table 28.9). The classification
with handy measures or a pictorial food chart can be used. guideline for exchange‐free commercial foods in PKU
Often parents become familiar with portion sizes that pro- can also be used for low protein diets. Generally foods
vide 1 g of protein and stop weighing food; however, it with <0.5 g protein/100 g can be allowed freely unless a
remains important to check accuracy by weighing regularly. large portion is likely to be eaten
The energy provided by exchange foods has a wide varia- • fruits and vegetables with <1.0 g protein/100 g
tion, e.g. an exchange (1 g protein) of baked beans provides (Table 28.50)
20 kcal (85 kJ) and crisps 110 kcal (460 kJ). It may be helpful, • specially manufactured very low protein foods; these
particularly if the child has a poor appetite, to give parents include bread (loaves, rolls), pizza bases, pasta, rice, cous-
advice on choosing protein exchanges that are more energy cous, pasta, flour mixes (for cakes, savoury), breakfast
dense and provide >60 kcal (250 kJ) per exchange. cereals and bars, savoury snacks, biscuits/crackers, soup
HBV protein foods can be incorporated in the diet as 3 or sachets, low protein desserts, low protein energy bars
6 g protein exchanges (i.e. one exchange is the amount of and egg replacers. In the UK most of these foods are
food which provides 3 or 6 g protein). Table 28.49 provides a available on prescription, endorsed Advisory Committee
list of 6 g protein exchange weights for higher protein foods. on Borderline Substances (ACBS). Manufacturers of low
This is more useful for older children or those with milder protein foods include Fate Special Foods, First Play
disorders who are on a much more generous protein Dietary Foods, Gluten Free Foods, Juvela, MetaX,
allowance. Mevalia, Nutricia, PK Foods, Promin, Taranis and Vitaflo.
Some vegan, plant‐based foods are as high in protein as The protein content of most of these foods is very low, but
HBV foods; however, some are lower in protein and can help they should be checked as some may need to be counted
Table 28.48 Basic list of 1 g protein exchange foods for low protein diets.
Weight (g) = 1 exchange Energy (kcal/g Energy (kJ/g

Food = 1 g protein protein) protein)
Infant formula SMA Pro First Infant Milk 80 mL 54 224

Cow & Gate First Infant Milk 75 mL 50 208
Aptamil Profutura First Infant Milk 75 mL 50 208
Milk and dairy Cow’s milk 30 mL 19 79
Coconut Single cream 30 mL 58 243
Double cream 60 mL 298 1251
Yoghurt* (whole milk, fruit) 25 27 114
Fromage frais* 20 20 83
Ice cream* ~30 88 370
Milk chocolate* 15 78 326
Plain chocolate* 20 102 428
Philadelphia* 20 45 186
Boursin* 12 48 201
Dairylea* 10 21 88
Coconut, creamed, block 15 100 420
Potatoes and starchy Potato, old 55 33 138
vegetables† Potato, new (flesh and skin) 55 35 148
Jacket (baked) potato (flesh only) 45 37 155
Jacket (baked) potato (flesh and skin) 40 39 163
Chips cooked 30 61 256
Roast potato 40 65 270
Crisps 15 74 311
Sweet potato 90 76 317
Plantain 125 32 136
Yam 60 59 247
Butternut squash (baked) 110 35 147
Pulses† Baked beans in tomato sauce* 20 15 63
Beans: aduki, haricot, black‐eye, chick 12 14 59
peas, red and white kidney
Beans: broad, butter 20 10 42
Beans: soya 7 10 42
Tofu (soya bean steamed) 12 9 38
Lentils 12 12 50
Peas 15 12 50
Marrowfat peas 15 13 55
Hummus* 15 37 154
Vegetables† Asparagus 30 8 34
Beansprouts, mung (raw) 35 11 46
Brussels sprouts 35 12 50
Broccoli tops 30 8 34
Cauliflower 50 15 63
Curly kale 40 10 42
Mangetout 30 8 34
Okra 40 11 46
Spinach, fresh baby and frozen 30 6 25
Spring greens 55
Sweetcorn kernels 40 10 42
Weight (g) = 1 exchange Energy (kcal/g Energy (kJ/g

Food = 1 g protein protein) protein)
Fruits and dried fruits (varies Avocado 55 95 399

depending on the fruit, check Banana flesh, no skin 85 69 290
individually)
Raisins 50 136 571
Sultanas 40 110 462
Apricots dried 25 63 265
Figs 30 63 265
Cereals Cornflakes* 10 58 243
Rice Krispies* 15 58 243
Honey Monster Puffs* 20 53 224
Weetabix* 10 36 152
Oatmeal 10 36 152
Rice white, long grain
raw 15
boiled 35 46 193
Pasta white: fusilli, twists, spaghetti 20 28 118
(dried, then boiled)
Noodles rice 55 49 206
Semolina (raw) 10
Couscous (cooked) 15 27 113
Flour: 10 35 147
white, wholemeal, plain or self‐raising
Breads White* 12 29 120
Wholemeal* 10 22 92
Rolls (soft, crusty)* 10 29 120
Chapatti* 15 43 180
Nan* 15 40 164
Pitta* 10 28 118
* For manufactured foods the weight for one exchange and energy value will be more accurate if calculated from the nutritional label on the food. The
figures given can be used as a guide.
†
The weight of one exchange for vegetables, potatoes and pulses is for cooked (boiled) weight (except for baked beans) unless otherwise stated.
Source: From Finglas et al. [54]. Licensed under Open Government UK.
as part of the daily protein allowance. Availability of swallow due to neurological disability, or vomiting, gastro‐
choice is important for quality of life and dietary adher- oesophageal reflux (GOR) and retching depend on energy
ence, but cost of products and quantity used should be supplements as their main energy source, which are invari-
considered if obtained on prescription. Manufacturers ably part of a modular tube feed. If energy supplements are
produce recipe booklets and online resources for their needed, it is important to maintain a healthy balance between
low protein food products, e.g. www.lowproteinconnect. fat and carbohydrate (CHO) energy.
com, www.vitafriendsmsud.com/recipes
• energy supplements: glucose polymer, fat emulsions or
Vitamins, minerals and trace elements
combined fat and glucose polymer supplements
Mineral deficiencies, particularly associated with low pro-
Manufactured low protein foods are not always necessary tein diets, have been reported in patients with OAA and
or popular with children on low protein diets although low UCD [202–204]. Vitamin and mineral supplements are invar-
protein milk replacements, e.g. Prozero and Loprofin Drink, iably essential as dietary intake will be severely limited.
are useful and can be well accepted. Some children obtain Adequate intake of vitamins A and C and folic acid can be
sufficient energy from normal foods and prefer to eat these. provided by fruits and vegetables, if eaten in amounts rec-
In contrast others with a poor appetite, inability to suck or ommended for healthy children. Iron, zinc, copper, calcium,
Table 28.49 Basic list of 6 g protein exchange foods for low protein dissolved in water and can be used from age 3 years.
diets. Alternatively for older children Forceval Soluble Junior
(suitable from age 6 years) or Forceval Soluble or Capsules
Weight (g) = 1 exchange
(suitable from age 12 years) can be given. Forceval Soluble
Food = 6 g protein
Junior does not contain calcium, phosphorus or sodium,
Egg (hen’s) 1 medium egg inositol and choline and only small amounts of magnesium.
Meat, trimmed of all fat, e.g. beef, pork, 20–25 depending on cut A separate calcium supplement must be given. Forceval
lamb, chicken Soluble and Capsules differ in composition from Soluble
Processed meats, e.g. sausage, burger, Vary – calculate from Junior; they contain no sodium or vitamin K and only a
salami, ham, chicken nuggets nutritional label small amount of calcium, phosphorus and potassium. An
additional calcium supplement is needed. Phlexy‐Vits (pow-
Fish
der or tablets) is a comprehensive vitamin and mineral sup-
White fish, e.g. cod, haddock, plaice, 25
plement suitable from age 11 years. The powder is generally
baked
taken mixed with a strong flavoured drink. If commercial
Oily fish, e.g. salmon, mackerel, sardines 30 vitamin and mineral supplements available from supermar-
Shellfish, e.g. prawns, crab 30 kets and pharmacies are used, it is essential their composi-
Scampi in breadcrumbs Approx. 60 – calculate tion is checked as this varies greatly between brands and
from nutritional label invariably will not provide an adequate intake of all neces-
Fish fingers, fish cakes Vary – calculate from sary micronutrients. Supplements should be given with a
nutritional label drink of water or mixed with water to dilute (as recom-
Cheese mended by manufacturer).
Cheddar, Edam, Gouda 25
Feta 40 Essential fatty acids
Cottage cheese Approx. 60 – calculate Children on low protein diets may be at risk of inadequate
from nutritional label intakes of essential fatty acids (EFA) and their longer chain
Nuts derivatives docosohexaenoic acid (DHA) and arachidonic
Peanuts 25 acid (AA). LCPUFA deficiency, specifically DHA, has been
reported in patients with UCD and MMA, and supplementa-
Peanut butter 25
tion recommended [207]. Low plasma and red cell DHA con-
Cashew 30 centrations in patients with UCD and branched chain organic
Chestnuts 50 acidurias have also been reported [208]. Low protein diets
and modular feeds [206] need to be assessed for EFA and
Source: From Finglas et al. [54]. Licensed under Open Government UK. LCPUFA content. In the UK at least 1% of total energy intake
from linoleic acid and 0.2% from α‐linolenic acid is recom-
mended for infants [205]. FAO/WHO 2008 [209] recom-
vitamins B12 and D are most likely to be deficient in low pro- mends for children >6 months, 3%–4% linoleic acid and
tein diets based mainly on LBV protein foods. Children who 0.4%–0.6% α‐linolenic of daily energy intake, and DHA for
are less mobile and those who are less exposed to sunlight or infants to be based on amounts in breastmilk and for chil-
with dark skin are at greater risk of vitamin D deficiency. dren: 100–150 mg for 2–4 years; 150–200 mg for 4–6 years;
Together, the diet and vitamin and mineral supplement 200–300 mg for 6–10 years. Red cell and plasma fatty acid
should provide at least the reference nutrient intakes (RNI) profiles should be measured if there are concerns about pos-
for vitamins and minerals [205], except for children with sible deficiency. Red cell measurements more accurately
MMA who have chronic kidney disease (CKD) (p. 262). reflect long‐term EFA and LCPUFA status. DHA is added to
The amount of supplement required varies depending on some of the disorder‐specific precursor‐free amino acid sup-
the child’s diet and must be assessed for the individual, plements used in treatment of OAA such as the Infant
including those on modular tube feeds [206]. The supple- Anamix and Cooler ranges. KeyOmega and Doc Omega are
ment is best given as a divided dose to enhance absorption. AA and/or DHA supplements that can be added if dietary
A list of ACBS prescribable micronutrient supplements is or modular feed sources are inadequate.
provided in Table 28.14. These vary in format (powders,
capsules, effervescent tablets). Paediatric Seravit (unfla-
voured or pineapple flavour) provides a comprehensive Monitoring a low protein diet
vitamin and mineral supplement (except for sodium, potas-
sium and chloride). The unflavoured powder can be added Clinical and biochemical
to infant formula or modular tube feeds, taking into account Nutritional adequacy of the low protein diet needs to be
what the feed already provides, or mixed into a strong fla- carefully monitored as deficiency states have been reported
voured drink to mask its flavour. FruitiVits is a comprehen- [202–204]. The following are necessary at clinic appoint-
sive supplement, an orange flavoured powder that is ments: clinical examination (skin, looking specifically for
Table 28.50 Low protein fruits and vegetables allowed freely in the diet.
Fruits
Fresh, frozen protein/100 g or tinned (fruit only weight) <1 g protein, unless stated otherwise. Fruits with >1 g protein/100 g may need
to be counted as part of the daily protein intake if eaten in large portions. Many dried fruits are higher in protein content and need to
be counted.
Apples Jack fruit Pineapples
Apricots Kiwi fruit Plums
Bilberries Kumquats Pomegranates (1.3 g protein/100 g)
Blackberries Lemons Pears
Blackcurrants Limes Prunes
Blueberries Loganberries Quince
Clementines Lychees Raisins
Cherries Mandarins Raspberries (1.4 g protein/100 g)
Cranberries Mangoes Redcurrants
Damsons Melons Rhubarb
Dragon fruit Medlars Satsumas
Figs, not dried Mulberries Sharon fruit
Figs, green, raw Nectarines (1.4 g protein/100 g) Star fruit
Gooseberries Olives Strawberries
Grapefruit Oranges Tamarillos
Grapes Passion fruit (2.6 g protein/100 g) Tangerines
Greengages Papaya Water melon
Guava Peaches Mixed peel
Vegetables
Fresh cooked (vegetable weight only) <1 g protein/100 g, unless stated otherwise. Vegetables with >1 g protein/100 g may need to be
counted as part of the daily protein intake if eaten in large portions.
Artichoke Cucumber Parsley
Aubergine Fennel Parsnip (1.6 g protein/100 g)
Beans, French, green Garlic Peppers
Beetroot boiled (2.3 g protein/100 g) Gherkins Pumpkin
Cabbage boiled (1.5 g/100 g) Herbs Radish
Carrot Leek (1.2 g protein/100 g) Rocket, raw (3.6 g protein/100 g)
Capers Lettuce, raw (1.2 g/100 g) Squash, butternut (0.9 g protein/100 g)
Cassava Marrow Swede
Celeriac Mustard and cress Tomato
Celery Mushrooms, raw (1 g protein/100 g) Tomato purée
Chicory Onion Turnip
Courgette (2 g protein/100 g) Spring onion Watercress (3 g protein/100 g)
Source: From Finglas et al. [54]. Licensed under Open Government UK.
Growth
signs of protein deficiency such as rashes, hair and nails),
anthropometric measurements, biochemical assessment Poor growth can occur in some of these disorders and may
(such as quantitative amino acids and electrolytes) and die- be attributed to the disorder and low protein diet; therefore,
tary assessment (checking all nutrients). At least annual regular monitoring is essential. It has been demonstrated
assessment of the following is also important: plasma status [210] that a protein-energy ratio range of 6%–12% correlates
of vitamins A, D, E, B12, minerals (ferritin, Hb), trace ele- with an optimal growth, BMI and % fat mass in OAA and
ments (copper, zinc, selenium) (Table 1.6), bone mineral den- UCD on a restricted natural protein diet (median natural
sity scans (by DEXA) and plasma and red cell status of EFA protein intake at or above safe intakes [8], without use of
and LCPUFA. l‐amino acids). However, no description of type or amount
Initial Dietary Treatment of the Critically Unwell, Newly Diagnosed Patient 567
of HBV or LBV protein was given. It was recognised that a adequate enteral energy intake difficult; a higher energy
protein intake at the upper end of this ratio may not be pos- intake can often be achieved from parenteral nutrition
sible due to the underlying metabolic defect. Data on 263 (PN) via a central venous catheter (CVC) or peripher-
MMA/PA patients from the European registry and net- ally inserted catheter (PICC) and may be preferable
work for Intoxication type Metabolic Diseases (E‐IMD) [211] during the initial stabilisation period. Assess for the
showed that a higher natural protein energy prescription ratio individual.
and plasma l‐valine and l‐arginine levels were positively • Reintroduce protein within 24–48 hours of stopping and
associated with height z‐score, but negatively associated with before if the acute metabolic derangement, including aci-
amount of synthetic protein prescription and age at visit. dosis, has been corrected and plasma ammonia is
The nutritional intake of infants needs to be monitored fre- <100 μmol/L (normal <40 μmol/L). This may be delayed
quently as they grow rapidly during the first few months in very sick infants on dialysis.
and year of life. Newly diagnosed neonates and young • Protein is usually commenced at 0.5 g protein/kg body
infants should be weighed 1–2 weekly at local baby clinics; weight/day and increased to the final safe level of pro-
this can usually be decreased to monthly intervals by one tein intake (Table 28.47) within a few days (typically 2–3
year of age if growth is satisfactory. Parents should initially days), depending on blood biochemistry. An age‐appro-
be contacted every 1–2 weeks to review weight gain and priate feed is used: for infants either infant formula or
assess feed intake; thereafter, the frequency can be based on EBM; for older children a paediatric enteral feed.
progress. Adjustments to composition and volume of low • If enteral feeds are not tolerated, PN is given (p. 71). A
protein feeds are then made based on weight gain (to give standard parenteral amino acid solution such as
the safe level of protein intake, provided the child is meta- Vaminolact or Vamin can be used, but only the desired
bolically stable) and guidance given on the feeding pattern, amount of protein (amino acids g/kg/day) given.
including frequency of feeding. This regular contact can also For example: to provide 2 g amino acids/kg for a 3.5 kg
identify any feeding problems at an early stage. infant
Vaminolact provides 65.3 g amino acids (9.3 g nitrogen =
58 g protein)/1000 mL
Initial dietary treatment of the critically unwell,
110 mL provides 7.2 g amino acids = 2 g/kg.
newly diagnosed patient Vaminolact, glucose and electrolytes solutions are given
together, as well as lipid and vitamin solutions; com-
Patients with ‘intoxication type disorders’ generally present
bined they provide the total energy and nutrient
following a symptom‐free period, which can be acute or
requirements.
chronic. Neonates and young infants may present with a his-
• As the child stabilises the IV fluids or PN can be gradu-
tory of poor feeding, lethargy, hypotonia with relentless
ally decreased, and enteral feeds (providing the same
deterioration and progression to coma. Older children, or
protein and energy content) increased concurrently. A
even adults, may present acutely at the time of an intercur-
PN titration plan is calculated to decrease both solutions
rent infection or other catabolic event. The newly diagnosed
that enables tolerance to be assessed and an adequate
patient may be very sick with metabolic encephalopathy, in
energy intake and the desired protein prescription to be
intensive care with a severe metabolic acidosis and/or
constantly provided.
hyperammonaemia requiring ventilation and extracorporeal
• The titration plan is based on the volume and adminis-
procedures and drug management to remove toxic com-
tration rate of each PN solution and the volume of enteral
pounds. Reversal of catabolism is essential to prevent fur-
feed to be given.
ther production of toxic metabolites and to help stabilise the
• Electrolytes (sodium and potassium) may need to be
child’s condition.
added to the feed to provide normal requirements for
The principles of dietetic treatment to promote anabolism
age, taking into account any contribution of these from
are similar for both OAA and UCD:
IV fluids and medicines such as sodium bicarbonate (to
• Stop all protein sources (to reduce the production of treat acidosis) and sodium benzoate (to treat hyperam-
toxic metabolites from exogenous sources) for the mini- monaemia). Blood electrolytes should also guide intake.
mum time possible to avoid protein deficiency and • For infants, if the mother wishes to breastfeed, she should
catabolism. be encouraged to express several times a day to maintain
• Give a protein‐free, high energy intake to promote anab- a good supply of breastmilk until the baby becomes more
olism: IV fluids comprising 10% glucose and electrolytes, metabolically stable; then BF can be reintroduced. This
combined with or progressing to continuous nasogastric changeover from NG feeds to BF may take a few days in
(NG) feeds of 10%–20% glucose polymer (depending on a baby who is still not fully alert post‐extubation, has
age) ± fat emulsion; infants can be given a protein‐free been encephalopathic and has never established full BF
feed such as Energivit, as tolerated, or for older children, due to poor feeding prior to presentation. Initially a com-
Basecal. Some patients progress directly to introduction bination of some BF and NG/oral feeds may be best with
of protein (see below) and may not have a period of pro- progression towards full BF as the infant’s oral feeding
tein‐free feeds, once stabilised. improves. Careful monitoring is necessary to ensure the
• Fluid restrictions in the ventilated child and sometimes infant receives an adequate intake during this period.
poor tolerance of enteral feed can make provision of an EBM can be used to provide the protein requirement
until BF is fully established. Protein‐free feeds are usu- • Once the child transitions from acute to chronic manage-
ally given in combination with BF while metabolic stabil- ment, the principles of a low protein diet (p. 562) should
ity is being established and often long term to limit be followed. Practical aspects of feeding and ongoing
protein intake (see below). dietary treatment are described below.
• For children who present at an older age, a low protein • Prior to discharge the parents need to be fully educated
tube feed (short or long term), particularly for those and given clear written instructions about the dietary
with a severe neurological insult or to establish a low treatment and emergency regimen for management of
protein diet, may be needed. When starting a low pro- illness (discussed in detail under specific disorders) and
tein diet, taking a diet history is important as some chil- a list of contact information for the metabolic team.
dren may already self‐select a low protein diet and/or Liaison with local healthcare professionals, such as
have specific eating habits and food choices. This is health visitors and the local hospital team, is also an
seen typically, but not exclusively, in those with UCD. essential part of the ongoing care package.
This information is useful to plan the low protein diet
and to help the family cope. It may be possible to con- Examples of low protein feeds and diets for the manage-
tinue with a self‐selected low protein diet and just ment of OAA and UCD are given in Tables 28.51 and 28.52
ensure adequate protein‐free energy, vitamins and min- (infant feeds), Table 28.53 (older child’s diet) and Tables 28.54
erals are given. and 28.55 (tube feeds).
Table 28.51 Standard infant formula and Energivit (protein‐free feed) for 3‐month‐old male infant.
Weight = 5 kg, to provide 1.36 g protein/kg, 150 mL/kg (total volume = 750 mL)
Energy
(kcal) (kJ) Protein (g) CHO (g) Fat (g)
540 mL SMA Pro First Infant Milk (68 g powder) 362 1520 7 39 19
250 mL Energivit 185 777 – 25 9.5
Total 547 2297 7.0
Per kg 109 459 1.4 – –
Energy requirement per kg* 96 403
480/day 2106/day
Safe protein intake¶ 1.36 g/kg/day
Energy % 5.1 47 47
* Dietary reference values for energy, SACN [212].

¶
FAO/WHO/UNU safe level of protein intake (Table 28.47). Provides only 5% of daily energy (see p. 566).
Table 28.52 Protein‐free modular feed.
Energy
Sodium Potassium
(kcal) (kJ) CHO (g) Protein (g) Fat (g) (mmol) (mmol)
55 g Maxijul 209 888 52 — — 0.5 0.1

40 mL Calogen 180 756 — — 20 0.1 —
10 g Paediatric Seravit* 30 126 7.5 — — 0.1 0.1
25 mL Normasol 3.9
5 mL KCl solution (2 mmol/mL) 10.0
Plus water to 600 mL
Total 419 1770 61 — 20 4.6 10.2
Per 100 mL 70 295 10.2 — 3.3 0.8 1.7
* The dose of Paediatric Seravit is adjusted according to normal recommendations [205] taking into account the amount provided by infant formula (i.e.
the protein source).
Sodium and potassium per 100 mL is similar to standard infant formula.
Diet in Childhood 569
Infant feeding finger foods during the first year. The first solids given are
protein‐free such as fruit or low protein vegetable purées
Breastmilk or a whey‐based infant formula should provide the (Table 28.50) or very low protein manufactured foods such
main protein source for infants. Some centres choose to pro- as Aminex rusk and Promin low protein pasta meal that are
vide some of the daily protein allowance as EAA for UCD available on ACBS prescription, or commercial baby foods
infants or precursor‐free amino acids for MMA/PA/IVA containing <0.5 g protein/100 g (predominantly fruit purées),
infants; this will be discussed in the disorder‐specific sections. so, if refused, the total protein intake is not affected. Once
Breastmilk has many immunological and nutritional ben- these are accepted, protein‐containing solids are introduced
efits. In the normal population breastfed babies produce sig- from either commercial baby foods or homemade foods such
nificantly less propionic acid compared with formula‐fed as potato, vegetables or cereals. Protein exchanges should be
babies [213], so theoretically breastfed infants with MMA or gradually introduced, and intake carefully monitored to
PA may have the additional benefit of reduced gut propion- ensure adequate is being provided at all times from a combi-
ate production. Despite only a few published reports of BF in nation of feed and food and thus avoid risk of protein defi-
babies with UCD and OAA [214–216], demand BF can be ciency. It is best to have a flexible approach as to when the
successful provided there is regular monitoring of growth protein food should be given; some infants may take this
and metabolic status. BF can be difficult to establish in a best before (if not too hungry) or between feeds. One gram of
baby who has been sick and not breastfed for several days; protein from infant formula is replaced by 1 g of protein from
mothers need support and encouragement to express. They solids. This is less easy to regulate in the breastfed infant as
may feel anxious about not knowing how much protein the the protein intake is not known. Therefore, an aim for total
breastmilk is providing. If demand BF provides too much protein intake (usually the safe level of protein intake) is set;
protein, this can be reduced by supplementary protein‐free each breastfeed will then equate to an amount of protein, e.g.
bottle feeding before some or all breastfeeds. The volume of one feed = 2 g protein, and as the protein exchanges from
protein‐free infant formula to give before breastfeeds can be solids are introduced, the number of breastfeeds is reduced
calculated: (daily fluid requirements) − (volume of breast- to compensate.
milk to provide prescribed amount of protein) = volume of It is important to ensure that an adequate energy intake is
specialised infant formula required. provided by exchanges and free foods; otherwise breast-
feeds will not be reduced sufficiently; each 1 g protein from
For example, for a 4 kg infant, age 1 month: breastmilk provides around 52 kcal (217 kJ). The energy con-
Total daily fluid requirements = 170 mL/kg/day; safe level tent of protein exchanges can be increased by adding butter
of protein intake = 1.77 g/kg/day (Table 28.47) = 7 g or margarine to savoury foods. In both the bottle and breast-
protein/day fed infant, this process of introduction of solids is continued
Daily fluid requirements = 680–540 mL breastmilk (1.3 g throughout the first year of life or so and is dictated by what
protein/100 mL = 7 g protein) = 140 mL protein-free the infant can manage, until all the protein is provided by
infant formula given as 35 mL before four breastfeeds solid food. Ideally the protein exchanges should be evenly
If a whey‐based infant formula is used, the volume is distributed between main meals. During this changeover
adjusted to provide at least the safe level of protein intake period, it is important to ensure that vitamin and mineral
for age, or more if clinically indicated, and combined with a intake is adequate, the supplement being introduced or
protein‐free infant formula (Table 28.51). If not available, a increased with the progressive change to solids, as these
modular low protein feed that is similar in composition foods are a poorer source of micronutrients than infant for-
to standard infant formula, but protein‐free, can be used mula and breastmilk.
(Table 28.52); this is more complex for parents. Several Some patients never progress onto solids or take very
nutritional companies (e.g. Abbott, Mead Johnson, MetaX, small amounts because of feeding difficulties. This is dis-
Milupa, Nutricia) produce protein‐free infant formulas, but cussed in more detail in disorder‐specific sections. If precur-
only Energivit (Nutricia) is available in the UK. The protein‐ sor‐free l‐amino acids form part of the diet, progression to a
free formula can be either mixed with the standard formula product suitable for older infants or children is appropriate.
or given on demand after each protein feed. It is useful to If the infant does not progress onto solid foods, then a change
specify a minimum amount the infant should consume. from infant formula to a paediatric enteral feed during early
Dietary management of GA1 differs. The amount of natu- childhood is indicated to provide the base (and protein
ral protein from breastfeeds or standard infant formula is source) of a low protein feed. This may be an oral or tube
based on lysine intake and combined with a lysine‐free, low feed or combination of both.
tryptophan infant formula (p. 583).
Introduction of solid foods

Diet in childhood
Normal weaning practices are followed, starting at the usual Throughout childhood protein intake is increased to provide
time of around 6 months (26 weeks) of age: solids are intro- around the safe level (Table 28.47) for age or more if clini-
duced at one meal then two and three times per day and the cally indicated. This is given in conjunction with an adequate
infant progresses from smooth purées to lumpier foods and energy, vitamin and mineral intake for age as described
above. It is important to ensure the child consumes a variety Table 28.53 Low protein diet for 6‐year‐old girl.
of LBV protein foods (Table 28.48). HBV foods, if the daily
protein intake allows, can provide some protein (Table 28.49). Very low protein foods such as fruits and some vegetables are allowed
freely and not counted as part of the daily protein intake.
Choices could include thin sliced meats (ham, chicken or
turkey), fish in oil, cheeses (processed cheese triangles, Weight = 18 kg, to provide safe protein intake = 0.89 g protein/kg
(16 g protein)
cream cheese), hot dog sausages, fish fingers, Quorn prod-
ucts, eggs, fromage frais and yoghurt (choosing the highest
Protein (g)
energy varieties) and custard‐style desserts. If the daily pro- (using 1 g protein exchanges)
tein allowance as food is not all eaten, it should be replaced
with fluids; a measured volume of cow’s milk with added Breakfast
glucose polymer to 15%–20% final CHO concentration is 20 g Cornflakes and sugar 2
often the simplest way to do this. Some children are poor
Protein‐free milk*
eaters and will not achieve an adequate energy intake from
the diet. Some ideas to help are: Potato waffle (weight will vary) 1
Mid‐morning
• frying foods, adding butter, margarine, vegetable oil, Biscuit, crisps, cake 2
mayonnaise or double cream (1 g protein and 270 kcal Packed lunch
[1.1 MJ] per 60 mL) to savoury foods such as pasta, rice or
2 thin slices bread 4
potato
• adding sugar, glucose polymer or double cream to Butter or margarine
desserts Lettuce, tomato, cucumber and
• high CHO drinks (>10% concentration) or adding glu- mayonnaise
cose polymer to drinks to a final concentration of 15%– Violife cheese 0
25% CHO, depending on age 40 g fromage frais 2
• low protein crisps, e.g. cassava snacks, prawn crackers,
Portion fresh fruit
corn curls
• very low protein milks, e.g. Prozero, SnoPro, can be used to Evening meal
make milkshakes and desserts and can be poured onto 105 g cooked rice fried with chopped 3
breakfast cereals onion, garlic, tomato, green beans
40 g sweetcorn 1
Table 28.53 provides an example of a low protein diet.
30 g ice cream 1
Tinned fruit in syrup
Feeding problems and tube feeding
Bedtime
Some children with UCD [199, 217, 218] and OAA [206, Protein‐free milkshake*
219, 220] have extensive feeding difficulties, and tube feed-
ing is necessary to maintain metabolic stability and pro- Energy supplements: A daily dose of glucose polymer and/or fat
emulsion may be necessary if insufficient energy is provided by the diet.
mote normal growth, which can be difficult. Feeding issues
may be due to neurological impairment, poor appetite, Low protein special foods: Can provide extra energy and variety in the
slow feeding and food refusal, vomiting, retching, GOR diet as necessary.
and biochemical instability. Some of these problems can be Vitamin and mineral supplement: e.g. 1 sachet of FruitiVits or 25 g
present from diagnosis or be acquired, particularly during Paediatric Seravit is recommended for this age, but a lower dose may
provide an adequate intake depending on vitamins and minerals
episodes of metabolic decompensation. Poor appetite, lim-
provided by the diet.
ited food variety and lengthy mealtimes have been reported
as the main feeding problems identified by caregivers of * Protein‐free milk alternatives, e.g. ProZero, SnoPro, Loprofin Drink.
children with OAA and UCD [221]. This pilot study also
identified inadequate attention to the social aspects of eat-
ing as a key issue, with most children regularly eating with other single ingredients added to meet normal energy
alone. Involvement of a speech and language therapist and and nutrient requirements: glucose polymer, fat emulsions,
a psychologist at an early stage may help manage some vitamins, minerals and electrolytes. Alternatively, a protein‐
feeding and behavioural problems. Issues to consider free feed such as Basecal, which is a similar composition to
when feeding different age groups of children with PKU paediatric feeds but protein‐free, can be used and is easier
are provided in Table 28.20 and some of these suggestions for parents and helps ensure overall nutritional adequacy
may be useful. [206, 222]. It is important to ensure adequate fluids and fibre
If tube feeding is necessary, a low protein modular feed is are given (using a paediatric feed containing fibre or adding
designed to meet the specific therapeutic dietary needs of a fibre supplement to the feed). Some children have increased
the child’s disorder. A measured volume of a standard pae- fluid requirements, including those with GA1 who have
diatric feed is used to provide the prescribed protein intake, increased muscle tone or those with MMA and CKD. The
Feeding Problems and Tube Feeding 571
additional fluid is given as water, either between feeds or that parents and caregivers have adequate training in safety
extra water with tube feed flushes; this is often better toler- aspects of home enteral feeding and regular training updates
ated than adding to the feed volume. Examples of low pro- as incorrect practices may increase a child’s risk of meta-
tein feeds are shown in Tables 28.54 and 28.55. Gastrostomy bolic decompensation [221]. PEG‐J (percutaneous endoscopic
feeding is recommended in preference to NG feeding for gastro‐jejunostomy) feeding is a useful option for those with
children who require long‐term tube feeding. It is important ongoing vomiting problems.
Table 28.54 Low protein tube feed for a 4‐year‐old girl.

Weight = 15 kg
Energy
(kcal) (kJ) CHO (g) Protein (g) Fat (g) Sodium (mmol) Potassium (mmol)
550 mL PaediaSure 556 2335 60 15.4 27.5 14.3 15.4

120 g Maxijul 456 1915 114 – –
60 mL Calogen 270 1134 – – 30.0 0.2 –
5 g Paediatric Seravit 24 102 6.0 – – – –
16 mL NaCl (1 mmol/mL) 16
8 mL KCl solution (2 mmol/mL) 16.0
Total 1306 5486 180 15.4 57.5 32 31.6
Per 100 mL 108 457 15 1.3 4.8 2.7 2.6
Per kg 87 365 1.0 2.1 2.1
Energy requirement per kg* 85 357 12–30 15–28
1275/day 5.3 MJ/day
Safe level of protein intake† 0.86 g/kg/day
Energy % 55 5 40
Electrolytes, vitamins and minerals need to be individually determined considering any additional intake from food or medicines.
†
FAO/WHO/UNU safe level of protein intake (Table 28.47).
Table 28.55 Low protein tube feed for a 10‐year‐old boy.

Weight = 32 kg
Energy
(kcal) (kJ) CHO (g) Protein (g) Fat (g) Sodium (mmol) Potassium (mmol)
1040 mL Nutrini 1040 4368 128 29 46 27 29

215 g Basecal (5 sachets) 1000 4195 150 – 44.5 18 25
Total 2040 8563 278 29 90.5 45 54
Per 100 mL 113 475 15.4 1.6 5 2.5 3
Per kg 64 268 0.91
Energy requirement per kg* 64 270 15–50 24–50
2030/day 8.5 MJ/day
Safe level of protein intake† 0.91 g/kg/day
Energy % 54 6 40

†
FAO/WHO/UNU safe level of protein intake (Table 28.47).
Disorders of propionate metabolism: methylmalonic acidaemia (MMA)

and propionic acidaemia (PA)
Enzyme MMA – methylmalonyl‐CoA mutase‐apoenzyme or its cofactor 5‐deoxyadenosylcobalamin (vitamin B12)

PA – propionyl‐CoA carboxylase
Biochemical defect Defects in the final steps of the catabolic pathways of the four EAA isoleucine, valine, threonine and methionine. Cholesterol
side chain and thymine and uracil metabolism are also affected but are of lesser significance (Figure 28.8):
• PA results from mutations in the PCCA or PCCB genes encoding the α‐ and β‐subunits, respectively, of propionyl‐CoA
carboxylase, a biotin‐dependent enzyme which catalyses the conversion of propionyl‐CoA to D‐methylmalonyl‐CoA.
Metabolites increased include high plasma propionylcarnitine, glycine, alanine and urinary methylcitrate and 3‐
hydroxypropionate [223].
• MMA results from mutations in either the MUT locus encoding the methylmalonyl‐CoA mutase‐apoenzyme causing low to
moderate (mut−) or absent (mut°) activity or one of the proteins involved in the synthesis of its active cofactor
adenosylcobalamin, classified as cobalamin (cbl) A, B, D (variant 2, which is very rare) deficiency. The conversion of
methylmalonyl‐CoA to succinyl‐CoA (for entry into the Krebs cycle) is impaired, so methylmalonyl‐CoA accumulates with
greatly increased amounts of methylmalonic acid in plasma and urine. The compounds found in propionic acidaemia also
accumulate (as above) [223].
Propionate (in the form of propionyl‐CoA) is formed from three main sources, not just from amino acid catabolism,
approximately:
• 50% from the catabolism of the precursor amino acids isoleucine, valine, threonine and methionine [224]
• 25% from anaerobic bacterial fermentation in the gut [224]
• 25% from the oxidation of odd‐numbered long chain fatty acids (C15 and C17) [225] and other metabolites. These odd‐
chain fatty acids are synthesised by the normal pathway of fatty acid synthesis, but propionyl‐CoA acts as the primer
instead of acetyl‐CoA – hence the additional odd number of carbons in the chain [226]
Newborn screening No newborn screening in the UK. The impact and clinical benefits of screening in other countries continue to be discussed
[227, 228].
Isoleucine, threonine, methionine and valine

Precursors Odd-chain fatty acids
of propionyl-CoA Side chain of cholesterol
Gut bacteria
Thymine, uracil
Propionate
Propionyl-CoA Propionic acid

3-Hydroxypropionate
Methylcitrate
Alternative metabolites formed
1 Propionylglycine
Propionylcarnitine
Tiglylglycine
D-Methylmalonyl-CoA
L-Methylmalonyl-CoA
Succinyl-CoA (TCA cycle)
1 Propionic acidaemia due to deficiency of propionyl-CoA carboxylase, a biotin dependent

enzyme
2 Methylmalonic acidaemia due to deficiency of Methylmalonyl-CoA mutase, an adenosylcobalamin
dependent reaction
Figure 28.8 Disorders of propionate metabolism.

Disorders of Propionate Metabolism 573
Clinical onset Patients can present at any age with acute or chronic symptom, but usually in the neonatal period: 65% PA, 48% MMA [229].
presentation, features Common biochemical and clinical features occur due to accumulation of propionyl‐CoA and other metabolites:
• early‐onset form: acute deterioration with poor feeding, vomiting, lethargy, hypo‐ or hypertonia and dehydration that can
progress to coma and death if untreated; biochemical findings include a severe metabolic acidosis with elevated anion gap
(although not always) [228, 230], ketoacidosis, lactic acidosis and hyperammonaemia
• late‐onset form: later in infancy or childhood with less severe symptoms including failure to thrive and developmental
delay, recurrent vomiting, ketoacidosis, acute metabolic decompensation; a movement disorder may also develop [223]
Long‐term Outcome varies widely – The mechanisms of toxicity are complex and not completely understood; for detailed reviews of the
complications and pathophysiology, refer to Kölker et al. [231] and Haijes et al. [232]. Accumulating toxic metabolites and mitochondrial
outcome impairment are considered causative factors. Survival rates have improved in the last decade, but early deaths still occur
[220, 233, 234]. Early onset is associated with poorer outcome. Outcome in MMA is best predicted by vitamin B12
responsiveness, enzymatic subgroup, age at onset and birth decade. Mut° and cblB patients have the poorest outcome,
mut− and vitamin B12 responsive patients have a much better long‐term outcome, although they remain at risk of metabolic
decompensation and long‐term complications such as CKD [233, 234].
Multiple body systems – Can be affected in both disorders even with current treatment strategies. Recognised complications
include acute injury of the basal ganglia (known as metabolic stroke) causing mental and motor retardation and movement
disorders, epilepsy (more prevalent in PA), cardiomyopathy [235] and long QT syndrome (more prominently in PA) [236],
pancreatitis [237], optic nerve atrophy [238], immune dysfunction, recurrent infections and pancytopenia and CKD (in MMA)
[239, 240]. These complications may arise during episodes of metabolic decompensation and/or are due to a more chronic
deterioration of organ function [241].
IQ/developmental outcomes – Range from normal to significant intellectual disability in both disorders [233, 234, 241]. In PA
the frequency of metabolic crises is reported to be negatively correlated with IQ [220].
Faltering growth is common – The causative factors are likely to be multifactorial and remain to be fully elucidated [220,
234]. Early‐onset and progressive growth retardation is seen in PA [220]. Growth retardation is also reported in MMA [211,
241]; CKD may be one of the contributing factors as this is a feature of CKD per se [242]. Failure to thrive is reported as more
common in MMA mut° patients than the other enzymatic subgroups [233].
Acute management The newly diagnosed patient may be very sick, with a severe metabolic acidosis (with increased anion gap), ketoacidosis,
lactic acidosis and hyperammonaemia in intensive care requiring ventilation and extracorporeal detoxification (to remove
ammonia and toxic compounds). Protein intake is stopped, and IV glucose (at least 10%) is given to reverse catabolism and is
a crucial part of the initial management to help stabilise the child (p. 567), [241].
Medical treatment Pharmacotherapy
Treated with some or all of these medications:
• l‐Carnitine 100 mg/kg/day – conjugates with propionic acid to form propionylcarnitine and increases its excretion in urine.
A lower carnitine dose may be given in MMA patients who have deteriorating kidney function and have high plasma
concentrations of propionylcarnitine.
• Sodium benzoate – for treatment of hyperammonaemia.
• Vitamin B12 – pharmacological doses by intramuscular (IM) injection are given routinely to MMA B12 responsive patients.
• Sodium bicarbonate – to correct any acidosis in MMA.
• Carglumic acid (N‐carbamylglutamate) – for treatment of hyperammonaemia during acute decompensations. Carglumic
acid combined with nitrogen scavengers is reported as more effective in reducing plasma ammonia concentrations [243].
It may also be used in long term management.
• Metronidazole (antibiotic) – to suppress gut production of propionate [244]. It is usually given intermittently, but
administration between centres varies. Its clinical efficacy has never been proven in randomised controlled trials.
Metronidazole is not used by all centres routinely.
• Additional medicines are given to treat specific complications such as CKD in MMA, or in PA‐related cardiomyopathy,
CoQ10 supplementation may help [245].
Transplantation
Liver transplant in PA and in MMA, kidney, liver or combined liver and kidney transplants [246–248]; however, these are
associated with significant risk at the time of transplant. Peri‐ and post‐operative planning of nutritional management is
crucial to avoid catabolism and possible metabolic decompensation [249]. Liver transplant is not a cure, but minimises risk of
further decompensation and improves quality of life [241]; however metabolic complications may still arise, such as
metabolic stroke [250]. With liver transplant some relaxation of protein is possible, but patients still have increased
concentrations of plasma organic acids; ongoing close monitoring of diet is essential [249–251]. MMA children with kidney
transplant need to remain on a low protein diet.
Dietetic management The main aim is to reduce production of the toxic organic acids by:
• restriction of precursor amino acids (isoleucine, valine, threonine and methionine) by limiting natural protein intake
• avoidance of fasting to limit lipolysis and thus the oxidation of odd‐chain fatty acids with release of propionyl‐CoA
• provision of an adequate energy intake to limit catabolism
Parenteral nutrition should be administered when enteral protein is not tolerated at diagnosis, episodes of pancreatitis,
intolerance of enteral feeds
Monitoring Biochemical, nutritional and anthropometric monitoring are essential for optimisation of medical and dietetic management.
These are described in detail (p. 577).
Emergency regimen • During intercurrent illnesses or episodes of vomiting and GOR with intolerance of enteral feeds, patients become catabolic
and are at risk of developing metabolic decompensation
• Standard emergency regimen (ER) (p. 673) and/or IV fluids (10% glucose and electrolytes) are given; the usual medicines
are continued (or increased) to help prevent decompensation (www.bimdg.org)
Clinical management Baumgartner et al. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidaemia [241].
guideline Reid Sutton et al. Chronic management and health supervision of individuals with propionic acidaemia [252].
Chapman et al. Acute management of propionic acidaemia [253].
Jurecki et al. Nutrition management guidelines for propionic acidaemia: An evidence and consensus‐based approach [254].
Aldubayan et al. Acute illness protocol for organic acidaemias, methylmalonic and propionic acidaemia [255].
Parent support group www.metabolicsupportuk.org/
Dietary management acids (isoleucine and valine) are prescribed by some centres
to correct low plasma levels [256, 258]; it seems ironic to have
Low protein diet to supplement the amino acids that cannot be catabolised.
The 2014 MMA/PA guideline [241] advises PFAA should
The precursor amino acids (isoleucine, valine, threonine and form part of the total protein intake if natural protein toler-
methionine) do not accumulate in plasma so it is not possible ance is below 2007 FAO/WHO/UNU safe levels of protein
to use measurement of their plasma levels to determine the intake [8], making up any deficit. The 2019 PA guideline
intake of natural protein. Treatment is to limit dietary pro- from the USA [254] recommends for individuals tolerating
tein intake to around the safe level of protein for age (g/kg/ <100% of the dietary reference intake from intact protein to
day) (Table 28.47). Dietary protein is increased according to consider adding PROP medical food (i.e. PFAA) to meet
age, weight, clinical condition and quantitative plasma 100%–120% of total protein requirement.
amino acid concentrations. However, it can be difficult to Metabolic balance can be achieved without PFAA; they
achieve a balance between provision of sufficient protein are unpalatable and can be difficult to administer to children
and avoiding an excess of protein that may precipitate meta- unless they are tube fed. If used, the amount prescribed
bolic decompensation. Too low a protein intake can have should provide only part of the total protein intake and be
serious effects, such as poor growth, skin rashes, hair loss, based on growth and biochemical parameters, including
vomiting and metabolic decompensation [202–204, 241]. protein status such as plasma amino acids. Dietary intakes of
Practical aspects of provision of low protein diets and feeds isoleucine, valine, threonine and methionine should be cal-
have been discussed (p. 560). culated and compared to FAO/WHO/UNU [8] require-
ments to avoid deficiency states. Leucine intake should also
Precursor-free amino acids be calculated to avoid a high ratio of leucine to other large
neutral amino acids that could cause imbalance.
Some centres provide part of the total protein intake from PFAA supplements are available as infant formula, drink
precursor‐free l‐amino acid (PFAA) supplements (no mixes, gels or pure amino acids designed for different ages.
methionine, threonine, valine, isoleucine) to further reduce For details of presentation, composition, age suitability and
their intake from natural protein in an effort to improve met- preparation, refer to the manufacturers’ websites: www.
abolic stability, improve the quality of the low protein diet or nutricia.co.uk, www.vitaflo.co.uk. Similar products are
achieve protein requirements. This appears to be a more available outside the UK (www.abbottnutrition.com, www.
common practice in some central European metabolic cen- meadjohnson.com, www.milupa‐metabolics.com).
tres [200, 256, 257] and the USA [258] but is seldom used in
UK centres. Prescription of PFAA supplements is highly var-
iable and may provide up to 40%–50% of total protein intake Avoidance of fasting
[220, 256, 259]. However, the clinical value of PFAA remains It is recommended that long fasts are avoided to limit the
controversial. A retrospective review of MMA/PA (137 production of propionyl‐CoA from the oxidation of odd‐
patients) [219] concluded that PFAA supplementation did numbered long chain fats [225]. Mobilisation of fatty acids
not seem to have an important role in the long‐term nutri- can be suppressed by regular 3–4 hourly daytime feeding
tional and developmental outcome. Concerns have been and overnight tube feeding. Currently, overnight tube feed-
raised about the high leucine content of PFAA [258]; cross‐ ing is not used universally although many do receive this
sectional data on 61 patients with MMA identified iatrogenic because of feeding problems.
amino acids deficiencies (low plasma isoleucine and valine)
and poor growth outcomes attributable to increased leucine
Energy requirements
intake. Data from the E‐IMD registry on 250 MMA/PA
patients [256] also identified low plasma valine and isoleu- Resting energy expenditure (REE) is reported to be decreased
cine levels mainly in those receiving PFAA and related this in some patients when they are well [260]; however, others
with the high leucine content of these products. Single amino have described no difference between predicted and reported
REE [261]. Standard predictive equations of REE may not be Dietary manipulations
a good guide to energy requirements in children with MMA
The low protein diet used for MMA is also appropriate die-
as they can have an altered body composition (increased fat
tary treatment for CKD:
mass, reduced fat‐free mass) and decreased renal function,
which are both known to affect REE [262]. • Increased fluids are needed to prevent dehydration. The
amount given is determined by kidney losses, blood
pressure, blood urea and electrolytes. Additional water
MMA B12 responsive patients
is given separate from the feed to ensure the full volume
Vitamin B12 (as hydroxycobalamin) is given as an IM injection of feed is delivered. In our experience families find it
or, rarely, as an oral supplement. The dose frequency is indi- easier to give water flushes between feeds rather than
vidualized. In a cohort of 11 patients from the author’s centre, adding extra fluid to the feed.
this ranged from every 1–7 days (median 2 days) [263]. On • Phosphate, calcium and vitamin D. Renal bone disease is
treatment, urine and plasma methylmalonic acid decreases to complex and begins even in the milder stages of CKD,
low but not normal concentrations. Some urinary methyl- seen biochemically as a rise in parathyroid hormone
malonic acid (UMMA) is still produced; concentrations vary (PTH). Renal bone disease is managed by a combination
between patients and may typically range from 200 to of medicines and diet:
900 μmol/mmol creatinine (normal 0–30 μmol/mmol) that is ◦◦ vitamin D analogues, e.g. 1α‐hydroxycholecalciferol
significantly less than non‐responsive patients where concen- (alfacalcidol) to increase calcium absorption from
trations can be >20 000 μmol/mmol creatinine. Horster et al. the gut
describe no kidney disease (creatinine clearance <60 mL/ ◦◦ if plasma phosphate is increased, dietary phosphate
min/1.73 m2 with UMMA excretion <2000 μmol/mmol creati- is restricted, although intakes may already be low
nine [233]). Plasma methylmalonate (PMMA) is also much because patients are on tube feeds or do not eat high
lower in B12 responsive compared with non‐responsive phosphate foods because of protein restriction.
patients. In the author’s cohort of 11 patients, PMMA ranged Phosphate binders are given to lower plasma phos-
from 4 to 482 μmol/L (median 44 μmol/L), normal phate, either calcium‐based (e.g. calcium carbonate)
0–0.29 μmol/L [263]. Concentrations of PMMA increase with or a calcium‐free binder if there is hypercalcaemia
loss of kidney function. Dietary treatment with a low protein (e.g. sevelamer hydrochloride)
diet and ER is the same as for B12 non‐responsive patients, • In children with CKD (non‐MMA), it is suggested that
although a more generous protein allowance may be possible. total calcium intake from nutritional sources and phos-
phate binders be in the range of 100%–200% of DRI for
Complications of methylmalonic acidaemia calcium for age (p. 253).
• Electrolytes
and propionic acidaemia
◦◦ Supplements of sodium bicarbonate are often needed
both to replace sodium losses and reduce acidosis.
MMA and chronic kidney disease
◦◦ If blood pressure is raised, dietary sodium intake may
Impaired renal function is a common complication in B12 need to be reduced.
non‐responsive MMA, manifesting initially with a defect of ◦◦ Hyperkalaemia is not usually a problem until the end
urinary concentrating and acidification ability due to renal stages of kidney disease when potassium intake may
tubular dysfunction [264]. Glomerular failure can develop at need to be reduced.
an early age with progression to chronic and then end‐stage • Vitamin A can accumulate in serum in CKD, and this
renal failure (ESRF) during childhood or adolescence [233, may be linked to hypercalcaemia [267]. In the UK a prac-
240, 265]. Deterioration of kidney function is likely to be tice guideline suggests that vitamin A intake in CKD
multifactorial with methylmalonic acid itself considered (non‐MMA) should be less than twice the RNI; however,
nephrotoxic [266]. Development of CKD correlates with uri- recent work suggests even this amount may be too high
nary MMA excretion, manifesting earlier in those with high- [268]. In MMA vitamin A intake should be assessed, par-
est mean MMA concentrations [233] and in those with mut° ticularly the contribution from vitamin and mineral
or cobalamin B [234]. Kidney function can deteriorate mark- supplements and any precursor free amino acid supple-
edly during episodes of dehydration, which can be caused ments. Intake of vitamin A around the RNI seems sensible,
by GI complications such as vomiting and GOR, inadequate but this may need to be reduced if plasma concentra-
fluid intake, repeated illness and metabolic decompensations are raised.
tions. At the author’s centre the glomerular filtration rate is • Anaemia is a chronic complication of CKD and is
measured by the IOHEXOL method, 1–2 yearly from age 2 treated with iron supplements and injections of eryth-
years in MMA patients. The management of MMA and CKD ropoiesis stimulating agents: erythropoietin β or darbe-
(undertaken jointly with nephrologists) can be particularly poetin α. It is important to ensure adequate iron is
challenging and involves ongoing modification of nutrient provided from the low protein diet (most likely to be
intakes, fluids and medicines based on biochemical monitor- provided from a combination of feeds and vitamin and
ing results and clinical symptoms. mineral supplements).
Haemodialysis or peritoneal dialysis can result in sympto- the type of foods that they will eat. Some are difficult feed-
matic and biochemical improvement, with fewer episodes of ers; parents complain of children being slow, fussy, retching
metabolic decompensation [239, 269–271]. On dialysis the or self‐inducing vomiting. Children with MMA have a pref-
dietary restrictions remain necessary and are modified erence for salty foods, e.g. crisps, tomato ketchup, chips and
according to biochemical results; protein intake may be salt, and may select these to compensate for increased uri-
slightly increased compared with intake pre‐dialysis. nary losses of sodium.
Glucose absorbed from the perotineal dialysis fluid contrib- Achieving optimal growth in MMA and PA can be diffi-
utes to the daily energy intake and should be taken into con- cult and although considered to be attributable to the low
sidered when assessing energy intake (p. 258). protein diet, other factors may also contribute. Enteral feed-
ing via gastrostomy (particularly if there is vomiting) or NG
tube is essential to provide an adequate dietary intake, to
Kidney transplant
prevent metabolic decompensation and to help the parents
Peri‐ and post‐operative planning of nutrition is crucial to cope with a child who is difficult to feed. In the author’s
avoid complications of catabolism and metabolic decompen- centre 12 of 14 patients with B12 non‐responsive MMA had
sation. Haemodialysis is performed pre‐kidney transplant to feeding problems, and 11 required long‐term tube feeding;
improve biochemical parameters. IV fluids, at least 10% glu- feeding problems were much less common in MMA B12
cose, are given during surgery. Post‐transplant the child’s responsive patients, and only 1 was tube fed [272]. In a
usual enteral feeds and protein intake can normally be intro- European cohort, gastrostomy feeding was necessary in 27
duced immediately in the first few days based on clinical of 55 patients with PA to ensure growth and metabolic sta-
progress. PN may be used by some centres, initially. MMA bility [220]. European surveys of dietary practices in PA
children need to remain on a low protein diet. report 63% (117/186) [200] and in MMA 42% (90/215)
patients [273] were tube fed. Early insertion of a gastros-
tomy in infants and young children has been recommended
Gastrointestinal problems
[252]. A PEG with a jejunal extension tube (PEG‐J) can also
Gastro‐oesophageal reflux, recurrent vomiting and retching be helpful in the management of episodes of vomiting and
are common in MMA B12 non‐responsive patients and often pancreatitis.
necessitate hospital admission. In the author’s cohort, 7 of 14
patients had GI symptoms; all were treated with anti‐reflux
Pancreatitis
medicines, and additionally a continuous overnight feed
with slow daytime bolus feeds given via an enteral feeding Pancreatitis is a recognised complication of both MMA and
pump was beneficial [272]. A hydrolysed protein feed helped PA and may be either a single acute episode or recurrent
some with GI symptoms, including diarrhoea. acute episodes [220, 234, 237]. In some cases it is associated
Constipation is a problem observed in some, particularly with an intercurrent illness. The pathophysiology of pancre-
in patients with PA. Maintenance of gut motility to prevent atitis is not clear. The child’s usual dietary restrictions should
constipation is important as it may reduce propionate pro- continue irrespective of the feeding intervention used to
duction. In a small study of four children, Senokot (vegeta- treat pancreatitis. A period of PN (in mild and severe) is
ble laxative) was reported to be biochemically beneficial and likely to be needed. Alternatively NG/gastrostomy/jejunal
to increase transit time [257]. Guidelines recommend that feeds may be possible. A standard parenteral amino acid
constipation should be treated promptly [241], and laxatives solution such as Vaminolact or Vamin can be used but should
have been recommended for PA [252]. Movicol is the laxative only provide the desired amount of protein (amino acids g/
of choice at the author’s centre. Adequate fluids and feeds kg/day). However, in severe pancreatitis additional protein
containing fibre (in tube fed patients) may also help prevent may be needed as protein catabolism can be substantial in
constipation. Probiotics may be useful to restore and balance response to the severe inflammation and, thus, increase
intestinal flora [241, 254], but evidence to support this in requirements [274]. Further details about the dietetic man-
MMA and PA is lacking. agement of pancreatitis can be found on p. 186.
Feeding problems and tube feeding Emergency regimens for management

Anorexia and feeding problems of varying degrees are of intercurrent illness
almost invariably present in children with more severe dis-
orders. Feeding problems can be present at diagnosis and During intercurrent illnesses or episodes of vomiting and
may not improve with treatment. Food and fluid refusal can GOR with intolerance of enteral feeds (common in some),
be acquired during the course of the disease and is frequently patients are at risk of developing metabolic decompensation.
associated with repeated intercurrent infections. The causa- Development of new neurological signs, including meta-
tive factors of feeding problems are unclear, but increased bolic stroke, are reported following episodes of acute meta-
plasma propionate is a possibility. Many children have a bolic decompensation [220, 275]. In MMA there is the added
poor appetite for solid foods. Some will only eat a few risk of dehydration and deterioration of kidney function. To
selected foods in very small amounts, occasionally changing help prevent catabolism and metabolic decompensation, the
standard ER (p. 673) and extra fluid are given, and usual on p. 678. Continuation of an adequate energy intake is
medicines are continued (e.g. carnitine, sodium bicarbo- important throughout this period.
nate); doses may be increased and additional medicines
given if ammonia levels are high. It is important to treat
pyrexia. If the child is vomiting at home and the full volume Emergency regimen – fluid recommendations
of ER is not able to be administered or tolerated, the child
should be admitted to hospital without delay, because of risk In MMA a generous fluid intake needs to be given to prevent
of metabolic acidosis, for treatment with IV fluids (10% glu- dehydration and deterioration of kidney function. The ER
cose and electrolytes) (www.bimdg.org). The usual protein should provide the child’s usual maintenance fluid intake
intake is stopped for the minimum time possible to prevent and more (this needs to be assessed on an individual basis
protein deficiency, which could greatly exacerbate the effects taking into account the child’s kidney function); 24 hour con-
of illness. Protein is normally reintroduced early (within tinuous tube feeds are suggested to administer the full fluid
24–48 hours) and over a period of 1–2 days depending intake. The usual dose of sodium bicarbonate may need to
on biochemical results (such as ammonia, blood pH and be increased. For IV fluids the BIMDG emergency protocols
gas, bicarbonate, ketones) and the clinical condition of the suggest that 120% maintenance fluids are given. If a child
child. Obviously, a more rapid reintroduction of protein is becomes dehydrated, more fluids will be needed, the daily
beneficial. Practical advice on protein reintroduction is given amount usually guided the nephrologist.
Table 28.56 Routine biochemical monitoring in methylmalonic acidaemia and propionic acidaemia.
Blood Comments
Quantitative plasma amino acids Glycine is usually increased

Alanine is generally increased if lactate is increased
If precursor amino acids or or other essential amino acids are low, consider
increasing natural protein
Plasma acylcarnitines Propionyl carnitine is increased
Higher concentrations are seen in MMA as kidney disease progresses
Other acylcarnitines can also be increased, e.g. free carnitine, acetyl carnitine
Plasma methylmalonate (MMA only) Increases to higher concentrations as kidney function deteriorates in MMA
Urea, creatinine and electrolytes Urea is often low on a restricted protein diet
Urea and creatinine increase as kidney function deteriorates in MMA
Full blood count May have neutropenia, particularly during illness
Blood gas, bicarbonate Possible metabolic acidosis
Ammonia May be raised
Lactate May be raised
Urate May be raised, treated with allopurinol
Amylase and lipase Will be raised during episodes of pancreatitis
GSH, GSSG Not routinely measured in all centres, a measure of oxidative stress
GSSG oxidised and reduced Concentrations can be low [276]
MMA only – urine monitoring
Urine MMA/creatinine μmol/mmol Much lower concentrations in B12 responsive MMA
Urine methylcitrate/creatinine μmol/mmol Much lower concentrations in B12 responsive MMA
MMA only – to monitor kidney function
PTH, vitamin D, calcium, phosphate, alkaline phosphatase To monitor renal bone disease
Ferritin, Hb, TIBC, TSAT To monitor iron status and anaemia of chronic kidney disease
Vitamin A in MMA Can be raised
Lipids – triglycerides and cholesterol Can be raised
Glomerular filtration rate 1–2 yearly from age 2 years, less frequently may be appropriate in B12 responsive MMA
MMA, methylmalonic acidaemia; GSH, glutathione; GSSG, glutathione disulfide; PTH, parathyroid hormone; Hb, haemaglobin; TIBC, total iron‐
binding capacity; TSAT, transferrin saturation.
Parenteral nutrition at age 10 years and follow‐up according to bone health status
[241].
Inadequate nutrition in these disorders leads to catabolism,
making the metabolic disturbance worse. Some patients can
have frequent episodes of vomiting and acidosis and need Learning points: methylmalonic acidaemia and propionic
repeated hospital admissions. If protein reintroduction is acidaemia
often interrupted or delayed or not possible, an early resort
to PN is essential as there is risk of catabolism and deficiency. • Dietary management is a restricted protein diet (further
PN can reverse the catabolic spiral and improve the meta- manipulations of diet and fluids are needed when there is
bolic state. Provision of PN in these disorders is described chronic kidney disease) and emergency regimen for use
p. 567. Placement of a portacath may be considered in any during intercurrent illness
child who has frequent episodes of illness and if their IV • Outcome varies with Mut° and cblB patients having the
access is difficult. However, this needs to be carefully consid- poorest outcome, followed by mut− and cblA
ered because of the risk of line infection precipitating meta- • Vitamin B12 responsive patients have a much better long‐
bolic decompensation [252]. term outcome
• Multiple body systems can be affected with complications
Clinical and biochemical monitoring in MMA including cardiomyopathy, chronic kidney disease, pancre-
and PA atitis and optic nerve atrophy
• Episodes of metabolic decompensation need to be treated
Monitoring of the nutritional aspects of a low protein diet promptly to help prevent further organ damage and neuro-
has been discussed (p. 565). Routine biochemical monitor- logical insult
ing is shown in Table 28.56. Baseline DEXA is recommended
Isovaleric acidaemia
Enzyme Isovaleryl‐CoA dehydrogenase

Biochemical defect Deficiency of isovaleryl‐CoA dehydrogenase, which catalyses the third step of leucine catabolism: the conversion of isovaleryl‐
CoA to 3‐methylcrotonyl‐CoA (Figure 28.3). Isovaleryl‐CoA, isovaleric acid, isovaleryl (C5) carnitine and other metabolites
accumulate. During remission the majority of isovaleryl‐CoA is conjugated to glycine to form isovalerylglycine that is not toxic
and is excreted in large amounts in urine. Similarly isovaleryl‐CoA is also conjugated to carnitine to form isovalerylcarnitine
and excreted in the urine. During acute episodes the natural capacity of this detoxification pathway is exceeded, and
isovaleryl‐CoA is deacylated to produce large amounts of toxic isovaleric acid, which may cause an overwhelming illness
[277]. The mechanism of toxicity is not clear, but accumulating toxic metabolites are known to cause synergistic inhibition of
the TCA cycle and ureagenesis [229].
Genetics Autosomal recessive inherited disorder. Mutations in the IVD gene are highly heterogeneous, and no genotype–phenotype
correlation has been identified [277], except in those diagnosed on newborn screening (NBS) with the c.932C > T mutation,
who have a much milder phenotype [278].
Newborn screening NBS on day 5 of life in the UK. Screening is by measurement of C5 acylcarnitines in dried blood spots using tandem mass
spectrometry. More information on UK screening, diagnostic and clinical management protocols can be found at www.bimdg.
org and www.gov.uk. Newborn blood spot screening: laboratory guide for IMDs (inherited metabolic diseases). Some infants
present clinically before the screening test or the results are reported.
Clinical onset Early‐onset (acute) form: Neonates present within the first days/weeks of life [279], commonly with poor feeding, vomiting,
presentation, metabolic acidosis, hyperammonaemia and lethargy progressing to coma. Their subsequent course follows the chronic
features intermittent course. A characteristic smell of ‘sweaty feet’ may occur when the child is unwell.
Late‐onset (chronic) form: Children may present with more chronic, non‐specific symptoms of failure to thrive and/or
developmental delay or mental retardation. Late onset can also present with vomiting, impaired consciousness and acute
metabolic crises. The spectrum of presentation with chronic forms is wide.
The E‐IMD registry provides detailed information about symptoms seen at the presentation in early‐ and late‐onset patients
with isovaleric acidaemia (IVA) (n = 52) [229].
Long‐term Outcome is variable ranging from normal neurocognitive outcome/psychomotor development and less commonly to severe
complications and mental retardation [279]. Neonatal presentation is associated with high mortality, but those who survive the acute episode
outcome have a better neurocognitive outcome than patients with a late diagnosis [279]. Expanded NBS may improve the mortality of
neonatal onset, provided screening is done early; those with neonatal onset will present within the first week. IVA is not
considered to be a progressive disorder. There are no reported major long‐term complications. Acute pancreatitis is reported in
a few cases both pre‐ and post‐diagnosis. [279, 280]. The author is aware of several other unpublished cases in the UK.
Isovaleric Acidaemia 579
Acute management The newly diagnosed, clinically presenting infant is likely to be very sick with metabolic acidosis (with elevated anion gap),
hyperammonaemia, elevated lactate and urinary ketones and requires intensive care. Initial management to stabilise the infant
is to promote anabolism by giving IV glucose 10% and to reduce production and increase excretion of isovaleric acid by
giving IV carnitine. Protein intake is stopped temporarily.
l‐glycine
and l‐carnitine, either or both, may be prescribed:
• l‐glycine (150–300 mg/kg/day)
• l‐carnitine (50–100 mg/kg/day) [281]
Both conjugate with isovaleric acid producing non‐toxic conjugates (isovalerylglycine, isovalerylcarnitine) that are excreted in
urine; hence isovaleric acid levels are reduced [282–284]. These medicines are particularly important during periods of
metabolic decompensation. The need for both medicines in a stable child is controversial [284–286], and prescribed doses
vary [279]. Medicines should be individually prescribed as response can vary [287, 288].
Dietetic The aim is to minimise the formation of isovaleric acid by:
management • limiting dietary intake of leucine (protein). Leucine does not accumulate in plasma so measurement of this cannot be used
to determine protein intake
• provision of adequate energy intake to prevent catabolism and promote normal growth and development
Mutation c.932C > T is a mild phenotype – protein restriction is not necessary, but an ER for management of illness is
recommended [278].
Monitoring – There is no established laboratory marker for monitoring therapeutic control. Plasma amino acids and carnitine should be
biochemical and monitored at routine clinic reviews. Plasma leucine is normal; it does not accumulate. Plasma glycine is increased in patients
nutritional taking glycine. Isovalerylcarnitine concentrations are increased. Monitoring of the nutritional aspects of a low protein diet has
been discussed (p. 565).
Emergency regimen • During intercurrent infections, catabolism greatly increases production of isovaleric acid with risk of metabolic
for management of decompensation
illness • The standard ER of frequent 2 hourly drinks/feeds of glucose polymer is given day and night to prevent catabolism (p. 673)
• Protein intake is stopped temporarily (24–48 hours)
• Glycine and carnitine continue to be given; doses may be increased temporarily as necessary
• Hospital admission for IV fluids (10% glucose, saline 0.45%) is necessary if ER is not tolerated (www.bimdg.org)
• IV carnitine can be given; no IV glycine preparation exists
• If pancreatitis develops the usual dietary restrictions should continue irrespective of the feeding intervention used to
treat the pancreatitis
• PN may be necessary; alternatively NG or NJ feeds may be possible (see p. 186)
Episodes of metabolic decompensation appear to be less frequent with age [289] with no reported episodes beyond age 9
years in 21 patients [279]. However, the author is aware of episodes in older children in UK metabolic centres.
Clinical Currently there are no published consensus treatment guidelines for IVA.
management European proposed guidelines using SIGN methodology for IVA can be accessed from E‐IMD [290]
guideline
Parent support Metabolic Support UK www.metabolicsupportuk.org
group
Practical aspects
Dietary management
• Practical management of low protein diets and feeds is
A European survey [201] of 133 patients from 38 centres described on p. 560
reports that dietary management varies and natural pro- • Natural protein should be limited, but to provide at
tein intake does not always provide the FAO/WHO/UNU least the FAO/WHO/UNU 2007 safe intake of protein
safe level of protein intake [8]. Leucine‐free l‐amino acid for age [8, 290]. A more relaxed protein intake than this
(LFAA) supplements were prescribed by 18 centres (none is often possible (around 2 g/kg in infants and young
from UK). The data was collected prior to the E‐IMD web‐ children, decreasing to between 1.5 g and 1 g/kg in
based IVA guidelines [290], which recommend limiting older patients, although some have higher intakes and
natural protein intake to provide at least the safe intake of remain metabolically stable)
protein. No recommendation to supplement LFAA is • Some patients, often those who present later, are not on a
given. In the author’s experience, the use of LFAA is gen- ‘counted’ protein intake and remain stable on a self‐
erally not warranted as metabolic stability is achievable on selected low protein diet, or they just avoid high protein
natural protein restriction alone, plus carnitine and/or foods, which can be the case in older patients who are on
glycine. a more relaxed diet [291]
• Infants can be exclusively breastfed and remain stable. If

Learning points: isovaleric acidaemia
necessary a small volume of protein‐free formula can be
given pre‐breastfeeds to limit protein intake (p. 569)
• Dietary management is a restricted protein diet and emer-
• An adequate energy intake provided to promote anabo-
gency regimen during illness
lism and normal growth and development and to help
• l‐carnitine and l‐glycine are given to conjugate with toxic
limit production of isovaleric acid
isovaleric acid
• Vitamin and mineral supplements are usually needed
• Outcome varies from normal neurocognitive outcome/psy-
even in those on a relaxed protein diet. Intakes should be
chomotor development to, less commonly, severe mental
assessed and biochemically monitored (p. 565)
retardation and is better in early‐onset compared with late‐
• Most children with IVA appear to have a reasonable
onset presentation
appetite and grow normally, but major feeding problems
can occur in some, and tube feeding may be necessary
[279, 289]. Only 8 of 133 patients were reported to be tube
fed in a European survey of feeding practices [201]
Glutaric aciduria type 1

Glutaric aciduria type 1 (GA1) is a neurometabolic disorder, first described in 1975 [292].
Enzyme Glutaryl‐CoA dehydrogenase

Biochemical A deficiency of the enzyme glutaryl‐CoA dehydrogenase (GCDH) in the catabolic pathway of the amino acids l‐lysine,
defect l‐hydroxylysine and l‐tryptophan that catalyses the dehydrogenation of glutaryl‐CoA to glutaconyl‐CoA and its decarboxylation
to crotonyl‐CoA (Figure 28.9). Biochemically there is accumulation of the metabolites glutaric acid, 3‐hydroxyglutaric acid,
glutaryl‐CoA, glutaconic acid (to a lesser extent) and glutaryl carnitine in body fluids (urine, plasma and cerebrospinal fluid)
and tissues [293]. Lysine and tryptophan do not accumulate. Patients can have either low or high urinary excretion of
metabolites, termed low or high excretors; irrespectively they both remain at the same risk of striatal damage.
Genetics An autosomal recessive disorder due to mutations in the GCDH. Worldwide the incidence is reported as 1 in 100 000 although
there is a much higher incidence in some specific communities: Irish travellers [294], the Amish community in Pennsylvania,
USA [295] and the Canadian Oji‐Cree Indians [296]. There is no genotype/clinical phenotype correlation although there is
some correlation with biochemical phenotype; those with residual GCDH activity have a low urinary metabolite excretion,
while those with high excretion have no residual GCDH activity; this does not, however, predict severity [297].
Newborn NBS on day 5 of life in the UK by measurement of glutaryl acylcarnitine (C5‐DC) in dried blood spots using tandem mass
screening spectrometry. More information on UK screening, diagnostic and clinical management protocols can be found at www.bimdg.
org and www.gov.uk Newborn blood spot screening: laboratory guide for IMDs (inherited metabolic diseases).
Clinical onset Clinical presentation – Babies with GA1 who present clinically usually appear normal in the first months of life, although some
presentation, have macrocephaly. The majority of patients typically present before 2 years of age with a median age of 9 months [298] following
features an intercurrent illness such as a respiratory or GI illness, which precipitates an acute encephalopathic crisis. Characteristically this
causes irreversible striatal damage and a complex movement disorder. Severely affected patients are consequently left with a
severe dystonic–dyskinetic disorder that is similar to cerebral palsy and ranges from extreme hypotonia to choreoathetosis to
rigidity and spasticity [298, 299]. There is loss of mobility (partial), swallowing difficulties and dysarthria. Intellectual function is
generally preserved initially. Morbidity and mortality is high in patients who have had a crisis. Some cases of GA1 never present
clinically and may only be diagnosed on sibling screening following presentation of the index case [300, 301].
L‐tryptophan L‐lysine L‐hydroxylysine
Glutarylcarnitine Glutaryl-CoA Glutaric acid
Glutaconyl-CoA Glutaconic acid
3-Hydroxyglutaric acid
Crotonyl-CoA
Acetyl-CoA
Glutaryl-CoA dehydrogenase deficiency
Figure 28.9 Glutaric aciduria type 1 – catabolic pathway of lysine, hydroxylysine and tryptophan.
Glutaric Aciduria Type 1 581
Insidious onset – A minority of patients have a more insidious onset with no obvious encephalopathic episode preceding the
development of the movement disorder [293, 302].
Late onset – Patients diagnosed after age 6 years who present with non‐specific and sometimes longstanding symptoms but no
dystonia; on MRI there are no striatal lesions, but predominantly white matter changes [303].
Newborn screening – Patients diagnosed on expanded newborn screening are asymptomatic [304].
Long‐term Patients appear to be at greatest risk of striatal injury during a finite period of brain development, between birth and 6 years. The
complications and neuropathogenesis of GA1 is not fully delineated; an overview is given by Jafari et al. [297]. Intraneuronal accumulation of high
outcome concentrations of glutaric acid (GA) and 3‐hydroxyglutaric acid (3‐OH‐GA) formed by de novo synthesis in the central nervous
system during catabolic episodes is considered to be the most important factor in precipitating neuronal damage, probably via
several mechanisms: excitotoxic cell damage, impairment of energy metabolism and oxidative stress [297]. As the transport
capacity for GA and 3‐OH‐GA across the blood–brain barrier (BBB) is low, they accumulate in very high concentrations during
catabolic episodes (10‐ to 1000‐fold higher than in plasma) and are ‘trapped’ in the brain [305]. Studies in GCDH‐deficient
mice provide evidence that lowering lysine intake and l‐arginine (or homoarginine) supplementation and an increased glucose
intake reduces the concentration of GA and 3‐OH‐GA in brain; carnitine supplementation increases formation of non‐toxic
glutarylcarnitine, but does not alter GA and 3‐OH‐GA production [306, 307].
Early detection by NBS and pre‐symptomatic initiation of treatment can greatly improve the outcome, preventing the
neurological handicap that develops with the clinical presentation and onset of neurological crises, provided there is good
adherence to dietary treatment and emergency regimen [304, 308]. A study of 87 patients diagnosed by NBS identified that
delayed emergency treatment in 12 patients caused acute‐onset motor disorder (mostly severe and moderate) and of those who
did not strictly follow maintenance treatment 8 of 16 developed an insidious‐onset dystonia (moderate to mild) without a
preceding acute event [304]. Even with good adherence, cerebral changes can still be seen on neuroimaging [309], and some
may still have fine motor and speech deficits [310]. Chronic kidney disease has been reported and may manifest irrespective of
treatment and good adherence [304].
Medical treatment Carnitine supplementation: 100 mg/kg/day to facilitate production of non‐toxic glutarylcarnitine from glutaryl‐CoA and to avoid
secondary carnitine deficiency as a consequence of its increased formation. Carnitine is also reported to have antioxidant
benefits [311]. A higher dose may be needed if free carnitine levels are low. A lower dose is given beyond 6 years of age
(30–50 mg/kg/day) [293].
Management of any movement disorder: Is complex and beyond the scope of this publication; recommendations are made in
the 2017 guideline [293].
Dietetic Lowering cerebral lysine influx and lysine oxidation limits production and accumulation of neurotoxic GA and 3‐OH‐GA and is
management considered neuroprotective in pre‐symptomatic patients who have not experienced a neurological crisis [308, 309].
Dietetic management is the same for high and low excretor patients and those with insidious onset:
• restriction of lysine and tryptophan (protein) intake

• lysine‐free, low tryptophan amino acid supplements (LFAA) containing arginine
• provision of an adequate energy intake to limit catabolism, specifically lysine oxidation
Emergency Emergency treatment is probably the most important aspect of treatment. Prompt implementation of an ER during intercurrent
regimen illness is essential to prevent striatal injury and onset of a complex movement disorder [304]:
• The standard ER of frequent 2 hourly drinks/feeds of glucose polymer is given day and night to prevent catabolism
(p. 673)
• Usual dose of LFAA continues to be given
• Usual carnitine dose is doubled (up to 200 mg/kg/day in infants and young children)
• Aggressive and prompt treatment of pyrexia
Monitoring – • Nutritional monitoring of low protein diets is discussed on p. 565. Severe protein and mineral deficiencies have been
biochemical and reported in those on low protein diets [312, 313].
nutritional • Biochemical monitoring of maintenance treatment is difficult as there is no reliable biochemical marker. Urine GA, 3‐OH‐
GA and plasma glutarylcarnitine do not correlate with outcome [314]. Lysine and tryptophan do not accumulate in plasma.
• The 2017 guideline [293] recommends routine biochemical monitoring and frequency (1–6 monthly in children <6 years of
age): quantitative plasma amino acids (in particular lysine, tryptophan) to assess nutritional status, carnitine to check
depletion and adherence, full blood count, liver function tests and albumin and bone chemistry.
• Plasma lysine should be maintained in the normal reference range [293], although it can be in the lower normal
reference range [314], and this is the author’s practice. If plasma lysine is lower than this, the diet is reviewed as an
increase in natural protein or change in type of food may be necessary, i.e. more milk‐based foods if the diet is high in
cereal content.
• Growth needs to be regularly monitored, particularly in dystonic patients as weight gain can be significantly reduced [314].
Clinical Boy et al. Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type 1: second revision
management [293].
guideline
Parent support Metabolic support UK www.metabolicsupport.org.uk
group
Dietary management all EAA [293]. Amino acid intakes (g/kg/day) from sup-
plements are given in Table 28.57.
The low lysine diet recommendations in the 2017 GA1 guide- • If the diet is not supplemented with LFAA, natural pro-
line [293] are based on the original 2007 [312] and 2004 [315] tein intake should provide the safe levels of protein
publications: intake or more, if necessary, to ensure adequate daily
lysine intake.
• A diet based on lysine is considered to be more precise • A potential benefit of giving amino acid supplements is
than a low protein diet because the lysine content of pro- that they provide a good source of arginine. Lysine and
tein‐containing foods varies considerably. The original arginine share the same cerebrovascular cationic trans-
recommendations for lysine and tryptophan intake (mg/ port system (y + system), and arginine competes with
kg/day) are based on clinical practice from Germany and lysine for uptake at the BBB and inner mitochondrial
published safe intakes at that time for the normal popula- membrane. However, high dose arginine is not recom-
tion (Table 28.57) [315]. mended as a low lysine diet is considered to be more
• More recent publications (FAO/WHO/UNU 2007) [8] set effective in lowering cerebral toxic metabolites [293].
lysine requirements lower (Table 28.57). However, the use
of these values has not been reported in clinical practice,
and it is, therefore, not known if further restriction of
Low protein (lysine) diet: practical aspects
lysine has any therapeutic advantage. It should also be
borne in mind that a good outcome can be achieved with The analysis of lysine content of foods in the UK is very
the current guideline recommendations. limited and old [46]. It is, therefore, not easy to provide a
• From age 6 years the risk of striatal damage diminishes; low lysine diet, except in early infancy when the lysine and
relaxation of the low lysine diet to a diet based on safe tryptophan content of infant formula and breastmilk is
levels of protein intake is, therefore, possible and recom- known. As weaning on to solid food progresses, a low pro-
mended [293]. However, no guidance on further relaxa- tein diet based around the safe level of protein intake may
tion of diet with increasing age is given. be a more practical option to limit lysine intake. As low pro-
• Recommendations for total protein intake (g/kg/day) tein foods vary in lysine content (Table 28.58), a combina-
(from natural protein and amino acid supplement) were tion of cereal‐, vegetable‐ and milk‐based foods is needed to
given in the 2007 guideline [312], but not in the 2017 ensure an adequate lysine intake. If the diet contains pre-
revised guidelines [293] because the natural protein intake dominantly cereal foods, lysine intake will be less than rec-
varies widely depending on the type of food consumed to ommended. The low protein diet is combined with
provide lysine. lysine‐free, low tryptophan amino acid supplements given
• Supplements of lysine‐free, tryptophan‐reduced amino according to, or at least in similar amounts to, the guideline
acids are recommended to ensure an adequate intake of recommendations (Table 28.57).
Table 28.57 Maintenance dietary treatment for glutaric aciduria type 1.
Treatment Age
Low lysine diet 0–6 months 7–12 months 1–3 years 4–6 years >6 years
Lysine (natural protein source)* 100 90 80–60 60–50 Recommendation 6 [293]

(mg/kg/day) After age 6 years dietary treatment
should follow an age‐adapted,
FAO/WHO/UNU 2007 [8] 119–65 64 (6 months) 45 (1–2 years) 35
protein controlled protocol based
(lysine (mg/kg/day)) 35 (3 years+) on safe levels for protein intake
Tryptophan* (mg/kg/day) 20 17 17–13 13
FAO/WHO/UNU 2007 [8] 29–16 16 6.4 (1–2 years) 4.8
(tryptophan (mg/kg/day)) 4.8 (3 years+)
Lysine‐free, low tryptophan 1.3–0.8 1.0–0.8 0.8 0.8
amino acid supplement (g/kg/day)
Protein (natural)† (g/kg/day) 1.4–1.3 1.5–1.3 1.4–1.3 1.3–1.1
FAO/WHO/UNU 2007 [8](safe 1.77–1.14 1.31–1.14 1.14–0.9 0.9–0.89
level of protein intake (g/kg/day)) (1–6 months) (6 months–1 year)
Protein (total)† (g/kg/day) 2.7–2.1 2.5–2.1 2.2–2.1 2.1–1.9
* Lysine and tryptophan recommendations are based on the 1st European Workshop on GA1 (Heidelberg, 1993) and international dietary
recommendations available at that time [315].
†
Recommendations were given for protein and total protein intake in the 2007 guideline only [312].
Source: Adapted from [293, 312, 315].
Table 28.58 Lysine content of selected food groups. [315]. Table 28.57 provides the FAO/WHO/UNU 2007
requirements [8] for tryptophan; these are mostly lower than
Food Lysine mg/g protein the 2017 guideline recommendations [293]. For details of pres-
Fish 90 entation, composition, age suitability and preparation of these
supplements refer to the manufacturers’ websites: www.
Nuts 80
nutricia.co.uk, www.vitaflo.co.uk. Similar products are avail-
Meat 70 able outside the UK www.abbottnutrition.com, www.mead-
Milk, cheese, yoghurt 70 johnson.com, www.metax.org, www.milupa‐metabolics.com.
Eggs 60 Biochemical and haematological nutritional status are
reported to be better in those taking lysine‐free, low trypto-
Potato 60 phan supplements with added vitamins and minerals [316].
Vegetables 50
Cereal/baked goods 50 Infant feeding
Rice/barley/oats 40
Bread/pasta 30 On receipt of a positive newborn/diagnostic screening
result, treatment (diet and carnitine) should be commenced
Source: Data adapted from [312, 315]. promptly even before confirmation of diagnosis by enzyme
and/or mutation analysis. Infants can be breastfed and/or
An alternative approach to providing the low lysine diet is bottle fed. The BIMDG guidelines recommends that from
to provide the daily lysine intake as a prescribed number of diagnosis to age 1 year, lysine intake is restricted to 114 mg/
protein exchanges from cereal‐based foods and milk and kg/day (1.3 g natural protein) and 1.3–1.4 g protein equiva-
milk‐based foods (Table 28.58). At the author’s centre, LBV lent from LFAA, these being slightly higher than the
protein foods are averaged to 40 mg lysine/100 g (foods GA1 guideline (Table 28.57). Full details can be accessed
shaded in grey in Table 28.58), and milk and milk based foods from www.bimdg.org. Lysine intake from either breastfeeds
70 mg lysine/g protein. More protein is given from cereal- or standard infant formula is restricted by giving supple-
based foods as this is more practical and manageable. Using mentary lysine‐free, low tryptophan infant formula, e.g.
this method the natural protein generally exceeds the safe GA1 Anamix Infant formula. A BF regimen will give more
level of protein intake; the total protein figures included in natural protein as lysine content is lower than in standard
the 2007 guideline also show this (Table 28.57). infant formula (89 vs. 114 mg/100 mL).
Example calculation of a low lysine diet for a 2‐year‐old boy,

Breastfed infant
weight = 12 kg
Diet to provide: 70 mg lysine/kg/day (Table 28.57) = 840 mg Breastmilk provides around 68 mg lysine/g of protein or
lysine 89 mg lysine/100 mL [8]. Demand BF of 150–200 mL/kg/day
Milk and milk‐based foods = 5 × 1 g protein exchanges would provide 133–178 mg/kg/day of lysine. To limit lysine
(70 mg/g protein) = 350 mg intake from breastmilk, the lysine‐free, low tryptophan infant
Cereal‐based foods = 12 × 1 g protein exchanges (40 mg formula is given before breastfeeds; the total volume is
lysine/g protein) = 560 mg divided and distributed evenly before five to six breast feeds.
Total = 350 mg + 560 mg = 840 mg lysine
Natural protein = 17 g/day = 1.4 g/kg Example of a breastfeeding regimen for an infant age 3 weeks,
Safe intake of protein [8] = 12 g protein/day = 1 g protein/ weight = 4 kg
kg/day Aim: Limit lysine to 114 mg/kg/day (456 mg lysine) from
natural protein
Lysine‐free, low tryptophan L‐amino acid supplements Total fluids = 170 mL/kg = 680 mL/day
Estimated intake of breastmilk = 510 mL = 114 mg lysine/
Lysine‐free, low tryptophan amino acid supplements are kg/day = 6.6 g protein (1.6 g/kg/day)
available as infant formula, e.g. GA1 Anamix Infant, or for GA1 Anamix Infant = 170 mL (680 – 510 mL) = 3.4 g protein
older infants and children in a variety of formats such as gel equivalent/kg = 0.9 g/kg/day)
mixes, powdered drinks, ready to drink liquid bottles, e.g. GA Feeds: 35 mL × 5, before five breastfeeds, followed by breast-
gel from 6 months; GA1 Anamix Junior powder from 1 year; feeding on demand
GA Express15 from 3 years. These products contain added Total protein = 6.6 g natural and 3.4 g protein equiva-
energy as CHO ± fat and vitamins and minerals. The trypto- lent = 10 g = 2.5 g/kg/day
phan content of amino acid supplements available in the UK
is 4–6 mg/g of amino acids and arginine 69–78 mg/g of
Bottle‐fed infant
amino acids. GA amino5 and XLYS TRY Glutaridon are pure
amino acid supplements. As Glutaridon is tryptophan‐free, it Standard infant formula provides around 88 mg lysine/g of
is essential that the diet provides the requirement for trypto- protein or 114 mg lysine/100 mL. Demand feeding of infant
phan as deficiency can induce neurological dysfunction formula at 150–200 mL/kg would provide 171–228 mg/kg/
day of lysine. The volume of standard infant formula is lim- protein intake for age from a variety of cereal, vegetable
ited to restrict lysine to around 114 mg/kg/day and divided and dairy foods (p. 582 and Table 28.58). Protein from
between six to eight feeds, depending on feeding frequency. standard infant formula or breastmilk is replaced by food,
Lysine‐free, low tryptophan formula, e.g. GA1 Anamix Infant, gradually introducing 1 g exchanges of natural protein at
is then fed to appetite after the standard infant formula. a time using: purée potato, pasta, rice, lentils, vegetables
or commercial weaning foods (dried or wet varieties in
Example of a bottle feeding regimen for an infant aged 2 jars, pouches, packets) such as ordinary rusks, baby cere-
months, weight = 5 kg als or vegetable‐based savoury foods and yoghurt and
Aim: Limit lysine to 114 mg/kg/day (570 mg lysine) from milk‐based desserts.
natural protein • Start second stage lysine‐free, low tryptophan amino
Total fluids = 170 mL/kg = 850 mL/day acid supplement, e.g. GA Gel. Practical aspects of intro-
Standard infant formula 500 mL = 570 mg lysine = 114 mg/ ducing more concentrated amino acid supplements are
kg/day = 6.5 g protein (1.1 g/kg/day) given on p. 529. Less supplement is required in GA1
GA1 Anamix Infant 350 mL (850 mL – 500 mL) = 7 g protein compared to the amino acid disorders. One teaspoon of
equivalent = 1.4 g/kg/day GA Gel is introduced from around 6 months at one meal,
Feeds: 140 mL × 4 hourly × 6 feeds gradually increasing the quantity and giving at two and
First feed of 80 mL standard infant formula followed by sec- then three meals before solids. As Gel is increased, less
ond feed of 60 mL GA1 Anamix Infant to appetite (more is GA1 Anamix is given but ensuring adequate energy,
given if the infant is hungry) vitamins and minerals are provided by the diet and
A nutritional analysis for the daily feed plan is given in lysine‐free, low tryptophan supplement. GA1 Anamix
Table 28.59. Infant feeds may continue to be given on waking and
before bed until around 1 year of age. The guideline rec-
ommends 1.0–0.8 g protein equivalent/kg/day from the
Weaning supplement for infants aged 7–12 months, e.g. for a 10 kg
Weaning onto solid foods is started at the usual time of child, aged 1 year, one sachet of GA Gel provides 10 g
around 6 months (26 weeks) of age and proceeds in a similar protein equivalent = 1 g/kg and 67 mg tryptophan
method to low protein and amino acid diets, described in (=6.7 mg/kg/day), which does not provide the guide-
more detail on p. 569. Normal weaning practices are fol- line amount of 17 mg/kg/day (Table 28.57), but does
lowed: solids are introduced at one meal and then given 2–3 provide the more recent recommendation of 6.4 mg/kg/
times per day, and the infant progresses from smooth purées day [8]. The diet will provide more tryptophan. GA1
to lumpier foods and finger foods during the first year. An Anamix Junior powder given as a drink mix can be used
overview of weaning stages: from 1 year of age, each sachet providing 5 g protein
equivalent and 40 mg tryptophan. Some centres intro-
• Introduce free weaning foods, e.g. fruits, vegetables duce before 1 year.
(Table 28.50), low protein manufactured foods (p. 562). • Low protein manufactured foods can be given to provide
• Introduce 1 g protein exchanges to provide the lysine extra energy and variety, if necessary, e.g. low protein
requirement (90 mg/kg/day) or at least the safe level of rusk or cereal (p. 562).
Table 28.59 Nutritional analysis of daily feed plan for male infant with glutaric aciduria type 1.
Age 2 months, weight = 5 kg
Energy
Protein Lysine Tryptophan Fluid
kcal kJ Protein (g) equivalent (g) (mg/day) (mg/day) (mL/kg)
500 mL Cow & Gate First Infant Milk (68 g powder) 330 1386 6.5 — 569 103 100
350 mL GA1 Anamix Infant (54 g powder) 251 1004 7 — 36 70
Total 581 2390 6.5 569 139
Intake per kg/day 116 478 1.3 1.4 114 20
Aim per kg/day 96* 403 1.3† 100† 20‡ 170
114 #
29 §
* Ref. [212].
†
Ref. [293].
‡
Refs. [312, 315].
§
Ref. [8].
#
www.bimdg.org
• Vitamins and minerals will be provided by the lysine‐ difficulties, due to dyskinesia, and GOR and vomiting, due
free, low tryptophan supplement (if enriched with vita- to truncal hypotonia. The extent of these feeding problems
mins and minerals), but depending on dose may not is related to the severity of the neurological disease, with
provide the full requirements. It is important to assess acute onset being much worse than insidious onset. Dietary
the additional contribution from the diet and supple- advice is tailored to the individual child’s needs: the use of
ment as necessary. thickened fluids, energy dense foods of the correct consist-
ency and energy supplements may be required to achieve
an adequate energy and fluid intake. Tube feeding is often
Young children
essential to maintain an adequate energy intake and to
achieve satisfactory growth. Nissen fundoplication (and
During early childhood the diet is provided by a combina-
insertion of gastrostomy) may be necessary in some patients
tion of foods to provide the recommended lysine intake
for treatment of GOR and vomiting. Assessing energy
(Table 28.57) or the safe level of protein intake (Table 28.47)
requirements in this group of patients can be difficult; the
for age. The LFAA supplement should provide around 0.8 g/
worst patients cannot walk so should need less energy, but
kg/day of protein equivalent (Table 28.57). The LFAA sup-
often energy expenditure is reported to be increased due to
plement plus protein exchange foods will provide adequate
high muscle tone and dystonic movements and to distur-
tryptophan.
bances in temperature control [299], thus emphasising the
need for adjusting the diet to the requirements of the indi-
Diet after 6 years of age vidual. Additional fluids may be required in patients who
have disturbances in temperature control with excessive
As striatal damage occurs only during a finite period of sweating. An example of a low protein/lysine tube feed for
brain development, the low lysine diet can be relaxed beyond a symptomatic patient is given in Table 28.60. Not all
6 years of age; the GA1 guideline recommends avoidance of patients are on protein restricted feeds.
an excessive intake of natural protein and to use protein
sources with a low lysine content according to safe levels of
protein intake [293]. For some the natural protein intake Emergency regimens for management
may, however, already be greater than the safe intake, of intercurrent illness
depending on food choice. No specific guidance is given on
continued use of LFAA supplements. Lysine intakes of chil- Prompt and aggressive treatment of intercurrent illness by
dren on relaxed diet in the seventh year of life are reported to implementation of a high energy ER is critical to prevent
be mean ± SD 135 ± 50% of the recommendation for 4–6 year neurological damage in pre‐symptomatic patients and fur-
olds (60–50 mg lysine/kg/day) and a decreased LFAA intake ther injury in symptomatic patients [293, 308]. Delayed treat-
of mean ± SD 88 ± 17%; no information of actual natural pro- ment can have serious consequences with irreversible striatal
tein intake was given [314]. damage and a complex movement disorder [304]. Strategies
Current practice varies, with some centres continuing the to help prevent this need to be in place and include written
LFAA supplement and others changing to a more relaxed treatment protocols for home and local hospital and ade-
controlled protein intake without using supplements. It is quate education and training of parents/caregivers [293].
important relaxation of diet, and LFAA is discussed with fam- With increasing age, and in particular from 6 years of age,
ilies, and they are able to make an informed choice based on the risk of acute neurological insult appears to be reduced;
current evidence. however, the use of an ER is an important part of manage-
ment. The GA1 guideline provides comprehensive emer-
gency treatment guidelines and detailed strategies to prevent
Dietary management of symptomatic patients
its delayed implementation. GA1 emergency management
can also be accessed from www.bimdg.org.
Dietary treatment in symptomatic patients who have pre-
The main aim of the ER is to reduce production and accu-
sented with encephalopathy and neurological crises is
mulation of neurotoxic GA and 3‐OH‐GA by:
reported to be of no or limited neurological benefit [298, 317,
318]. It is known that protein restriction cannot reverse neu- • provision of a high energy intake, at least normal require-
rological damage that has already occurred and dietary pro- ments for age to prevent catabolism; 120% of daily energy
tein restriction alone is not sufficient to prevent brain injury requirement is recommended by some centres [294]
[317–319]. The rationale for a restricted lysine or protein diet • omitting or temporarily reducing (by 50%) natural pro-
in symptomatic patients is unclear, but for some it may be tein intake
helpful in prevention of any possible progressive neurologi- • provision of usual dose of lysine‐free, low tryptophan
cal deterioration [299, 319] and is used in some centres. amino acids
• double dose of usual carnitine supplementation (carnitine
can be given IV)
Feeding problems
The general principles of implementation, administration
Feeding problems are common in the group of patients with of the ER and reintroduction of usual diet are the same as
neurological disease and include chewing and swallowing the standard ER (p. 673). It is particularly important to
Table 28.60 Low protein/low lysine gastrostomy feed for a girl with glutaric aciduria type 1.
Age 4 years, weight = 13 kg
Energy
Protein Lysine Tryptophan Sodium Potassium Fluid
kcal kJ Protein (g) equivalent (g) (mg/day) (mg/day) CHO (g) Fat (g) (mmol) (mmol) (mL)
450 mL PaediaSure Fibre 454 1899 12.6 – 945 180 50.4 22.4 12 12.7 450
GA1 Anamix Junior (54 g) 198 831 – 15 – 120 16.2 6.9 15.0 8.4
Duocal (85 g) 418 1751 – – – – 62 19 <0.8 <0.1
Add water to 1200 mL
Total 1070 4481 12.6 15 945 300 128.6 48.3 27 21.1
per 100 mL 83 373 10.7 4.0 2.1 1.6
Intake/kg/day 1.0 1.1 73 23

Aim per day 81/kg* 340/kg 0.86 †
0.8 ‡
60–50 ‡
13‡ 30* 28* 1200
1053 4422
Additional electrolytes may be necessary. Electrolytes from Duocal are not included in calculation. Adequate vitamins and minerals are provided from
the combination of PaediaSure Fibre and Anamix Junior. A fibre‐containing feed is used to help maintain normal bowel function.
* Refs. [205, 212].
†
Ref. [8]. Safe level of protein intake.
‡
Refs. [293, 312].
implement the ER for any fever (high temperature). Episodes • If the ER is not tolerated, it is crucial that the child is
of vomiting and diarrhoea (even if no fever) necessitate hos- admitted to hospital without delay for IV therapy of 10%
pital admission. For very minor illnesses, ER may not always dextrose/0.45% saline and carnitine. The BIMDG pro-
be required, and continuation of the usual diet is appropriate. vides emergency protocols for IV management and can be
It is essential that this provides the normal energy intake accessed at www.bimdg.org
(extra energy supplements may be needed) and the usual • A low volume, continuous tube feed of pure LFAA (e.g.
amount of lysine‐free, low tryptophan amino acids. XLYS TRY Glutaridon, GA amino5) to provide 1 g protein
Administration, composition and practical aspects of the ER: equivalent/kg/day can be given along with IV fluids, as
tolerated. A concentration of 8–10 g amino acids/100 mL,
• Stop natural protein intake temporarily for 24 hours to a
as necessary, can be given. It may also be possible to add
maximum of 48 hours
glucose polymer to 10% CHO or higher
• Provide ER feed, a combination of the usual LFAA and
• In the UK there are no PN solutions designed specifically
glucose polymer solution ranging from 10% to 25%, as
for GA1
per for age (p. 676).
• Once the child begins to improve, the usual natural pro-
• For children <6 years old, give around 1 g/kg/day pro-
tein intake and diet/feed is reintroduced as for standard
tein equivalent from their usual LFAA supplement
ER, ensuring an adequate energy intake at all times
• Alternatively pure lysine‐free, low tryptophan amino
acids products such as GA amino5 are suitable for all age A calculated example of an ER for a 9‐month‐old infant
groups and can be easily added directly to the glucose who is unwell is given in Table 28.61. Examples of other feed
polymer solution (10%–25% CHO depending on age) recipes can be accessed from www.bimdg.org.
• Amino acid supplements are hyperosmolar (see manufac-
turers’ information) and need to be considered if the child
has a GI illness, e.g. GA1 Anamix Junior, osmolality Learning points: glutaric aciduria type 1
>1220 mOsm/kg H2O
• In children aged ≥6 years, there is no consensus about the • Newborn screening and early treatment, with strict adherence,
use of LFAA supplements, but it may be advantageous to can prevent striatal damage and onset of movement disorder
continue to give if this helps prevent catabolism and lim- • Management is low lysine diet, carnitine and emergency
its lysine uptake across the BBB regimen (during catabolic stress)
• Fluid volume is the same as for standard ER • A high energy emergency regimen is critical to prevent
• The ER can be implemented at home, but patients need to neurological damage in pre‐symptomatic patients and fur-
be reassessed by professionals several times per day with ther injury in symptomatic patients
a low threshold for hospital admission • Low lysine diet can be relaxed >6 years of age, but the emer-
• NG feeding can help ensure the full volume of ER is gency regimen is still needed
given, but parents must be competent in doing this [320]
Urea Cycle Disorders 587
Table 28.61 Emergency regimen feed for an unwell infant with glutaric aciduria type 1.
Age 9 months, weight = 8 kg

Unwell with temperature of 38 °C, mild diarrhoea, no vomiting
Aim: Provide 1 g protein equivalent/kg/day from LFAA formula and at least energy intake for age. 120% of EAR for energy would be 86 kcal
(360 kJ)/kg and is appropriate for infants
Energy
Protein Protein Lysine Sodium Potassium
kcal kJ natural (g) equivalent (g) (mg/day) CHO (g) Fat (g) (mmol) (mmol)
GA1 Anamix Infant 400 mL 276 1148 – 8 Nil 29.6 14 4.8 7.6
Maxijul 100 g 380 1615 – – – 95 – tr tr
Total volume 1200 mL 656 2763 8 124
per 100 mL 55 230 0.7 – 10.4 1.2 0.4 0.6
Intake per kg/day 82 345 1.0
Aim per kg/day 72* 302* – 1.0†
Administration Feed: 100 mL every 2 hours day and night or 50 mL/hour as continuous tube feeds
EAR, estimated average requirement; LFAA, lysine-free amino acid.

†
Refs. [293, 312].
* Ref. [212].
Urea cycle disorders

The urea cycle (UC) has two main functions: generated from dietary amino acids and obligatory
endogenous protein catabolism
• converts toxic ammonia, formed from waste nitrogen • biosynthesis pathway for arginine, which is the precursor
compounds, via a series of biochemical steps to form non‐ for the synthesis of several important metabolites includ-
toxic urea for excretion by the kidney. Waste nitrogen is ing nitric oxide (NO), creatine and glutamate
Enzymes and disorders Normal function of the UC depends on a series of six consecutive enzymatic reactions, and inborn errors at each step have
been identified (Figure 28.10):
• N‐acetylglutamate synthetase deficiency (NAGS)

• carbamoyl phosphate synthetase 1 deficiency (CPS1)
• ornithine transcarbamoylase deficiency (OTC)
• argininosuccinate synthetase deficiency (ASS) or citrullinaemia
• argininosuccinate lyase deficiency (ASL) or argininosuccinic aciduria (ASA)
• arginase deficiency
The ASS and ASL enzymes additionally form part of the overlapping nitric oxide production pathway.
There are also disorders of transport proteins of UC intermediates because the cellular steps are in two cellular
compartments:
• citrin deficiency or citrullinaemia type II (CTLN2) (due to glutamate/aspartate antiporter citrin deficiency)
• hyperornithinaemia, hyperammonaemia, homocitrullinaemia (HHH) syndrome (due to ornithine/citrulline antiporter
ORNT1 deficiency)
These are rare disorders and are discussed in Clinical Paediatric Dietetics 4th edition [321].
Biochemical defect Any enzyme deficiency in the UC reduces flux through it blocking normal ureagenesis; waste nitrogen accumulates as
ammonia in blood and brain, which is neurotoxic and may cause a severe encephalopathy. Secondary metabolic changes
also contribute to central nervous system (CNS) toxicity, such as increased glutamine. Plasma ammonia is raised and can
be very high, e.g. in acute neonatal onset patients it can be >1000 μmol/L (normal <40 μmol/L). Plasma amino acids are
deranged, glutamine and alanine accumulate and arginine is low, except in arginase deficiency where it accumulates.
Citrulline accumulates to high concentrations in citrullinaemia and similarly argininosuccinic acid in ASA. These
metabolites are excreted in urine and provide alternative pathways for nitrogen excretion.
The pathology is complex and an overview of current understanding is given by Braissant [322]. Arginase deficiency is
distinct from the other disorders and is discussed separately.
Genetics All are inherited as autosomal recessive traits apart from OTC deficiency, which is X‐linked and the most common of these
disorders. There is a wide phenotypic spectrum within each disorder, with some ability to predict the course of some based
on mutations [323].
Legend
Enzyme Name of disorder
1. Carbamoyl phosphate synthetase 1 CPS 1 deficiency
2. Ornithine transcarbamoylase OTC deficiency
3. Argininosuccinate synthetase ASS deficiency
or citrullinaemia type 1 Phenylbutyrate
4. Argininosuccinate lyase ASL deficiency HEPATIC NITROGEN
or argininosuccinic
aciduria (ASA) POOL
Alanine Phenylacetate
5. Arginase Arginase deficiency
Aspartate
or hyperargininaemia
Glutamine
6. N-Acetyl glutamate NAGS deficiency Glutamate
synthetase (NAGS)
Glycine
Transporters Benzoate
and other compounds
7. Mitochondrial aspartate-glutamate Citrin deficiency
carrier (AGC2)
8. Mitochondrial ornithine transporter HHH syndrome Phenylacetyl glutamine

AMMONIA
(ORT1)
N-ACETYL-
Acetyl-CoA 1 Hippurate
GLUTAMATE
6
CARBAMYL PHOSPHATE
Aspartate
ORNITHINE
Mitochondrial matrix CITRULLINE
7 8
8
Aspartate CITRULLINE ORNITHINE

UREA
5
3
Cytosol
ARGININE
Orotic acid
Orotodine ARGININOSUCCINATE
4
Fumarate
URINE
Figure 28.10 Disorders of urea cycle and related disorders.
Newborn screening No newborn screening in the UK. Expanded NBS is problematic, suitable screening markers and their specificity being key
issues [323].
Clinical onset Presents at any age from the neonatal period, throughout childhood and in adulthood. A detailed review of clinical
presentation, features symptoms and presentation is described by Haberle et al. [323]:
• Presentation may be acute, chronic or, rarely, acute intermittent. Signs and symptoms can be neurological (most
frequently), hepatic–gastrointestinal and psychiatric
• Most severe defects present acutely with hyperammonaemia in the neonatal period, most commonly within the first
7 days of life, or later at any age (which may be precipitated by a catabolic event such as an intercurrent infection),
and may cause a severe neurological handicap or even death
• Loss of appetite, poor feeding, lethargy and vomiting are common in all ages
• In the newborn there is often respiratory distress with signs of hyperpnoea, altered level of consciousness and seizures,
acute encephalopathy and collapse [324]
• Respiratory alkalosis is initially present in about 50% of acute onset patients [325]
• In later onset, confusion, headache, disorientation, abnormal behaviour, ataxia, focal neurological signs or coma can
occur, and in some there is also delayed physical growth and developmental delay [324]
• Protein aversion as revealed in diet histories of later presenting patients is common in urea cycle disorders (UCD), with
selective avoidance of high protein foods [326]
• Heterozygote OTC deficient females can present with postpartum psychosis
Long‐term High mortality and morbidity are associated with UCD [325, 327, 328]. The outcome is related to duration of coma at
complications and presentation and peak ammonia levels. The outlook for infants is very poor if the ammonia level is >1000 μmol/L, and a
outcome decision not to treat may be made [323]. The neurodevelopmental outcome can range from mild to profound cognitive
deficits [325, 327, 329]. In late‐presenting patients many have some degree of learning and neurological disability [325,
330]. Patients with ASL deficiency have poorest cognitive outcome, and this supports the theory that toxins other than
ammonia may affect this, such as argininosuccinate [327, 331, 332], increased guanidinoacetate concentrations or
deficiency of nitric oxide production. Some develop hepatic complications [331], systemic hypertension [332], GI
problems [333] and renal tubulopathy [333, 334].
Liver transplant is successful in preventing further episodes of metabolic decompensation in UCD, but cannot reverse
any neurological damage. Low protein diet and UCD medicines are not required post‐transplant [335].
Cell‐based therapies, gene therapy and enzyme replacement therapy are currently under trial as alternative possible
treatment options [323].
• Sodium benzoate and sodium phenylbutyrate (phenylacetate) conjugate with specific amino acids destined for
ammonia formation and thus reduce the nitrogen load to the UC (Figure 28.10). They are termed alternative pathway
medicines or nitrogen scavengers because of their mode of action. Both are available in different formats. They are
unpleasant tasting and can cause mucositis and gastritis, so it is important they are taken with meals and plenty of fluids
to help prevent this. Some patients have a gastrostomy tube specifically to administer these. Standard doses provide a
significant sodium load to infants, which can be a problem.
• Phenylbutyrate is metabolised in vivo to form phenylacetate that is conjugated with glutamine in liver and kidney to
form phenylacetylglutamine. If the reaction were complete, then 2 moles of nitrogen would be excreted for each mole
of phenylbutyrate given. However, more recent studies indicate only 1 mole is excreted [336, 337]. Phenylbutyrate is
also reported to deplete BCAA. Careful monitoring of plasma amino acids is essential to avoid deficiency, and
supplementation of BCAA may be necessary.
• Sodium benzoate is conjugated with glycine in the liver and kidney to form hippurate so that 1 mole of nitrogen is
excreted for each mole of sodium benzoate given.
• Glycerol phenylbutyrate is a new alternative to sodium phenylbutyrate. It has the added benefits of being sodium‐free
and tasteless and may be more effective [338].
• Practices differ with choice of nitrogen scavenger (one or both may be given), and doses vary; this to some extent depends
on the severity of the disorder and the patient’s tolerance. Higher doses may be used temporarily during episodes of acute
hyperammonaemia.
• Arginine becomes an essential or semi‐EAA in UCD because its synthesis is greatly reduced [339]. Arginine can be
administered orally or IV. It is available in liquid, powder or tablet form for oral use. It is given as a divided dose and
usually in conjunction with the other medicines.
• In OTC and CPS deficiencies, arginine supplements of 100–200 mg/kg body weight/day are given to replace that which
would normally be formed. The aim is to increase the flux through the UC and urea synthesis and to maintain a normal
plasma arginine concentration (normal reference range 40–120 μmol/L). Alternatively in OTC, in order to meet the
arginine requirements, supplements of citrulline can be given as it is rapidly converted to arginine via the intact part of
the UC. Also, citrulline contains one less nitrogen atom than arginine, thereby reducing waste nitrogen production;
however, it is more expensive than arginine.
• In citrullinaemia and ASA deficiency, arginine is given, up to 100–300 mg/kg/day [323], to replenish ornithine supply;
traditionally, higher doses have been given. The carbon skeleton of ornithine is needed for the formation of citrulline
and argininosuccinic acid that accumulate and are excreted in citrullinaemia and ASA, respectively, and provide
another method for nitrogen removal. Argininosuccinic acid is more effective than citrulline as it carries two waste
nitrogen atoms and has a higher renal clearance. Arginine, however, increases plasma concentrations of both citrulline
and argininosuccinic acid, the full consequence of which is unknown; concerns have been expressed that high
concentrations of argininosuccinic acid in ASA deficiency may have adverse effects on the brain and be hepatotoxic
[340–342] and is a main reason why lower arginine doses are prescribed, nowadays.
• N‐Carbamyl‐l‐glutamate (or carbamylglutamate or carglumic acid) – Defects of NAGS affect production of N‐
acetylglutamate. Patients with NAGS deficiency are treated with carbamylglutamate, the orally active form of N‐
acetylglutamate that is essential for activation of CPS1 (first step of the UC).
• Carbamylglutamate – Can be given during acute neonatal hyperammonaemia as an emergency drug to help lower
ammonia levels.
Dietetic management The aim (in combination with medicines) is to reduce the nitrogen load to the UC and prevent hyperammonaemia and
consequent neurological sequelae:
• restrict natural protein intake to provide around the safe levels of protein intake for age [8] (Table 28.47)
• EAA supplementation if natural protein tolerance is below the safe level of protein intake, with poor growth and
metabolic instability [323]
• branched chain amino acid (BCAA) supplementation in patients on high doses of sodium phenylbutyrate who have
persistently low plasma BCAA
• provision of an adequate energy intake to ensure normal growth and prevent endogenous protein catabolism.
Energy requirements in ASA may be lower than other UCD and could be related to an imbalance of the Krebs
cycle [343]
• regular feeding and avoidance of prolonged fasts to help maintain good biochemical control. Plasma glutamine and
ammonia concentrations increase with fasting and catabolism
Acute management Patients who present acutely with hyperammonaemia are generally very sick, in intensive care requiring ventilation and
haemodiafiltration to remove ammonia. Reversal of catabolism and prevention of hyperammonaemia is a crucial to help
stabilise the child. Treatment must be initiated promptly to reverse catabolism and hyperammonaemia, as outcome is
correlated with duration of coma and peak ammonia levels [344].
Immediate management is to:
• stop protein intake
• start IV 10% glucose and electrolytes
• give IV medicines – nitrogen scavengers, arginine and carbamylglutamate (in some)
• start protein‐free feeds once the child is stabilised (dietetic management of a newly diagnosed neonate, infant or child is
discussed on p. 567)
• protein reintroduction may induce hyperammonaemia; an EAA supplement may be given to reduce waste nitrogen
(p. 590) and then replaced with natural protein once the patient is more stable
Monitoring – Clinical and biochemical monitoring are essential to assess metabolic stability and to guide treatment, protein intake and
biochemical and medicine doses [323].
nutritional Clinical monitoring: Includes growth, assessment for signs of any vitamin and mineral deficiencies (e.g. skin rashes, sparse
hair), liver ultrasound, blood pressure (in ASLD), neuroimaging, neurological and neurocognitive assessments
Dietary assessment: The nutritional monitoring of low protein diets has been discussed on p. 565.
Biochemical monitoring of plasma concentrations: Ammonia, glutamine, arginine and amino acids, particularly BCAA,
argininosuccinic acid in ASS, citrulline in ASL, creatine
Emergency regimen Prompt implementation of an ER during intercurrent illness is essential to prevent catabolism and hyperammonaemia:
• Stop natural protein intake and EAA supplements
• Give standard ER of frequent 2 hourly drinks/feeds of glucose polymer (p. 673)
• Give at least the usual doses of medicines (nitrogen scavengers and arginine)
• Admit to hospital, if not tolerating or not improving on ER
Clinical management Haberle et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision [323].
guideline US Urea Cycle Disorders Consortium guidelines www.rarediseasenetwork.epi.usf.edu.
Parent support group Metabolic support UK www.metabolicsupport.org.uk
Dietary management Essential amino acid and branched chain amino acid

supplements
Low protein diet
A 2013 study of dietary treatment practices across Europe
The major route for excretion of waste nitrogen is urea. Its reported that 38% (174/464 patients) were prescribed EAA
production and excretion are linearly related to increasing supplements [347] and that doses varied widely: 10%–90%
protein intake [345]. A low protein diet will reduce the accu- of total protein intake. More recent data from the E‐IMD
mulation of waste nitrogen as ammonia, glutamine and ala- registry [256] reported 32% (114/361patients) were pre-
nine. A reduction of 0.1 g/kg/day of protein reduces the scribed EAA supplements, with a mean dose of EAA
nitrogen load on the urea cycle by 16 mg/kg/day [346]. Even (including single amino acids) of 28%–31% of total protein
on the minimum protein intake for normal growth and prescription and a median protein prescription of 0.28 g/
maintenance, there is always some flux through the UC, as kg/day (range 0.04–1.17 g/kg/day). Plasma amino acids
tissue protein is constantly being synthesised and broken levels were reported in 277/361 of all patients, 20%–30%
down [8]. For those with severe defects the dietary protein had BCAA levels below reference ranges, but no differences
intake is reduced to around the safe level of protein intake were observed between those prescribed EAA or not.
(Table 28.47), but this needs to be titrated against biochemi- Sodium phenylbutyrate dose correlated with low BCAA
cal parameters (ammonia, glutamine and EAA [323]). levels. It is important to note the many limitations of this
Patients with milder defects will tolerate more protein than cross‐sectional study.
the safe intake; these patients are also likely to be on lower EAA supplements as part of the total daily protein intake
doses of one of the nitrogen scavengers. Protein require- may be beneficial because, theoretically, by limiting the
ments per kilogram bodyweight are highest during early intake of non‐EAA, waste nitrogen is utilised to synthesise
infancy (at 1 month, 1.77 g/kg) and decrease with age to these and hence nitrogen destined for excretion as urea will
0.8 g/kg/day in late adolescence. Neonates may tolerate and be reduced. This, however, has never been proven in clinical
need higher protein intakes of 2–2.5 g/kg/day to achieve studies and is not routine practice across Europe. The UCD
growth (author’s experience). The E‐IMD registry study guidelines [323] suggest EAA supplements of 20%–30% of
[256] reported the median natural protein intake of 289 total protein intake be given only when natural protein toler-
patients on protein restricted diets to be close to or above the ance is below safe protein intake for age and too low to
WHO recommended daily allowance (RDA). However for achieve normal growth and metabolic stability. This con-
certain disorders, some patients who were on EAA supple- trasts with US recommendations of use from diagnosis and
ments had a natural protein intake less than WHO, RDA. to give at a higher dose of 25%–50% of total protein as EAA
The practical management of a low protein diet for infants in severe defects [348] and in infancy to give 50% of protein
and children is described on p. 562. as EAA; as growth rate slows, the percentage is decreased
[349]. The rationale for use during infancy is not completely ability of phenylbutyrate to cause an enhanced flux through
clear as protein requirements per kilogram per day are high- the branched chain α‐keto acid dehydrogenase complex,
est and nitrogen retention is at a maximum, but this could be which catalyses the reversible oxidative decarboxylation of
related to using nitrogen scavengers. There are no studies the BCAA [352]. The effects of lowered BCAA are unknown,
that compare the two methods of management. but it may cause patients to be less stable [353]. Despite these
A trial of EAA supplements may be useful if: reports, BCAA supplement use across Europe is uncommon;
cohort studies from 2013 to 2019 report only 3% patients were
• blood biochemistry (glutamine, alanine, ammonia) can- prescribed supplements [256, 347], which suggests little
not be corrected by altering the medicines because the change in practice during this period. BCAA or single amino
child is either on maximum doses of medicines or refus- acid supplements can be given; there is no BCAA product
ing to take more and the protein intake is around the safe readily available in the UK.
intake and cannot be reduced further
• plasma amino acids are persistently low, with poor
growth and metabolic instability Feeding behaviour and tube feeding
• biological value of a low protein diet is lacking in one or Protein aversion (before and after diagnosis), poor appetite,
more EAA, which may occur if the protein is provided food refusal and poor variety of foods eaten, frequent vomit-
from a limited range of LBV protein foods ing and abnormal eating behaviour are features of some chil-
• natural protein intake is inadequate due to poor oral dren with UCD [217, 256, 326]. Some children may have an
intake (a tube may be the preferred option to provide ade- inadequate oral energy and nutrient intake due to mechani-
quate natural protein) cal feeding problems and unsafe swallow associated with
• metabolic control is poor, or there are repeated episodes neurological handicap or severe developmental delay,
of metabolic decompensation caused by hyperammonaemia or poor appetite. If a child is
• needed temporarily to help stabilisation in newly diag- unable to take sufficient orally, NG or gastrostomy feeding is
nosed patients essential to prevent hyperammonaemia and metabolic
decompensation. In a European study of feeding practices
EAA are generally given as a divided dose between feeds
[256], <20% received enteral tube feeds, and in a UK study
or two or three meals. Products differ in composition and age
25% [199]. Tube feeding may also be used specifically for
suitability (Table 28.62). It is important to be aware that all
administration of EAA and/or medicines, although the need
EAA provide a source of nitrogen (8.5%–13.7%), but this is
for this appears to be limited. The provision of a low protein
lower than the nitrogen content of food that ranges from
tube feed has been described on p. 570.
13.4% to 19.1% depending upon its amino acid composition
[347]. Similar products are available outside the UK (www.
abbottnutrition.com, www.meadjohnson.com, www.milupa‐ Nutritional and biochemical monitoring
metabolics.com).
Sodium phenylbutyrate is reported to selectively lower Recommended clinical, nutritional and biochemical moni-
plasma BCAA, and supplementation with BCAA has been toring of the diet is described (p. 565). In a study of 311 UCD
recommended [350, 351]. A possible mechanism for this is the patients, height z‐score was positively associated with the
Table 28.62 Essential amino acid products used in urea cycle disorders.
Amino acids Protein equivalent Energy kcal CHO Fat Vitamins and
Product (manufacturer) g/100 g g/100 g (MJ)/100 g g/100 g g/100 g minerals Comments
Dialamine (Nutricia) 30 25 360 (1.5) 65† nil ‡

Orange flavoured. Suitable from
6 months
Can be added to a feed, drink or
given as a paste
Essential Amino Acid Mix 94.5 79 316 (1.3) nil nil nil Suitable for infants under 6 months
(Nutricia)
EAA supplement (Vitaflo) 48 40 288 (1.2)¶ 31.8 0.1 ** Tropical flavour. Suitable from age
3 years
12.5 g/sachet
UCD amino5 (Vitaflo) 94.85 75.4 302 (1.28) nil nil nil Unflavoured. Suitable from 3 years
6.6 g sachet
EAA, essential amino acids.

Refer to manufacturers’ data information for full nutritional composition of products.
†
Contains a mixture of glucose polymer and sugar.
‡
Contains vitamin C and trace amounts of sodium, potassium, chloride, calcium, phosphorus and magnesium.
¶
Contains glucose polymer, sugar and sweeteners.
** Contains a comprehensive range of vitamins, minerals and trace elements.
natural protein‐energy ratio, and low plasma leucine and medicines: growth, dietary intake, type and doses (including
valine associated with height z‐score < − 2SD [211]. Although timings and frequency) of medicines, compliance with diet
there are limitations to this study, it serves to highlight the and medicines, age (puberty can be a difficult time), use of
importance of ongoing monitoring, careful interpretation EAA, use of ER and timing of blood sample in relation to
and management decisions. Frequency of monitoring foods/EAA intake. Looking for patterns in results over time
depends on the child’s overall metabolic stability in relation can be helpful.
to treatment and compliance. Younger and more severe High concentrations of glutamine and ammonia in plasma
patients need more frequent monitoring, 3–4 monthly being may be caused by:
typical for most patients who are stable. A 24 hour profile of
• inadequate medicines, too high or too low a protein intake
plasma ammonia and glutamine can be helpful in patients
(causing catabolism); both factors may be a compliance
who are difficult to manage. Timing of the blood sample is
issue. It is also important to ensure that medicines are
important as there is variation in relation to meals and medi-
given as divided doses over the 24 hour day.
cines. Ideally, samples should be obtained at the same time
• periods of chronic catabolism caused by either an inade-
and at trough levels 3.5–4 hours after a meal. This will avoid
quate energy and protein intake due to poor appetite or
high concentrations of amino acids (seen following con-
repeated use of ER; so growth and clinical status must
sumption of EAA supplements at mealtimes) and low con-
always be considered when interpreting the results.
centrations being missed [354]. However, it is not always
possible to collect samples under optimal conditions, so Poor appetite is observed in some children [355], with high
results need to be interpreted in the light of the conditions. glutamine levels implicated, possibly causing an increased
Plasma ammonia may be falsely elevated due to poor or dif- influx of tryptophan (the precursor of serotonin) into the
ficult blood sample collection. The overall aim is to maintain brain and promoting serotonin synthesis. Serotonin increases
plasma concentrations: ammonia (normal), glutamine (nor- a feeling of satiety [356]. If plasma glutamine is maintained
mal range or at least <1000 μmol/L), arginine (high, normal) within the normal range, then, in some children, appetite may
and amino acids, particularly BCAA, within normal improve. Low plasma BCAA may be due to phenylbutyrate
reference ranges to achieve normal growth and the best pos- (p. 591). Good biochemical control may be difficult to achieve
sible development [323, 354] (Table 28.63). It is important to during periods of slow growth before and particularly after
be aware that plasma glutamine does not directly influence puberty [355]. When the adolescent stops growing, there may
brain glutamine concentration, as this is synthesised mainly be a period of instability because protein is no longer needed
in the brain. It is not known if this is altered if plasma glu- for growth; protein intake and medicines may require adjust-
tamine concentrations are high [354]. ment to restore stability.
Changes to dietary protein, EAA intakes, arginine and Argininosuccinic acid accumulates in ASA and high dose
medicines (sodium benzoate and phenylbutyrate, and argi- arginine will also increase its production; the full conse-
nine in ASA and citrullinaemia) are based on the results of quences of this are not known, or if there is a specific plasma
these investigations, and alterations vary depending on the concentration, that ASA should be kept below. A high
disorder (Table 28.63). Blood results need careful interpreta- plasma arginine may also be harmful by causing an
tion (particularly if they are unsatisfactory) because they are increased cerebral guanidinoacetate concentration [357]; a
influenced by a number of different factors that need to be fasting plasma arginine concentration of up to
considered before implementing any change to diet or 70–120 μmol/L is considered acceptable [323]. Liver
Table 28.63 Guide to management decisions for urea cycle disorders (excluding arginase deficiency).
All influencing factors should be considered before making changes to diet or medicines.
Ammonia (μmol/L) normal Glutamine (μmol/L) normal Quantitative plasma

reference range <40 reference range 400–800 amino acids Suggested action
>80–100 >1000 Low EAA/BCAA Increase medicines in OTC and CPS*

Increase medicines in ASA and citrullinaemia;†
Increase natural protein or EAA
>80–100 >1000 Normal Increase medicines in OTC and CPS*
Increase medicines in ASA and citrullinaemia†
No change to diet
<80 <1000 Low EAA/BCAA No change to medicines. Increase natural protein
<80 <1000 Normal No change to medicines or diet
EAA, essential amino acids; BCAA, branched chain amino acids; OTC, ornithine transcarbamoylase deficiency; CPS, carbamoyl phosphate synthetase
deficiency; ASA, argininosuccinic aciduria.
†
ASA and citrullinaemia – arginine, sodium benzoate or phenylbutyrate. If plasma arginine is much above the normal reference range 40–120 μmol/L,
arginine dose is not increased; sodium benzoate and/or phenylbutyrate would be increased instead. If plasma citrulline or argininosuccinic acid is too
high, arginine is not increased; sodium benzoate and/or phenylbutyrate would be increased instead.
* OTC and CPS – sodium benzoate and/or phenylbutyrate.
Arginase Deficiency 593
functions tests (LFT) are routinely monitored in ASA to • Protein is usually reintroduced within 24–48 hours of
detect the presence of liver disease early. A lower dose of starting the ER and over a period of 1–2 days depending
arginine may help normalise LFT; however, nitrogen scav- on the child’s clinical condition and biochemical results.
engers will need to be increased to compensate [357]. • Practical advice on protein reintroduction is given on
Arginine is necessary for the synthesis of creatine (Cr), p. 678.
which is used in energy storage and transmission. Decreased • If the child is not improving at home or does not tolerate
Cr levels have been reported in OTC deficiency, citrullinae- oral/enteral ER and medicines, which is common, they
mia and HHH syndrome; in contrast, in ASA Cr levels are should be admitted to hospital without delay for IV 10%
increased [358]. It is not yet known if altered Cr metabolism dextrose and medicines. The BIMDG (www.bimdg.org)
effects CNS function in UCD. Monitoring of Cr may help to provides emergency protocols for IV management.
guide the dose of arginine in UCD as both high and low • Oral fluids can usually be recommenced within 24–48
plasma levels of arginine may have adverse effects [358]. hours, with a gradual changeover from IV to oral, thus
Dietary Cr intake may also be reduced on low protein diet always ensuring an adequate energy intake.
as meat is the main source. • Plasma ammonia should be measured frequently to help
guide protein reintroduction. Once the plasma ammonia
is falling and is <80–100 μmol/L, protein is gradually rein-
Emergency regimens for management of illness
troduced usually over the same 24–48 hour period. This
should not be delayed as inadequate protein will cause
• The standard ER of frequent feeds of glucose polymer
catabolism and increase ammonia levels further.
(p. 673) is given to prevent the effects of illness and accu-
• If hyperammonaemia is induced during protein reintro-
mulation of ammonia and glutamine and to promote
duction, giving an EAA supplement temporarily may help.
anabolism.
• Protein intake is stopped temporarily, and a high energy
intake is given from glucose polymer. The need to com-
pletely stop protein has been challenged [359]; the major- Learning points: urea cycle disorders
ity of patients studied were protein deficient on admission
with hyperammonaemia. However, there are no reports • Dietary management is a restricted protein diet with emer-
of undertaking this in practice. gency regimen during illness
• The usual doses of sodium benzoate, phenylbutyrate and • Nitrogen scavengers reduce waste nitrogen load to the urea
arginine are administered. If necessary during acute ill- cycle and thus ammonia
ness, the dose of both benzoate and phenylbutyrate can • Arginine becomes an essential or semi‐essential amino acid
be temporarily increased to 500 mg/kg/day. • Monitoring of plasma amino acids is essential to make med-
ical and dietetic management decisions
Arginase deficiency
Enzyme Arginase 1 (ARG1)

Biochemical defect ARG1 catalyses the conversion of arginine to urea and ornithine (Figure 28.10). Hyperargininaemia and a mild
hyperammonaemia occur due to defective hydrolysis of arginine.
Genetics Autosomal recessive inheritance, very rare disorder
Newborn screening No newborn screening
Clinical onset Arginase deficiency is distinct from the other UCD. Patients rarely present in the neonatal period but typically present with
presentation, features first symptoms between 2 and 4 years of age [360]. It is characterised by a progressive spastic paraplegia and cognitive
impairment (mild to severe mental retardation) that may continue to deteriorate, seizures and poor growth [360–362].
Episodes of hyperammonaemic encephalopathy can occur and appear to be more common than previously reported [361].
Similar to other children with UCD, some patients self‐limit protein prior to diagnosis. Interestingly, it has been reported
that this has been observed in children by their parents only after the age of 5 years [362].
Long‐term complications Treatment should help prevent further neurological damage and may induce a partial recovery of skills over time [360,
and outcome 363, 364]. Three patients treated from birth are reported to be largely without symptoms but are still at an age when they
are usually asymptomatic [361, 365]. In patients who already have spastic diplegia, dietary treatment will not improve this,
but can help prevent hyperammonaemia. The pathophysiology is yet to be fully delineated, but arginine and its guanidino
metabolites and alterations in NO synthesis are possible factors [360, 361, 366].
Medical and dietetic Management is to prevent accumulation of arginine and ammonia by:
management • a low protein diet (to limit dietary arginine), usually provided as a combination of natural protein and EAA supplements
• provision of an adequate energy intake (to prevent catabolism)
• sodium benzoate sodium or glycerol phenylbutyrate to provide an alternative pathway for waste nitrogen excretion
Clinical trials of enzyme replacement therapy are underway https://clinicaltrials.gov/ct2/show/NCT03921541.
Monitoring Clinical, nutritional and biochemical monitoring is same as for other UCD (p. 565, 591). The diet is monitored by regular
measurements of plasma ammonia and plasma amino acids, including arginine. Distinct from the other UCD, plasma
arginine is raised. The aim is to maintain plasma arginine levels <200 μmol/L (normal reference range 40–120 μmol/L),
which is extremely difficult to achieve, and a near normal plasma ammonia (normal range <40 μmol/L).
Emergency regimen Prompt implementation of an ER during intercurrent illness is essential to prevent hyperargininaemia and
hyperammonaemia and implemented as described for other UCD (but with no arginine medication):
• Stop natural protein intake and EAA supplements
• Give standard ER of frequent 2 hourly drinks/feeds of glucose polymer (p. 673)
• Give at least the usual doses of medicines (nitrogen scavengers)
• Admit to hospital, if not tolerating or not improving on ER
Clinical management Haberle et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision [323].
guideline
Dietary management suggested [323, 365]. The practical management of the low
protein diet and EAA supplementation are provided on
All dietary nitrogen has the potential to be converted to argi- pp. 562 and 590.
nine, this source being considerably greater than the small
amount of arginine that is naturally present in protein. In the
past, in order to restrict nitrogen intake, diets comprised an
Other metabolic disorders
EAA supplement with a very limited intake of natural pro-
The following rarer disorders are discussed in Clinical
tein. Nowadays, by giving sodium benzoate and phenylbu-
Paediatric Dietetics 4th edition [321]: lysinuric protein intoler-
tyrate, a more generous intake of natural protein may be
ance (p. 507), gyrate atrophy of the choroid and retina (orni-
possible while still maintaining acceptable plasma arginine
thine amino transferase deficiency) (p. 510), guanidinoacetate
and ammonia levels. Protein is restricted to the safe level of
methyltransferase deficiency (p. 513), alkaptonuria (p. 515),
intake (Table 28.47), and is provided by a low protein diet, or
isolated sulphite oxidase deficiency (p. 516), non‐ketotic
some of the protein as an EAA supplement, which is more
hyperglycinaemia (p. 517), trimethylaminuria or fish odour
common practice. Studies report: 17/23 patients had EAA
syndrome (p. 519), glucose‐6‐phosphate dehydrogenase
supplements, providing 25%–50% of total protein intake in
deficiency and favism (p. 523).
children <16 years of age [347]; in 10/19 patients providing a
median 0.65 g/kg/day range 0.25–0.9 g/kg/day [361]. The
precise composition of protein intake must be determined by
the balance of requirements for growth and the medicines
necessary for good biochemical control. A combination of
50%–75% as natural protein and 25%–50% as EAA has been
28.A Appendix
Table 28.A.1 Types of protein substitute available on prescription (ACBS) for PKU in the UK.
Phe content Energy CHO g

Protein Protein g per mg per unit kcal per per unit Fat g per Vitamins and
Name Company Unit size source Protein g/100 g unit size size unit size size unit size minerals LCPUFAs Age suitability flavours
PKU Anamix N 100 mL l‐Amino 13.1 2.0 0 70 7.5 3.5 Yes DHA, AA Infant formula
Infant acids Contains prebiotics
PKU Start V 100 mL* l‐Amino 14.3 2.0 0 68 7.2 3.5 Yes DHA, AA Infant formula
acids
PKU Anamix N 12.5 g l‐Amino 40 5 0 41 4.8 0.2 Yes DHA, AA From 6 months to 5 years
First Spoon acids Unflavoured
PKU Anamix N 125 mL l‐Amino 8/100 mL 10 0 118 8.8 4.8 Yes DHA From 1 to 10 years
Junior LQ acids Unflavoured, orange, berry
flavours
PKU Anamix N 36 g l‐Amino 27.8 10 0 135 11.5 4.5 Yes DHA From 1 to 10 years
Junior acids Unflavoured, orange, berry,
vanilla, chocolate flavours
PKU Explore 5 V 12.5 g l‐Amino 40 5 0 43 5.3 0.2 Yes DHA, AA From 6 months to 5 years
acids Unflavoured
PKU Explore 10 V 12.5 g l‐Amino 40 10 0 83 9.8 0.4 Yes DHA, AA From 12 months to 5 years
acids Orange, raspberry flavours
PKU Gel V 24 g l‐Amino 41.7 10 0 81 10.3 0.02 Yes No From 6 months to 10 years
acids Unflavoured
Orange, raspberry flavours from
12 months to 10 years
PKU Squeezie V 85 g l‐Amino 12 10 0 135 22.5 0.5 Yes DHA, AA From 6 months to 10 years
acids Apple, banana flavours
PKU Express 15 V 25 g l‐Amino 60 15 0 74 2.4 0.05 Yes No From 3 years
acids Unflavoured, orange, lemon,
tropical flavours
PKU Express 20 V 34 g l‐Amino 60 20 0 101 3.3 0.07 Yes No From 3 years
acids Unflavoured, orange, lemon,
tropical flavours
PKU Cooler 10 V 87 mL l‐Amino 11.5/100 mL 10 0 65 4.4 0.8 Yes DHA From 3 years
acids Orange, purple, red, white and
yellow flavours
acids Orange, purple, red, white,
yellow flavours
acids Orange, purple, red, white,
yellow flavours
Table 28.A.1 (continued)

PKU Air 15 V 130 mL l‐Amino 11.5/100 mL 15 0 75 2.0 0.8 Yes DHA From 3 years
acids Yellow (mango breeze), gold
(coffee fusion, contains <20 mg
of caffeine per pouch), white
(Caribbean crush), green (citrus
twist), red (berry blast) flavours
PKU Air 20 V 174 mL l‐Amino 11.5/100 mL 20 0 100 2.6 1.0 Yes DHA From 3 years
acids Yellow (mango breeze), gold
(coffee fusion, contains <20 mg
of caffeine per pouch), white
(Caribbean crush), green (citrus
twist), red (berry blast) flavours
PKU Lophlex N 62.5 mL l‐Amino 16/100 mL 10 0 58 4.4 Nil Yes DHA From 4 years
LQ 10 acids added Juicy orange, juicy berry, juicy
tropical, juicy citrus, berry,
orange flavours
PKU Lophlex N 125 mL l‐Amino 16/100 mL 20 0 115 8.8 Nil Yes DHA From 4 years
LQ 20 acids added Juicy orange, juicy berry, juicy
tropical, juicy citrus, berry,
orange flavours
XPHE Jump 10 M 63 mL l‐Amino 16/100 mL 10 0 63 5 0.3 Yes DHA (except From 3 years
acids unflavoured) Cola (without caffeine), wild
berries, orange flavours
Neutral (unflavoured)
XPHE Jump 20 M 125 mL l‐Amino 16/100 mL 20 0 126 10 0.6 Yes DHA (except From 3 years
acids unflavoured) Cola (without caffeine), wild
berries, orange flavours
Neutral (unflavoured)
PKU Easy Liquid G 130 mL l‐Amino 11.5/100 mL 15 0 98 2 0.5 Yes DHA, EPA From 3 years
acids Orange/citrus, mixed berries
flavours
PKU Easy Shake G 34 g l‐Amino 45 15 0 125 14 0.1 Yes No From 3 years
and Go acids Orange flavour
PKU Lophlex N 27.8 g l‐Amino 72 20 0 91 2.5 0.1 Yes No From 8 years
Powder acids Unflavoured, berry, orange
flavours
PKU Lophlex N 109 g l‐Amino 18.3 20 0 166 20.2 0.4 Yes DHA From 3 years
Sensation acids Berry flavour
Glytactin C 49 g CGMP 31 15 23 160 23 4.5 Yes DHA From 3 years
Bettermilk 15 Neutral flavour
Original Contains probiotic
Glytactin C 52 g CGMP 29 15 24 200 26 3.9 Yes DHA From 3 years

Bettermilk 15 Strawberry crème, orange crème
flavours
Contains probiotic
Glytactin C 16 g CGMP 63 10 10 54 2.1 0.6 Yes No From 3 years
Build 10 Neutral flavour
Contains probiotic
Glytactin C 46 g CGMP 43 20 35 150 12 2 Yes DHA From 3 years
Bettermilk Neutral flavour
Lite 20 Contains probiotic
Glytactin C 81 g CGMP 19 15 32 330 35 12 Yes No From 3 years
Complete 15 Fruity taste chewy bar
Fruit Frenzy
Glytactin C 81 g CGMP 19 15 37 320 42 8 Yes No From 3 years
Complete 15 Peanut butter taste chewy bar
Peanut Butter
Glytactin RTD 10 C 250 mL CGMP 4 10 18 153 21 3.5 Yes No From 3 years
Original Original, chocolate flavours
Glytactin RTD 15 C 250 mL CGMP 6 15 27 200 23 5 Yes No From 3 years
Original Original, chocolate flavours
Glytactin Restore C 20 g CGMP 25 5 9 73 14 0 No No From age 3 years.
Powder 5 Incomplete Orange, berry flavours
Glytactin Restore C 19 g CGMP 53 10 18 65 6.4 0 No No From 3 years

Lite Powder 10 Incomplete Orange flavour
Orange
GMPro N 33.3 g CGMP 30 10 18 128 12.5 3.9 Yes DHA From 3 years
Use with caution 3–6 years
Vanilla flavour
GMPro LQ N 250 mL CGMP 4 10 18 112 8.5 4 Yes DHA, EPA From 3 years
Use with caution 3–6 years
Vanilla flavour
PKU sphere 15 V 27 g CGMP 56 15 28 91 4.9 1.3 Yes DHA From 4 years
Red berry, vanilla, chocolate
flavours
Table 28.A.1 (continued)

PKU sphere 20 V 35 g CGMP 56 20 36 120 6.3 1.6 Yes DHA From 4 years
Red berry, vanilla, chocolate
flavours
PKU synergy N 33 g l‐Amino 60.6 20 <5 98 3.5 0.33 Yes DHA From 10 years
acids Citrus flavour
Phlexy 10 N 20 g l‐Amino 42 8.3 0 69 8.8 Nil No No From 8 years
Drink mix acids added Apple and blackcurrant, tropical
surprise, citrus burst flavours
Phlexy 10 tablets N 10 tablets l‐Amino 58 8.3 0 38 0.7 0.2 No No From 8 years
acids
PK Aid 4 N 100 g l‐Amino 79 g 79 g/100 g 0 71 Nil Nil No No For infants, children and adults
acids added Unflavoured
ACBS, Advisory Committee for Borderline Substances; PKU, phenylketonuria; Phe, phenylalanine; CHO, carbohydrate; LCPUFA, long chain polyunsaturated fatty acids; N, Nutricia; V, Vitaflo;
M, MetaX; Galen; C, Cambrooke Therapeutics; DHA, docosahexaenoic acid; AA, arachidonic acid; EPA, eicosapentaenoic acid; GCMP, casein glycomacropeptide.
All nutritional analysis is for unflavoured products.
* Pack size = 400 g.
29 Disorders of Carbohydrate Metabolism
Anita MacDonald, Marjorie Dixon and Fiona J. White
Disorders of Galactose Metabolism

Anita MacDonald
Galactosaemia
The common forms of galactosaemia are classical galactosaemia and biochemical (Duarte) variant galactosaemia.
Enzyme Galactose‐1‐phosphate uridyl transferase (GALT)

Biochemical defect An inability to metabolise galactose in the Leloir pathway, leading to hypergalactosaemia [1] (Figure 29.1).
Galactose‐1‐phosphate increases and is metabolised to galactitol and galactonate, both accumulating in abnormal
quantities in tissues. Galactose is a hexose monosaccharide that has an important role in energy delivery and in the
biosynthesis of complex carbohydrates, glycoproteins and glycolipids [2]. Abnormal glycosylation of glycoproteins and
glycolipids may occur.
Genetics Autosomal recessive inheritance. Incidence in Western Europe is estimated to be 1 in 16 500–44 000. The most
common classical galactosaemia mutation in Caucasian populations is Q188R (c.563A N G), associated with null red
blood cell GALT activity. Patients with Duarte variant galactosaemia have one GALT allele that is severely impaired
and a second GALT allele (Duarte‐2, D2) that is partially impaired [3].
Newborn screening No newborn screening (NBS) in the UK. No universal agreement about NBS.
Clinical onset The common forms are:
presentation, features • classical galactosaemia - is associated with neonatal symptoms and long‐term complications
• biochemical (Duarte) variant galactosaemia - infants and children may rarely present with this milder form. Patients
are usually asymptomatic and mainly identified due to abnormal NBS with moderate elevations in total blood
galactose and decreased GALT activity [4]. It is not associated with an increased risk of developmental abnormalities
and does not require dietary treatment [3]

Classical galactosaemia presents in the newborn period with life‐threatening illness when fed either breastmilk or
milk‐based infant formula (both contain galactose):
• Symptoms and signs include poor feeding, vomiting and diarrhoea, weight loss, jaundice, hypotonia, hepatic failure
and coagulopathy. Without urgent treatment, infants are at risk of Escherichia coli sepsis, multi‐organ failure and
death [5].
• Biochemical findings include abnormal liver function tests, abnormal clotting, hypoglycaemia, raised plasma amino
acids and renal tubular dysfunction. Rapid improvement occurs on stopping galactose‐containing feeds.
• Rarely, patients may present after the newborn period with faltering growth and developmental delay.
Long‐term complications Despite early diagnosis and strict galactose‐restricted diet, many treated patients develop one or more long‐term
and outcome complication(s).
Speech defect: Delayed speech vocabulary and childhood apraxia of speech are common [1]. More general speech/
language delays also occur associated with producing, rather than understanding, speech and language [4].
Cognitive development, executive and neurological function: Cognitive development, memory and executive
functions are commonly in the low average range, but there is a range of ability with some achieving university
education and attaining higher degrees.
Psychiatric symptoms: These include obsessive–compulsive disorder and autism spectrum disorder [6]. Anxiety and
depression may occur.
Primary ovarian dysfunction (POI): Ovarian damage resulting in POI occurs in 80% of women with classical
galactosaemia despite treatment [7], and the severity is variable [8]. Despite the high prevalence of POI, several
spontaneous pregnancies are documented, both in classical galactosaemia [9] and women with milder mutations. A
small number of women with galactosaemia have successfully breastfed their infants.
Reduced bone mineral density: 10%–25% of patients with classical galactosaemia are at risk of low bone mass density
(BMD z‐score <−2) as compared with the general population [10]. Diet restriction and ovarian insufficiency in women
both increase risk of compromised bone health. Blood vitamin D levels are commonly in the low reference range.
Growth disturbance: Growth may be delayed in childhood and early adolescence, but final height is usually normal,
although decreased height z‐scores compared to mid‐parental target height is described [11]. There is also a decrease
in fat mass and lean tissue mass compared with actual height z‐scores [12].
Medical treatment If galactosaemia is suspected, a galactose‐free formula should be given instead of breastmilk or standard infant
formula. Long‐term management includes:
• assessment of developmental milestones, intellectual development and speech and language should be done at
regular intervals such as preschool, primary, middle school and senior school ages according to International
Galactosaemia Guidelines [3]
• ophthalmological screening/follow‐up is necessary for cataracts
• many females need puberty induction and/or hormone replacement therapy to prevent sequelae of POI
The case study in Table 29.11 provides an example of initial medical management.
Dietetic management Galactose‐restricted diet. Glucose and galactose form the disaccharide lactose, present in most animal milks. It is also
available as free and bound galactose in carbohydrates such as oligosaccharides and polysaccharides, glycoproteins
and glycolipids.
The International Galactosaemia Guidelines [3] recommend a lifelong galactose‐restricted diet that only eliminates
sources of lactose and galactose from dairy products. At present there is insufficient evidence to support a specific
age‐related recommendation for the quantity of galactose allowed in the diet.
Monitoring – biochemical There is no consensus as to the most relevant biomarker(s) for monitoring as there is no clear association between
galactose metabolites, other markers and the development of both acute and long‐term complications:
• Red cell galactose‐1‐phosphate is widely used to monitor dietary adherence and should be measured at diagnosis
after 3 and 9 months, then annually [3]. More frequent measurements are only necessary if there is poor dietary
adherence.
• Galactose‐1‐phosphate is high at diagnosis and falls progressively after commencing galactose‐free formula/diet, but
can take up to 1 year or even longer to decrease to the local treatment reference range (laboratories use varying
target ranges). Concentrations do not decrease to normal levels found in healthy individuals [3].
• Vitamin D status: serum 25‐hydroxyvitamin D, 25(OH)D, levels should be measured annually in children [3].
• Dual‐energy X‐ray (DEXA) scans: every 4–5 years from onset of puberty.
Clinical management International Galactosaemia Guidelines 2016 [3].

guidelines
Patient support group The European Galactosaemia Society (EGS) www.galactosaemia.eu

The UK Galactosaemia Support Group www.galactosaemia.org
Galactosaemia 601
Endogenous production of galactose fat) and mayonnaise include milk components to improve
their flavour. The lactose content of whey derivatives such as
Significant amounts of endogenous galactose are produced whey powder is high, comprising 70% of total solids.
in patients with galactosaemia, being several‐fold higher for There are exceptions in a galactose‐restricted diet:
body weight in infants than in adults [13] who produce • caseinates: foods containing caseinates are permitted as
approximately 13 mg/kg body weight/day compared with they contain trace amount of lactose only. They are used
approximately 41 mg/kg body weight/day in newborns in coffee whiteners, meat products and baked goods. The
[14]. Endogenous galactose is thought to originate from the Casein and Caseinates Regulations [18] state that the
transformation of glucose and from the recycling of glyco- maximum anhydrous lactose content of casein should
sylated proteins and lipids. It is considered a major cause of not exceed 1% by weight
late complications [15]. • butter oil and ghee: these contain minimal lactose
and galactose and are permitted in the diet for galac-
Dietary management: galactose‐restricted diet tosaemia in the UK. Butter oil is used by the food
industry for the following functions: flavour, flavour
The International Galactosaemia Guidelines (2016) [3] rec- carrier, food gloss, creaming, air incorporation, anti‐
ommend: ‘treating patients with classical galactosemia staling and shortening [19]
with a life‐long galactose‐restricted diet that only elimi- • non‐milk derivatives that may be added to food prod-
nates sources of lactose and galactose from dairy products ucts are shown in Table 29.4. These do not need to be
but permits galactose from non‐milk sources that contrib-
ute minimal dietary galactose. Within this definition we
accept that small amounts of galactose are present in spe- Table 29.1 Lactose and galactose content of foods [17].
cific mature cheeses and caseinates. At present there is
insufficient evidence to support a specific age‐related rec- Lactose content Galactose content
Food (g/100 mL or g/100 g) (g/100 mL or g/100 g)
ommendation for the quantity of galactose allowed in
the diet’. Milk, skimmed 4.4 2.2
Milk, whole 4.5 2.3
Sources of galactose Cream, single 2.2 1.1
Lactose Yoghurt, low 4.4 2.2

Lactose is the main source of dietary galactose; it cleaves to fat, fruit
glucose and galactose when digested. Cow’s milk is the main Butter 0.6 0.3
dietary source of galactose and contains approximately Milk chocolate 10.1 5.1
2400 mg galactose/100 mL, and high amounts are found in Ice cream, dairy 5.2 2.6
yoghurt, soft cheese and other dairy foods [16]. All milk and
Lactofree milk 0.02 1.65
manufactured foods containing milk need to be avoided
(Arla)*
(Tables 29.1 and 29.2). Constituents of milk are likely to be
found in foods such as biscuits, some sweets and tinned and *Data analysed by UK Galactosaemia Support Group.
processed meats (Table 29.3). Many spreads (including reduced Source: Licensed under Open Government.
Diet
(1) kinase
Galactose Galactose-1-phosphate UDP-glucose
(2) (3)
Transferase Epimerase
Galactitol
Glucose-1-phosphate UDP-galactose
Glycolipids
Glycoproteins
Figure 29.1 Pathways of glucose metabolism.

Table 29.2 Milk, milk products and milk derivatives that should Table 29.3 Galactose‐restricted diet.
be avoided in galactosaemia.
Manufactured foods that contain or could contain milk or milk
Milk and milk products derivatives are shown in italics. Food labels should always be checked
Cow’s milk, goat’s milk, sheep’s milk as constituents change
Cheese, cream, butter Milk, milk products and milk derivatives
Ice cream, yoghurt, fromage frais, crème fraiche These should all be avoided (Table 29.2)
Chocolate
Plant and cereal milks
Milk derivatives Infant soya formula
Skimmed milk powder, milk solids, milk protein, non‐fat milk solids, Liquid soya milk, other plant milks (e.g. almond, coconut, oat,
separate milk solids rice*) – calcium enriched (not before 1 year of age)
Whey, hydrolysed whey protein, margarine or shortening containing
whey, whey syrup sweetener, casein, hydrolysed casein, sodium Fats and oils
caseinate, calcium caseinate Milk‐free margarine
Many margarines and low fat spreads contain milk
Lactose* Vegetable oils
Buttermilk, butter, artificial cream Lard, dripping, suet, ghee
Cheese powder
Meat and fish
Filtrated/enzymatically treated low lactose dairy products (containing Meat, poultry, fish, shellfish (fresh or frozen)
galactose) Ham and bacon (lactose may be used as a flavour enhancer – see
Low lactose milk, cheese, yoghurt, cream and spreads ingredient label)
Lactose as a filler may be used in Fish fingers
Flavourings Quorn
Tabletop or tablet artificial sweeteners Tofu
Medicines Many meat or fish products such as sausages, burgers, pies, breaded or
battered foods or in sauce may not be suitable
*Lactose powder is added to a diverse range of food products including Eggs
bakery goods, confectionery, dry mixes, dried vegetables and crisps. Cereal, flour, pasta
It is added: All grains; wheat, oats, corn, rice, barley, maize, sago, rye, tapioca
• To prepared foods to prevent caking or as a coating Pasta, spaghetti, macaroni, dried noodles, couscous
• To bakery goods to enhance browning and to reduce sweetness (it has Tinned pasta such as spaghetti hoops may contain cheese
one sixth the sweetness of sucrose) Flour: plain, self‐raising; cornflour, rice flour, soya flour, pastry products
• As a filler and flowing agent in seasoning mixes for foods such as Semolina
instant pot noodles or as a carrier for flavours and seasonings Carob
• Maybe to ham, bacon and salami Breakfast cereals
• To some artificial tabletop or tablet sweeteners Most are suitable, e.g. Weetabix, cornflakes, Rice Krispies
Some cereals may contain chocolate derivatives or milk
avoided except for lactitol, a polyol made from galactose. Bread and yeast products
Most bread is suitable
Some residual galactose is left after its fermentation in
Milk bread and naan bread contain milk, croissants and brioche
the gut, so it is unsuitable Pitta, chapatti
Muffins, crumpets and teacakes may not be suitable
Galactosides Cakes, biscuits, crackers
The α‐galactosides are part of the oligosaccharides (raffi- Many cakes, biscuits and crackers contain milk
nose, stachyose and verbascose) and are a potential source of Desserts
galactose. They are found in foods such as peas, beans, len- Sorbet, jelly, soya/plant desserts, soya/plant ice cream, soya/plant yoghurt
tils, soya beans, cocoa, nuts, wheat, oat flour and vegetables Most desserts/dessert mixes contain milk in some form
(Table 29.5). Fruit
Studies investigating the effects of galactosides in galac- All fresh, frozen, tinned or dried fruit
tosaemia are rare, include limited numbers of subjects and Vegetables
are short term and inconclusive. The α‐galactosidase linkage All fresh, frozen, tinned or dried vegetables
in oligosaccharides is not hydrolysable by the human small Most dried and tinned pulses, e.g. red kidney beans, chickpeas, lentils
Baked beans and ready‐made vegetable dishes such as coleslaw and
intestinal mucosa in vitro or in vivo. Instead, the galactosides
potato salad may contain milk
are rapidly degraded and fermented by the caecal microflora
to produce volatile short chain fatty acids. Galactosides are Savoury snacks
Plain crisps, poppadom
not avoided in the diet.
Nuts, peanut butter
The International Galactosaemia Guidelines (2016) [3] Flavoured crisps may not be suitable because they contain cheese or
recommend ‘allowing any amount and type of fruits, lactose as a filler in the flavouring
vegetables, legumes, unfermented soy‐based products.
Dry roasted nuts and popcorn may contain milk/butter
Although higher in galactose, all fermented soy‐based Seasonings, gravies
products can be allowed in the small quantities that are Pepper, salt, pure spices and herbs, mustard
typically used in the diet’.
Galactosaemia 603
Table 29.3 (continued) Table 29.6 Free galactose in fruit and vegetables (mg/100 g).
Marmite, Bovril, Bisto Food UK* USA

Gravy granules and stock cubes may contain milk
Soups Tomato 10 23
Tinned, packet and carton soups may contain lactose Grape <10 2.9
Sugar, sweet spreads Cucumber 20 4.0
Sugar, glucose, fructose
Banana 10 9.2
Pure artificial sweeteners
Powdered and tablet artificial sweeteners may contain lactose Watermelon 14.7
Jam, syrup, honey, marmalade, lemon curd Kiwi fruit 10
Confectionery
Boiled sweets, most mints, marshmallow, plain fruit lollies, chewing *Unpublished data analysed by UK Galactosaemia Support Group [20].
gum
Milk chocolate, most plain chocolate, butterscotch, fudge and toffee
contain milk
<50 mg/100 g serving [22], and an adult diet rich in fruits
Plain or carob chocolate may contain milk and vegetables was found to contain only 54 mg of galac-
tose per day [23]. Free and bound galactose food sources
Drinks
Soya, plant or nut drinks are not restricted in the diet. Fermented soybean products
Milk shake syrup or powders may contain milk (e.g. soya sauce, miso, tempeh) contain a greater concen-
Fizzy drinks, squash, fruit juice tration of free galactose since the fermentation process can
Cocoa, tea, coffee release galactose from various oligosaccharides; they are
Drinking chocolate may contain milk still permitted in small quantities [3].
Instant milk drinks and malted milk drinks – avoid
Miscellaneous – used in baking Galactose storage organs
Baking powder, yeast, gelatine, marzipan Offal is a source of galactocerebrosides and gangliosides.
Flavourings Small amounts of galactose may be present in free form and
Lactose may be used as a ‘carrier’ for flavourings, particularly in crisps bound to proteins as glycoproteins and galactolipids. Cell
and similar snack foods. In sweets lactose is rarely used for this purpose lipids and proteins continuously undergo d egradation,
except in some dairy flavours
See Table 18.4
releasing glycerol, fatty acids, amino acids and their carbo-
hydrate components, including galactose [24]. Their galac-
*Not recommended for children <4½ years old due to its high arsenic tose content is unknown, but there is no evidence of any
content. harmful effects in galactosaemia. In the UK they are not
avoided, although the International Galactosaemia
Table 29.4 Non‐milk derivatives. Guidelines suggest they be taken in moderation only [3].
Lactic acid E270, sodium lactate E325, potassium lactate E325,

calcium lactate E327 Practical management of a low galactose diet
Lactalbumin, lactoglobulin, lycasin, stearoyl lactylates, glucono‐delta‐
lactone, monosodium glutamate, cocoa butter, non‐dairy cream As the main source of galactose in foods, the avoidance of
lactose is the key element in a galactose‐restricted diet.
Table 29.5 Dietary sources of galactosides. Milk substitutes

Galactosides Peas, beans, lentils, legumes, chickpeas, dhal, gram Breastfeeding and cow’s milk‐based infant formulas are con-
flour, spinach traindicated because they contain galactose. It is important
Texturised vegetable protein
that infants and young children be given a suitable nutrition-
Soya (other than soya protein isolates), soya beans,
soya flour
ally adequate formula.
Fermented soya products, e.g. soya sauce
Cocoa, chocolate Soya infant formula
Nuts The Medical Advisory Panel of the Galactosaemia Support
Group (GSG) and the British Inherited Metabolic Disease
Group (BIMDG) recommend that soya infant formula con-
Free and bound galactose tinues to be used as the first‐choice low galactose infant for-
Free galactose is present in many fruits, vegetables and mula for galactosaemia. While it is accepted that it contains
legumes (Table 29.6). Free galactose content may vary
a source of phytoestrogens with its associated mild risk of
from <0.1 mg/100 g to 40 mg/100 g [21]. In selected plant oestrogenicity, the potential disadvantages of other formulas
materials, it ranges from 2 ± 0.1 mg/100 g in red potato to far outweigh any concerns about the phytoestrogen content
39.7 mg/100 g in red pepper. The free galactose content of of soya infant formula. It is widely used by other countries
most fresh or processed fruits, vegetables and legumes is and it has been safely given to infants with galactosaemia for
over 40 years. Nevertheless, caregivers should be informed Amino acid‐based formulas

about the phytoestrogen content of soya infant formula and Amino acid‐based formulas are lactose‐free and used by
be reassured about its safety for their infant. some centres. They are more likely than soya infant formulas
Nutritionally complete soya infant formula, e.g. SMA to be fortified with novel nutrients, such as long chain poly-
Wysoy, is lactose‐free. There is no evidence soya infant formula unsaturated fatty acids, but are considered less palatable.
is a factor in the fertility problems seen in galactosaemia.
Plant, cereal and nut drinks for children over 1 year of age
Low lactose and protein hydrolysate formulas Many commercial nutritionally enriched plant, cereal and
Other suitable infant formulas include low lactose formulas nut drinks (e.g. soya, oat, rice, coconut, hazelnut and almond)
and casein hydrolysate formulas (Table 29.7). Medium chain are suitable. Most contain approximately 120 mg/100 mL of
triglyceride (MCT)‐based casein hydrolysate infant formula, calcium and 0.8 μg/100 mL of vitamin D. There are also
such as Pregestimil Lipil, may be advantageous when there nutritionally enriched follow‐on soya milks designed for
is significant liver disease and should be administered until children >1 year with added calcium, iron, vitamin D, some
this complication has resolved. B vitamins and an energy profile similar to cow’s milk (e.g.
All low lactose and protein casein hydrolysate formulas Alpro Soya Growing Up milk). Calcium absorption from
based on cow’s milk protein contain some residual lactose, soya drinks is similar to that from cows’ milk.
and the amounts vary. Manufacturers of these formulas Rice milk, which is suitable in galactosaemia, contains
declare their lactose content at <10 mg/100 kcal (420 kJ) as traces of inorganic arsenic, and the UK Food Standards
defined by the European Food Safety Authority [25]. A 5 kg Agency recommend children aged between 1 and 4½ years
infant taking 200 mL/kg of formula would have <14 mg/ should avoid rice milk.
kg/day (or a maximum of 69 mg/day) of galactose from this
source. Whey hydrolysate formulas contain a higher concen- Unsafe milks/drinks
tration of residual lactose and are unsuitable. Enteral feeds Since lactose is the carbohydrate source in animal milks, e.g.
for older children based on whey hydrolysates are also goat’s and sheep’s milks, these are unsuitable. A low lactose
unsuitable. dairy drink, Lactofree (Arla), where approximately half the
lactose content is removed by filtration and the remainder is
removed enzymatically, is available. However, it contains a
significant quantity of galactose, rendering it unsuitable for
Table 29.7 Low lactose, casein hydrolysate and amino acid formulas
galactosaemia (Table 29.1) [20].
for infants with galactosaemia. Lactase enzyme drops, which reduce the lactose content of
cow’s milk, are also unsuitable as the drops digest the lactose
Lactose into glucose and galactose.
content
Infant formula Protein source (per 100 mL) Cheeses
Low lactose Hard mature cheeses
Galactomin 17 (Nutricia) Caseinate 6 mg Cheese is a good source of calcium and other nutrients and
Casein hydrolysate provides additional variety in the diet. The International
Nutramigen 1 with LGG (Mead Enzymatically <5 mg
Galactosaemia Guidelines [3] recommend that any mature
Johnson) hydrolysed casein cheese with a galactose content <25 mg/100 g is suitable
(Table 29.8). The fermentation process and bacterial fermen-
Nutramigen 2 with LGG (Mead Enzymatically <5 mg
Johnson) (not suitable for infants hydrolysed casein
tation lower the lactose content. Most mature cheese types
under 6 months) have high levels of casein (which contains no more than 1%
lactose) and low levels of whey (which contains 70% lactose).
Pregestimil Lipil (Mead Johnson) Enzymatically <5 mg
hydrolysed casein The lactose content is reduced by the removal of whey by
Similac Alimentum (Abbott Enzymatically <5 mg
Laboratories) hydrolysed casein Table 29.8 Types of mature cheese allowed in galactosaemia (galactose
content <25 mg/100 g).
Amino acids
Alfamino (Nestle Health Science) l‐Amino acids Nil Extra mature cheddar (typically 12–15 months old)
Vintage cheddar (typically 15–18 months old)
Neocate LCP (Nutricia) l‐Amino acids Nil Emmental
Neocate Syneo (Nutricia) l‐Amino acids Nil Gruyere
Jarlsberg
Nutramigen Puramino (Mead l‐Amino acids Nil
Comte
Johnson)
Italian parmesan (Parmigiano Reggiano and Grana Padano)
Infant weaning food
Neocate Spoon (Nutricia) (not l‐Amino acids Nil These cheeses have been extensively tested for their lactose and
suitable for infants under 6 months) galactose content [26] and have been shown to contain minimal lactose
and galactose on repeated analysis.
Galactosaemia 605
drainage (during this stage approximately 98% of the lactose regulatory role in the mineralisation and remodelling of bone
will be removed). The type of starter culture, coagulating [28]. Vitamin K supplementation may be beneficial when
enzyme and the acid produced can all alter lactose content combined with an adequate intake of calcium and vitamin D,
by influencing the properties of the curd and the degree of but currently there is not enough evidence to recommend
whey expulsion. this.
For harder cheeses the curd is cut into small cubes, which
allows fluid to drain from the individual pieces of curd. Any Calcium and vitamin D
residual lactose in cheese curd is metabolised during its rip- It is important to ensure the reference nutrient intake (RNI)
ening process [27], and, generally, the longer the cheese has for all bone‐related nutrients is provided. Calcium intake
matured, the lower its lactose content. may be low. The UK RNI for calcium varies between 325 and
Other cheeses are not permitted. Specific analysis has been 1000 mg daily in children and teenagers [29]. Wherever pos-
commissioned by the UK Galactosaemia Medical Advisory sible, calcium requirements should be achieved from food.
Panel to test gouda, edam and some soft and processed Soya infant formula can provide RNI for calcium (age 0–2
cheeses, but all contain lactose and galactose and are not years) provided an adequate amount is taken. With advanc-
suitable [26]. ing age it may be necessary to change to a calcium‐enriched
plant drink (preferably supplemented with vitamin D).
Plant cheeses Suitable food sources should be encouraged to ensure ade-
Plant cheeses are suitable. They are dairy‐free and made quate intake: low galactose cheese, plant yoghurts, sardines,
from nuts, such as cashew, almond and pine nuts; soybeans; mackerel, sesame seeds and lentils (Table 29.9).
coconut oil; rice; and other ingredients. However, some are A calcium supplement may be needed. This can be chal-
low in protein and other nutrients, such as calcium. lenging mainly because of the size, type of presentation
(mostly tablets rather than liquid) and nutritional composi-
Enzyme‐treated cheese products tion available for children. Additional vitamin D supple-
Lactofree cheese produced from Lactofree milk is not mentation will aid calcium absorption, e.g. Healthy Start
recommended. vitamin drops (Table 1.22). Alternatively, there are several
prescribable calcium supplements with added vitamin D
Manufactured foods (Table 29.10). The latter are mainly chewable or dissolvable
in water. They are bulky and unpopular with children and
Interpreting galactose on food labels adherence is an issue. There are no suitable liquid calcium
As galactose is found in milk sources, it is important to teach supplements listed in the British National Formulary (BNF)
caregivers and patients how to identify milk on food labels. for children. If the diet as a whole is poor, it may be neces-
It is mandatory that a milk source is identified on the ingre- sary to give a more comprehensive vitamin and mineral sup-
dient list of pre‐packed foods (listed either in bold, in an plement, e.g. Paediatric Seravit or FruitiVits (suitable from 3
alternative colour or by underlining). The word ‘milk’ does years of age). Ideally calcium supplements should be
not need to appear if a milk product such as cheese, cream, co‐administered with vitamin D and given in more than one
yoghurt or butter is an ingredient because these foods,
legally, can only be made from animal milks. It is mandatory
to identify milk when the reference is to a less familiar dairy Table 29.9 Food sources of calcium for galactosaemia [17].
product or ingredient, e.g. quark (milk) and whey (milk).
Calcium (mg) Vitamin D (μg)
Cross‐contamination of manufactured foods with milk
Both milk‐free and milk‐containing foods may be manufac- per 100 mL/100 g
tured in the same plant or even using the same machinery. Calcium/vitamin D enriched 100–140 0.8
Cross‐contamination with milk is always possible, and if soya drinks
there is a risk of a food product being cross‐contaminated, the Soya dairy‐free yoghurts 120 Variable
label should include one of the following statements: ‘may
Low lactose hard cheese 730 0.3
contain milk’ or ‘not suitable for someone with milk allergy’.
The UK Galactosaemia Support Group Medical Advisory Whitebait 860 Not available
Panel permits foods that are labelled with a risk of cross‐ Sardines in oil/brine 500 5
contamination with milk. It is likely the quantity of milk is Pilchards 250 14
minimal.
Sesame seeds 670 0
Red kidney beans 100 0
Vitamin and mineral supplementation Bread 170 0
Many nutrients are involved in optimum bone metabolism, Spinach 170 0
particularly calcium, phosphate and vitamin D. Vitamin K Apricots 73 0
also has an important role, acting as a cofactor in the post‐
translational carboxylation of osteocalcin, which has a Source: Licensed under Open Government.
Table 29.10 Suitable calcium supplements for galactosaemia.
Presentation Available calcium (mg) Vitamin D (μg)
Adcal‐D3 (Kyowa Kirin Ltd). Calcium carbonate. Chewable tablet/effervescent Tablet 600 10
tablets. Not licensed for children under 12 years.
Cacit‐D3 (Warner Chilcott UK Ltd). Calcium carbonate. Granules. Not licensed Sachet 500 11
for use in children.
Calceos (Galen). Calcium carbonate. Chewable tablet. Tablet 500 10
Calcichew D3 (Takeda UK Ltd). Calcium carbonate. Chewable tablet. Tablet 500 5
Calcichew D3 Forte (Takeda UK Ltd). Calcium carbonate. Chewable tablet. Tablet 500 10
Natecal D3 (Chiesi Ltd). Calcium carbonate. Chewable tablet. Tablet 600 10
Information from manufacturers’ data cards.
daily dose. The International Galactosaemia Guidelines UK Galactosaemia Support Group

(2016) [3] recommend ‘an annual dietary assessment of cal-
cium and vitamin D intake with measurement of plasma The UK Galactosaemia Support Group (www.galactosaemia.
total 25‐OH‐vitamin D levels. Both calcium and vitamin D org) produces a wide range of educational materials for par-
should be supplemented as necessary following the age‐spe- ents and caregivers including a galactose‐restricted diet
cific recommendations for the general population’. guide for children and adults, a small dietary shopping card,
Easter and Christmas lists of suitable treats, information
Iodine about healthy bones and a glossary of food ingredient defini-
Cow’s milk is usually a rich source of iodine in the diet tions. It has also commissioned the analysis of several foods
(depending on dairy farming practices). Many plant milks for their lactose and galactose content and employs a dieti-
are not fortified with iodine [30]. If patients with galactos- tian who produces much of the dietary information.
aemia use these, it is important to encourage alternative
dietary sources such as seafood and eggs. An iodine‐
containing supplement (not kelp or seaweed owing to risk
Dietary restriction in pregnancy
of iodine excess) may need to be considered. A 3‐day
There is no advantage to restricting milk in the mother’s diet
dietary food record to assess iodine intake should be under-
during pregnancy.
taken annually.
Lactose in medications Case study

Lactose is an excipient with properties that make it ideal as a
A case study demonstrating the dietary management of an
tablet filler or binder, and it is found in many medications;
infant diagnosed in the neonatal period is given in
for most the amount of lactose is unlikely to be significant,
Table 29.11.
particularly if the medication is being used for a short time
period [31], but it is still important to check the amount.
Lactulose contains high quantities of lactose and galactose: Learning points: galactosaemia
1 mL contains <100 mg galactose and 67 mg lactose [32] and
is contraindicated in galactosaemia. • Galactosaemia usually presents as a life‐threatening illness
Contraceptive pills prescribed for oestrogen insufficiency in infancy and early symptoms resolve with a galactose
contain lactose as an excipient and provide approximately restricted diet
20–65 mg lactose/day (manufacturers’ data sheets). • Comprehensive international guidelines for the medical
Some toothpastes and shampoos may contain milk deriva- and dietary management of galactosaemia are available [3]
tives. No recommendation is given to avoid these. Although • The UK Galactosaemia Support Group produces practical
young children may swallow some toothpaste, the amount resources to help patients with dietary management
should only be small.
Long‐term dietary treatment

Galactokinase deficiency and
A lifelong galactose‐restricted diet is recommended for UDP‐galactose‐4‐epimerase
galactosaemia although there is debate about how strict die-
tary treatment should be in teenage years and beyond. These are very rare disorders of galactose metabolism.
Overall there is little evidence to support the safety of dis- Clinical, biochemical and dietetic overview can be found in
continuation of the galactose‐restricted diet. the 4th edition of Clinical Paediatric Dietetics [33].
Introduction to Glycogen Metabolism 607
Table 29.11 Case study: clinical presentation of galactosaemia in the neonatal period.
Baby boy, born full term, discharged home from local hospital on day 3
Fully breastfed, birthweight = 4.5 kg
Appeared well except for jaundice
Feeding deteriorated and he started vomiting
Admitted to a local hospital, diagnosed with a urine infection and commenced antibiotics. However, he was also found to have liver dysfunction with
deranged clotting and intermittent hypoglycaemia and was transferred to a paediatric liver ward. Galactosaemia was suspected; breastfeeding was
stopped; soya infant formula was given; fluids were restricted
Over the next 3 days, fluid intake was gradually increased to normal requirements; liver function similarly improved; he tolerated the soya infant
formula and his clinical symptoms ameliorated within 48 hours
Classical galactosaemia was diagnosed with a galactose‐1‐phosphate concentration >2000 μmol/L and determination of galactose‐1‐phosphate
uridyltransferase activity. He was homozygous for the Q188R mutation.
Discharged home on a galactose‐restricted diet only
He drank soya infant formula without difficulty, and galactose‐restricted solids were introduced at 20 weeks of age. Parents gradually expanded his
diet according to his age, introducing low lactose cheese, plant yoghurts and other suitable products
His galactose‐1‐phosphate concentration only slowly lowered to within treatment range during the first year despite excellent dietary adherence
He continued to feed well and gained weight appropriately
At the age of 2 years, he was changed onto a toddler calcium and vitamin D enriched commercial soya drink. His weight and length were adequate,
as were his intakes of calcium and vitamin D
At the age of 3 years, his clinical progress is good, but speech is slightly delayed. His nutrient intake, growth and galactose‐1‐phosphate concentrations
are assessed twice per year
Glycogen Storage Disorders

Marjorie Dixon and Fiona J. White
Introduction to glycogen metabolism branch (which glycogen phosphorylase then shortens), leav-
ing one glucose moiety at the α‐1,6 branch point, and the
Glycogen, the storage form of carbohydrates (CHO), is glucosidase component releases the single glucose moiety
found predominantly in the liver and skeletal muscle; minor and breaks the branch point – hence the name debrancher
stores are found in the heart and brain. It is a large molecule enzyme. Phosphoglucomutase then converts glucose‐1‐
containing up to 60 000 glucose moieties that are linked in phosphate into glucose‐6‐phosphate (G6P). Skeletal muscle
straight chains with α‐1,4 glycosidic bonds, and branched glycogen is predominantly degraded to glucose‐6‐phos-
with α‐1,6 glycosidic bonds, at intervals of 4–10 glucose resi- phate where it is used by muscle fibres during contractions
dues, thus forming a glucose reservoir. Glycogen is a major and converted to lactate, as detailed below.
fuel source. In the fed state glucose forms glycogen (glyco- G6P has three fates:
genesis). Glycogen synthase catalyses the formation of the
• conversion to free glucose via glucose‐6‐phosphatase,
α‐1,4 linkages between glucose molecules, enabling the glu-
which occurs predominantly in the liver, for release into
cose chain to elongate, forming amylose. Glycogen branch-
the bloodstream
ing enzyme then catalyses the formation of the α‐1,6‐linked
• as the initial substrate for energy production via glycoly-
branch points to enable assembly of side chains of glucose
sis, forming pyruvate. Under aerobic conditions p yruvate
molecules, amylopectin, resulting in the polymer, glycogen.
is oxidised to form ATP; under anaerobic conditions in
In the fasting state liver glycogen is degraded (glycogenoly-
active muscle tissue, it is converted to lactate. Lactate
sis) to glucose‐6‐phosphate via a series of enzymatic
generated from muscle glycogen or glucose can be trans-
reactions. Phosphorylase kinase activates glycogen phos-

ported via the bloodstream to the liver and, via the
phorylase, the rate‐limiting step in glycogenolysis, which
gluconeogenic pathway, to reform glucose. This recy-
shortens the unbranched outer α‐1,4 links of the glycogen
cling pathway is known as the Cori cycle
molecule to release glucose‐1‐phosphate and leave four glu-
• processed by the pentose phosphate pathway to yield
cosyl units at the α‐1,6 branch point. The debrancher enzyme
NADPH and ribose derivatives
then performs two catalytic functions: the transferase com-
ponent transfers three glucose residues (from the shortened Gluconeogenesis is the reversal of glycolysis and is
glycogen branch) to the end of a neighbouring glycogen another major pathway for glucose formation via G6P from
lactate, pyruvate, gluconeogenic amino acids and glycerol. as the glycogen storage disorders (GSD). These are notated
Fructose and galactose can also enter the gluconeogenic by a Roman numeral, the deficient enzyme or the person
pathway to form glucose or, via glycolysis, forms pyruvate who first described the disorder (Figure 29.2, Table 29.12). In
and lactate (Figure 29.2). A more detailed review of glycogen this section the hepatic GSD are discussed as these are treated
metabolism is given elsewhere [34]. primarily by diet. Treatment ranges from complex intensive
Defects of most enzymatic reactions involved in glycogen feeding routines with overnight tube feeds to more straight-
metabolism have been identified and collectively are known forward avoidance of fasting and management of illness.
Glucose
Lysosomal
Degradation
Phosphorylase b kinase
Glycogen VI IX
Phosphorylase a Phosphorylase b
Amylopectin
0 PLD
UDP-glucose
IIIa, IIIb
Glucose-1-phosphate
Galactose Galactose-1-phosphate
(Figure 29.1)
Pentose phosphate pathway la, lb

Ribose-5-phosphate Glucose-6-phosphate Glucose
glut 2 Cell membrane

XI
Gluconeogenesis Glycolysis
Uric acid
Extracellular glucose
Fructose (Figure 29.6)
Pyruvate
alanine
Lactate
acetyl-CoA Free fatty acids
TCA cycle
Triglycerides
Figure 29.2 Pathway of liver glycogen metabolism. UDP‐glucose, uridine diphosphate glucose; PLD, phosphorylase limit dextrin; TCA, tricarboxylic acid.
Table 29.12 Hepatic glycogen storage disorders, nomenclature and main organs involved.
Type Eponym Enzyme deficiency Principal organs involved
0 Glycogen synthase Liver

Ia Von Gierke Glucose‐6‐phosphatase Liver, kidney
Ib Glucose‐6‐phosphatase translocase Liver, kidney and leucocytes
III a/b Cori, Forbes Debranching enzyme and subtypes Liver +/− muscle
VI Hers Phosphorylase Liver
IX Phosphorylase kinase and subtypes Liver and/or muscle
XI Fanconi Bickel Glut 2 Liver, kidney
Glycogen Storage Disease Type I 609
Glycogen storage disease type I

Marjorie Dixon
Enzyme Glucose‐6‐phosphatase system

Biochemical Two subtypes:
defect
• GSD type Ia – Deficiency of glucose‐6‐phosphatase that hydrolyses G6P into glucose and inorganic phosphate. Expressed in
liver, renal cortex and intestinal mucosa, but not muscle.
• GSD type Ib – Deficiency of glucose‐6‐phosphate transporter protein (G6P translocase) that transports G6P from the cytoplasm
across the endoplasmic reticulum membrane into the lumen for hydrolysis [35]. Expressed ubiquitously.
The glucose‐6‐phosphatase system is the final common pathway reaction for endogenous glucose synthesis from both glycogenolysis and
gluconeogenesis (Figure 29.2). Glucose production is inadequate if either enzyme is deficient. Hypoglycaemia results after relatively short
periods of fasting when exogenous glucose sources are depleted, typically around 2 hours. As G6P cannot form glucose, there is increased
glycolytic flux, which leads to secondary metabolic derangements of lactic acidosis (with or without hyperventilation), hyperuricaemia and
hyperlipidaemia, with triglycerides more markedly elevated than cholesterol [36]. Hyperlipidaemia is likely due to increased de novo lipid
synthesis from excess acetyl‐CoA (formed from pyruvate) and decreased lipid serum clearance [37]. Hyperuricaemia is caused by
decreased renal clearance due to competition with lactate for excretion and increased breakdown of adenine nucleotides to uric acid [38].
Ketone body production, as an alternative fuel during fasting, is reduced because excess acetyl‐CoA leads to increased concentrations of
malonyl‐CoA, which promotes lipid synthesis rather than oxidation of fatty acids to form ketones.
Genetics GSD types Ia and Ib are autosomal recessive inherited disorders. GSDIa occurs more frequently (about 80% of GSDI patients) than
type Ib and is the most common of the hepatic GSD.
Clinical Can present in the neonatal period, but more typically occurs later in infancy between 4 and 6 months when periods of fasting are
presentation, extended, particularly overnight. The resulting fast‐induced hypoglycaemic episode can cause seizures and lactic acidosis. Features
features include growth retardation, truncal obesity and muscle wasting, rounded doll‐like facies and hepatomegaly (causing a protuberant
abdomen) due mainly to fatty infiltration of the liver; bruising and bleeding can occur due to platelet dysfunction [38, 39]. These
features can also be seen in treated patients, but generally to a lesser extent.
Additionally in type Ib, there is chronic neutropenia and impaired neutrophil function, which increases susceptibility to recurrent
bacterial infections, oral and intestinal mucosal ulcerations and a chronic inflammatory bowel disease (IBD) similar
histopathologically to Crohn’s disease [40–43]. Neutropenia is considered due to increased apoptosis of mature neutrophils and the
movement of neutrophils from blood to inflamed tissues.
Long‐term Renal disease (both glomerular and tubular dysfunction) and hypertension in some [44]; hepatic tumours (mostly benign
complications adenoma, but with the potential for malignant transformation), which develop predominantly during and after puberty [45];
low bone mineral density and osteopenia [46, 47]; anaemia [48]; polycystic ovaries in females [49, 50]. GSDIa patients are at
risk of developing insulin resistance and metabolic syndrome [51, 52]. There are only a few reports of diabetes in the
literature [53].
Medical Acute management of hypoglycaemia and correction of biochemical abnormalities. Medicines are prescribed to correct the latter
treatment and to help prevent long‐term complications, e.g. allopurinol if plasma urate is raised, an ACE inhibitor for persistent
microalbuminuria, both to help preserve kidney function. There are reports of successful liver [54, 55] and hepatocyte transplants
[56] in GSDI patients. Liver transplant corrects the metabolic derangement, but some type Ib patients still experience frequent
infections [55, 57]. Hematopoietic stem cell transplant is an option to treat neutropenia and neutrophil dysfunction in GSDIb, but
the need for intensive dietary treatment remains [58]. Post‐liver transplant dietary treatment is no longer indicated, but tube feeding
may still be necessary because of ongoing feeding problems [59].
Type Ib
Granulocyte‐colony stimulating factor (G‐CSF) treatment increases neutrophil count and decreases fever, infection and severity of
IBD; however, splenomegaly with abdominal pain is a complication and limits dosage [40, 58]. Vitamin E supplementation, given
for its antioxidant properties, is reported to improve neutrophil function, reduce infections and enable a decrease in G‐CSF doses
[60, 61].
Dietetic Infants and children need a frequent supply of CHO both day and night to maintain normoglycaemia. Provision of CHO varies by
management age and fasting tolerance; typically 2 hourly daytime feeds for infants and young children. From around 1 to 2 years: introduction of
uncooked cornstarch (UCCS) may extend fasting tolerance; for older children: continuous tube feeds or UCCS at night. Post‐
puberty, CHO therapy is still needed, but may be less frequent.
Emergency During intercurrent infections, glucose polymer solution is given to maintain normoglycaemia and prevent hypoglycaemia and
regimen lactic acidosis. The emergency regimen (ER) should provide at least adequate CHO to meet endogenous glucose production rates
for age (Table 29.13) or the child’s usual CHO requirement. A standard ER may provide too much glucose and cause
hyperglycaemia and thus risk of rebound hypoglycaemia.
Monitoring Clinical, anthropometric and biochemical monitoring is essential to assess efficacy and guide dietary treatment, which aims to
promote normal growth, minimise secondary biochemical abnormalities and help delay the onset and severity of long‐term
complications. More detailed clinical and biochemical monitoring is given on p. 617.
610 Disorders of Carbohydrate Metabolism Introduction to Glycogen Metabolism 610
Clinical Kishnani P, Austin SI, Abdenur JE et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the
management American College of Medical Genetics and Genomics. Genet Med. 2014, 16(11) e1 [63].
guideline Rake JP, Visser G, Labrune P et al. Guidelines for management of glycogen storage disease type I – European Study on Glycogen
Storage Disease Type I (ESGSDI). Eur J Pediatr. 2002, 161(1) S112–119 [64].
Visser G, Rake JP, Labrune P et al. Consensus guidelines for the management of glycogen storage disease type 1b – European Study
on Glycogen Storage Disease type 1. Eur J Pediatr, 2002, 160(1) S120–3 [40].
Parent support Association for Glycogen Storage Disease (UK) (www.agsd.org.uk)
group
Dietary management • large quantities of glucose exacerbate swings in blood

glucose levels and make patients more prone to hyper-
Aims are to: glycaemia and rebound hypoglycaemia [64]
• CHO usually needs to be given at 2 hourly intervals
• maintain a constant normal blood glucose concentration or more often in infants and young children not on
without large swings. Hypoglycaemia carries the risk of UCCS and Ib patients who often have a poor response
neurological complications [65], and hyperglycaemia can to UCCS
cause hyperinsulinism and, long term, may lead to insu- • CHO is given during the day as infant formula and glu-
lin resistance [52, 53] cose polymer, complex CHO from food and UCCS
• help correct secondary biochemical abnormalities by • CHO is given overnight as continuous tube feeds (infant
maintenance of normoglycaemia, though it is recognised formula, paediatric enteral feed with glucose polymer or
that these cannot be completely normalised [66]; hyper- just glucose polymer) or UCCS
lipidaemia is frequently observed on treatment [36, 37] • guidance on amounts of CHO foods to eat at each meal
• optimise and promote normal growth and maintain a and snack should be given, as around 40% of energy
healthy body mass index (BMI) as overweight and obe- intake may be provided by night feeds, UCCS and glu-
sity is a common problem [51, 67, 68] cose polymer
• promote exercise, although it is recognised that exercise • avoidance of foods with a high sugar content is impor-
capacity can be reduced in some [69]; less active children tant to prevent swings in blood glucose levels and exces-
should have a lower energy intake sive glucose and energy intake
• help delay or prevent long‐term complications • vitamin and mineral supplements are necessary because
of the high energy intake from pure starch and glucose
Provision of carbohydrate
Fructose and galactose
• Per cent energy intake of the diet in children who are eating
is typically: 40% from UCCS and glucose polymer and from • fructose and galactose are not metabolised to G6P for
food 20%–30% CHO, 20%–30% fat and 10%–15% protein glucose production, but instead may lead to increased
• glucose intakes are calculated to be similar to normal lactate production via glycolysis [73]
hepatic endogenous glucose production rates [62, 70–72], • there is no consensus about the need to restrict these sug-
but should be adjusted to achieve good biochemical con- ars, and management between countries differs [63]; UK
trol (p. 617); more or less glucose may be needed. centres generally do not limit these sugars
• glucose requirements (g/kg/hour or mg/kg/min) • a mildly elevated blood lactate level of up to 4.0 mmol/L
decrease with age (Table 29.13) is considered acceptable by some because lactate provides
• insufficient CHO leads to high plasma lactate levels and an alternative source of energy to the brain and, therefore,
growth retardation; excessive CHO induces peripheral body has a protective effect against fuel depletion [74]
fat storage due to glycogen overload and hyperlipidaemia • hypoglycaemia can have a detrimental impact on brain
function [65]
• some children have near‐normal plasma lactate despite
Table 29.13 Glucose requirements based on endogenous glucose including dietary fructose and lactose
production rates [62]. • intake of these sugars will inadvertently be reduced
because pure starch (UCCS) and glucose polymer pro-
Glucose (g/kg/hour) vide around 40% of energy intake
Glucose (mg/kg/
• if plasma lactate is persistently elevated on an unre-
Age minutes) Day Night
stricted diet, a trial of reducing fructose and galactose
Infants 8–9 0.5 0.5 may be warranted
Toddlers and children 5–7 0.3–0.4 0.3–0.4 • as the intake of fruit, vegetables, milk and dairy products
is limited, vitamin and mineral supplements (specifically
Adolescents and adults 2–4 at night 0.2–0.25
calcium and vitamin D) are necessary
Fat • infants <4–6 months of age require around 0.5 g glucose/

kg/hour (Table 29.13), which can be provided by the lac-
• fat intake needs to be decreased to compensate for
tose in standard infant formula fed at normal volumes of
increased CHO intake
150–180 mL/kg; both galactose and glucose contribute
• replacement of saturated with polyunsaturated fats is
towards the glucose requirement
recommended by some in an attempt to improve hyper-
• glucose polymer is added to infant formula if:
lipidaemia, but this is much less important than supply-
◦◦ the normal fluid volume for age and weight provides
ing a frequent CHO intake and avoiding overtreatment
insufficient glucose
• despite persistent hyperlipidaemia, no evidence of
◦◦ inadequate feed volume is consumed
endothelial dysfunction or premature atherosclerosis has
◦◦ blood glucose and lactate control is not optimal
been observed [75–77]; however, others suggest patients
• NB: adding glucose polymer increases energy content;
may be at increased risk of cardiovascular disease [78]
therefore, the feed volume may need to be decreased to
• two small cohort studies [79, 80] have reported that using
maintain a normal energy intake and avoid overfeeding.
MCT as a fuel may allow a reduction of energy from
Maintenance of adequate protein and micronutrient
CHO; concerns have been raised about the possible ben-
intake is essential; supplements may be required if feed
efits of all the biochemical changes from adding MCT [52]
volume limits these. Alternatively, a modular feed could
• MCT is not standard dietary treatment of GSDI
be considered with reduced fat to compensate for the
increased CHO energy and thus to achieve a normal total
Tube feeding overnight energy intake
• some centres use a soya infant formula to avoid galactose
• continuous gastrostomy feeding is used to provide
and provide all the glucose as glucose polymer
overnight feeds in type Ia, but gastrostomy is contrain-
• at night the feed is given continuously via a pump, usu-
dicated in type Ib because of infection risk and poor
ally administered for 8–10 hours. At the beginning and
wound healing [65]
end of the night feed, an oral or bolus feed providing
• continuous nasogastric (NG) feeding is used to provide
sufficient glucose to last for 30 minutes is given (i.e. 50%
overnight feeds in type Ib, but there are risks, including
of the volume given for 1 hour from the night feed)
aspiration [81]. Some families have a care package for
• breastfeeding is possible though is demanding for a
home with a healthcare professional to manage and
mother: at least 2 hourly daytime feeding is necessary; a
monitor the overnight NG tube feeding
very small volume top‐up feed of 10%–20% glucose pol-
• parents need to undergo competency training for any
ymer solution with each breastfeed may be necessary to
form of tube feeding
maintain normoglycaemia. Expressed breastmilk can be
• the feed pump must accurately control flow rate and
used for the continuous overnight feed or infant formula
alarm immediately if there is electrical or mechanical
could be given instead. Additional breastfeeds may be
failure; fatalities have been reported because of
given during the night
unplanned cessation in delivery of the glucose feed or
• regular 1–2 weekly monitoring of growth is essential to
failure to switch on the pump delivering the feed [81]
adjust feeds and optimise management
• to prevent any leaks, the tubing used for feed delivery
must be secure An example of an infant’s feeding regimen is shown in
• an enuresis alarm may be helpful in identifying any leak- Table 29.14.
age of feed into the bed
• some parents use baby alarms to hear if their child is rest- Weaning onto solid foods
less or wakens during the night as this can be a sign of The introduction of solid foods can begin around 6 months
problems with the overnight feed or hypoglycaemia (26 weeks) of age:
• continuous overnight feeds usually continue until the
• continue to provide 0.5 g glucose/kg/hour
child stops growing when it may be possible to maintain
• often the infant is not hungry because of the frequent day
normoglycaemia overnight with UCCS; more than one
and overnight feeding; establishing food intake is often
dose overnight may be required
difficult and invariably there is reliance on tube feeding
• solids should contain complex CHO foods such as baby
Diet for infants rice, oat/wheat‐based cereal, rusk, potato, pasta to provide
glucose and low fat protein foods such as chicken, lean
Newly diagnosed infants will be managed in hospital where
red meat, white fish and pulses
fasting tolerance needs to be determined:
• as starchy food intake increases, it can replace part or all
• most infants need to be fed at 2 hourly intervals with of the infant feed at main meals as the source of glucose
some needing feeds every 90 minutes (often type Ib) for the following 2 hours
• bedside blood glucose monitoring is used to guide die- • parents need to count CHO to ensure sufficient is given
tary treatment; ideally 24 hour blood glucose and lactate at each meal and to avoid excess; a list of the weights of
profile (1–2 hourly measurements) should be done before starchy foods that will provide specified amounts of
discharge CHO for 2 hours is given, and parents are taught to
Table 29.14 Example feeding regimen for a female infant, age 10 weeks, with GSDI.
Aim 0.5 g* glucose/kg/hour (Table 29.13)
Energy
CHO
Weight = 5 kg Fluid (mL) (kcal) (kJ) (lactose) (g) Protein (g) Fat (g)
SMA PRO 1 840 562 2352 60 10.5 30

Amount/kg 170 112 470 12.0 2.1
Amount/kg/hour 0.5*
Amount/hour 2.5
% energy intake 43% 8% 48%
Daily feed distribution

Day: Oral feeds 70 mL
06.30, 08.00, 10.00, 12.00, 14.00, 16.00, 18.00, 20.00 = 560 mL
Night: Continuous nasogastric feeds 35 mL every hour from 22.00, finishing at
06.00 = 280 mL
Bolus nasogastric feeds 20 mL at 22.00 and 06.30 (extra to calculated fluid
requirement)
*Lactose = 0.25 g glucose and 0.25 g galactose. Glucose polymer can be added to provide more glucose, as indicated
by blood glucose and lactate results.
calculate and weigh the amount of food required using Diet for children
the CHO analysis on food labels, for example, an infant
• provide 0.3–0.5 g glucose/kg/hour (Table 29.13)
weighing 8 kg requires 0.5 g glucose/kg/hour, which
• under 2 years of age the daytime glucose continues to be
equates to 8 g CHO for 2 hours:
given at 2 hourly intervals (or more often) either from a
◦◦ Step 1: Look at total CHO content per 100 g of food
meal or snack containing complex CHO or a paediatric
(on nutrition analysis label)
enteral feed with added glucose polymer
◦◦ Step 2: Then 100 ÷ by the CHO content per 100 g of
• starchy foods such as potato, rice, pasta, bread and break-
food
fast cereals are encouraged in preference to sugary foods
◦◦ Step 3: Multiply the answer by 8 (or other amount of
as these are more slowly digested to produce glucose
CHO required) = weight of food, which provides 8 g
• from around 1 year of age the night feed is changed to
CHO (or other amount of CHO required)
a solution of glucose polymer up to 15% CHO con-
• if insufficient food is eaten, then a full feed or a top‐up
centration in 1 to 2 year olds, providing weaning is
feed of infant formula with a total concentration of 12%–
well established; 20% CHO for 2 to 6 year olds; 25%
15% CHO is given to provide the 2 hourly CHO
up to a maximum of 30% CHO for older children.
requirement
Often a vitamin and mineral supplement is added to
• boluses of pure glucose polymer are best avoided because
this feed
it is rapidly absorbed, may cause swings in blood glu-
• occasionally, a paediatric enteral feed is administered at
cose and may not maintain blood glucose for 2 hours in
night in preference to glucose polymer alone, particu-
some patients
larly if growth or food (and nutrient) intakes are
• for the overnight feed the volume of infant formula is
inadequate
decreased, and glucose polymer added to provide
• many children find it very difficult to eat breakfast due to
around 0.5 g glucose/kg/hour, with the ultimate aim of
being fed overnight; CHO may need to be provided from
providing all CHO as glucose polymer from about 1 year
simple sugar such as glucose polymer, milk or fruit juice
of age, provided weaning is well established and the
as a drink or mixed with the dose of UCCS
child has a good food intake
• in type Ib bacterial infections, oral and intestinal mouth
• the daily feeding regimen must be nutritionally adequate
ulcers and chronic IBD may necessitate further dietary
and meet protein requirements; this can be compromised
manipulation
in patients on high CHO diets and who also do not
• mouth ulcers can make oral feeding difficult and painful;
eat well. Vitamin and mineral supplements are often
meals and snacks may need to be temporarily replaced
necessary
with nutritionally complete fluid supplements, and if
An example of a weaning diet is shown in Table 29.15. necessary these can be given via NG tube
Table 29.15 Example of a diet for a 10‐month‐old infant with GSDI.
Weight = 8 kg Aim 0.5 g glucose/kg/hour (4 g CHO/hour) (Table 29.13)
Energy
Time Food or drink Total CHO (g) CHO* (g/kg/hour) Protein (g) Fat (g) (kcal) (kJ)
08.15 ½ Weetabix (10 g) 6.5 0.4 1.1 0.2 34 143

100 mL semi‐skimmed milk 2.9 0.2 2.2 1.1 30 125
10.00 100 mL SMA PRO 2 7.9 0.5 1.3 3.2 67 280
12.00 Baby pouch (130 g) chicken 11.8 0.7 4.3 1.3 80 336
casserole and rice
14.00 Small banana (40 g) 8 0.5 0.5 0.1 36 151
16.00 1 potato waffle (58 g) 13 0.8 1.4 5.1 106 445
1 grilled fish finger (28 g) 6.0 0.4 3.5 2.3 61 256
salad: cucumber, tomato,
lettuce
18.00 Fromage frais (60 g) 4.9 0.3 2.5 1.1 41 174
Raspberries 70 g 3.2 0.2 1.0 0.2 22 93
20.00 to 08.00 SMA PRO 2 (200 mL) 48.0 0.5 2.6 6.4 254 1067
12 hours + glucose polymer (30 g)
+ water to 360 mL
(13.3 g CHO/100 mL)
30 mL hourly
20.00 and 08.00 SMA PRO 2 (recipe above) 4.0 0.2 0.5 21 89
15 mL bolus
Total 116 21 22 752 3158
94 kcal/kg 395 kJ/kg
% energy intake 62 12 26
*The portion size of CHO foods (appropriate for age) will make the CHO content of main meals in excess of the specified requirement of 0.5 g/kg/hour
(calculated as a combined intake).
Uncooked cornstarch to be induced by oral starch [91]. Once UCCS is introduced

and 2 hourly fasting tolerance is extended, feeding problems
UCCS, ‘household cornflour’, is a branched chain glucose
often gradually begin to abate.
polymer (92% CHO) made up of amylose (linear chain) and
amylopectin (branched chain). The ratio can vary; some have
UCCS practical aspects: dose and frequency
a high amylopectin to amylose ratio. Uncooked, it is slowly
digested, primarily by pancreatic amylase to gradually
of administration
UCCS should be given in the following way:
release glucose into the circulation. In GSDI it is given to
help maintain normoglycaemia [82]. When compared with • uncooked; cooking or heating disrupts the starch gran-
glucose polymer feeding, a smoother blood glucose profile is ules by hydrolysis and thus makes it much less effective
produced, and less glucose is required [83, 84]. Lee at al. • ideally mixed with cold water or milk; it has a chalky taste
reported only achieving satisfactory glycaemia for a median • mixed with squash or carbonated drinks is reported to
of 4.25 hours (range 2.5–6.0) [85]. The variation in response make it less effective because of increased insulin pro-
may be due to malabsorption [86]. Glycosade is a hydro- duction [83, 84]
thermally processed high amylopectin starch, which is a slow‐ • can be mixed with semi‐liquid food such as yoghurt,
release CHO. A number of studies [87–90] have reported fruit purée and thin cold custard or mixed with milk and
improvements in duration of fasting, glucose and insulin then poured onto breakfast cereal, but this provides more
profile in some older children and adults, when compared bulk for the child to eat and is also a source of sugars
with UCCS. Further trials are underway to assess response • can be given via feeding tube if refused orally, but the
in younger children. UCCS is usually introduced between 1 oral route should still be encouraged; it can block the
and 2 years of age. In younger children it may not be ade- feeding tube so needs to be administered with adequate
quately digested to maintain normal blood glucose because fluids and the tube flushed afterwards
pancreatic amylase activity only reaches mature levels • it settles out on standing and needs to be mixed or shaken
between 2 and 4 years of age, although its activity is reported prior to consuming
Dosing of UCCS: the usual daytime dose, to extend normoglycaemia, is

suggested; this should be trialled in hospital
• a dose is typically required every 3–6 hours, but this is
• some families routinely give overnight continuous tube
based on the results of the UCCS load test (see below)
feeds, but for certain circumstances, e.g. holidays or
• each dose is up to 2 g/kg body weight in young children,
sleepovers, will instead give UCCS
decreasing to around 1.5 g/kg in older children and 1 g/
kg in adolescents who have stopped growing
Example of continuous glucose monitoring before
• overweight and obese children are given lower doses
based on ideal rather than actual weight for height
and after introduction of small dose of UCCS
A 12‐month‐old child with GSDIb had 2 hourly feeds of Cow
• responses differ and need to be individually assessed;
& Gate 1 infant formula with added glucose polymer to 11%
low doses even in young children should be tried and
total CHO concentration, providing 0.45 g glucose/kg/hour
used if possible to lower energy intake from pure CHO
during the day and overnight feeds providing 0.41 g glucose/
• dose and frequency need to be reviewed regularly and
kg/hour. During the day blood glucose levels fluctuated with
tailored to requirements taking into consideration
hypoglycaemia and hyperglycaemia (Figure 29.3). A dose of
growth velocity, frequency of hypoglycaemia and bio-
2.5 g of UCCS was added to each 2 hourly daytime feed. Blood
chemical results. It should only be increased as indicated
glucose results improved with a smoother blood glucose pro-
rather than routinely based on increasing body weight
file and maintenance of normoglycaemia (Figure 29.4).
• success has been reported in children <2 years of age
using smaller more frequent doses [92–94]
• small doses added to 2 hourly day feeds has helped to
UCCS load test
When initiating UCCS treatment, a fasting ‘UCCS load test’
maintain blood glucose levels in older infants rather than
takes place in hospital to assess the child’s metabolic
by increasing glucose polymer (Figures 29.3 and 29.4)
response by serial hourly measurements of blood glucose
• using the standard doses/kg appear to be less effective
and lactate, initially hourly, but more frequently as blood
in maintaining normoglycaemia in type Ib compared
glucose concentration falls. The process is as follows:
with Ia (personal experience); smaller more frequent
doses may be beneficial • prior to the load test, UCCS is introduced at home to test
• the diet usually comprises two or three doses of UCCS its palatability and acceptance; this may be helped by
during the daytime, after breakfast, lunch and some- giving a small amount from a young age, around 12–18
times evening meal depending on the time the night feed months
starts • the dose is gradually increased to a maximum of 2 g/kg
• some families prefer to use UCCS at night as it is less (or other target lower dose/kg) at one meal, beginning
complicated and more socially acceptable than tube feed- with 5 g and increasing by 5 g every week to the required
ing, but the main disadvantage of this for young children dose with no change to usual regimen
is the need to wake frequently at around 4 hourly inter- • some patients may experience side effects such as diar-
vals, thereby interrupting sleep. Parents also need to rhoea, abdominal distension and flatulence, but these are
wake up to give the dose and rely on an alarm clock to do usually transient
so. Failure to waken does occur and is a risk [81] • the load test in hospital should use the UCCS brand the
• if UCCS is given at night, a larger dose compared with family use at home
Sensor data (mmol/L)

Wed 09-Nov Thu 10-Nov Fri 11-Nov Sat 12-Nov Sun 13-Nov Mon 14-Nov Average
20
15
10
8.0
Blood
glucose 5
3.5
2.2
0
00:00 02:00 04:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 00:00
Time of day
Figure 29.3 24 hour continuous glucose monitoring before uncooked cornstarch. Normoglycaemia is shown by shaded grey band.
Sensor data (mmol/L)

Thu 16-Aug Fri 17-Aug Sat 18-Aug Sun 19-Aug Mon 20-Aug Average
20
15
10
8.0
Blood
glucose 5
3.5
2.2
0
00:00 02:00 04:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 00:00
Time of day
Figure 29.4 24 hour continuous glucose monitoring after uncooked cornstarch. Normoglycaemia is shown by shaded grey band.
• an example of the results of an UCCS load test is given in Cornflour load test GSDIb – age 6 years, 1.5 g/kg
Figure 29.5. Over time blood glucose decreases and lac- 6
tate increases. The test is stopped when blood glucose Glucose
5 Lactate
is <3 mmol/L and/or the child has symptoms of
hypoglycaemia 4
• the biochemical test results are used to determine the fre-
mmol/l
quency and quantity of UCCS doses 3

• some children have a poor response to UCCS; in 2
young children the maximum fasting period is
usually 3–4 hours, but this usually improves with 1
increasing age
• if fasting tolerance to a standard dose of UCCS for age 0
1 2 3 4
is short, giving a larger dose is unlikely to extend the
Hours
time
• ideally patients should have 24 hour glucose and lactate Figure 29.5 Uncooked cornstarch (cornflour) load test.
profiles and UCCS load test repeated annually. UCCS
load test is performed on initiation of UCCS, increasing Adolescents
age, consideration of discontinuation of night feed, poor
growth or biochemical indices and starting or changing • after puberty some form of nocturnal glucose therapy
school needs to continue to prevent fasting hypoglycaemia and
• when planning the UCCS regimen, it is important to be biochemical abnormalities [95]
aware it can take around 30 minutes before glucose is • adolescents should be reassessed at this time to deter-
released mine their fasting tolerance as this may differ from that
• UCCS is best given after a meal so it does not reduce in childhood
appetite; actual timings need to be planned around the • discontinuing the overnight tube feed can be difficult
child’s daytime routine even when growth ceases, as UCCS does not maintain
normoglycaemia for sufficiently long periods
An example of a diet incorporating UCCS is given in
Table 29.16.
Cornflour, Glycosade (from age 2 years) and glucose pol- Vitamins and minerals
ymer are approved by the Advisory Committee on • vitamin and mineral deficiencies can occur particularly
Borderline Substances (ACBS) for prescription. Cornflour as a high percentage of the dietary energy intake is pro-
is usually a shop brand and, therefore, is food rather than vided as glucose polymer and pure starch
pharmaceutical grade. The dose of cornflour is measured • thiamin is essential for normal glucose metabolism and
either by scoops or more accurately by weighing. Glycosade at least the RNI for age should be supplied
is presented in a sachet: each 60 g sachet provides 53 g CHO • inadequate calcium intakes and reduced bone mineral
(which equates to a dose of 55 g UCCS); the required dose is density (BMD) has been found [47, 96] although this also
then measured. occurs with normal calcium intakes in GSD [97]
Table 29.16 Example diet for a 7‐year‐old boy with GSDI.
Weight = 27 kg 75th–91st centile, ideal body weight = 22 kg 25th–50th centile.

Aim 0.3 g glucose/kg/hour overnight and cornflour 1.5 g/kg/dose (using ideal body weight)
Time Food or drink
08.00 CHO foods, e.g. breakfast cereal, bread; often only small amount eaten
Breakfast 35 g cornflour mixed with up to 100 mL water or semi‐skimmed/skimmed milk
10.30 Snack if no breakfast eaten to provide 10 g CHO, e.g. portion fruit, small slice bread with
Mid‐morning margarine, 1 semi‐sweet biscuit
12.00 CHO foods to provide 20–30 g CHO, e.g. bread, pitta, wrap as sandwich
Lunch suggestions Fillings, e.g. ham, low fat cheese, egg, chicken, tuna and salad vegetables
Fruit or low fat/low sugar yoghurt
13.00 35 g cornflour mixed with up to 100 mL water or semi‐skimmed/skimmed milk
17.00 CHO foods to provide 20–30 g CHO, e.g. potato, pasta, rice, chapatti, couscous, noodles
Evening meal suggestions Meat, chicken, eggs, fish, dhal
Vegetables or salad
Fruit or low fat/low sugar fromage frais
19.00 CHO foods to provide 10–15 g CHO, e.g. toast, crackers, crumpet, muffins, semi‐sweet
Bedtime snack biscuit, cereal and semi‐skimmed milk
suggestions
20.00 to 07.30 20% glucose polymer 35 mL hourly (provides 0.3 g CHO/kg/hour)
20.00 and 07.30 15 mL bolus of 20% glucose polymer
Energy requirement = 71 kcal (295 kJ)/kg/day = 1562 kcal (6.5 MJ)/day (Scientific Advisory Committee on Nutrition. Dietary

Reference Values for Energy, 2011).
Provide around 60% daily energy intake from CHO = 937 kcal (3.9 MJ)/day.
% CHO energy intake from UCCS and glucose polymer = 616 kcal (2.6 MJ)/day, 154 g CHO = 40% energy.
% CHO energy from food limited to 20% energy = 321 kcal (1.3 MJ), 80 g CHO.
The meal plan suggests amounts of CHO to give at main meals and snacks.
• vitamin D and calcium intakes need to be adequate CHO with prolonged exercise. Parents often report the need
together with good metabolic control to optimise bone to give food or sugary drinks before, during or after exercise.
health [46, 47] Pre‐exercise dietary treatment may need to be adjusted
according to the intensity and duration of the exercise being
undertaken with complex CHO for low to moderate inten-
Quality of life
sity and a sugary snack/drink for high intensity. Guidance is
The intensive 24 hour feeding regimen is demanding and required on quantities as too much sugar will result in
time consuming for parents, particularly if feeding 2 hourly. hyperglycaemia. It is important that children are encouraged
It is disruptive to normal living during the day and particu- to be physically active to help prevent overweight or obesity
larly night for both parents and child, with potentially seri- and associated risks of diabetes and cardiovascular disease.
ous consequences if treatment is not adhered to [81].
Management requires constant watching of the clock and Hypoglycaemia
great attention to detail as delay in feeding will result in
hypoglycaemia; human errors do occur including forgetting Hypoglycaemia occasionally occurs and may be related to
to switch on the pump or alarm clock [81]. Feeding problems delayed meals/drinks/UCCS, illness, poor dietary compli-
are common and can manifest as a poor food intake or qual- ance or prolonged exercise. Parents should contact the meta-
ity of diet and overfeeding because of concern about hypo- bolic team if there is repeated hypoglycaemia. Parents need
glycaemia. A lower quality of life has been reported in GSDI to recognise early warning signs such as sweating, pallor,
patients; this study also highlights the burden of care on par- irritability or drowsiness and respond by immediately giv-
ents [98]. Disordered eating and body esteem is also reported ing a sugary or glucose polymer drink orally or via the tube
[99]. Support from a paediatric psychologist is valuable. and, on recovery, some starchy foods. Excessive amounts of
glucose can cause rebound hypoglycaemia; 10–20 g glucose
is usually adequate. Dextrose gels such as Glucogel (40%
Exercise
dextrose) can be rubbed into the buccal cavity and is an
A major reduction in exercise capacity in adult patients with invaluable treatment for the semiconscious or uncooperative
GSDI has been reported, with mean blood glucose levels for child. If the child is unresponsive or fitting, emergency ser-
patients showing a progressive decrease throughout exercise vices should be urgently called. Patients with GSDI do not
and recovery [69]. Children are likely to require additional respond to glucagon (as it normally increases blood glucose
via glycogenolysis and gluconeogenesis); IV glucose (10%) children may not be symptomatic at these blood glu-
or a dextrose gel (as above) is necessary to treat a child with cose levels as lactate may be providing an alternative
hypoglycaemia who is unconscious. fuel source. Single blood glucose and lactate levels in a
routine clinic appointment are not a good indicator of
Managing the unwell child: emergency regimen for GSDI long‐term metabolic control
◦◦ plasma lactate <4.0 mmol/L. Some centres aim to
During intercurrent infections, adequate glucose must be maintain lactate in the normal reference range: 0.5–
maintained to prevent hypoglycaemia and, in GSD type I, 1.0 mmol/L (mild to moderate hyperlactataemia:
lactic acidosis: 2.0–4.0 mmol/L). This can be very difficult to achieve
• the standard ER concentrations of glucose polymer for in some patients, and a moderately increased lactate
age used for management of illness in other metabolic may be beneficial as it provides fuel to the brain
disorders (p. 677) may provide too much glucose, par- when blood glucose is low [74]. Lactate can be chron-
ticularly at 20%–25% glucose polymer concentration, ically elevated despite seemingly good dietary treat-
resulting in hyperglycaemia and potential rebound ment. The concentration at which lactate contributes
hypoglycaemia when discontinued to long‐term complications is not known
• the ER glucose solution for GSD1 should provide the ◦◦ plasma triglycerides (TG) <6 mmol/L [64], normal
endogenous glucose production rate for age or the child’s fasting levels 0.5–2.2 mmol/L. The American College
usual hourly glucose intake (Table 29.13) and an ade- of Medical Genetics and Genomics (ACMG) guide-
quate intake of fluids (similar volumes to standard ER) lines [63] do not suggest an aim for plasma TG. Wang
• often 24 hour continuous tube feeds of glucose polymer will et al. [45] reported significantly increased adenoma
replace either the usual 2 hourly dietary regimen or UCCS progression in patients with a mean 5‐year TG value
• IV fluids may be necessary and must provide adequate, of >5.6 mmol/L. TG can be chronically raised and
but not excessive, glucose compared to the usual require- probably reflect decreased metabolic control [36].
ment of g glucose/kg/hour or mg/kg/min (Table 29.13) Ideally TG should be as near normal as possible
• an overall adequate glucose intake must be given when • Weight and height should be monitored regularly and
titrating from IV fluids back to the usual feeding plan BMI calculated. BMI should ideally be normal range, but
• if IV fluids have provided more glucose than the usual this can be difficult to achieve in some patients. The
overnight feed, there is a risk of hypoglycaemia; this suggested aim is to maintain BMI between 0 and +2
needs to be considered when planning the titration plan standard deviation scores [64]. Mid‐upper arm circum-
and blood glucose should be monitored ference is another useful assessment tool particularly if
there is hepatomegaly, but is not standard practice.
An example of an ER is given in Table 29.17. • Growth retardation occurs with inadequate treatment
and even on intensive treatment [100, 101]. Mundy et al.
Clinical and biochemical monitoring have reported improved growth with intensive dietary
treatment, but a subset within their patient group who,
Clinical, anthropometric and biochemical monitoring is despite therapy, have poor growth. These patients had
essential to assess the efficacy of dietary treatment and to measured endocrine responses similar to those reported
guide the composition of the diet (Table 29.18): for untreated patients, but the reasons for this are not yet
• Continuous glucose monitoring is a useful tool (p. 629). clear [100]. Interestingly, the more obese patients were
Blood glucose monitoring at home may be useful, but is tallest, although as a group they were significantly
not perceived essential for daily management. shorter than average.
• Biochemical aims of dietary treatment are: • Regular biochemical monitoring of vitamin and miner-
◦◦ preprandial blood glucose >3.5 mmol/L. Hypoglycaemia als, in particular calcium and vitamin D, is recommended
is defined as a blood glucose <3.0 mmol/L. Some because of risk of low BMD and osteopenia. BMD should
be assessed by DEXA scan from 5 years of age every 1–2
years [64].
Table 29.17 Example of an emergency regimen for a 3‐year‐old girl
with GSDI.
ER to provide 0.4 g glucose/kg/hour. Body weight = 14 kg Learning points: glycogen storage disease type I
Calculate the daily amount of glucose = 0.4 g × 14 kg × 24 hour = 134 g • Dietary treatment involves avoidance of fasting, frequent
(5.6 g glucose/hour) provision of glucose day and night, with individualised
feeding regimens
Recipe for 24 hours:
• Diet regimens are particularly demanding in young children
140 g glucose polymer • Maintenance of normoglycaemia is essential to normalise
+ water added up to 1400 mL (10% CHO concentration) blood biochemistry, although this is difficult to achieve, and
to delay onset or prevent long‐term complications
Feed 60 mL/hour continuously for 24 hours = 0.4 g CHO/kg/hour
Table 29.18 Biochemical monitoring for GSDI.
Checked at each outpatient appointment unless otherwise indicated
Fanconi Bickel
GSD type 0 Ia/b IIIa/b VI and IX syndrome
CGM * * * * *
Glucose +/− lactate profiles * * * * *
in hospital
UCCS load test * * * * *
Glucose √ √ √ √ √
Lactate √ √ √ √
Ketones √ √ √ √
Creatinine kinase √
(IIIa)
Liver profile √ √ √ √ √
Urate √
Triglycerides √ √ √ √ √
Cholesterol √ √ √ √ √
Bone profile, vitamin D †
√ √ √ √ √
FBC, WBC, iron status √ √ √ √ √
Renal profile √ √ √ √ √
Urine protein–creatinine ratio √ √
(or equivalent)
CGM, continuous glucose monitoring; UCCS, uncooked cornstarch; LFT, liver function tests; FBC, full
blood count; WBC, white blood cells.
*Glucose and lactate profiles, CGM and UCCS load test are usually performed annually, but may vary as
clinically indicated.
†
Vitamin D – annually.
Glycogen storage disease type III
Enzyme Debrancher enzyme is bifunctional with two catalytic sites (p. 609, Figure 29.2).
Biochemical defect Two main subtypes:
• debrancher enzyme deficiency in liver, skeletal muscle and heart (GSD type IIIa, 85% of cases)
• debrancher enzyme deficiency in liver only (GSD type IIIb, 15% of cases) [38]
Production of free glucose from glycogenolysis is limited, and the partially degraded glycogen is stored
as an abnormal structure, termed ‘limit dextrin’. The gluconeogenic pathway, however, is functional for
endogenous glucose production, and this prevents the development of profound hypoglycaemia during
fasting, although it can still occur. Glycolysis proceeds normally. Functionally these patients have only
partial glycogenolysis, while glycolysis and gluconeogenesis are preserved.
Genetics Autosomal recessive inherited disorder. A high predicted prevalence is reported in the Faroese
(approximately 1 in 3100) [102] and North African Jews from Israel (1 in 5400) [103].
Clinical onset presentation, features Presents in infancy and early childhood (usually before 18 months) with predominantly liver‐related
features: fasting intolerance, severe hepatomegaly (due to both glycogen and fat accumulation) and
markedly elevated liver transaminases, hyperlipidaemia (triglycerides and cholesterol), ketotic
hypoglycaemia and failure to thrive [104]. Lactate is normal. Biochemical abnormalities improve on
treatment, but may not normalise.
Glycogen Storage Disease Type III 619
Long‐term complications and outcome Cardiac manifestations and skeletal myopathy may develop with increasing age. Accumulation of limit
dextrin may be involved in their pathogenesis. Cardiac involvement is variable, typically manifesting as
asymptomatic left ventricular hypertrophy starting in the first decade of life [104], which can progress to
symptomatic hypertrophic cardiomyopathy, severe cardiac dysfunction, congestive heart failure and
(rarely) sudden death [105–108]. Predictive features for cardiac outcome are not known. Skeletal
myopathy presents as weakness and wasting and gradually progresses, being a greater problem for adults
[107, 109]. Many children, however, tire easily with exercise. Skeletal muscle glycogen normally
provides an essential energy source to contracting muscle, especially at high intensities. Exercise
intolerance in six GSDIIIa patients has been attributed to a block in muscle glycogenolytic capacity
[110]. Creatine kinase (CK), a marker of muscle damage, may increase as children become more active;
the ISGSDIII study data reports a raised CK at some time point in 100/124 patients, median age 10 years
(range 0.3–56.1 years) [104]. CK in adult patients, although often still above the normal reference range,
is reported to decrease, probably due to progressive muscle loss [109]. Whole‐body muscle magnetic
resonance imaging is a useful monitor of muscle involvement; signal alteration was predominant in the
lower limbs and postural muscles in a cohort of 15 patients (age 16–59 years) [111]. Liver symptoms
improve with age; thus hypoglycaemia is less of a problem. A small number of patients develop hepatic
cirrhosis and adenomas and, rarely, hepatocellular carcinomas, but this is much less than in type I [107].
BMD is markedly reduced in GSDIII with type IIIa patients being much worse than IIIb [112]. A high
incidence of bone fractures in paediatric patients is reported [104], suggesting reduced BMD may
develop early. Melis et al. [113] propose the pathogenesis of impaired bone mineralisation is
multifactorial, attributable to poor metabolic control. Hyperlipidaemia occurs, but complications of
pancreatitis and atherosclerosis are not reported [104]. Poor growth can also be seen in childhood,
although spontaneous catch‐up growth usually occurs during puberty [114]. Overweight and obesity are
recognised complications [68, 104]. Liver transplant has been reported [54, 107, 109].
Acute management Initial acute management may necessitate management of hypoglycaemia and correction of biochemical
abnormalities with IV fluids and/or frequent feeds.
Dietetic management Dietary management is the primary treatment. The aims are to:
• prevent hypoglycaemia and ketosis in the infant and young child
• promote normal growth and BMI
• help delay onset of cardiac manifestations and muscle myopathy in type IIIa
• pre‐exercise dietary management to prevent risk of hypoglycaemia
Infants who present with hypoglycaemia and poor fasting tolerance require a more intensive dietary regimen
with increased CHO, similar to GSDI (p. 610). Children who present later with short stature and
hepatomegaly are treated with UCCS or Glycosade, which is given to try and improve their growth rate.
Symptomatic hypoglycaemia is generally not a problem. As gluconeogenesis is functional, the gluconeogenic
precursors such as the glucogenic amino acids, lactate and glycerol can be converted to glucose. High
protein and high fat diets are being used to reverse hypertrophic cardiomyopathy as the traditional high CHO
diet may actually be harmful due to accumulation of limit dextrin. As gluconeogenesis is functional, it is not
necessary to limit fructose and galactose containing foods.
Monitoring Clinical, anthropometric and biochemical monitoring is essential to assess the efficacy of dietary
treatment, to guide composition of the diet and to promote normal growth. Most of the guidelines given
for GSDI (p. 617) can be used for GSDIII, taking into account any differences. Table 29.18 provides
guidelines for biochemical monitoring. Other recommendations for monitoring include
echocardiography (for ventricular hypertrophy), neuromuscular assessment, DEXA scans and liver
ultrasound [107]. CK is a useful measure of muscle damage (see above).
Emergency regimen During illness a frequent supply of glucose must be maintained to prevent hypoglycaemia and ketosis.
The ER information for managing the unwell child with GSDI can also be used for patients with GSDIII
(p. 617).
Clinical management guideline Kishnani PS, Austin SL, Arn P et al. Glycogen storage disease type III diagnosis and management
guidelines. Genet Med. 2010, 12 446−463 [107].
Parent support group Association for Glycogen Storage Disease (UK) (www.agsd.org.uk)
Dietary treatments: high CHO, high protein or high or prevent cardiomyopathy and skeletal muscle myopathy.
fat diets Either CHO intake can be increased to provide a continu-
ous supply of glucose (similar to GSDI) or protein intake
Controversy surrounds which dietary therapy is best for can be increased to enable gluconeogenesis to provide the
patients to maintain normoglycaemia and also to improve main source of glucose.
High CHO diet Current published literature describes different approaches:

Provision of a regular high CHO intake using UCCS can • an infant (2 months) with asymptomatic hypertrophic
maintain normoglycaemia and reduce the need for pro- cardiomyopathy, whose sibling had GSDIII and died at
duction of glucose via gluconeogenic substrates [115– 11 months from cardiac arrest, was given a 2 : 1 ketogenic
117]. This treatment may be as effective as the high protein diet (65% energy from lipid, 15% from protein, 20% from
diet, provided overtreatment is avoided. One small cross- CHO) and synthetic ketone bodies as d,l‐3‐OH butyrate,
over study of five children over a period of 2.5 years com- which resulted in permanent ketosis. Cardiomyopathy
pared UCCS diet with a high protein diet and showed improved and muscle strength remained normal [125]
unchanged glycaemic control, liver function tests and • an infant (7 months) with hypertrophic cardiomyopathy
lipid profiles with both regimens, but better growth and was given a high fat (60% energy), high protein (20%
reduced liver spans when using UCCS. Two of the energy), low CHO (20% energy) diet. The cardiomyopa-
patients with muscle involvement showed increased cre- thy fully resolved after 7 months of treatment and has
atine phosphokinase levels on UCCS diet; no cardiac data not recurred; fasting tolerance improved [126]
were given [118]. • two siblings (5 and 7 years) were given a high fat (60%
energy), high protein (25% energy energy) (unchanged),
High protein diet low CHO (15%) diet. Heart wall thickness decreased and
biochemistry improved; UCCS could gradually be
Studies recommending a high protein diet are limited. stopped [127]
Studies from the 1980s [119–121] report an increased • two boys (9 and 11years) were given a modified Atkins
demand for gluconeogenesis with loss of muscle amino diet (10 g CHO per day, unrestricted protein increased
acids (supported by observations in change of plasma ala- from 3 to 7 g/kg/day, fat from 1.6 to 8 g/kg/day); UCCS
nine, a major gluconeogenic precursor) may be a contribu- was gradually stopped. The % energy intake was not
tory factor to the skeletal myopathy seen in some patients provided in the paper (the author has calculated the val-
with GSDIIIa. Slonim et al. [119] reported a high protein ues as 1.6% CHO, 71% fat, 27% protein for comparison).
daytime diet and night feed (20%–25% energy from protein) Cardiac function, stamina and CK improved [128]
improved muscle strength in myopathic patients, but six of
seven patients studied were not on any dietary treatment,
and so perhaps similar improvements could have been Diet choice: high CHO or high protein?
achieved with a high CHO diet and night feed. Fernandes
and van de Kamer demonstrated that protein, galactose and Intermittent administration of either UCCS or a high protein
fructose induced a rise in blood glucose concentration using supplement is necessary throughout 24 hours with both diets;
hexose and protein tolerance tests in five children with GSD acceptance of either can be difficult. Achieving a high protein
[122]. These early studies did not distinguish between type intake from food may be more difficult than a high CHO diet
IIIa/b. Two more recent adult case reports describe reversi- in a young child. Both diets can maintain normoglycaemia.
bility of hypertrophic cardiomyopathy (demonstrated by There are no long‐term published data to determine which
echocardiography) with a high protein diet. The diets had diet therapy is best for patients with myopathy. On current
different macronutrient energy ratios: case 1, an adult, was evidence it is not yet clear if a high protein diet is more benefi-
given 30% protein (no data were given on CHO and fat) cial than high CHO in treating/delaying onset of cardiac
[123]; case 2, an obese adult, was given 37% protein, 2% manifestations and muscle myopathy in type IIIa patients. No
lipid, 61% CHO and total energy intake reduced to 900 kcal cohort studies of high protein diets have been reported in
(3.8 MJ)/day [124]. It is not possible to distinguish which infants or young children. Such a high protein intake may not
element of the diet was of most benefit. These studies impli- be tolerated or warranted in this age group. A gradual increase
cated a high CHO diet and UCCS as possible contributing in protein intake with age, or if there is evidence of myopathy,
factors to the development of cardiomyopathy as excess may be more appropriate. The final choice of dietary manage-
CHO can cause deposition and accumulation of abnormal ment for children with GSDIII will also vary depending on the
glycogen in heart [108, 124]. severity of the disorder and ultimately what is practically
achievable for the child and family. The diet needs to be indi-
vidually tailored to the child’s specific clinical features. A high
High fat diets protein diet in GSD type IIIb patients may not be warranted as
High CHO diets in GSDIII suppress lipolysis. A newer they do not develop myopathy.
approach to reverse cardiomyopathy and improve muscle The optimal macronutrient composition of the diet in
myopathy is the ketogenic or modified Atkins diet, which GSD III is unknown; various differing energy ratios are
provides fatty acids and ketones instead of CHO as the main reported in the literature. Problems and the long‐term com-
energy source. Fatty acids are the principal energy source for plications may result when too much CHO is given; any
cardiac muscle and skeletal muscle in the resting state and increase in protein or fat intake should decrease CHO
during prolonged exercise. Ketone bodies can be used by intake. Bhattacharya et al. suggest both macronutrient ratio
most tissues including the brain, and the heart uses ketones and quality of CHO are important; lower glycaemic index
in preference to glucose. foods are preferable [129].
Glycogen Storage Disease Type III 621
Practical provision of high CHO, high protein diet (concentrated milk protein powder, 89% protein) are likely to
be necessary. Protifar can be added to UCCS and skimmed
Infants who present early with hypoglycaemia and poor fast- milk drinks and to a continuous overnight feed of skimmed
ing tolerance require a more intensive dietary regimen with milk, replacing some of the glucose polymer (gram of CHO
increased CHO, as for GSDI (p. 610). The suggested energy for gram of protein). This latter change should be instituted
ratio in GSDI is 60%–70% from CHO, 20%–25% from fat and in hospital, so blood glucose can be formally monitored. Most
10%–15% from protein. At night, continuous tube feeding is high protein drinks or dessert supplements are too high in
used and regular 2 hourly feeding or UCCS during the day- energy intake to be very useful. Exceptions are ProSource
time. The feed regimen examples for GSDI (p. 612) can be Plus Liquid (neutral and flavoured), which provides 15 g pro-
used for GSDIII if the patient is not on a very high protein tein, 11 g CHO, 100 kcal (420 kJ) in 30 mL and can be given
diet. Starchy foods should be used in preference to simple orally or by tube, and ProSource Jelly with 20 g protein, <2 g
sugars to limit peak glucose excursions and insulin release. CHO, 90 kcal (375 kJ) per 118 g serving. Older children may be
As discussed, there should perhaps be greater emphasis on able to replace nocturnal feeds with UCCS before they have
the inclusion of high protein foods and lower CHO in the stopped growing if their fasting tolerance is >6–8 hours.
diet, particularly if a child has or develops a cardiac or skel- Fasting tolerance should be assessed in hospital, as described
etal myopathy. Table 29.19 gives guidance on provision of for GSDI, and can then be monitored at home using continu-
combinations of high CHO diet, high protein and low fat ous glucose monitoring (CGM).
diet. The ACMG guidelines [107] recommend a high protein It is important to carefully monitor the energy distribution
diet and refer to the energy ratios used by Slonim et al. of the diet and when making changes to macronutrient energy
(20%–25% energy from protein, 50%–55% from CHO and intakes. CGM can be used to further monitor these changes at
20%–25% from fat) [119–121]. These protein intakes are very home. Further CHO reductions can be made if blood glucose is
high, e.g. 100 g protein provides 25% of energy in a diet pro- at upper level of normal. Too high an energy intake from CHO
viding 1600 kcal (6.7 MJ). High protein foods at meals and can cause rebound hypoglycaemia [130]. If a child has limited
snack times need to be increased and parents need guidance exercise capacity, this should be considered when planning the
on portion sizes, suitable low fat foods such as skimmed overall energy intake to avoid excess weight gain.
milk, low fat yoghurt and fromage frais. Achieving a suffi- Children who present later with short stature and hepato-
ciently high protein intake, even from protein rich foods, is megaly are treated with UCCS or Glycosade to try and
very difficult, and pure protein supplements such as Protifar improve their growth rate. Symptomatic hypoglycaemia is
Table 29.19 High CHO, normal protein, low fat diet or high protein, normal/reduced CHO, low fat diet for GSDIII.
Carbohydrate foods (starch and sugar)

Starchy foods At least one serving at three main meals and bedtime snack, e.g. bread, chapatti, pitta, cereal, potato, rice, pasta, fruit, plain biscuits or
crackers, tea cake, muffins
Sugar and sugary foods These are allowed, but should be kept to a minimum, e.g. table sugar, sweets, cakes, ice cream, preserves
High protein, low fat foods*
Milk Semi‐skimmed or skimmed milk, low fat fromage frais or yoghurt
Meat Lean red meat (5%–10% fat content), trim off all visible fat
Poultry
Fish White fish instead of oily
Cheese Low fat cheese, e.g. cottage, edam type, half-fat cheddar, quark
Pulses Beans, lentils, peas (and sweetcorn)
Eggs
Meat alternatives Tofu, Quorn
Fats
High fat foods should be used sparingly, e.g. butter, margarine, vegetable oil, animal fats, cream (double, whipping, single), imitation cream,
mayonnaise, salad dressings, pastry, batter and breaded foods
Avoid fried or roasted foods. Spread butter or margarine thinly on bread
Snack foods
Most children choose high fat or sugary snack foods, e.g. crisps, nuts, sweets and chocolate. Low fat, high protein or high carbohydrate snack foods
should be used instead, e.g. yoghurt, fromage frais, crackers and low fat cheese, glass of milk for the high protein diet or sandwich, plain biscuits,
crumpet, fruit for the high starch diet
*High protein diet for GSD III – at least one serving of high protein, low fat food at three main meals and bedtime snack. Generous intakes of milk should
also be given.
High CHO diet for GSD III – one serving of high protein, low fat foods at two meals. Can include milk (or milky foods) in the daily diet.
generally not a problem for these children, although after an for GSDI, may help. Preisler et al. [132] report exercise toler-
overnight fast they may have high ketones. Frequency of ance improved with fructose ingestion in three adults with
administration and dose of UCCS (1–2 g/kg/dose) will vary GSD III.
depending on fasting tolerance, age, growth rate and response.
Usually a dose is given before bed, and sometimes daytime
doses are necessary to improve growth. Children should have Hypoglycaemia
regular meals and a bedtime snack that contain both starchy The guidelines given for management of GSDI can also be
and protein food. Fat intake should be decreased to compen- used for patients with GSD type III (p. 616).
sate for the increased CHO intake and for weight control.
A high starch, normal protein, low fat diet and high pro-
tein, normal/reduced starch, low fat diet for GSDIII is given Managing the unwell child: emergency regimen
in Table 29.19. information for GSDIII
The guidelines given for management of GSDI can also be
Vitamins and minerals used for patients with GSD type III with the aim to prevent
Vitamin and mineral intakes need to be regularly assessed. If a hypoglycaemia and ketosis (p. 617). As not all children with
high percentage of the dietary energy intake is provided as pure GSDIII are tube fed, glucose polymer drinks need to be given
starch or glucose polymer, there is greater risk of vitamin and orally, 2–3 hourly day and night, depending on usual fasting
mineral deficiencies. Calcium and vitamin D intakes are particu- tolerance.
larly important because of risk of decreased BMD [112, 113].
Alcohol Learning points: glycogen storage disease type III

Adolescents and adults must be made aware that alcohol is
a potent inhibitor of gluconeogenesis and even quite moder- • Infants who present with hypoglycaemia are managed with
ate amounts may reduce glucose production. Alcohol intake a high CHO diet and frequent 2–3 hourly feeds during the
should be limited and must always be taken in combination daytime and continuous tube feeds overnight
with food [131]. • Children who present later need a less intensive feeding
regimen
• UCCS is introduced from around 1 to 2 years of age
Exercise • High protein, high fat diet and low CHO diets are being
Exercise intolerance is attributed to severely limited ability trialled to help prevent complications, but the optimal
to breakdown glycogen [110]. If a child fatigues and tires macronutrient ratio is not yet defined
early with exercise, giving CHO pre‐exercise, as described
Glycogen storage disease type VI

Fiona J. White
Enzyme Glycogen phosphorylase (Figure 29.2)

Biochemical Deficiency of glycogen phosphorylase:
defect • prevents release of glucose‐1‐phosphate from the linear chains of α‐1,4‐linked glucose molecules, thus limiting the production
of glucose by glycogenolysis
• glucose can still be produced via gluconeogenesis, which helps prevent significant hypoglycaemia during prolonged periods of
fasting, e.g. overnight
Genetics Autosomal recessive inheritance resulting from mutations encoding for the enzyme hepatic glycogen phosphorylase (PYGL, EC
2.4.11). There is a common mutation in the Mennonite population where the incidence is around 1 in 1000 [133].
Glycogen Storage Disease Type VI 623
Clinical onset, Usually presents in childhood, around 2–3 years of age, with:
presentation • abdominal distension, hepatomegaly (due to increased liver glycogen storage) and growth retardation. Clinical presentation is
features the same as in hepatic forms of GSDIX (p. 624) and similar, but generally milder to that seen in GSDIII
• there may be some muscle or central nervous system involvement with symptoms such as mild hypotonia, delayed motor
development, muscle weakness and cramps [134]
• significant ketosis may be present particularly after an overnight fast or during illness. This represents inadequate production of
glucose from liver glycogen with stimulation of counter‐regulatory hormones, glucagon, adrenaline and growth hormone to
maintain normoglycaemia, which reduce insulin levels and increase lipolysis and further ketosis [135]. Cases with
normoglycaemic ketonaemia have been described [136]
• mild increase in liver transaminases, alkaline phosphatase and gamma‐GT [135]. Blood lipids, particularly triglycerides, are
usually raised. Normal uric acid and lactate levels [137]
• large glucose loads may increase postprandial lactate levels; this was seen in 6/6 patients following a glucose loading
test [134]
Long‐term Clinical symptoms generally improve with age; hepatomegaly has usually resolved by puberty [133] and complete catch‐up in
complications final height achieved:
and outcome • osteoporosis is a risk factor if there is chronic ketosis [38]
• GSD VI was thought to be a benign condition, but long‐term complications have been reported with cases of likely liver
fibrosis and hepatocellular carcinoma [138, 139] as well as mild cardiomyopathy [138]
Initial Assessment of any hypoglycaemia or significant ketosis on the usual dietary intake by serial blood glucose monitoring and early
management morning ketone measurement. This can be done in hospital or at home with a period of CGM (p. 629) and early morning ketone
measurement:
• hypoglycaemia is not always symptomatically obvious and may only become apparent if monitored overnight or after an
overnight fast. If hypoglycaemia is present, it is usually less severe than in GSDI or GSDIII
• hyperketosis may be present after an overnight fast indicating the occurrence of lipolysis to preserve blood glucose and the
need for additional CHO intake overnight, even if absolute hypoglycaemia has not occurred
Dietetic Dietary manipulation is the primary treatment aiming to:
management • maintain normal blood glucose levels and prevent ketosis
• correct hyperlipidaemia
• promote normal growth and maintain a healthy BMI
Dietary advice is based on fasting tolerance:
• many patients do not require specific dietary treatment
• depending on fasting tolerance management ranges:
◦◦ from regular meals and a bedtime snack that are high in complex CHO and with generous protein, with ER for illness
◦◦ to those additionally requiring daily UCCS therapy at night to prevent hypoglycaemia or ketonaemia
• a high protein intake may be advantageous in providing precursors for gluconeogenesis and reducing reliance on CHO, thus
decreasing glycogen storage
• avoidance of both under‐ and overtreatment is important. Undertreatment results in hyperketosis due to utilisation of lipolysis,
β-oxidation and ketogenesis +/− hypoglycaemia as gluconeogenesis and fatty acid oxidation are functional. Overtreatment
with excess food, milk formula or UCCS results in excess liver glycogen storage and peripheral body fat storage.
Alcohol It is important to discuss alcohol intake with adolescents as it is a potent inhibitor of gluconeogenesis. Recommendations for
GSDIII can be used (p. 622).
Hypoglycaemia Guidelines for GSDI can be used (p. 616).
Monitoring Clinical, anthropometric and biochemical monitoring is essential in assessing dietary treatment efficacy, dietary composition
changes and promoting normal growth. Most of the monitoring described for GSDIII (p. 619) is applicable, accounting for any
differences in dietary treatment and affected biochemistry. Biochemical monitoring guidelines are detailed in Table 29.18.
Abdominal ultrasound of the liver or, in older children, magnetic resonance imaging (MRI) is performed every 12–24 months to
assess for complications of liver cirrhosis and adenoma [135].
Emergency Illness or prolonged fasting, e.g. for surgery, could precipitate hypoglycaemia. It is essential that a supply of glucose is given
regimen frequently:
• ER guidance for GSDI can be used for GSDVI (p. 617)
• ER drinks need to be taken 2–3 hourly depending upon usual fasting tolerance
Clinical Kishnani PS, Goldstein J, Austin SL et al. Diagnosis and management of glycogen storage diseases type VI and IX: a clinical
management practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2019, 21(4) 772–789. [135].
guidelines
Parent support Association for Glycogen Storage Disease (AGSD) (https://agsd.org.uk/)
group
Learning points: glycogen storage disease type VI
• GSDVI is generally a less severe form of hepatic GSD

• Ongoing monitoring is needed due to reports of fibrosis,
hepatocellular carcinoma and cardiomyopathy
Glycogen storage disease type IX
Enzyme Phosphorylase b kinase (PHK) (Figure 29.2)

• PHK is composed of four copies each of four subunits (α, β, γ, and δ), encoded by four separate genes (PHKA1, PHKA2,
PHKB, PHKG2), and deficiency can be present in the liver, liver and muscle or, rarely, in muscle only. There are five
different subtypes depending upon clinical presentation and mode of inheritance [38, 140].
Biochemical defect Deficiency of PHK (Figure 29.2) prevents activation of glycogen phosphorylase, thus limiting the production of glucose by
glycogenolysis:
• glucose can still be produced via gluconeogenesis, which helps prevent significant hypoglycaemia during prolonged
periods of fasting, e.g. overnight
Genetics • X‐linked hepatic PHK deficiency, GSDIXa (type IX alpha), is caused by a wide range of mutations in the PHKA2 gene and
is the most frequent form occurring in approximately 75% cases of GSDIX [141], with a mild phenotype often thought to
be benign, but in some cases there may be a more severe phenotype
• X‐linked muscle glycogenosis, GSDIXd, is due to mutations in the PHKA1 gene and results in a mild phenotype
• combined liver and muscle PHK deficiency, GSDIXb (type IX beta), results from mutations in the PHKB gene, with
autosomal recessive inheritance, and is usually a mild phenotype
• autosomal recessive liver PHK deficiency, GSDIXc (type IX gamma), results from mutations in the PHKG2 gene located on
chromosome 16 and results in a severe phenotype
• autosomal recessive muscle PHK deficiency, GSDIXe, has a mild phenotype
Clinical onset Types IXa (alpha), IXb (beta) and IXc (gamma), present with hepatomegaly, growth retardation, fasting hypoglycaemia,
presentation, features ketosis, hypercholesterolaemia, hypertriglyceridaemia and elevated liver transaminases:
• hypoglycaemia may not always be pronounced as both gluconeogenesis and fatty acid oxidation are functional and
ketosis may be more significant
• hyperlacticacidaemia, usually postprandial, is also observed in some cases, especially in GSDIXc
They are in general milder disorders than GSDIII, but there is wide variation in severity of symptoms. Although
hypoglycaemia is usually mild, only occuring after prolonged fasting or infection, in some, particularly GSDIXc (gamma),
there can be severe hypoglycaemia, ketosis and raised transaminases as seen in GSDI or GSDIII [138, 140]. There is gross
accumulation of glycogen in the liver.
Long‐term Usually a late growth spurt allows complete catch‐up in final height [142–144]. There is usually normalisation of liver
complications and enzymes in the majority and most adults will be entirely asymptomatic with a normal life expectancy:
outcome • the more severe GSDIXc (gamma) form is associated with liver fibrosis, which can progress to cirrhosis and development
of adenoma [138, 140]
• hypertrophic cardiomyopathy has also been reported in GSDIXc [138]
• uncommonly X‐linked GSDIXa (alpha) has also been associated with liver fibrosis and cirrhosis [141, 145]
Initial management • as for GSD type VI (p. 623)
• some cases with the severe form GSDIXc (gamma) may have severe nocturnal hypoglycaemia
Dietetic management • as for GSD type VI (p. 623)
• depending on fasting tolerance management ranges:
◦◦ from regular meals and bedtime snack with ER for illness
◦◦ to those additionally requiring daily UCCS therapy at night to prevent hypoglycaemia or ketonaemia
• a high protein intake may be advantageous in providing precursors for gluconeogenesis and reducing reliance on CHO,
thus decreasing glycogen storage
• some cases with the severe form GSDIXc (gamma) may have severe nocturnal hypoglycaemia and shorter fasting tolerance
than in milder forms. To maintain normoglycaemia, prevent fasting ketosis and improve growth [138], they need:
◦◦ a more intensive regimen, as in GSDI or severe GSD III, with overnight continuous tube feeding, or
◦◦ 1–2 doses of UCCS plus protein (as gluconeogenesis is functional) overnight and daytime UCCS plus protein (p. 625)
Monitoring As for GSDVI (p. 623).
Glycogen Storage Disease Type IX 625
Emergency regimen Illness or prolonged fasting, e.g. for surgery, could precipitate hypoglycaemia. It is essential that a supply of glucose is given
frequently:
• ER guidance for GSDI can be used for GSDIX (p. 617)
• where a feeding tube is in situ, ER can be given continuously
Clinical management Kishnani PS, Goldstein J, Austin SL et al. Diagnosis and management of glycogen storage diseases type VI and IX: a clinical practice
guidelines resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2019, 21(4) 772–789. [135].
Parent support group Association for Glycogen Storage Disease (AGSD) (https://agsd.org.uk/)
early morning (pre‐breakfast) blood glucose and ketone

Learning points: glycogen storage disease type IX
levels.
• Cases of GSD type IXc may require more intensive treat-
• The majority of cases of GSDIX will be male with X‐linked
ment as in GSDI or severe GSDIII.
forms and are generally mild disease
• It is suggested that even where there is no hypoglycae-
• GSDIXc (gamma) is a severe form and may require inten-
mia or ketosis, UCCS at night is beneficial in improving
sive dietary management as in GSDI or severe GSDIII
any delayed growth [38].
• Ongoing monitoring is needed due to reports of liver adeno-
• Micronutrient intakes should be optimized.
mas and cirrhosis
Severe GSDIXc
Dietary management principles for GSD types A more intensive dietary regimen will be required to main-
tain euglycaemia, prevent ketosis and promote growth, sim-
VI and IX
ilar to GSDIII (p. 619).
The aim is to maintain normoglycaemia, which reduces the
need for lipolysis and fatty acid oxidation and so prevents Diet for infants with GSD VI, GSD IX and GSD0
the development of ketosis:
Presentation in early infancy would be unusual apart from
• Avoidance of hypoglycaemia and significant ketosis.
those of an affected older sibling; thus there is little experi-
These can normally be managed by regular 3–4 hourly
ence of the practical management in such situations. In the-
daytime meals and a bedtime snack comprising complex
ory, from knowledge of the disorders and their management,
CHO and generous protein (Table 29.19). The precise
cases identified in infancy would require:
ideal energy distribution of the diet is not known.
Additional protein may be useful: • regular feeding at 3–4 hourly intervals throughout the 24
◦◦ to provide gluconeogenic precursors hour period to maintain normoglycaemia and prevent
◦◦ to be a direct fuel for muscles ketosis
◦◦ simultaneously replacing the energy from additional • a controlled fast with monitoring of blood glucose, lac-
protein with a reduction in CHO energy may reduce tate and ketones could be used to determine the safe
glycogen storage [129, 135] maximum fasting time between feeds
ACMG guidelines recommend an overall diet relatively • monitoring of blood glucose, lactate (in GSD0) and
high in complex CHO (45%–50% energy), generous pro- ketones could be used to assess the adequacy of the fre-
tein (2–3 g/kg/day, 20%–25% energy) with reduced fat quency of feeding and volumes taken
(approx. 30% energy) [135]. It can be difficult to achieve • breastfed infants may need supplementary feeds of
high protein intakes solely from food protein and protein infant formula or glucose polymer if breastfeeds alone
supplements may be required (p. 621): are insufficient to maintain euglycaemia
• If there is overnight hypoglycaemia or significant early • weaning onto solid foods would be advised to start as
morning ketosis (>0.5 mmol/L), UCCS should be intro- normal around 26 weeks of age; as the intake of solids
duced, approx. 1 g/kg/dose given at bedtime or late containing complex CHO and protein increase these can
evening (p. 613). A second dose of UCCS may be required replace some of the milk feeds
overnight to adequately maintain blood glucose and pre- • frequency of feeding, particularly overnight, needs reas-
vent ketosis. UCCS dosing requirements may be deter- sessing regularly throughout infancy as fasting tolerance
mined by an UCCS load test (p. 614) or by monitoring of may increase
Glycogen storage disease type 0
Enzyme Glycogen synthase (Figure 29.2)

• there are two isoforms, a hepatic isoform (GSY2) and a muscle isoform (GSY1). Only the hepatic form is discussed
Biochemical Deficiency of glycogen synthase, the rate‐limiting enzyme in glycogenesis (Figure 29.2), results in
defect • reduced availability of glycogen for the production of glucose via glycogenolysis during fasting periods. Although this is in
contrast to the other hepatic GSD where glycogenolysis is disrupted, the clinical phenotype is similar to other forms of hepatic
GSD [38]
Genetics Autosomal recessive inheritance resulting from mutations in the GSY2 gene that encodes the enzyme glycogen synthase. The gene is
located on chromosome 12. To date 18 mutations have been described [146]:
• many mutations are unique to particular families
• only one common mutation (c.736C > T) has been reported, found throughout Europe and North and South America [147]
• GSD0 appears rare, or under‐diagnosed, as from its initial description to 2006, only 20 cases had been published [148]. A review
of mutation analysis of 50 children with ketotic hypoglycaemia, from a single centre, only identified one case of GSD0 with no
mutations found in the other 49 patients [146]
Clinical onset GSD0 typically presents in late infancy or early childhood with fasting ketotic hypoglycaemia, precipitated by increased length of
presentation, overnight fast, intercurrent illness with a lack of dietary intake, or gastrointestinal symptoms of vomiting and/or diarrhoea causing
features reduced energy intake:
• despite significant hypoglycaemia some patients may be relatively asymptomatic as the high levels of blood ketones can provide
an alternative fuel for brain energy metabolism
• seizures are uncommon; developmental delay has only been described in 22% of cases [148], and neurological sequelae appear
infrequent [147]
• growth retardation may be present due to chronic ketosis
• a review of the 20 published cases identified a variety of presenting clinical symptoms, the most common being seizures 5/20,
hypoglycaemia 2/20, short stature/faltering growth 2/20 and family history 5/20 [147]
• the diagnosis should be considered not only in cases of ketotic hypoglycaemia but also if hyperglycaemia and glycosuria occur
that are not caused by diabetes mellitus
• the youngest age of diagnosis reported is in an 8‐month‐old child presenting with recurrent hypoglycaemic seizures [149]
Biochemistry at • in infants and young children overnight hypoglycaemia is a common feature
presentation • blood glucose monitoring may reveal postprandial hyperglycaemia
• due to absence of stored glycogen, prolonged fasting will result in:
◦◦ hypoglycaemia
◦◦ hyperketonaemia and elevated free fatty acids
◦◦ low levels of lactate and alanine (skeletal muscle release of alanine is inhibited by high levels of free fatty acids and ketones);
thus precursors for gluconeogenesis are reduced, further exacerbating the risk of hypoglycaemia [147, 150]
• in the fed state, as a result of the reduced ability to produce glycogen in the liver, glucose derived from the diet is mainly
channelled into the glycolytic pathway, resulting in the postprandial biochemical picture of hyperglycaemia, hyperlactataemia and
hyperlipidaemia [151]; a standard oral glucose tolerance test produces an excessive rise in blood glucose and lactate (Table 29.20)
Long‐term • long‐term outcomes have yet to be described
complications • fasting tolerance may improve with increasing age although there is considerable individual variation and it may remain a
and outcome significant problem, particularly with prolonged fasting, illness, pregnancy and increased physical activity [147]
Initial • as for GSD type VI (p. 623)
management
Dietetic Aims:
management • maintain normal blood glucose level, preventing both hypoglycaemia and hyperglycaemia
• correct secondary biochemical abnormalities of postprandial lactic acidosis and fasting ketosis by maintenance of
normoglycaemia
• promote normal growth and maintain a healthy BMI
Normoglycaemia can be achieved by provision of complex CHO, which will minimise postprandial rise in blood glucose and lactate:
• simple CHO may cause a transient sharp rise in blood glucose and an increase in blood lactate; thus intake of highly refined
CHO, e.g. sugary drinks, fruit juice, confectionery, cakes, sweet biscuits and high sugar cereals, should be limited
• a high protein intake is beneficial by providing substrate for glucose production via gluconeogenesis; maintenance of
normoglycaemia limits fatty acid oxidation, thus preventing free fatty acid and ketone accumulation
Dietary management is based on fasting tolerance and advice centres on:
• regular meals, including a bedtime snack, containing complex CHO and protein
• managing overnight hypoglycaemia or significant early morning ketonuria (>0.5 mmol/L) with UCCS (p. 613) introduced at
bedtime/late evening at a dose of 1.0–1.5 g/kg/dose. One or two doses of UCCS may be required overnight, determined by a
UCCS load test (p. 614) and/or by monitoring of early morning (pre‐breakfast) blood glucose and ketone levels
• continuous overnight tube feeds if UCCS is not tolerated or fails to maintain blood glucose levels adequately. There is one case
report [146] of a child requiring overnight feeds of 25% glucose polymer as 6 hourly UCCS overnight failed to prevent
hypoglycaemia
Fanconi Bickel Syndrome (FBS, GLUT 2 Defect, GSDXI) 627
Alcohol It is important to discuss alcohol intake with adolescents as it is a potent inhibitor of gluconeogenesis. Recommendations for GSDIII
can be used (p. 622).
Monitoring As for GSDVI.
Emergency Illness or prolonged fasting, e.g. for surgery, could precipitate hypoglycaemia. It is essential that a supply of glucose is given
regimen frequently:
• ER guidance given for GSDI can be used for GSD0 (p. 617)
• the CHO concentration may need to be reduced from the standard age‐related ER to prevent hyperglycaemia and maintain blood
sugars within a reasonable range (3.5–8 mmol/L)
Clinical None published
management
guidelines
group
Table 29.20 Blood glucose and lactate following an oral glucose load

in a 6‐year‐old patient as part of the diagnostic workup for GSD0.
Blood glucose mmol/L Blood lactate mmol/L Learning points: glycogen storage disease type 0
(reference range (reference range
Time (minutes) 3.3–5.5 mmol/L) 0.6–2.5 mmol/L)
• GSD0 is generally a less severe form of GSD
0 2.5 1.42 • Usually requires management with regular meals of com-
+40 2.6 Haemolysed plex CHO and protein, limiting intake of refined CHO
• UCCS may be required at night to prevent nocturnal hypo-
+70 7.8 8.15
glycaemia and hyperketosis
+120 6.9 8.18
Fanconi Bickel syndrome (FBS, GLUT 2 defect, GSDXI)
Transporter Glucose transporter 2 (GLUT2), a facilitative glucose (and galactose) transporter expressed in pancreatic islet cells, on the
basolateral aspect of small intestine epithelial and proximal convoluted renal tubular cells and in hepatocytes
Biochemical • deficiency of GLUT 2
defect • deficiency affects glucose homeostasis [152] due to GLUT 2’s involvement in intestinal glucose uptake, renal reabsorption of
glucose, glucose sensing in the pancreas and hepatic uptake and release of glucose (and galactose). It is essential for glucose
entry into pancreatic islet cells, a process that is insulin dependent [153]
Genetics • autosomal recessive inheritance due to mutations in the SLC2A2 gene
• >70% of cases are in consanguineous families
• >100 mutations have been described [153, 154], the majority being private, i.e. unique to a single family [155]
Clinical onset • clinically FBS presents in early childhood in those with a severe phenotype: hepatomegaly and nephromegaly due to glycogen
presentation, accumulation in liver and kidney
features • growth failure with severe short stature
• delayed bone age
• hypophosphataemic rickets
• delayed motor development
• bone deformities, including genu valgum and kyphosis, may be present
• malabsorption is not always a presenting feature; in a review of cases [156], 16% had intestinal symptoms including chronic
diarrhoea or failure to thrive in infancy
• cognitive development is normal
• some cases may be identified on NBS for galactosaemia with galactosuria
• cataracts, due to hypergalactosaemia, have been seen in a few cases although they were not found in the original patient
despite a large milk intake throughout his life [153]
• symptomatic hypoglycaemia in untreated patients is rare, presumably due to increased blood levels of ketone bodies and
lactate
Biochemistry at Biochemical features of Fanconi Bickel syndrome (FBS) are of glucose and galactose intolerance and a Fanconi‐type nephropathy:
presentation • postprandial hyperglycaemia caused by decreased glucose uptake by the liver and low insulin secretion due to impaired
glucose sensing by pancreatic β cells
• fasting hypoglycaemia due to altered glucose transport from hepatocytes [157] with ketosis
• tubular nephropathy results in glycosuria, galactosuria, amino aciduria and increased renal losses of bicarbonate, phosphate,
calcium and potassium
• urine testing for amino acids and galactose is usually diagnostic in these patients, in conjunction with the clinical phenotype
• increased gluconeogenesis increases intracellular glucose, which cannot exit the cells, and inhibits glycogenolysis; this results
in glycogen accumulation within the liver, enterocytes and renal tubular cells
• hydrogen breath tests following a glucose load are normal indicating that intestinal uptake of monosaccharides is not impaired;
an additional transport system for glucose, SLGT1 (sodium‐dependent glucose co‐transporter) in the apical membrane and at the
basolateral membrane, a vesicle mediated pathway, appears to enable intestinal glucose uptake [156]
Long‐term Despite careful management of symptoms FBS, due to its severe phenotype, is difficult to manage:
complications • the clinical symptoms of the original patient described persisted into adulthood and he had severe short stature [158]
and outcome • four cases had extremely poor linear growth (well below the 0.4th centile), severe tubulopathy and persistent nephrocalcinosis;
heptomegaly, although reduced in 2/4 cases, remained along with abnormal glucose control, particularly postprandial
hyperglycaemia [159]. Similar outcome is seen in cases in the author’s unit
• UCCS has been proposed to improve metabolic control and growth [160]; however, the beneficial effects on growth seen in
other GSD with the use of UCCS do not appear to be replicated in FBS
• in two siblings with a mild phenotype [161], the elder boy, diagnosed at 9 months, presented with faltering growth; his younger
sister was investigated in the neonatal period and never had clinical symptoms. They have never had the classic symptoms of
hepatomegaly, nephromegaly or hyperphophataemic rickets and only had mild glycosuria and proteinuria. Both had elevated
blood galactose levels. At age 9½ and 4½ years, they achieved normal growth on frequent feeds of a diet restricted in glucose and
galactose and avoidance of prolonged fasting. UCCS, 0.5 g/kg, was given at bedtime for the first 2 years. There have been no other
published cases of mild phenotypes with good clinical outcome; other mild cases may exist as a cause of isolated glycosuria
• a first case of hepatocellular carcinoma has been described, which did not appear associated with hepatic adenomas, as is the
case in other hepatic GSD [162]
Initial • assess fasting tolerance and institute dietary therapy to maintain normoglycaemia and prevent ketosis
management • assess renal tubular losses of glucose, galactose, amino acids, calcium, phosphate, potassium and bicarbonate
• assess plasma calcium, vitamin D and phosphate status
Medical • renal tubulopathy requires supplementation of bicarbonate, potassium and phosphate
treatment • calcium and vitamin D supplementation may be required
• adequate fluids must be given because of polyuria
Dietetic Management of FBS is based on symptomatic treatment. Dietary aims:
management • maintaining normal blood glucose level, preventing both hyperglycaemia and hypoglycaemia
• preventing ketosis
• correcting hyperlipidaemia
• promoting normal growth and maintaining a healthy BMI
Control of blood sugars is managed by frequent intake of complex CHO, UCCS and, in some cases, continuous overnight feeds:
• large intakes of glucose and galactose (including that provided from sucrose and lactose) at a single time should be minimised
to help prevent hyperglycaemia
• frequency of feeding can be determined by fasting tests, but is usually at least 3 hourly
• fasting tolerance may be improved by using UCCS
• euglycaemia and prevention of ketosis overnight might be possible with several doses of UCCS
• if overnight continuous feeding is required, the composition of the feed depends on daytime nutritional intake and growth,
varying from glucose polymer to a nutritionally complete feed
• increased protein intake is needed to compensate for aminoaciduria
• there are no definitive recommendations to restrict galactose
• fructose can be tolerated as part of the diet as it is absorbed in the intestine via GLUT5, a transporter specific to fructose that is
found in both the apical and basolateral membranes of the enterocyte [153]. Fructose may, therefore, be useful as an alternative
monosaccharide to enable reduction in glucose intake, e.g. in overnight feeds. Fructose does not need to be converted to
glucose for release from cells and is released by a different pathway to glucose [163]
Monitoring Regular clinical and biochemical monitoring is important to evaluate the adequacy and efficacy of current dietary treatment,
appraise if any dietary management changes are required and assess the family’s understanding and delivery of the management.
Monitoring is required to ensure:
• adequate provision of CHO and protein from diet
• adequate dosing of UCCS if required (this may be based on results of biochemical monitoring)
• nutritional adequacy of vitamin and mineral intake
• normal growth
• appropriate management of illness and that ER is updated for age and weight
• appropriate management of hypoglycaemia
Further monitoring is as for GSDI (p. 617). Routine biochemical and annual monitoring and aims are shown in Table 29.18.
Continuous Glucose Monitoring in Glycogen Storage Disorders 629
Emergency The CHO concentration may need to be reduced from the standard age‐related ER to prevent hyperglycaemia and maintain blood
regimen sugars within a reasonable range (3.5–10 mmol/L).
Illness or prolonged fasting, e.g. for surgery, could precipitate hypoglycaemia. It is essential that a supply of glucose is given
frequently:
• ER guidance given for GSDI can be used for FBS (p. 617)
• the CHO concentration may need to be reduced from the standard age‐related ER to prevent hyperglycaemia and maintain
blood sugars within a reasonable range (3.5–10 mmol/L)
• additional fluids may be required if there is significant polyuria
• ER drinks need to be taken 2–3 hourly depending upon usual fasting tolerance or given as a continuous infusion where a
feeding tube is in situ
Clinical None published
management
guidelines
group
Learning points: Fanconi Bickel syndrome (FBS, GLUT 2 Continuous glucose monitoring (CGM) has become a valu-
defect, GSDXI) able tool in the routine monitoring of GSD patients to assess
metabolic control and appropriateness of the dietary regimen.
• FBS is a rare form of GSD caused by a defect in transport- CGM allows an individual’s glucose levels to be continually
ing glucose into cells monitored over a period of time by an indwelling glucose sen-
• Both hypoglycaemia and hyperglycaemia can occur and sor. It is a relatively non‐invasive technique. There are advan-
require management with regular meals with complex tages over intermittent glucose monitoring in that information
CHO and may require inclusion of UCCS to extend fasting on direction, magnitude, duration and frequency of fluctua-
period or continuous overnight tube feeding tions in blood glucose levels is also obtained [164, 165].
• In addition to the defect in glucose homeostasis, there is also Initial reports in small numbers of GSD patients demon-
a Fanconi picture resulting in increased renal losses of fluid, strated that CGM provided useful longitudinal data on
glucose, galactose, amino acids, calcium, phosphate and blood glucose concentrations rather than single time points
potassium; supplementation to replace losses is essential [166] and the detection of unrecognised hypoglycaemia
[167]. A study including an audit of 55 profiles in 26 patients
(mainly children) showed 95% of profiles produced mean-
ingful data and highlighted the usefulness of CGM, in asso-
Continuous glucose monitoring in glycogen ciation with diet diaries +/− lactate and ketone measurements
storage disorders and growth data, in optimising GSD biochemical parameters
and nutritional management [164]. A further study of CGMS
Assessment of blood glucose control is pivotal to the man- in 20 patients (40% ≥17 years old) showed the usefulness of
agement of hepatic GSD forming an integral part of the the technique throughout the age continuum [168]. In addi-
broader clinical and biochemical monitoring (Table 29.18). tion to its role in detecting subclinical hypoglycaemia, the
Regular assessment of the child’s dietary intake, growth and study also highlighted the detection of periods of hypergly-
relevant biochemistry is essential to optimise treatment and caemia, which equally need to be recognised and managed
outcome by avoidance of under‐ and/or overtreatment [39]. to prevent longer‐term consequences of chronic hypergly-
Historically assessment of appropriateness of treatment caemia (obesity, metabolic syndrome, type 2 diabetes).
regimens, in most UK and European metabolic centres, has
been an annual inpatient admission for a 24 hour blood glu- Continuous glucose monitoring systems
cose +/− lactate profile, other relevant biochemical parame-
ters and growth measurements. Although such admissions How they work
are able to provide true blood glucose +/− lactate measure-
• continuous glucose monitoring systems (CGMS) consist
ments, their benefit is limited due to:
of an indwelling glucose sensor attached to a wireless
• giving only single point in time measurements, typically data recorder
pre‐ and post‐meals or as a maximum every 1 or 2 hours, • the sensor, a very fine microelectrode coated with glu-
with no indication as to the trajectory of glucose levels cose oxidase, is inserted under the skin, usually into the
• the hospital environment differing from home and the abdomen although other areas can be used, e.g. upper
inability to reproduce normal home life, e.g. mealtimes arm and buttock, and connected to a small recorder
and types of food are different, and normal activity levels • the sensor measures glucose concentrations indirectly via
at home and school cannot be maintained an electrical signal produced by a glucose‐oxidase elec-
• changes in dietary regimens may need a further period trochemical reaction in the interstitial fluid. Measurements
of inpatient assessment are taken every 10 seconds, and an average reading every
5 minutes is recorded and wirelessly transmitted to the and results should be interpreted with some caution,
data recorder, producing up to 288 measurements per particularly if they appear unusually abnormal for
day the child. For example, if blood glucose and lactate
• sensor signals are converted to glucose concentration by levels are well controlled, a one‐off very high lactate
a calibration process utilising finger stick blood glucose level would be unusual, but following a period of
measurements [169]: hypoglycaemia, a high lactate level would be in keep-
◦◦ to reduce errors in calibration, capillary blood sam- ing. Lactate, however, can be high in seemingly well‐
ples should be taken at times when these should be managed patients, despite normoglycaemia; in these
more stable, e.g. preprandial cases lactate levels may be more consistently raised
◦◦ a major cause of sensor error is calibration with capil- • CGM profiles should be carried out with normal activi-
lary glucose levels that are rapidly changing as there ties, including school days and sports, and no changes to
is a lag time between changes in plasma and changes dietary intake unless advised
in interstitial glucose levels [170]. This, in addition to • following the monitoring period, the sensor data are
the sensor reaction time for glucose to diffuse into the downloaded using specific computer software, and the
sensor and for a signal to be processed, give an over- data are then reviewed:
all lag time of 5–15 minutes [171] ◦◦ lower and upper limits for glucose levels are defined,
• retrospective and ‘real‐time’ systems are available. In which the software uses to look at time periods above
GSD management the use of ‘real‐time’ systems is dis- and below the target glucose range. In the author’s
couraged as this may result in families making frequent centre these are set at a lower glucose limit of
management changes, without discussion, which may 3.5 mmol/L and upper limit of 8 mmol/L, except for
not be appropriate [164] Fanconi Bickel syndrome where the upper limit is set
at 10 mmol/L due to the extremes of hyperglycaemia
observed in the condition
Practicalities of using CGM
• data generated includes:
• sensors can remain in situ for around 6–14 days depend- ◦◦ individual daily graph of glucose profile
ing on type ◦◦ overlay of each day’s profile on one graph
• blood glucose meter measurements are taken four times ◦◦ data on total number, highest, lowest and average
daily prior to main meals and before a bedtime snack, start sensor values and standard deviation (SD) of glucose
of continuous overnight feed or evening dose of UCCS readings – the lower the SD, the less fluctuation there
• a daily food diary is kept throughout the study and is is in glucose values
essential for accurate interpretation of CGM results ◦◦ accuracy criteria, which includes correlation between
(Table 29.21) sensor and calibration capillary glucose measure-
• lactate and ketone monitoring, as clinically relevant, is done ments and the mean absolute difference (% MAD).
alongside CGM. Lactate meter measurements are done MAD is the average % difference between sensor
concurrently with blood glucose measurements. Ketones and capillary glucose values. Values <28% are opti-
(urine or blood using a dual‐purpose blood glucose/ketone mal or <18% if glucose is maintained within a nar-
meter) are usually measured before breakfast only: row range [173]
◦◦ measurement of blood lactate is particularly relevant ◦◦ excursion summary, which describes the number of
in GSDI. The Lactate Pro portable meter has been glucose levels above or below target glucose levels
validated in GSDIa [172] ◦◦ duration distribution, giving % time below, within
◦◦ lactate measurements, however, can be inaccurate and above target in 24 hours
particularly if the blood sample was not free flowing • CGM profiles should be reviewed looking at trends and
the presence of repeated patterns rather than relying on
single measurements, in conjunction with all other test
Table 29.21 Home monitoring indicating the different parameters
monitored according to disorder.
results to inform management advice
An example of the use of CGM in practice is shown in
GSD type 0 Ia/b IIIa/b VI and IX FBS Figures 29.3 and 29.4. Home monitoring for types of GSD is
CGM ✓ ✓ ✓ ✓ ✓ shown in Table 29.21.
Blood glucose (capillary) ✓ ✓ ✓ ✓ ✓
meter levels
Benefits of CGM
Lactate ✓ ✓ • avoidance of hospital admissions and associated
Ketones ✓ ✓ ✓ ✓ repeated venepuncture
• may be inserted and removed at home by nurses trained
Food diary ✓ ✓ ✓ ✓ ✓
• Time
in CGMS
• Quantities • improved representation of normal lifestyle including
dietary intake, activity patterns and adherence to pre-
CGM, continuous glucose monitoring. scribed dietary regimens
Hereditary Fructose Intolerance 631
• glucose profile results are a visual educational tool for

• allows comparison of weekend and school day profiles
families; they can highlight adherence issues that can be
• profiles provide significantly more information and are
addressed to improve biochemical control or illustrate
more ‘visual’ than a list of numbers produced during a
specific foods that may cause high blood glucose levels,
standard inpatient blood glucose profile
typically refined CHO
• information gained includes confirmation of the ade-
• increased information on overall dietary intake that can
quacy of the usual dietary regimen or identification of
inform targeted advice on improving nutritional ade-
trends indicating regimen changes are needed, e.g. glu-
quacy of the diet
cose levels falling overnight or before feeds, even if the
• the process is positively accepted by the families
level is not below the lower target glucose range, indicate
• is well tolerated by all age groups of patients
the potential for hypoglycaemia and the need to re‐eval-
uate the dietary regimen CGM should normally be done at least annually. In infants
• ability to adjust and compare different dietary regimens and young children with the most severe forms of GSD
during a profile period, which is valuable in attempting requiring intensive regimens, or in newly diagnosed or
to optimise an individual’s treatment without the need unstable patients, more frequent CGM will be needed to
for repeated inpatient admissions, over a period of time, evaluate the effectiveness of management. In very stable or
to assess different regimens mild patients less frequent CGM may be acceptable.
Hereditary Fructose Intolerance

Fiona J. White
Hereditary fructose intolerance (HFI) is a very rare, possibly under‐diagnosed, inherited metabolic disease.
Enzyme Aldolase B (fructose‐1, 6‐bisphosphate aldolase) found in the liver, kidney and small intestine
Biochemical Block in the conversion of fructose‐1‐phosphate (F‐1‐P) to glyceraldehyde and dihydroxyacetone. This results in accumulation
defect of F‐1‐P and lack of intracellular phosphate/ATP causing inhibition of glycogenolysis and gluconeogenesis and reduced glucose
production (Figure 29.6).
Genetics Autosomal recessive inheritance. There are some common mutations in the ALDOB gene that can be analysed initially if HFI is
suspected.
Clinical onset Generally presents after weaning when fructose‐containing foods are introduced. May have an aversion to sweet foods and
presentation, sugar‐containing medicines, which may delay the diagnosis for years. Presenting clinical features can vary between:
features • acute severe presentation with hypoglycaemia, seizures and coma following ingestion of fructose, sucrose or sorbitol. In
neonates this may lead to acute liver failure, kidney failure and death [174]. Acute presentation is less likely before weaning
when infants are fed non‐fructose‐containing feeds, i.e. breastmilk or infant formulas where lactose is the carbohydrate
source. However, there are case reports of neonates presenting, precipitated by being fed sucrose‐containing formula [175]
• non‐specific features of poor feeding, vomiting, abdominal distension, restlessness, lethargy and growth faltering. A good diet
history in these situations may reveal self‐avoidance of sweet foods and drinks and vomiting with sugar‐containing
medications and gives a clue to the diagnosis
• progressive liver dysfunction, hepatosplenomegaly, hypoglycaemia and renal tubular dysfunction
Long‐term The long‐term prognosis is good provided a fructose‐free diet is followed, although hepatomegaly and fatty changes in the liver
complications and may persist [176].
outcome The diet needs to be continued for life.
Acute IV dextrose to correct any hypoglycaemia
management Avoidance of IV fluids containing fructose or sorbitol (this is not an issue in the UK)
Dietetic Minimal fructose, sucrose and sorbitol diet (Table 29.22)
management Supplementation of vitamin C and folic acid to meet requirements
Medications Pharmacy check regarding suitability of medicines as they can contain sucrose, fructose, sorbitol and artificial sweeteners.
Monitoring • growth
• dietary adherence
• liver and renal function tests, full blood count, plasma folate and iron status (haemoglobin and ferritin)
• clinical assessment of skin and gums, checking for signs of vitamin C deficiency (swollen tissue, tender and bruises easily and
bleeding gums). Vitamin C status can be measured in white blood cells, but analysis is not performed routinely by all
laboratories (www.clinbiochem.info). Adult range: 26.1–84.6 μmol/L (there is no paediatric range); deficiency level:
<11.1 μmol/L
• vitamins A, E and D, selenium and zinc to measure general nutritional status as indicated
• plasma lactate, urate and urinary protein to assess renal tubular dysfunction as indicated
References Steinmann B, Santer R. Disorders of fructose metabolism. In: Saudubray JM, Baumgartner M, Walter J (eds) Inborn Metabolic
Diseases: Diagnosis and Treatment, 6th edn. Berlin: Springer‐Verlag, 2016. [174].
Baker P, II, Ayres L, Gaughan S, Weisfeld‐Adams J Hereditary fructose intolerance. In: Adam MP, Ardinger HH, Pagon RA et al.
(eds) GeneReviews. Seattle: University of Washington, 2015. [177] www.ncbi.nlm.nih.gov/books/NBK333439/.
Parent support Metabolic Support UK (www.metabolicsupportuk.org/)
group
Sorbitol Glucose Glycogen
Fructose Glucose-6-phosphate Glucose-1-phosphate
Fructose-1-phosphate Fructose-6-phosphate
(1) (2)
Dihydroxyacetone Glyceraldehyde Fructose-1,6-bisphosphate

phosphate
Glyceraldehyde-3-phosphate Dihydroxyacetone phosphate
Pyruvate
Glycerol-3-phosphate
(3)
Lactate
Glycerol
(1) Aldolase B – deficient in hereditary fructose intolerance

(2) Fructose-1,6-bisphosphatase – deficient in fructose-1,6-bishosphatase deficiency
(3) Glycerol kinase – deficient in glycerol kinase deficiency
Figure 29.6 Fructose and glycerol metabolism.
Dietary treatment Carbohydrates that can be included in the diet
HFI is managed primarily by avoidance of fructose, sucrose • starch

and sorbitol in the diet and in medicines (Table 29.22). • glucose – can be used as an alternative sweetener to
Dietary aims are: sucrose and can also provide a useful source of energy:
◦◦ glucose has only half the sweetness of sucrose, so addi-
• the complete elimination of fructose, sucrose, sorbitol and
tional sweetening can be added to baked goods using
other potential sources of fructose. However, this is not
as intense sweetener, e.g. Sweetex can be successfully
realistic or possible as very small amounts of fructose are
added to cooked food; others that decompose on heat-
found in many staple foods, particularly plant‐based foods
ing, e.g. aspartame, are not suitable for baking
• in practice fructose intake is restricted to <2 g/day from
◦◦ in practice this may not be necessary as children with
all sources, i.e. the lowest intake that is practically achiev-
HFI generally dislike and avoid sweet tasting foods
able (Table 29.22). On these intakes patients remain
◦◦ glucose is not prescribable for treatment of HFI
symptom free
• lactose
In adults with long‐term daily intakes of up to 2.5 g • polyols: erythritol, xylitol and lactitol
sucrose/day (1.25 g fructose, approx. 15–20 mg/kg), symp- • sucralose (E955), previously known as Splenda, is about
toms did not develop [181]. 600 times as sweet as sucrose. It is increasingly used in
Table 29.22 Minimal fructose, sucrose and sorbitol diet (aim <2 g fructose/day).
Analysis of fructose and sucrose content of foods [178–180]
Foods allowed Foods to avoid
Sugars, sweeteners and preserves

Glucose, glucose polymers, glucose syrup, dextrose, lactose, Sugar or sucrose (cane or beet) – white, brown, caster, icing
starch, maltose, maltodextrin, malt extract, glycerol Fruit sugar, fructose, laevulose
Saccharin, aspartame, acesulfame K, Honey, treacle, molasses
Sweetex (aspartame and saccharin), sucralose (E955) Polyols: sorbitol, maltitol, mannitol, isomalt, Lycasin
Polyols: erythritol, xylitol, lactitol Golden syrup, corn syrup, invert syrup, high fructose or isoglucose syrups,
hydrogenated glucose syrup, maple syrup
Jam, marmalade, lemon curd
Fruits
Avocado, rhubarb (occasionally) All other fruits and fruit products
Vegetables
Seaweed, vine leaves allowed freely Beans (French, green, runner), beetroot, Brussels sprouts, carrots, gherkins, green
See Table 29.23 beans, kohl rabi, okra, onion, parsnip, peas, pepper, plantain, shallots, spring onion,
squash, sweetcorn, sweet potato, tomato, tomato purée
See Table 29.23 Baked beans, tinned vegetables with added sugar, mayonnaise or salad cream, coleslaw
Flavoured crisps
Pickles, chutney
Milk and dairy products
Infant formula and follow‐on milk (check there is no added Flavoured milk, condensed milk, milkshake powders and syrups
sucrose, fructose or honey)
Cow’s milk, unsweetened evaporated milk Liquid soya milk
Coffee mate, dried milk powder Aerosol cream
Cream Cheese with added ingredients, e.g. nuts, fruit
Cheese, plain cottage cheese Fruit and flavoured yoghurt, fromage frais
Natural yoghurt Ice cream
Eggs
Meat and poultry
All fresh meat and poultry Processed meats that have added sucrose, e.g. meat pastes, frankfurters, salami,
pâté, sausages, tinned meat
Processed meat products (check there is no added sucrose, Tender sweet meats, e.g. ham, honey cured meats
fructose or honey) Ready‐made meat meals (possible sources are gravies, sauces, vegetables,
breadcrumbs, batter, pastry)
Meat substitutes
Soya products, tofu, Quorn Ready‐made meals with these products may contain sucrose
Fish
Fresh and frozen fish Fish tinned in tomato sauce
Shell fish Fish paste
Fish tinned in brine, oil or water Fish cakes, fish fingers
Ready‐made fish meals (possible sources are sauces, vegetables, breadcrumbs,
batter, pastry)
Flour and cereals
Flour (white in preference to wholemeal), buckwheat, cornflour, Bran, wheat germ
custard powder, sago, semolina, tapioca, oatmeal, barley
Flaky pastry, filo pastry, shortcrust pastry (not sweetened) Dessert pastry
Pasta and rice
Spaghetti, macaroni, other pasta (white in preference to Pasta tinned in tomato sauce
wholemeal)
Noodles, egg noodles Pot savouries, e.g. pot noodle
Rice (white in preference to brown)
Breakfast cereals
Porridge, Puffed Wheat, Ready Brek, Shredded Wheat Most manufactured breakfast cereals
Analysis of fructose and sucrose content of foods [178–180]
Bread and crackers

White bread (pre‐packed), tortilla wraps Wholemeal bread, sweetened breads, e.g. malt bread, soda bread, currant bread,
Baker’s bread (check if sugar is added to dough mixture) malt loaf, brioche, pain au chocolat
Cream crackers, matzo crackers, water biscuits, Ryvita, plain Savoury snack biscuits
rice cakes
Crumpets (not all are suitable, check label)
Cakes, biscuits and pastries
Home‐made – using permitted ingredients and sweeteners All cakes, muffins, pancakes, waffles, biscuits and pastries
Desserts
Home‐made – using permitted ingredients, e.g. custard Most desserts, e.g. jelly, meringue, mousse, gateaux, fruit pie or crumble, yoghurt,
sweetened with glucose, choux pastry ice cream, sorbet, ice lollies
Fats and oils
Butter, margarine, vegetable oils (including olive oil), lard, suet
Drinks
Lucozade Original (not fruit flavoured), soda water, mineral Fruit juices, vegetable juices, fruit squash, fizzy drinks, diabetic squash containing
water (not fruit flavoured) sorbitol or fructose, tonic water, fruit ice, Slush Puppie
Squashes and fizzy drinks flavoured with saccharin or Drinking chocolate, malted drinks
aspartame only (free from sugar, sorbitol, fruit flavourings or Instant tea mixes, coffee essence
comminuted fruits) Fruit teas
Tea, coffee, cocoa, herbal teas (no sugar)
Confectionery
Lucozade Sport Glucose Energy tablets – original Sweets, chocolate, toffee, jelly, ice lollies, chewing gum, diabetic sweets
(sweetened with fructose or sorbitol)
Dextro energy – dextrose and maltodextrin Flavoured glucose tablets
Glucotabs (BBI healthcare)
Gravies, sauces and soups
Marmite, Bovril Gravy granules, stock cubes
White or cheese sauce made with milk, flour, fat and cheese Bottled sauces and dressings, e.g. tomato ketchup, horseradish sauce, mint sauce,
only soy sauce, sauce mixes, e.g. sweet and sour, curry
Mayonnaise, salad cream
All soups (packet, tinned or fresh)
Herbs, spices, nuts and seeds
Pure herbs, mustard and spices, salt, pepper Nuts, peanut butter, marzipan
Sesame seeds
Pumpkin and sunflower seeds (maximum 10 g per day)
Baking products
Baking powder, bicarbonate of soda, yeast, arrowroot, food
colourings, food essences, gelatine
Alcohol (not suitable for children)
Beer – bitter, lager, mild, pale ale, stout (Guinness), Low alcohol bitter, alcohol free/low alcohol lager, shandy, fruit beers
strong ale/barley wine
Note: Sucrose or fructose may be added to bottled, canned or Cider
keg beers to adjust the sweetness of the final product
Sucrose is usually added to cask conditioned beers (sometimes
referred to as ‘real’ beers) to generate secondary fermentation
within the container
Wine – red only Wine – champagne, mulled wine, rose, white fortified wines – port, sherry, tonic
wine, vermouth
Spirits Liqueurs
Alcopops
• Always read the label of manufactured foods to check for sucrose, fructose, sorbitol, polyols or unsuitable sweeteners.
• Check toothpaste for sorbitol.
Dietary Treatment 635
Table 29.23 Vegetables allowed in a minimal fructose, sucrose Table 29.23 (continued)
and sorbitol diet [180].
Swede
Total daily fructose intake from vegetables should not exceed
Turnip
1.0–1.5 g/day
Beans – black eye, broad, butter, soya
Group 1 – potatoes (old)
Peas – marrowfat, mushy, processed peas in water
1 portion = approximately 0.3 g fructose
Chickpeas or hummus
Boiled – 2 small egg size (100 g)
Jacket (flesh only) – 1 medium (100 g) Source: Licensed Under CC BY 4.0.
Mashed – 2 tablespoons (100 g)
Roast potatoes – 2 small (100 g) products including medicines. Pharmacokinetic studies
in humans given sucralose showed that the majority was
Chips – medium portion (120 g)
recovered unchanged, predominantly in faeces [182]. It
Plain crisps – 2 small packets
would appear unnecessary to exclude sucralose in HFI
*Potato waffles (1) because the amount added to foods is likely to be
*Potato croquettes (2) extremely small, it is mostly not absorbed, and its intense
*Check to ensure does not contain sugar sweetness will probably be disliked
Group 2 – vegetables containing <0.5 g fructose/100 g

1 portion = approximately 0.15 g fructose where a small portion is
Sources of fructose that need to be avoided in HFI
1 tablespoon (30 g) unless indicated otherwise
Sugars
Celery
Globe artichoke (1 globe, 50 g) In addition to fructose per se, fructose is also derived from
sucrose and sorbitol. A number of compounds can also be
Mange tout
potential sources of fructose and need to be avoided:
Mushrooms
Sauerkraut
• fructose is the natural sugar present in fruits, vegetables
and honey
Spinach
• sucrose, a disaccharide, is cleaved in the small intestine
Watercress (1∕2 bunch) by sucrase‐isomaltase forming a molecule each of glu-
Beans, e.g. haricot, mung, red kidney cose and fructose. Sucrose is found in:
Lentils ◦◦ small amounts in fruits and vegetables
◦◦ sugarcane or beet, refined to produce table sugar that
Yam – boiled or baked (amount = ½ small potato)
is used extensively in baking and in food manufac-
Dried split peas ture as a sweetener and bulking agent
Group 3 – vegetables containing 0.5–1.0 g fructose/100 g ◦◦ cakes, biscuits, desserts and soft drinks
1 portion = approximately 0.3 g fructose where a small portion is ◦◦ commercial foods (e.g. stock cubes, tinned meats, bot-
1 tablespoon (30 g) unless indicated otherwise tled sauces, savoury snack biscuits) contain sugar, but
Aubergine – 1 slice (30 g)
are much less obvious sources. Indeed, very few man-
ufactured foods are suitable for inclusion in the diet
Asparagus – 2 spears (50 g)
◦◦ high fructose corn syrup is used as a sweetener, particu-
Bean sprouts larly in the USA where it is a large contributor [183, 184]
Broccoli – 1 spear (50 g) • sorbitol and other polyols. Polyols are sugar alcohols,
Cabbage classed as sugar‐free, low energy bulk sweeteners that are
used in many foods and medicines. They are potential
Cauliflower
sources of sorbitol and fructose. Their absorption is slow
Cucumber – 8 thin slices (40 g) and incomplete, for example, only 10%–30% of sorbitol is
Fennel – (45 g) absorbed. Although sorbitol does not contain fructose, in
Jerusalem artichoke – (40 g) the liver it is rapidly converted via sorbitol dehydroge-
Celeriac – (35 g) nase to fructose in the sorbitol‐aldolase or polyol path-
way. Polyols are thus a possible source of fructose or
Leeks – 1∕4 medium (30 g)
sorbitol [185].The most widely used and to be avoided in
Lettuce – 4 small leaves (25 g) HFI are sorbitol (E420, derived from dextrose), mannitol
New potato – 1 small (50 g) (E421, derived from fructose), maltitol (E961, derived
Pumpkin from maltose) and isomalt (E953, derived from sucrose)
◦◦ foods and medicines, e.g. sugar‐free syrups, lozenges
Radish (red) × 4 (40 g)
and jelly preparations, suitable for children may con-
Spring greens
tain these - check for suitability
◦◦ there are different brands of polyols available, e.g. • Group 1 – potatoes

Lycasin (contains maltitol) and Neosorb (contains • Group 2 – vegetables containing <0.5 g fructose/100 g
sorbitol). Polyols should be declared on the food • Group 3 – vegetables containing 0.5–1 g fructose/100 g
ingredient and nutritional labels in the UK, making
Within each group portion sizes are indicated to provide a
them relatively easy to identify
certain amount of fructose. These can then be used to calcu-
◦◦ some toothpastes contain sorbitol - avoid as young
late daily fructose intake from vegetables.
children may swallow toothpaste
It is important to note the difference in fructose content
• oligosaccharides, raffinose (trisaccharide) and stachyose
between raw and cooked vegetables:
(tetrasaccharide) comprise fructose and glucose to which
galactose is linked in an α‐galactosidic linkage; it is thought • cooking causes a loss of free sugars; consequently cooked
that in humans these are not hydrolysed due to the absence vegetables have a lower fructose content and are recom-
of α‐galactosidase [186]. They are found in small quantities mended in preference to raw
in food: raffinose in sunflower seeds, chicory, onions and • water from boiled vegetables should be discarded and
other vegetables (about 1 g/100 g food or less); legumes are not used to make gravy or sauces
the richest source of stachyose (1–5 g/100 g food) • new potatoes have a higher fructose content than old
• fructans and fructo‐oligosaccharides. Inulin is a fructan (0.65 g/100 g vs. 0.25 g/100 g)
found in various plants, e.g. artichokes and chicory [187]. • sucrose content of stored potatoes has previously been
Fructo‐oligosaccharides (FOS), also known as oligofruc- reported to both decrease and increase on storage [191,
tose, are produced through enzymatic hydrolysis of inu- 192]. Information from the Institute of Food Research,
lin. Both inulin and FOS are primarily sources of dietary Norwich, reports that potatoes in cold storage (<8 °C)
fibre. Being resistant to hydrolysis by digestive enzymes, have a higher fructose content compared with those
they are not absorbed, but instead are fermented by stored in warm temperatures (>15 °C)
anaerobic bacteria in the colon. However, as they have an
energy value of 1.5–2 kcal (6–8 kJ)/g, it is possible that Manufactured foods
some fructose may be absorbed and that commercial inu-
lin and oligofructose syrups may contain small amounts Ingredient labels on manufactured foods should be checked
of fructose and sucrose: for the presence of sucrose, fructose or sorbitol and other
◦◦ FOS, as prebiotics, are added to some infant formu- polyols or unsuitable sweeteners (Table 29.22). In the UK
las and enteral feeds to promote the growth of intes- regulations on sugar labelling are available at www.
tinal flora similar to that of the breastfed baby [188, legislation.gov.uk/uksi/2003/1563/contents/made.
189]. It is also added to weaning foods and func- Products covered by these rules include:
tional foods. At low doses it is unlikely to cause • white sugars, dextrose, glucose syrups and fructose
adverse effects [175, 181] • where a product is labelled to contain ‘sugar’ this indi-
◦◦ the ingredients of special infant formulas and enteral cates the ingredient is sucrose
feed products should be checked for sucrose and fruc- • where glucose syrup or dried glucose syrup contains
tose. In the EU only lactose as a carbohydrate source is more than 5% fructose, ‘fructose’ will be indicated as an
allowed in normal infant formulas [190]. However, this ingredient
may not be the case in other countries; Li et al. reported
four cases of acute liver failure in neonates fed fructose‐
Flour, bread, rice
containing formulas, subsequently diagnosed with HFI
[175] • wholemeal flour and other wholegrain foods, e.g. brown
• flavourings can be another potential source of sucrose rice and wholemeal pasta, contain more fructose than
and fructose as these sugars are sometimes used as carri- white versions because the germ and bran contain
ers for flavouring compounds, which will not necessarily sucrose
be labelled • no accurate analysis for the fructose content of bread is
available; however, it would appear prudent to choose
white in preference to wholemeal. Bread has previ-
Vegetables
ously been restricted in the diets of children with HFI.
Vegetables contain significant amounts of fructose (as fructose Nowadays this restriction is probably unnecessary
and sucrose) so most must be avoided, and only vegetables because most flour improvers for bread making do not
with a very low fructose content, predominantly containing contain sugar. If the bread does contain sugar, it has to
starch, can be included in the diet in restricted amounts only be declared on the ingredient label. If there is any doubt
(Table 29.22). The total daily fructose intake from vegetables about suitability of a particular bread, the manufac-
should not exceed 1–1.5 g/day as small amounts of fructose turer should be contacted. Caution should be applied
from cereals in the diet will increase the total intake to around where richer doughs are used (e.g. in soft rolls) because
the 2 g/day maximum. As the total fructose content (fructose often the flour improver does contain sugar in these
plus half the sucrose content) varies between different vegeta- instances. Bread bought from craft bakers may also
bles, they have been divided into three groups: contain sugar. Under EU law products sold loose are
Fructose‐1,6‐Bisphosphatase Deficiency 637
under no legal obligation to declare this information to • lack of dietary fibre may also be a problem. This can
the consumer as sucrose, fructose and sorbitol are not be overcome by including pulses and oats, which
allergens [193] contain only very small amounts of fructose, or inclu-
sion of Resource Optifibre (Nestle); the fibre source is
guar gum
Nutritional problems
Nutritional deficiencies may arise in children with HFI: Learning points: hereditary fructose intolerance
• risk of vitamin C and possibly folic acid deficiency due to
the exclusion of the major dietary sources of these vita- • Many patients will have self ‐selected a low fructose diet
mins, i.e. fruits and vegetables [194] prior to diagnosis
• supplementation with vitamin C and folic acid is neces- • A good diet history taken can alert healthcare professionals
sary to provide reference nutrient intake [29] to the possibility of HFI in undiagnosed patients
• commercial vitamin and mineral preparations should be • Dietary avoidance of fructose continues lifelong to avoid
checked to ensure ingredients do not contain sucrose, deleterious effects on liver and kidney
fructose, sorbitol, sucralose or other polyols
Fructose‐1,6‐Bisphosphatase Deficiency
Anita MacDonald
Enzyme Fructose‐1,6‐bisphosphatase (FBPase)

Biochemical defect FBPase is a key gluconeogenic enzyme that catalyzes the hydrolysis of fructose‐1,6‐bisphosphate to fructose‐6‐
phosphate and inorganic phosphate (Figure 29.6) [195]. Deficiency affects gluconeogenesis by impairing the formation
of glucose from all gluconeogenic precursors including dietary fructose [196]. Hypoglycaemia occurs after prolonged
fasting when glycogen stores are depleted [195].
Genetics Autosomal recessive inheritance. It is caused by mutations within the FBP1 gene on chromosome 9q22.2–q22.3 and
consists of 8 exons; incidence is rare, but is more common in countries with higher rates of consanguinity [197].
Presentation Signs and symptoms include hypoglycaemia, ketoacidosis, lactic acidosis, hepatomegaly, coma and tachypnoea (occurs
in neonates, about 50% of cases) or later during fasting or induced by fructose (approx. 1 g/kg body weight in one dose),
especially after fasting [174]. Diagnosis may be delayed, and children may have experienced more than one episode of
acute metabolic decompensation. Poor appetite, intercurrent infections, vomiting and prolonged fasting can precipitate
metabolic decompensation.
Long‐term complications Mortality is high in the neonatal period, usually before diagnosis is made [196]. Once the diagnosis is established, the
and outcome outcome is generally good. Children remain asymptomatic between acute episodes of metabolic decompensation.
Growth and development of patients are usually normal. However, profound hypoglycaemia may lead to neurological
deficits. Fasting tolerance should improve with age [199], and the frequency of acute metabolic decompensations
decrease [174]. Symptoms have been reported in adulthood associated with illness and fasting during Ramadan [200],
pregnancy [201], alcohol consumption [202], weight loss and extensive exercise training (the latter requires careful
management) [203].
Dietary management Dietary management is not well characterized, but should prevent hypoglycaemia and lactic acidosis. There is a
dependence on exogenous sources of glucose, and the primary dietary goal is to avoid prolonged fasting.
Fasting:
• in infants and young children fasting times are limited, and infants commonly develop clinical symptoms following
withdrawal of night feeds
• infants should be fed 3–4 hourly until fasting tolerance is established (NB: fasting tolerance of only 3 hours has been
reported in some case studies in infancy [196])
• in children >1 year of age regular meals containing starchy foods is important, including a bedtime snack, and
breakfast should not be missed
• in childhood it is often reported that fasting does not exceed 8 hours, but individual fasting tolerance varies [204] and
should improve with age [205]
Cornstarch (UCCS):
• a late evening single dose of UCCS (household cornflour) is recommended by some centres to provide a source of
slow‐release glucose overnight [206]
• the mean dose by age reported is as follows: 1–10 years, 1.2 g/kg; 11–16 years, 1.3 g/kg; >16 years, 1.0 g/kg) [205]
• there is little data to support its effectiveness in FBPase deficiency
• if UCCS is not given, a bedtime snack containing complex CHO, e.g. bread or cereal, is advocated
Further information about provision of UCCS is given on p. 613.

Fructose and sucrose restriction:
• although fructose is a gluconeogenic precursor, the severity of sucrose and fructose restriction remains undefined, and
dietary practices vary [205]
• loading tests with fructose induced hypoglycaemia [207], suggesting reduced fructose tolerance; however, in non‐
catabolic states, fructose (sweet food) is generally tolerated in children when distributed over the day [200]
• although many international centres avoid an excessive intake of confectionery and sugary drinks, particularly in
young children [199, 205], most (64%) UK centres do not restrict fructose, sucrose or sorbitol intake when patients
are well [208]
Alcohol:
• care must be taken if alcohol is consumed as it inhibits gluconeogenesis and in excess may precipitate
hypoglycaemia; therefore, it should be taken in moderation only and always with food [209]
Clinical and biochemical Clinical: somatic findings (liver size)
monitoring Neurological: cognitive function, developmental monitoring
General monitoring: growth, nutritional status, dietary intake
Biochemistry: liver function, assessment of fasting tolerance
Illness: glucose (low), lactate (high), pH, blood gases, full blood count
Emergency regimen and • Metabolic decompensation occurs during illness, trauma and surgery because the gluconeogenic pathway for glucose
acute management production is blocked. During acute episodes, there is lactate accumulation, decreased pH and an increased lactate/
pyruvate ratio, hyperalaninaemia and glucagon‐resistant hypoglycaemia [199].
• Treatment aims to prevent metabolic decompensation by giving glucose orally or IV. If tolerated, the standard oral ER
for age should be given (Tables 31.1 and 31.2). The ER should be glucose polymer only; sweetened squash or other
drinks should not be added as fructose, sucrose and sorbitol should be temporarily avoided during the acute illness.
Fat should be avoided during decompensation as glycerol may exacerbate the illness.
• Some patients may decompensate rapidly, becoming very ill with marked acidosis. If the child is unwell, a bolus of IV
glucose is immediately administered [210] before providing an infusion of IV glucose (10%) at maintenance fluid
requirements. Metabolic acidosis is treated by giving sodium bicarbonate. This treatment should promptly ameliorate
symptoms [208]. In acute metabolic decompensation, IV administration of fructose is contraindicated and may lead
to death [199].
• Once the child improves, a normal diet can be resumed, with a gradual reintroduction of fructose and sucrose.
During the recovery period, extra glucose polymer drinks should continue to be given, particularly at night.
• Fructose, sugar‐ and sorbitol containing medications should be avoided during intercurrent illness. Only sugar‐free
medicines should be given, but constituents should still be checked.
• In Asian countries, including Japan, IV glycerol therapy may contain fructose, and this can cause hypoglycaemia and
metabolic acidosis, even under stable conditions in patients with FBPase deficiency [208].
Learning points: fructose‐1,6‐bisphosphatase deficiency
• Clinical symptoms of FBPase deficiency may overlap with

many other metabolic disorders, and diagnosis is commonly
delayed
• Dietary management in infancy and early childhood is
avoidance of prolonged fasting +/− bedtime UCCS (for
children >1 year of age)
• The standard ER is essential at all ages to prevent metabolic
decompensation during illness and prolonged fasting
• Fructose, sucrose and sorbitol should be avoided during
acute metabolic decompensation
Glycerol Kinase Deficiency (GKD) 639
Glycerol Kinase Deficiency (GKD)

Marjorie Dixon
Enzyme Glycerol kinase

Biochemical Glycerol kinase catalyses the phosphorylation of glycerol to yield glycerol‐3‐phosphate (G3P) and ADP (Figure 29.6); around
defect 70%–90% of G3P is oxidised to dihydroxyacetone phosphate and enters the glycolysis or gluconeogenic pathway at the level of
glyceraldehyde‐3‐phosphate; 10%–30% of G3P combines with free fatty acids to form triglycerides [211]. Glycerol kinase
deficiency (GKD) is characterised by hyperglycerolaemia and glyceroluria. Normal plasma glycerol levels (<0.2 mmol/L) may
increase to 8 mmol/L, resulting in urine levels >150 mmol/L (normally undetectable) [212]. In non‐fasting situations, glycerol (via
gluconeogenesis) contributes little to hepatic glucose production. In prolonged fasting conditions, its contribution increases to about
20% energy as gluconeogenesis and fatty acid oxidation become essential to meet energy needs [211].
Genetics GKD1 is an X‐linked recessive disorder resulting from the deletion or mutation of the gene for the enzyme glycerol kinase [211].
Clinical onset There are three clinical forms:
presentation, Infantile form
features • GK deficiency, or the ‘GK complex’, results from the Xp21 contiguous gene deletion syndrome with congenital adrenal
hyopoplasia and/or Duchenne muscular dystrophy and is associated with severe developmental delay [211, 213]
Adult form
• ‘isolated GK deficiency’, benign with pseudohypertriglyceridaemia [214]
Juvenile form
• ‘isolated GK deficiency’ occurs in the first few years of life and is often precipitated by catabolism due to illness or poor feeding
and can include episodic vomiting, metabolic acidosis, ketotic hypoglycaemia, lethargy, hypotonia, seizures and
unconsciousness
Dietetic Juvenile form only – isolated GK deficiency:
management • avoidance of prolonged fasting
• during illness the standard ER (p. 673) is given to provide glucose as an energy source
• glucose is needed to prevent hypoglycaemia as the capacity to convert glycerol to glucose via gluconeogenesis is limited
• if IV fluids are required, only glucose should be given and not lipids
• refer to www.bimdg.org for IV management

30 Disorders of Mitochondrial Fatty Acid
Oxidation and Lipid Metabolism
Marjorie Dixon, Rachel Skeath and Fiona J. White
Disorders of Mitochondrial Fatty

Acid Oxidation and Related Disorders
Marjorie Dixon
Introduction to fatty acid oxidation formed from the ketogenic amino acids (p. 503). Electron
carriers (FADH2 and NAD) enter the electron transfer
Fatty acids are a major fuel source for most tissues of the chain to produce ATP. Enzyme defects can occur in the
body, especially during fasting, when glucose supply is lim- carnitine and fatty acid oxidation pathways, in the trans-
ited. They are the principal energy source for cardiac muscle fer of electrons and in the production and utilisation of
and skeletal muscle in the resting state and during prolonged ketone bodies, with resultant inadequate energy produc-
exercise. Fatty acid oxidation is also essential for the production (Figure 30.1).
tion of ketone bodies, another important fuel, which can be The metabolic disorders that manifest in these pathways
used by all tissues, particularly the brain during prolonged are treated primarily by diet. Some aspects of management
fasting as it cannot use fatty acids to generate energy. Ketones are universal, but others vary with the underlying disorder,
are also the preferred fuel for the heart. age at onset and severity. The main aim of treatment is to
Most naturally occurring fatty acids have a chain length ensure an adequate energy intake and avoidance of fasting
of 16–18 carbon atoms (long chain fatty acids [LCFA]). Fat to minimise the oxidation of fatty acids and by using an
metabolism begins in adipose tissue in response to falling emergency regimen (ER) during illness. Additionally, in
levels of blood glucose. Insulin activates hormone‐sensi- more severe long chain fatty acid oxidation disorders (LC‐
tive lipase, which promotes the release of free fatty acids FAOD), a minimal long chain fat diet, with increased carbo-
from triglycerides into the blood stream. Fatty acids are hydrate (CHO) intake and supplements of medium chain
then transported to the tissues bound to albumin. In tis- triglyceride (MCT), is needed. In other disorders, such as
sues where they are used, fatty acids enter the mitochon- medium chain acyl‐CoA dehydrogenase deficiency and the
dria bound to carnitine via the carnitine cycle pathway. ketone body disorders, MCT is best avoided.
Within the mitochondria, β‐oxidation is the primary Metabolic Support UK (www.metabolicsupportuk.org) is
breakdown pathway of fatty acids to produce acetyl‐CoA the UK patient organisation for inherited metabolic disor-
and electron carriers. Acetyl‐CoA can enter the citric acid ders; it encompasses all FAOD and offers bespoke support to
cycle or form ketone bodies in the liver. Ketones are also families and patients.

Carnitine
Plasma membrane CT
Acyl-CoA Long chain fatty acid + CoA
Mitochondrial
CPT I
outer membrane
Acylcarnitine + CoA
Carnitine
LCKAT Mitochondrial
CACT
inner membrane
VLCAD
LCHAD
CPT III
LCEH Acyl-CoA
CoA
MTP complex
Mitochondrial
matrix
Acetyl-CoA Acyl-CoA
FAD
MCKAT M/SCAD ETF

FADH2 e–
CoA
3-Ketoacyl-CoA Enoyl-CoA
H 2O
SCHAD Crotonase
NADH
3-Hydroxyacyl-CoA
NAD+ e–
e–
e– e– ETF Mitochondrial
Cx I Q QO inner membrane
Figure 30.1 Biochemical pathways of mitochondrial fatty acid oxidation.

Enzymes involved: CT, carnitine transporter; CPTI, carnitine palmitoyltransferase I; CACT, carnitine acylcarnitine translocase; CPTII, carnitine palmitoyl
transferase; VLCAD, very long chain acyl-CoA dehydrogenase; LCEH, long chain enoyl Co-A hydratase; LCHAD, long chain 3-hydroxyacyl-CoA dehydroge-
nase; LCKAT, long chain ketoacyl-CoA thiolase; MTP, mitochondrial trifunctional protein; M/SCAD, medium or short chain acyl-CoA dehydrogenase;
SCHAD, short chain acyl-CoA dehydrogenase; MCKAT, medium chain ketoacyl-CoA thiolase; CxI, complex I of respiratory chain; Q, ubiquinone;
e−, electrons; ETF, electron transfer flavoprotein; ETFQO, electron transfer flavoprotein ubiquinone oxidoreductase. Reprinted with permission of Springer.
Medium chain acyl‐CoA dehydrogenase

deficiency (MCADD)
Enzyme Medium chain acyl‐CoA dehydrogenase (MCAD) (Figure 30.1).

Biochemical MCAD is necessary for the oxidation of medium chain fatty acids (MCFA) (C6–C12). Deficiency results in reduced energy and
defect ketone body production. MCFA accumulate as their acyl carnitines and CoA esters, specifically octanoyl carnitine (C8) with an
increased C8/C10 ratio, and are considered responsible for the clinical sequelae.
Genetics Autosomal recessive inheritance. In Northern Europeans, the c.985A > G mutation is common and associated with classical
clinical disease. In the UK all babies are treated irrespective of mutation.
Newborn screening MCADD is included in the UK NBS programme. The prevalence in England is about 1 in 10 000 [1]. The screening test is the
quantitative assay of C8 and decanoylcarnitine (C10). More details on screening and diagnostic protocols can be found at www.
gov.uk and www.bimdg.org.
Clinical onset In countries without NBS, MCADD usually presents between 6 months and 4 years of age, but neonatal and adult onset also occur.
presentation, Some may never present. Patients present with a ‘hypoketotic’ hypoglycaemia that can lead to encephalopathy and is precipitated
features by metabolic stress such as fasting, gastrointestinal (GI) illness or respiratory infections [2, 3]. Alcohol intoxication as a cause is
described in adults [4]. Early symptoms may be poor feeding, lethargy and drowsiness. Hypoglycaemia is a late finding.
Outcome There is risk of high morbidity and mortality if not treated promptly; some patients die suddenly, probably due to cardiac
arrhythmias [2, 3]. Between episodes patients are usually completely well. Once diagnosed the outcome is very good [5].
Acute management Intravenous (IV) 10% glucose – www.bimdg.org/guidelines
Dietetic Under normal conditions oxidation of MCFA is normal due to overlapping enzyme substrate specificity [6]. The problem arises
management when there is increased demand for fatty acids to produce energy such as during fasting and illness. Management is to avoid
prolonged fasting and provide a regular endogenous energy supply to inhibit mobilisation of fatty acids. Fatty acid oxidation
increases after a shorter duration of fast in infants, so they need to be fed more frequently. There remains a paucity of published
data on safe fasting times [7]. The 2009 UK safe fasting times (Table 30.1) are based on the limited available evidence at the
time of writing. Added MCT needs to be avoided because their oxidation is reduced.
Emergency regimen The standard ER of frequent feeds of glucose polymer is required during intercurrent illness (p. 673).
Clinical guidelines Clinical, dietary management guidelines and information leaflets for screened patients can be accessed from www.bimdg.org.uk.
642 Disorders of Mitochondrial Fatty Acid Oxidation and Lipid Metabolism
Dietary guidelines for managing an at risk neonate SMA Gold Prem 1 (refer to manufacturers’ data on C8,
with a family history of MCADD C10 fatty acid content)
• If for any medical reason parenteral nutrition (PN) is
Neonatal deaths have been reported in breast‐ and formula‐ required, the volume of lipid solution to be administered
fed babies who were undiagnosed [8]. Newborns are at great- should be decided on an individual basis, and those that
est risk during the first 72 hours of life, especially if they are contain MCT, e.g. SMOF, should not be given
being breastfed. A prospective birth plan should be made to
avoid any delay in screening or clinical problems. Management Dietary guidelines for managing the well child
of MCADD at birth can be found online (www.bimdg.org): with MCADD
• Any at risk baby should be screened at 24–48 hours, and
results made available promptly Children (from 1 year of age)
• A term baby should be fed at least 4 hourly and, if pre-
• Advise a healthy balanced diet with regular meals (three
term, 3 hourly day and night until a diagnosis of MCADD
main meals, including breakfast, which must not be missed)
is confirmed or excluded
• Restriction of LCT is not necessary
• Special or preterm formulas that contain added MCT
• Fast for a maximum of 12 hours overnight (Table 30.1)
should be avoided (see below)
• Include a bedtime snack containing starchy foods such
• Top‐up feeds of formula milk are recommended for a
as bread, crumpets, muffins, rice cakes, crackers, biscuits,
breastfed baby (www.bimdg.org) as the energy content
pitta bread, chapatti or cereals
of breastmilk is low for the first few days of life and only
• Replace missed meals with a starchy snack, if necessary
small volumes are consumed
• Maintain a ‘healthy lifestyle’ through diet and exercise; a
• If there are concerns about feeding volumes, the baby should
CHO snack can be given before or after exercise if neces-
be transferred to the neonatal unit and fed by nasogastric
sary, but is not always essential
tube or given an IV infusion containing 10% glucose
• If teenagers consume alcohol, the amount should be
limited and always taken in combination with food (see
Dietary guidelines for managing the well infant below)
with MCADD • Avoidance of special feeds or energy supplements that
contain added MCT, e.g. most paediatric hydrolysed
Infants (under 1 year of age) protein feeds and some enteral feeds (refer to manufac-
turers’ data on C8, C10 fatty acid content)
• Breastfeeding or normal infant formula is suitable • If for any medical reason PN is required, the volume of
• Long fasts should be avoided (Table 30.1) lipid solution to be administered should be decided on
• Demand feed every 3–4 hours throughout the day an individual basis, and those containing MCT, e.g.
• Night feeds should be given according to guidelines for SMOF, should not be given
‘maximum safe fasting times’ (Table 30.1)
• Wean onto a normal diet at the usual time around 6
Alcohol
months (26 weeks) of age
• Encourage a regular intake of starchy foods as weaning Alcohol inhibits gluconeogenesis, so both fatty acid oxida-
progresses tion and gluconeogenesis, which provide fuel during fast-
• Restriction of long chain triglycerides (LCT) is not neces- ing, will be impaired. Excessive alcohol intake can lead to
sary [5] inadequate food intake and vomiting, which can be life
• The vegetable oils added to standard infant formula contain threatening [4]. Alcohol intake should be limited and always
only very small amounts of MCT, so this is not a problem taken in combination with food. If a teenager does start to
• Avoidance of special infant formulas or preterm formu- vomit, they must be admitted promptly to hospital for IV
las, which contain added MCT, e.g. Pregestimil Lipil and fluids and glucose. Friends should be made aware that the
individual has MCADD, so they know to get medical help
promptly enabling more rapid treatment.
Table 30.1 Medium chain acyl‐CoA dehydrogenase (MCAD) deficiency:
guidelines for ‘maximum safe fasting times’ for the well child.
Coconut
Age Time in hours
Coconut oil contains 13% and coconut 5% of the total fatty
Positive screening result to 4 months of age* 6 acid composition as C8 and C10. This amount of MCT is
From 4 months 8 small and unlikely to cause any problems. If coconut oil
From 8 months 10 were to be consumed in large amounts, suitability should be
considered. Coconut based foods (e.g. coconut flakes,
From 12 months onwards 12
chunks, yoghurt, water, spreads) or foods with coconut as an
*Around 2 weeks of age. added ingredient do not need to be avoided as these will
Source: www.bimdg.org. contain only small amounts of MCT.
Long Chain Fatty Acid Oxidation Disorders (LC‐FAOD) 643
Carnitine • Avoidance of fat during the acute period (although

there is little evidence to support if this is absolutely
Carnitine is found mainly in muscle (98% of total body
essential)
carnitine) and in blood (<1%). Blood carnitine reflects
• Monitoring of blood glucose at home is not recom-
only a small percentage of total body carnitine. Some chil-
mended because precision is poor at low concentrations
dren with MCADD may sometimes have a decreased
and hypoglycaemia is a relatively late finding during
amount of free carnitine in their blood. There is no strong
illness; the child can be very unwell before the blood
evidence to prove that carnitine supplements improve the
glucose falls [11]
general condition, and it is, therefore, not routinely pre-
• If for any reason the child needs to be commenced on a
scribed in the UK.
special infant formula or paediatric enteral feed during
illness, it should not contain added MCT
Dietary guidelines for managing the unwell child
with MCADD Learning points: medium chain acyl‐CoA dehydrogenase
deficiency (MCADD)
Illness in any child is usually associated with loss of a ppetite
and prolonged fasting, and fatty acid oxidation rates • The standard ER is given during illness
increase to provide energy. In MCADD this process is • Long fasts need to be avoided
limited, and the child is at risk of serious illness and enceph- • Feeds with added MCT are contraindicated
alopathy. Sudden death has been reported in screened
patients specifically associated with vomiting [9]. To
help prevent metabolic decompensation, the standard
ER needs to be given. The ER will provide energy, stimulate
insulin secretion and thereby minimise lipolysis and fatty Long chain fatty acid oxidation disorders
acid oxidation. ER guidelines (IV and oral) for hospital use (LC‐FAOD)
can be accessed from www.bimdg.org.uk. A Canadian
study reported that children with MCADD have increased LC‐FAOD include:
use of health services (in‐ and outpatient care) compared • disorders of the carnitine cycle: carnitine palmitoyl trans-
with children in the general population, although this ferase deficiency I and II (CPTID and CPTIID) and
diminishes beyond 24 months [10]. carnitine acylcarnitine translocase deficiency (CACTD)
(Figure 30.1)
ER information specific for MCADD: • disorders of the mitochondrial β‐oxidation pathway:
very long chain acyl‐CoA dehydrogenase deficiency
• Follow the standard ER guidelines for age of very (VLCADD), mitochondrial trifunctional protein deficiency
frequent feeds/drinks of glucose polymer solution, day (MTPD) and long chain 3‐hydroxy acyl‐CoA dehydroge-
and night (p. 673) nase deficiency (LCHADD) (Figure 30.1)
Enzymes Carnitine palmitoyl transferases I and II

Carnitine acylcarnitine translocase (CACT)
Very long chain acyl‐CoA dehydrogenase
Mitochondrial trifunctional protein complex (encompasses the three MTP enzymes)
Long chain 3‐hydroxy acyl‐CoA dehydrogenase (enzyme within the MTP complex)
Biochemical defects The enzymes of the carnitine cycle are required to transport LCFA into the mitochondria, and the enzymes of the four‐step
spiral pathway of mitochondrial β‐oxidation to breakdown LCFA to produce energy (Figure 30.1). Oxidation of fatty acids
produces acetyl‐CoA that enters the Krebs cycle to produce ATP or is converted into ketone bodies (in the liver). Enzyme
deficiencies lead to inadequate energy and ketone body production, toxic intermediates (such as long chain acylcarnitines)
accumulate; these are all considered responsible for the clinical features.
Genetics All are autosomal recessive inherited disorders. The clinical spectrum is very heterogeneous. Prevalent mutations have been
identified in some, e.g. in LCHADD most Caucasian patients are homozygous for the c.1528G > C mutation. Three different
isoforms of CPTI exist, CPTIa (liver and kidney) only identified in man, CPTIb (muscle and heart). Paradoxically, cardiac
problems or raised creatine kinase (CK) are seen in some CPTIa patients [12]. CPTIa is very common in the Inuit population
[12]. Three phenotypes of CPT II deficiency are known: a lethal neonatal form, a severe infantile hepatocardiomuscular form
and a mild myopathic form. Muscle CPT II deficiency is the most frequent type of CPT II deficiency [13].
Newborn screening LC‐FAOD are not screened for in the UK but are included in NBS panels elsewhere worldwide.
Clinical onset LC‐FAOD vary in severity and may present at any time from the neonatal period, during infancy, childhood to adulthood
presentation, features with associated mortality and possible morbidity. Attenuated forms are seen in CPTII and VLCAD deficiencies. The organs
affected are the heart, liver and skeletal muscles. The clinical presentation for all disorders commonly includes one or all
of these problems [12, 14, 15]:
• an acute ‘hypoketotic’ hypoglycaemia and encephalopathy with associated liver failure, hyperammonaemia and
hyperlactacidaemia
• cardiomyopathy and arrhythmias (often in infancy)
• skeletal muscle involvement that may cause hypotonia, weakness, muscle pain and exercise intolerance with acute
episodes of muscle breakdown (rhabdomyolysis) and high CK; in CPTID and CACTD rhabdomyolysis does not occur
• muscle CPT II deficiency is the most frequent type of CPT II deficiency; it more commonly presents in early childhood
(1–12 years) than adolescence and adulthood; symptoms of myalgia, myoglobinuria and muscle weakness occur
intermittently and are triggered mainly be exercise or intercurrent illness [12]
• rhabdomyolysis can be the only clinical symptom in patients with mild VLCADD
• some patients with CPTI have renal tubular acidosis during infancy
Outcome Most patients with LCHADD or MTPD develop pigmentary retinopathy and/or a progressive peripheral neuropathy (more of
a problem in MTPD). Patients with LCHADD have a more severe chorioretinopathy than MTPD [16]. Diet may help delay
the onset and progression, but not prevent retinopathy [16]. Retinopathy is also reported to be milder and develop later in
those diagnosed by NBS [17]. Early diagnosis and diet therapy may also delay onset and severity of peripheral neuropathy
[18]. Outcome data from a cohort of 14 Austrian patients with LCHADD (9 confirmed by NBS), all with common mutation,
reports normal growth and psychomotor development in 12 patients (except for 2 born premature) and less frequent
hospitalisations with age [19]. Children may develop muscle pain with exercise, and some have a very limited exercise
capacity. Patients with partial deficiencies of VLCADD often remain asymptomatic throughout childhood and sometimes
throughout life. Longitudinal outcome data on VLCADD from the IBEM‐IS USA database reported that most newborns
identified by NBS remain asymptomatic and cardiomyopathy is uncommon. Elevations in CK as a marker of rhabdomyolysis
associated with illness were common and typically first appeared in 1‐ to 3‐year‐olds [20]. CPTII neonatal form is lethal.
Acute management Clinically diagnosed infants may be very sick and be managed in intensive care. IV 10% glucose is essential to reverse
lipolysis and promote anabolism.
Dietetic management Treatment is primarily by diet and varies depending upon the severity of the disorders and the centre treating the child.
Nevertheless, the main aim is to minimise lipolysis and LCFA oxidation and to prevent the accumulation of potentially
toxic acyl‐CoA intermediates and the acylcarnitines formed from these. The abnormal metabolites that accumulate are
disorder specific and present in higher concentrations during times of metabolic stress such as illness. Abnormal plasma
acylcarnitines are not seen in CPTID [12].
Avoidance of long fasts and illness and exercise management are needed in those with mild and severe onset defects. For
CPTIID the treatment recommendations for VLCADD (mild to severe) can be used [21]. In more severe defects in the
carnitine cycle and β‐oxidation pathway, typically those presenting early, a minimal long chain fat diet, with increased
CHO intake and supplements of MCT and regular feeding, is needed. Overnight tube feeding in infants and young
children is used in the UK and some other countries, such as Finland [18], to limit fatty acid oxidation overnight, but this is
not universal practice. In CPTI deficiency relaxation of a strict diet may be possible if there are normal CK and liver
transaminase levels (personal communication). During exercise additional CHO and/or MCT is required to provide an
endogenous energy supply to exercising muscles.
Emergency regimen During illness patients are at risk of metabolic decompensation due to increased lipolysis and fatty acid oxidation. To help prevent
this the standard ER (p. 673) for age of frequent feeds of glucose polymer with or without MCT is given to provide energy.
Monitoring Key monitoring is biochemical, nutritional and cardiac, additionally in LCHADD and MTPD nerve conduction studies and
ophthalmology.
Clinical management Treatment recommendations in long chain fatty acid oxidation defects: Consensus from a workshop, 2009 [21].
guidelines VLCAD Nutrition management guidelines: Genetics Metabolic Dietitians International, 2019 (access at www.gmdi.org),
based on a Delphi consensus.
There are no clinical management guidelines for disorders of the carnitine cycle.
Dietary management of LC‐FAOD The Treatment recommendations in long chain fatty acid oxida-
tion defects: consensus from a workshop by Spiekerkoetter et al.
Long chain triglycerides [21] advises:
Long chain fat intake is restricted because LCFA cannot • LCHADD and MTPD: Asymptomatic and symptomatic
be either transported into the mitochondria or undergo patients should limit long chain fat intake as low as pos-
β‐oxidation, depending on the enzyme defect. The safe sible. There is evidence that diet may delay onset and pro-
upper limit for long chain fat intake is unknown and varies gression of peripheral neuropathy and retinopathy
with the severity of the disorder. Normalisation of acylcarni- [15–19]. Infants should be started on a low LCT, high
tine profiles is observed in LCHADD and MTPD when LCT MCT infant formula. Once on solid food, fat intake should
intake is <10% total energy and MCT are given [22]. In those be 25%–30% of total energy with 20%–25% of this as MCT,
with a milder myopathic form of VLCADD or CPTIID, LCT although in practice more typically 15% is LCT, including
restriction may not be necessary. 3%–4% essential fatty acids (EFA), and 15% is MCT
For infants with VLCADD at NBS: β‐oxidation disorders

• MCT have led to the resolution of cardiomyopathy in
• VLCADD: Asymptomatic infant’s treatment depends on
patients with VLCAD and LCHAD deficiencies [25, 26].
the clinical presentation and biochemistry: if normal CK
• MCFA may also suppress LCFA oxidation without being
and liver transaminases, a combination of half breast-
converted to ketone bodies; they have been shown to
milk (or standard infant formula) and half low LCT
inhibit the accumulation of potentially toxic long chain
infant formula can be given. Some asymptomatic new-
intermediates in cultured skin fibroblasts from LCHAD
borns, whose acylcarnitines normalised after 1 week,
and MTP deficient patients [27].
have remained on normal feeds without VLCADD
• The optimal amount or ratio of C8 and C10 fatty acids to
symptoms so far. After age 4 months and solid food
provide is not known. Skin fibroblast studies have shown
introduction, fat energy should be 30%–40% of total
that C10 undergoes elongation prior to oxidation, so it
energy of which 10%–15% is MCT
has been suggested that C8 may be preferable [28, 29].
• VLCADD: Symptomatic infants or those with abnormal CK
• The Treatment recommendations in long chain fatty acid oxi-
or transaminases should be started on a low LCT, high
dation defects: consensus from a workshop by Spiekerkoetter
MCT infant formula. After age 4 months and solid food
et al. [21] suggest 20%–25% total daily energy intake be
introduction, fat energy should be 25%–40% of total energy
provided from MCT for severe LCHADD, MTPD and
of which 20% is MCT and 3%–4% is EFA; therefore, LCT
VLCADD.
could range from 5% to 20% of total daily energy intake
• Genetic Metabolic Dietitians International (GMDI):
Genetic Metabolic Dietitians International (GMDI): VLCAD VLCAD Nutrition management guidelines (www.gmdi.org)
Nutrition management guidelines (www.gmdi.org) advise: recommendation is total fat intake (LCT and MCT) should
not exceed the dietary reference intake (DRI) for age. The
• VLCADD: restriction of LCT intake in moderate form to
amount of MCT to give will, therefore, depend on pre-
be 15%–30% and in severe form to be 10%–15% of esti-
scribed LCT intake. In severe VLCADD they suggest
mated total daily energy needs and that decreasing
daily energy intake from MCT to be 30%–45% energy for
below 10% may provide no additional clinical benefit
infants aged 0–6 months; 25%–30% for 7–12 months;
For infants with VLCADD at NBS: 10%–30% for 1–3 years and 15%–25% for 4–18 years.
• mild phenotype and asymptomatic: to allow breastfeeding
without MCT supplements Carnitine cycle disorders
• severe or moderate phenotype and asymptomatic: to consider The role of MCT is slightly less clear in defects of the carni-
a combination of breastfeeds with a low LCT, high MCT tine cycle:
infant formula • In several infants with CPTI deficiency, renal tubular
• severe phenotype and symptomatic: the primary source of acidosis has only resolved when they have been changed
nutrition should be a low LCT high MCT feed, consider- to an MCT‐based feed [30].
ing allowing some breastmilk • MCT has also been used with apparent benefit in patients
A Proposal for an individualized dietary strategy in patients with mild CACTD. However, in cases of severe CACTD
with VLCADD by Bleeker et al. [23] suggests choice of dietary and CPTIID, MCT has been reported to have caused
treatment for those identified by NBS be based on results of markedly abnormal blood acylcarnitines and dicarboxylic
fatty acid oxidation (FAO) flux score in fibroblasts: aciduria and suggests that MCT may need to be limited
and dose adjusted because it may in part enter the mito-
• if >90%, no diet or ER chondria by a carnitine‐dependent mechanism [31, 32].
• if 10%–90%, mild diet (no fat restriction or MCT supple- • It has also been suggested that MCT should be low in
ments), ER during illness C10 due to evidence that C10 requires CACT for oxida-
• if 10% strict diet (LCT restricted, MCT supplements, tion [31]. The C8 and C10 contents of available products
restricted fasting), ER during illness vary, but the amount of C10 is always lower than C8
(Table 30.6).
Medium chain triglycerides • In the author’s centre and others (personal communica-
Dietary MCT are mainly absorbed through the hepatic portions), MCT has been added to the diet in a similar way
tal vein; they pass directly into the mitochondria primarily to the long chain β‐oxidation disorders with both severe
independent of the carnitine cycle. They are then rapidly and mild onset, using currently available MCT infant
converted to ketone bodies, bypassing the long chain formula and energy supplements.
β‐oxidation enzymes. Ketones inhibit the mobilisation of
fatty acids from adipose tissue and the oxidation of fatty
Triheptanoin
acids by cardiac muscle [24]. MCT (C8, C10) is a useful
energy source, 8.3 kcal (35 kJ)/g, and may also have other Triheptanoin is a synthetic, odd‐carbon, medium chain tri-
beneficial effects in some disorders, as discussed below. glyceride oil (C7, heptanoate), which is being trialled as an
MCT supplements need to be added to the diet, as the normal alternative energy source to MCT. The use of MCT leads to
diet contains insignificant amounts. the production of acetyl‐CoA, but it is hypothesised that a
shortage of oxaloacetate prevents this from being oxidised in lycogen stores. However, in LCHADD this may be
g
the citric acid cycle. Heptanoyl‐CoA is oxidised by medium more important to delay retinopathy and peripheral
chain fatty acid enzymes to generate acetyl‐CoA and propi- neuropathy [17, 18].
onyl‐CoA as well as 4‐ and 5‐carbon ketone bodies. • Uncooked cornstarch (UCCS) is used by some centres,
Propionyl‐CoA is converted to oxaloacetate, which acts as an including the author’s, to provide a source of ‘slow
‘anaplerotic’ substrate for the citric acid cycle and may help release glucose’ to help limit fasting [35]. In older chil-
to restore the energy deficiency state, so triheptanoin appears dren continuous tube feeding overnight may be replaced
to be superior to MCT [33]. Clinical trials are under way to with UCCS (personal practice). This may be a better
study the efficacy of C7. Results from an open‐label phase 2 option than stopping overnight feeds completely. Before
study in 29 patients with severe LC‐FAOD suggest that there use, the metabolic response to UCCS should be assessed
appear to be some benefits: decreased major clinical events since this varies between patients [35]. The GMDI
and reduced hospitalisations due to rhabdomyolysis com- VLCAD Nutrition management guidelines (www.gmdi.org)
pared to existing treatments including MCT [33]. Triheptanoin suggest that there is little evidence to support the use of
is not yet widely available outside the USA. UCCS at night and advise a complex CHO snack at bed-
time, if necessary.
• There are no published studies comparing the metabolic
Frequency of feeding profiles of patients with LC‐FAOD on overnight feeds or
on UCCS and those who fast overnight or comparing the
Frequent feeding is recommended to reduce lipolysis. The
long‐term outcome of these different treatments.
safe duration of fasting for different disorders and ages has
• Patients with milder defects are likely to tolerate over-
not been well defined, and practices, including the need for
night feeds, differ between countries and centres. A stable night fasting without problems.
isotope study used to assess fasting intolerance in LCHADD
(five children aged 5.5–9.5 years) demonstrated increased
Prevention of deficiencies on a low LCT diet
lipolysis and accumulation of long chain acylcarnitines after
4 hours of fasting, which occurred before hypoglycaemia. Patients on minimal LCT diets require supplements of fat‐
The authors suggest fasting tolerance may be more limited soluble vitamins, EFA and long chain polyunsaturated fatty
than previously suggested and fasting assessment should be acids (LCPUFA). Additional supplements such as B12 and
related to the complete metabolic situation and not only iron may be needed depending on food choices. An adequate
hypoglycaemia [34]: calcium intake is usually provided from low fat dairy foods.
• The treatment recommendations in long chain fatty acid oxi-
EFA and LCPUFA
dation defects: consensus from a workshop [21] suggest in
In the UK at least 1% total energy intake from linoleic acid
VLCADD, MTPD and LCHADD during stable metabolic
and 0.2% from α‐linolenic acid are recommended [36]. Others
condition to feed 4 hourly during the day and a maxi-
recommend a much higher intake of 4.5% daily energy
mum safe fasting time at night of 4 hours for <3 months
intake in infants <4 months of age, decreasing to 3% from
of age if the infant is well nourished, then 6 hours from
age 4 years [21]. The joint FAO/WHO 2008 report on fatty
3 months of age, 6–8 hours from 6 months of age and
acids recommends an adequate daily intake for children
10–12 hours from 12 months.
>6 months to be linoleic acid 3%–4% and α‐linolenic 0.4%–
• The GMDI VLCAD Nutrition management guidelines
0.6% of daily energy intake [37].
(www.gmdi.org) suggest maximum fasting times to be
Most sources of EFA (such as walnut oil) do not provide
3–4 hours for age 0–4 months, 4–6 hours for age 4–6
LCPUFA, such as arachidonic acid (AA) and docosahexae-
months, 6–8 hours for age 6–9 months, 8–10 hours for age
noic acids (DHA), but these are expected to be synthesised
9 to <12 months of age and 10–12 hours for >12 months.
from the parent EFA that are provided. However, it may be
Fasting times for more severe phenotypes should be set
prudent to add DHA and AA supplements on very low LCT
at the lower end of the recommended range.
diets to ensure adequate intake, avoiding the need to increase
• In the UK, fasting is more limited in severe defects to
walnut oil and, hence, LCT intake. It has also been suggested
help reduce the risk of cardiomyopathy and in LCHADD
that DHA deficiency may contribute to the pathogenesis of
and MTPD the onset and progression of long‐term com-
chorioretinopathy of LCHADD, although this is not pre-
plications of retinopathy and neuropathy (although there
vented by supplementation [38]. Nevertheless supplements
is little evidence for this). Children with severe defects
of DHA at a dose of 60 mg/day in children <20 kg and
are fed 3–4 hourly during the day, and nasogastric (only
120 mg/day in children >20 kg are recommended in MTPD
bolus) or continuous gastrostomy feeding overnight, or
and LCHADD [21]. FAO/WHO [37] recommends an ade-
the child is woken for feeds during the night. Overnight
quate daily intake of DHA for normal children to be:
feeding is not standard practice; the literature suggests
that some countries do this [17], but others consider • the amounts found in breastmilk for infants
management should be achievable without this [19]. It is • 100–150 mg for children aged 2–4 years
difficult to be sure whether overnight feeding is neces- • 150–200 mg for children aged 4–6 years
sary, particularly in older children who have larger • 200–300 mg for children aged 6–10 years
Fat‐soluble vitamin supplements required. Whey protein powder does contain small amounts
Vitamins A, D and E are essential for those on low LCT diet. of LCT but can be used as the protein base with glucose pol-
Vitamin E deficiency is associated with a peripheral neurop- ymer and added minerals and vitamins, EFA and LCPUFA
athy, which is one of the long‐term complications of MTPD to provide recommended intakes (p. 646). Suitable commer-
and LCHADD and should, therefore, be provided in normal cial minimal fat feeds with no added MCT are Low Fat
requirements for age, at least. Module (0.14 g fat/100 mL) and basic‐f (<0.1 g fat/100 mL)
(Table 30.2).
Clinically diagnosed infants are likely to be very sick,
Carnitine managed in intensive care and receiving IV 10% glucose and
It remains uncertain whether carnitine supplements should electrolytes. Once clinically stabilised, nasogastric feeds
be given to patients with LCFA oxidation disorders. Plasma‐ should be introduced and titrated against IV fluids to main-
free carnitine concentrations are often below the normal tain adequate energy intake and prevent further metabolic
range, particularly after episodes of illness, but tissue levels decompensation. The feed should be distributed evenly over
are probably not low enough to affect fatty acid oxidation. 24 hours to limit fasting and provide energy from both CHO
Supplements may facilitate the excretion of metabolites, but, and MCT regularly, e.g. for an infant weighing 6 kg feeding
by increasing the level of long chain acylcarnitines, it is pos- 150 mL/kg/day (900 mL):
sible that they may increase the risk of arrhythmias [39]. • 120 mL 3 hourly × 5 feeds during the day (at 8 am, 11 am,
2 pm, 5 pm, 8 pm)
• 300 mL given at 40 mL/hour continuously overnight for
Energy distribution of the diet in severe defects 8 hours from 10 pm to 6 am (the night feed can be com-
As LCT is restricted, more energy needs to be provided from menced 2 hours after the last day feed and discontinued
CHO and supplements of MCT. The optimal distribution of up to 2 hours before the morning feed)
energy intake from CHO and MCT is not known. The fol-
lowing provides a guide to the typical energy distribution Weaning diet
and long chain fat intake of the diet in severe defects (based Weaning is commenced at the normal time around 6 months
on personal practice): (26 weeks) of age. Feeding problems have been reported in
• 60%–65% energy from CHO (CHO energy will vary children with LCHADD, particularly in early childhood,
depending on LCT and MCT intake) despite good metabolic and clinical condition [40]. With age
• 10%–15% energy from protein these problems either improved or resolved in this cohort.
• 20%–25% energy from medium chain fat (depending on An example of a suggested menu plan for infants is pro-
the disorder) vided in Table 30.3. Solids should have a minimal fat content
• 1.2%–2% energy from EFA (based on FAO/WHO [37]; and be high in CHO. Rice, cereal, potato, fruit and vegetables
higher intakes may be appropriate) are suitable as first weaning foods. Low fat, high protein
foods can also be given, e.g. chicken or turkey breast, white
LCT is often expressed as g/day. fish, lentils, very low fat cottage cheese and yoghurt.
Infants 0–6 months: 2–7 g LCT/day (4%–7% of daily energy Commercial baby foods can be included in the diet: wet baby
intake) if either Monogen or Lipistart (Table 30.2) provides foods (fat content <0.5 g/100 g) and dried baby foods (fat
the sole source of nutrition. LCT intake will increase with the content <2 g/100 g) can be given freely. Baby foods with a
introduction of solid food. higher fat content need to be counted as part of the daily fat
Older infants and children: It is possible to continue to intake. Parents can be taught how to calculate the amount of
restrict intake of long chain fat to provide ≤6% total energy fat a food provides from the nutritional labelling (p. 649). As
intake, ≤7 g LCT/1000 kcal (4.2 MJ), excluding EFA. Similar solid food increases, it can replace some of the 3 hourly day
dietary practices are reported to be used by others [39]. This feeds, ensuring it provides at least the same amount of
is a very strict diet and not all agree this is warranted. energy as the feed. MCT oil/emulsion/ powder (p. 651) is
incorporated gradually into the diet to maintain MCT at
20%–25% of daily energy intake. As weaning progresses, the
Minimal long chain fat diet
volume of infant formula should be decreased, and glucose
polymer ± MCT added to provide the required amount of
Infants
energy. Eventually the night feed can contain glucose poly-
Infants with severe long chain defects (diagnosed clinically mer and MCT only.
or by NBS, not in the UK) need a minimal LCT feed supple- Monogen or Lipistart, as the sole source of nutrition, pro-
mented with MCT such as Monogen or Lipistart; both are vides more than the UK suggested requirement for EFA. As
nutritionally complete infant formulas with minimal LCT infant formula decreases, an additional source of EFA is
content (Table 30.2). needed. Walnut oil provides a good source of EFA and allows
As previously discussed it is possible MCT cannot be fully minimum LCT to be given (Table 30.4). The dose of oil to
oxidised in some severe CACTD or CPTIID [31, 32], and a give should be calculated taking into account the EFA
modular feed without fat (long or medium chain) may be from the infant formula. To provide the UK suggested
Table 30.2 Low LCT infant formulas per 100 mL.
Monogen (Nutricia) Lipistart (Vitaflo) basic‐f (Milupa)* Low Fat Module (Nutricia)
Dilution 17.5% 15% 13% 18%

Scoop size 5 g 5 g 4.3 g 6 g
Energy kcal 74.6 (314 kJ) 69 (290 kJ) 49 (207 kJ) 67.3 (286 kJ)
Protein g 2.2 (12% E) 2.1 (12% E) 1.8 1.6
Carbohydrate g 11.6 (62% E) 8.3 (48% E) 10.2 14.9
Fat g 2.2 (26% E) 3.1 (40% E) <0.1 0.14
MCT g 1.8 2.48 Nil Nil
% fat E 84% 80%
% total E 16% 30%
C8 g 1.0 1.5
C10 g 0.67 0.93
LCT g 0.35 0.57
% fat E 16% 18%
% total E 4% 7.4%
Linoleic acid mg 151 259 Nil Nil
%E 1.9% 3.4%
α‐Linolenic acid mg 28.6 36 Nil Nil
% total E 0.35% 0.5%
DHA mg 10.1 15 Nil Nil
AA mg 10.1 30 Nil Nil
Vitamins
E mg 0.82 1.7 0.3 0.4
A mg 54.6 69.9 52 71.3
D mg 2 1.4 0.9 1.2
E, energy; MCT, medium chain triglycerides; LCT, long chain triglyceride; DHA, docosahexaenoic acid; AA, arachidonic acid.
• Reconstitution: Monogen 1 scoop added to 25 mL water.
• Reconstitution: Lipistart 1 scoop added to 30 mL water.
• In UK only Monogen and Lipistart are prescribable.
*Not available in the UK.
Source: Manufacturers.
Table 30.3 Minimal long chain fat weaning diet. Sample menu.
8 am breakfast *Commercial baby cereal mixed with Lipistart or Monogen

11 am Lipistart or Monogen
1 pm lunch Purée turkey, chicken (white only), white fish or lentils
Purée or mashed potato, sweet potato
Pasta, rice
Purée or mashed vegetables
*Commercial baby savoury foods
4 pm tea Purée or mashed fruit and sugar or *commercial baby fruit dessert
Very low fat yoghurt or fromage frais
Milk pudding (custard, cornflour, ground rice) made with infant feed or skimmed milk
7 pm Lipistart or Monogen
9 pm to 6 am Continuous overnight feed for a 7 kg infant (270 mL):
Monogen: 30 mL/hour provides 0.5 g CHO/kg/hour (197 kcal, 825 kJ)
Lipistart: 30 mL/hour provides 0.36 g CHO/kg/hour (186 kcal, 782 kJ) but provides more energy from MCT than Monogen
Extra feeds or baby juice can be given with meals
Finger foods may be introduced from 6 to 9 months: soft cooked vegetables, soft ripe fruit (pasta, bread and cereals may also be suitable, but LCT
content must be checked first)
*Suitable commercial baby foods (p. 647). Baby foods with a higher fat content are best avoided.
Table 30.4 Walnut oil. Essential fatty acid composition. include in the diet and given as a reasonable portion. Parents
can be taught to calculate and then weigh the amount of
1 mL walnut oil provides food that provides a certain amount of fat. This also makes it
Energy 8.4 kcal easier to monitor the daily fat intake, for example:
35 kJ
Weight of food to provide 1 g fat
Fat 0.93 g
100
Linoleic acid 0.58 g
fat content per 100 g of food
α‐Linolenic acid 0.12 g
Ratio n6:n3 fatty acids 4.5 Medium chain triglycerides
A daily intake of 20%–25% of total energy intake is advised.
For analysis of other oils, see Fatty acids, 7th Supplement to McCance
The optimal timing of administration has not been defined;
and Widdowson’s The Composition of Foods, 5th edn. Cambridge: Royal
Society of Chemistry and London: Ministry of Agriculture, Fisheries and however, it is common practice to divide the dose and give
Food, 1992. three to four times a day, as it is rapidly absorbed and used
and high doses may cause GI symptoms in some patients. In
young children MCT often remains part of the night feed.
requirement of EFA, the dose of walnut oil needed is MCT can be added to the diet as an oil, emulsion or powder
0.1 mL/56 kcal (235 kJ). The walnut oil is administered as a (Table 30.6). MCT oil can increase the palatability of the diet.
single dose and given as a medicine from a spoon or via the It has a low smoke point compared with other cooking oils.
feeding tube. Other oils such as sunflower, safflower (mainly Care must be taken when cooking foods in MCT oil to ensure
linoleic acid), soya and flax are also rich sources of EFA, and it does not burn or become overheated as it develops a bitter
a combination of these can also be used if walnut oil is dis- taste and an unpleasant odour. The optimum cooking tem-
liked. Monogen (600 mL) and Lipistart (400 mL) provide the perature for MCT is 160 °C. MCT oil can also be used in bak-
suggested intake of 60 mg DHA/day advised for LCHADD ing, e.g. cakes, biscuits and pastry, and can be added to a
[21]. An alternative source of LCPUFA (such as KeyOmega) variety of foods such as pasta and soups. MCT emulsion, e.g.
can be given as less or no infant formula is given. Liquigen, can be easily mixed into food and liquids without
Fat‐soluble vitamin supplements are likely to be required separating such as skimmed milk, low fat yoghurt, desserts
once the intake of low LCT infant formula falls below and sauces, and used in baking. MCT Procal powder comes
500 mL/day (Table 30.2). in pre‐measured sachets and can be added to hot or cold
food or drinks (not fruit juice as it curdles) and used in bak-
Children ing recipes. Recipes are available for all products from their
manufacturers. Table 30.7 gives an example of how to
Long chain triglycerides provide the daily intake of MCT.
Children need a minimal LCT diet with an energy distribu-
tion as previously outlined (p. 647). Inevitably, daily intake Other nutrients
of long chain fat increases with age. The figures quoted are EFA can be added as walnut oil or combinations of other oils
based on the lowest possible long chain fat intake that is as described for infants. LCPUFA can be given as KeyOmega
practicably achievable for a given age. However, as the safe (1 sachet = 100 mg DHA, 200 mg AA) and DocOmega
upper limit for long chain fat is not known, such a low LCT (1 sachet = 200 mg DHA) as needed to provide the daily
intake may not be of clinical benefit and, therefore, unneces- requirements [37].
sary (p. 644). Ideally, the diet should be a combination of The choice of fat‐soluble vitamin supplement will depend
starchy foods (e.g. rice, pasta, potato, bread, cereals) and on need, age and desired format: powder, tablets or soluble
very low fat sources of protein, such as white fish, white tablets are available. Ketovite tablets and liquid provide an
chicken or turkey meat and pulses (Table 30.5). To enable adequate intake of fat‐soluble vitamins and B12 and are suit-
suitable low fat food choices, parents need guidance on able for all ages. Alternatively, more complete vitamin and
interpreting food labels, in particular to understand words mineral supplementation can be provided: FruitiVits (from
used to describe the fat content of food, which can be mis- age 3 years), Paediatric Seravit (all ages), Phlexy‐Vits sachets
leading (reduced fat, low fat, virtually fat‐free, 90% fat‐free), or tablets (from age 10 years), Forceval Soluble Junior (from
and that different types of fat (monounsaturated and poly- age 6 years) and Forceval Soluble (from age 12 years) (p. 524).
unsaturated) are all long chain fat and total fat content Intakes of iron, zinc and B12 should be regularly calculated as
should be used to calculate fat intake. these can also be low in minimal LCT diets.
Nutritional labelling expresses the total fat content as
grams of fat per 100 g and often grams of fat per portion. Frequency of feeding
Manufactured foods that have a fat content <0.5 g/100 g can Lipolysis can be minimised by 3–4 hourly feeding during the
generally be allowed in the diet freely, unless large amounts day and continuous overnight tube feeds. If feeding over-
are being consumed. Those with a higher fat will need to be night, the amount of energy required is not known. One
counted as part of the daily fat allowance. Foods with a fat approach to minimise overfeeding is to provide glucose
content of up to 5 g fat/100 g are more likely to be suitable to polymer to equal basal glucose production rates for age
Table 30.5 Minimal long chain fat diet.
Milk Skimmed milk, condensed skimmed milk Full fat and semi‐skimmed milk
Natural yoghurt, very low fat yoghurt and fromage frais (<0.2 g/100 g) Cream (all types)
Low fat cottage cheese (<0.5 g/100 g) Full fat yoghurt and fromage frais
*Very low fat cheeses Full and half fat cheeses
Quark (skimmed milk soft cheese) †
Ice cream
Low fat ice cream
Egg Egg whites, egg white replacer, meringue Egg yolks
Fish White fish (no skin), e.g. haddock, cod, sole, plaice Oily fish, e.g. sardines, kippers, salmon, mackerel
Crab, crabsticks, tuna, prawns, shrimps, lobster Fish in breadcrumbs, batter, sauces, pastry
Tinned: tuna in brine or water, crab, prawns, shrimps Tinned: fish in oil
Poultry *Chicken, *turkey (white breast meat, no skin) Chicken, turkey (dark meat and skin), basted poultry,
duck, goose
Chicken in breadcrumbs, batter, sauces, pastry
Meat *Lean red meat (<5% fat content) Fatty meat, sausages (normal and low fat), burgers, meat
paste, paté, salami, pies
Meat substitutes Soya mince, *Quorn, *tofu
Pulses Peas, e.g. chick peas, split peas None, unless in made‐up dishes containing fat
Beans, e.g. red, white, borlotti, black‐eyed
Fats/oils Medium chain triglyceride oil as advised Butter, margarine, low fat spread, vegetable oils, lard,
dripping, suet, shortening
Pasta and rice Spaghetti, macaroni, other pasta, noodles, couscous, rice (white) Wholemeal pasta, pasta in dishes, e.g. macaroni
cheese, carbonara
Brown rice, egg noodles
Flours and Flour (white), cornflour, custard powder, semolina, sago, tapioca Flour (wholemeal), soya flour, oats, bran
cereals Foods made with flour that contain fat, e.g. pastry,
sauces, cake, biscuits, batter, breadcrumb coatings
Breakfast cereals Many are suitable Cereals with nuts and chocolate, e.g. muesli
Wholewheat cereals, e.g. Weetabix, Bran flakes, are higher in fat All‐bran, Ready Brek
content than non‐wholewheat cereals, e.g. Rice Krispies, cornflakes
Bread and *White bread, white pitta, crumpets, muffins. Some crackers have a Wholemeal, wholegrain breads, naan bread, chapatti made
crackers low fat content, e.g. rice cakes, matzos, Ryvita (not sesame) with fat, croissants, oatcakes, cheese crackers, †crackers
Cakes, biscuits Only those made from low fat ingredients †
Cakes, †biscuits, buns, pastry for sweet and savoury
and pastry 95% fat‐free cakes and biscuits foods, e.g. apple pie, quiche
Desserts Jelly, meringue, sorbet, very low fat ice cream, skimmed milk Most desserts, e.g. whole milk puddings, trifle,
puddings, e.g. rice, custard cheesecakes, gateaux, †mousse, fruit pie or crumble
Fruit Most varieties – fresh, frozen, tinned, dried Avocado pears, olives, yoghurt/chocolate covered dried
fruit, banana chips
Vegetables All vegetables and salad Chips, †crisps, †low fat crisps, roast potato, potato or
Very low fat crisps vegetable salad in mayonnaise or salad dressing, †coleslaw
Herbs and spices Pickles, chutney
Herbs, spices, salt, pepper
Nuts and seeds Nuts, peanut butter, seeds, e.g. sesame, sunflower
Sauces and Tomato ketchup, brown sauce, soy sauce, Marmite, Oxo, Bovril, †
Gravy granules, †stock cubes
gravies very low fat gravy mixes Salad cream, mayonnaise, oil and vinegar dressings
Fat‐free dressings and mayonnaise †
Sauce mixes (jars, tins, packets)
Minimal fat sauces (jars, tins, packets)
Soups Some low calorie and ‘healthy eating type’ soups are very low fat Most soups, cream soups
Confectionery Boiled sweets, jelly sweets, fruit gums, pastilles, marshmallow, Chocolate, chocolate‐covered sweets, toffee, fudge,
mints, ice lollies butter mints
Sugars and Sugar, golden syrup, jam, marmalade, honey, treacle Lemon curd, chocolate spread
preserves
Baking products Baking powder, bicarbonate of soda, yeast, arrowroot, essences,
food colouring
Drinks Fruit juice, squash, fizzy drinks, milkshake flavourings, tea, coffee †
Instant chocolate drinks, cocoa, malted milk type
drinks, e.g. Horlicks
*Intake of these foods may need to be restricted because of their fat content.
†
These foods in the ‘avoid list’ often have very low fat equivalents, which can be included in the diet.
Table 30.6 Medium chain triglyceride products.
MCT g/100 g fatty acids
Product Energy kcal (kJ) MCT C8 C10 C12 Other nutrients
MCT oil (Nutricia) 855 (3.6 MJ)/100 mL 94 g/100 mL 58 38 1.7 Nil

Liquigen emulsion (Nutricia) 450 (1.9 MJ)/100 mL 50 g/100 mL 82.1 15.9 1.3 Nil
MCT Procal powder (Vitaflo) 657 (2.7 MJ)/100 g 62.2 g/100 g 54 39 – Per sachet: 2 g
105 (440 kJ)/16 g sachet 10 g/16 g sachet protein, 3.3 g CHO
MCT, medium chain triglyceride.

Other MCT products such as MCT margarine can be sourced from www.ceres‐mct.com or www.drschar.com. These are not prescribable in the UK.
Table 30.7 Example providing daily medium chain triglyceride intake. Table 30.8 Examples of an overnight feed for long chain fatty acid
oxidation disorders.
Daily MCT intake for a 4‐year‐old girl
Estimated average requirement for energy for age = 1400 kcal Overnight feed for a 6‐year‐old boy, weight = 22 kg
(5.9 MJ)/day [36] 25% CHO from glucose polymer, administered at 25 mL/hour from
Provide 20%–25% energy from MCT = 280–350 kcal 10 pm to 6 am via gastrostomy
(1.2–1.5 MJ) ÷ (8.3 kcal, 35 kJ/g MCT) = 34–42 g/day
Fluid 200 mL
Breakfast 20 mL MCT emulsion (10 g MCT) added to Energy 200 kcal (840 kJ)
breakfast cereal Glucose polymer 53 g (95% CHO)
Lunch 1 sachet MCT Procal (10 g MCT) added to CHO 0.3 g CHO/kg/hour
very low fat yoghurt at school
Or
Evening meal 10 mL MCT oil (10 g MCT) added to
cooked pasta Glucose polymer and MCT feed, administered at 25 mL/hour from
10 pm to 6 am via gastrostomy
Another 10 g of MCT added to the night feed (Table 30.8) from MCT Fluid 200 mL
emulsion
Energy 200 kcal (840 kJ)
Glucose polymer 30 g (95% CHO) = 114 kcal (479 kJ)
MCT = 1∕4 of daily dose (10 g MCT) as 20 mL Liquigen
(around 0.3–0.4 g CHO/kg/hour) (p. 610). Addition of MCT (= 5 g MCT/100 mL) = 90 kcal (370 kJ)
as an energy source should enable the energy from CHO to
CHO, carbohydrate; MCT, medium chain triglyceride.
be reduced. Table 30.8 gives examples of overnight feeds.
Fasting tolerance increases with age; therefore, in older chil-
dren it may be possible to stop overnight feeds completely or children may not be able to do prolonged periods of exercise
substitute with one or more doses of UCCS. Typical doses of without developing muscle pain, so it has to be avoided.
UCCS used are 1–1.5 g/kg/dose. It is first introduced at The symptoms may occur due to limited ability to oxidise
home to test its palatability and tolerance, similar to the pro- LCFA as a fuel source for exercising muscle or the accumu-
cess in glycogen storage disease (p. 613). Before changing lation of toxic intermediates. Short burst exercise may be
management, it is good practice [35] to assess the child’s more suitable than prolonged low intensity exercise because
metabolic response under controlled conditions in hospital CHO will be used in preference to LCFA. As yet, no treat-
by serial measurement of plasma‐free fatty acids, blood ment has conclusively been shown to prevent rhabdomyol-
glucose, acylcarnitines and CK on their usual regimen and ysis, but several papers suggest that dietary modification
after a dose of UCCS. The results of these studies are used to may reduce the risk of this. Some patients with CPTIID
plan how frequently a dose of UCCS is given. appear to benefit from taking a diet rich in polysaccharides
pre‐exercise [41]. Pre‐exercise boluses of MCT (0.3–0.4 g/
Exercise management kg/dose) have been reported to improve exercise capacity
Glucose is the initial fuel during any exercise. Under normal in patients with various FAOD [42]. Dietary treatment may
circumstances CHO is the main fuel used for moderate to need to be adjusted according to the intensity and duration
high intensity exercise such as sprinting, whereas fatty acids of the exercise being undertaken. CHO foods and/or MCT
are the main fuel for low to moderate intensity exercise. can be trialled before or during or even after exercise to see
Patients with VLCADD, LCHADD, MTPD and CPTIID can if this exercise capacity is improved. MCT can be given as a
experience muscle pain, rhabdomyolysis, elevated CK and, prescribed dose of Liquigen, or MCT Procal, and CHO can
in severe cases, myoglobinuria with exercise. These epi- be given from food such as a low fat cereal bar, banana,
sodes may begin to occur in children as they become more bread or a glucose polymer drink. If a child does develop
active and want to play sports for longer periods. Some muscle pain during or, more likely, following exercise, this
must be treated promptly as there is a risk of rhabdomyoly- example, in LCHAD deficient patients, cumulative long
sis, myoglobinuria and subsequent renal failure. The stand- chain 3‐hydroxyacylcarnitine concentrations appear to cor-
ard glucose polymer ER ± MCT, with extra fluids, should be relate with the progression of retinal disease [44].
implemented. Rest is important until symptoms resolve. Monitoring of acylcarnitines may, therefore, be useful in
Children are likely to find it very difficult and painful to guiding dietary management. Plasma‐free carnitine levels
walk for the first 24–48 hours. It is essential that parents and should also be monitored, although there is dispute about
patients know to look for signs of myoglobinuria (dark, cola‐ supplementing carnitine if levels are low (p. 647), except in
coloured urine) and to go to their local hospital and make OCTN2. Plasma transaminases and CK are helpful markers
immediate contact with their metabolic team for further of clinical status. CK increases markedly during episodes of
management advice. Plasma CK can be markedly elevated exercise or illness‐induced rhabdomyolysis and returns to
during episodes of rhabdomyolysis and is helpful in deter- normal once treated. Fat‐soluble vitamins and EFA and
mining the extent of muscle damage and management LCPUFA concentrations should be monitored annually and
needed. ER guidelines (IV and oral) for hospital use can be more often if there are concerns about dietary deficiencies.
accessed from www.bimdg.org.uk. Erythrocyte measurements of EFA/LCPUFA are a better
marker of long‐term nutritional status than plasma. Other
nutritional markers such as iron and B12 status may also be
Dietary monitoring
necessary if there are concerns about nutritional adequacy
of the diet.
Once an infant or child is established on dietary treatment,
families need continued support and advice. Regular moni-
toring of this complex diet is essential to:
Dietary guidelines for managing the unwell child
• ensure the diet is nutritionally adequate, particularly for with a LC‐FAOD
fat‐soluble vitamins, EFA and LCPUFA
• ensure the overnight feeds provide adequate CHO (or Illness in any child is usually associated with loss of appetite
energy) for age and prolonged fasting, and fatty acid oxidation rates increase
• check the intake of LCT and MCT to provide energy. In LC‐FAOD this process is limited, and
• provide new ideas and information on low fat manufac- the child is at risk of serious illness. The ER needs to be
tured foods started promptly to inhibit the mobilisation of fatty acids
• assess exercise tolerance and provide advice on CHO/ and to prevent rhabdomyolysis and myoglobinuria, as there
MCT intake is risk of acute renal failure. The standard ER guidelines
• check the ER for CHO concentration and volume and should be used for LC‐FAOD.
parents’ understanding of its use
Clinical monitoring LC‐FAOD specific ER information

• Follow the standard ER (p. 673) of very frequent feeds/
This should include a review of weight, growth and devel-
drinks of glucose polymer, day and night
opment. There has been little documented on the growth of
• Long chain fat is strongly contraindicated
children with LC‐FAOD. Gillingham et al. reported excess
• MCT can be added for extra energy if it forms part of the
weight gain with time in most of their LCHADD and MTPD
usual diet
patients [43], but others have not observed this, including
• Parents and patients must look for signs of rhabdomyol-
the author’s centre [17, 35]. If a child is overweight, this
ysis and myoglobinuria (dark, cola‐coloured urine);
needs to be managed carefully as weight loss could precipi-
admission to hospital is essential for IV fluids if there is
tate metabolic decompensation. A gradual reduction in
myoglobinuria
energy intake is needed. If a child develops muscle pain
• Patients with cardiomyopathy should be admitted to
with exercise, this can make weight management more
hospital as there is a risk of deteriorating cardiac
difficult. Cardiomyopathy usually resolves on institution
function
of a minimal LCT diet supplemented with MCT. Thereafter,
• IV carnitine should not be given because long chain
cardiac function (echo and electrocardiogram) should be
acylcarnitines may be arrythmogenic
monitored annually. Liver ultrasound is also performed
• Plasma CK can be markedly elevated at 20 000–40 000 U/L
annually to assess for steatosis. In LCHADD and MTPD
and higher (50–240 U/L is the normal range, local labora-
annual ophthalmological (electrophysiology) and neuro-
tory figures) during episodes of rhabdomyolysis with
physiological follow‐ups are important.
myoglobinuria; daily measurement of CK can be used to
guide management of hyperhydration, which is neces-
Biochemical monitoring sary to increase myoglobin excretion and help prevent
acute renal failure
Blood acylcarnitine concentrations may correlate with • Rest is important until rhabdomyolysis symptoms
outcome in these disorders, but this is not certain. For resolve
Multiple Acyl‐CoA Dehydrogenase Deficiency (MADD) 653
• Blood glucose monitoring by parents at home is not Carnitine transporter deficiency

recommended as a marker of metabolic status, since
hypoglycaemia is a relatively late finding, and treat- Patients with carnitine transporter deficiency (CT or OCTN2;
ment should be initiated long before this develops [11] Figure 30.1) have low plasma and intracellular concentrations
of carnitine. This impairs fatty acid oxidation as carnitine is
necessary for the transport of LCFA into the mitochondria.
Learning points: long chain fatty acid oxidation disorders Abnormal plasma acylcarnitines are not seen in OCTN2.
(LC‐FAOD) Patients generally present between 1 and 7 years of age with
the typical features of an LC‐FAOD; other patients remain
• Dietary treatment varies depending on the severity asymptomatic [12]. Heart failure is a common presentation that
• In severe defects opinions differ about dietary management, can rapidly deteriorate with risk of death if patients are not
particularly the use of overnight feeds and uncooked corn- treated with carnitine (around 100 mg/kg/day divided into
starch (p. 646) two or three doses). No dietary treatment is necessary except
• In all disorders the use of an ER is essential during illness during illness when there is a risk of metabolic decompensa-
to prevent metabolic decompensation tion. The standard ER of frequent glucose polymer drinks day
• Additional CHO and/or MCT is needed for pre‐exercise in and night should be given to prevent increased lipolysis (p. 673).
some patients A more detailed overview of clinical manifestations, diag-
nosis and management is described elsewhere [45].
Multiple acyl‐CoA dehydrogenase deficiency (MADD)
This disorder is also known as glutaric aciduria type II.
Transfer protein Electron transferring flavoprotein (ETF) or ETF ubiquinone oxidoreductase ETFQO (Figure 30.1)
Biochemical defect Due to defects of ETF or ETFQO that carry electrons from dehydrogenation reactions (in β‐oxidation, lysine, tryptophan,
branched chain amino acids, choline) to the mitochondrial respiratory chain. Results in an energy deficiency.
Genetics Autosomal recessive inheritance. ETF: mutations in ETFA, ETFB. ETFQO: mutations in ETF dehydrogenase gene
Clinical onset MADD ranges in clinical severity. Some patients are completely responsive to riboflavin [46]. Severe MADD presents
presentation, features within the first few days of life with hypoglycaemia, hyperammonaemia, acidosis, hypotonia and hepatomegaly; some also
have congenital malformations, and cardiomyopathy may develop.
The less severe form may present from infancy to adulthood with hypoglycaemia, liver problems and muscle weakness [12].
Outcome Neonatal onset cases do not survive. Sudden death can occur at any time.
Drug treatment Trial of riboflavin (some cases are completely responsive). Oral sodium d‐3‐hydroxybutyrate is given to more severe
patients [47]. CoQ10 supplements are recommended for late onset ETFQO [48].
Dietetic management Little is published on dietary treatment of MADD. In patients with severe congenital malformations, no treatment is effective or
appropriate. If riboflavin is responsive, no dietary modification is necessary. Patients with more severe MADD are commenced on:
• a low fat, protein‐restricted diet as the dehydrogenase enzymes of β‐oxidation and some amino acids are affected
• regular feeding during the day with a high CHO intake to provide an adequate energy intake and limit lipolysis
• overnight fasting should be limited; young children are given continuous overnight feeds that can be replaced by UCCS
in older children to provide a ‘slow release’ source of glucose; it is essential to assess tolerance individually
• MCT should be avoided as they may precipitate problems [49]. Medium chain fatty acids enter the mitochondria
primarily independent of carnitine so bypassing CPTI, the step at which β‐oxidation is normally regulated; therefore,
high concentrations of toxic metabolites could be generated
• typical energy distribution of the diet in severe defects (based on personal practice):
–– 65%–70% energy from CHO
–– 8%–10% energy from protein (at least the safe level of protein intake for age [50]
–– 20%–25% energy from fat (the use of MCT is probably best avoided)
–– frequent feeding
For infants a modular feed with the above energy ratio is given, ensuring it provides all nutrients including EFA and LCPUFA in
recommended amounts. Partial breastfeeding is possible when combined with a fat‐free modular feed [51]. The diet can be based on
protein and fat exchange foods: each 1 g protein exchange should provide a maximum of 3 g fat. Additional fat may be necessary if
the protein exchanges are very low in fat. Very low protein and fat and high CHO foods can be given freely, e.g. fruit, most vegetables,
sugar. Some low protein manufactured foods are suitable and can provide additional energy, e.g. low protein pasta, rice, flour.
Monitoring – nutritional Regular monitoring is essential to ensure nutritional adequacy and normal growth. There is no useful biochemical marker
to determine the response to diet. Even on diet, acylcarnitine profiles generally remain abnormal but in less severe disease
can be normal. Routine biochemical nutritional monitoring should be undertaken for patients on low fat diets similar to
LC‐FAOD (p. 652). If the child is on a very low protein diet, monitoring of plasma amino acids may be indicated.
Emergency regimen During illness the standard ER (p. 673) of very frequent feeds, day and night, of glucose polymer should be given (oral or
tube) to minimise protein catabolism and increased fatty acid oxidation, thereby reducing risk of metabolic
decompensation. Fat should be avoided during the acute period.
Learning points: multiple acyl‐CoA dehydrogenase

deficiency (MADD)
• Dietary management is a low fat, protein‐restricted diet;

MCT is best avoided
• Catabolism is limited by providing regular daytime and
overnight feeding
• Use of an ER is essential during illness to prevent metabolic
decompensation
Malonyl‐CoA decarboxylase deficiency
This disorder is also known as malonic aciduria.

Enzyme Malonyl‐CoA decarboxylase (MLYCD)
Biochemical defect MLYCD catalyses the decarboxylation of malonyl‐CoA to form acetyl‐CoA and regulates the intracellular concentration of
malonyl‐CoA, which is involved in the regulation of fatty acid oxidation through inhibition of CPTI [52]. Biochemically there is
raised malonylcarnitine in the blood and high urinary excretion of malonic and methylmalonic acids.
Genetics Autosomal recessive inheritance: MLYCD gene
Newborn screening No NBS in the UK
Clinical onset Clinical features are of variable presentation and severity: cardiomyopathy (around 40% of cases), muscle weakness,
presentation, features developmental delay, seizures, short stature, hypoglycaemia and metabolic acidosis [53]. Malonic acid is found mostly in
heart muscle, skeletal muscles and central nervous system.
Drug treatment Carnitine, as total and free carnitine concentrations in plasma are low
Dietetic management A trial of a low fat, MCT‐supplemented diet may be indicated in MLYCD deficiency patients who have cardiomyopathy.
Improvement in cardiac function and biochemical response to diet has been reported in some published cases [54–57]. MCT
primarily enter mitochondria directly, bypassing CPT1, and can provide an alternative fuel for the heart. There is limited detail
and description of the diet used for many of the published cases. The author’s centre reported improvement of cardiac function
in a child when MCT provided around 25% of energy intake and LCT was minimal; she was also on an angiotensin‐converting
enzyme (ACE) inhibitor [54]. It is not known at the molecular level which patients may develop cardiomyopathy. There is
inadequate evidence to know if diet may help in prevention of onset of cardiomyopathy in patients diagnosed early or via NBS
or on relaxation of diet with age, once cardiac function has normalised.
Monitoring Biochemistry: acylcarnitines, including plasma malonyl carnitine, malonic and methylmalonic acid excretion. Echocardiography
Monitoring ‐ diet Refer to guidelines for monitoring low LCT diets for LC‐FAOD (p. 652)
Emergency regimen During illness the standard ER (p. 673) of very frequent feeds, day and night, of glucose polymer should be given to
prevent metabolic decompensation
Disorders of biosynthesis of ketones (ketogenesis)

and ketone body utilisation (ketolysis)
The biochemical pathways of ketogenesis and ketolysis and

site of metabolic defects described are shown in Figure 30.2.
Enzymes Enzymes involved in ketogenesis:

• 3‐hydroxy‐3‐methylglutaryl‐CoA (HMG‐CoA) synthase
• 3‐hydroxy‐3‐methylglutaryl‐CoA lyase (HMGCL)
Enzymes involved in ketolysis:
• succinyl‐CoA 3‐oxoacid‐CoA transferase (SCOT)
• beta‐ketothiolase (mitochondrial acetoacetyl‐CoA thiolase)
Biochemical defects Ketone bodies are formed from acetyl‐CoA, produced mainly from the oxidation of fatty acids, but also from the ketogenic
amino acids leucine and isoleucine (Figure 30.2).
Disorders of ketogenesis (defects in biosynthesis of ketone bodies):
• HMG‐CoA synthase deficiency. Necessary for ketone body formation from fatty acid oxidation
• HMGCL deficiency. Necessary for ketone body formation from fatty acid oxidation and final step of leucine degradation
Disorders of ketolysis (defects in utilisation of ketone bodies):
• succinyl‐CoA 3‐oxoacid‐CoA transferase (SCOT) deficiency. Necessary for the utilisation of ketone bodies
• beta‐ketothiolase, T2 deficiency (also involved in the isoleucine degradation pathway). Necessary for the utilisation of ketones bodies
A more detailed description of the biochemical pathway for these disorders can be found elsewhere [58, 59].
Disorders of Biosynthesis of Ketones (Ketogenesis) and Ketone Body Utilisation (Ketolysis) 655
Newborn screening No NBS in the UK

Clinical onset Ketone bodies (acetoacetate and 3‐hydroxybutyrate) are an important energy source for all tissues, particularly the brain during
presentation, fasting. Ketone body production increases during physiological stress situations such as illness. Excess ketones results in
features ketoacidosis.
Disorders of ketogenesis: Typically present with vomiting and lethargy with a ‘hypoketotic’ hypoglycaemia, acidosis, elevated
transaminases and hepatomegaly (not seen in all HMGCL cases) and hyperammonaemia (in HMGCL) [60]. HMGCoA synthase
deficiency typically presents in the first or second year of life [61, 62], whereas HMGCL presents primarily within the first year
of life with around half as neonatal cases [60]. In both disorders there is risk of death at the initial presentation.
Disorders of ketolysis: Typically present with vomiting and high levels of ketones (which cannot be utilised), ‘hyperketotic
hypoglycaemia’ (which can cause a severe ketoacidosis), a reduced level of consciousness and dehydration. In T2 deficiency
typical onset of a first ketoacidotic episode is between 6 and 36 months and commonly precipitated by an intercurrent illness;
neonatal onset is rare [62]. SCOT deficiency can present in the neonatal period and early childhood [63].
In all disorders, following diagnosis not all cases will experience a further episode of metabolic decompensation.
Outcome Clinical outcome is generally good if identified early with prompt treatment and avoidance of further acute episodes, except in
HMGCL deficiency. However, neurological complications are reported in T2 deficiency, including a few cases with no
metabolic crises [64]. In HMGCL deficiency many patients develop long‐term neurological complications, which include
epilepsy, muscular hypotonia and spasticity [60].
Acute Acute decompensation is treated by IV glucose to suppress ketogenesis; refer to BIMDG emergency guidelines (www.bimdg.org).
management
Drug treatment HMGL deficiency: l‐carnitine supplementation 75–100 mg/kg/day to avoid secondary deficiency
Dietetic Ketogenesis and ketolysis disorders
management Between episodes of metabolic decompensation, most patients are likely to be clinically asymptomatic. Once diagnosed some cases
never experience another episode. In the well child avoidance of prolonged fasts and provision of adequate energy is important to
limit catabolism. There are no published guidelines on safe fasting times for these disorders; therefore, as clinical severity varies, it is
important to establishing fasting tolerance on an individual basis, particularly in infants and young children. Infants should have
regular feeds, day and night, and it seems reasonable to continue a middle‐of‐the‐night feed until the age of 1 year. Older children
should tolerate overnight fasting (10–12 hours) without problems, but they should be given a starchy bedtime snack and not miss
breakfast. Missed meals should be replaced with a starchy snack or high CHO drink if there is any risk of impending illness.
HMG‐CoA lyase deficiency
A moderate protein restriction (1–2 g protein/kg/day) has been recommended to reduce leucine load [65, 66]. In addition to
protein restriction, some centres add leucine‐free amino acids to the diet of some patients [60]. In some cases protein restriction
has been combined with a modest fat restriction [60, 65]. However, opinions differ about the necessity of these dietary
manipulations. Stable isotope studies suggest that protein catabolism contributes little to the abnormal metabolites and that fatty
acid catabolism may be more important [67]. In the well child it is reasonable to suggest a generous CHO intake and avoidance
of a high protein and fat intake. Avoidance of alcohol consumption has been recommended in HMGCL because it can
precipitate Reye‐like syndrome episodes [68].
T2 deficiency
Mild protein restriction (1.5–2.0 g/kg/day) to reduce isoleucine load is theoretically considered reasonable, but is not evidence
based, and benefit is unproven [63].
SCOT deficiency
Mild protein restriction (1.5–2.0 g/kg/day) has been described, probably to limit increased concentrations of ketones being
formed from the ketogenic amino acids, and avoidance of a fat‐rich diet which would cause ketosis [63, 69]. In the well child it
is reasonable to suggest a generous CHO intake and avoidance of a high protein and fat intake.
Medium chain triglycerides
MCT are best avoided as either they cannot be used to form ketones or they will add to the total ketone load, which cannot be
utilised. Theoretically, in SCOT and T2 deficiencies, MCT may increase concentrations of ketones (which cannot be utilised)
and inhibit long chain fatty acid oxidation, thus contributing to the energy deficit. In HMGCoA synthase and HMGCL, the
conversion of MCT to ketones may be limited and so will not provide an energy source. Special infant formulas or paediatric
feeds with added MCT should be avoided.
Emergency regimen During illness the standard ER (p. 673) of frequent glucose polymer feeds, day and night, should be given to minimise fatty acid
oxidation and endogenous protein catabolism (specifically the ketogenic amino acids) and suppress ketogenesis. If specialised
infant formulas or paediatric enteral feeds are needed, due to inadequate oral intake, MCT‐containing feeds should not be given.
Disorders of ketogenesis
The ER will help prevent hypoglycaemia and limit the production of potentially toxic metabolites. Blood glucose monitoring by
parents is not recommended, since hypoglycaemia is a relatively late finding and treatment should be initiated long before this
develops.
Disorders of ketolysis
The ER will help prevent illness from leading to ketoacidosis. Patients can become anorexic at an early stage if refusing ER
drinks. Early admission to hospital is essential for administration of ER via tube or IV fluids. Sodium bicarbonate may be
necessary to correct acidosis and extra fluids to correct dehydration, which is common in the ketone body utilisation defects.
Clinical management Guidelines for diagnosis and treatment for patients with ketone body utilisation disorders have been produced based on clinical
guidelines information from Japan and worldwide [70].
Isoleucine Fatty acids Leucine
Tiglyl-CoA 4
Acetoacetyl-CoA Acetyl-CoA
2-Methyl-3-hydroxybutyryl-CoA 3-Methylcrotonyl-CoA
1
2-Methylacetoacetyl-CoA HMG-CoA 3-Methylglutaconyl-CoA
4 2
3-Methylglutaryl-CoA
Propionyl-CoA Acetyl-CoA
Acetoacetate 3-Hydroxybutyrate
Succinyl-CoA
3
Succinate
Acetoacetyl-CoA
Acetyl-CoA
Figure 30.2 Biochemical pathways of ketogenesis and ketolysis. HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A. 1, Mitochondrial(m) HMG-CoA synthase;
2, HMG-CoA lyase; 3, succinyl-CoA 3-oxoacid CoA transferase (SCOT); 4, mitochondrial acetoacetyl-CoA thiolase (T2). Reprinted with permission of Springer.
Learning points: disorders of biosynthesis of ketones

(ketogenesis) and ketone body utilisation (ketolysis)
• Management is avoidance of fasting, particularly during

physiological stress, and treatment with standard ER or IV
glucose (10%) (www.bimdg.org)
• Mild protein restriction is advised, but supporting evidence
is limited
• MCT are best avoided
Disorders of Lipid Metabolism

Rachel Skeath
Introduction the surface. The four main classes of lipoproteins are classified
according to their density (Table 30.9). Apolipoproteins
Triglycerides, cholesterol and phospholipids are the three main
enable the packaging and transport of lipids; they are also
forms of lipid in the body. Their production and transport through
cofactors for enzymes and ligands for lipoprotein receptors [71].
the body is based on three interrelated pathways known as the
Disorders of lipid metabolism managed by dietary inter-
exogenous, the endogenous and the reverse cholesterol transport
vention can be categorised into:
pathways (Figure 30.3, Table 30.9). Lipids are transported in
plasma as lipoproteins, which have a hydrophobic core of triglyc- • hypolipoproteinaemias: serum lipoproteins are deficient
erides and cholesteryl esters with hydrophilic molecules (phos- or absent
pholipids, cholesterol and proteins known as apolipoproteins) on • hyperlipoproteinaemias: serum lipoproteins are increased
Macrophage
apoB-100 HL apoB-100 ADIPOCYCTES

LDL IDL
FFA apoE
FFA MUSCLE
LDLR
FFA apoB-100 LPL
CE
TG apoB-100
FC VLDL
MTP apoE
LIVER TG
BA CE
CE
CE HDL
FC LCAT
LRP
nascent
HDL
apoB-48
CMR
apoE
LPL
apoB-48
FFA
CM
ADIPOCYCTES
MUSCLE
CE FC TG FC CE PL FC
BA CE PL BA TG INTESTINE
Figure 30.3 Lipid transport. Adapted from Kwiterovich et al. [72].

BA, bile acid; C, cholesterol; CE, cholesterol ester; CM, chylomicrons; CMR, chylomicron remnants; FC, free cholesterol; FFA, free fatty acid; HDL, high
density lipoproteins; HL, hepatic lipase; IDL, intermediate density lipoproteins; LCAT, lecithin cholesteryl acyl transferase; LDL, low density lipoproteins;
LDLR, LDL receptor; LPL, lipoprotein lipase; LRP, lipoprotein receptor‐related protein; MTP, microsomal triglyceride transport protein; PL, phospholipid; TG,
triglyceride; VLDL, very low density lipoproteins.
Table 30.9 Lipoprotein composition and function.
% wt
from % wt % wt
Lipoprotein TG PL C + CE Apolipoproteins Function
CM 90 6 3 ApoB‐48, ApoA‐I, Secreted from enterocytes. CM transport dietary TG and FC from the
A‐IV intestine. CE, FC and TG are hydrolysed by pancreatic lipase in the intestine,
emulsified by BA, absorbed into enterocytes and then packaged into CM. TG
in the CM is hydrolysed by endothelium‐bound LPL in adipose tissue and
muscle. CMR taken up by liver delivering CE and FC (endogenous pathway)
VLDL 55 15 22 ApoB‐100, ApoC‐I, Secreted from hepatocytes. TG (synthesised in liver) is packaged with CE and
C‐II, C‐III, ApoE apoB‐100 to form VLDL and then transported to adipose tissue and muscle
(endogenous pathway). TG on VLDL is hydrolysed by LPL
LDL 5 25 50 ApoB‐100 Catabolic product of VLDL formed by activity of HL. LDL transport
cholesterol from liver to peripheral tissues (endogenous pathway). LDL
normally removed by LDLR on liver, excess taken up by macrophages
HDL 5 25 20 ApoA‐I, A‐II, Transport cholesterol from peripheral tissues to liver (reverse cholesterol
ApoC‐I, C‐II, C‐III, transport). FC and PL form nascent HDL, which becomes a larger HDL
ApoE particle through action of LCAT. Low levels of HDL are associated with
higher risk of cardiovascular disease
BA, bile acid; C+CE, sum of cholesterol and cholesterol ester; CM, chylomicrons; CMR, chylomicron remnants; FC, free cholesterol; HDL, high density
lipoproteins; HL, hepatic lipase; LCAT, lecithin cholesteryl acyl transferase; LDL, low density lipoproteins; LDLR, LDL receptor; LPL, lipoprotein lipase;
TG, triglyceride; VLDL, very low density lipoproteins, wt, weight.
Source: Adapted from Kwitervich PO [73].
Schaefer and Levy [74] describe grouping disorders of causes. Advances in understanding lipoprotein metabolism
lipid metabolism by the lipid profile characteristic of the continue to be made, assisted by the ongoing discovery of
condition. Further classification becomes more complicated cases with novel mutations. Table 30.10 summarises the
as similar phenotypes can result from different underlying disorders reported in children.
Table 30.10 Overview of lipid metabolism disorders reported in children.
Disorder Defect/problem Lipid and lipoprotein profile Dietary management
Deficiencies in apoB lipoproteins (gene involved is shown in italics)

Abetalipoproteinaemia (ABL) Defect in the MTP protein ↓↓ CM, ↓↓ VLDL, ↓↓ LDL, Low LCT
(MTP) responsible for processing of ↓↓apoB, ↓↓ TG Although <20%–30% energy from LCT
apoB lipoprotein is recommended [75], in clinical
practice a very much lower intake is
necessary (p. 660)
Adequate energy
Caution in use of MCT
High dose vitamin E
EFA and fat‐soluble vitamin supplements
Familial (heterozygous) Decreased levels of functional ↓ LDL, ↓ apoB, normal TG Usually asymptomatic – normal diet
hypobetalipoproteinaemia (APOB) apoB‐100 lipoprotein, involved
in VLDL and LDL structure
Primary (homozygous) ↓↓ CM, ↓↓ VLDL, ↓↓ LDL, Low LCT
hypobetalipoproteinaemia (HBL) ↓↓ apoB, ↓↓ TG Although <20%–30% energy from LCT
(APOB) is recommended [75], in clinical
practice a very much lower intake is
necessary (p. 661)
Adequate energy
MCT added to diet
High dose vitamin E
Chylomicron retention disease Defect in the intracellular ↓↓ CM, ↓↓ LDL, ↓↓ HDL, Low LCT
(CRD) (SAR1B) transport of CM ↓↓ apoB, normal TG Although <30% energy from LCT is
recommended [76], in clinical practice a
very much lower intake is necessary (p. 661)
Adequate energy
MCT added to diet
High dose vitamin E
Disorders of reverse cholesterol transport
Tangier disease Defect in ABCA1 protein that is ↓↓ HDL, ↓ TC, ↓ apoA‐I, Low LCT
essential for exporting normal TG or slightly ↑ TG
cholesterol and phospholipids
to nascent HDL
Lecithin‐cholesterol Unable to esterify cholesterol to ↓↓ HDL, ↓ apoA‐I, ↑ TG
acyltransferase deficiency produce HDL
Exogenous hypertriglyceridaemia
Familial lipoprotein lipase Defective or absent LPL causing ↑↑ TG, ↑↑ CM, ↓ HDL, Approximately 10–15 g LCT/day
deficiency (LPL) accumulation of CM ↓ LDL, normal VLDL MCT added to diet
ApoC‐II deficiency (APOC2) Defect in apoC‐II that is a co‐
factor for LPL
Defective Defect in the GPIHBP1 protein
glycosylphosphatidylinositol that is involved in binding LPL
(GPIHBP1)
apoAV deficiency (APOA5) Exact mechanism of apoAV is
unclear but is a modulator of
TGs [77]
Lipoprotein maturation factor 1 LMF1 aids in LPL folding and
(LMF1) transport
Hypolipoproteinaemias 659
Disorder Defect/problem Lipid and lipoprotein profile Dietary management
Endogenous hypertriglyceridaemia
Familial hypertriglyceridaemia Abnormal hydrolysis of TG ↑↑ TG, ↑ VLDL 10–15 g LCT/day
(APOA5 and LIPI) Usually later onset MCT added to diet
Present in childhood if EFA and fat‐soluble vitamin supplements
secondary risk factors for
hyperlipidaemia are present
Combined exogenous and endogenous hypertriglyceridaemia

Dysbetalipoproteinaemia/type III Defective apoE (APOE) that binds ↑ TG, ↑ CM remnant, ↑ IDL 10–15 g LCT/day
hyperlipoproteinaemia CM, IDL and VLDL to LDLR remnant, ↑ VLDL remnant MCT added to diet
Usually later onset. Presents in EFA and fat‐soluble vitamin supplements
childhood if secondary risk factors
for hyperlipidaemia are present
Hepatic lipase deficiency (LIPC) Reduced hydrolysis of TG from ↑↑ TG, ↑ VLDL, ↑ HDL,
IDL, LDL and HDL normal LDL
Hyperlipidaemia due to disorders of LDL removal

Familial hypercholesterolaemia Defective LDLR function ↑ LDL Fat <30% of energy
(FH) (heterozygous) (LDLR) Saturated fatty acids <10% of energy
Cholesterol <300 mg/day
FH (homozygous) (LDLR) Defective LDLR function ↑↑ LDL
Oily fish once/week
Familial defective apoB‐100 Defective apoB‐100 protein ↑ LDL Fruit and vegetables – five portions/day
(APOB) which decreases binding to LDLR
Autosomal recessive Defective internalisation of ↑ LDL
hypercholesterolaemia (LDLRAP1) LDLR
PCSK9 disorders (PCSK9) Decreased LDLR activity ↑ LDL
Other hyperlipidaemias
Sitosterolaemia (also known as Defect in ATP‐binding cassette ↑↑ plant sterols in blood and Low saturated fat diet
phytosterolaemia) [78–80] transporter ABCG5/8 that tissues, ↑ LDL Avoid foods high in cholesterol, plant
Increased absorption and transports sterols back into gut sterols and sterol fortified foods [78–80]
decreased biliary excretion of for excretion https://ndb.nal.usda.gov/
plant sterols and cholesterol Ezetimibe therapy (sterol absorption
inhibitor) (p. 667) ± bile acid
sequestrants
Lysosomal acid lipase deficiency Defect in lysosomal degradation ↑ TG, ↑ LDL, ↓ HDL See Wolman disease (p. 669)
of cholesteryl esters and (less marked increases than
Infant onset (Wolman disease) triglycerides in cholesterol ester storage
disease, CESD)
Lysosomal acid lipase deficiency Defect in lysosomal degradation of ↑ TG, ↑ LDL, ↓ HDL May require modified lipid diet
Childhood/adult onset (CESD) cholesteryl esters and triglycerides
CM, chylomicrons; EFA, essential fatty acids; HDL, high density lipoproteins; HL, hepatic lipase; IDL, intermediate density lipoproteins; LCT, long chain
triglyceride; LDL, low density lipoproteins; LDLR, LDL receptor; LPL, lipoprotein lipase; MCT, medium chain triglyceride; MTP, microsomal triglyceride
transport protein; TG, triglyceride; VLDL, very low density lipoproteins.
Hypolipoproteinaemias
Abetalipoproteinaemia (ABL)
Protein Microsomal triglyceride transfer (MTP) protein
Defect Defect in MTP protein resulting in impaired processing of apoB. Dysfunctional apoB causes impaired CM packaging
and formation of VLDL and consequently LDL. Overall, it leads to the defective secretion, i.e. low levels, of the
plasma lipids: chylomicrons, VLDL, LDL and fat‐soluble vitamins.

Incidence: <1 in 1 000 000 [81]
Clinical onset Age of onset is within first 24 months of life, typically the first few weeks.
presentation, features Biochemical features:
• very low levels chylomicrons, VLDL, LDL, apoB and TG in plasma
• deficiency of fat‐soluble vitamins (vitamin E levels are almost undetectable [82]); deficient EFA levels
• anaemia due to iron and folate deficiencies secondary to fat malabsorption
• elevated prothrombin time and in severe cases gastrointestinal bleeding associated with vitamin K deficiencies
Clinical symptoms involve many organ systems and include:
• gastrointestinal: diarrhoea and steatorrhoea leading to faltering growth, abdominal distension
• neurological: areflexia, ataxia, dysarthria and possible cognitive decline due to vitamin E deficiency; EFA
deficiency may also be a contributing factor [82]; symptoms tend to develop by 10 years [81], and, left untreated,
individuals can become immobile [82]; neurological symptoms are worse in ABL than HBL [75].
• ophthalmic: retinitis pigmentosa and less commonly corneal ulcers, ptosis and ophthalmoplegia due to vitamin E,
A and EFA deficiency
• liver: steatosis and elevated serum transaminases with hepatomegaly; although rare, hepatic complications such
as cirrhosis has been reported [83, 84]
• acanthocytosis: spiky red blood cells
Long‐term complications Prognosis is good with adherence to diet and vitamin supplementation. Early recognition and treatment can delay or
and outcome prevent further deterioration of the presenting symptoms. GI symptoms resolve on commencing a low LCT diet.
Vitamin E supplementation reduces retinal degeneration [81]. Hepatic steatosis is not uncommon, but further
complications such as fibrosis or cirrhosis are rare [75]
Hypobetalipoproteinaemia (HBL)
Protein ApoB protein
Defect Defect in the synthesis of apoB (the step before the defect in ABL) causing impaired apoB. Leads to low levels of
plasma LDL and fat‐soluble vitamins
Genetics Autosomal co‐dominant inheritance. Mutation in APOB gene causes an error in the translation of apoB protein. Most
mutations in APOB cause a truncated apoB protein, but some mutations affect intracellular transport of apoB.
Another mutation in PCSK9 gene causes upregulation (reduced degradation) of the LDL receptor that causes
increased clearance of VLDL and LDL cholesterol [81]. Inheritance of one mutation in APOB gene causes
heterozygous HBL, inheriting two mutations causes compound heterozygous or homozygous HBL (the term
homozygous HBL will be used throughout to include compound heterozygotes). Heterozygous HBL has a milder
clinical presentation than homozygous HBL.
Incidence heterozygous HBL: 1 in 1000–3000 [85]
Incidence homozygous HBL: 1 in 1 000 000 [81]
Clinical onset Heterozygous HBL: Usually asymptomatic; there is a three‐ to fivefold greater liver fat content than the general
presentation, features population; some develop hepatic steatosis.
Biochemical features: LDL cholesterol and apoB level are one quarter to one third normal [81].
Homozygous HBL: Onset is within first 24 months of life; biochemical and clinical features are indistinguishable
from ABL [85]
Long‐term complications The long‐term outcome in heterozygous HBL is unknown; ongoing follow‐up, particularly monitoring liver function,
and outcome is recommended. In homozygous HBL early recognition and treatment with fat‐soluble vitamins can slow the
progression of neuromuscular and ophthalmological degeneration [81]. Malabsorption resolves with a fat‐restricted
diet. Hepatic steatosis may be more prevalent in HBL than ABL [75].
Chylomicron retention disease (CRD)
Protein Sar 1b protein
Defect Product of SAR1B gene is needed for intracellular trafficking of CM particles. The mutation causes accumulation of
lipid (pre‐CM transport vesicles) in the enterocytes and decreased, but not absent, LDL and apoB.
Genetics Autosomal recessive inheritance. Mutation in SAR1B gene. Incidence 1 in 1 000 000 [81]
Clinical onset presentation, Clinical features normally present in early infancy and are similar to ABL [81]
features Biochemical features:
• low levels (approximately 50% less than normal [76]) of total cholesterol, LDL, HDL, chylomicrons, but normal TG
• elevated CK in many cases especially those with muscle complications
• fat‐soluble vitamin and EFA deficiency; plasma vitamin E levels are very low; omega‐3 deficiency was less of a
problem than omega‐6 in one study population [76]
• anaemia due to iron and folate deficiencies secondary to fat malabsorption
• elevated prothrombin time and in severe cases GI bleeding associated with vitamin K deficiency
Clinical symptoms involve many organ systems and include:
• gastrointestinal: diarrhoea, steatorrhoea, abdominal distension and faltering growth
• neurological: areflexia, ataxia, myopathy and muscle pain and sensory neuropathy have been reported [76] less
severe than in ABL and HBL and tend to occur in those with a delayed diagnosis or poor compliance to treatment
• ophthalmological: if present, mild compared to ABL and HBL
• liver: hepatomegaly and steatosis in a few cases; cirrhosis has not been reported [81]
• cardiomyopathy: has been described in adults [76]
Long‐term complications With early diagnosis, catch‐up growth can be achieved. Diarrhoea and steatorrhea resolve with dietary modifications.
and outcome Long‐term data on outcome is lacking; ongoing follow‐up is required.
ABL, HBL, CRD: Summary of management
Dietetic management Low LCT diet

Adequate energy
MCT supplements
Fat‐soluble vitamin supplements; vitamin E in pharmacological doses; long‐term
EFA and/or LCPUFA supplements
Monitoring – biochemical Total cholesterol, LDL, HDL cholesterol
and nutritional Liver function tests, clotting factors, albumin, uric acid
Vitamins A, D, E, K, B12, folate, calcium, phosphate
Monitoring Growth, stool output, abdominal distention
Neurological examination, nerve conduction studies
Ophthalmology
Bone mineral density by dual energy X‐ray absorptiometry (DEXA)
Hepatic ultrasound
Echocardiography
Clinical management Lee J, Hegele RA Abetalipoproteinaemia and homozygous hypobetalipoproteinaemia: a framework for diagnosis and
guidelines management. J Inherit Metab Dis, 2014, 37 333–339 [75]
Peretti N, Sassolas A, Roy CC et al. Guidelines for the diagnosis and management of Chylomicron Retention Disease
based on a review of the literature and the experience of two centers. Orphanet J Rare Dis, 2010, 5 24 [76]
Dietary management of ABL, HBL and CRD LCT restriction needs to be individually determined to
relieve the GI symptoms of diarrhoea, steatorrhoea and
Low LCT diet abdominal distention and typically varies from 5 g fat/day
in infants up to 20 g/day in older children. The diet is based
Lee and Hegele [75] recommend in ABL that total fat intake, on low fat carbohydrate foods such as white fish, lean meat,
particularly LCT, should be <30% of energy intake and if pulses, fruit and vegetables and very low fat dairy products
possible closer to 20%; however, this differs markedly from such as skimmed milk and very low fat yoghurt. The LCT fat
clinical practice: GI symptoms generally only resolve on a allowance should be distributed evenly through the day.
much lower LCT intake. Homozygous HBL resembles ABL
and so requires a similar LCT restriction. Children with het-
Adequate energy
erozygous HBL are usually able to absorb the fat provided
by a normal diet without restriction [86]. Peretti et al. [76] Faltering growth at presentation needs correction. Throughout
recommend in CRD that total fat intake should be <30% childhood energy deficit caused by LCT restriction should be
energy intake; this too differs in clinical practice as a very compensated for with an increase in energy from low LCT,
much lower intake is necessary to prevent GI symptoms. carbohydrate‐based foods and MCT supplements.
Medium chain triglycerides Ketovite tablets and liquid, Dalivit, Paediatric Seravit and
FruitiVits (p. 526). Plasma concentrations are monitored to
Medium chain triglycerides (C8 and C10) do not require
guide whether doses need to be adjusted beyond this.
chylomicrons for their absorption as they are absorbed and
transported directly from the intestine to the liver via the
hepatic portal system. MCT oil or MCT supplements Essential fatty acid supplements
(Table 30.6) can partially replace dietary LCT to enable more
EFA intake is restricted when following a low fat diet. In CRD
choice, improve palatability and provide additional energy.
neither intravenous (IV) nor oral supplementation with EFA
For example, MCT oil can be used in baking to make biscuits
was able to normalise plasma concentrations [76]. Plasma lev-
or pastry in place of margarine or used for frying foods.
els did not seem to impact outcome as, despite low plasma
Further information on using MCT oil and alternative
omega‐6 fatty acid levels, the cohort of patients described still
products can be found on p. 649.
made very good clinical progress. There are no specific guide-
Historically, the use of MCT as an energy source in ABL
lines for EFA supplementation in HBL; therefore, supplemen-
was controversial due to case reports of it possibly causing
tation with walnut oil (EFA) and KeyOmega (LCPUFA) to
hepatic fibrosis [87, 88]. However, there are single case
provide at least population requirements should be given
reports of children who developed cirrhosis independent of
(p. 646). Regular monitoring of EFA is essential with biochem-
using MCT oil [75, 84]. Furthermore, there are case reports of
ical analysis of red blood cell (RBC) membrane fatty acids,
benefit of MCT for catch‐up growth and absence of adverse
rather than plasma fatty acids. RBC fatty acids reflect long‐
effects with its use [89]. Some metabolic centres, including
term fatty acid balance in tissues and are not influenced by
the author’s, include MCT in the diet with caution, in
recent dietary fat intake [92]. If tolerated the fat derived from
prescribed amounts; regular liver ultrasound scans and bio-
walnut oil is not included as part of the daily fat allowance,
chemical monitoring of liver function are required. Similar
although this practice may differ between centres.
concerns have not been reported in HBL or CRD.
Infant feeds
Fat‐soluble vitamins
Newly diagnosed cases are often referred via gastroenterol-
Vitamin E and beta‐carotene are fully reliant on transport in ogy services, with a history of having been fed various spe-
apoB‐containing lipoproteins for their delivery to the tissues cialist formulas in an attempt to manage the malabsorption
of the body. Vitamins A, D and K, however, especially if caused by fat‐laden enterocytes. Infants should be fed from
taken in sufficiently large doses, are understood to be able to diagnosis with a minimal LCT formula. Diarrhoea may con-
utilise the MCT transport pathway [75, 83]. tinue for several weeks, but the infant begins to thrive with
Recommendations for supplementing fat‐soluble vita- the minimal LCT formula. If MCT is tolerated, a formula
mins are: supplemented with MCT may be given, e.g. Monogen or
Lipistart; both are nutritionally complete and contain 1.8–
• vitamin E: 67–200 mg/kg/day [75, 90]
2.5 g MCT per 100 mL (Table 30.2). Exclusive feeding with
• vitamin A: 30–120 μg/kg/day [75] or 450 μg/day [76]
Lipistart or Monogen will provide approximately 0.5–0.9 g
• vitamin D: 20–30 μg/day [75, 76]
LCT/kg based on an intake of 150 mL/kg.
• vitamin K: 5–35 mg/week [75] or 15 mg/week [76]
If MCT is to be avoided, basic‐f and Low Fat Module
Long‐term supplementation of vitamin E in high doses (Table 30.2) are suitable products on which to base a feed.
increases serum vitamin concentrations, but levels remain low Both require addition of vitamins, minerals and EFA supple-
in ABL, often <30% of the lower limit of normal [76, 91] and ments to meet requirements; basic‐f also needs added glucose
in CRD [83]. Different oral vitamin E preparations (liquid, polymer to meet energy requirements. A minimal fat modu-
tablets) are available including water‐soluble forms. Liquid lar feed may be just as practical to use; an example providing
preparations are often in an oil‐based suspension and in approximately 5 g LCT is outlined in Table 30.11. The modu-
larger doses contribute to the daily LCT fat allowance. In the lar feed requires a minimal fat protein source (e.g. Protifar,
author’s centre alpha‐tocopherol acetate is mainly used Hydrolysed Whey Protein/Maltodextrin Mixture, Complete
(1 mL contains 100 mg vitamin E and l400 mg castor oil). Amino Acid Mix), glucose polymer (e.g. Polycal, Vitajoule),
In contrast, deficiencies of Vitamin A, D and K seen at electrolytes, EFA (e.g. walnut oil), LCPUFA (e.g. KeyOmega)
presentation can be corrected. The initial dose of vitamin A is and vitamins and minerals (e.g. Paediatric Seravit). If neces-
high so it is important to monitor accordingly, as there is risk sary a restricted amount of LCT (e.g. Calogen fat emulsion)
of toxicity [75, 84]. Fat‐soluble vitamin supplementation may be added to the feed as an additional source of energy.
should be given orally as this route is effective. There have Alternatively, and probably preferably, the amount of walnut
been reports of hepatic complications in patients with ABL oil can be increased until it provides all the allowance of LCT
who have received parenteral vitamin supplementation; as invariably EFA levels remain low. As walnut oil is not a fat
however, the association is not explicit [75]. At the author’s emulsion, it should not be added to the feed, but given as a
centre, once initial deficiencies have been corrected, ongoing bolus divided into 2–3 equal doses through the day.
supplementation of vitamins A, D and K is provided through Historically, breastfeeding has been considered to be con-
standard multivitamin and mineral supplements such as traindicated in ABL, HBL and CRD; however, a small amount
Table 30.11 Minimal fat feed (approx. 5 g LCT) when MCT is to be avoided.
A 16‐week‐old boy, prior to weaning. Weight = 5.4 kg (2nd centile). Length = 60 cm (9th centile)
Daily requirements:
Fluid 150 mL/kg. Energy 96–130 kcal (400–545 kJ)/kg. Protein 1.8 g/kg
EFA given as walnut oil to meet requirements (p. 646)
Feed volumes: 140 mL × 6
Energy (kcal) Protein (g) CHO (g) LCT (g) Na (mmol) K (mmol)
Vitajoule 120 g 456 (1908 kJ) – 114 – 1.1 –

Protifar 20 g 74 (310 kJ) 17.4 0.2 0.3 1.0 0.7
Paediatric Seravit 10 g 30 (126 kJ) – 7.5 – 0.1 0.1
Walnut oil 5 mL 42 (176 kJ) – – 4.7 – –
KeyOmega 4 g sachet 18 (74 kJ) 0.1 3.2 0.5 0.3 0.3
KCl 7 mL (2 mmol/mL) – – – – – 14.0
NaCl 1.5 mL (5 mmol/mL) + water to 900 mL – – – – 7.5 –
Per 100 mL 69 (289 kJ) 1.9 13.9 0.6 1.1 1.7
Per kg 107* (435 kJ) 2.9 21.6 0.9 1.7 2.6
% of energy 11 80 8
Total per 24 hours (840 mL) 580 (2427 kJ) 16.3 116.6 5.7 9.3 14.1
*A higher energy intake may be needed in infants with faltering growth.
of breastfeeding may be possible in combination with a min- these disorders; additional feeds can be given during the
imal or fat‐free formula. Breastmilk intake needs to be day instead).
restricted based on LCT allowance, e.g. 120 mL breastmilk
can be estimated to provide 5 g LCT. Close monitoring is
Children
required, and the ratio of breastfeeding to formula feeding
altered according to biochemical parameters, clinical symp- A fat (LCT)‐restricted diet needs to continue into childhood.
toms and growth. Daily fat allowance may increase slightly as already dis-
Glucose polymer, such as Maxijul or Vitajoule, can be cussed. A guideline for achieving a minimal fat diet in
added to infant formula to increase the energy density of the children is to aim for main meals to contain ≤3 g fat per meal,
feed for those with faltering growth. Feed volumes may also snacks ≤0.5 g fat per item and desserts ≤0.5 g fat per portion.
need to be increased to provide additional energy; if the The LCT content of suitable foods is given in Table 14.14.
extra feed volume results in exceeding the LCT allowance, A sample menu providing ≤10 g fat/day is given in Table 30.12.
additional feeds of glucose polymer and a protein source
should be given instead.
Older children and adolescents
It can be particularly difficult to achieve an adequate energy
Weaning diet
intake for growth and development on such a low fat diet in
Transition to solid foods can begin as usual at around 26 this age group. Foods such as skimmed milk (made into
weeks of age with a minimal fat diet consisting of baby milkshake with low fat flavouring), very low fat yoghurts,
cereal mixed with the minimal fat feed, fruits and vegeta- low fat breakfast cereals, fruit (including dried), fruit juices,
bles (excluding avocados and olives), pulses, meats and meringue, jelly, jam and sorbet are suitable low fat sources of
fish naturally low in fat. Families need to be taught how energy. Low fat food brands designed for weight loss can be
to calculate daily fat intake. As a guide for using commer- useful and are increasingly available in the supermarkets;
cial baby foods, wet baby foods and dried baby foods their fat content per portion needs to be considered before
containing ≤0.5 g fat/100 g and ≤2 g fat/100 g, respec- including in the diet. Standard recipes (e.g. for biscuits, cakes
tively, are allowed freely if given in typical portion sizes. and savoury foods) can be adapted to make low fat versions.
Other baby foods with a higher fat content need to be MCT oil will help to improve the palatability and the energy
counted as part of the total daily fat allowance. Families density of the diet (used with caution in ABL). See p. 648 for
can be taught to calculate fat content of food from nutri- further details of using MCT supplements. Glucose poly-
tional food labels (p. 649). A sample menu for a low LCT mers (e.g. Maxijul, Polycal, Vitajoule) may need to be used if
weaning diet is given in Table 30.3 (excluding the advice adequate energy cannot be achieved with food alone.
regarding overnight feeding, which is not necessary for Finding suitable snack foods can be a particular challenge,
Table 30.12 A sample minimal fat menu providing ≤10 g fat/day. especially when out with friends. Advice should be given to
families about minimal LCT choices when eating out.
Quantities will vary according to age and appetite
Ongoing dietary assessment and monitoring is required to
Breakfast Low fat cereal (<2 g fat/100 g, per 30 g serving = 0.5 g ensure the diet remains nutritionally adequate. EFA and fat‐
fat) e.g. cornflakes, Rice Krispies with skimmed milk
soluble vitamin supplements continue to be needed. To achieve
Very low fat yoghurt (<0.2 g fat/100 g)
White bread* toast (no spreading fat) and jam/honey/
adequate calcium intake, minimal fat calcium sources should
marmalade be encouraged in the diet, e.g. skimmed milk (0.1% fat) and
Fruit juice very low fat yoghurt (<0.2 g fat/100 g). Haemoglobin and fer-
Lunch Sandwich made with bread*/bread roll* with filling ritin levels should be monitored in view of the low intakes of
of chicken/lean ham/tuna in brine or spring water/ haem sources (particularly red meat) in the diet.
low fat cheese spread and salad Adherence to a low fat diet can be difficult, and young
OR baked beans and jacket potato people and their families need ongoing support. As young
OR egg white omelette with peppers and mushrooms people get older and more independent, they need to learn
with boiled potatoes to manage the diet themselves. This requires them to under-
Fruit/jelly/very low fat yoghurt
stand the reasons for the diet as well as receiving education
Snack Fruit/vegetable sticks/suitable low fat snack items, on a practical level to enable suitable dietary choices as they
e.g. low fat cereal bar
move to adulthood.
Evening Chicken/turkey (light meat)/very lean beef (<5% fat)
meal with fat drained or removed/white fish
Vegetables or salad Learning points: hypolipoproteinaemias
Boiled/jacket/mashed potato or boiled pasta/rice/
chapattis (no fat) • ABL, HBL and CRD are very rare
Meringue and very low fat yoghurt/milk pudding • Treatment is a low LCT diet with supplementation of fat‐
made with skimmed milk
soluble vitamin and essential fatty acids
Bedtime Glass of skimmed milk • MCT can be used, but with caution in ABL
Low fat cereal with skimmed milk • Vitamin E is supplemented in very high doses, but plasma
levels remain low in ABL
*Check fat content of product.
Hyperlipoproteinaemias
Primary hyperlipoproteinaemias present due to genetic As many of the primary hyperlipoproteinaemias are very
disorders, whereas secondary hyperlipoproteinaemias are rare, only the two most prevalent disorders are discussed:
acquired due to another underlying disease or environmen- familial lipoprotein lipase (LPL) deficiency (type I hyperlipi-
tal factors, e.g. diabetes, obesity and excessive alcohol intake. daemia) and familial hypercholesterolaemia.
Familial lipoprotein lipase (LPL) deficiency
Protein LPL
Biochemical defect Defect in LPL gene causing decreased activity of LPL. Results in increase in chylomicrons, triglyceride, total cholesterol
and inability to clear dietary fat
Incidence of homozygous: 1 in 500 000–1 000 000 [93]
Clinical onset presentation, Heterozygous carriers are usually asymptomatic
features Homozygous: Presents in first year of life
Biochemical features:
• very high plasma TG, up to 10 000 mg/dL (114 mmol/L) [71] (normal fasting levels 0.5–2.2 mmol/L)
• high levels of CM, low HDL, low LDL, with normal VLDL
Clinical symptoms at presentation include:
• creamy blood
• abdominal pain
• eruptive xanthomas, hepatosplenomegaly and lipaemia retinalis
• pancreatitis
• immune dysfunction has also been hypothesised [94] in a case report of a child who appeared to develop
immunodeficiency with altered neutrophil function
Long‐term complications Episodes of pancreatitis can be life threatening.
and outcome The role of plasma TG as an independent risk factor for coronary heart disease (CHD) in the general population is
unclear due to insufficient evidence looking at TG in isolation from other plasma lipids [95, 96]. Kwiterovich [71] states
that premature atherosclerosis does not occur in LPL deficiency.
Hyperlipoproteinaemias 665
Acute management If there is pancreatitis at presentation, this will need to be treated foremost.
If there is no pancreatitis at presentation, chronic dietary management can be commenced.
Medical treatment Aim to control plasma triglyceride levels to avoid pancreatitis.
Dietetic management Low LCT diet
Adequate energy
MCT supplements
Fat‐soluble vitamins
EFA and LCPUFA supplements
Aim plasma TG <10 mmol/L
Monitoring – biochemical Total cholesterol, TG, LDL, HDL
and nutritional Liver function tests, albumin, clotting factors
Vitamins A, D, E, K, B12, folate, calcium, phosphate, iron
Pancreatic enzymes (amylase, lipase)
Monitoring tests Liver ultrasound, not always done routinely
Dietary management of LPL deficiency nutrient intakes [36]. Additional mineral supplements such
as calcium and iron may also be needed if the diet does not
The aim of dietary treatment is to control plasma triglyceride provide sufficient sources. Plasma levels are monitored to
levels and avoid pancreatitis. guide any adjustments that need to be made. Be aware that
fat‐soluble vitamin levels may be falsely elevated in the pres-
ence of high levels of circulating triglyceride.
Restricted LCT intake
Restriction of LCT to 5 g/day will result in optically clear
fasting serum and lowering of serum triglycerides. Such
severe fat restriction is difficult to maintain in the long term, EFA supplements are needed as requirements will not be
so fat allowance should be determined by individual toler- provided by the fat‐restricted diet. At the author’s centre,
ance. A restriction of dietary fat to 10%–15% of total energy, walnut oil is given to provide EFA and KeyOmega to pro-
or up to 25 g LCT fat/day, is usually sufficient to reduce vide LCPUFA to meet population requirements (p. 646).
plasma triglyceride levels and avoid pancreatitis [97, 98]. There are individual case reports of LPL deficient patients
Plasma triglycerides will not normalise; the aim is to main- responding to treatment with 15–30 g MCT oil or 4 g omega‐3
tain at a level <10 mmol/L, although a more realistic target fatty acids daily with a dramatic decrease in fasting plasma
for some will be <20 mmol/L provided there is no abdominal triglycerides [100–102]. One case was found to respond with
pain. Experience from the author’s centre suggests abdomi- an increase in mass and activity of LPL [100]. The mecha-
nal symptoms can occur with TG >15 mmol/L and pancreati- nism for these findings is not fully understood, but is likely
tis with TG >20–30 mmol/L or higher. The diet is similar to to be due to a unique genotype rather than the more common
that described for the hypolipoproteinaemias (p. 661). genetic defects seen in classical LPL [100].
MCT intake Acute episodes

MCT oil and supplements can be included in the diet as During episodes of acute abdominal pain or pancreatitis, a
MCT do not require chylomicron formation for transport strict minimal LCT diet providing <5 g/day should be com-
[98]. They are a useful energy source and can be added to the menced with adequate energy from MCT and complex
diet as discussed for the hypolipoproteinaemias (p. 662). carbohydrate (Tables 14.13 and 14.14).
As discussed on p. 664, prompt enteral feeding (oral/
nasogastric/nasojejunal) rather than extended periods of nil
Carbohydrate intake by mouth should be attempted in cases of pancreatitis [103,
Some centres in the USA advise reducing intake of simple 104]. The author’s experience of one patient without pan-
carbohydrate [98]. This approach is used in the general pop- creatitis, but with severe abdominal pain, was that a short
ulation where hypertriglyceridaemia is associated with high period (24–48 hours) of IV glucose fluids was all that could
carbohydrate diets [99]. In the UK restrictions on carbohy- be tolerated initially due to the pain. Skimmed milk and glu-
drate intake are not applied in children with primary cose polymer may be taken orally to support dietary intake.
hypertriglyceridaemia. If a child requires enteral tube feeding, ‘juice’‐style oral
nutritional supplements, e.g. PaediaSure Plus Juce, Ensure
Plus Juce, Fortijuce and Fresubin Jucy, can be given
Fat‐soluble vitamins (Table 12.5); these are fat‐free. Alternatively, a low LCT
Due to the low fat diet, fat‐soluble vitamin supplements (e.g. modular feed similar to that detailed in Table 30.11, but
Ketovite, Dalivit) are needed to provide UK recommended containing MCT such as Liquigen in place of some of the
glucose polymer, could be given. If PN is required due to Children and adolescents

intolerance of enteral feeds, lipid will need to be restricted. LCT restriction continues into childhood and adolescence.
Concerns about ensuring adequate energy intake as discussed
Infants for the hypolipoproteinaemias also apply in LPL deficiency.
A minimal LCT formula supplemented with MCT such as MCT supplements can be used to improve the energy content
Monogen or Lipistart can be given and is nutritionally and palatability of the diet as well as broadening choice. Issues
complete if given at age appropriate amounts. They include with dietary adherence are relevant in LPL deficiency, and it is
EFA and fat‐soluble vitamins, so additional supplements important that young people are enabled to take responsibil-
should not be needed. Partial breastfeeding (although a ity for their dietary choices, so they avoid complications such
source of LCT) may be possible in combination with a mini- as pancreatitis and nutritional deficiencies.
mal LCT formula, aiming to maintain TG levels <10 mmol/L.
Learning points: familial lipoprotein lipase deficiency
Weaning
When solid foods are introduced, a minimal LCT diet should • Treatment aim is to maintain TG <10 mmol/L to prevent
be followed as discussed for the hypolipoproteinaemias pancreatitis
(p. 663). Minimal LCT infant formula, Monogen or Lipistart, • Dietary treatment is a low LCT diet with MCT supple-
should continue during infancy. EFA and fat‐soluble vitamin ments, fat‐soluble vitamins and essential fatty acids
supplements will be needed as the volume of infant formula • Pancreatitis develops when TG are high
decreases as more food is eaten.
Familial hypercholesterolaemia (FH)
Protein LDL receptor

Defect LDL cholesterol uptake and clearance by hepatocytes is reduced, and so cholesterol accumulates with deposition in the blood
vessels, causing progressive atherosclerosis. Caused by a defect in the LDL receptor or defective binding of the LDL particles to
an intact receptor [105].
Genetics Autosomal dominant inheritance. Mutation in low density lipoprotein receptor (LDLR) or apolipoprotein B‐100 (APOB)
or proprotein convertase subtilisin/kexin type 9 (PCSK 9) genes [77]. FH exists in homozygous and heterozygous forms.
See p. 507 for an explanation of inheritance. The term homozygous FH is often used to include compound heterozygous
FH [106].
Screening Population screening strategy through cascade testing following a positive FH diagnosis. Early detection of FH is important
as prompt treatment is likely to be more effective. Screening by measurement of serum cholesterol is most effective if
done in early childhood between 1 and 9 years when a high detection rate can be achieved with a false positive of only
0.1% [107].
The 2017 National Institute for Health and Care Excellence (NICE) Clinical Guideline 71 [106] recommends that:
• primary care records are systematically searched to identify people younger than 30 years with a total cholesterol
concentration >7.5 mmol/L and people 30 years or older with a total cholesterol concentration >9.0 mmol/L; this will enable
early detection of those at highest risk of FH
• in an index case a diagnosis of FH should be made using the Simon Broome Criteria or Dutch Lipid Clinic Network (DLCN)
criteria; an outcome of possible or definite FH on the Simon Broome criteria, or a DLCN score >5, should pre‐empt referral
for DNA testing
• if a genetic diagnosis is made, cascade screening of first‐, second‐ and third‐degree biological relatives should be undertaken
• in children at risk of FH due to an affected parent, DNA tests should be carried out before 10 years of age; if confirmed,
children should be referred to a specialist centre with management expertise for this age group
Homozygous FH is more severe and much less common. Prevalence is at least 1 in 500 (perhaps up to 1 in 250) for heterozygous
FH and 1 in 1 000 000 for homozygous FH [105].
Clinical onset Presenting features include elevated levels of LDL cholesterol and total cholesterol in the blood and deposits of cholesterol in the
presentation, peripheral tissues, tendon and skin xanthomas and corneal arcus. Total cholesterol will be >6.7 mmol/L or LDL cholesterol
features >4.0 mmol/L in a child <16 years with heterozygous FH. If total cholesterol is >11 mmol/L, homozygous FH can be suspected.
Most children with heterozygous FH are clinically asymptomatic [105] but can begin to show signs of atherosclerosis, e.g.
endothelial dysfunction, even before puberty [108].
Long‐term Premature atherosclerosis leading to cardiovascular disease (CVD). Early identification allows initiation of therapy in order to
complications prevent CVD and can minimise progression [105, 108]. Heterozygous FH causes a >50% risk of CHD by the age of 50 years in
and outcome men and at least 30% in women by the age of 60 years [109–111]. In homozygous FH there can be either a total absence of or
defect in LDL receptors, so individuals usually develop coronary artery disease in the second decade; severity of
hypercholesterolaemia may determine disease course (based on the outcome of a small number of cases) [112].
Acute Treatment is a combination of dietary intervention, drug therapy and lifestyle modification. More aggressive treatment, such as
management plasma LDL apheresis or liver transplantation, may need to be considered for homozygous FH [112, 113].
Hyperlipoproteinaemias 667
Medical The aim of treatment for both heterozygotes and homozygotes is to lower plasma LDL levels and reduce the risk of CVD [106].
treatment The aim for adults is to reduce LDL cholesterol by 50%; no specific target is given for children.
Statins (HMG‐CoA reductase inhibitors):
• The first choice of drug therapy [114] and offered lifelong
• NICE recommends statins offered to children with FH by the age of 10 years or at the earliest opportunity thereafter; not all are
licensed for this age group
• Systematic reviews [115–117] summarise that statins are well tolerated and effective (reduce LDL cholesterol levels by
20%–40%) and are not associated with increased risk of adverse effects in children (aged 8–18 years) in the short term
• The need for longer‐term studies is recognised
Other lipid lowering drug therapies:
• bile acid sequestrants: bind bile acids in the intestine, causing upregulation of bile acid synthesis and, therefore, utilisation of
cholesterol
• fibrates: reduce triglyceride levels and increase HDL
• ezetimibe: a cholesterol absorption inhibitor that impairs dietary and biliary cholesterol absorption from the small intestine [118]
These may all be used in cases of intolerance to statins or in combination with statins for management of homozygotes or
exceptional circumstances, such as a family history of heart disease at a very young age. Until the use of statins, bile acid
sequestrants were the preferred treatment in children; however, due to poor tolerance long‐term adherence was low [105].
Dietetic NICE Clinical Guideline 71 recommends a lipid‐modified diet. Due to insufficient data on the effectiveness of lipid lowering diets
management in FH, this recommendation is based on three high quality reviews of dietary interventions in the general population [119–121].
NICE Clinical Guideline 71 [106]:
• total fat intake 30% or less of total energy intake
• saturated fats 10% or less of total energy intake
• intake of dietary cholesterol <300 mg/day
• saturated fats replaced by increasing the intake of monounsaturated and polyunsaturated fats
Additional recommendations:
• include at least five portions of fruit and vegetables a day
• eat two portions of fish a week, one of which should be oily fish; do not routinely recommend omega‐3 fatty acid
supplements
• if food products containing plant stanols and sterols are consumed, these products need to be taken consistently to be effective
If bile acid sequestrants are used long term, then supplementation with fat‐soluble vitamins (A, D and K) and folic acid should be
considered.
Monitoring – Fasting total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides
biochemical and Liver enzymes (transaminases), bilirubin and CK if on statins
clinical Weight and body mass index
Carotid artery assessment, carotid intermedia thickness and carotid plaque score may be measured to monitor progression of
disease in homozygous FH; it is not routinely monitored in clinical practice in heterozygous FH
Monitoring – If a modified lipid‐lowering diet is followed, fat‐soluble vitamin supplements should not be required; however, it is assiduous to
nutritional check fat‐soluble vitamin levels annually. If lean red meat is restricted, then iron stores need to be monitored. Calcium intakes
should be assessed, and supplements given if there is poor intake of low fat dairy products.
Clinical NICE Clinical Guideline 71 www.nice.org.uk/guidance/CG71 [106]
management
guideline
Parent support www.heartuk.org.uk/ [122]
group
Lifestyle modification Dietary management of FH
It is important that families are given information about Total fat intake <30% of energy intake
exercise, smoking, alcohol and weight management along-
Assessing each child’s diet individually is essential. Some
side lipid‐modifying drug therapy and dietary intervention.
families may already follow a ‘healthy’ diet and achieve the
Where relevant, support should be given to individuals
recommended guidelines for total fat intake because a p arent
about weight reduction to achieve a healthy weight, as obe-
has FH. Others will require education and help to interpret
sity is a further risk factor for CHD. Further details of the
food labels. As a guide and in line with NHS Live Well, a
lifestyle interventions can be found in the NICE CG71 [106]
high fat food contains >17.5 g fat/100 g, and a low fat food
with some practical resources including increasing activity
contains <3.0 g fat/100 g or 1.5 g fat/100 mL for liquids [123].
levels and healthy eating recipe ideas on the NHS Live Well
In order to achieve this, simple adjustments in the diet can be
website www.nhs.uk/live‐well/ [123] and Heart UK www.
made, such as using low fat dairy products. Full fat milk
heartuk.org.uk/ [122].
(3.5% fat) can be replaced with skimmed milk (0.1% fat), 1% total and LDL cholesterol [99]. As a guide, foods low in SFA
fat milk or semi‐skimmed milk (1.7% fat). Decreasing the contain ≤1.5 g/100 g or 0.75 g/100 mL for liquids [123]. Foods
intake of hidden sources of fat in manufactured foods, such high in SFA contain ≥5.0 g/100 g and include foods such as:
as from cakes and biscuits, will help in achieving the target
• fatty cuts of meat, meat products such as sausages and
fat intake. Some centres advise reducing intake of red meat
pies
and replacing with alternative protein sources such as beans,
• butter, ghee and lard
pulses, poultry (light meat, no skin) and white fish (not
• cheese, especially hard cheese
fried). Suggestions for making suitable food choices when
• cream, soured cream and ice cream
eating out should also be given as required. Table 30.13 gives
• savoury snacks, e.g. crisps and salted nuts
a suggested meal plan for a 10‐year‐old boy with newly
• chocolate confectionery, biscuits, cakes and pastries
diagnosed FH.
• palm oil, coconut oil and coconut cream
Saturated fatty acids (SFA) intake <10% of energy intake Dietary cholesterol <300 mg/day
Meta‐analyses have shown that manipulating the type of fat A reduction in dietary cholesterol has only a small effect on
in the diet of the general population can modify serum lipid plasma cholesterol levels. This is thought to be due to the
profiles [99, 121]. Changes in plasma total cholesterol con- body’s feedback mechanism that alters endogenous produc-
centrations are largely achieved through changes in LDL tion depending on exogenous intake [121]. Dietary choles-
level [124]. An increased intake of SFA raises plasma levels of terol is found in eggs, high fat dairy products, shellfish and
offal. Foods containing dietary cholesterol need not be
restricted unless they also have a high SFA content. There is
no recommended limit on egg consumption. They can be
Table 30.13 A suggested meal plan for a 10‐year‐old boy newly
diagnosed with familial hypercholesterolaemia. included in a healthy balanced diet, but the method of cook-
ing needs to be considered, boiling or poaching instead of
Weight = 31 kg (50th centile). Height = 143 cm (75th centile) frying or scrambling with butter. Reducing the SFA intake
Breakfast Large bowl of low fat breakfast cereal with skimmed often has the secondary effect of decreasing dietary choles-
milk and chopped fruit terol intake.
2 slices wholemeal toast/bagel + olive oil‐based
margarine or margarine enriched with plant stanol/
sterols + honey Increasing monounsaturated fats and
Glass of water polyunsaturated fats
Mid‐morning Banana Polyunsaturated fats (PUFA) and monounsaturated fats
snack Glass of water
(MUFA) have been shown to have a hypocholesterolaemic
Lunch Tuna in spring water (drained) with ‘extra light’ effect when substituted for SFA in the diet in the general
mayonnaise and cucumber slices in a tortilla wrap* population [97, 99]. Replacement of SFA with PUFA reduces
OR a mini baguette filled with low fat hummus and
both HDL and LDL cholesterol, whereas MUFA reduces
tomato slices
Low fat crisps* OR low fat cereal bar* LDL, but has less of an impact on HDL. Omega‐6 PUFA are
Carrot or celery sticks found in sunflower oil, corn oil and soya oil. These oils can
Apple replace saturated fats and oils in the diet for use as a spread
Low fat yoghurt and in cooking. LCPUFA from fish oils (omega‐3 fatty acids),
Glass of water compared with other PUFA, cause HDL cholesterol to rise
Mid‐afternoon 1 slice wholemeal bread toast + olive oil‐based margarine and TG to decrease [77]. Oily fish such as pilchards, mack-
snack or margarine enriched with plant stanol/sterols erel or salmon should be included in the diet at least once a
Handful of grapes week. MUFA are found in avocados, olive oil, rapeseed oil (a
Diluted squash
cheaper alternative to olive oil) and fat spreads made from
Evening meal Chicken curry (using light meat) with onions, green these oils.
beans in a tomato‐based sauce cooked in rape seed
oil with boiled rice (white or brown) OR grilled
salmon and new potatoes with steamed carrots, peas
and sweetcorn
Plant stanols and sterols (phytosterols)
Meringues and low fat yoghurt with chopped Sterols and stanols are components of cell membranes and
strawberries OR fruit and low fat custard made with
produced in both animals and plants. All sterols and stanols,
skimmed milk
Glass of water
whether animal or plant, contain a sterol ring (in stanols
this ring is saturated, in sterols it is unsaturated) [125].
Bedtime Cereal* and skimmed milk OR hot chocolate using
Phytosterols, therefore, resemble cholesterol (an animal
low fat drinking chocolate and skimmed milk OR a
glass of skimmed milk sterol), and their ingestion competes with cholesterol absorp-
tion in the intestine [126]. Several small and short‐term stud-
*Check nutrition label for fat content. ies have shown that incorporation of phytosterol‐containing
Infant Onset Lysosomal Acid Lipase Deficiency (LAL‐D) 669
foods in the diet of children with FH reduces LDL choles- but soluble fibre, e.g. oats or linseed, may also have a lipid‐
terol by 10%–15% [108, 127]. This was achieved by taking modifying effect. Good quality evidence in FH is limited;
2.3 g/day plant sterol and 2.8 g/day plant stanol as enriched one small study in adults with FH showed a significant
spreads. They need to be taken consistently to be effective. reduction in LDL [126], which is consistent with studies in
The opinion of NICE [106] is that the evidence is insufficient hypercholesterolaemia [128]. Beta‐glucan, found in oats,
to draw definitive conclusions regarding effectiveness of may lower cholesterol by the formation of a gel in the diges-
phytosterols, and as longer‐term use is very limited, further tive tract that binds to cholesterol and bile salts, so prevent-
research is recommended. No evidence of associated vita- ing cholesterol absorption [129]. Some starchy foods can be
min deficiencies has been identified with the use of plant bulky and increase satiety levels and may have the unde-
sterols or stanols in children. sired effect of reducing energy intake in some children.
A variety of phytosterol‐enriched products can be found
in supermarkets, the Flora ProActiv and Benecol ranges
Other supplements
being widely available. Esters of sterols and stanols tend to
be used for food fortification as they are more easily incorpo- Psyllium‐enriched cereal, garlic, omega‐3 fatty acids and soy
rated into food. Products vary in the amount they contain, protein are just some of the other foods or supplements that
e.g. 10 g of fortified spread contains 0.5–0.7 g of sterol/stanol have been assessed for benefits in FH. The studies that have
per 10 g and a serving (68–100 g) of yoghurt drink contains been undertaken to date are small and inconclusive, and no
2 g sterol/stanol. Yoghurts, bars and chewy sweets are also recommendations for practice can be made currently.
available. These products are a significant expense for fami-
lies as they need to be consumed regularly.
Learning points: hypercholesterolaemia
Fruit and vegetables • NICE Clinical Guideline 71 provides recommendations on

Families should be encouraged to increase their intake of the management of familial hypercholesterolaemia [106]
fruit and vegetables (fresh, frozen or tinned), aiming for five • Treatment aims to reduce total and LDL cholesterol levels
portions a day and a wide variety. For children, as a guide, a through dietary intervention, drug therapy and lifestyle
portion is the amount that fits in the palm of their hand. Fruit modification
juice (150 mL) counts as one portion a day. • Statins are a safe and effective treatment for children with
FH; they should be offered to children by the age of 10 years
or the earliest opportunity [106]
Complex carbohydrates • Adherence with dietary intervention is variable as symptoms
Starchy foods such as cereals, bread, pasta, rice, chapattis, are not experienced during childhood; motivation may be
noodles and potatoes should be included at most meals. higher in families with a history of parental death from CHD
Encouraging sources of fibre is beneficial for general health,
Infant Onset Lysosomal Acid Lipase Deficiency (LAL‐D)
Fiona J. White
This disorder is also known as Wolman disease.

Enzyme Lysosomal acid lipase (LAL)
Biochemical defect Deficiency of LAL prevents the normal lysosomal degradation of cholesteryl esters and triglycerides to produce free
cholesterol and fatty acids, which are released into the cell’s cytoplasm. To compensate for the apparent lack of
cytoplasmic free cholesterol, it is thought there is upregulation of endogenous cholesterol synthesis causing increases
in blood lipid levels and further lysosomal storage [130].
Clinical onset presentation, Infant LAL‐D is a multisystem disorder in which lipids accumulate in organs and tissues, particularly the liver,
features gastrointestinal tract, spleen, macrophages, blood vessel walls and lungs:
• onset of gastrointestinal symptoms, diarrhoea and vomiting, from the first weeks of life resulting in cachexia and
severe growth failure and at presentation fulfil the WHO definition for severe acute malnutrition [131, 132]
• distended abdomen due to hepatosplenomegaly, progressing to liver failure without treatment
• anaemia
• deranged clotting (vitamin K deficiency) and other fat‐soluble vitamin deficiencies (A, D, E)
• calcified adrenal glands
• systemic inflammatory disease with high ferritin levels; some cases may have been thought to have
haemophagocytic lymphohistiocytosis (HLH) at presentation but is in fact secondary to infant onset LAL‐D [133]
Long‐term complications Infant LAL‐D has only had a licenced treatment, enzyme replacement therapy (ERT), since 2015, so long‐term
and outcome outcome data is not yet available:
• historically infants with LAL‐D died before a year of age, median 3.7 months [134]
• with ERT and dietary therapy, survival and growth are improving [131, 135, 136]; the oldest patient surviving of
those in the initial clinical trial is 7 years old, functioning normally and attending mainstream school (as of May
2019, author’s centre)
• although there is improvement in gastrointestinal function, severe dietary fat‐restriction remains necessary
• oral feeding aversion and reliance on long‐term enteral tube feeding is common
Acute management At diagnosis most infants will be extremely sick due to the underlying disease process and malnutrition. Acute
management will depend upon the individual’s clinical state, but as a minimum will include:
• stopping all dietary lipid intake
• correcting any dehydration
• correcting any haematological and clotting abnormalities
• starting ERT as soon as possible
Drug treatment ERT: weekly IV infusion of KANUMA® (sebelipase alfa)
Supportive treatment for any associated medical issues
Fat‐soluble vitamin supplementation
Dietetic management Dietary management is essential alongside ERT. It is based on management of the consequences of abnormal lipid
Rationale storage due the underlying enzyme defect including:
This is the practice of the • lipid storage in macrophages within the lamina propria of the small intestine results in blunting and expansion of
author’s centre, which other villi; digestive enzymes and absorptive capacity are reduced causing decreased digestion and absorption of
centres treating infant onset nutrients and persistent frequent diarrhoea [137]: minimal fat, amino acid, monosaccharide feed
LAL‐D have also used • evidence of protein losing enteropathy (increased faecal alpha‐1‐ antitrypsin) and gut inflammation (increased
faecal calprotectin): high protein intake
• persistent vomiting, probably due to gut dysmotility, and abdominal distension due to hepatosplenomegaly and
‘intestinal gas’ compromise the feed volume tolerated: small, frequent or continuous tube feeds are better tolerated
Further details on the practical dietary management are discussed on p. 670:
Nutritional monitoring • growth: weight, length, occipital frontal circumference (OFC) and mid‐upper arm circumference (MUAC) (probably
the best growth parameter to measure as it is not affected by organomegaly)
• gastrointestinal symptoms
• nutritional bloods including:
⚬⚬ fat‐soluble vitamin status – monthly until levels have normalised and then 3 monthly
⚬⚬ red cell EFA status – 3 monthly initially
Emergency regimen Onset of increased vomiting and/or diarrhoea to the child’s norm can rapidly lead to dehydration and should be
treated quickly:
• stop usual feeds and start oral rehydration solution (ORS) at 120% of child’s usual maintenance fluids
• take to the emergency room for assessment of dehydration (weight loss), hypernatraemia (urea and electrolytes
[U&Es]), acidosis (blood gas):
⚬⚬ if blood results are normal, continue with ORS, daily weights and U&Es; reintroduce feeds after 24 hours
⚬⚬ if blood results are abnormal, stop enteral feeds. Treat with IV fluids including correcting deficit and any
hypernatraemia. Reassess every 12–24 hours. Once diarrhoea reverts to ‘normal for individual’, reintroduce usual
feeds; this can be over 24 hours, titrating with IV fluids. If diarrhoea persists, but weight regained, U&Es and
blood gas normal, introduce enteral ORS and reassess in 24 hours
• if not re‐established on usual feeds within 3 days, consider modified PN as nutritional status can decrease quickly
Clinical management Not yet published
guideline
References Jones SA, Rojas‐Caro S, Quinn AG et al. Survival in infants treated with sebelipase Alfa for lysosomal acid lipase
deficiency: an open‐label, multicenter, dose‐escalation study. Orphanet J Rare Dis, 2017, 12(1) 25 [135]
Jones SA, Valayannopoulos V, Schneider E et al. Rapid progression and mortality of lysosomal acid lipase deficiency
presenting in infants. Genetics Med, 2015, 18 452 [134]
Parent support group www.mpssociety.org.uk/
• protein: minimum 4 g/kg/day to account for increased

Dietary management of infant LAL‐D losses and rapid catch‐up growth
• lipid: it is probably prudent to avoid giving any fat before
The following is based on the author’s practice and experi- ERT starts:
ence with the largest single cohort of infant onset LAL‐D ⚬⚬ LCT is very restricted to provide only EFA and
worldwide and has been used by other centres. LCPUFA (p. 646)
Nutritional intake aims, at least initially, are to provide ⚬⚬ MCT may be tolerated as it is thought to be mainly
through modified feeds: absorbed through the hepatic portal vein directly to
Infant Onset Lysosomal Acid Lipase Deficiency (LAL-D) 671
the liver where it used for energy. Intakes of up to with onset of increased gastrointestinal symptoms, wors-
2 g/kg/day have been used, at least initially, to pro- ening liver function and declining growth.
vide an additional energy source For patients who remain fully reliant on enteral feeds,
• carbohydrate: usually as glucose polymer, up to 20% LCT intake can be restricted to that providing for EFA
concentration. If increased gradually, from an initial 10%, and LCPUFA requirements. In those who eat LCT, intakes
higher concentrations are tolerated. High CHO concen- should be as minimal as possible, e.g. 0.5 g/kg/day to a
trations are required for catch‐up and maintenance of maximum of 5 g/day
growth as fat energy intake is very restricted • MCT: it is unclear whether some MCT is tolerated or not
• sodium: 6–8 mmol/kg/day. Infants usually have low long term. Small amounts, a maximum of 2 g/kg/day,
plasma sodium levels and are likely to have increased have been used in infancy and appear to be tolerated. In
losses due to diarrhoea. Glucose requires sodium for some cases where growth has remained poor, even with
absorption, so it would, therefore, seem that a high glucose increased total energy intake, removing MCT has
intake will require additional sodium [138]. Urinary improved growth even if the energy deficit is not made
sodium measurements can provide a guide to sufficiency up with additional carbohydrate or protein energy [131]
of sodium status. Where there are continued fluid and
electrolyte losses, i.e. continued diarrhoea, maintaining a
Initial dietary management
urinary sodium–potassium ratio of at least 2:1 is important
[139]. The aim is to maintain urinary sodium >20 mmol/L
Change of feed to an amino acid, monosaccharide (glucose
• micronutrients: ensure meeting reference nutrient
polymer) and minimal LCT feed with moderate MCT
intakes (RNI) [36]. Additional supplements of fat‐soluble
content:
vitamins are often required
• fluids: tolerance of feed volume may be compromised • In the UK this requires individualised modular feeds as no
with an enlarged abdomen due to hepatosplenomegaly, suitable amino acid (or peptide)‐based commercial feeds
and large volume feeds may affect respiratory function. are suitable, all having too high LCT and total fat content.
Small frequent feeds or continuous tube feeds are often Commercial feeds that are available in some countries are
better tolerated Vivonex T.E.N. and Tolerex (Nestle). Practical details for
modular feed are given in Tables 30.14 and 30.15
• Many infants will have intestinal failure and, even when
Lipid intakes long term changed to an appropriate amino acid‐based feed, will
continue to have diarrhoea and vomiting and become
It is not known how much fat can be tolerated. Despite ERT dehydrated. There should be a prompt decision to stop
and minimal fat intakes, there appears to be ongoing lipid enteral feeds and start modified PN
storage in the gut:
Modified PN aiming to provide:
• LCT: tolerance to dietary LCT appears extremely limited.
In the author’s and others’ experience, increases in LCT • protein: 4 g protein (0.64 g nitrogen)/kg/day
either intentionally, in very small increments, or inad- • glucose: start with approximately 12 g/kg/day and
vertently have resulted in worsening clinical condition increase by 2 g/kg/day up to approximately 25 g/kg/day;
Table 30.14 Amino acid, monosaccharide (glucose polymer) and minimal LCT feed with moderate MCT content (per 100 mL, based on full feeds
of 100 mL/kg/day).
Amount Energy Protein CHO LCT MCT Na K

g kcal (kJ) g g g g mmol mmol
Complete Amino Acid Mix (Nutricia) 5 16 (67) 4.1 0 0 0 0 0

Glucose polymer, e.g. Vitajoule 18 68 (284) 0 17.1 0 0 0 0
(Vitaflo)
Liquigen (Nutricia) 4 18 (75) 0 0 0 2 0.05 0
ORS, e.g. Dioralyte powder (Sanofi) 2.5 7 (29) 0 1.8 0 0 6 2
KeyOmega (Vitaflo) 4 g* 2 (8) 0 0.3 0.08 0 0.06 0
Paediatric Seravit (Nutricia) 5 1 (4) 0 1.3 0 0 0 0
+ water to 100 mL Per 100 mL 112 (467) 4.1 20.5 0.08 2 6.1 2
ORS, oral rehydration solution.

*Can be added to 1 feed per day or to the full 24 hour volume.
Table 30.15 Commercially available amino acid, monosaccharide and minimal LCT formulas (available in some countries outside UK).
Per 100 mL Energy Protein CHO LCT MCT Na K

Standard dilution kcal (kJ) g g g g mmol mmol
Vivonex T.E.N.
(Nestle Health Sciences) 100 (420) 3.83 20.6 0.3 0 3.2 2.3
Tolerex
(Nestle Health Sciences) 100 (420) 2.05 22.6 0.2 0 2.2 3.0
this will depend on energy needs to gain weight and (Abbott), Fortijuce (Nutricia) and Fresubin Jucy Drink
grow. Blood glucose levels should be monitored (Fresenius) (Table 12.5)
• lipid: avoid any lipid until ERT has been started:
Probiotics have helped abdominal distension, due to large
⚬⚬ restrict fat to 1 g/kg/day using a lipid source con-
amounts of ‘gas’ seen in many infants and older children.
taining MCT, e.g. SMOF (30% MCT); there are other
MCT lipid emulsions available Weaning onto a very low fat diet can start around 6 months of
⚬⚬ account for the lipid content of the fat‐soluble vitamin age or once re‐established on enteral feeds:
source in the total lipid intake
• sodium: increased requirements, usually at least 6 mmol/ • suitable very low fat weaning foods (Table 30.3, exclud-
kg/day ing the advice regarding overnight feeding)
• continuing a minimal fat diet as weaning progresses;
Once diarrhoea subsides (vomiting usually stops too), for discussion of long‐term lipid intake, see p. 671.
trophic feeds (1 mL/kg/hour) of ORS should be started to Tables 14.13 and 14.14 provide information on free foods
maintain gut integrity either by continuous enteral feed or for a minimal LCT diet and LCT content of foods.
orally if the infant will take it, divided into 6–8 feeds over the Table 30.5 gives information on a minimal LCT diet, and
day (total 24 mL/kg/day). This fluid should be additional to a sample minimal fat meal plan containing ≤10 g LCT is
that provided by the PN. given in Table 30.12. Portion sizes may need controlling
Re‐establishing oral/enteral feeds once growth rate is to maintain the daily LCT allowance. Parents can be
satisfactory: taught how to calculate portion size from nutritional
• Enteral feeds are started, using an amino acid‐ and information given on food labels (p. 649)
monosaccharide‐based, minimal LCT and MCT feed as • depending upon growth and intake of solids, it may be
described above and in Table 30.14 possible to reduce feed volume; generous protein intakes
• The feed should be increased gradually as tolerated, e.g. >RNI [36] should probably be continued
by 1–2 mL/hour every 24–48 hours as tolerated • the addition of fibre to feeds should be considered if
• Decrease PN as enteral feeds are increased the child does not eat any significant amount; in older
children who no longer have watery diarrhoea, but
It is important to be aware that vomiting and increased have unformed stools, the addition of fibre has helped
stool output will occur with the reintroduction of oral/ • oral feeding aversion is common, particularly if there has
enteral feeds. Feeds should not be decreased unless either been a very protracted period of frequent vomiting
dehydration is occurring (indicated by significant weight loss
or biochemical evidence) or MUAC is static or decreasing. Learning points: infant onset lysosomal acid lipase
deficiency
Ongoing dietary management
• Treatment is a combination of enzyme replacement and
Introduction of whole protein, disaccharide‐containing minimal fat feeds dietary therapy
can be considered once gastrointestinal symptoms are very much • Nutritional therapy is complex
reduced, and growth is satisfactory. This may be after many • Any changes in dietary therapy must be made quickly if
months or even years. Feed changes should be made slowly, things are going wrong and slowly and gradually when
titrating with the current feed, e.g. starting with 10% of the new things are going well
feed and 90% of the current feed with 10% increases weekly as • Treated infant onset LAL‐D is a new phenotype; knowledge
tolerated. Some may not tolerate the change and get onset of and evidence for best management is being gained; consen-
increased diarrhoea; the introduction should be stopped and a sus guidelines on management are in progress
return to the previously tolerated feed. Suitable formulas would be:
• Low Fat Module (Nutricia), basic‐f (Milupa), minimal fat
feeds (Table 30.2) References, further reading, guidelines, support groups
• a modular feed based on skimmed milk powder and other useful links are on the companion website:
• fat‐free ‘juice‐style’ enteral supplements (>1 year age),
e.g. PaediaSure Plus Juce (Abbott), Ensure Plus Juce
31
Marjorie Dixon
Emergency Regimens for Inherited
Metabolic Disorders
Introduction management for use by an emergency department or

aediatric assessment unit/ward. They are due to be
p
This chapter provides information on emergency regimens updated in 2020.
(ER), which form an essential part of the management of
some disorders of intermediary metabolism, both the intoxi
cation type and those involving energy metabolism (p. 508). Principles of the emergency regimen
Idiopathic ketotic hypoglycaemia (IKH) is also included in
this chapter. For metabolic disorders treated by ketogenic The ER provides an exogenous energy source to promote
diets, e.g. glut 1 deficiency syndrome (GLUT1DS) or pyru anabolism and:
vate dehydrogenase deficiencies (PDHD), illness and excess
ketone management plans are discussed elsewhere (p. 344). • prevent an energy deficit and hypoglycaemia when
For some inborn errors of intermediary metabolism, any energy substrates cannot be produced from their usual
physiological stress situation, such as intercurrent infection, metabolic pathways, e.g. glucose from glycogenolysis
surgery or trauma, combined with a poor oral intake and and/or gluconeogenesis in glycogen storage disorders,
fasting can precipitate severe metabolic decompensation ketones in defects of fatty acid oxidation and glucose
with possible neurological sequelae. Metabolic decompensa via gluconeogenesis in fructose 1,6‐bisphosphatase
tion, the accumulation of disorder specific toxic metabolites deficiency
causing metabolic encephalopathy, is primarily a c onsequence • reduce production of toxic metabolites from protein and
of the effects of catabolism and/or the failure to utilise or amino acid catabolism, e.g. ammonia in urea cycle disor
produce sufficient energy. Under normal conditions, as ders (UCD), leucine in maple syrup urine disease
fasting continues, glycogen stores are depleted, and gluco (MSUD) and organic acids in methylmalonic acidaemia
neogenesis and ketogenesis become the main energy supply. (MMA), propionic acidaemia (PA), isovaleric acidaemia
This process occurs more rapidly in infants and younger chil (IVA) and glutaric aciduria type 1 (GA1)
dren. To help prevent metabolic decompensation, an ER is • reduce production of potentially toxic metabolites from
given to provide energy and to minimise fasting in situations lipolysis, e.g. accumulation of long chain acyl carnitines
when dietary energy intake is reduced, commonly illness [1]. and free fatty acids in long chain fatty acid oxidation
The correct use of ER can be extremely effective and is known disorders
to reduce hospital admissions and episodes of metabolic
The child’s usual metabolic treatment medicines are con
decompensation [2, 3].
tinued but may temporarily be increased in some disorders
to help reduce accumulation of toxic metabolites, e.g.
Emergency regimen guidelines nitrogen scavengers to prevent hyperammonaemia in UCD,
l‐carnitine in GA1 to form glutarylcarnitine and so prevent
Disorder specific emergency regimen guidelines can be high concentrations of glutaric acid. Medicines are
accessed from www.bimdg.org. These provide informa also adjusted based on results of blood levels monitored
tion on the disorder and intravenous (IV) and oral ER during illness, e.g. blood gases in organic acidaemias (OAA).

674 Emergency Regimens for Inherited Metabolic Disorders
Some blood tests can be monitored at home, such as glucose Fat

and ketones, and help in making decisions about ongoing
management. Trials are currently under way to assess the Fat can provide an additional energy source but may be less
use of home blood ammonia monitors. Additional medicines well tolerated, particularly in the child who is vomiting as
are given to treat the underlying illness, such as antipyretics gastric emptying will be delayed. However, some metabolic
for fever. centres successfully use a protein‐free feed containing fat,
Disorders requiring ER are described in (Table 31.1) as: such as Energivit, in OAA and UCD. The ER for MSUD and
• standard ER only GA1 may contain fat from the protein substitute, protein‐
• standard ER with disorder specific instructions, such as free milk substitute or Calogen. Fat (long and/or medium
branched chain-free amino acids in MSUD, additional chain) is contraindicated in some disorders of fatty acid oxi
fluids in MMA. Disorder specific therapies are described dation (Chapter 30).
in the chapters detailing the treatment of these disorders
• non‐standard ER for citrin deficiency (p. 589), infantile Fluids
onset lysosomal acid lipase deficiency (Wolman disease)
(p. 669) The daily fluid volume of glucose polymer solution given
depends on age, weight and clinical condition of the child.
Detailed information about disorders and management
The suggested figures are maintenance fluid requirements
are provided in the related chapter.
(Table 31.2). Higher fluid volumes will be needed in certain
circumstances such as dehydration caused by diarrhoea
Composition of emergency regimens and/or vomiting, rhabdomyolysis with myoglobinuria in
long chain fatty acid oxidation disorders (LC‐FAOD), and in
The standard ER is a solution of glucose polymer, simple to MMA to prevent dehydration and protect the kidneys.
administer, rapidly absorbed, usually well tolerated and
suitable for most disorders. The carbohydrate (CHO) con Oral rehydration solutions
centration (10%–25%) of the solution given depends upon
the age of the child, with the lowest concentrations given to In cases of acute diarrhoea, the European Society of Paediatric
infants and younger children (Table 31.2). The standard Gastroenterology, Hepatology and Nutrition (ESPGHAN)
ER must not be continued for long periods of time (ideally [7] recommends oral rehydration for 4 hours, reassessment
24–48 hours) because it does not provide adequate nutrition. and then a return to normal diet. A longer period of rehydra
If use is prolonged and/or frequent, protein depletion, tion may be necessary. The energy content of oral rehydra
particularly in children on low protein diets, can develop tion solutions (ORS) is very low (approximately 7 kcal
surprisingly rapidly. Severe lactic acidosis caused by acute [30 kJ]/100 mL) and, therefore, insufficient to prevent catab
thiamin deficiency has been reported in two patients with olism. If an ORS is prescribed for a metabolic patient, then
PA who had high energy parenteral nutrition (PN) to restore parents need to seek advice from their metabolic team about
anabolism, but no vitamins were given [4]. using this alongside the ER. It is likely that any metabolic
child with gastroenteritis will require admission to hospital
Energy for IV fluids. For mild gastroenteritis reconstituted ORS
sachets can be given in addition to the standard ER feeds.
The precise energy requirements to prevent catabolism in met ESPGHAN recommends an osmolality of 200–250 mOsm/kg
abolic patients during illness are not known. Energy require H2O for an ORS; adding glucose polymer would increase the
ments increase during illness and specifically with a fever, so osmolality. Too concentrated a solution of glucose polymer
they are likely to exceed the child’s usual energy intake. will be hyperosmolar, worsen diarrhoea and exacerbate the
Bodamer et al. [5] reported that resting energy expenditure effects of the illness. ORS with glucose polymer added to a
was increased by up to 30% in two children with MMA during final concentration of 10% CHO has an osmolality of approx
acute illness. At lower CHO concentrations, standard ER imately 320 mOsm/kg H2O. Such a feed will be low in energy
solutions do not always provide the estimated average
and may not be suitable for all patients. Van Hove et al. [2]
requirement (EAR) for energy for age [6]. Therefore, a higher report successful use of such feeds in patients with mild
concentration of CHO or greater volume may be necessary diarrhoea. In addition, generous amounts of sodium will be
to prevent catabolism. The standard ER may, however, be provided from medicines such as sodium benzoate in UCD,
adequate to prevent hypoglycaemia providing feeding is
sodium bicarbonate in MMA and ketone bodies in multiple
frequent. Van Hove et al. [2] recommend higher concentrations acyl‐CoA dehydrogenation deficiency (MADD).
of glucose polymer solutions be given to younger children to
provide more energy (Table 31.2). Enteral ER is preferable to Practical provision of ER
IV management as higher CHO concentrations, therefore,
more energy can be given and it is less invasive. Nevertheless, Glucose polymer is available as a powder, e.g. Maxijul,
IV fluids are essential in certain circumstances, such as vomit Polycal, and Vitajoule. Pure liquid glucose polymer solu
ing, metabolic acidosis and hyperammonaemia seen in OAA. tions such as Polycal liquid have a very high CHO content
Practical Provision of ER 675
Table 31.1 Inherited metabolic disorders requiring an emergency regimen.
Emergency regimen
Disorder group Disorder Usual medicines and doses Disorder specific therapy
Organic acidaemias Propionic acidaemia ER*

(Chapter 28) Usual medicines may be increased,
e.g. carnitine
Methylmalonic acidaemia ER* Usual daily fluids or ≥120% maintenance fluids if there is chronic
B12 responsive and Usual medicines may be increased, kidney disease
B12 non‐responsive e.g. sodium bicarbonate, carnitine
Isovaleric acidaemia ER*
Usual medicines may be increased,
e.g. carnitine and/or glycine
Glutaric aciduria type 1 ER** Lysine‐free, low tryptophan amino acids, usual dose, if usually on
Carnitine, double standard dose supplements
Aggressive treatment of pyrexia to prevent neurological damage [3]
Amino acid disorders Maple syrup urine disease ER** Branched chain-free amino acids supplements, usual dose
(Chapter 28) Isoleucine and valine supplements, at least usual dose, often
increased
Urea cycle disorders NAGS, CPS, OTC deficiencies, ASA, citrullinaemia ER*
(Chapter 28) Nitrogen scavengers and arginine may
be increased. Carbaglu in NAGS
Arginase deficiency ER*
Nitrogen scavengers may be
increased
Hyperornithinaemia, hyperammonaemia, HHH ER*
Nitrogen scavengers may be
increased
Citrin deficiency Non‐standard ER No glucose polymer
(p. 589) ER – high fat and protein, low CHO
Full fat cow’s milk has suitable energy ratio (protein 20%, fat 53%,
CHO 27%)
IV fluids to be CHO‐free
Lysinuric protein intolerance ER
(p. 594) Citrulline and nitrogen scavengers,
may be increased
Fatty acid oxidation β‐oxidation defects: LCHAD, VLCAD, MTP ER* No long chain fat
defects (Chapter 30) deficiencies
Carnitine pathway disorders: ER* No long chain fat
CPTI, CPTII, CACT deficiencies
Carnitine transporter deficiency ER*
Multiple acyl‐CoA dehydrogenase deficiency ER* No long chain fat
Malonyl‐CoA decarboxylase deficiency ER* No long chain fat
Medium‐chain acyl‐CoA dehydrogenase deficiency ER* No MCT
Emergency regimen
Disorder group Disorder Usual medicines and doses Disorder specific therapy
Disorders of ketolysis HMG‐CoA synthase deficiency ER* Avoid MCT

(Chapter 30) HMG‐CoA lyase deficiency
Ketone body SCOT deficiency ER* Avoid MCT
utilisation defects beta‐ketothiolase (T2) deficiency
(Chapter 30)
Glycogen storage Glycogen storage disorders (GSD) types 0, I, III, VI, ER* ER to provide at least adequate CHO to meet basal glucose
disorders IX, Fanconi Bickel syndrome (Glut2 deficiency) requirements or child’s usual requirement
(Chapter 29) Avoid excess CHO to prevent hyperglycaemia.
Usual CHO requirement
Miscellaneous
Fructose 1,6‐bisphophatase deficiency (Chapter 29) ER* Avoid fructose, sucrose and sorbitol (drinks and medicines) and fat
during acute period
Glycerol kinase deficiency (Chapter 29) ER* Avoid fat during acute period
Ketotic hypoglycaemia (Chapter 31) ER*
NAGS, N‐acetylglutamate synthase; CPS, carbamoyl phosphate synthetase; OTC, ornithine transcarbamylase; ASA, argininosuccinic aciduria; HHH, hyperornithinaemia, hyperammonaemia,
homocitrullinuria; CHO, carbohydrate; IV, intravenous; LCHAD, long chain 3‐hydroxyacyl‐CoA dehydrogenase; VLCAD, very long chain acyl‐CoA dehydrogenase; MTP, mitochondrial
trifunctional protein; MCT, medium chain triglycerides; CPT, carnitine palmitoyltransferase; CACT, carnitine‐acylcarnitine translocase; HMG, 3‐hydroxy‐3‐methylglutaryl‐CoA synthase or lyase;
SCOT, succinyl‐CoA:3‐oxoacid‐CoA transferase.
*Emergency regimen is the standard emergency regimen shown in Table 31.2.
**Emergency regimen is based on standard emergency regimen plus precursor-free amino acids (see related chapter for specific disorder).
Practical Provision of ER 677
Table 31.2 Standard emergency regimens.
Glucose polymer Energy/100 mL

concentration Osmolality*
Age (years) (% CHO) [1] (kcal) (kJ) (mOsm/kg H2O) Suggested daily fluid volumes for age/weight
Up to 1 10 40 165 103 <6 months 150 mL/kg up to a maximum of 1200 mL

7–12 months 120–150 mL/kg up to a maximum of 1200 mL
1–2 15 60 250 174 11–20 kg: 100 mL/kg for first 10 kg, plus 50 mL/kg for next 10 kg
2–9 20 80 335 245 >20 kg: as above for first 20 kg + 25 mL/kg thereafter up to
2500 mL maximum
>10 25 100 420 342
Administration of ER Divide total volume over 24 hours: give 1–3 hourly orally or via feeding tube (bolus or continuously)
Van Hove et al. [2] suggest alternative glucose polymer % CHO:

0–12 months 15%, 1–3 years 20%, 3–6 years 25%, 6–12 years 25% or 30%, 12–15 years 30%, >15 years 30%
* Data provided by Scientific Hospital Supplies International Limited, Clinical Paediatric Dietetics, 3rd edn.
Table 31.3 Example emergency regimen for a 4‐year‐old girl with idiopathic ketotic hypoglycaemia.
A 4‐year old with ketotic hypoglycaemia who is unwell with a sore throat and not eating well
Weight = 16 kg
ER: 20% glucose polymer solution
Preparation: 1 sachet of S·O·S 20 (or 4 × 5 g scoops of glucose polymer*), add water to 200 mL, flavour with squash as desired
Fluids: 1300 mL/24 hours of glucose polymer solution
Day and night: 110 mL × 2 hourly × 12 drinks or 160 mL × 3 hourly × 8 drinks
ER provides: 1040 kcal (4.4 MJ), EAR for energy = 1290 kcal (5.4 MJ) [6]
Day 1: Give full ER for 24 hours and encourage to eat, if appropriate
Day 2: On recovery, reintroduce usual diet, continue some ER drinks, particularly at night, with guidance on volume and frequency, until eating
normally again
*Glucose polymer powders contain approximately 95% CHO; if using 20 g powder the CHO concentration is 19%.
(61.9%) and are not suitable for ER. Parents should be Commercial drinks
taught to measure glucose polymer powder accurately
using handy scoop measurements or weighing scales and Some children dislike the taste of glucose polymer (even
then to add water to a final volume (usually 200 mL). when flavoured) and prefer commercial drinks, but the CHO
Recipes for individual feeds/drinks or larger volumes concentrations of these are lower than the standard ER.
should be provided. Pre‐measured, colour‐coded sachets of Commercial drinks can be used but with caution. Glucose
glucose polymer are available: S·O·S 10, 15, 20, 25; the num polymer powder must be added to the required CHO concen
bers indicate the percentage of CHO concentration once tration, e.g. to make a 20% CHO ER drink with fruit juice, 10 g
prepared. One sachet is made up with water to 200 mL. glucose polymer (using a scoop to measure) is added to
Sachets are more accurate than using scoops or weighing 100 mL fruit juice (10 g CHO/100 mL). Written instructions on
[8]. They are more convenient, portable and easily stored preparation of the chosen commercial drink need to be given.
for use in an emergency situation at, e.g. nursery or school. As CHO concentrations of drinks can change and alternative
It is worthwhile trialling the glucose polymer solution flavours and formats of the same product have different CHO
when the child is well in a non‐emergency situation to concentrations, parents must be taught to read the nutrition
ascertain if they will take it and to familiarise the parent information label for the CHO concentration per 100 mL and
with the reconstitution process. Glucose polymer solution to always check before using. Low calorie, sugar‐free drinks
can be flavoured with squash to help palatability. Table 31.3 and no added sugar drinks contain very little or no CHO and
gives an example of an ER for a 4‐year‐old girl with ketotic should be avoided. Parents need to be informed of this and to
hypoglycaemia. seek advice from their metabolic team if prescribed locally.
Implementation of ER: guidelines Hospital admission
At home • If the child persistently vomits and is not recovering, they

should go to their local hospital promptly for assessment
• Commence the ER at home at the first signs of illness, • For most disorders stabilisation with IV fluids of 10%
particularly if appetite is reduced or usual feeds not glucose and 0.45% saline by peripheral drip or more con
tolerated (e.g. colds, flu-like symptoms, viral infections, centrated glucose through a central line is needed
any illness a ssociated with fever >37 °C, chest infection, • The metabolic team should contact the local paediatric
tonsillitis, gastroenteritis) services to inform them the child needs urgent medical
• For minor illnesses the child should be assessed by their assessment, thus avoiding delay in starting appropriate
primary care team treatment
• Give ER orally or via tube or both depending on intake • Placement of a portacath may be considered in those
and tolerance who have frequent episodes of illness and if IV access is
• Administer frequently at 2–3 hourly intervals day and difficult. There is a risk of line infection precipitating
night to optimise energy intake and reduce the period of metabolic decompensation, so the benefits need to be
fasting carefully considered
• 2–3 hourly overnight feeding may be difficult to achieve, • The oral ER or usual fluids/diet is reintroduced once
particularly if there is no feeding tube, and more realistic metabolically stabilised. This needs to be done promptly
targets should be considered, if feasible as typically it will be beyond the recommended 24–48
• For most disorders the child’s usual diet or feed should hour period of ER only
be reintroduced within 24–48 hours of commencing • If the child has a low protein feed, ideally the usual full
the ER strength feed (not ER, as this prolongs protein depriva
• While the child’s appetite is returning to normal, some tion) should be titrated directly against the IV 10% glu
ER feeds should still be given to reduce the period of fast cose fluids, gradually as tolerated, back to normal feeds
ing (particularly at night) and to maximise energy intake before discharge
• Children with OA and UCD on low natural protein diets Titration example: start with 10 mL/hour of usual feed
are often managed in hospital when unwell, but if at concurrently decreasing IV fluids by 10 mL/hour; then
home a guide is: continue to increase and decrease each respectively by
–– day 1: ½ full ER volume and ½ usual protein feed or 10 mL/hour every 4 hours until full usual feeds are estab
natural protein intake lished. Volumes to titrate can be lower or higher depend
–– day 2: return to full protein allowance (or more rap ing on the age of child, usual feed volume and expected
idly if clinically indicated), taking care to ensure an tolerance. This process may take more than 24 hours
adequate energy intake • If oral or enteral feeds cannot be re‐established, then an
• Vitamin and mineral supplements should also be early resort to PN is indicated, e.g. pancreatitis and meta
restarted, if they have been stopped bolic acidosis with vomiting are common indications for
• Close liaison, at least daily with the metabolic team, is PN in MMA and PA
essential when a child is unwell at home to assess pro • Weaning from PN to the usual low protein feeds needs to
gress, tolerance and intake of ER and clinical state and to be carefully planned. Ideally the PN prescription will be
advise on reintroducing the usual diet similar in composition to the enteral feed. Clear guid
ance on volume rate decreases of the Vamin/glucose
solution and lipid solution vs. feed volume increases will
be required. This will ensure the correct protein and ade
Tube feeding quate energy is always achieved
• Poor growth and nutritional deficiencies will occur in
• Tube feeding should be used if oral ER volume is patients on low protein diets who have repeated infec
insufficient; this may necessitate a hospital admission tions and are frequently on their ER. It may be necessary
• Continuous nasogastric (NG) feeding is generally better to increase protein intake temporarily when the child is
tolerated than bolus feeds, but is not safe at home for well to compensate for this
overnight feeds
• Some parents prefer to be taught to do NG feeding at
home solely for provision of ER Instructions for parents
• Parents need to remain confident and competent in
passing an NG tube to administer the ER feed Management of intercurrent infections can be an anxious and
• Some children may have a tube passed in the local difficult time for parents, knowing their child is at greater risk of
hospital, observed for a few hours and discharged to metabolic decompensation and/or h ypoglycaemia. To make
continue this treatment at home if already trained to give this easier, parents can be taught a three‐staged action plan to
NG feeds help with decision making [1]. Parents are asked to phone the
Idiopathic Ketotic Hypoglycaemia 679
metabolic team (doctor, dietitian, clinical nurse specialist) for understanding of ER, instructions and recipes need to be
advice at an early stage and also to consult their primary care regularly reviewed with parents in outpatient clinics and
team for assessment and treatment of common childhood updated in accordance with the child’s current dietary treat
illnesses. One or more of the metabolic team will make contact ment, age and clinical condition. If a child is reported to be
with the parents throughout an episode of illness: frequently on their ER, this warrants further investigation. A
MedicAlert bracelet may be useful for some children.
1. If the parents are unsure whether their child is showing
the first signs of impending illness (pallor, dark eyes,
Holiday and travelling overseas
lethargy, irritability, loss of appetite, fever, headache,
aches and pain, cough, sore throat or ears), then a single
Families can travel abroad, but it is best they go to countries
ER drink is given as a precaution. Clinical observations
that have expertise in the management of metabolic disease,
are reported to be generally better than biochemical
should their child become unwell. This needs to be discussed
measurements for detecting decompensation; subtle
with the metabolic team at an early stage of planning a trip.
changes in behaviour are usually the earliest signs of this
Parents must take all ER products and up‐to‐date medical
and are most easily detected by parents [9]. The child’s
and dietetic management information and have details for a
clinical state is then reviewed regularly within 1–2 hours.
hospital and consultant to go to in the event of an emergency.
2. If on reassessment their child has improved, the normal
Sensible precautions need to be taken on holidays abroad,
diet is resumed; if, however, their child has deteriorated
particularly in hot countries, to reduce the risk of dehydra
or shown no signs of improvement, the full ER is com
tion and infections. ORS is essential because of an increased
menced for a period of 24 to a maximum of 48 hours,
risk of gastroenteritis.
always alert for signs of improvement or deteriorations.
Once their child is recovering, parents are instructed
how to reintroduce the usual diet.
3. If the child is not tolerating the ER (i.e. refusing ER Learning points: emergency regimens
drinks, vomiting, persistently high temperature, not
responding or becoming encephalopathic), they should • ER should be used during episodes of illness to prevent
be taken to their local hospital for assessment. Parents metabolic decompensation and or hypoglycaemia
should take all ER information and products with them. • The standard ER is suitable for most disorders, but some
require additional specific ER instructions
Parents are taught to recognise signs of encephalopathy • Emergency guidelines (IV and enteral) can be accessed
such as disorientation and poor responsiveness, accompa from www.bimdg.org
nied by a glazed look. Measurement of blood glucose is • Good daily communication is needed between parents,
helpful if there is a risk of hypoglycaemia, e.g. glycogen metabolic team and local paediatric hospital team to

storage disorders, but is not appropriate in disorders of optimise management
fatty acid oxidation where hypoglycaemia is a late finding
and the child may already be very unwell before this devel
ops. Blood glucose tests can be inaccurate at low levels.
Therefore, if there are clinical signs suggesting hypoglycae
mia, this should always be treated immediately. Blood Idiopathic ketotic hypoglycaemia
ketones may be present during illness and used as a marker
of catabolism (and, therefore, a possible surrogate marker IKH is the most common cause of hypoglycaemia beyond
of metabolic stability) in some disorders such as MSUD infancy. Children typically present between 18 months and
and OAA. Some parents are taught to monitor ketones at 7 years of age with an episode of hypoglycaemia accompa
home. Ketone monitoring in MSUD is described on p. 540. nied by high levels of ketones in plasma and urine, precipi
Monitoring of temperature is important and should be tated by a period of prolonged fasting often associated with
treated in the normal way. intercurrent illness. Seizures may occur, but neurological
It is essential that there is close liaison and good commu sequelae are rare [10]. IKH improves with age and rarely
nication between the metabolic centre, the local hospital manifests beyond about 8 years of age [11]. The prognosis is
team and parents to help with management. It is also useful generally good, and some children never experience a sec
to organise open access to the local hospital’s paediatric ond episode. IKH is considered to be due to a failure to
ward. Parents should be given written instructions on sustain sufficient hepatic glucose production [10, 12]. This
implementation of the ER including recipes, suggested fluid may, however, just represent the ‘lowest percentile of nor
volumes for increases with age or weight, feeding frequency, mative distribution of fasting tolerance in children’, and, as
contact telephone numbers, an initial and provision for such, IKH should not be classified as a pathological condi
ongoing supply of glucose polymer and a copy of the tion; diagnosis is only made after exclusion of any specific
British Inherited Metabolic Diseases Group (BIMDG) endocrine or metabolic disorder that can cause a ketotic
emergency protocol as a ‘parent‐held guideline’. Use and hypoglycaemia [12].
Presentation and management performed under controlled conditions in hospital, usually

by a specialist metabolic or endocrine team. Younger chil
The clinical history is characteristic. Normally the child will dren have a faster decrease in blood glucose levels and
present acutely to their local hospital A&E department with a faster increase in ketone body levels than older children;
history of being unwell, having gone to bed with a poor food thus fasting tolerance improves with age [15]. The results
intake the day/evening before, and the next morning is pale, can help establish the diagnosis and determine the
floppy and unrousable. On arrival at hospital they are found maximum safe fasting time for the child at that age. Most
to be hypoglycaemic. This is treated immediately with either children with IKH will not develop hypoglycaemia d uring
IV glucose, or oral glucose such as Glucogel (a 40% dextrose the fasting test. If on fasting the child does become hypogly
gel) rubbed into the buccal cavity, or a sugary drink. The caemic, further dietary intervention is necessary, usually at
child usually responds promptly to glucose. A short stay in night, by either:
hospital on IV fluids and for observation may be needed until
the child recovers and begins to eat and drink normally again. • reducing the length of the overnight fast and giving a
Before discharge parents should be advised on the use of the starch‐rich bedtime snack and early breakfast
standard ER and their child referred to a specialist metabolic • giving the above plus provision of a high CHO drink (at
centre for a diagnosis of IKH to be made or excluded. least 10% concentration) or milk drink in the middle of
the night
• giving a dose of 1.0–1.5 g/kg of uncooked cornstarch
Dietetic management: advice to parents (UCCS) before bed. Practical aspects of giving UCCS are
described on p. 613
• Implement standard ER during episodes of illness to pre
vent fasting and risk of hypoglycaemia A small number of children with IKH complain of hypo
• Provide written ER instructions and supplies of glucose glycaemic symptoms even when completely well. Parents
polymer powder often just treat these symptoms with a high CHO drink or
• Recognise the early warning signs of hypoglycaemia food, without knowing the actual blood glucose level.
such as irritability, sweatiness, dizziness, confusion, pal McSweeney et al. [16] reported that a continuous glucose
lor and drowsiness monitoring system (CGMS) over several days at home pro
• Specialist nurses/doctors to advise on use of dextrose gel vided more real‐time information and helped identify the
to treat the semi‐conscious or uncooperative child true incidence of hypoglycaemia in children with IKH,
• In the well child healthy eating with regular meals (three despite them having a normal fasting test in hospital. CGMS
main meals) including starchy foods enabled a more individualised treatment plan to be given.
• Avoidance of prolonged overnight fasts by giving a bed The use and understanding of ER, instructions and recipes
time snack and not to miss breakfast (this may change need to be regularly reviewed in outpatient clinics and
with results of fasting studies, see below) updated in accordance with age and clinical condition.
• Give more frequent feeding if the appetite is poor and Follow‐up also allows identification of further possible
during illness hypoglycaemic episodes necessitating repeat investigation
• Management of hypoglycaemia: give 10–20 g CHO of or further dietary manipulation.
oral glucose from glucose polymer or equivalent CHO
drink followed by a starch snack
Fasting tests and management

Fasting tests are commonly used to help establish the cause
of hypoglycaemia and fasting tolerance [13, 14]. Tests are www.wiley.com/go/shaw/paediatricdietetics-5e
Index
Abdominal wall defects, 157–159 preterm infants, 99 sensory processing difficulties, 407–408
Abetalipoproteinaemia, see South Asian infants, 496 therapeutic diets, supplements, 413–418
Hypolipoproteinaemias Anaphylaxis, food allergy, 317, 318, 325, Autoimmune enteropathies, IPEX
Absorptive function of the gut, 159–160 331–333, 337 syndrome, 127
Acute kidney injury, 238–245 Angioedema, food allergy, 317, 332 Autoimmune hepatitis, 168, 169, 180, 183
biochemical assessment, 240 Anorexia nervosa, 393–404 Avoidant restrictive food intake disorder
enteral feeding, 240 Anthropometry, 2–5 (ARFID), 33, 393, 410
haemolytic uraemic syndrome, 238, 243 Antiepileptic drugs, 344, 358
insensible fluid requirements, 243 Arachidonic acid, see Long chain Bartter syndrome, 279–280
nutritional guidelines, 240–245 polyunsaturated fatty acids (LCP) Basal metabolic rate (BMR), 86–87
parenteral nutrition, 240 Arginase deficiency, 587, 593–594 Betaine, in homocystinuria, 544
renal replacement therapy, 239 Arginine, in urea cycle disorders, 589, Beta‐ketothiolase, T2 deficiency, 654
Acute liver failure, see Liver failure, acute 592–593 Bile salts
Adrenoleukodystrophy, X‐linked, 508, Argininosuccinate lyase (ASL) cystic fibrosis, 225
510, 512 deficiency, 587 liver disease, 172, 180, 183
Advisory Committee on Borderline Argininosuccinate synthetase (ASS) preterm infants, 98
Substances (ACBS), 16 deficiency (citrullinaemia), 587 short bowel syndrome, 160, 163
Afro‐Caribbean diet, 498–499 Arginosuccinic aciduria (ASA), 587 Bilirubinaemia, conjugated
Air displacement plethysmography, 3 Asian diet, 488–498 hyperbilirubinaemia (CHB), 172
Alagille’s syndrome, 179 Asthma, food allergy, 315, 334, 337 Binge eating disorder, 394
Alkaptonuria, 594 Atopic dermatitis, 315, 318–320, 326, Bioelectrical impedance analysis, 3
α‐1‐antitrypsin deficiency, 179 332, 338 Bite reflex, 435
Amino acid‐based formulas, 141, 144, 324 Atresia Blood glucose (sugar) levels
cancer, 377, 379 biliary, 172, 179, 182, 184 congenital hyperinsulism, 208, 211,
food allergy, 321–324, 331–332 duodenal, 155 213–214
enteral feeding, 53, 55 intestinal, 159 diabetes mellitus, 203–204
gastroenterology, 130, 132, 140–141, 144 oesophageal, 149–155 glycogen storage diseases, 610, 614, 617,
immunodeficiency syndromes, 387–391 Attention deficit hyperactivity disorder 623, 626, 629
short bowel syndrome, 161–162 (ADHD) liver disease, 170, 174
surgical babies, 158 autism, 407, 409 Body mass index (BMI), 4
Amino acids, classification, 503 food allergy, 318, 337 Body composition, measurements, 2–4
Anaemia Autism, 405–418 Bone marrow transplant (BMT), see Stem
Afro‐Caribbean children, 499 co‐morbidities, 407, 410 cell transplant
chronic kidney disease, 255 diagnosis, 405 Branched chain amino acids
epidermolysis bullosa, 447–448 dietary issues, 410–413 liver disease, 169, 173–175
faltering weight, 468 management, medical, social, 409–410 maple syrup urine disease, 532,
iron deficiency anaemia, 29, 38–39 nutritional assessment, management, 535–541
nephrotic syndrome, 268 410–414 urea cycle disorders, 589–592

682 Index
Breastfeeding, 7, 8, 18–22, 44 malonyl‐CoA decarboxylase Chylothorax, 299–304

contraindications, 20 deficiency, 654 fat exchanges, 303
Breastmilk, expressed (EBM), 10, 13, 22–23, medium chain acyl‐CoA dehydrogenase infant feeding, 301–302
44, 52 deficiency, 643 minimal LCT diet, 302–304
donor breast milk, 48, 103, 106–107 long chain fatty acid oxidation Cirrhosis, liver, see Liver disease, chronic
enteral feeding, 52 disorders, 647 Citrin deficiency (citrullinaemia type II,
fortifiers, 104, 110–111 organic acidaemias, 572 CTLN2), 587
pasteurisation, 48, 52 parenteral nutrition, 72 Clean diet, see Neutropenic diet
preterm infants, 103, 104, 107, 110 Prader–Willi syndrome, 481 Cleft palate, 436
storage, 23, 46 Carnitine acylcarnitine translocase (CACT) Clinical assessment, 7–9
supplemented, 13 deficiency, 643 Coeliac disease, 121–125
British National Formulary (BNF), 16 Carnitine palmitoyl transferases I, II autism, 410
B12, vitamin (CAPTI, CAPTII) deficiencies, 643 bone health, 124
methylmalonic acidaemia, 573 Carnitine transporter deficiency, 653 gluten challenge, 125
short bowel syndrome, 159, 160, 164 Centile (growth) charts, 2–4 gluten‐free diet, 122–124
vegetarian, vegan diets, 487, 488, 490, 493, Cerebral palsy, see Neurodisabilities gluten‐free foods (Codex Alimentarius),
497, 499 Chinese diet, see Ethnic groups and cultural 122–123
Bulimia nervosa, 394 diets oats, 123
Burns, 456–463 Chloride losing diarrhoea, congenital, 120 screening and diagnosis, 121–122
assessment of injury, 456 Choledochal cysts, 180 Complementary feeding, weaning, 25–29
metabolic response to injury, 456–466 Cholestasis developmental stages, 27
monitoring and outcomes, 460–461 critically ill child, 81 fluids, 10, 12, 28
novel substrates, immunonutrition, 459 cystic fibrosis‐related liver disease, 234 foods, 26–28, 30
nutritional management, 460–463 liver diseases, 166, 167, 169, 172, 177, preterm infants, 111–112
nutritional requirements, 457–459 179, 180 recommendations, 25–26
parenteral nutrition, 65, 66, 70, 74 Concentrating feeds, see Feed
Cachexia preterm infants, 101 supplementation
cancer, 374, 382 short bowel syndrome, 164 Congenital disorders of glycosylation, 512
chronic kidney disease, 246, 258, 259 Cholesterol Congenital heart disease, 282–307
Calcium, sources in vegan and vegetarian lipid disorders, 656–661, 664–669 chlyothorax, see Chylothorax
diet, 495 Smith–Lemli–Opitz syndrome, 509, 512 energy expenditure, 290–291
Calcium supplements, 606 Chronic liver disease, see Liver disease, fluid restriction, 296
Cancer, 371–383 chronic growth, 287–290, 292
alternative diets, 381 Chronic kidney disease, 245–266 hepatic dysfunction, 305
bone morbidity, 379–380 acid–base balance, 251, 258 necrotising enterocolitis, 303–305
eicosapentaenoic acid, 382 anaemia, iron, 246, 255 nutrition pre‐surgery, 293–295
enteral feeding, 376–378 assessment, 247–248 nutrition post‐surgery, 296–299
glutamine, 381–882 calcium, 251, 253 outcomes, feeding, growth, 306–309
ketogenic diet, 382–383 cardiovascular disease, 253, 255, 262, 265 protein losing enteropathy, 305
malnutrition, aetiology, 374 energy, 249–250, 257–258 vocal cord palsy, feeding difficulties,
nutritional requirements, 375 enteral feeding, feeding problems, 247, 305–306
nutritional risk and assessment, 374–375 250, 263–264 Congenital hyperinsulinism (CHI), 207–215
oral feeding, 376 fluid, 248, 250–251, 260 blood glucose monitoring, 209, 215
parenteral nutrition, 378 gastro‐oesophageal reflux, 263 dietetic management, 211–215
probiotics, 382 growth failure, 246–247 feeding difficulties, 212–214
side/late effects of treatment, 379–381 hypertension, 254, 265 glucose infusion rate, 208
transplant, nutrition, 378–379 micronutrients, 244–245, 262 medical management, 209, 210
vitamin supplementation, 381 mineral bone disorder, 251 surgical management and complications,
Carbamyl phosphate synthetase 1 (CPS1) nutritional management, conservative, 209–211
deficiency, 587 249–256 uncooked cornstarch, 215
Carbohydrate nutritional management, dialysis, Constipation
concentration in feeds, 14–15 256–263 burns, 463
counting, 193–194 phosphate, 251–253 children with neurodisabilities, 428, 433
parenteral nutrition, 72 phosphate binders, 253–254, 262 enteral feeding, 54
Caries, dental, 31, 39 potassium, 251, 260–262 epidermolysis bullosa, 448, 455
Carnitine protein, 249–250, 258–259 fibre, 38
chronic kidney disease, 260 protein energy wasting, 258–259 food allergy, 138, 317
cystinosis, 275 sodium, salt, 250–251, 254–255, 260, 265 functional, 138–140
epidermolysis bullosa, 448 transplantation, 263–266 Hirschprung’s disease, 156–157
glutaric aciduria type I, 579 vitamin D, 253 ketogenic diet, 367
isovaleric acidaemia, 577 Chylomicron retention disease, see Continuous glucose monitoring
ketogenic diet, 358 Hypolipoproteinaemias congenital hyperinsulinism, 215
lipid metabolism, 503, 640 Chylomicrons, 69, 300, 659–662, 664 diabetes mellitus, 191
Index 683
glycogen storage diseases, 629–631 Developmental delay, see Neurodisabilities Elemental formulas, see Hydrolysed protein
idiopathic ketotic hypoglycaemia, 680 Diabetes insipidus, see Nephrogenic formulas; Amino acid‐based
Copper, in Wilson’s disease, 181, 183 diabetes insipidus formulas
Cornstarch, cornflour, uncooked cornstarch Diabetes mellitus, type 1, 189–205 Elimination diets, food allergy, 319–321
(UCCS) adolescents, 198 Emergency regimens (ER), 673–680
congenital hyperinsulinism, 215 babies and toddlers, 196 acute liver failure, 169
dumping syndrome, 155 carbohydrate counting, 193–194 congenital hyperinsulism, 209, 215
fatty acid oxidation disorders, 646 children, 196–197 implementation guidelines, 678–679
fructose‐1,6‐bisphosphatase deficiency, 637 coeliac disease, 205 instructions for parents, 679
glycogen storage diseases, 609, cystic fibrosis‐related, 205 metabolic disorders requiring ER,
613–615, 637 education and review, 195–198 674–676
idiopathic ketotic hypoglycaemia, 680 glucose monitoring, 191 standard emergency regimens, 677
liver diseases, 174 glycaemic index, 198–199 Empirical diet, food allergy, 319–320
Cow’s milk protein allergy hypoglycaemia, 203–205 Energy
alternative ‘milks’, 143–144 illness, 205 protein‐energy ratio for growth, 14
amino acid‐based formulas, 140–141, insulin to carbohydrate ratio (ICR), 193–194 requirements, 8–10
331–332 insulin therapy, pumps, 199–200 supplements, modules, 13–15
breastfed infant, 139 nutritional management, 192–195 Enteral nutrition, 52–63
hydrolysed protein formulas, 140–141 physical activity and exercise, 200–203 administration, methods, routes, 55–59
mammalian milks, 139, 333 secondary to medication, 206 amino acid‐based feeds, 53, 54
milk‐free diet, 142 Diabetes mellitus, type 2, 205–206 blended diets, 62
milk, egg, wheat and soya‐free diet, Dialysis, 239, 256–257 dumping syndrome, 40
142–143 Diarrhoea, see Malabsorption equipment, 59–60
soy protein formulas, 139–140, 333 Dietary intake, assessment, 7, 467 expressed breast milk, 52–53, 58
Critical care, nutrition in, 80–95 Dietary reference values (DRV), 8 feed intolerance, 61
energy metabolism, 82 Diet kitchen/bay, 49 feed thickeners, 54–55
enteral nutrition, 88–90 Disaccharidase deficiencies, 115–117 follow‐on milks, 53
immunonutrition, 91–95 Distal intestinal obstruction syndrome hanging time, 60
monitoring, 91 (DIOS), 235 home enteral feeding, 60–61
nutritional assessment, 85–86 Docosahexaenoic acid (DHA), see Long chain hydrolysed protein feeds, 53, 54, 56, 57
nutritional requirements, 86–88 polyunsaturated fatty acids (LCP) indications, 53
refeeding syndrome, 91–92 Down’s syndrome, see Neurodisabilities infant formulas, 52–53
substrate utilisation, 82–83 Dual‐energy x‐ray absorptiometry modular feeds, 53, 54
Crohn’s disease, 128–132 (DEXA), 3 monitoring, 61–62
exclusive enteral nutrition, 129–131 Dumping syndrome, 155 nutrient‐dense infant formulas, 53
introduction of foods, special diets, Duodenal atresia, 156 oromotor skills, 62
131–132 D, vitamin paediatric enteral feeds, 53–54
nutritional requirements, 129 ethnic and cultural diets, 490, 495, 497 refeeding syndrome, 63
refeeding syndrome, 131 deficiency, 39–40 Enteropathy
Cultural diets, see Ethnic groups and serum 25‐hydroxyvitamin D autoimmune, 127
cultural diets concentrations, 380 coeliac disease, 121–125
Cystic fibrosis, 216–237 Dysphagia congenital, 120–121
assessment, 218–219 diet food texture descriptors, 435–436 gastrointestinal food allergy, 138–148
bone mineral density, 226, 228, 234–235 neurodisabilities, 434–436 protracted diarrhoea, 120–121
CF‐associated liver disease, 232–234 oesophaeal atresia, 153 Eosinophilic gastrointestinal diseases
CF‐related diabetes, 228–234 (EGID), 125–126
CFTR modulator therapies, 236–237 Eating disorders, 393–404 eosinophilic gastroenteritis, 126
clinical features, 217 anorexia nervosa, 393–394 eosinophilic oesophagitis (EoE), 125–126
enteral feeding, 223–225 assessment, 395 Epidermolysis bullosa (EB), 438–451
gastrointestinal issues, 235–236 binge‐eating disorder, 394 anaemia, 447–448
nutritional advice, moderate deficit, body mass index, 394, 395, 398 bone health and mobility, 447, 451
222–223 bone health, 396–397 complications influencing nutritional
nutritional advice, preventative, 221–222 bulimia nervosa, 394 status, 441–442
nutritional advice, significant deficit, dietetic management, 396–400 dental caries, 450
223–225 family based treatment, 396, 404 dilated cardiomyopathy, 448
nutritional management, aims, 217–218 exercise, 399–400 enteral feeding, 442–443
pancreatic enzyme replacement therapy, expected weight gain, 698 fibre, 448
219–221 refeeding syndrome, 396, 400–404 gastrointestinal issues, 449–450
sodium, salt, 226–227 Eczema, see Atopic dermatitis infant feeding, 439–442
vitamins and minerals, 225–228 Eicosapentaenoic acid, see Long chain nutritional assessment, 444–445
Cystine, supplementation in polyunsaturated fatty acids (LCP) nutritional requirements, 445–449
homocystinuria, 547 Electrolyte mixtures, see Oral Rehydration nutrition support, 439–443
Cystinosis, 274–275 Solutions puberty, 450
684 Index
Epilepsy, see also Ketogenic diets Familial hypercholesterolaemia, 666–669 amino acid‐based formulas, 324, 331
food allergy, 318, 336 dietary management, 667–669 anaphylaxis, 317, 318, 325, 331–333, 337
Erythema, 317 drug therapy, 667 breastfeeding, 330–331
Essential amino acids (EAA) fat intake, 667–668 controversial elimination diets, 336–337
arginase deficiency, 593–594 screening, 666 diagnosis, 318–319
parenteral nutrition, 71 stanols and sterols, 668–669 dietary management, 329–334
urea cycle disorders, 589–590 Familial lipoprotein lipase (LPL) deficiency, elemental diet, 321
Essential fatty acids (EFA), 302, 565, 646 663–666 elimination diets, use in diagnosis,
chylothorax, 301–303 acute episodes, 665–666 319–321
disorders of fatty acid oxidation, 646 dietary management, 665 empirical diet, 319–320
healthy diet, 15, 41 Fat emulsions, 14 few foods diet, 320–321
hypolipoproteinaemias, 662–663 Favism, 594 food challenges and reintroduction of
intestinal lymphangiectasia, 118 Fatty acid oxidation, disorders of, 640–672 foods, 322–328
ketogenic diets, 358 Feed preparation area (special feeds unit), food labelling, 329–330
liver diseases, 172, 177 45–49 hydrolysed protein formulas, 323, 331
low protein diets, 565 bottles, 47 mammalian milks, 333
modular feeds, 146 legislative requirements, 45, 47 natural progession, ‘allergic march’,
parenteral nutrition, 69–71 microbiology, 47–49 334–336
preterm infants, 98–99, 101 pasteurisation and blast chilling, 46–47 nutritional requirements, 329
short bowel syndrome, 161 plant and equipment, 46–47 pollen food (oral allergy) syndrome, 320,
vegetarian and vegan diets, 488, 490, preparation and ingredients, 47–48 326, 336
494, 497 staffing, 47 probiotics, prebiotics, synbiotics, 337–338
walnut oil, 118, 177, 302, 389, 646–647, 649 structural design, 46 soya formulas, 333
Estimated Average Requirement (EAR), 8 thermal disinfection, 47 symptoms, clinical manifestations,
Ethnic groups and cultural diets, nutrition, Feed supplementation, 13–16 316–318
486–501 concentrating formulas, 13–14 Food intolerance, see Food hypersensitivity
Afro‐Caribbean communities, 498–499 energy and protein modules, 14 Food protein‐induced allergic proctocolitis
infant feeding and weaning, 499 nutrient‐dense formulas, 14–16 (FPIAP), 127
nutritional problems, 499 Fever induced refractory epilepsy of Food protein‐induced enterocolitis
Rastafarians, 498 childhood syndrome (FIRES), 346, 359 syndrome (FPIES), 126–127
Chinese communities, 499 Few foods diet, food allergy, 320–321 Food Safety Regulations, 45, 47
infant feeding and weaning, 500 Fibre Fructosaemia, see Hereditary fructose
Yin and Yang foods, 500 constipation, 136 intolerance
fruitarian diet, 488 Crohn’s disease, 131 Fructose
infant formulas, 491–493 diabetes, 193, 195 diabetes mellitus, 195, 202
Jewish communities, 501 faltering weight, 469 feed component, 15, 145, 162
religious and cultural influences on fibre-containing feeds, 54 FODMAP diet, 138
diet, 499 healthy diet recommendations, 18, 38 functional diarrhoea, 137
Somalian communities, 501 neurodisabilities, 423, 428 glucose‐galactose malabsorption, 118–119
infant feeding, 501 vegetarian and vegan diets, 487, 497 glygogen storage disease, 610
nutritional problems, 501 Fluid, requirements, 8–13 hereditary fructose intolerance, 635–636
South Asian dietary customs, 488–498 insensible fluid losses, 243 sucrase‐isomaltase deficiency, 116
infant feeding and weaning, 496 FODMAP diet, 138 Fructose‐1,6‐bisphosphatase deficiency,
nutritional problems, 496–498 Follow‐on milks, 10, 24 637–638
vegetarian and vegan diet, 486–488 enteral feeding, 53 Fruitarian diet, 488
infant feeding and weaning, 486–487 Food additives Fundoplication, 152–153
children, 487–488 attention deficit hyperactivity disorder, 337 chronic kidney disease, 263
Vietnamese communities, 500–501 Food allergy, see Food hypersensitivity enteral feeding, 56, 59
infant feeding, 500–501 Food allergy, prevention of, 339–343 gastro‐oesophageal reflux disease, 134
nutritional problems, 501 ‘allergic march’, 339
Exomphalos, see Abdominal wall defects breastfeeding, pregnancy, 339–340 Galactokinase deficiency, 606
Extremely low birthweight, 96 hydrolysed protein infant formulas, 340 Galactosaemia, classical, 599–606
introduction of solids, 340–342 cheese, suitability, 604–605
Faltering weight (failure to thrive), 464–471 maternal and infant diet, 342–343 galactose‐restricted diet, 601–605
assessment, 466–468 micronutrients, 342 galactosides, nucleoproteins, free and
behavioural management, 469 prebiotics, probiotics, 343 bound galactose, 602–603
causes, 465–466 recommendations, 343 milk substitutes, 603–604
definition and identification, 464–465 Food challenges, 322–328 vitamins and minerals, 605–606
mealtimes and snacks, 468–469 double blind placebo controlled food Gastric hypersecretion, 163
nutritional management, requirements, challenge (DBPCFC), 325 Gastroenteritis, 113–115
468–469 Food groups, 23, 29–31 acute infective diarrhoea, 113
outcome, 466 Food hypersensitivity (allergy, intolerance), lactose‐free formulas, 114
social care, 469 315–338 oral rehydration solutions (ORS), 114
Index 685
Gastrointestinal food allergy, 138–148 Glycogen storage disease type 0, 625–627 preschool children, 29–33, 37
amino acid‐based formulas, 140–144 Glycogen storage disease type I, 609–618 responsive feeding, 27–28
hydrolysed protein formulas, 140–141, dietary management, 610–617 salt, 18
143–144 emergency regimen, 609, 617 school meals, 35–36
mammalian milks, 139 glucose requirements, 610 schoolchildren, 33–37
milk‐free diet, 142 hypoglycaemia, 616–617 snacks, packed lunches, 35–36
milk, egg, wheat and soya‐free diet, infants, 611–612 teenage pregnancy, 36
142–143 monitoring, 617–618 vitamin D, 28, 39–40
modular feeds, 145–148 older children, 612 vitamins, 31
soya formulas, 139–140 uncooked cornstarch, 609–611, 613–615 Height, measurement, 2–3
Gastro‐oesophageal reflux (GOR), GOR vitamins and minerals, 615–616 alternative measurements, 423–424
disease, 133–134 Glycogen storage disease type III, 618–622 height age, 4–5, 8, 11
chronic kidney disease, 263 dietary management, 619–622 Hereditary fructose intolerance (HFI),
congenital heart disease, 292, 295 emergency regimen, 619, 622 631–637
congenital hyperinsulinism, 212 uncooked cornstarch, 619–622 dietary management, 632–637
cystic fibrosis, 221 Glycogen storage disease type VI, 622–625 fructose, sources, 635–637
enteral feeding, 54, 56, 58 Glycogen storage disease type IX, 624–625 minimal fructose, sucrose and sorbitol
eosinophilic oesophagitis, 125 Glycogen storage disease type XI, Fanconi diet, 633–634
epidermolysis bullosa, 449 Bickel syndrome, 627–629 nutritional deficiencies, 637
feed thickeners, 133–134 Glycomacropeptide, in Hirschsprung’s disease, 156–157
feeding problems, 134 phenylketonuria, 520 Homocitrullinaemia (HHH) syndrome, 587
food allergy, 138 Goat’s milk, 139, 333, 487, 501, 551, 603 Homocystinuria, classical, 541–551
fundoplication, 134 Growth children, late diagnosis, feeding, 550–552
infant feeding, 133–134 catch‐up, 14 cystine supplementation, 547
medications, 134 charts, 3–4 dietary management, 545–551
neurodisabilities, 433 cerebral palsy, 420 infant feeding, 548–549
oesophageal atresia, 152–155 Down’s syndrome, 421 methionine exchanges, 545–548
positioning, 133 Prader–Willi syndrome, 479 protein substitute, 546–547
Gastroschisis, see Abdominal wall defects Williams syndrome, 284 pyridoxine, 542
Gastrostomy feeding, see Enteral feeding expected growth, 7–8 Human milk, see Breastmilk
Glucagon, 201, 205, 210, 213–214, 504–506 thrive lines, 4 Human milk fortifier, see Breastmilk
Glucose z‐scores, 4 Hydrolysed protein formulas
feed component, 15 Guanidinoacetate methyltransferase cancer, 377, 379, 385
monitoring, 191, 209, 232, 629 deficiency, 594 cystic fibrosis, 225, 235
oxidation rate, 72, 82, 169 Guar gum, 162 enteral feeding, 53–57, 61
production rate, 610, 617, 651 Gut motility disorders, 132–138 food allergy, 323, 331–332
requirements, 610 abdominal pain‐related disorders, 137 gastrointestinal diseases, 116, 140–141
Glucose‐galactose malabsorption, 118–119 constipation, 136–137 immunodeficiency syndromes, 387–390
infant feeding, 118–119 diarrhoea, 137 liver diseases, 180
minimal glucose, galactose diet, 119 functional gastrointestinal disorders, peptide chain, epitope, 140, 331
Glucose‐6‐phosphate dehydrogenase 135–138 prevention of allergy, 340
deficiency, 594 gastro‐oesophageal reflux, 133–134 short bowel syndrome, 161–162
Glucose polymers, 14 intestinal pseudo‐obstructive disorder, surgical babies, 152, 158
Glucose transporter 1 deficiency syndrome, 134–135 3‐hydroxy‐3‐methylglutaryl‐CoA lyase
344–345, 355 irritable bowel syndrome, 137–138 (HMGCL) deficiency, 654
Glutamine low FODMAP diet, 138 3‐hydroxy‐3‐methylglutaryl‐CoA synthase
burns, 458–459 Gyrate atrophy of the choroid and (HMG‐CoA) deficiency, 654
cancer, 381–382 retina, 594 Hyperactivity, see Attention deficit
critical care, 82, 93–94 hyperactivity disorder (ADHD)
parenteral nutrition, 71–72 HbA1c, 190 Hyperammonaemia, 587
short bowel syndrome, 162 Haemolytic uraemic syndrome, 238, 243 Hypercalcaemia, 283–286
urea cycle disorders, 589–593 Harlequin ichthyosis, 452–453 idiopathic infantile hypercalcaemia,
Glutaric aciduria type 1, 580–587, see also Head circumference, measurement, 3 283–284
Organic acidaemias Healthy eating, 18–42 Williams syndrome, 284–286
diet in children, 585 breastmilk and breastfeeding, 19–23, 37 Hypercalciuria, 281–284
dietary management, 582–587 complementary feeding, 25–28 Hypercholesterolaemia, see Familial
emergency regimen, illness, 585–587 dental caries, 39 hypercholesterolaemia
infant feeding, 582–585 expressed breastmilk, 22–23 Hyperkalaemia, 238, 251, 260–261
low lysine diet, low protein diet, 582–586 food groups, 29–31 Hyperlipoproteinaemias, 664–672
Gluten‐free diet, 122–124 formula feeding, 23–25 Hyperornithinaemia, 587
Glycaemic index, 174, 177, 193, 196, 346, Healthy Start, Sure Start, 3 Hyperoxaluria, primary, 281–282
354, 619 iron deficiency anaemia, 38–39 Hypertension, 250–251, 254–255, 260, 265
Glycerol kinase deficiency, 639 lactating mothers, 23 Hyperuricaemia, 608
686 Index
Hypoallergenic formulas, see Hydrolysed Inherited metabolic disorders, rare, hypercalciuria, 277
protein formulas; Amino acid 511–512, 594 hyperoxaluria, primary, 281–282
based‐formulas Inspissated bile syndrome, 179–180 nephrogenic diabetes insipidus, 276–279
Hypobetalipoproteinaemia, see Insulin nephrotic syndrome, 266–269
Hypobetalipoproteinaemias carbohydrate ratios, ICR, 193–194 renal stones, 279–283
Hypolipoproteinaemias, 659–664 preparations, 191 renal tubular disorders, 272–279
abetalipoproteinaemia, 659 therapy, pumps, 199–200 Knee height, measurement, 424
chylomicron retention disease, 660 Intestinal‐associated liver disease (IFALD),
dietary management, 661–664 66, 101, 164, 178 Labelling, food regulations, 122–123, 142,
essential fatty acids, 662 Intestinal failure, 66, 79, 160 329, 350, 518, 601, 604, 636
hypobetalipoproteinaemia, 660 Intestinal lymphangiectasia, 117–118 Lactase deficiency
infants, 662–663 essential fatty acids, 118 lactose intolerance, 317
medium chain triglycerides, 662 MCT supplementation, 118 lactose‐free formulas, 115, 117
older children, 663–664 minimal fat infant formulas, diet, 118 primary deficiency, 117
vitamins, 662 protein supplementation, 118 secondary deficiency, 117
Intrauterine growth retardation, 96 Afro‐Caribbean communities, 499
IgE, non‐IgE, food allergy, 125–127, 138–142, Iron, sources in vegan and vegetarian diet, Chinese communities, 499
315–338 490, 493 Vietnamese communities, 500
Ileus Isolated sulphite oxidase deficiency, 594 Length, see Height
functional, post‐surgical, 158, 160 Isoleucine, see Maple syrup urine disease Leucine, see Maple syrup urine disease
meconium, 222, 224 Isovaleric acidaemia, 578–580, see also Leukaemias, 372
Immunodeficiency syndromes, 383–392 Organic acidaemias Linoleic acid, see Essential fatty acids
autoimmune enteropathy, 386 dietary management, 579–580 α‐Linolenic acid, see Essential fatty acids
chronic granulomatous disease, 386–387 Lipid metabolism disorders, 656–672
dietetic management, HSCT, 389–390 Jaundice, 73, 101, 167–182, 600 Lipoproteins, composition, 657
dietetic management, SCID, 387–388, 391 Jejunal feeding, see Enteral feeding Liver disease, chronic, 171–178
DiGeorge syndrome, 386 causes, 172
gene therapy, 388 Ketogenesis and ketolysis, disorders of, cirrhosis, 175–176
IgA deficiency, 385–386 654–656 faltering growth, 174–175
IgG deficiency, 386 Ketogenic diets, 344–370 hepatosplenamegaly, ascites, 175
haemophagocytic lymphohistiocytosis adverse effects, 367–368 hypoglycaemia, 174
(HLH), 387 classical diet, 349–350 jaundice, conjugated hyperbilirubinaemia
haemopoetic stem cell transplantation considerations pre‐diet, 347–348 (CHB), 172
(HSCT), 388 discontinuing diet, 369 malabsorption, fat, 172–174
severe combined immunodeficiency enteral feeding, 361–363 MCT formulas, supplements, 173
(SCID), 387–388 fine tuning, 365–366 oesophageal varices, 175
Wiskott–Aldrich syndrome, 387 glucose transporter 1 deficiency pancreatic enzyme deficiency, 172
Immunonutrition syndrome, 344–345, 355 portal hypertension, 175
burns, 458 indications, contraindications, 346–347 transplant, 176–178
cancer, 381–382 infants, 358–360 vitamins, 174
critical care, 92–93 intercurrent illness, 366–367 Liver disorders, leading to chronic liver
epidermolysis bullosa, 447 ketones, 357 disease, 178–183
Infant milk formulas, standard, 10, 12 low glycaemic index treatment, 354–355 Alagille’s syndrome, 179
concentrated, 13–14 MCT diet, 350–352 α‐1‐antitrypsin deficiency, 179
enteral feeding, 36 mode of action, efficacy, 345–346 autoimmune hepatitis, 180
ready‐to‐feed, 13, 14, 44 modified Atkins diet, 351–353 biliary atresia, 179
supplemented, 13–15 modified ketogenic diets, 354 choledochal cysts, 180
Infant onset lysosomal acid lipase monitoring, 374–376 cystic fibrosis‐related liver disease, 181
deficiency (LAL‐D) (Wolman parenteral nutrition, 361–365 galactosaemia, 178
disease), 669–672 pyruvate dehydrogenase deficiency, haemangioma, 179
dietary management, 670–672 345, 355 inspissated bile syndrome, 179
very low fat diet, 672 vitamins and minerals, 357–358 intestinal failure‐associated liver disease
Infantile Refsum’s disease, 510, 512 Ketotic hypoglycaemia, idiopathic, (IFALD), 178
Inflammatory bowel disease, see Crohn’s 679–680 neonatal hepatitis, 178
disease; Ulcerative colitis Kidney diseases, 238–286 non‐alcoholic fatty liver disease
Inherited metabolic disorders, introduction acute renal failure, see Acute kidney (NAFLD), 181
to, 502–512 injury progressive familial intrahepatic
carbohydrate, lipid, protein metabolism, Bartter syndrome, 272–274 cholestasis (PFIC), 180
502–504 chronic renal failure, see Chronic kidney Wilson’s disease, 181, 183
inheritance, 504–508 disease Liver failure, acute, 168–171
newborn screening, 510 congenital nephrotic syndrome, 269–271 clinical management, 168–169
nutritional interventions, rare disorders, cystinosis, 274–275 dietetic management, 170–171
511–512 hypercalcaemia, 283–286 glucose oxidation rates, 170
Index 687
hepatic encephalopathy, 169 Low phenylalanine diet, see Medium chain fat/triglyceride (MCT),
hypoglycaemia, 168–170 Phenylketonuria emulsion, 14, 15
malnutriton, 168 Low protein diet chylothorax, 301–303
Long chain fat/triglyceride (LCT) emulsion, organic acidaemias, 560–571 disorders of long fatty acid oxidation,
14–15 tyrosinaemias, 554–557 644–652
Long chain fatty acid oxidation disorders, urea cycle disorders, 560–571 enteropathy, 140–146
643–653 Low sucrose diet, 115–117 intestinal lymphangiectasia, 118
children, minimal LCT diet, 649–652 Lower leg length, measurement, 424 ketogenic diet, 345, 350–352, 355, 366, 368
essential fatty acids, 646, 649 Lymphomas, 372 lipid disorders, 661–663, 665–666, 670–672
exercise, 651–652 Lysinuric protein intolerance, 594 liver diseases, 172–173, 177, 180, 182–183
infants, minimal LCT diet, 647–649 Lysosomal storage disorders (LSD), 511 MCT oil, 649, 651
intercurrent illness, 652–653 medium chain acyl‐CoA dehydrogenase
long chain triglycerides, 644–645, 647 Malabsorption deficiency, 642–643
medium chain triglycerides, 645–647, acute gastroenteritis, 113–115 parenteral nutrition, 69–70
649, 651 cancer, 377 preterm infants, 98, 101
monitoring, 652 coeliac disease, 121–125 short bowel syndrome, 161, 162, 165
triheptanoin, 645–646 congenital chloride‐losing diarrhoea, 120 Methionine, see Homocystinuria
uncooked cornstarch, 646, 651 congenital enteropathies, 120–121 Methylmalonic acidaemia and propionic
vitamins and minerals, 647, 649 congenital heart disease, 294 acidaemia, 572–578, see also Organic
walnut oil, 647, 649 Crohn’s disease, 128–132 acidaemias
Long chain 3‐hydroxyacyl‐CoA cystic fibrosis, 219–221 complications, 575–576
dehydrogenase deficiency disaccharidase deficiencies, 113–117 dietary management, 574–578
(LCHADD), see Long chain fatty acid eosinophilic diseases, 126–127 emergency regimen, illness, 576–577
oxidation disorders food allergy, 138, 317–318 low protein diet, 574
Long chain polyunsaturated fatty acids functional (toddler) diarrhoea, 137 monitoring, 577–578
(LCP, LCPUFA) glucose‐galactose malabsorption, 118–119 precursor‐free amino acids, 574
allergy prevention, 340, 342 gut motility disorders, 134–135 Microvillous inclusion disease, 120
congenital heart disease, 302 immunodeficiency syndromes, 385–387 Mid upper arm circumference,
familial hypercholesterolaemia, 668 intestinal lymphangiectasia, 117–118 measurement, 3, 464
healthy eating, 10, 23, 41 irritable bowel syndrome, 137–138 Migraine, food allergy, 318, 336–337
hypolipoproteinaemias, 661–664 lipid disorders, 660–662 Milk, egg, wheat and soya‐free diet,
ketogenic diets, 368 liver diseases, 172, 175, 179, 180, 182–183 142–143
long chain fatty acid oxidation disorders, modular feeds, 145–148 Milk‐free diet, 142
646–647, 649 pancreatitis, 188 Mineral bone disorder, chronic kidney
low protein diet, 525, 565 protracted, 120–121 disease, 251–254
parenteral nutrition, 69 requirements for infants with, 114 Minerals, supplements, and vitamins, 16–17
preterm infants, 98, 101 short bowel syndrome, 160, 163–164 Mitochondrial fatty acid oxidation
short bowel syndrome, 161 surgical babies, 152, 157, 158 disorders, 640–672
sources, 494 Malnutrition Modular feeds
vegan diets, 488 classification, 5 enteral feeding, 53, 55
Long chain triglyceride (LCT) content of hospitalised children, 43 intractable diarrhoea, 145–148
foods, 304 physical signs, 5 ketogenic diet, 358, 361
Low birthweight, 96 screening tools, 1 minimal fat, 662, 665
Low calcium diet, 284–286 Malonyl‐CoA decarboxylase deficiency, 654 protein‐free, 567
Low glucose‐galactose diet, 118–119 Maple syrup urine disease (MSUD), short bowel syndrome, 162
Low lactose diet 532–541 Monosaccharides, 15
galactosaemia, 600–601 branched chain amino acids, 535–541 Multiple acyl‐CoA dehydrogenase
lactose intolerance, 115, 117 diet in children and young people, 538–539 deficiency (MADD), 653–65
Low LCT diet dietary management, 535–541
abetalipoproteinaemia, 661 emergency regimen, illness, 538–541 N‐acetylglutamate synthetase (NAGS)
chylomicron retention disease, 661 infant feeding, 535–538 deficiency, 587
chylothorax, 299–304 leucine exchanges, 536–537 Nasogastric feeding, see Enteral nutrition
familial hypercholesterolaemia, 666–669 protein substitute, 537–538 Necrotising enterocolitis, 66, 89, 101, 103,
familial lipoprotein lipase deficiency, Maternal dietary protein 109–110, 159–160, 212, 303–305
665–666 prevention of food allergy, 339, 340, Neonatal hepatitis, 178
hypobetalipoproteinaemia, 661 342–343 Nephrogenic diabetes insipidus, 276–279
intestinal lymphangiectasia, 117–118 treatment of food allergy, 127, 134, 139, 331 renal solute load, 276
long chain fatty acid oxidation disorders, MCT oil, 173, 302–303, 362, 649, 651, 662, 665 salt restricted diet, 277–279
644–652 Medium chain acyl‐CoA dehydrogenase Nephrotic syndrome, acquired, 266–269
Low leucine diet, see Maple syrup urine deficiency (MCADD), 641–643 dyslipidaemia, 267
disease avoidance of MCT, 642 food allergy, 267
Low methionine diet, see Homocystinuria dietary guidelines, 642–643 growth, 267–268
Low microbial diet, see Neutropenic diet intercurrent illness, 643 nutritional management, 268–273
688 Index
Nephrotic syndrome, congenital, 269–271 feeding, 151–154 Pasteurisation, of feeds, 47–48

dialysis and transplantation, 270 fundoplication, 152–153, 155 Pectin
nutritional management, 270–271 growth, 154 dumping syndrome, 155
Netherton syndrome, 453–455 oesophageal dysfunction, 152–153 short bowel syndrome, 162
Neurodisabilities, feeding children with, sham feeding, 151 Peroxisomal disorders, 512
419–437 surgical interventions, 151–152 Phenylalanine, see also Phenylketonuria
anthropometry, 778–782 Omega‐3 fatty acids, omega‐6 fatty acids, see supplementation in tyrosinaemia
bone health, 434, 436 Long chain polyunsaturated fatty acids type I, 556
cerebral palsy, 419–420 Open reintroduction of foods, 322, 325 Phenylketonuria (PKU), 514–531
cleft lip and palate, 436 Oral allergy syndrome, see Pollen food diet in children and young people, 529–530
constipation, 433–434 syndrome dietary management, 517–531
dental caries, 434 Orofacial granulomatosis, 132 illness, management, 530–531
Down’s syndrome, 420 Oral nutritional supplements (ONS), 224 infant feeding, 525–529
dysphagia, 434–436 Oral rehydration solution (ORS), 114 phenylalanine exchanges, 517–520
enteral nutrition, 430–432 Organic acidaemias, 560–571, see also protein substitutes, 520–525
faltering growth, 431–432 Methylmalonic acidaemia; Propionic Phosphate
gastro‐oesophageal reflux disease, 433 acidaemia; Isovaleric acidaemia; acute kidney injury, 240, 242–244
micronutrients, 434, 436 Glutaric aciduria type 1 binders, 253–243
monitoring, 431 diet in childhood, 569–570 chronic kidney disease, 251–254
multidisciplinary assessment and social feeding problems, tube feeding, 570–571 phosphate-rich foods, 244
issues, 426–427 infant feeding, 569 Phospholipids, 656
neuromuscular and progressive low protein foods, 562–564 Phytanic acid, 512
neurological disorders, 421–422 monitoring, 565–567 Pollen food (oral allergy) syndrome, 320,
nutritional requirements, assessment, newly diagnosed, dietary treatment, 326, 336
421–425 567–568 Portion sizes, children’s diet, 7, 32, 34, 45
oral nutrition, 427–430 protein exchanges, 562–565 Potassium
overweight, 431 protein requirements, 560–561 acute kidney injury, 239, 242–243
thickened drinks and desserts, 428 protein substitutes, 561 chronic kidney disease, 250–251
Neutropenic diet, 49–51, 379, 390 Ornithine transcarbamoylase deficiency potassium-rich foods, 243
Non‐ketotic hyperglycinaemia, 594 (OTC), 587 Prader–Willi syndrome, 478–485
Nitisinone, in tyrosinaemia, 552 Osmotic, diarrhoea, 13 behaviours, 481–482
Nutrient‐dense infant formulas, 13, 14 Oxalate, 282 dietary treatments, 480–481
enteral nutrition, 53 growth assessment, 479–480
Nutritional assessment and monitoring, 2–8 Paediatric intensive care unit (PICU), 80 nutritional phases, 478–479
anthropometry, 2–5 Pancreatitis, 184–188 nutritional requirements, 480
biochemical and haematology tests, 6–7 acute, 186 Prebiotics, 338, 343, 448, 635
clinical assessment, 5–7 acute‐recurrent, 186–187 Prescribable products, 16
dietary intake, 7 chronic, 187–188 Preterm, infants, 96–112
growth charts, 3–4 Pancreatic enzyme deficiency/replacement breastmilk, 103–107
Nutrition, provision in hospital, 43–51 therapy (PERT) breastmilk fortifiers, 104
children, 44–45 congenital hyperinsulinism, 210 chronic lung disease, 110
diet kitchen/bay, 49 cystic fibrosis, 219–222 enteral nutrition, 102–107
infants, 44 liver diseases, 172 feed intolerance, 110
low microbial (neutropenic) diet, 49–51 pancreatitis, 187 growth, 108–109
nutrition screening, 43 Parenteral nutrition, 64–79 necrotising enterocolitis, 109–110
special feeds unit, 45–49 amino acids, 71–72 nutritional assessment, 107–109
therapeutic diets, 49 carbohydrate, 72 nutritional requirements, 96–99
undernutrition, incidence, 43 carnitine, 72 parenteral nutrition, 100–102
Nutrition screening tools, 1–2 cholestasis, 66–67 post‐discharge nutrition, 110–112
Nutrition Support Team, 43, 64 delivery methods, 77–78 preterm formulas, 107
Nutritional requirements, 8–10 essential fatty acids, 69–71 weaning onto solid foods, 111–112
fluid requirements, 8 glutamine, 71–72 Probiotics, 47, 50, 95, 110, 136, 137, 142, 282,
home PN, 79 337–338, 343, 382, 417, 448, 576, 672
Obesity, 472–478 hypoglycaemia/hyperglycaemia, 72, 78 Propionic acidaemia, see also Methylmalonic
aetiology, 472–473 indications and considerations, 65–67 acidaemia; Organic acidaemias
assessment and management, 473–474 lipid, 69–71 Protein
body mass index, 472, 474, 475, 477 micronutrients, 72–75 protein–energy ratio, 14
dietary advice, 475 nutrient and fluid requirements, 67–75 reference nutrient intake, 8, 9, 14
infants and preschool children, 476–477 nutrition support team, 64–65 safe level of intake, 561
lifestyle changes, 474 PNALD, 66–67, 70–71 supplements, modules, 15
physical activity, 475 vascular access, 72–77 Pruritus, 317
prevention, 803–804 weaning to enteral feeding, 78–79 Pseudo‐obstructive disorder, intestinal,
Oesophageal atresia, 149–155 Parenteral nutrition‐associated liver disease 134–135
cervical oesophagostomy, 151 (PNALD), see Intestinal failure‐ Purging disorder, 394
dumping syndrome, 155 associated liver disease (IFALD) Purine, 282
Index 689
Pyridoxine, in homocystinuria, 542 transplantation, 165 Thrive lines, 4

Pyruvate dehydrogenase deficiency, trophic factors, 162 Toddler diarrhoea, see Gut motility
345, 355 Shwachman–Diamond syndrome, 120–121 disorders
Skin fold thickness, measurement, 3 Tracheo‐oesophageal fistula (TOF), see
Refeeding syndrome Skin prick tests (SPT), 318 Oesophageal atresia
critical care, 91–92 Small for gestational age, 96 Transit time, gut, 58, 115, 135–137, 157,
Crohn’s disease, 131 Smith–Lemli–Opitz syndrome, 512 159–160, 162, 163, 165
eating disorders, 400–404 Sodium benzoate Triheptanoin, 645–646
enteral feeding, 63 attention deficit hyperactivity disorder, 337 Trimethylaminuria (fish odour
Reference Nutrient Intake (RNI), 8, 9 food additive, allergy, 322 syndrome), 594
Refsum’s disease, adult, 509, 512 liver disease, 169 Tufting enteropathy, 120
Regurgitation, 61, 133–134 urea cycle disorders, 589, 593 Tyrosine, supplementation in
Renal failure, see Acute kidney injury, Sodium (salt), guideline daily amounts, 18 phenylketonuria, 525
Chronic kidney disease acute kidney injury, 239, 243–244 Tyrosinaemia type I, 551–558
Renal solute load, 276–279 Bartter syndrome, 273 diet in children, late onset, 558
Renal stones, 279–283 chronic kidney disease, 244, 250–251, dietary management, 554–558
fluid, 280–281 254–255 infant feeding, 556–557
nutritional management, 281–283 congenital heart disease, 298 nitisinone, 552
Renal tubular disorders, 272–279 cystic fibrosis, 226–227 protein exchanges, 554–555
Bartter syndrome, 272–274 liver diseases, 175 protein substitute, 556
cystinosis, 274–275 nephrogenic diabetes insipidus, 276–278 Tyrosinaemia type II, 558–559
nephrogenic diabetes insipidus, 276–279 nephrotic syndrome, 269 dietary management, 558–559
Resection, gut, 110, 157, 159, 163 no added salt diet, 244, 278 Tyrosinaemia type III, 559–560
Respiratory disease, cystic fibrosis, 216–217 normal infant formulas, 24 dietary management, 560
Rett syndrome, 346, 421, 422 renal stones, 281
Rhinitis, 315, 334, 336 short bowel syndrome, 161, 162, 164 UDP‐galactose‐4‐epimerase deficiency, 606
Richner‐Hanhart syndrome, see Sodium phenylbutyrate, in urea cycle Ulcerative colitis, 128
Tyrosinaemia type II disorders, 589, 593 Upper arm length, measurement, 423–424
Rickets, 39–40 Solid tumours, 372–374 Urea cycle disorders, 587–593
Afro‐Caribbean children, 499 Somali diet, 501 dietary management, 590–593
cancer, 380 Sorbitol, 358, 630–637, 675 emergency regimen, illness, 593
cystic fibrosis, 226 Soya essential amino acid and BCAA
cystinosis, 275 formulas, 139–140, 333 supplements, 590–592
Fanconi Bickel syndrome, 626 galactosaemia, 603–604 low protein diet, 590
healthy eating, 28, 39 parenteral nutrition, oil, 69–70, 98–99, 101 monitoring, 591–593
South Asian children, 497 soya milks and food products, 117, 143 Urinary sodium, 68, 113, 121, 164, 226, 298,
tyrosinaemian type I, 552 soya‐free diet, 142, 330 388, 403, 449, 671
Williams syndrome, 284 vegetarian, vegan diet, 490, 493–495 Urticaria, food allergy, 317, 326, 332,
Riboflavin, in multiple acyl‐CoA Special feeds unit, see Feed preparation area 337, 338
dehydrogenase deficiency, 653 Stanols, sterols, 668–669
Stem cell transplant, haemopoietic (HSCT) Valine and isoleucine supplementation, see
Sapropterin, in phenylketonuria, 516 cancer, 282, 378, 379 Maple syrup urine disease
Salt, guideline daily amounts, 18 immunodeficiency syndromes, 385, Vegan diet, see Ethnic groups and cultural
Schofield equation 388–392 diets
anorexia nervosa, 402 neutropenic diet (clean, low microbial), Vegetarian diet, see Ethnic groups and
burns, 458 49–51, 379, 390 cultural diets
congental heart disease, 296 Sterol biosynthesis disorders, 512 Very long chain acyl‐CoA dehydrogenase
critical care, 87 Stricture, oesophageal, 147–149, 152, 153, deficiency (VLCADD), see Long
haemopoetic stem cell transplantation, 389 449–500 chain fatty acid oxidation disorders
neurodisabilities, 422 Succinyl‐CoA 3‐oxoacid‐CoA transferase Very low birthweight, 96
School meals, 35–36 (SCOT) deficiency, 654 Vitamins, supplements and minerals, 16–17
Severe combined immunodeficiency Sucrase‐isomaltase deficiency, congenital,
(SCID), 387–388 115–117 Waist circumference, measurement, 3
Sham feeding, 57, 59, 151, 154 enzyme substitution therapy, 116–117 Walnut oil, see Essential fatty acids
Sheep’s milk, 139, 285, 333, 512, 603 low sucrose, low starch diet, 116 Weight, measurement, 2
Short bowel syndrome, 159–165 sweeteners, 116 weight for height, 4–5
absorptive function of gut, 159–160 Swallowing, stages of, dysphagia, 435 Williams syndrome, 284–286
complications, 164 Wilson’s disease, 181, 183
enteral feeding, 160–163 Test weighing, 7 WHO, rehydration salts, 114
monitoring, 164 Thickened drinks and feeds Wolman disease, see Infant onset lysosomal
parenteral nutrition, 160, 163–164 enteral feeding, 54 acid lipase deficiency (LAL‐D)
pharmacological agents, 163 gastro‐oesophageal reflux, 133–134
preterm infants, 110 neurodisabilities, 427–428 Yin and Yang foods, 500

Clinical Paediatric Dietetics 2020

Uploaded by

Copyright:

Available Formats

Clinical Paediatric Dietetics 2020

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Clinical Paediatric Dietetics 2020

Uploaded by

Copyright:

Available Formats

Clinical Paediatric Dietetics

0004760602.INDD 1 6/12/2020 11:14:11 AM

Vanessa Shaw, MBE, MA, PG Dip Dietetics, RD, FBDA

0004760602.INDD 3 6/12/2020 11:14:13 AM

Limit of Liability/Disclaimer of Warranty

Cover Design: Wiley

Set in 9.5/11.5pt Palatino by SPi Global, Pondicherry, India

0004760602.INDD 4 6/12/2020 11:14:13 AM

List of Contributors vii 11 Endocrinology 189

1 Principles of Paediatric Dietetics: Nutritional 13 Kidney Diseases 238

7 Preterm Infants 96 19 Eating Disorders 393

8 Gastroenterology 113 20 Autism 405

9 Surgery in the Gastrointestinal Tract 149 21 Feeding Children with Neurodisabilities 419

10 The Liver and Pancreas 166 22 Epidermolysis Bullosa and Rare Skin Disorders 438

ftoc.indd 5 6/4/2020 10:27:17 PM

23 Burns 456 28 Disorders of Amino Acid Metabolism, Organic

ftoc.indd 6 6/4/2020 10:27:17 PM

Marjorie Dixon BSc, RD Karen King BSc, RD

fbetw.indd 7 6/12/2020 11:20:41 AM

Julie Lanigan BSc, PhD, RD Dasha Nicholls FRCPsych, MD (Res), FAED

fbetw.indd 8 6/12/2020 11:20:41 AM

Chris Smith BSc, RD Fiona J. White BSc, RD

fbetw.indd 9 6/12/2020 11:20:41 AM

0004760604.INDD 10 6/12/2020 11:16:11 AM

0004760605.INDD 11 5/22/2020 11:33:14 PM

The book is accompanied by a website:

The website features:

• Figures in PowerPoint format.

0004760605.INDD 12 5/22/2020 11:33:15 PM

Introduction protein–energy undernutrition [1]. Despite the recommenda-

Clinical Paediatric Dietetics, Fifth Edition. Edited by Vanessa Shaw.

STAMP PYMS Head

Visit 2 Decimal age = 6.8 years Tongue Colour changes B vitamins

Table 1.6 Biochemical and haematological tests.

Nutrient Test Normal values in children Comments

Table 1.9 Selected dietary reference values, 1991.

RNI per day

EAR, estimated average requirement; RNI, reference nutrient intake.

Table 1.10 Estimated average requirement (EAR) for energy for infants, 2011.

Breastfed Breastmilk substitute fed Mixed feeding or unknown

Source: Scientific Advisory Committee on Nutrition [49].

Table 1.12 Guide to energy requirements in clinical practice.

Energy (EAR) Energy (EAR)* Energy (EAR) Energy (EAR)*

1−2 months 5.0 96−120 4.7 96−120

Table 1.13 Guide to increased oral and enteral requirements.

Infants 0–1 year* Children

Energy High: 130−150 kcal (545−630 kJ)/kg/day High: 120% EAR†

* Based on actual weight, not expected weight.

Whey‐based infant Casein‐based EFSA 2010* [56] IoM 2005† [57]

Overweight children will need less fluid than the

• He is 122 cm tall = 50th centile Concentrating infant formulas

PE, protein–energy ratio; EBM, expressed breastmilk.

Table 1.19 Energy modules.

Per 100 g Ingredients* Energy (kcal)* kJ Na (mmol) K (mmol) PO4 (mmol)

Glucose polymer powders

MCT, medium chain triglycerides.

Table 1.21 Protein modules (powders).

Table 1.22 Vitamin supplements.

5 drops for all infants 0.3 mL < 1 year 0.3 mL < 1 year

Thiamin (B1) mg − 0.4 1 3.0

Refeeding syndrome hysical activity. Following a review of the literature, Afzal