Ann Allergy Asthma Immunol 127 (2021) 28−35

Contents lists available at ScienceDirect

Review

The practical dietary management of food protein-induced

enterocolitis syndrome

Marion Groetch, MS, RDN*; Mary Grace Baker, MD*; Raquel Durban, RDNy;
Rosan Meyer, PhD, RDz; Carina Venter, PhD, RDx; Antonella Muraro, MDk
* Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York
y
Asthma & Allergy Specialists, Charlotte, North Carolina
z
Department of Paediatrics, Imperial College London, London, United Kingdom
x
Section of Pediatric Allergy and Clinical Immunology, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
k
Food Allergy Referral Centre, Department of Woman and Child Health, Padua University Hospital, Padua, Italy

Key Messages
 Suboptimal oral intake, limited food choices, and knowledge deficits related to feeding have contributed to overt malnutrition and malnu-
trition risk for children with food protein-induced enterocolitis syndrome (FPIES).
 Children with FPIES to 3 or more foods are at increased risk of developing food aversion and having poor body weight gain.
 Caregivers of children with FPIES report a high degree of psychosocial burden.
 Dietary management of FPIES entails avoidance of allergens, supporting normal growth and development and advancement of comple-
mentary foods.
 Providing a detailed individualized feeding plan may help prevent feeding aversions and nutritional deficiencies and ease the burden on
caregivers.

A R T I C L E I N F O A B S T R A C T

Article history: Objective: Food protein-induced enterocolitis syndrome (FPIES) is a non−immunoglobulin E-mediated food
Received for publication November 14, 2020. allergy with potential risk of malnutrition related to the early onset of disease, frequent avoidance of cow’s milk,
Received in revised form March 3, 2021. and the possibility of multiple food triggers. This publication is aimed at providing an evidence-based, practical
Accepted for publication March 16, 2021.
approach to the dietary management of FPIES.
Data Sources: This is a narrative review summarizing information from national and international guidelines,
retrospective studies, population studies, review articles, case reports, and case series to evaluate for nutritional
risk and develop guidance for risk reduction in children with FPIES.
Study Selections: We have included retrospective clinical cohort studies, population-based studies, case reports,
and case studies. We did not exclude any studies identified owing to the small number of studies addressing the
nutritional management of individuals with FPIES.
Results: Children with FPIES are at risk of malnutrition owing to suboptimal oral intake, limited food choices, and
knowledge deficits related to feeding. In particular, children with 3 or more FPIES triggers seem to be at
increased risk for poor weight gain and developing food aversion. Caregivers of children with FPIES also report a
high degree of psychosocial burden.

Reprints: Marion Groetch, MS, RDN, Division of Pediatric Allergy and Immunology, Johnson, Abbott, and Nestle  and research support from Danone/Nutricia and
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy reports to be on the CoMISS board from Nestl e . Dr Venter reports to have pro-
Place, Box 1198, New York, NY 10029. E-mail: Marion.groetch@mssm.edu. vided and reviewed educational material for Danone, Mead Johnson Nutrition,
Disclosures: Ms Groetch receives royalties from UpToDate, FARE, and AND; serves Abbott Laboratories, and Nestle Nutrition Institute and to have received research
on the Medical Advisory Board of IFPIES, as a Senior Advisor to FARE, and as a support from Reckitt Benckiser, The National Peanut Board, and the INTENT
Health Sciences Advisor for APFED; and has no commercial interests to disclose. group. Dr Muraro reports to have received honoraria for educational lectures
Ms Durban reports to have received honoraria for educational lectures from from Aimmune, DVB Technologies, Nestle  Health Institute, Nestle
 Purina, Nutricia,
Abbott Nutrition, Mead Johnson Nutrition, and Nutricia North America and con- and Mylan. The remaining authors report no conflict of interest.
sultant fees from AstraZeneca and Mead Johnson Nutrition. Dr Meyer reports to Funding: The authors have no funding sources to report.
have received honoraria for educational lectures from Nutricia/Danone, Mead

https://doi.org/10.1016/j.anai.2021.03.007
1081-1206/© 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
 M. Groetch et al. / Ann Allergy Asthma Immunol 127 (2021) 28−35 29

Conclusion: Appropriate dietary management entails the following 3 essential components: supporting normal
growth and development, avoidance of allergens, and advancement of complementary foods. Education to avoid
the trigger food and assisting caregivers in creating an individualized, well-designed complementary feeding
plan to meet the infant’s nutritional needs for optimal growth and development are essential management
strategies.
© 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Introduction metabolic acidosis, and/or electrolyte disturbances; these findings

may initially be mistaken for sepsis.13-17 Imaging may reveal dilated
Food allergies present nutritional challenges and risks in the pedi-
loops of bowel, sometimes with air-fluid levels and intramural gas.
atric population. The term food allergy covers a wide spectrum of
Treatment is supportive, with intravenous fluids, electrolyte reple-
clinical diseases, each with its own nutritional implications. Children
tion, and avoidance of the food trigger. With elimination of the culprit
with cow’s milk allergy, early onset food allergy, and non−immuno-
food, recovery is expected in days to weeks.11 If the culprit food is
globulin (IgE)-mediated disease and mixed IgE-/non−IgE-mediated
briefly avoided then re-introduced, patients may experience an acute
disease are at greatest nutritional risk.1,2 Food protein-induced
FPIES reaction, confirming the diagnosis.6,11
enterocolitis syndrome (FPIES) meets the criteria for increased nutri-
Acute FPIES is typically diagnosed in older infants or young chil-
tional risk, as it is a non−IgE-mediated food allergy disorder with
dren, often around the time of solid food introduction. With acute
early onset of disease, frequently triggered by cow’s milk, possible
FPIES, children experience repetitive, profuse vomiting 1 to 4 hours
involvement of multiple food triggers, and may result in persistent
after ingestion of the culprit food. The vomiting may be accompanied
gut inflammation when the food triggers remain in the diet.1,3 A
by pallor and lethargy, with diarrhea that may contain blood and/or
recent retrospective study of 203 patients with FPIES found that com-
mucus occurring 5 to 10 hours after ingestion.12 Owing to the profuse
pared with FPIES cases with 2 or fewer triggers, patients with multi-
vomiting, children with a severe presentation are at risk for dehydra-
ple triggers were more likely to develop food aversion (43.2% vs
tion and even shock. Laboratory evaluation often reveals a leukocyto-
16.9%; P < .001) and to have poor weight gain (21.6% vs 6.6%;
sis with a neutrophilic predominance, mimicking infectious
P = .005).4 To compound the risk, a 2017 survey found that approxi-
etiologies and potentially delaying the FPIES diagnosis.9,12 Treatment
mately one-third of pediatricians surveyed had never heard of FPIES
is supportive with intravenous fluids, antiemetics, and steroids,
and another one-third were not familiar with diagnostic criteria or
related to the theory that FPIES is cell mediated. Symptoms often
appropriate management.5
resolve completely within hours, although diarrhea may be a delayed
Appropriate dietary management entails the following 3 essential
symptom that is more persistent.
components: supporting normal growth and development, avoid-
Atypical FPIES describes patients with a compelling history of
ance of allergens, and advancement of complementary foods. Educa-
FPIES who also have evidence of IgE sensitization to the trigger food.9
tion to avoid the trigger food and assisting caregivers in creating an
It is estimated that atypical FPIES may occur in 5% to 25% of cases,
individualized, well-designed complementary feeding (CF) plan to
and it is thought to be more common for cow’s milk and egg.13,14,18-
meet the infant’s nutritional needs for optimal growth and develop- 24
Atypical FPIES has been associated with a more prolonged course,
ment are essential management strategies. This publication is aimed
with possible persistence of FPIES reactivity even into adulthood.9,25
at providing an evidence-based, practical approach for health care
In addition to the sensitization to their FPIES triggers, children with
professionals working with patients with FPIES.
FPIES may be more likely to develop IgE-mediated allergy to other
foods.13,19,26

Overview of Food Protein-Induced Enterocolitis Syndrome

Diagnosis and Oral Food Challenge
FPIES is characterized by delayed, often dramatic, gastrointestinal
symptoms.6 FPIES classically presents in infancy or early childhood, The diagnosis of FPIES is based on a compelling clinical history.6
with most children developing tolerance by school age, although There are currently no laboratory or imaging tests to confirm the
reports of adults with suspected FPIES are increasing.7,8 Although diagnosis. A positive oral food challenge (OFC) result to the suspected
much remains to be learned on the pathophysiology of FPIES, it is FPIES trigger is confirmatory, but often not necessary for diagnostic
thought to be cell mediated with cytokine release contributing to purposes in the setting of a suggestive history. Therefore, more often,
increased intestinal permeability and inflammation.6 Of note, 2 phe- OFCs are used to evaluate tolerance development.6
notypes of FPIES have been described, acute and chronic. Some FPIES OFC protocols have not been studied systematically. Guid-
patients with FPIES also become sensitized to the FPIES trigger, and ance from the International Consensus Guidelines for the Diagnosis
this is termed atypical FPIES.9 and Management of Food Protein-Induced Enterocolitis Syndrome
(ICG) recommends OFCs in patients with suspected FPIES to a specific
Phenotypes
trigger food in a medically supervised setting where prolonged
Chronic FPIES occurs when the culprit food is ingested regularly, observation and fluid resuscitation are available.6 The consensus dos-
resulting in chronic symptoms not temporally related to feedings.6 ing recommends 3 equal doses in a 30-minute period, with a cumula-
This condition has been described exclusively in early infancy, and tive dose between 0.06 and 0.6 g food protein/kg body weight
most cases are triggered by cow’s milk- or soy-based formula, with (usually 0.3 g food protein/kg body weight), not to exceed 3 g of total
symptom onset within 1 to 4 weeks of introducing formula.10-12 food protein, 10 g total food or 100 mL liquid for the initial feeding.
Symptoms include intermittent but progressive vomiting and watery Recommended observation is 4 to 6 hours. The OFC protocol is at the
diarrhea that may contain blood or mucus or both.9,13 As feedings discretion of the physician, and lower starting doses or longer obser-
with the culprit formula continue, infants become ill with lethargy/ vation periods may be reasonable depending on the individual clini-
irritability, failure to thrive (FTT), weight loss, abdominal distention, cal presentation. If a very low starting dose is used and tolerated,
and/or dehydration, which may be severe and cause hypotension or then a second full dose may be offered 2 to 3 hours after the initial
shock. On evaluation, infants often demonstrate laboratory abnor- feeding, followed by an observation of 4 hours. Alternative
malities including leukocytosis with a neutrophilic predominance, approaches have been published and further research is required to
anemia, thrombocytosis, methemoglobinemia, hypoalbuminemia, provide an international standardized approach to OFC for FPIES.27
30 M. Groetch et al. / Ann Allergy Asthma Immunol 127 (2021) 28−35

Atypical FPIES requires a hybrid OFC approach, beginning with a noted, and this is speculated to be related to differences in feeding
small dose and offering gradually increasing doses every 15 to 30 practices.
minutes as is typical with IgE-mediated food allergy, followed by a Most children (65%-80%) have FPIES to only a single food
prolonged observation period common with FPIES.28 trigger.6,13,19-22,31,38 However, it has been observed that children
Decisions on timing of OFC to determine tolerance may depend on with FPIES to cow’s milk or soy early in life are at risk for FPIES to
a number of factors including the clinical history, food trigger, time solid foods. In addition, children with FPIES to 1 solid food seem
lapse since the last reaction to the food, and even the patient’s coun- more likely to react to other food triggers, with especially high cor-
try or region as geographic disparities in FPIES presentation and reso- eactivity among grains.13,22,25 Some case series report up to 30% of
lution are reported. The ICG recommends offering an OFC 12 to 18 patients with multiple FPIES triggers.24,39 In a recent cohort, 69.4% of
months after the last reaction to the food, although this has not been caregivers reported that their children avoided at least 2 food groups
critically evaluated and is based on expert opinion. Looking at the because of FPIES.34 Although multiple food FPIES is not the norm,
natural history of FPIES to specific foods, Wang et al29 reported that prophylactic multiple food avoidance may be more common.
the mean age of tolerance development to milk, soy, and grain was
earlier than that to other solid foods in a US population (35 months
of age at the time of passed challenge for milk, 38 months for soy, Nutrition and Feeding
and 36 months for grains). Other solid foods included egg, corn, beef, Dietary Avoidance Education
poultry, sweet potato, butternut squash, carrot, white potato, peanut,
coconut, and peach, with 12% outgrowing FPIES by 2 years, 31% by ICG summary statement on avoidance states the following: “Do
3 years, 60% by 4 years, and 70% by 5 years. The mean age of passing not routinely recommend avoidance of products with precautionary
a challenge to these foods was 44.9 months (n = 19; SD = 23.6). allergen labeling in patients with FPIES,” though the guidelines group
acknowledges the limited data set on which this recommendation is
based.6 Currently, no studies have been performed to set reliable
thresholds in children or adults with FPIES. Katz et al24 reported that
Food Triggers 82% of children tolerated 50 mL of milk before a reaction developed.
Sopo et al21 reported that 78% of their patients reacted only after con-
Common chronic and acute FPIES triggers are summarized in suming a full portion of the trigger food. Finally, Fogg et al reported
Table 1. Given that chronic FPIES seems to occur only in early infancy reactions to 0.15 g of protein/kg body weight.40 This relates to 30 mL
with regular ingestion of the culprit food, almost all cases are linked of milk, 45 mL of soy milk, or one-quarter of large egg in a 6-month-
to cow’s milk- and soy-based formulas, with only case reports sug- old infant (7.8 kg £ 0.15 g = 1.15 g of protein), which is still much
gesting a role for traces of these and other food triggers in higher than amounts of protein detected in products with or without
breastmilk.9,11,12,14,22,30 Coreactivity to cow’s milk and soy is reported precautionary advisory labelling. Ford et al41 reported detectable lev-
in 20% to 40% of infants in the United States but does not seem to be els of 0.084 to 0.26 mg egg per serving, 0.13 to 7.3 mg milk per serv-
as common in other parts of the world.13,21,22,24-26,31-33 ing, and 0.17 to 5.8 mg peanut per serving in products with
Acute FPIES reactions occur on ingestion of foods that are eaten precautionary labels for these allergens.
intermittently or after a period of avoidance of chronic FPIES triggers. Caregivers should be educated on how to read a label to identify
The most common acute FPIES triggers include grains (particularly the food trigger as an intentional ingredient. The key to successful
oat and rice), cow’s milk, soy, egg, seafood, poultry, and select fruits/ culprit food elimination is sufficient avoidance to prevent reactions
vegetables.13,18-21,23,26,31,34-36 Reports of acute FPIES to peanut seem without excessive avoidance that may hinder food choices and nutri-
to be increasing, possibly related to early introduction.37 Geographic tional intake.
variation in the prevalence of individual FPIES triggers has been

Table 1 Breastfeeding
Major Food Triggers for Chronic and Acute FPIES and Major Acute FPIES Triggers Listed
by Region Based on Presently Available Data Human milk is the best source of nutrition for infants, and breast-
Condition FPIES triggers
feeding should be supported by health care professionals.42 Limited
data exist on the occurrence of FPIES in exclusively breastfed infants.
Chronic FPIES >99% of cases9,11,12,14,15,30
Meyer et al43 summarized data from 1 population study,22 6 retrospec-
Cow’s milk-based formula
Soy-based formula
tive studies,9,13,20,21,39,44 4 review publications,45-48 1 international
<1% of cases guideline publication,6 and 4 case studies/case series30,49-51 in a recent
Food triggers in breast milk European Academy of Asthma, Allergy and Clinical Immunology posi-
Acute FPIES United States13,26,31,34,36 tion statement (Table 2). The position statement concludes that it is
Cow’s milk
uncommon to see FPIES in exclusively breastfed infants. This is in agree-
Soy
Grains ment with the ICG, which do not recommend routine maternal allergen
Egg avoidance unless a child presents with symptoms while breastfeeding,
Fruits and vegetables in which case, maternal allergen avoidance may be considered.6
Europe18-21,23
Cow’s milk
Fish
Formula Choices
Egg
Grains High rates of coreactivity to cow’s milk and soy have been
Soy
reported for infants in the United States, so avoidance of both food
Australia22
Rice triggers is recommended for affected infants.6,9,12,13,25,32,33 Breast-
Cow’s milk feeding or hypoallergenic formulas are preferred sources of nutrition
Egg and are recommended by the National Institute of Allergy and Infec-
Oat tious Diseases52 and the ICG in the presence of milk- or soy-triggered
Poultry
FPIES.6 There are no specific recommendations from these US groups
Abbreviation: FPIES, food protein-induced enterocolitis syndrome. regarding which hypoallergenic formula should be offered, amino
NOTE. Chronic FPIES triggers are consistent worldwide. acid-based formula (AAF) or extensively hydrolyzed formula (EHF),
 M. Groetch et al. / Ann Allergy Asthma Immunol 127 (2021) 28−35 31

Table 2
Presentation of FPIES During Exclusive Breastfeeding

Country Study characteristics Number Findings

Australia22 Population-based survey 240 infant and children 5% (n = 11) acute FPIES while exclusively breastfed (milk, grains, chicken)
Japan14 Clinical cohort 46 children 6.5% reacted during exclusive breastfeeding (rice and soy)
Israel44 Birth cohort 64 children 9.3% presented with first FPIES reaction while breastfed
United States9 Clinical cohort 16 children 50% presented with first FPIES reaction while breastfed
Sopo et al21 Clinical cohort 66 children 95% of children with FPIES were breastfed, but it is unclear if exclusively breastfed
Tan et al51 Case 1 infant Infant; exclusively breastfed developed acute FPIES from maternal ingestion of a
large amount of soy
This group reported that 21 breastfed infants with acute FPIES presented during
breastfeeding, but not clear if they were exclusively breastfed
Man et al50 Case study 1 infant Infant exposure to rice and sweet potato while exclusively breastfeeding
Italy50 Case studies 2 children Chronic FPIES caused by maternal cow's milk ingestion
United States13 Retrospective study 160 children and adults 3 children presented with chronic FPIES by while exclusively breastfed (milk)

Abbreviation: FPIES, food protein-induced enterocolitis syndrome.

although the ICG reports 10% to 20% will not tolerate EHF and AAF greater in the patients who had villous atrophy with FPIES soon after
will be required. There is a lack of research directly comparing differ- diagnosis.3 This cytokine, in addition to interleukin-6 and interleukin
ent hypoallergenic formulas. International guidelines for the man- 1-b, has been found to have a significant impact on the longitudinal
agement of cow’s milk allergy provide different formula growth plates through decreased chondrocyte proliferation and
recommendations for FPIES. The European53,54 and World Allergy hypertrophy and increased apoptosis.63 However, there are no data
Organization guidelines55 recommend the use of an EHF. The British on these cytokines in asymptomatic children with appropriately
Society of Allergy and Clinical Immunology56 recommends the use of treated FPIES.
an AAF. The choice of formula may be clearer by focusing on other In addition, children with FPIES may also have other atopic disor-
factors and not just the clinical diagnosis. EHF may be suitable for ders including eczema and asthma,13 which may further affect longi-
many infants and children with FPIES, but according to guidance by tudinal growth. This implies that there are factors outside of dietary
Meyer et al,57 the use of AAF should be considered in children with elimination and vitamin/mineral deficiencies that may contribute to
FPIES who also present with growth faltering and multiple food aller- poor growth.
gies. AAF may also be considered, on an individual basis, when a sup- A recent study has highlighted the psychosocial impact on parents
plemental formula or transition to complete formula feeding is of children with FPIES with increased anxiety, stress, and worry,
desired for infants who have had a severe FPIES presentation to which can have a negative impact on the introduction and expansion
cow’s milk protein formula or who have reacted to the small amount of nutritious solid foods in growing infants.64 This delay may also
of milk protein present in breast milk.58 lead to missing oral-motor and behavioral milestones essential in
developing normal eating skills, thereby increasing the risk of feeding
difficulties that may also negatively affect growth.65,66 Several micro-
nutrients are critical for ongoing growth, including sodium, chloride,
Impact on Growth and Nutrition
zinc, vitamin D, and iron.67 Children with FPIES may have impaired
The impact of food allergy on growth has been well described in absorption, reduced intake, and excessive losses as part of their clini-
both IgE- and non−IgE-mediated food allergy.59 Although under- cal presentation.6 All of these may negatively affect micronutrient
weight, defined by weight-for-age z-score of less than negative 2 is status (Fig 1).
described in just above 5% in an international survey, stunting,
defined by a height-for-age less than negative 2 z-score is much
more prevalent, affecting approximately 10% of pediatric patients
Preventing and Correcting Vitamin and Mineral Deficiencies
with food allergy.1 Although several studies have evaluated growth
in children with non−IgE-mediated allergy1,60,61 and FTT is part of Vitamin and mineral deficiencies, in particular vitamin D, vitamin
the diagnostic definition for chronic FPIES, there are limited data A, calcium, iron, and zinc, have been well described in patients with
regarding the prevalence of malnutrition specifically in FPIES. In food allergy.61,68-70 Although there are limited data on specific vita-
2019, Blackman et al36 in a retrospective case series of 76 patients min and mineral deficiencies in FPIES, it is assumed that this popula-
with FPIES from a US allergy center reported FTT in 16 (22%) children. tion has the same risk as other children with food allergy. Health care
Of the 16 children with FTT, 10 were evaluated by the dietitian, 6 of providers should, as a baseline, follow country-specific guidelines for
whom were given the nutrition diagnosis of malnutrition with asso- vitamin/mineral supplementation for all children (ie, iron, vitamin
ciated etiologies of suboptimal oral intake and limited food choices D).71 In addition, dietary assessment, ideally performed by a dietitian,
related to FPIES, whereas the remaining 4 were identified as at may be useful in gauging necessity of further specific vitamin and
increased risk of malnutrition related to FPIES knowledge deficits. It mineral supplementation advice.6 It is important to understand that
is therefore crucial as part of the diagnosis and ongoing monitoring particularly in inadequately managed food allergies, vitamin and
of FPIES patients to assess weight, stature, and where appropriate, mineral deficiencies are difficult to predict through dietary intake
head circumference to inform both diagnosis and dietary manage- alone, as this does not account for poor absorption or excessive
ment and provide feeding guidance that addresses avoidance and losses.72 Therefore, targeted nutritional laboratory biomarkers may
nutritional needs. be useful in some patients, but knowledge of the accuracy of meas-
Other factors may influence growth, including ongoing inflamma- ures and influencing factors is crucial in the interpretation of the
tion owing to other atopic comorbidities, persistent unnoticed markers.73
inflammation, and feeding difficulties as hypothesized by Meyer Any identified micronutrient deficiency should be corrected with
et al,62 but these have been poorly studied in FPIES. In 2002, a study supplementation but also the cause should be identified and
highlighted the increased expression of tumor necrosis factor-alpha addressed, which may be dietary or related to reduced absorption or
on both epithelial and lamina proprial cells, which was significantly excessive losses or both. Identification of the nutrition problem and
32 M. Groetch et al. / Ann Allergy Asthma Immunol 127 (2021) 28−35

Figure 1. Potential contributing factors to growth faltering in FPIES. FPIES, food protein-induced enterocolitis syndrome.

the etiology is part of the nutrition care process and highlights the food, waiting until the symptoms have fully resolved before introduc-
importance of the dietitian in the management of FPIES. Table 3 pro- ing a new food is a practical approach.
vides practical tips on prevention and treatment of vitamin and min- During the CF period, beginning around 6 months of age, micro-
eral deficiencies. nutrient intake must increasingly be met by complementary food. A
systematic review by Obbagy et al75 found strong evidence that high-
iron complementary foods helped maintain iron stores and prevent
Guidance for Early Complementary Feeding to Minimize Nutritional Risk iron deficiency anemia in the first year of life for breastfed infants.
In 2014, Venter and Groetch48 already recognized the impor- Recent published draft guidance by the US Dietary Guidelines Advi-
tance of providing clear feeding advice to parents with FPIES to sory Committee Report suggests including 0.5 ounce of fortified
minimize the nutritional risk and ensure optimal and timely infant cereal in the early complementary diet for the breastfed infant
exposure to new tastes and textures. The recent ICG has to help meet iron and zinc needs—nutrients with critical gaps.74
expanded this further, based on new research, with a suggested For infants with FPIES, however, adding grains in the early CF
CF plan for patients with FPIES.6 Figure 2 provides guidance for period may be challenging owing to the risk of multiple food FPIES
CF; it includes foods that are nutritionally dense (meat, fish, poul- reported in case series in 15.8% to 69.4%,6,13,19,22,29,36 with grains being
try, eggs, nuts, seeds, legumes, fruits, vegetables, grains), follows the most often avoided food group in some recent reports.4,22,36 The
current infant feeding guidelines,74 and stratifies foods by their risk of coreactivity is higher between rice and oat13,76,77 than between
risk for triggering FPIES based on case series.6 It is, however, these 2 grains and wheat or corn. Wang et al29 reported that no patient
important that clinicians individualize these CF recommendations (n = 13) challenged to wheat owing to oat- or rice-triggered FPIES had
based on the foods that are current triggers for that patient, the a positive challenge, with a mean challenge age of 27 months (range,
cluster patterns associated with those foods, the patient’s nutri- 9-50 months). Blackman et al36 also reported low cross reactivity with
tional needs, and locally acceptable/available foods. wheat (5%) in those with rice FPIES (n = 39), as did Mehr et al22 with a
A common question among caregivers is how quickly to introduce cross reactivity of 5% for wheat and 1% for corn. These reports should
new foods. Mehr et al15 reported in their cohort of 350 infants that be reassuring when introducing grains, especially fortified grains for
just more than half (51%) reacted on the first exposure to the food, the breastfed infant, as wheat and corn are more often fortified.
14% on the second exposure, 11% after 2 tolerated exposures, and Whole-grain wheat plus other ancient and pseudograins such as mil-
24% after 3 or more tolerated exposures.15 It is often recommended let, quinoa, buckwheat, and amaranth are all excellent grain options,
that caregivers introduce higher risk foods as a single ingredient and especially for bottle-fed infants receiving sufficient iron-fortified for-
continue feeding for at least 4 days before introducing any other new mula who do not benefit from fortified grains.74
food to observe for the development of a reaction.6 As the infant tol- The American Academy of Pediatrics recommends supplemental
erates a greater number of foods, the amount of time between food iron (1 mg/kg/day) for infants with no dietary source of iron after 6
introductions should be reduced to prevent delays in feeding a months of age to prevent iron deficiency.71 The Dietary Guidelines
diverse and balanced diet. In the event of an FPIES reaction to the Advisory Committee Report suggests screening those at risk of iron

Table 3
Practical Tips on Prevention and Treatment of Vitamin and Mineral Deficiencies

Tips of prevention of vitamin and mineral deficiencies Tips on correcting vitamin and mineral deficiencies

 Ensure baseline supplementation, as suggested by  Consider nutritional biomarkers in particular in children with growth failure, ongoing/
country-specific guidelines frequent diarrhea, and vomiting
 Provide guidance on foods that are rich in iron and other essential  Provide targeted supplementation for the nutrient that is deficient
micronutrients in breastfed infants  Understand potential gastrointestinal adverse effects of supplements (ie, iron)
 Give advice on fortified foods (ie, cereals) when appropriate  Understand interaction between supplemented micronutrients (ie, copper and zinc)
 Avoid oversupplementation in a child where no  Monitor supplementation to ensure supplements are stopped when required
deficiency is suspected  Assess and address causes of deficiency
 Monitor patient frequently to ensure that complementary foods have been
introduced in a timely manner

Abbreviation: FPIES, food protein-induced enterocolitis syndrome.

 M. Groetch et al. / Ann Allergy Asthma Immunol 127 (2021) 28−35 33

Figure 2. Guidelines for early feeding. The letter “a” indicates that the limited variety of foods in this table provides a starting point for feeding based on available data. Categories
listed are no guarantee of tolerance or adverse effect. In addition, there are many foods not listed that should be added to the infant diet as age and tolerance dictates. FPIES, food
protein-induced enterocolitis syndrome.

deficiency before supplementation.74 Country-specific dietary sup- caregiver and infant should also be evaluated to ensure successful
plement guidance should always be considered as nutritional intake implementation of recommendations in the event of parental worry
and needs can be affected by the distinctive regional and culturally to proceed with feeding.48 Building a repertoire of safe food fosters a
relevant infant foods. positive relationship with food, facilitates oral-motor skill develop-
ment, and nurtures the relationship between infant and caregiver as
it relates to feeding.80
Feeding Skill Development
In addition, responsive feeding (RF) should be encouraged. RF
FPIES is associated with oral feeding aversion and delay in achiev- involves reciprocity between the child and caregiver during the feed-
ing feeding milestones.65 In a retrospective review by Su et al,4 the ing process and is characterized by caregiver recognition of and
risk of developing food aversion in a cohort of children with FPIES response to the child's cues of hunger and satiety.81 RF guides care-
increased in cases triggered by 3 or more foods compared with just 1 givers on how to feed their infants and young children, which com-
or 2 foods (adjusted odds ratio, 3.07; 95% confidence interval, 1.38- plements existing global guidance on what to feed young children
6.82; P = .006). Early food avoidance imposes limitations, not only on and also emerging US guidance on what to feed children 0 to 2 years
food choices, but also on mealtime structure, feeding skill develop- of age.74 RF fosters healthy eating habits and has the potential to opti-
ment, and frequency of feeding interaction with the caregiver, mak- mize child growth and development outcomes, especially where mal-
ing the consequences of FPIES in the CF period multifaceted.65 nutrition is a risk.
Although an infant’s age provides a goal timeline for acquired Should appropriate food selection, diverse preparation, and secure
infant feeding skills to begin CF, each child will develop skills within caregiver bond and responsiveness not result in successful progres-
a range of suggested months. In the 3 phases of CF, stage 1 initiates sion of feeding, feeding therapy may be considered. Early recognition
introduction of solids to infants around 6 months of age beginning of feeding difficulties can initiate an appropriate referral for collabo-
with smooth purees. In stage 2, between 6 and 9 months of age, the rative care with a speech language pathologist or occupational thera-
infant will have acquired skills needed to consume soft lumpy, pist or comprehensive feeding clinic. Techniques to support feeding
mashed food and soft finger foods. By stage 3, the infant is 9 to 12 skill development can be facilitated by these therapists to lessen the
months of age and has typically developed the ability to eat chopped, burden of impact from feeding aversion.65
minced foods and firm finger foods48 (Fig 2).
However, all feeding skills in this time period are learned through
the presentation of foods, so CF of diverse flavors and textures is
Conclusion
important to skill development. To achieve diet diversity, it is recom-
mended that nutritionally valuable, low-risk, complementary foods Food protein-induced enterocolitis syndrome (FPIES) is a non
be introduced beginning by 6 months of age to meet growing nutri- −IgE-mediated food allergy with onset in early infancy and risk of
tional demands while progressively advancing the variety and tex- multiple food triggers, which presents nutritional challenges that are
tures of foods to support feeding skill development.6,48 The selection best addressed preemptively by the health care provider. Dietary and
of low-risk complementary foods should be valued during the initial nutritional management of FPIES entails appropriate avoidance of
CF stages for its versatility to provide an assortment of textures to the trigger food(s) without excessive avoidance, guidance on early
support timely feeding skill acquisition. The range of flavors and tex- introduction of safe and nutritious complementary foods, and pro-
tures a food offers directly correlates with prevention of feeding gressive advancement of skill-appropriate food textures that will
aversion.78,79 If an infant’s diet is limited in variety, texture advance- provide the backdrop for feeding skill development. Close growth
ment can still be achieved, even with just 1 food, by changing meth- monitoring of children with FPIES is warranted to identify and
ods of preparation from smooth puree, mashed food, foods with address poor growth, which is a risk factor in this population. Finally,
lumps and bumps, and finally soft finger foods. an awareness of the psychosocial impact of the disease will help clini-
Although food selection and its creative preparation can lead to cians work closely and collaboratively with families to address their
achieving nutrition and feeding skill goals, the dynamic between feeding concerns. This highlights once more the need for a
34 M. Groetch et al. / Ann Allergy Asthma Immunol 127 (2021) 28−35

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