Indian Pediatrics January 2023 Issue

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Indian
Pediatrics
Editor-in-Chief Devendra Mishra
January 2023 Volume 60 Number 1
CONTENTS
FROM THE EDITOR’S DESK
Editing the Academy’s Journal in the Peri-COVID Era – A Different Ball Game Altogether!–DEVENDRA MISHRA 7
PRESIDENT’S PAGE
Diamonds are Forever!–UPENDRA KINJAWADEKAR 9
INVITED COMMENTARIES
Measuring Overnutrition in Children: Do We Know Enough?–SHIVANI A PATEL, NATALIA E POVEDA 11

Effect of Kangaroo Mother Care on Cerebral Hemodynamics in Preterm Infants
–RUCHI N NANAVATI, PRASHANTH RR 13
Urgent Need of Research on Neurodevelopmental Outcome of Preterm/Very Low Birth Weight Neonates
From India–KANYA MUKHOPADHYAY 15
RESEARCH PAPERS
Comparison of Weight for Height and BMI for Age for Estimating Overnutrition Burden in Under-Five
Populations With High Stunting Prevalence–L NAGA RAJEEV, MONIKA SAINI, ASHISH KUMAR, CLIVE OSMOND,
HARSHPAL SINGH SACHDEV 17
Effect of Kangaroo Mother Care on Cerebral Hemodynamics in Preterm Neonates Assessed by Transcranial
Doppler Sonography in Middle Cerebral Artery–ANAL J CHAUDHARI, SOMASHEKHAR M NIMBALKAR, DIPEN V PATEL,
AJAY G PHATAK 27
Growth and Neurodevelopmental Outcomes of Very Low Birth Weight Infants From Southern India at Corrected
Age of One Year–SUSHIL GUPTA, ADHISIVAM B, VISHNU BHAT B, NIVEDITA MONDAL 33
LATCH Score for Identification and Correction of Breastfeeding Problems - A Prospective Observational Study
–SNEHA MARIYA RAPHEAL, BALAKRISHNAN RAJAIAH, RAJENDRAN KARUPANAN, THANGARAJ ABIRAMALATHA,
SRINIVAS RAMAKRISHNAN 37
Six-Year Surveillance of Acquired Bloodstream Infection in a Pediatric Intensive Care Unit in Israel
–HALIMA DABAJA-YOUNIS, MAHA ALAIYAN, RANAA DAMOUNI SHALABI, JOSEF BEN-ARI, TAMAR ALON,
AMIR HADASH, YAEL SHACHOR-MEYOUHAS, IMAD KASSIS, KHETAM HUSSEIN 41
Evaluation of AIIMS Modified INCLEN Tool for Diagnosis of Epilepsy–PRIYANKA GOYAL, MONIKA SHARMA,
VARUGHESE PV 45
Antibiotic Susceptibility, Carrier State and Predictors of Outcome of Staphylococcus aureus Infections in
Hospitalized Children–KIRANPREET KAUR, SUMAIRA KHALIL, NP SINGH, POOJA DEWAN, PIYUSH GUPTA, DHEERAJ SHAH 49
5
CONTENTS (contd.)
REVIEWARTICLE
Management of Hepatitis C in Children – A New Paradigm–UJJAL PODDAR, DV UMESH REDDY 55
UPDATE
Management of Hyperbilirubinemia in Newborn Infants 35 or More Weeks of Gestation: American Academy of

Pediatrics, 2022–UMANG BHARDWAJ, VASUDHA KOHLI, ANU THUKRAL 63
REMINISCENCES FROM INDIAN PEDIATRICS: A TALE OF 50 YEARS
Lead Toxicity: The Unbeaten Menace–NIDHI BEDI 67
RESEARCH LETTER
Multisystem Inflammatory Syndrome in Children (MIS-C): Comparison of the First and the Second Waves
–MIMI GANGULY, PURBASHA GUPTA, DEBOPAMA BISWAS, SUBHAJIT DEY SARKAR, PRIYANKAR PAL 71
Neonatologist-Performed Ultrasound-Guided Internal Jugular Vein Cannulation–ANUP THAKUR, MANOJ MODI,

NEELAM KLER, PANKAJ GARG 72
CORRESPONDENCE
Effect of Favoritism on Junior and Mid-Level Faculty–SUPRITA KALRA 75
Iron Overload in an Infant With Rh-Isoimmunization–SANTOSH KUMAR PANDA, CHINMAY JENA 76
NEWS IN BRIEF 77
CLIPPINGS 78
BOOK REVIEW 79
NOTICE 54
OBITUARY 70
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Impact Factor of Indian Pediatrics is 3.839

Indian Pediatrics, the official journal of the Indian Academy of Pediatrics, is a peer-reviewed journal with monthly
circulation of print/e-copies to over 34,000 pediatrician members. The journal is indexed in Current Contents/Clinical
Medicine, Science Citation Index Expanded, Medline, PubMed, Indian Science Abstracts, getCITED, POPLINE,
CANCERLIT, TOXLINE, Psych Line, and Dermline. The journal gives priority to reports of outstanding clinical and
experimental work, as well as important contributions related to common and topical problems related to children and
adolescents. Information for Authors is available on the website of the journal. Indian Pediatrics is available free online at
www.indianpediatrics.net. There are no charges for publishing in the journal.
All rights reserved. The views and opinions expressed in the articles are of the authors and not of the journal.
Indian Pediatrics does not guarantee directly or indirectly the quality or efficacy of any product or service featured in
the advertisements in the journal, which are purely commercial.
Address for ordinary letters: The Editor-in-Chief, Indian Pediatrics, P. Box No. 3889, New Delhi-110 049, India.
Address for registered/speed post letters: Dr. Devendra Mishra, Editor-in-Chief, Indian Pediatrics,
115/4, Ground Floor, Gautam Nagar, New Delhi 110 049, India. Tel: (011) 46052593
E-mail: jiap@iapindia.org; Website: www.indianpediatrics.net; LinkedIn: indianpediatrics
Facebook: www.facebook.com/Indianpediatrics; Twitter: @EditorIndPed; Instagram: @indianpediatrics
6
F R O M T H E E D I T O R' S D E S K
Editing the Academy’s Journal in the Peri-COVID Era –

A Different Ball Game Altogether!
H
aving been associated with Indian Pediatrics pediatric dermatology [1]. Despite wide publicity, hardly
editorial board for more than 15 years, I any submissions were received, and these too did not
complete my three-year tenure as editor-in- clear the peer-review process. On the other hand, ‘Iconic
chief (EIC), and move on to the fourth year. pediatric institutions of India’ section saw an enthusiastic
This post was the culmination of a long academic journey, response from the invited authors, and also received
and was taken up with lofty ideals and a bunch of new bouquets from the readers. This section was meant to
ideas [1]. I find this an appropriate time to reflect on issues provide a historical perspective on the development of
related to editing the journal of a professional society, child health in India, through the lens of the major
especially in the coronavirus disease (COVID-19) times, institutions working in this field [1].
and also touch upon the changes in the journal.
Journal ki baat, a monthly online discussion bet-
COVID-19 and the Journal ween authors, editors, and readers (one pediatrician in
practice and one postgraduate pediatric resident from
The effect of the COVID-19 pandemic on the publication
different regions of the country), was well received both
of medical journals has not received as much interest, as
by the panelists and the viewers. Having held 16 episodes
the other effects of the epidemic. The intervening
till now [5], this platform, in addition to connecting the
pandemic presented unique challenges to the publication
journal to the academy’s members, also provides an
of the journal. The COVID-induced lockdowns in the city
important post-publication review for the authors. The
forced the closure of the printing press, and also the
whole-hearted involvement of the moderators Dr. Amit
journal office. However, the extensive support of the
Upadhyay and Dr. Abhijit Saha remains the cornerstone
journal staff and the editorial board worked as a buttress
of this activity.
to the publication process, which continued unhindered
[2]. This led to the timely publication of all the online Indian Pediatrics Case Reports (IPCaRes)
issues of the journal, which were later sent to the
Initiated by Prof. Piyush Gupta, CIAP President, 2021,
subscribers through the ever-reliable India Post, once the
IPCaRes was started in 2021 by the journal to provide an
lockdown partially lifted.
avenue to the academy members to publish case reports,
The editorial response of the journal to the pandemic without strict restrictions on word count and numbers of
was also spot-on, with the first COVID-related guidelines figures/tables [6]. With eight issues published in the last
to inform readers published on March 29, 2020 [3], within two years, it continues to be a vibrant medium of scientific
two months of the first case of the disease in India. One reporting and discussion, with additional content on soft
unintentional effect of the lockdown was the increased skills like ethics and communication [7]. The journal is
number of submissions to the journal (many of these going from strength to strength under the tutelage of Dr.
COVID-related), and a very quick response from editors Sharmila M Bannerjee, and getting it indexed is the next
and reviewers. Later, this was reflected in the Journal activity scheduled.
Citation Report, 2022, when the journal’s metrics had a
Social Media Presence
major increase, a trend that was seen by many other
journals [4]. The journal already had a Facebook page and was on
Twitter since 2015. We debuted on Instagram in 2020
New Sections
(@indianpediatrics) and on LinkedIn in 2021 (www.
Quite a few innovations were thought-of and initiated, linkedin.com/in/indian-pediatrics-342975218). A team
some of which succeeded and others fizzled out. A of young pediatricians were taken onboard to take up the
‘Pediatric subspecialties’ section was introduced to responsibility of posting on these sites, under super-
promote publication of papers from the fields of pediatric vision of a designated editorial board member. Posting
radiology, pediatric dentistry, pediatric orthopedics and about important articles, and the early online articles, and

8 FROM THE EDITOR’S DESK
disseminating information about journal activities Funding: None; Competing interests: None.
became easier and more effective through these plat- DEVENDRA MISHRA
forms, and also increased the journal’s reach to the Editor-in-Chief, Indian Pediatrics
younger generation of pediatricians. ip.editor@iapindia.org
Editorial Freedom REFERENCES
Editorial freedom, as per the World Association of 1. Mishra D. From the editor’s desk. Indian Pediatr.
Medical Journal Editors (WAME), is that the EIC has full 2020;57:13.
authority over the entire editorial content of their journal, 2. Mishra D. COVID-19 and Indian Pediatrics. Indian Pediatr.
and the timing of publication of that content [8]. The 2020;57:287.
International Committee of Medical Journal Editors 3. Ravikumar N, Nallasamy K, Bansal A, et al. Intensive Care
additionally suggests that the EIC should have the final Chapter of Indian Academy of Pediatrics. Novel Corona-
virus 2019 (2019-nCoV) Infection: Part I - Preparedness
say in decisions about sponsored content/advertise-
and Management in the Pediatric Intensive Care Unit in
ments the journal carries [9]. Working with the office Resource-limited Settings. Indian Pediatr. 2020;57:324-34.
bearers and the executive board of Indian Academy of 4. Delardas O, Giannos P. How COVID-19 affected the
Pediatrics (IAP) over the last three years, I never found journal impact factor of high impact medical journals:
any of my editorial decisions hindered or ‘influenced.’ bibliometric analysis. J Med Internet Res. 2022;24:e43089.
5. Indian Academy of Pediatrics. Journal ki baat. Accessed on
Something New!
Dec 27, 2022. Available from:https://new.diapindia.org/
We plan to start a new section this year, ‘Pediatric index.php/journal-ki-baat-29th-may-2022/
Subspecialties in India.’ This section will trace the 6. Mishra D, Gupta P. Indian Pediatrics Case Reports
growth of pediatric subspecialties in India, for the benefit (IPCaRes): launching a new journal from the Indian
of the younger generation of pediatricians, and will also Academy of Pediatrics. Indian Pediatr. 2020;57:499.
7. Indian Pediatrics Case Reports. Accessed on Dec 27, 2022.
showcase the contribution of many senior pediatricians, a
Available from: https://www. ipcares.org/
few of whom remain unsung. 8. World Association of Medical Editors. The relationship
It was an exhilarating journey with many lessons between journal editors-in-chief and owners (formerly
learnt, but I end this tenure with the satisfaction that the titled editorial independence), updated July 25, 2009.
journal remained a platform for debate on issues per- Accessed on Dec 23, 2022. Available from: https://
wame.org/editorial-independence
taining to child health as a whole, and not limited it self to
9. International Committee of Medical Journal Editors.
being a journal just reporting on research alone. Recommendations for the Conduct, Reporting, Editing and
Ultimately, it is the readers and authors who are the final Publication of Scholarly Work in Medical Journals,
authority on the quality of a journal, and I feel that the Updated May 2022. Accessed on Dec 25, 2022. Available
journal scores highly with them. from: http://www.ICMJE.org

P R E S I D E N T ’S PAGE
Diamonds are Forever!

UPENDRA KINJAWADEKAR
President, Indian Academy of Pediatrics, 2023
upen228@gmail.com
T
o all the readers of Indian Pediatrics, I wish only in developed countries. These figures show that
you and your family a happy and healthy 2023. while one segment of society may not have access to
Over the last few months, the daily caseload of essential nutrients, another segment is relying more and
coronavirus disease (COVID-19) has been more on empty calories and junk food – both leading to
steadily declining in India, and we seem to be optimisti- the insidious outcome of child malnutrition. As a
cally entering a post-pandemic era. It is time now to collective, IAP must step up our advocacy efforts to
implement the numerous lessons learned over the last two enhance policies that aim to improve nutritional outcomes
years, as well as to reinvigorate pre-pandemic efforts to in children. But we should also look for instances in our
improve child health in India, which continues to be the daily practice where we can monitor and track growth
core mandate of the Indian Academy of Pediatrics (IAP). rates and identify danger signs early. Growth charts are
simple but powerful tools that we are all equipped with, to
The IAP celebrates its Diamond Jubilee year this year, identify children whose growth status is worrying and
which is a good time to reflect on all that we have needs more attention. The child does not enter obesity
collectively achieved while reminding ourselves of all that without crossing over the overweight line and the same
is yet to be done. Milestones like the diamond jubilee year holds at the other extreme of undernutrition. Though, we
allow us to feel a sense of pride and appreciation for what all have the growth charts printed and attached to the
our predecessors have achieved through the organiza- patient record file, timely plotting on the chart is as
tion. In 1964, the organization pledged to raise the important as documenting the immunization details.
standards of the medical profession and medical Weight for age is noted by most but somehow length/
education to provide quality care to every child in the height for age and weight for length/height is overlooked
country; to stimulate cordial relationships among all when we very well know that stunting is almost irreversi-
pediatricians and nurture the growth and diffusion of ble after two years of age. I urge you all to use the IAP
medical knowledge in every corner of the country. These growth chart to track the growth of every child who
founding tenets remain just as relevant in 2023, as IAP comes to your clinic.
strives to achieve the best possible preventive and
curative care for every child, irrespective of gender/ Secondly, we have made only marginal gains in
region/socioeconomic strata/caste etc. breastfeeding practices in the country, over the last half-
decade. The incidence of early initiation (within one hour
India still has a long way to go to ensure every child is of birth) has been almost stagnant since 2015. Every IAP
adequately nourished and receives the right develop- member attending a delivery must ensure that every
mental environment to grow to her full potential. NFHS-5 newborn baby is allowed direct skin to skin contact and
data [1], released in the thick of the pandemic, exposed thereby a chance to initiate breastfeeding within an hour
some worrying trends about the double threat of after birth, whether in the labor room or OT. While the
malnutrition in the country. On the one hand, the data uptake of exclusive breastfeeding in the first six months
shows an increase in severe wasting in children less than has improved in this period (54.9% in 2015-16 to 63.7% in
five years of age and only a marginal decrease in stunting. 2019-20), there is still a lot of scope to improve. For every
On the other hand, the survey made another startling challenge in the successful implementation of exclusive
revelation – an increasing number of under-five children breastfeeding, there is a scientific and evidence-based
are overweight. With rapid urbanization and easy access solution that only needs our time and total commitment.
to “ordering in,” we may be staring at the very real threat Complementary feeding practice after the six-month mark
of childhood obesity and diabetes, something we has improved only slightly (42.7% in 2015-16 to 45.9% in
thought (until very recently) is a public health challenge 2019-20). Only 11.3% of children in the 6-23 month bracket

10 PRESIDENT’S PAGE
are receiving an adequate diet – which means only one in protection to every child from vaccine preventable
ten infants is obtaining sufficient nourishment. With all diseases by advocating and offering age-appropriate
the discourse around early child development and the vaccines.
emphasis on the first 1,000 days of life, this finding serves
As the largest body of pediatricians in the country, we
as a rude reality check for all of us.
can make a significant difference to child health in India by
I would propose making the ‘6-month visit’ a adopting these simple yet impactful measures in our day-to-
milestone pediatric check-up for the child, wherein we can day practice. In a post-pandemic world, children are
use it as an opportunity to closely inspect the status of looking at a dizzyingly fast-paced, virtual and compe-titive
the child’s growth while also counseling the parents on future, set in deteriorating climatic conditions, which brings
the importance of a minimum acceptable diet, dietary along its own set of challenges to their mental and physical
diversity and initiating complementary feeding while well-being. We are also witnessing the co-existence of
continuing breastfeeding. Spending time on this routine contradictory public health challenges (e.g., rising number
6-month visit will surely pay rich dividends as it also of overweight and underweight children). The time is now
allows the pediatrician to assess not only the gross and to go in with all guns blazing to advocate and act on early
fine motor milestones but the social communication skills initiation of breast feeding, exclusive breast feeding for six
too, which can alert us for certain red flags. months, timely introduction of complementary feeding,
growth monitoring, strengthening our immunization
Nurturing Care-Early Care Development (NC-ECD), practices, and finally empowering and guiding every
the flagship program of IAP started in 2021, by the then parent/caregiver in applying principals of NC- ECD to
President Dr. Piyush Gupta [2], has reached a milestone of prevent a cascade of more serious child health problems in
hundred workshops conducted all over the country, and the future.
another hundred in the pipeline for 2023. Although, our
workshops train the pediatricians, the ultimate goal is that When it is said that ‘Diamonds are forever,’ it actually
this training reaches parents/caregivers, sensitizing them means a diamond never loses its value. Similarly, in IAP’s
about the importance of NC-ECD during the ‘well-child’ diamond jubilee year, let us all pledge to collectively work
visits and to bringing about a positive behavior change in to overcome newer challenges for better health and
them. We still need to ideate on simple, affordable and wellbeing of our children, keeping our core values intact.
feasible methods to reach a maximum number of In all things that are purely social, we can be as
beneficiaries. Dr Nandita Chatterjee, from team Udbhaas separate as the fingers, yet one as the hand in all things
CDC in collaboration with UNICEF Kolkata has published essential to mutual progress.
a novel idea of roping in frontline workers and young girls
from the community itself, to further disseminate the – George Washington
merits of NC-ECD to new parents [3]. I hope that such REFERENCES
voices from the field inspire more novel ideas, which is the
1. National Family Health Survey - 5. MoHFW, Government
need of the hour for the program to have a significant
of India, 2021. Accessed March 13, 2021. Available from:
reach and impact. http://main.mohfw.gov.in
Lastly, a word about strengthening our immunization 2. Gupta P, Basavaraja GV, Pejaver R, et al. Mumbai 2021
Call for Action. Addressing the need to incorporate
practices. Towards the end of last year, we had an
‘Nurturing care for Early Childhood Development’ in
unexpected and unfortunate surge of measles in many pediatric office practice. Indian Pediatr. 2021;58:215-6.
areas of the country. It has taught us the lesson that ‘not 3 Chatterjee N. ECD at the grassroot level: Reaching out to
lowering the guard’ was not meant only for COVID-19 but parents. Indian Journal of Growth Development and
in fact for all infectious diseases. Let us ensure complete Behavioural Pediatrics. 2022;14: 14-18.

INVITED COMMENTARY
Measuring Overnutrition in Children: Do We Know Enough?

SHIVANI A PATEL, *NATALIA E POVEDA
Hubert Department of Global Health, Rollins School of Public Health,
Emory University, Atlanta GA, USA.
*s.a.patel@emory.edu
G
iven the historical rarity of excess weight, was lower for weight for height compared with BMI for
assessment of pediatric weight status has long age from birth to 7-8 months, but higher thereafter [4].
been focused on detecting and correcting The discrepancies are more impactful in scenarios where
growth faltering in children. However, since child height is much lower than the global mean. The
the mid-1970s, changes in dietary intake and energy authors conclude that BMI for age is preferable to weight
expenditure that favor excess weight began to take hold for height for the classification of overweight due to its
the world over. This nutrition transition was first evident ability to produce estimates that are not sensitive to the
in the weight status of adults and in high-income settings, age or mean height of the population [4]. The authors are
but it is increasingly manifest in the youngest ones even in to be commended for the thorough and detailed statistical
low- and middle-income countries (LMIC). Available considerations of applying one measure rather than the
data suggest that roughly 6% of children in LMICs other. Here, we provide two additional considerations for
experience overweight, an average rise of one percentage discussion to advance the measurement of childhood
point over the past two decades [1]. The nutrition overweight.
transition has created a challenging panorama of child
First, the ultimate goal of assessing overnutrition and
health promotion priorities in places like India, which
excess weight is to gauge excess adiposity. In that regard,
simultaneously has among the largest absolute number of
BMI stands above weight for height because it breaks the
overweight and growth stunted children [1,2].
relationship between the index and height because of the
Despite the nutrition transition, there has been height-squared adjustment in the denominator. BMI for
relatively limited discussion on the best measure for the age additionally accounts for changes in body size over
classification of overnutrition compared with the extensive time (age). In this sense, BMI for age conceptually is a
debate regarding best measures of child undernutrition, better index to capture changes in excess weight (and
including short stature (low height for age), wasting (low adiposity) independent of height [5,6]. The importance of
weight for height), and underweight (low weight for age). the independence of different indices of body size and
Currently, the WHO-recommended weight for height composition from their denominators has been demons-
index is the predominant measure of child overweight trated in previous studies in LMICs, where individuals
and obesity in global settings [3]. Some have questioned and populations face a double burden of malnutrition
whether weight for height is the most appropriate index [7,8]. Nevertheless, from previous research in children, it
for overweight and obesity. is known that BMI is still an imperfect measure of body
composition (adiposity) [9].
In their recent publication in Indian Pediatrics, Naga
Rajeev, et al. [4] compare body mass index (BMI) Second, both debated definitions of child overweight
thresholds to define overweight, and the prevalence of and obesity are statistical in nature. Akin to the approach
overweight obtained from applying weight for height for classifying undernutrition, overweight definitions are
versus BMI for age. Through examination of NFHS-4 based on distributional thresholds anchored to a universal
data, the authors report that weight for height compared reference population. Whether a distributional threshold
with BMI for age yielded higher estimates of prevalent is the optimal approach to capture future metabolic risk is
overweight from birth to 6 months, but lower estimates of unclear. In adults, excess weight is defined so that it
prevalent overweight in children ages 6 months to 5 captures excess risk of health outcomes such as death and
years. Similarly, their simulation studies showed that in cardiovascular events, and the field may consider whether
short populations, the BMI threshold for overnutrition anchoring excess weight in children against metabolic

12 INVITED COMMENTARY
outcomes would add value. There is some evidence that requiring urgent action. BMC Med. 2019;17:212.
shows that both BMI for age and weight for height in 2. Varghese JS, Gupta A, Mehta R, Stein AD, Patel SA.
infants predict future health outcomes with comparable Changes in child undernutrition and overweight in India
validity [10], yet additional systematic investigation is from 2006 to 2021: an ecological analysis of 36 states. Glob
Health Sci Pract. 2022;10:e2100569.
needed to resolve which measure is best at predicting
3. Mei Z, Grummer-Strawn LM. Standard deviation of anthro-
metabolic risk. Furthermore, following on the lessons pometric z-scores as a data quality assessment tool using the
from adult anthropometry and metabolic risk, the 2006 WHO growth standards: a cross country analysis. Bull
appropriateness of universal versus population-specific World Health Organ. 2007;85:441-8.
thresholds can be explored. For example, the WHO 4. Naga Rajeev L, Saini M, Kumar A, Osmond C, Sachdev HS.
recommends lower “action point” thresholds for over- Comparison of weight for height and BMI for age for
weight and obesity in Asian adults because of observed estimating overnutrition burden in under-five populations
elevated risk of diabetes and cardiovascular disease even with high stunting prevalence. Indian Pediatr. 2022 Nov
in the normal weight range [11]. A similar exercise may 19:S097475591600470. Epub ahead of print.
5. Cole TJ. Weight/heightp compared to weight/height2 for
enhance our ability to appropriately classify excess
assessing adiposity in childhood: influence of age and bone
weight in children. age on p during puberty. Ann Hum Biol. 1986;13:433-51.
In summary, a measure of overweight should not only be 6. Gasser T, Ziegler P, Seifert B, Prader A, Molinari L, Largo
statistically robust but also appropriately identify, categorize, R. Measures of body mass and of obesity from infancy to
adulthood and their appropriate transformation. Ann Hum
and rank children with respect to excess adiposity and risk of
Biol. 1994;21:111-25.
future adverse health outcomes. Considering the results of
7. Judd SE, Ramirez-Zea M, Stein AD. Relation of ratio
Naga Rajeev, et al. [4], BMI for age offers a statistical indices of anthropometric measures to obesity in a stunted
robustness across varying ages. Additionally, recognizing population. Am J Hum Biol. 2008;20:446-50.
that BMI for age is an inexpen-sive and practical measure to 8. Wells JC, Victora CG. Indices of whole-body and central
assess weight status in community and clinical settings, that adiposity for evaluating the metabolic load of obesity. Int J
BMI measures excess weight for height independent of Obes. 2005;29:483-9.
height, and that BMI correlates with metabolic outcomes in 9. Vanderwall C, Randall Clark R, Eickhoff J, Carrel AL. BMI
children, we concur with the authors that BMI for age is a is a poor predictor of adiposity in young overweight and
obese children. BMC Pediatr. 2017;17:135.
preferred index to classify childhood overweight given
10. Aris IM, Rifas-Shiman SL, Li LJ, et al. Association of
present knowledge.
weight for length vs body mass index during the first 2 years
Funding: None; Competing interests: None stated. of life with cardiometabolic risk in early adolescence. JAMA
Netw Open. 2018;1:e182460.
REFERENCES 11. WHO Expert Consultation. Appropriate body-mass index
1. Di Cesare M, Soric M, Bovet P, et al. The epidemiological for Asian populations and its implications for policy and
burden of obesity in childhood: a worldwide epidemic intervention strategies. Lancet. 2004;363:157-63.

INVITED COMMENTARY
Effect of Kangaroo Mother Care on Cerebral Hemodynamics

in Preterm Infants
RUCHI N NANAVATI,* PRASHANTH RR
Department of Neonatology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra.
*drruchinanavati@gmail.com
K
angaroo mother care (KMC) has evolved as critically ill infants [2]. This creates an increased
sine qua non intervention to meet the preterm vulnerability to both ischemic and hemorrhagic brain
baby’s fundamental needs of warmth, injuries and increased risk of long term neurological
nutrition, and protection from infection. insults. A fluctuating pattern of blood pressure,
KMC re-establishes the synchrony between mother and characterized by marked, continuous alterations in both
fetus interrupted by preterm birth. Maternal sensory systolic and diastolic flow velocities, are associated with
inputs regulate the physiology of the newborn and attain similar trends in the CBF velocity tracings and a high risk
homeostasis. Research suggests that for all mammals, the of subsequent occurrence of intraventricular hemorrhage
maternal environment is the primary requirement for (IVH). Because of the pressure-passive cerebral
regulation of all physiological needs (homeostasis), and circulation in sick premature infants, hypotension can
maternal absence leads to dysregulation and adaptation to lead to a parallel decrease in cerebral blood flow. It is
adversity. The cardio-respiratory instability seen in important to note that carbon dioxide – CBF reactivity is
separated infants in the first 6 hours is consistent with more robust than pressure-flow reactivity. Moderate
mammalian “protest-despair” biology, and “hyper- hypocarbia results in the reduction in CBF while
arousal and dissociation” response patterns described in moderate hypercarbia results in increase in CBF and also
human infants. Thus, zero separation achieved with KMC abolishes the autoregulatory response due to marked
facilitates normal biology and neurodevelopment [1]. vasodilation resulting in ischemic brain injury.
Cerebral hemodynamics is very unique in preterm The impact of KMC on cerebral hemodynamics in
population – cerebral autoregulation and cerebral blood preterm neonates has been an area of research interest. The
flow (CBF) being sensitive to the changes in the mean maintenance of normal temperature, heart rate, blood
blood pressure (MBP), oxygenation, heart rate (HR) and pressure, oxygen, carbon dioxide, and glucose are vitally
carbon dioxide variability. Impaired cerebral auto- important to maintain cerebral hemodynamics [3]. KMC
regulation, increasingly observed with decreasing gesta- stabilizes these cardiorespiratory parameters and posi-
tional age and birth weight, results in pressure passive tively influences the physiological stability. KMC in stable
cerebral circulation and imbalance in the normal physio- preterm infants has resulted in fewer bradycardic events,
logic reflex worsens the possibility of neurologically fewer desaturations and apneic events. The improvement in
intact outcomes. Immaturity of the autonomic nervous oxygenation can be attributed to the upright position of
system, especially the parasympathetic control of CBF is KMC which increases the efficiency of the diaphragm and
particularly underdeveloped in preterm infants. Intact pulmonary function [4]. The lesser variation of HR,
cerebrovascular autoregulation is found in clinically respiratory rate, and stable oxygen saturation while in
stable preterm infants, CBF being unaffected by KMC contributes to the better hemodynamic stability and
fluctuations of MBP within the physiologic range of 25 to sudden fluctuations of blood pressure are prevented since
60 mm Hg [2]. CBF autoregulation is functional in there is positive regulation of serum cortisol and β-
normotensive but not in hypotensive very low birth endorphins. KMC has also shown to improve the perfusion
weight (VLBW) and extremely low birth weight (ELBW) index and reduce HR variability [5,6]. KMC enhances
infants in immediate neonatal period. Studies have shown peripheral perfusion through vaso-relaxation by releasing
that the ability of newborn brain to respond to changes in acetylcholine from parasympathetic nerves and induces
perfusion pressure is not only limited as compared to vaso-relaxation by regulating the release of nitric oxide
adults, its range is further quite diminished in sick and (NO) in arteries through M3 acetylcholine receptors on the

endothelium. Higher heart rate variability is a result of an from the moment of birth.” Hence the effect modification
immature autonomic nervous system and a dominant by immediate KMC on cerebral hemodynamic para-
sympathetic nervous system in a preterm that tends to meters that occur during the first 24 hours after birth in
overshoot during auto-regulation and chronic exposure to stable preterm infants as well as clinically unstable in-
stress. KMC is thought to enhance parasympathetic fants needs to be further explored along with subsequent
signaling by improving the myelination of the vagal long term neurodevelopment outcome to strengthen the
branches leading to better regulation of HR, cardiac output evidence base for promoting KMC and protecting the
and autonomic responses [7]. Near-infrared spectroscopy, vulnerable preterm brain.
before, during, and after KMC, have shown stable mean
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On world prematurity day 2022, UNICEF is 10. Thippeswamy T, McKay JS, Quinn JP, Morris R. Nitric oxide,
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INVITED COMMENTARY
Urgent Need of Research on Neurodevelopmental Outcome of Preterm/

Very Low Birth Weight Neonates From India
KANYA MUKHOPADHYAY
Neonatology Division, Department of Pediatrics, PGIMER, Chandigarh.
kanyapgi@gmail.com
P
reterm birth varies from 8.7-13.4% globally and low birth weight children and who were less than 2 kg [8].
nearly 15 million preterm babies are born
We reported 3% CP, 11% gross motor delay and 8%
annually, of which 60% births are in Africa and
language delay among our VLBW (≤1500 g) and preterm
South Asia [1]. India contributed about 3.1 mil-
(≤34 week gestation) cohort at 18 months corrected age. In
lion births in this cohort and which accounts to nearly
this cohort, 17% had a score of less than 70 in MeDQ and
23.4% of global burden of preterm birth [2]. With improv-
25.7% in MoDQ and 84% had high behavioral scores [9].
ing facilities, training, infrastructure and newer technolo-
gies, there is increasing survival of preterm neonates Preterm small for gestational age (SGA) children are
across the globe including India which recorded a 40-60% more at risk of neurodevelopmental disabilities due to
reduction in preterm mortality between 1990 to 2019 [1]. double whammy of prematurity and growth retardation.
In our country nearly 30% are LBW and some are pre-
These preterm neonates are at high risk of neuro-
term too. Murki, et al. [10] reported neuro-development
developmental disabilities, almost 5-10% of very low birth
at 12-18 months of corrected age among preterm (<35
weight (VLBW) babies have major sequelae like cerebral
week) small for gestational age (SGA) infants and found
palsy (CP) while 25-50% have various cognitive and
higher incidence of motor and mental delay as compared
behavioral issues and lower academic performance [3-6].
to preterm appropriate for age (AGA) infants. We also
An Italian cohort of preterm VLBW infants showed normal
observed 24% had low DQ (<90) and 74% had average
neuro-developmental outcome in 75.3% and the rest had
and above average DQ (>90) among ≤1250 grams cohort
minor (13.9%) and major sequelae (10.8%) including 3.8%
at CA 18 months. SGA infants had significantly higher
CP [3]. The Neuroprem study reported 12.5% severe
risk of low scores [11]. Sacchi, et al. [12] also reported in
disability and 4.5% cerebral palsy rate among preterm
a systematic review and meta-analysis, higher cognitive
VLBW infants (23-33 weeks gestation) at 24 months
impairments among the children who were preterm and
corrected age [5]. Epipage-2 cohort of preterm babies had
SGA. Gupta, et al. [13], in this issue of Indian Pediatrics,
severe to moderate disabilities in 36% cases at 27-31 weeks
report neurodevelopmental disabilities and growth
gestation and in 34% at 32-34 weeks gestation. Behavior
failure in VLBW neonates at 1 year CA, thereby high-
was a major concern for most parents [6].
lighting the need for long-term follow up.
With nearly 25 million births and approximately 13.6%
Hence, VLBW infants (AGA and SGA both) need
(11.1-16.1%) prematurity rate in India, a large number of
long-term follow up for early detection of neuro-
preterm babies are born every year who needs a very long-
developmental disabilities including hearing screening
term neurodevelopmental follow up however there are very
and ophthalmological evaluation and early intervention
scanty reports from India. A systematic review from
by a team of multispeciality experts. There is a need for a
resource limited set ups reported 21.4% neurodevelop-
collaborative and systematic data collection from various
mental impairment, 16.3% cognitive im-pairment, and
NICUs as well as from SNCUs in our country, and
11.2% CP among preterm/low birth weight and very low
assessments should be carried out with standardized
birth weight infants; however, it included only three studies
scales so that uniformity of data can be maintained.
from India [7]. Another meta-analysis and systematic
Adequate and appropriate data collection and reporting
review from South Asia among low birth weight children
will help to compare the data over the years and quality of
showed significantly lower motor and cognitive scores as
care can be improved accordingly.
compared to normal birth weight children. This study
included ten studies from India, but they included mostly Funding: None; Competing interests: None stated.

REFERENCES literature. Paediatr Int Child Health. 2015;35:227-42.

8. Upadhyay RP, Naik G, Choudhary TS, et al. Cognitive and
1. Cao G, Liu J, Liu M. Global, regional, and national motor outcomes in children born low birth weight: a
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2. Chawanpaiboon S, Vogel JP, Moller AB, et al. Global, 9. Mukhopadhyay K, Malhi P, Mahajan R, Narang A. Neuro-
regional, and national estimates of levels of preterm birth in developmental and behavioral outcome of very low birth
2014: a systematic review and modelling analysis. Lancet weight babies at corrected age of 2 years. Indian J Pediatr.
Global Health. 2019;7:e37-46. 2010;77:963-7.
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outcome of preterm very low birth weight infants admitted to Growth and neurodevelopmental outcomes at 12 to 18
an Italian tertiary center over an 11-year period. Sci Rep. months of corrected age in preterm infants born small for
2021;11:16316. gestational age. Indian Pediatr. 2020;57:301-4.
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Elburg RM, Oosterlaan J. Academic performance of Language, and Visuomotor Abilities of Very Low
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Neuroprem: the Neuro-developmental outcome of very low Simonelli A. Association of Intrauterine Growth Restriction
birth weight infants in an Italian region. Ital J Pediatr. and Small for Gestational Age Status With Childhood
2020;46:26. Cognitive Outcomes: A Systematic Review and Meta-
6. Pierrat V, Marchand-Martin L, Marret S, et al. Neuro- analysis. JAMA Pediatr. 2020;174:772.
developmental outcomes at age 5 among children born 13. Gupta S, Adhisivam B, Vishnu Bhat B, Mondal N. Growth
preterm: EPIPAGE-2 cohort study. BMJ. 2021;373:n741. and neurodevelopmental outcome of very low birth weight
7. Milner KM, Neal EFG, Roberts G, Steer AC, Duke T. Long- infants at corrected age of 2 years from Southern India.
term neurodevelopmental outcome in high-risk newborns in Indian Pediatr. 2022 Nov 19:S097475591600468. Epub
resource-limited settings: a systematic review of the ahead of print.

RESEARCH PAPER
Comparison of Weight for Height and BMI for Age for Estimating
Overnutrition Burden in Under-Five Populations With High Stunting
Prevalence
L NAGA RAJEEV,1 MONIKA SAINI,1 ASHISH KUMAR, 1 CLIVE OSMOND, 2 HARSHPAL SINGH SACHDEV3
From Department of Mathematics and Statistics, Manipal University Jaipur and Data Scientist, Department of Pediatrics and Clinical
Epidemiology, Sitaram Bhartia Institute of Science and Research, New Delhi; MRC Lifecourse Epidemiology Unit, University of
Southampton, Southampton, UK; Department of Pediatrics and Clinical Epidemiology, Sitaram Bhartia Institute of Science and
Research, New Delhi.
Correspondence to: Prof Harshpal Singh Sachdev, Senior Consultant, Department of Pediatrics and Clinical Epidemiology, Sitaram
Bhartia Institute of Science and Research, B-16 Qutab Institutional Area, New Delhi 110016. hpssachdev@gmail.com
Received: July 13, 2022; Initial review: October 08, 2022; Accepted: November 05, 2022.
Background: Overnourished under-five children are anthro- India dataset (short population), overnutrition (>1SD) prevalence
pometrically classified as either being at possible risk of over- with weight for height was higher from 0-0.5 years (exclusive
weight, overweight or obese and defined so, when either weight breastfeeding age), but lower at subsequent ages. The
for height or body mass index for age (BMI-for-age) are >1SD to prevalence difference (weight for height - BMI for age) in 0.5-5
2SD, >2SD to 3SD and >3SD, respectively of the analogous years was -2.26% (6.57% vs 8.83%); this attenuated in 0-5
World Health Organization standards. years (-1.55%; 7.23% vs 8.78%). The discrepancy was maxi-
Aim: To compare weight for height and BMI for age definitions mal for stunted children and was lower in girls. A similar pattern,
for quantifying overnutrition burden. of lower magnitude, was observed for overweight (>2SD) com-
parison. In intermediate and tall populations, there were no
Methods: Theoretical consequences of ignoring age were meaningful differences.
evaluated by comparing, at varying height for age z-scores, the
age- and sex-specific cutoffs of BMI that would define Conclusion: The two definitions produce cutoffs, and hence
overnutrition with these two metrics. Overnutrition prevalence estimates of overnutrition, that differ with the age, sex, and
was then compared in simulated populations (short, intermediate height of under-five children. The relative invariance, with age
and tall) and real-life datasets from India. and height, of BMI for age, favors its use.
Results: In short (-2SD) children, the BMI cutoffs with weight Keywords: Anthropometric indicators, Growth assessment,
for height criteria were lower in comparison to BMI for age till 7-8 Overnutrition, Overweight,
months, but higher at later ages. In National Family Health Survey-4,
Published online: Nov 19, 2022; PII: S097475591600470
G
lobally, an estimated 5.7% or 38.9 million Overnutrition in under-five children can be identified
under-five children, almost half in Asia and a by either of the two anthropometric indices: a) Weight for
quarter in Africa, were affected by overweight height, and b) Body mass index for age (BMI for age).
in 2020 [1]. Since overweight and obesity in Overnourished individuals are categorized as either obese,
childhood and adolescence are associated with adverse overweight or at possible risk of overweight, if these
health consequences later in life, their prevention and indices are >3SD, between >2SD and 3SD, and between
control are important. Focusing on under-five children is >1SD and 2SD, respectively of the World Health Organi-
an important component of this strategy [2]. Indeed, zation (WHO) growth references [3,4]. Currently, there is no
prevalence of overweight in under-five children is one of
Invited Commentary: Pages 11-12.
the Sustainable Development Goals (SDGs). The global
nutrition targets endorsed by the World Health Assembly unanimity regarding the preferred index among these two,
include: i) no increase in childhood overweight prevalence to diagnose overnutrition in public health settings. Weight
as target for 2025; and ii) reduce and maintain childhood for height ignores the physiological changes in ponderosity
overweight to below 3% as target for 2030 [1]. An accurate with age, whereas by construct BMI for age accounts for
and bias free quantification of overnutrition burden is, such alterations [4,5]. Further, for a given weight and height
therefore, crucial both at the individual and population at a particular age, the WHO SD (or z) scores of the two
level. indices could also differ. We recently demonstrated that

18 OVERNUTRITION DEFINITION: WHZ VS BMIZ
these incongruencies resulted in appreciable and The artificial datasets were constructed independently
systematic differences in thinness estimates of populations for boys and girls to study the effects of choice of metric
[5]. A similar phenomenon is likely for overnutrition. on overnutrition estimates, in short: National Family
Following the introduction of the WHO growth charts, only Health Survey-4 (NFHS-4) [10], intermediate: WHO [4], and
few studies from HICs have partially explored this tall: National Health and Nutrition Examination Survey,
possibility [6-9]. However, there is no detailed and USA (NHANES), Greenland and Poland populations [11-
systematic evaluation from low and middle income country 13]. In six-monthly age-group intervals from 0-5 years,
(LMIC) settings, in which the children are generally shorter 100,000 subjects were generated homogeneously and
and thinner, but the double burden of malnutrition is now indepen-dently for both the sexes. The WHO z-scores of
assuming alarming proportions [2]. We, therefore, heights and weights were generated through bivariate
compared these two indices for diagnosing overnutrition in distribution with respect to their mean, SD, and
under-five children, in populations with different heights, correlations (Table I). The height and weight were back
through theoretical considerations, simulation, and real-life calculated by using the LMS parameters of the WHO
data sets from research and survey settings in India. reference [4].
METHODS Three real-life datasets were used for the analyses:
An ethical clearance for the study was not required as it a) the Meerut study, which was designed to assess the
deals with hypothetical considerations, simulations [4,10- prevalence of severe acute malnutrition and to propose
13], and the real-life analyses of secondary datasets for mid-arm circumference substitutes for the weight for
which the consent was taken from the parents of the height cutoffs [14]. This cross sectional, community-
participants and the ethical clearance was obtained from based study was conducted between September, 2012
the respective institutional boards [10,14-15]. and October, 2013 in the district of Meerut, Uttar
Pradesh, India. Two adjoining rural blocks were
The two metrics (weight for height and BMI for age)
identified, and their 70 contiguous villages were
were compared independently for both the sexes (boys
selected. The inclusion criteria were children aged
and girls) at monthly intervals from 0 to 60 months. We
between 6-59 months residing permanently in the
considered the values ht(t,z), bmi(t,z), and wt(t,z),
study area, who had no severe ailments or physical
respectively at age t where ht, bmi, and wt are height, BMI,
deformities (n=18,463). The research team members
weight (at height ht(t,z)) and z is the WHO standard score
were trained in recording anthropometry by standard
of height, BMI, and weight for height [4]. The plots were
techniques, assessment of age and examination for
made for bmi (t,+2) and wt(t,+2)/ht2(t,z) against age t (0 to
severe visible thinness and bipedal oedema. Length for
60 months), where z = -2, 0, +2 (short, intermediate, and tall),
the children below 24 months of age was measured
respectively. Further, at fixed weight for age with fixed
using SECA 417 infantometer and for 24-59 months of
height for age (both at 0SD, +1SD, and +2SD), we
age, SECA 213 stadiometer was used to measure the
compared the SD scores of weight for height and BMI for
height with a minimal count of 0.1cm. Weight was
age in both sexes, from 0 to 60 months, respectively.
recorded using SECA 383 digital weighing scale
Table I Details of Anthropometric Parameters Used for Creating the Simulated Populations
Simulated population, Height for age z-score Weight for age z-score Correlation
country Mean SD Mean SD
Short (National Family Health -1.89 to -0.44 1.28 to 1.92 -1.69 to 1.11 1.07 to 1.39 0.55 to 0.69
Survey-4), India [15]
Intermediate [7] 0 1 0 1 0.72
Tall
National Health and Nutrition -0.18 to 0.29 0.96 to 1.32 0.21 to 0.58 0.94 to 1.26 0.63 to 0.75
Examination Survey, USA [16]
Greenland [17] 0.80 to 0.83 1.17 to 1.18 0.80 to 0.83 0.98 to 1.07 0.72
Poland [18] 0.28 to 0.40 0.98 to 1.00 0.36 to 0.45 1.03 to 1.12 0.72
The values under various columns depict either a single value (if applicable) or a range for the stratified six-monthly age groups from birth to
five years of age. Reference numbers of studies from where these anthropometric details were collected for creating the synthetic populations
are provided in square parenthesis.

NAGA RAJEEV, ET AL. 19
closest to 10g. Inter-observer and intra-observer were excluded using the same filters and thus 34,898
technical errors of measurements were <2% [14]. subjects were available for the analysis. In Meerut study,
we considered missing values below -7z for height-for-age,
b) NFHS-4 is the cross-sectional Demographic Health weight-for-age, and weight-for-height, as seemingly
Survey conducted between 2015-2016. Data was aberrant measurements had been reverified in the field.
collected on 241,531 children throughout India Using this filter, 11 subjects were excluded, and 18,452
between 0-5 years age [10]. A two-stage stratified subjects were available for the analysis. Age categories
sampling was done in which the primary sampling were divided into ten six-monthly intervals between 0-5
units (PSUs) were villages in rural areas and census years age.
enumeration blocks (CEBs) in urban areas. The final
sample PSUs were selected with the probability Statistical analysis: The proportions that were classified
proportional to the size (PPS) sampling. In every as overnourished with weight for height (>1 SD or >2 SD)
selected rural and urban PSU, households and metric but not with BMI for age for the corresponding cut-
individuals were selected using a well-defined off, and vice versa, were estimated from 2×2 tables. The
process. Weights were measured using the SECA 874 prevalence of overnutrition with both metrics, including
digital weighing scale. Length was measured using for stratified ages, sex and height for age categories, was
SECA 417 infantometer for infants below 24 months of compared using the McNemar test. Correlation between
age and SECA 213 stadiometer was used to measure the two metrics was computed using Pearson correlation
the height of children between 24-59 months of age. coefficient. Agreement between weight for height and BMI
The least count and technical errors of measurements for age was examined by using Bland-Altman analyses
are not mentioned in the report. However, in this with 95% limits of agreement.
demographic survey, we expect more measurement
errors. The statistical analyses were done using STATA 16.0
version and the graphs were made using R software 4.0.2
c) The Comprehensive National Nutrition Survey (CNNS) version (R Core Team, 2020, www.R-project.org/) and
was a cross-sectional nutritional survey conducted STATA 16.0 version (StataCorp LLC).
between 2016-2018. The data were collected on 38,060
children in India between 0-5 years of age by following RESULTS
the standard procedures [15]. Multi-stage stratified The absolute BMI cutoffs for defining overweight (>2SD)
sampling was used in the survey with PSUs for villages according to weight for height and BMI for age criteria are
in the rural areas and CEBs in the urban areas. The final compared in Web Fig. 3. In short children (-2 SD), the
selection of the PSUs was done by using the PPS cutoffs with weight for height were lower till 7-8 months
sampling. Families and individuals were selected by a and after 48 and 54 months in girls and boys, respectively,
well-defined procedure from each of the chosen rural but were higher in between these ages. The two cutoffs
and urban PSUs. The weight of the children and adults were broadly similar at median height (0SD). In tall children
was measured using SECA digital weighing scale and (+2 SD), the cut-offs with weight for height were higher till
the length/height was measured using the three-piece 5-6 months and after 36 and 39 months in boys and girls,
wooden board. Children younger than two years of respectively, but were lower in between these ages.
age, were measured lying down while older subjects
were measured standing. In this survey, we expect less For a given weight for age (0, +1 and +2SD), the z-
errors as the measurements, except weight, were scores for weight for height and BMI for age were similar in
conducted in duplicate with quality control pro- children with median height for age (Web Fig. 4). However,
cedures in place. in children with height for age at -2SD, the weight for
height z-scores were higher than BMI for age z-scores till 6
We noted discrepancies between the z-scores of months of age and lower subsequently till 42-60 months of
various indices available in the NFHS-4 dataset and the z- age. A reverse pattern was observed in tall children (height
scores calculated from the raw weights and lengths/ for age +2SD).
heights. Thus, we used the calculated WHO z-scores
using the macro syntax for STATA [4]. WHO criteria were Fig. 1 compares the prevalence of possible risk of
followed to set the missing values (z-scores): length/ overweight (>1 SD) using the two metrics in simulated
height for age <-6 or >6, weight for age <-6 or >5, weight for- short, intermediate, and tall populations. The overall (0-5
height <-5 or >5, and BMI for age <-5 or >5. Using these years) prevalence with weight for height was lower in
filters, 2,07,364 subjects were available for the analysis comparison to BMI for age in short populations. However,
(Web Fig. 1 and 2). In the CNNS dataset, 3,162 subjects the prevalence was higher with weight for height criterion

Fig. 1 Comparison of estimated prevalence and 95% confidence intervals of possible risk of overweight (>1SD) using weight for height
and body mass index for age criteria on simulated populations. Panel A - short, based on the National Family Health Survey-4, India data
[15]; Panel B - intermediate [7]; Panels C, D and E - tall, based on Poland [18], Greenland [17] and the National Health and Nutrition
Examination Survey, USA [16] data, respectively.

Fig. 2 Comparison of estimated prevalence and 95% confidence intervals of possible risk of overweight (>1SD) using weight for height
and body mass index for age criteria in Meerut [14] (left) and National Family Health Survey-4 [15] (right), India datasets. Panel A –
Entire population, Panel B – Boys, and Panel C – Girls.
in 0 to 0.5 years (19.8% vs 8.1%) and lower in 0.5 to 5 years b oth metrics, whereas the 0-0.5 years prevalence was
(8.3% vs 11.1%). A reverse pattern was observed in tall slightly higher with weight for height criterion (17.2% vs
populations, except for the USA dataset where the overall 15.9%). A similar pattern, but with lower magnitude, was
prevalence with weight for height was marginally lower evident for overweight (>2SD) comparison in short
(35.7% vs 36.4%). In intermediate population, the 0-5 years population (Web Fig. 5). No differences were observed for
and 0.5-5 years prevalence estimates were similar with the intermediate population. In the tall populations from

Fig. 3 Comparison of estimated prevalence and 95% confidence intervals of possible risk of overweight (>1 SD, left) and overweight
(>2 SD, right) using weight for height and body mass index for age criteria in Comprehensive National Nutrition Survey, India datasets.
Panel A – Entire population. Panel B – Boys, and Panel C – Girls.
Poland and Greenland databases, the weight for height were 32.6 (15.5), -1.87 (1.22), -1.11 (0.94), and -0.91 (0.94),
estimates were slightly lower from 0-0.5 years, but respectively. Boys constituted 53% of the sample. Risk of
comparable thereafter and for overall prevalence. In the overweight (>1SD) was lower with weight for height from 2-
USA dataset, the overall and 0.5-5 years prevalence was 3 years and for overall (1.35% vs 2.15%) prevalence (Fig.
marginally lower with weight for height. 2). The difference was higher in stunted children and
The mean (SD) age (months), height for age, weight for decreased with increasing stature. The discrepancy was
height, and BMI for age (z-scores) of the Meerut study more in boys. No significant differences were apparent for

overweight (>2SD), but the overall prevalence
0.99 (125217);
0.99 (195249);
0.99 (197915);
0.99 (193607);
0.99 (128311);
0.98 (196870);
was only 0.17%-0.22% (Web Fig. 6).
0.99 (10073);
0.98 (33874);
Whether stunted; [95% CI]
[0.98, 0.99]
[0.97, 0.98]
[0.98, 0.99]
[0.98, 0.99]
[0.98, 0.99]
[0.98, 0.99]
[0.98, 0.99]
[0.98, 0.98]
No (n) The mean (SD) age (months), height for
age, weight for height, and BMI for age (z-
scores) in the NFHS-4 survey were 28.3 (16.2), -
0.95 (79053);
0.93 (74083); 1.46 (1.7), -0.93 (1.4), and -0.81 (1.4), respectively.
0.97 (8379);
0.93 (1024);
0.93 (6236);
0.93 (4611);
0.94 (1788);
0.93 (1576);
[0.92, 0.93]
[0.96, 0.97]
[0.92, 0.94]
[0.92, 0.93]
[0.93, 0.95]
[0.92, 0.93]
[0.94, 0.95]
[0.92, 0.93]
Boys constituted 52% of the sample. The
Yes (n)
Table II Bivariate Pearson Correlation Coefficients Between Weight for Height and Body Mass Index for Age (BMI for Age)
prevalence of possible risk of overweight with

weight for height metric was higher in 0-0.5
years, but lower in 0.5-5 and 0-5 years (Fig. 2).
0.91 (12541);
0.89 (14761);
0.77 (5635);
0.93 (151539); 0.71 (5344);
0.82 (1122);
0.94 (8741);
0.99 (188874); 0.91 (5079);
The absolute differences in 0.5-5 years and

[0.69, 0.72]
[0.90, 0.91]
[0.90, 0.91]
[0.82, 0.95]
[0.80, 0.84]
[0.88, 0.89]
[0.93, 0.94]
[0.76, 0.78]
>+2 SD (n)
0.90 (40);
overall sample were 2.26% (6.57% vs 8.83%)
and 1.56% (7.23% vs 8.78%). In severely and
moderately stunted children, the difference was
BMI-for-age; [95% CI]
much higher in 0-0.5 years (53.9% vs 11.6% and

0.99 (182392);
0.98 (181554);
0.88 (37871); 0.94 (163858);

0.98 (176385);
0.96 (16323);
0.96 (29529);
39.1% vs 19.8%, respectively) in comparison to
[0.98, 0.99]
[0.98, 0.99]
[0.92, 0.93]
[0.95, 0.96]
[0.96, 0.96]
[0.97, 0.98]
[0.97, 0.98]
[0.93, 0.94]
≥+2 SD (n)
≥-2 SD to
0.5-5 years (11.9% vs 18.2% and 8.1% vs 12.5%,

respectively). The differences decreased with
increasing stature. The discrepancy was higher
in boys. Similar patterns were evident for
0.91 (42417);
0.89 (2087);
0.89 (4251);
0.90 (5907);
0.92 (4770);
0.87 (2131);
0.89 (2344);
[0.91, 0.92]
[0.89, 0.90]
[0.90, 0.91]
[0.88, 0.89]
[0.88, 0.90]
[0.88, 0.90]
[0.85, 0.88]
[0.87, 0.88]
overweight (>2SD), but with a smaller
<-2 SD (n)
magnitude of overall prevalence and absolute

differences (Web Fig. 6). Kernel density plots
confirmed a shift in the entire distribution,
which was in opposite direction in 0-6 months
0.94 (12598);
0.92 (14905);
0.94 (20379);
0.58 (5050);
0.37 (4627);
0.92 (4991);
[0.91, 0.92]
[0.93, 0.94]
> +2 SD (n)
[0.93, 0.94]
[0.82, 0.95]
[0.73, 0.78]
[0.34, 0.39]
[0.91, 0.92]
[0.56, 0.60]
0.76 (982);
and 6-59 months and of a greater magnitude in

0.91 (32);
the stunted subjects (Web Fig.7).

The mean (SD) age (months), height for
Weight for height; [95% CI]
age, weight for height, and BMI for age (z-

0.99 (182644);
0.98 (181618);
0.98 (177011);
0.99 (189105);
0.90 (41761); 0.94 (160553);

0.93 (44437); 0.93 (150236);
0.96 (29066);
0.96 (15490);
scores) of the CNNS dataset were 30.53 (16.8), -

[0.92, 0.93]
[0.98, 0.99]
[0.98, 0.99]
[0.97, 0.98]
[0.95, 0.96]
[0.96, 0.97]
[0.97, 0.98]
[0.93, 0.94]
≥+2 SD (n)
1.15 (1.5), -0.72 (1.3), and -0.60 (1.3), respectively.

≥-2 SD to
Boys comprised 52% of the sample. Patterns

similar to NFHS were documented for both the
possible risk of overweight (>1SD) and
0.78 (2453);
0.89 (2930);
0.87 (5764);
0.87 (4461);
0.90 (4850);
0.58 (1923);
overweight (>2SD) and the kernel density plots;

[0.76, 0.80]
[0.92, 0.93]
[0.86, 0.87]
[0.88, 0.89]
[0.89, 0.91]
[0.55, 0.61]
[0.89, 0.90]
[0.86, 0.87]
<-2 SD (n)
however, the magnitude of overall prevalence

and differences was lower and not statistically
significant at more time intervals (Fig. 3, and
Web Fig. 8).
0.968 (<0.001)
0.971 (<0.001)
0.987 (<0.001)
0.974 (<0.001)
0.988 (<0.001)
0.990 (<0.001)
0.979 (<0.001)
0.982 (<0.001)
Misclassification occurred in both

Correlation
coefficients
(P values)
directions, being more evident in short

populations (Web Tables I and II). In 0-0.5
years, children classified as overnourished by
weight for height and not by BMI for age was
more frequent than opposite misclassification.
200000
200000
200000
200000
207364
200000
34898
18452
Simulated populations
The reverse pattern was observed in 0.5-5

N
years, except for the Poland and Greenland

simulated datasets.
Meerut Study
Greenland
Intermediate
NHANES
(NFHS-4)
The Bland-Altman analyses varied with age

Poland
Datasets
NFHS-4
CNNS
for the simulated short population. In the 0-6

Short
Tall
months age group, thinner infants had lower

weight for height z-scores whereas obese infants had lower Canadian children, the prevalence of stunting was 23%.
BMI for age z-scores (positive association between the Their BMI for age and weight for length percentiles
difference and average of weight for height and BMI for differed by >25 percentile points in ~9%, and ~16% in
age z-scores). An opposite but milder association was those below 6 months. Overweight (≥85th percentile)
evident for 6-59 months. A similar but relatively milder prevalence was higher with weight for length (21% vs
pattern was seen in other data sets (Web Table III). 18.3%), with differences (18.2% vs 12.5%) in 0-6 months
age, but comparable estimates (23.7% in both) for 6-24
There was an excellent correlation between the two months. Similar findings were evident for obesity (≥95th
metrics in all data sets (r= 0.97–0.99; r2 =0.94–0.98) (Table percentile; 12.2% vs 9.9%) [6]. In 0-2 years and under-five
II). In general, in thin and overweight subjects, the healthy children, from Canada [7] and USA [18],
correlation coefficients were significantly lower (non- respectively, the prevalence of stunting was low. Weight
overlapping 95% confidence intervals) than in those for length and BMI for age demonstrated high agreement
classified as normal with either the weight for height or with comparable overweight prevalence. These findings
BMI for age criteria. In the NFHS-4 and CNNS population, are similar to our analyses, factoring for stunting
the correlation was weaker for obese subjects in prevalence and age strata. In an analysis on global
comparison to thin subjects, whereas the converse was prevalence and trends of overweight and obesity among
true for the tall populations. Further, the correlations were preschool children, 450 nationally representative cross-
significantly, but slightly, weaker in stunted participants. sectional surveys from 144 countries were evaluated [19].
DISCUSSION Both metrics yielded com-parable prevalence estimates in
aggregated data from high income countries (HICs) (only
In under-five children, overnutrition definitions based on graphical depiction), with similar results for other regions
WHO’s weight for height and BMI for age standards (text statement). In the absence of estimates related to
produced cutoffs, and hence prevalence estimates, that stunting prevalence, age strata and sex, these findings
differed with the age, sex and height of subjects. Also, for a cannot be compared with our analyses.
given height and weight, these characteristics were
associated with subtle variations in the computed z-scores We depicted prevalence differences in under-five
for these two metrics. Consequently, in Indian real-life children with both 1SD and 2SD cutoffs. The former
datasets, representative of a short population, prevalence showed greater disagree-ment and are more relevant for
with weight for height was higher from 0-0.5 years LMICs, particularly India. First, this aligns the BMI for age
(exclusive breastfeeding age), but lower for 0.5-5 years. cutoffs for defining overweight in under-five (currently
The discrepancy was lower in girls and maximal for stunted 2SD) children and those aged 5-19 years (currently 1SD)
children. In simulated datasets from intermediate and tall [20], which allows pertinent comparisons across age
populations, there were no meaningful or marginal ranges. Second, metabolic perturbations associated with
differences. This study focuses on the systematic com- increased ponderosity start manifesting at lower cutoffs in
parison of these two metrics, using the WHO standards, older children, adolescents and adults in India [21].
for defining various grades of overnutrition in a LMIC However, prevalence estimates based on arbitrary cutoffs
setting. Consonance between theoretical considerations, (1SD or 2SD) may be of restricted utility, if the underlying
simulations and real-life data sets enhances confidence in process is continuous, and z-scores distribution could
the findings. therefore be more meaning-ful for population monitoring
[22]. We docu-mented a distributional shift too,
There is a paucity of published data from LMIC compatible with the prevalence discrepancy. In the NFHS-
settings for comparison. Theoretically, Cole first demons- 4 survey, the mean z-scores differences ranged from 0.16 to
trated with the National Centre for Health Statistics 0.21, which are roughly comparable to effective inter-
(NCHS), USA standards, that short children above 6 ventions at population level [23]. The excellent corre-
months of age appear thinner based on weight for height lations (r=0.97 to 0.99), observed by us and others [5-7, 17]
[16]. He suggested that weight/height2 should be the summarize only the degree of linear relation between these
preferred index to prevent misleading assessments in tall two metrics and do not establish the interchangeability of
or short under-five children. With NCHS standards, in 4348 the two stan-dards. The weaker correlations at the margins
children from USA, aged 2-5 years, overweight (≥85th (>2SD or <-2SD), Bland-Altman analyses and 2×2 tabular
percentile) prevalence by weight for height was lower depictions provide a deeper insight into the disagreement
(0.9%-6%) than by BMI for age with greater differences in patterns.
shorter children and at 4 years age [17].
Among limitations, real-life datasets from diverse
Using WHO standards, in 547 diseased, 0-2 years old settings of linear growth failure, and intermediate and tall

WHAT IS ALREADY KNOWN?

• Overnourished under-five children are anthropometrically classified as either being at possible risk of
overweight, overweight or obese and defined so, when either weight for height or body mass index for age are
>1SD to 2SD, >2SD to 3SD and >3SD, respectively of the analogous World Health Organization standards.
WHAT THIS STUDY ADDS?
• The two definitions produce cutoffs, and hence estimates of overnutrition, that differ with the age, sex, and
height of under-five children.
populations were not evaluated; however, simulations biological outcomes like adiposity and cardiometabolic
partly address this gap. Also, biological outcomes were not risk factors in later life.
studied for determining the comparative utility of these
In conclusion, weight for height and BMI for age
two metrics. Data from USA indicate that BMIZ and its
definitions produce estimates of overnutrition, which vary
change are better indicators of adiposity at 1 month age [8]
with the age, sex and height of children. In populations with
and fat accrual during the first 5 postnatal months [24],
substantial stunting, in under-five children and especially
respectively. However, analyses of USA and Belarus
those aged 6-59 months, overnutrition estimates are lower
cohorts concluded that choice of weight for length vs BMI
with weight-for-height criterion, but there are no
to define overweight during the first 2 years of life may not
meaningful differences in intermediate or tall populations.
greatly affect the association with cardio-metabolic
The relative invariance of BMI for age with age and
outcomes during early adolescence [9]. There is a paucity
stature, and establishment of a uniform metric definition
of similar studies from LMIC settings.
from birth to adulthood, justifies its preference for
There are potential policy implications of these
classifying overnutrition in under-five children.
findings. In contrast to intermediate or tall populations, in
nations with substantial stunting, weight for height com- Ethics clearance: Authors confirm that such approval is not
pared with BMI for age, inflates the undernutrition burden needed for these theoretical simulations and secondary analyses
[5] and simultaneously deflates the overnutrition esti- of data from other studies for which the requisite ethical
mates, especially in children aged 6-59 months. This permissions had been obtained. Authors declare that the study
procedures conform to the principles laid down in the
magnifies the gap between the HICs and LMICs for
Declaration of Helsinki.
‘malnutrition’ (combined under- and over-nutrition) Contributors: HSS: conceptualized the study; LNR: primary
burden, and distorts the ranking and progress of nations in analyses and interpretation under the supervision of MS, CO
achieving the related SDGs. In routine Demographic and HSS; LNR,HSS: drafted the initial manuscript. All authors
National Surveys conducted in LMICs, the discrepancies provided critical inputs into revision of the article and are willing
in absolute prevalence may appear small. Nevertheless, to be accountable for all aspects of the study.
with relatively lower overnutrition prevalence currently, Funding: None; Competing interests: None stated.
these differences assume importance for urgently Note: Additional material related to this study is available with
influencing investments and policy. The disagreements the online version at www.indianpediatrics.net
are likely to be larger and more relevant for granular REFERENCES
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NAGA RAJEEV, ET AL.
Web Table I Summary of Disagreement in Possible Risk of Overweight (>1 SD) Classification
Age-groups (years)
0.0-0.5 0.5 - 5.0
Not Not
Overweight
overweight Overweight by overweight
Datasets by weight-
by weight- weight-for- by weight-
for-height Total Ratio Total Ratio
for-height height but not for-height
but not by (a+b) (a/b) (c+d) (c/d)
but by by BMI-for- but by
BMI-for-
BMI-for- age (%) (c) BMI-for-
age (%) (a)
age (%) (b) age (%) (d)
Short
simulated
from NFHS-4 11.9 0.2 12.1 54.0 0.3 3.1 3.3 0.1
Intermediate
Population 3.4 2.1 5.4 1.6 1.0 1.1 2.1 0.9
Tall population simulated from
Poland 2.3 3.8 6.2 0.6 1.5 1.1 2.6 1.3
Greenland 2.3 5.8 8.2 0.4 2.5 1.4 3.9 1.8
NHANES 4.3 3.6 7.9 1.2 1.2 2.1 3.3 0.6
Real-life datasets
Not Not Not Not
Meerut study sampled sampled sampled sampled 0.0 0.8 0.9 0.0
NFHS-4 5.2 0.4 5.6 14.0 0.2 2.4 2.6 0.1
CNNS 2.8 1.1 4.0 2.6 0.2 1.9 2.1 0.1
Web Table II Summary of Disagreement in Overweight (>2SD) Classification
Age-groups (years)
0.0-0.5 0.5 - 5.0
Not Not
Overweight
overweight Overweight by overweight
Datasets by weight-
by weight- weight-for- by weight-
for-height Total Ratio Total Ratio
for-height height but not for-height
but not by (a+b) (a/b) (c+d) (c/d)
but by by BMI-for- but by
BMI-for-
BMI-for- age (%) (c) BMI-for-
age (%) (a)
age (%) (b) age (%) (d)
Short
simulated from
NFHS-4 5.30 0.03 5.33 176.67 0.13 1.06 1.19 0.12
Intermediate
Population 0.53 0.63 1.16 0.84 0.21 0.25 0.46 0.84
Tall population simulated from
Poland 0.54 1.82 2.36 0.30 0.58 0.46 1.04 1.26
Greenland 0.78 2.41 3.19 0.32 0.82 0.64 1.46 1.28
NHANES 1.53 1.65 3.18 0.93 0.57 1.00 1.57 0.57
Real-life datasets
Not Not Not Not
Meerut study sampled sampled sampled sampled 0.05 0.17 0.22 0.29
NFHS-4 3.57 0.13 3.70 27.46 0.08 0.77 0.85 0.10
CNNS 1.67 0.30 1.97 5.57 0.06 0.64 0.70 0.09
INDIAN PEDIATRICS VOLUME 60__JANUARY 15, 2023

OVERNUTRITION DEFINITION: WHZ VS BMIZ
Web Table III Regression Coefficients Between the Difference and Average of Weight-for-height and
Body-Mass-Index-for-Age Z-scores in Various Datasets
Datasets β coefficient (SE); P value

Male Female
0-6 months 6-59 months 0-6 months 6-59 months
Simulated Populations
Short (NFHS-4) 0.2 (0.0); <0.0001 -0.1 (0.0); <0.0001 0.2 (0.0); <0.0001 -0.1 (0.0);
<0.0001
Intermediate 0.0 (0.0); <0.0001 0.0 (0.0); <0.0001 0.0 (0.0); <0.0001 0.0 (0.0);<0.0001
Population
Tall
Greenland 0.1 (0.0); <0.0001 0.0 (0.0); <0.0001 0.0 (0.0); <0.0001 0.0 (0.0); <0.0001
NHANES 0.1 (0.0); <0.0001 0.0 (0.0); <0.0001 0.0 (0.0); <0.0001 0.0 (0.0); <0.0001
Real-life datasets
Meerut Study Not sampled 0.0 (0.0); 0.314 Not sampled -0.1 (0.0);
<0.0001
NFHS-4 0.2 (0.0); <0.0001 0.1 (0.0); <0.0001 0.2 (0.0); <0.0001 -0.1 (0.0);
<0.0001
CNNS 0.1 (0.0); <0.0001 0.0 (0.0); <0.0001 0.1 (0.0); <0.0001 -0.2 (0.0);
<0.0001
Web Fig. 1 Flowchart for arriving at the analytic sample in NFHS-4 dataset.

NAGA RAJEEV, ET AL.
Web Fig. 2 Flowchart for Showing the Details of Children (age-wise and gender-wise) in Each of the Datasets
Web Fig. 3 Comparison of absolute Body-Mass-Index cut-offs for defining overweight (>2SD) according to weight-for-height and
Body-Mass-Index-for-age criteria in boys (left side) and girls (right side) whose height is at -2SD, 0SD and +2SD of World Health
Organization growth standards.

Panel A
Panel B
Panel C
Web Fig. 4 Comparison of z-scores of weight-for-height and Body-Mass-Index-for-age for a fixed height-for-age (-2SD, 0SD, and
+2SD) in boys (left side) and girls (right side) whose weight-for-age is at 0SD (Panel A), +1SD (Panel B) and +2SD (Panel C) of WHO
g r o w t h

NAGA RAJEEV, ET AL.
Web Fig. 5 Comparison of estimated prevalence and 95% confidence intervals of risk of overweight (>2SD) using weight-for-height and
Body-Mass-Index-for-age criteria on simulated populations: Panel A - short based on the National Family Health Survey-4, India data;
Panel B - intermediate; Panels C, D and E - tall based on Poland, Greenland and the National Health and Nutrition Examination Survey,
USA data, respectively.

Meerut Study
NFHS-4
Web Fig. 6 Comparison of estimated prevalence and 95% confidence intervals of overweight (>2SD) using weight-for-height and Body-
Mass-Index-for-age criteria in Meerut (above) and National Family Health Survey-4 (below), India datasets: Panel A – Entire
population, Panel B – Boys, and Panel C – Girls.

NAGA RAJEEV, ET AL.
(0-6 months)
(6-59 months)
Panel A Panel B
Web Fig 7 Kernel density estimates for z-scores of Weight-for-height and Body-Mass-Index-for-age in NFHS 4 dataset: Panel A:
Overall and Panel B: Stunted.

(0-6 months)
(6-59 months)
Panel A Panel B
Web Fig. 8 Kernel density estimates for z-scores of weight-for-height and Body-Mass-Index-for-age in Comprehensive National
Nutrition Survey dataset: Panel A: Overall and Panel B: Stunted.

RESEARCH PAPER
Effect of Kangaroo Mother Care on Cerebral Hemodynamics in Preterm

Neonates Assessed by Transcranial Doppler Sonography in Middle
Cerebral Artery
ANAL J CHAUDHARI,1 SOMASHEKHAR M NIMBALKAR,1,2 DIPEN V PATEL,1 AJAY G PHATAK2
1Department of Neonatology, Pramukhswami Medical College, Bhaikaka University, Karamsad, Gujarat.
2Central Research Services, Charutar Arogya Mandal, Bhaikaka University, Karamsad, Gujarat.
Correspondence to: Dr Somashekhar M Nimbalkar, Professor and Head, Department of Neonatology, Pramukhswami Medical
College, Bhaikaka University, Karamsad, Gujarat. somu_somu@yahoo.com
Received: June 06, 2022; Initial review: July 06, 2022; Accepted: August 04, 2022.
Objective: To study the effect of KMC in premature newborns The mean (SD) cerebral blood flow velocities increased (peak
on cerebral hemodynamics in the middle cerebral artery (MCA) systolic velocity (PSV), P=0.03; end diastolic velocity, P<0.001;
using transcranial doppler sonography. mean velocity, P<0.001) and doppler indices decreased (resis-
Methods: In this descriptive study, 40 clinically stable preterm tive index, P=0.001; pulsatility index, P<0.001) significantly;
neonates admitted to the neonatal intensive care unit of our whereas, heart rate (P<0.001) decreased but SpO2 (P=0.001)
institute and undergoing Kangaroo mother care (KMC) were and mean blood pressure (P=0.003) increased significantly at 60
enrolled. Physiological and cerebral blood flow parameters of minutes of KMC as compared to baseline. Sixty minutes after
MCA were obtained by using transcranial doppler sonography at stopping KMC, all parameters (except PSV) were higher than
baseline, at 60 minutes of KMC, and after 60 minutes of stopping baseline, indicating post KMC effect.
KMC. Conclusion: KMC improves cerebral hemodynamics in clinically
stable preterm neonates.
Results: Of the 40 enrolled neonates (24 males), the mean (SD)
birth weight, gestation age, and postnatal age were 1698.25 Keywords: Benefit, Cerebral blood flow, Neonatal care,
(495.44) g, 33.00 (1.67) wk, and 6.80 (4.51) days, respectively. Outcome.
Published online: October 29, 2022; PII: S097475591600466
P
remature neonates, born across the globe, spend preterm neonates [7-10], positively influences the
their first few weeks of life in the neonatal premature brain networks, facilitates the formation of
intensive care unit (NICU) [1], where they are neural connections, and leads to better long-term
subjected to an abnormal environment and neurodevelopmental outcomes [11].
multiple invasive procedures. The neonatal period is the
critical period of brain development and maturation [2]. Invited Commentary: Pages 13-14
Preterm neonates are especially susceptible to brain injury
Most studies on KMC have focused on thermo-
as they have immature cerebral vasculature and ineffective
regulation, pain control intervention, physical growth,
cerebral autoregulation, leading to the marked fluctuation
mortality and sepsis reduction, success with breast-
in cerebral blood flow [3,4]. This results in cerebrovascular
feeding, and improvement in cardiorespiratory parameters.
events like intraventricular hemorrhage and ischemic injury
However, the effect of KMC on cerebral blood flow and its
to periventricular white matter, which have long-term
dynamics in preterm has not been studied well.
adverse neurodevelopmental problems in cognitive, motor,
Transcranial color Doppler sonography is an excellent,
and behavioral domains [5].
non-invasive modality for real-time assessment of cerebral
Globally, during the last two decades, there has been blood flow in newborns [12]. Color Doppler imaging of the
significant improvement in the survival of extremely middle cerebral artery (MCA) displays various cerebral
preterm neonates due to advanced perinatal and neonatal blood flow parameters, which helps to evaluate alterations
intensive care practices. Increased survival has also in cerebral hemodynamics [13]. The current study aims to
resulted in increased neuro-morbidity among the evaluate the changes in cerebral blood flow patterns and
survivors. Hence, neuroprotective strategies are required velocities in MCA by using transcranial color Doppler
to improve cerebral hemodynamics [6]. Kangaroo mother before and after KMC in clinically and hemodynamically
care (KMC), an evidence-based standard of care for stable preterm neonates.

28 KMC AND CEREBRAL HEMODYNAMICS IN PRETERMS
METHODS phased array transducer (Model P10x) of 8-4 MHz. All

cranial ultrasound examinations were performed by a
A single- arm interventional study was conducted between Neonatology fellow having expertise in neonatal cranial
September, 2020 to May, 2021 at Level 3 NICU in a Medical ultrasound. Color Doppler imaging with pulsed wave
college in Anand, Gujarat, India, enrolling all clinically and Doppler (PWD) was used to identify MCA from the
hemodynamically stable preterm neonates (28 0/7 to 36 6/7 temporal window. The cerebral blood flow velocities
weeks gestational age) admitted to NICU or KMC ward. (CBFVs) and Doppler indices (RI and PI) measured
Exclusion criteria were neurological impairment (perinatal included i) Peak systolic velocity (PSV): Highest velocity in
depression and hypoxic-ischemic encephalopathy, intra- the cardiac cycle; ii) End diastolic velocity (EDV): Lowest
ventricular hemorrhage, hydrocephalus, stroke, seizure or velocity at the end of the cardiac cycle; iii) Mean velocity
congenital malformation of the central nervous system), (MV): Calculated over a series of cardiac cycles; iv)
congenital heart disease, critical illness rendering the Resistive Index (RI): (PSV-EDV)/PSV; and v) Pulsatility
babies unstable (needing invasive mechanical ventilation index (PI): (PSV-EDV)/MV.
and/or inotropes), administration of pain control/sedative
medications within 24 hours before study interventions, Statistical analysis: Paired t test was used to compare
and neonatal abstinence syndrome. physiological and cerebral blood flow Doppler parameters
at baseline (before KMC), at 60 min KMC and after 60 min
In the absence of any regional estimates of the of KMC. Pearson correlation coefficient was used to
standard deviation of outcome variables, it was not correlate cerebral blood flow parameters with gestational
possible to calculate the exact sample size. The study age and birth weight. The analysis was performed using
period was planned for around nine months expecting to STATA (14.2). A P value of less than 0.05 was considered
enrol around 35 participants. significant.
After obtaining written informed consent from RESULTS
parents, the baseline physiological parameters [heart rate
Of a total of 152 preterm neonates admitted in NICU, 93
(HR), oxygen saturation (SpO2), and blood pressure (BP)]
neonates did not meet the inclusion criteria, mothers of 15
and cerebral blood flow parameters of MCA were obtained
eligible neonates were not available to provide KMC as
by using transcranial color Doppler ultrasonography in a
they were COVID-19 positive and sick, and mothers of
supine position under a radiant warmer. After that,
four neonates refused to participate. So, 40 (24 (60%)
neonates were given KMC for the first time as per
males) clinically stable preterm neonates were enrolled in
standard positioning technique, for a minimum of 60
the study, with 27(67.5%), 11(27.5%) and 24 (60%) being
minutes. All cerebral blood flow parameters and
appropriate for gestation age (AGA), small for gestation
physiological parameters were obtained at 60 min of KMC
age (SGA) and late preterm babies, respectively. The mean
and 60 minutes after stopping KMC. All neonates were
(SD) gestational age, birth weight, and postnatal age of
examined in a calm and resting state without any sedation.
the participants was 33.05 (1.68) weeks, 1698.25 (495.44) g,
Cerebral blood flow parameters were obtained by Doppler
and 6.8 (4.52) days, respectively.
imaging evaluation of the middle cerebral artery using
Transcranial color Doppler (TCD) ultrasonography All the mean cerebral blood flow parameters of MCA
machine (Sonosite, Model-EDGE-Fifth generation Doppler viz., PSV, EDV, MV, RI and PI improved
portable ultrasound, Sr. no-03P565) with a high resolution significantly at 60 minutes of KMC compared to baseline
Table I Cerebral Blood Flow Parameters of Middle Cerebral Artery Doppler at Different Durations of Kangaroo Mother
Care (KMC) (N=40)
Parameters Before KMC At 60 min MD (95% CI)a; 60 min after MD (95% CI)b;
(Baseline) of KMC P value stopping KMC P value
PSV (cm/s) 43.9 (3.76) 44.8 (3.94) -0.90 (-1.70,-0.90); 0.030 43.8 (3.45) 0.12 (-0.59,0.82); 0.74
EDV (cm/s) 10.8 (1.30) 11.8 (1.33) -0.97 (-1.41,-0.54); <0.001 11.4 (1.1) -0.66 (-0.96,-0.36); <0.001
MV (cm/s) 21.8 (1.90) 22.8 (1.91) -0.92 (-1.39,-0.46); <0.001 22.2 (1.64) -0.38 (-0.73,-0.03); 0.032
RI 0.7 (0.02) 0.7 (0.03) 0.02 (0.01,0.03); 0.001 0.7 (0.023) 0.16 (0.01, 0.020); <0.001
PI 1.5 (0.09) 1.4 (0.11) 0.07 (0.03,0.11); <0.001 1.4 (0.09) 0.06 (0.04,0.09); <0.001
All values in mean (SD). MD-mean difference. abefore KMC–at 60 min of KMC. bbefore KMC–60 min after stopping KMC. SpO2-oxygen
saturation; BP-blood pressure; PSV-peak systolic velocity; EDV-end diastolic velocity; MV-mean velocity; RI- resistive index; PI-pulsatility index.

CHAUDHARI, ET AL. 29
values. The values were higher than baseline at 60 minutes minutes of KMC from baseline, whereas systolic and
after stopping KMC except for PSV (Table I). Similarly, the diastolic blood pressure remained similar. The effect was
physiological parameters viz. SpO2, heart rate, and mean sustained only for mean blood pressure after 60 minutes of
blood pressure showed significant improvement at 60 stopping KMC (Table II).
Table II Physiological Parameters of Middle Cerebral Artery Doppler at Different Durations of Kangaroo Mother Care
(N=40)
Parameters Before KMC At 60 min MD (95% CI)a; 60 min after MD (95% CI)b;
(Baseline) of KMC P value stopping KMC P value
Heart rate (per min) 148.8 (10.42) 143.6 (11.24) 5.23 (2.95,7.50); <0.001 146.1 (10.55) 2.65 (-0.05, 5.35); 0.05
SpO2 (%) 95.7 (1.40) 96.5 (1.50) -0.88 (-1.38,-0.37); 0.001 95.8 (1.82) -0.18 (-0.76, 0.41); 0.55
Systolic BP(mmHg) 64.0 (7.81) 64.6 (8.73) -0.63 (-1.84, 0.59); 0.31 63.9 (8.38) 0.05 (-1.34, 1.44); 0.94
Diastolic BP (mmHg) 42.2 (6.96) 43.3 (6.75) -1.05 (-2.44, 0.34); 0.14 43.3 (6.83) -1.08 (-2.69, 0.54); 0.19
Mean BP (mmHg) 45.1 (7.59) 46.9 (8.32) -1.73 (-2.81,-0.64); 0.003 47.1 (7.81) -1.93 (-3.11,-0.74); 0.002
All values in mean (SD). KMC-kangaroo mother care; MD-mean difference, abefore KMC–at 60 min of KMC, bbefore KMC–60 min after
stopping KMC. SpO2-oxygen saturation; BP-blood pressure.
a) Correlation between GA and EDV b) Correlation between GA and MV
c) Correlation between GA and RI d) Correlation between GA and PI
EDV: end diastolic velocity, MV: mean velocity, RI: resistive index, PI: pulsatility index.
Fig. 1 Correlation between gestational age (GA) and cerebral blood flow (CBF) parameters in preterm infants undergoing kangaroo
mother care (KMC).

Table III Correlation Between Birth Weight and Cerebral stabilize, facilitating neural connections, enhancing
Blood Flow (CBF) Parameters of Middle Cerebral Artery synaptic efficacy and connectivity of cerebral motor
Doppler at Baseline Before Kangaroo Mother Care (N=40) pathways. It also enables better quality of quiet sleep and
CBF parameters Correlation coefficient P value induces non-chaotic sleep patterns and normal sleep
cycling [9]. Nelson and Panksept’s brain opioid theory of
PSV 0.362 0.022
social attachment, based on animal experimentation,
EDV 0.552 <0.001 postulates that maternal touch, smell, and milk release
MV 0.505 0.001 endogenous opiates, which are known to promote
RI -0.324 0.042 affiliative behavior [16]. Oxytocin is the primary hormone
promoting affiliation and appears to have anti-nociceptive
PI -0.361 0.022
effects. Activation of slow-conducting unmyelinated
PSV: peak systolic velocity; EDV: end diastolic velocity; MV: mean afferents by pleasant touch stimulates the cortex to
velocity; RI: resistive index; PI: pulsatility index.
produce various vasodilatory mediators and induces nitric
oxide-mediated smooth muscle relaxation of cerebral
microvasculature [17,18]. Hence, KMC might positively
On evaluating the correlation between cerebral blood
influence cerebral hemodynamics in the preterm brain by
flow parameters of MCA Doppler at baseline and gestation
these various proposed mechanisms.
age (Fig.1) and birth weight (Table III), it was seen that
while EDV (r=0.49) and MV (r= 0.40) were significantly Korraa, et al. [19], in a similar study in Egypt, recruited
positively correlated with gestation age, RI (r = -0.35) and 60 clinically stable preterms and measured CBF parameters
PI (r = -0.37) were significantly negatively correlated with in MCA before and after 30 min of KMC. This study
gestation age. Although, PSV (r=0.26) had a positive demonstrated a significant increase in CBFVs (EDV and
correlation with gestation age, it was not statistically MV) and a significant decrease in Doppler indices (RI and
significant. The correlation between cerebral blood flow PI) after 30 minutes of KMC, indicating improvement in
parameters of MCA Doppler and gestational age are CBF following KMC application. Other authors [20-22]
shown in Fig. 1. also observed a correlation between all CBFVs and
DISCUSSION gestational age. Thus, the current study results are
concordant with these previously published studies.
The current study determined the impact of KMC on
cerebral hemodynamics in MCA and physiological Similar to the study by Seibert, et al. [23], Doppler
parameters. There was a statistically significant improve- indices (RI and PI) showed a significant decrease with
ment in all CBF parameters at 60 minutes of KMC compared increasing gestational age in the current study. Nourian, et
to baseline. However, these changes in CBF parameters al. [24] suggested that the effect of KMC on the
were within the normal range. The trend of improving CBF physiological parameters remains sustained. Azeez, et al.
parameters was still evident at 60 minutes of stopping [25] also found that the majority of babies who received
KMC except for the PSV, which was closer to the baseline KMC showed significant improvement in vital parameters.
values. As this effect of KMC was studied only up to 60 Pezzati, et al. [22] generated normal reference data for MCA
minutes after stopping KMC, the effect after that is CBF parameters in preterm infants and demonstrated
unknown. We also found significant correlation between association with GA and BW. The current study
CBF parameters at baseline and gestation age and birth additionally helped in the establishment of a normative
weight. Further, this study showed a positive impact of database for MCA cerebral Doppler measurements in
KMC on cardiorespiratory parameters, the effect was stable preterm infants.
sustained only for mean blood pressure post 60 minutes of
The residual effect on many parameters even after 60
stopping KMC.
minutes suggests that KMC may be working through the
KMC has emerged as a safe, feasible, and low-cost release of various hormones or neurotransmitters which
intervention for neonates, with significant benefits [14,15]. have a half-life of more than 60 minutes. As KMC is a
The beneficial effects of KMC on cerebral hemodynamics multimodal intervention and achieves its actions through
in preterm neonates are yet to be fully explored. Neuro- various mechanisms, it is difficult to isolate a single or few
physiological effects of KMC might mediate improvement hormones/neurotransmitters that are responsible for it.
in cerebral blood flow. Skin-to-skin care by the mother Duration of KMC has a dose-relation-ship effect on the
provides multisensory stimulation, including tactile, size of the grey matter, especially the left caudate nucleus,
auditory, and olfactory. All these may have a tranquilizing as shown by a 20-year follow-up study [11]. We now have
effect on the baby, allowing physiological parameters to some evidence that KMC alters circulatory flow in the

CHAUDHARI, ET AL. 31
WHAT IS ALREADY KNOWN?

• Most of the studies on Kangaroo Mother Care have focused on thermoregulation, pain control intervention,
physical growth, breastfeeding, mortality, and sepsis reduction.
• KMC improves cerebral hemodynamics response by improving cerebral blood flow in hemodynamically
stable preterm neonates.
brain, which might ensure appropriate growth of neurons on preterm birth providing key facts and information on
and thus their function [26]. The residual effect following solution, geographical distribution and WHO response.
stopping KMC, as shown in the current study, suggests Accessed July 26, 2022. Available from https://www.who.int/
that short breaks between KMC sessions due to change in news-room/fact-sheets/detail/preterm-birth
2. Anand KJ, Scalzo FM. Can adverse neonatal experiences
KMC providers/KMC provider fatigue may not deprive
alter brain development and subsequent behavior? Neonato-
preterm neonates of the beneficial effects of KMC. A logy. 2000;77:69-82.
recently published i-KMC trial showed that low birth 3. Brew N, Walker D, Wong FY. Cerebral vascular regulation
weight babies who were provided continuous KMC and brain injury in preterm infants. Am J Physiol Regul
initiated immediately after birth experience a reduced risk Integr Comp Physiol. 2014;306:R773-86.
of mortality compared with a similar group in whom KMC is 4. Rhee CJ, Rios DR, Kaiser JR, Brady K. Cerebral hemo-
initiated only after clinical stabilization [27]. dynamics in premature infants. Neonatal Med. 2018;25:1-6.
5. Volpe JJ. Brain injury in the premature infant–from
The pre-requisite of enrolling only hemodynamically pathogenesis to prevention. Brain Dev. 1997;19:519-34.
stable newborns in this study limited the application of 6. Lien R. Neurocritical care of premature infants. Biomed J.
KMC to other newborns. The sample size was also small 2020;43:259-67.
across gestations, and we do not have data on the long- 7. Sharma D, Farahbakhsh N, Sharma S, et al. Role of kangaroo
term neurodevelopmental follow up. mother care in growth and breastfeeding rates in very low
birth weight (VLBW) neonates: A systematic review. J
The current study showed a positive impact of KMC Matern Fetal Neonatal Med. 2019;32:129-42.
on cerebral hemodynamic response by improving cerebral 8. Conde-Agudelo A, Díaz-Rossello JL. Kangaroo mother care
blood flow in hemodynamically stable preterm neonates. It to reduce morbidity and mortality in low birthweight infants.
Cochrane Database Syst Rev. 2016;2016: CD002771.
also shows it stabilized cardiorespiratory para-meters and
9. Feldman R, Eidelman AI. Skin to skin contact (kangaroo care)
thus positively influences the physiological stability of accelerates autonomic and neurobehavioural maturation in
preterm neonates. Further research could compare preterm infants. Dev Med Child Neurol. 2003; 45:274-81.
cerebral blood flow Doppler parameters between babies 10. Bera A, Ghosh J, Singh AK, et al. Effect of kangaroo mother
who were initiated on KMC after birth and those in whom care on vital physiological parameters of the low birth
KMC is initiated after clinical stabilization. weight newborn. Indian J Community Med. 2014;39:245-9.
11. Charpak N, Tessier R, Ruiz JG, et al. Twenty-year follow-
Ethics clearance: IEC, HM Patel Centre for Medical Care and up of kangaroo mother care versus traditional care.
Education; No. IEC/HMPCMCE/123/Faculty/2/246120, dated Pediatrics. 2017;139:e20162063.
Oct 22, 2020. 12. Kalyani R, Patil CB. Utility of cranial color Doppler
Contributors: AC: conceptualized and designed the study, sonography in preterm and term neonates. Int J Radiol Diagn
undertook data collection, and reviewed and revised the Imaging 2020;3:09-17.
manuscript; SN: conceptualized and designed the study, 13. Rhine WD, Blankenberg FG. Cranial ultrasonography.
coordinated and supervised the analysis, and substantially NeoReviews. 2001;2:3.
reviewed and revised the manuscript; DP: conceptualized the 14. Nimbalkar SM, Patel VK, Patel DV, et al. Effect of early
study, contributed to the data collection, and reviewed and skin-to-skin contact following normal delivery on incidence
revised the manuscript; AP: conceptualized the study, conducted of hypothermia in neonates more than 1800 g: Randomized
the analysis, and reviewed the manuscript for important control trial. J Perinatol. 2014;34:364-8.
intellectual content. All authors approved the final manuscript as 15. Nimbalkar SM, Chaudhary NS, Gadhavi KV, Phatak A.
submitted and agree to be accountable for all aspects of the work. Kangaroo mother care in reducing pain in preterm neonates
Funding: None; Competing interests: None stated. on heel prick. Indian J Pediatr. 2013;80:6-10.
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RESEARCH PAPER
Growth and Neurodevelopmental Outcomes of Very Low Birth Weight

Infants From Southern India at Corrected Age of One Year
SUSHIL GUPTA, ADHISIVAM B, VISHNU BHAT B, NIVEDITA MONDAL
From Department of Neonatology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry.
Correspondence to: Objective: To assess the growth and neurodevelopmental outcome of very low birth
Dr Adhisivam B, Professor, weight (VLBW) infants at corrected age of one year. Methods: This prospective cohort
Department of Neonatology, JIPMER, study enrolled VLBW infants delivered in a tertiary care hospital, and followed up till one-
Puducherry 605 006. year corrected age. The WHO Anthropo version 3.2.2 software was used to calculate
weight for age, length for age, and head circumference z-score during follow up. Neuro-
adhisivam1975@yahoo.co.uk
developmental assessment was done using Developmental Assessment Scale for Indian
Received: January 07, 2022; Infants (DASII) at the age of one year. Results: The mean (SD) z-scores at one-year for
Initial review: April 08, 2022; weight for age, length for age and head circumference were -2.1 (1.1), -1.4 (1.03) and -2.2
Accepted: September 17, 2022. (1.2), respectively. The mean (SD) DASII motor and mental scores were 90.8 (13.4) and 96.5
(13.2), respectively. Major and minor developmental abnormalities were noted in 9.4% and
18.2%, infants, respectively. Cerebral palsy was noted in 5.8% infants. Conclusion:
VLBW infants showed impaired growth and significant developmental abnormalities at the
corrected age of one year.
Keywords: Cerebral palsy, Development quotient, High risk follow up.
Published online: Nov 19, 2022; PII: S097475591600468
V
LBW neonates contribute to 1.4- 2.1% of Relevant antepartum and intrapartum details including
total live births [1,2]. With an increase in the mother’s age, parity, associated medical or pregnancy
incidence of prematurity and better neonatal related complications, ultrasound findings, antenatal
care, the number of very low birth weight steroid use, fetal distress, and mode of delivery were
(VLBW) survivors is increasing, who are prone to short recorded from maternal case records on a pre-structured
term adverse outcomes and long-term neurodevelop- form. Gestational age was determined by first trimester
mental problems [3]. In the earlier Pune study [4], preterm scan findings or new Ballad score. In case of discrepancy
small for gestational age infants and VLBW infants had the between these two methods, first trimester scan findings
poorest cognition at the age of 12 years. There is paucity of were preferred. Neonatal data including gender, birth
literature from southern India related to long-term out- weight, resuscitation details and Apgar scores were
comes of VLBW infants. This study was done to assess recorded. Co-morbidities observed during the NICU stay
the growth and neurodevelopmental outcomes of VLBW were also recorded. Enrolled infants were assessed within
infants at corrected age (CA) of one-year. 24 hours of birth, at discharge, 40 weeks of CA, and
subsequently at CA of 3, 6, 9 and 12 months with time
METHODS
tolerance limit of ± 7 days on the day of assessment at high
This prospective cohort study was conducted at a tertiary risk follow up clinic.
care teaching hospital in southern India from January, 2017
Invited Commentary: Pages 15-16.
to December, 2018 after approval from institutional ethics
committee. All VLBW inborn neonates delivered in the At each visit to the clinic, the infant was evaluated for
hospital during the study period were enrolled after obtain- anthropometric measurements, clinical assessment of
ing informed consent from the parents. Neonates with one vision and hearing, neurological examination and develop-
or more of the following were excluded: i) birth weight <500 mental assessment. Vision was assessed by the ability to
g and/or gestational age (GA) less than 25 weeks; ii) fix and follow a target and hearing was checked using a
presence of lethal congenital malformations, and iii) death bell. Screening for retinopathy of prematurity (ROP) was
within 6 hours of life. All neonates were managed as per done first at 3 weeks of CA in eligible neonates and was
standard neonatal intensive care unit (NICU) protocols. classified according to the International Classification of

34 HIGH RISK FOLLOW UP OF VLBW INFANTS
Retinopathy of Prematurity (ICROP) [5]. Hearing screening hearing impairment. The motor ability of infants with
was done by oto-acoustic emission (OAE) (Interacoustics cerebral palsy was graded using the Gross Motor Function
Titan TEOAE 440) at 34 weeks of gestation or prior to Classification System (GMFCS). A GMFCS level ≥II was
discharge, whichever was later. Infants who failed on OAE considered as functionally impaired. Visual impairment
were further assessed by brain evoked response auditory was defined as blindness with no functional vision in at
(BERA) in the Ear Nose and Throat (ENT) department of the least one eye [8]. Hearing impairment was defined as the
Institute. Cranial ultrasonography was done as per the unit need for sound amplification. Hearing loss was defined as
protocol. hearing loss greater than 30 dB in the better hearing ear [9].
Minor neurodevelopmental abnormality was defined as
Weight, length and head circumference were measured
the presence of any morbidity less than that classified as
using infant weighing scale, infantometer and non-
major neurodevelopmental abnormality. Intraventricular
stretchable tape, respectively. All equipment were
hemorrhage (IVH) was detected by ultrasonography, and
calibrated and standard precautions were taken during
graded according to Papile classification.
measurements by the first author. Growth was assessed by
measuring weight for age, length for age and head Statistical analysis: Comparisons were made using
circumference for age. Growth was plotted on Fenton independent t test, paired t test and repeated measure
charts for boys and girls till 40 weeks of CA, after which ANOVA, and chi-square test as applicable. Statistical
WHO child growth standards were used till one-year CA. analysis was done using Stata version 14. A value of
Growth parameters were entered in WHO Anthropo P<0.05 was considered statistically significant.
version 3.2.2 to calculate the z-score. A single trained
RESULTS
researcher carried out all the neurological and
anthropometric evaluations. A total of 260 VLBW infants were screened for eligibility at
the time of birth and 170 infants were included in the final
The neurodevelopmental assessment was done at
analysis (Fig.1). The baseline characteristics and morbi-
one-year CA using Developmental Assessment Scale for
dity profile of the VLBW cohort is described in Table I. The
Indian Infants (DASII), which is an Indian adaptation of
mean (SD) motor and mental scores of the babies were 90.8
Bayley scales of infant development (BSID) [6]. Develop-
(13.4) and 96.5 (13.2), respectively. A DASII score below
ment score less than 70 was considered as severe delay
70% (borderline intellectual functioning) was seen in 13
[7]. Major neurodevelopmental abnormality was defined if
(7.6%) and 10 (5.8%) babies for the motor and mental
at least one of the following was present i) Cerebral palsy,
domain, respectively. The serial anthropometric para-
ii) development quotient less than 70% in DASII (either
meters and neurodevelopmental parameters at one-year
mental or motor assessment), iii) vision impairment, or iv)
CA are shown in Table II.
Major and minor developmental abnormalities were
Very low birth weight infants screened (n=260)
found in 16 (9.4%) and 31(18.2%) infants, respectively. Ten
(5.8%) infants developed cerebral palsy at follow up. One
Excluded
infant was diagnosed to have moderate to severe hearing
Lethal congenital malformation (n=10)
Gestation < 25 wk (n=3) impairment. No infant was noted to have vision loss.
Birth weight < 500 g (n=4)
Death within 6 h of life (n= 4) Table I Baseline Characteristics of Very Low Birth Weight
Infants Enrolled in the Study (N=170)
Enrolled (n=239) Variables Value

Birthweight (g) a 1253 (170)
Survivors Non survivors Gestational age (wk)a 32.1 (2)
(n=190) (n=49) Small for gestational age 107 (62.5)
Male gender 83 (48.8)
Died before 1 year corrected age (n=6) Sepsis 52 (30.5)
Lost to follow up (n=14)
Intraventricular hemorrhage 18 (10.5)
Bronchopulmonary dysplasia 8 (4.7)
Growth and neurodevelopment assessment Hemodynamically significant PDA 24 (14.1)
at 12 months corrected age (n=170)
Retinopathy of prematurity 7 (4.1)
Fig. 1 Flow of participants in the study. Data expressed as no.(%) or amean (SD). PDA-patent ductus arteriosus.

GUPTA, ET AL. 35

• Very low birth weight infants have impaired growth and significant developmental abnormalities, at one-year
corrected age.
Table II Anthropometric Parameters at Different Time- Indian study [12], except that the improvement in z- scores
points in Very Low Birth Weight Infants (N=170) for weight and length were noted after three months in our
Timing of assessment WFA LFA HCFA cohort. Although, our study had a larger sample size
z-score z-score z-score compared to the earlier Indian studies [6,7,12,13], the
results are similar.
Birth -1.6 (1.3) -1.2 (1.6) -1.5 (1.3)
At dischargea -2.7 (1.1) -1.8 (1.3) -1.7 (1.0) According to the Neuroprem 2 study [15], among 502
Chronological age VLBW survivors who completed 24-month follow up,
3 mo -2.9 (1.3) -2.3 (1.3) -2.3 (1.3) severe functional disability, and cerebral palsy were seen in
6 mo -2.4 (1.08) -1.6 (1.2) -2.5 (1.1) 9.6% and 5.4%, respectively. The rates of severe functional
9 mo -2.2 (1.09) -1.3 (1.0) -2.5 (1.1) disability and cerebral palsy were higher in neonates with a
12 mo -2.1 (1.1) -1.4 (1.03) -2.2 (1.2) lower gestational age. In our study, the proportion of
Data expressed as mean (SD). ameasurements at discharge from developmental abnormalities and cerebral palsy were
neonatal intensive care unit. WFA-weight for age; LFA-length for similar. On comparing our data with the Western data,
age; HCFA-head circumference for age. ethnicity and development assessment tools used may
have affected the outcome assessment. Extra-uterine
DISCUSSION nutrition and comorbidities at birth could have influenced
both growth and development of the cohort studied.
The present study reported growth and neurodevelop-
mental outcomes of VLBW infant at one-year CA. The To conclude, at one-year CA, VLBW infants showed
anthropometry showed growth impairment and a signifi- impaired growth and significant developmental abnor-
cant proportion of infants had neurodevelopmental malities in this study. Appropriate nutritional and follow-
abnormality. up strategies should be implemented so that these vulner-
able infants achieve optimum growth and development.
The high rates of neurological and developmental
problems reported among VLBW infants are of concern. Ethics clearance: IEC (Human studies), JIPMER, Puducherry;
Birth weight, gestational age, sex, multiple births, antenatal No. JIP/IEC/2016/1145, dated Feb 16, 2017.
Contributors: SG: collected and analyzed data and drafted
corticosteroid administration, neonatal infection, necro-
manuscript; AB: designed the study, reviewed data analysis and
tizing enterocolitis, periventricular leukomalacia and IVH edited the manuscript; VB, NM: supervized clinical work and
are some of the risk factors that influence both short- and provided critical inputs. All authors have seen and approved the
long-term outcomes [11]. Local NICU data on expected submission of this manuscript and take full responsibility for the
mortality and adverse long-term outcomes may be useful manuscript.
to counsel parents of VLBW neonates. The birth weight Funding: Nil; Competing interests: None stated.
and gestation of our cohort was comparable to other
REFERENCES
Indian studies [12,13]. VLBW mortality rate was 20% in the
population studied. A birth weight <1000 g, severe grade of 1. Kabilan S, Kumar MS. Morbidity and mortality pattern of
IVH, hyperglycemia, and respiratory distress syndrome very low birth weight infants admitted in SNCU in a South
requiring surfactant therapy were the significant pre- Asian tertiary care centre. Int J Contemp Pediatr. 2018; 5:
720-5.
dictors of mortality among VLBW neonates [14].
2. Mooorthi MMS, Nadesan B, Ramalingam E, et al. A study
The mean z-scores at one-year CA were below the of maternal factors influencing very low birth weight babies.
corresponding z-scores at birth. The mean z-scores of Int J Contemp Pediatr. 2017; 4:1173-8.
weight and length were below and farthest from the 3. Longo S, Caporali C, Pisoni C, et al. Neurodevelopmental
outcome of preterm very low birth weight infants admitted
population median at 3 months CA, and subsequently
to an Italian tertiary center over an 11-year period. Sci Rep.
improved. However, head circumference z-scores 2021; 11:16316.
improved only after 9 months CA. This may suggest that 4. Chaudhari S, Otiv M, Chitale A, et al. Pune low birth weight
somatic growth in VLBW infants recovers earlier than the study -cognitive abilities and educational performance at
neural growth. These findings are similar to an earlier twelve years. Indian Pediatr. 2004;41:121-8

36 HIGH RISK FOLLOW UP OF VLBW INFANTS
5. International Committee for the Classification of Retino- developmental and growth impairment among extremely
pathy of Prematurity. The International Classification of low-birth-weight infants with neonatal infection. JAMA.
Retinopathy of Prematurity revisited. Arch Ophthalmol. 2004;292:2357-65.
2005;123:991-9. 11. Larroque B, Ancel PY, Marret S, et al. Neurodevelopmental
6. Mukhopadhyay K, Malhi P, Mahajan R, et al. Neuro- disabilities and special care of 5-year old children born before
developmental and behavioral outcome of very low birth 33 weeks of gestation (the EPIPAGE study): A longitudinal
weight babies at corrected age of 2 years. Indian J Pediatr. cohort study. Lancet. 2008;371:813-20.
2010;77:963-7. 12. Modi M, Saluja S, Kler N, et al. Growth and neuro-
7. Dwivedi D, Singh S, Singh J, et al. Neurodevelopmental developmental outcome of VLBW infants at 1 year corrected
status of children aged 6-30 months with severe acute age. Indian Pediatr. 2013;50:573-7.
malnutrition. Indian Pediatr. 2018;55:131-3. 13. Radhika S, Sobhakumar S, Soumya S, et al. Growth and
8. Kono Y; Neonatal Research Network of Japan. Neuro- neurodevelopmental outcome of very low birth weight
developmental outcomes of very low birth weight infants in babies at 1 year of age. J Med Sci Clin Res. 2017;5: 23836-
the Neonatal Research Network of Japan: Importance of 23840
neonatal intensive care unit graduate follow-up. Clin Exp 14. Gupta S, Adhisivam B, Bhat BV, et al. Short term outcome
Pediatr. 2021 ;64:313-21. and predictors of mortality among very low birth weight
9. Parab SR, Khan MM, Kulkarni S, et al. Neonatal screening infants - A descriptive study. Indian J Pediatr. 2021;88:351-7.
for prevalence of hearing impairment in rural areas. Indian J 15. Lugli L, Bedetti L, Guidotti I, et al. Neuroprem 2: An Italian
Otolaryngol Head Neck Surg. 2018 ;70:380-86. study of neurodevelopmental outcomes of very low birth
10. Stoll BJ, Hansen NI, Adams-Chapman I, et al. Neuro- weight infants. Front Pediatr. 2021;9:697100.
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RESEARCH PAPER
LATCH Score for Identification and Correction of Breastfeeding Problems

- A Prospective Observational Study
SNEHA MARIYA RAPHEAL,1 BALAKRISHNAN RAJAIAH,1 RAJENDRAN KARUPANAN,2 THANGARAJ ABIRAMALATHA,2
SRINIVAS RAMAKRISHNAN1
1Neonatal Intensive Care Unit, Kovai Medical Center and Hospital (KMCH), Coimbatore, Tamil Nadu.
2Department of Pediatrics and Neonatology, KMCH Institute of Health Sciences and Research, Coimbatore, Tamil Nadu.
Correspondence to: Objective: To determine early breastfeeding problems using LATCH tool, and analyze the
Dr Balakrishnan Rajaiah, impact of breastfeeding supportive measures in improving LATCH score. Methods: This
Consultant, Neonatal Intensive Care prospective study included all inborn term neonates born at our center between September,
Unit, Kovai Medical Center and 2019 and March, 2020. Breastfeeding problems were identified by LATCH score at 6-12h
after birth, and were addressed by the study team providing breastfeeding support,
Hospital (KMCH),
education and training to mothers. LATCH scores were reassessed at 24-48h. Results:
Coimbatore 641 014, Tamil Nadu. Among 400 mother-infant dyads, 399 (99.7%) required support to position the neonate, 190
drbalakrishnan1@yahoo.co.in. (47.5%) had poor latch and 52 (13%) had nipple problems during initial assessment.
Received: April 29, 2022; Breastfeeding supportive measures improved the LATCH score [median (IQR) 7 (5,8) vs 8
Initial review: June 23, 2022; (8,8) at 6-12 and 24-48 hours, respectively; P <0.001], and reduced the number of mothers
Accepted: Sept 19, 2022. with LATCH score <8 [288 (72%) vs 63 (15.8%); P <0.001]. Conclusion: LATCH is a
comprehensive yet simple tool to identify breastfeeding problems. Given the high incidence
of breastfeeding problems during early postpartum period, systematic assessment of
breastfeeding related problems using LATCH tool can help timely intervention and
improvement in the breastfeeding technique.
Key words: Breastfeeding support, Counselling, Latching, Neonatal feeding.
Published online: Sep 22, 2022; PII: S097475591600455
B
reastfeeding is considered an important inter- using LATCH tool [6], and to analyze the impact of
vention to reduce infant and under-5 mortality breastfeeding support in improving the LATCH score.
[1,2]. Though breastfeeding is a natural
process, some mother-infant dyads may have METHODS
problems in breastfeeding, particularly during the initial This prospective observational study was conducted in a
days after childbirth [3,4]. Improper breastfeeding tech- tertiary care neonatal centre from September, 2019 to
nique may result in inadequate feeds leading to excessive March, 2020, including all inborn term neonates. The
weight loss, hypernatremic dehydration, jaundice and re- exclusion criteria were neonates who required neonatal
hospitalization. Evidence suggests that early initiation of intensive care unit (NICU) admission, multiple births and
breastfeeding and exclusive breastfeeding at hospital sick mothers where LATCH score could not be assessed
discharge are associated with improved rates of exclusive within stipulated time. The study was approved by the
breastfeeding until six months and increased duration of Institutional Ethics Committee. Informed written consent
breastfeeding [5]. was obtained from the mother prior to recruitment.
As we ardently promote institutional deliveries, the
LATCH is an acronym that stands for latch, audible
initial hospitalization period is a good opportunity for
swallowing, type of nipple, comfort and hold [6]. Each
health care workers to assess breastfeeding, educate
component is scored from 0-2 and the total score ranges
mothers on correct breastfeeding techniques, and boost
from 0-10. A total score less than 8 is considered low/
their confidence in breastfeeding before discharge from
unsatisfactory.
hospital. There is a need for a systematic way to evaluate
the breastfeeding technique, identify problems related to LATCH score was assessed at 6-12 hour after birth.
breastfeeding and take appropriate corrective actions in a The scoring was performed by a group of eight senior
timely manner. In this study, we aimed to determine the nurses (two in each postnatal ward), who had been trained
incidence and nature of early breastfeeding problems in LATCH score assessment and breastfeeding support,

38 LATCH SCORE IN BREASTFEEDING
before commencing the study. The training was provided in Table I Scores of Individual Components of LATCH scoring
multiple sessions using images and videos, and by hands- System at 6-12 Hour and 24-48 Hour After Delivery (N=400
on training under direct observation by the study investi- Mother-Infant Dyads)
gators. Depending on the problem in breastfeeding that Component Score
was identified during the initial assessment, counselling, 6-12 h 24-48 h P value
education and support were provided to the mothers by
the study team. Mothers were trained in cradle or cross- Latch 2 (1, 2) 2 (2, 2) < 0.001
cradle hold of the baby while breastfeeding. Mothers who Audible swallowing 1 (0, 1) 1 (1, 2) < 0.001
had undergone caesarean delivery were taught breast- Type of nipple 2 (2, 2) 2 (2, 2) < 0.001
feeding in side-lying position. Signs of good attachment Comfort 2 (2, 2) 2 (2, 2) 0.121
were explained to the mothers using visual aids. Mothers Hold 1 (0, 1) 1 (1, 1) < 0.001
were encouraged to evaluate and correct the positioning
Scores in median (IQR).
and attachment of the baby by themselves during
subsequent feeding sessions, which was supervised by
the study team. Tactile stimulation and/or nipple pullers to 63 (15.8%) at 24-48 hour after the breastfeeding support
were prescribed to mothers with flat or inverted nipples. and training (P< 0.001). The median (IQR) LATCH scores
Following the interventions, LATCH scores were reasses- also improved significantly [7 (5,8) vs 8 (8,8); P<0.001].
sed at 24-48 hour from the time of delivery. For most
mother-infant dyads, both the initial assessment and post- The scores of individual components are given in
inter-vention assessment were performed by the same Table I. The ‘latch’ component improved significantly with
nurse. 95.5% mother-infant pairs having a score of 2 at 24-48 hour.
Though there was improvement in ‘audible swallowing’
Demographic and clinical details of the mother and the and ‘hold’ components, the proportion of mother-infant
baby were collected in a pretested study form. Sample size pairs achieving a score of 2 was less even after the training.
obtained was 400 mother-infant pairs, assuming a 50% Most of the mothers had a score of 2 for ‘comfort during
incidence of breastfeeding problems in term neonates, breastfeeding.’ Number of mothers who have a flat or an
taking precision of 5%. inverted nipple decreased from 13% to 2.7% after the
intervention.
Statistical analysis: Descriptive statistics are presented as
median and interquartile range (IQR) or number and
Table II Comparison of Low Scores (<8) Between Different
percentage, as appropriate. Chi-square test was used to
Sub-groups of Mother-Infant Dyads
compare categorical data between independent samples,
McNemar test for categorical data between paired Mother-infant groups (n) LATCH score < 8
samples, and Wilcoxon signed rank test for ordinal data At 6-12 h At 24-48 h
between paired samples. All statistical analyses were (n=288) (n=63)
performed using SPSS 20.0. A P value <0.05 was Birthweight
considered statistically significant. < 2500 g (n=19) 14 (73.7) 4 (21.1)
> 2500 g (n=381) 274 (71.9) 59 (21.5)
RESULTS
Delivery
Among the 400 study neonates, 217 (54.2%) were boys Cesarean (n=252) 223 (88.5)a 51 (20.2)c
and 19 (4.8%) had a birth weight <2500 g. Nearly half of the Vaginal (n=148) 65 (43.9) 12 (8.1)
mothers (197, 49.2%) were primiparous, and 252 (63%) had Parity
delivery by cesarean section. Maternal age was <20, 20-30 Primipara (n=197) 161 (81.7)a 39 (19.8)d
and > 30 years in 4 (1%), 290 (72.5%) and 106 (26.5%), Multipara (n=203) 127 (62.6) 24 (11.8)
respectively. Of these, 29 (7.2%) mothers had high-school Maternal age
education, 342 (85.6%) were graduates and 29 (7.2%) were >30 y (n=106) 78 (73.6) 19 (17.9)
professionals. 20-30 y (n=290) 206 (71) 42 ((14.5)
<20 y (n=4) 4 (100) 2 (50)
During the initial assessment at 6-12 hour, 399 (99.7%) Mother’s education
mothers required support to position the neonate, 190 High school (n=29) 23 (79.3)b 9 (31.0)d
(47.5%) mother-infant dyads had a poor latch with a score Graduate (n=342) 239 (69.9) 46 (13.5)
of 0 or 1, and 52 (13%) mothers had a flat or inverted nipple. Professional (n=29) 26 (89.6) 8 (27.6)
While 288 (72%) mother-infant dyads had a LATCH score Values in no. (%). At 6-12 h, aP<0.001; bP<0.05; At 24-48 h,
of < 8 at 6-12 hour after delivery, this reduced significantly cP<0.001; dP<0.05.

RAPHEAL, ET AL. 39

• Timely intervention, following early identification of breastfeeding related problems using the LATCH tool, help
in significant reduction of such problems.
Analysis of the association between demographic Better LATCH scores in the early postnatal period
characteristics and LATCH scores showed that caesarean were shown to correlate positively with exclusive breast-
delivery, primiparity and mother’s education were risk feeding rates at discharge and at 6-8 weeks of life [8-10].
factors for a lower LATCH score at 6-12 hours (Table II). Hence, we are of the view that systematic assessment of
Though, the scores improved significantly after breast- breastfeeding using the LATCH tool and timely initiation
feeding support in all these subgroups, they had of appropriate measures to address the problems that are
persistently lower scores at 24-48 hours when compared to identified will help to improve exclusive breastfeeding
their fellow groups. rates at and after hospital discharge.
DISCUSSION The study has some limitations. We did not follow the
Our study showed that almost all the mothers required mother-infant pairs beyond 48 hours. Hence, several
assistance in positioning the neonate during breast- problems related to breastfeeding that appear later were
feeding and almost half of mother-infant dyads had not assessed. We did not include neonates who required
problems related to latching, with 13% mothers having NICU admission and late preterm neonates, who may be at
nipple issues soon after delivery. We found a significant greater risk of improper breastfeeding. We did not assess
reduction in breastfeeding problems with timely support, inter-observer agreement in assessment of the LATCH
training and counselling of mothers. score among the study nurses. Finally, other factors could
also have contributed to the improvement in the LATCH
LATCH score provides a systematic method to score. Nevertheless, identifying the nature of breast-
evaluate five key components of the breastfeeding feeding problem in each mother-infant dyad and address-
technique [6]. It helps to identify the nature of the problem, ing the problem through breastfeeding counselling,
so that appropriate corrective measures can be taken by education and support was undeniably a major factor
counselling and training the mothers with simple visual contributing to the improvement in the scores.
aids. Improper latching and positioning of the neonate
during breastfeeding may result in the baby sucking only To conclude, the incidence of problems related to
on the nipple, which in turn will lead to inadequate feeds to breastfeeding is high during the initial days after child
the neonate and sore/cracked nipples and breast birth. LATCH is a comprehensive, yet simple and easy to
engorgement in the mother. We found a significant use tool to identify these problems and guide us to initiate
improvement in nipple problems such as flat or inverted appropriate intervention. Breastfeeding support, counsel-
nipples by 24 hours after delivery with simple ling and education during the postpartum hospital stay
interventions such as tactile stimulation or nipple puller. significantly reduce problems in breastfeeding.
The ‘comfort’ component had good scores at both 6-12 Ethics clearance: Name of IEC: KMCH Ethics Committee; No.
and 24-48 hours post-delivery, probably because problems EC/AP/762/08/2019, dated August 24, 2019.
causing discomfort while breastfeeding, such as breast Contributors: SMR, BR: Concept, design, data collection, data
engorgement or sore/cracked nipples usually develop analysis, manuscript writing; RJ, TA, SR: Concept, design, data
analysis and manuscript review. All authors approved the final
later during the postpartum period. ‘Audible swallowing’
manuscript and agree to be accountable for all aspects of the
component scored low at both assessments and this is research.
probably due to the less quantity of milk secreted by Funding: None; Competing interests: None stated.
mothers on day 1 and 2 after delivery. The frequency of
audible swallowing improves after the secondary REFERENCES
lactogenesis, when mother starts secreting more milk [6]. 1. Sankar MJ, Sinha B, Chowdhury R, et al. Optimal
Primipara mothers who have no previous experience breastfeeding practices and infant and child mortality: a
systematic review and meta-analysis. Acta Paediatr. 2015;
with breastfeeding and mothers who have a caesarean
104:3-13.
delivery and hence have pain and cannot sit up are more 2. Azuine RE, Murray J, Alsafi N, Singh GK. Exclusive breast-
likely to have problems in breastfeeding, as shown by our feeding and under-five mortality, 2006-2014: A cross-
study and previous studies [6,7]. These subgroups of mothers national analysis of 57 low- and-middle income countries. Int
would require more support to establish breastfeeding. J MCH AIDS. 2015;4:13-21.

40 LATCH SCORE IN BREASTFEEDING
3. Feenstra MM, Jørgine Kirkeby M, Thygesen M, et al. Early 225:353-60.

breastfeeding problems: A mixed method study of mothers’ 7. Hobbs AJ, Mannion CA, McDonald SW, et al. The impact
experiences. Sex Reprod Healthc. 2018;16:167-74. of caesarean section on breastfeeding initiation, duration and
4. Suresh S, Sharma KK, Saksena M, et al. Predictors of difficulties in the first four months postpartum. BMC
breastfeeding problems in the first postnatal week and its Pregnancy Childbirth. 2016;16:90.
effect on exclusive breastfeeding rate at six months: 8. Sowjanya SVNS, Venugopalan L. LATCH Score as a pre-
Experience in a tertiary care centre in Northern India. Indian J dictor of exclusive breastfeeding at 6 weeks postpartum: A
Public Health. 2014;58:270-3. prospective cohort study. Breastfeed Med. 2018;13:444-9.
5. van Dellen SA, Wisse B, Mobach MP, Dijkstra A. The effect 9. Tornese G, Ronfani L, Pavan C, et al. Does the LATCH
of a breastfeeding support programme on breastfeeding score assessed in the first 24 hours after delivery predict
duration and exclusivity: a quasi-experiment. BMC Public non-exclusive breastfeeding at hospital discharge? Breastfeed
Health. 2019;19:993. Med. 2012;7:423-30.
6. Fadiloglu E, Karatas E, Tez R, et al. Assessment of factors 10. Riordan J, Bibb D, Miller M, Rawlins T. Predicting breast-
affecting breastfeeding performance and latch score: A feeding duration using the LATCH breastfeeding assessment
prospective cohort study. Z Geburtshilfe Neonatol. 2021; tool. J Hum Lact. 2001;17:20-3.

RESEARCH PAPER
Six-Year Surveillance of Acquired Bloodstream Infection in a Pediatric

Intensive Care Unit in Israel
HALIMA DABAJA-YOUNIS,1,2,4 MAHA ALAIYAN,4 RANAA DAMOUNI SHALABI,1 JOSEF BEN-ARI,3,4 TAMAR ALON,1,2 AMIR
HADASH,3,4 YAEL SHACHOR-MEYOUHAS,1,4 IMAD KASSIS,*1,4 KHETAM HUSSEIN*2,4
1Pediatric Infectious Diseases Unit, 2Infection Prevention and Control Unit, and 3Pediatric Intensive Care Unit,
Rambam Health Care Campus, Haifa, Israel.

4The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
*These authors contributed equally to the article.
Correspondence to: Objectives: We studied the profile of bloodstream infections (BSI) in the pediatric intensive
Dr. Halima Dabaja-Younis, care unit (PICU) and identified predictors of mortality. Methods: The study collected data
Pediatric Infectious Disease Unit, from hospital records for children younger than 18-years who developed BSI during their
Rambam Health Care Campus, PICU stay between 2014 and 2019. Results: In 114 patients, 136 PICU-acquired BSIs with
152 pathogens were documented. The incidence of BSI was 47.12/1000 PICU admissions
Haifa 31096, Israel.
and 7.95/1000 PICU hospital days. Gram-negative rods accounted for 75% of isolates,
h_dabaja@rambam.health.gov.il Gram-positive cocci accounted for 21.7% of isolates, and fungi accounted for 3.3% of
Received: June 06, 2022; isolated pathogens. ICU mortality was observed in 25 (21.9%) patients with a BSI compared
Initial review: June 27, 2022; to 94 (3.1%) patients without a BSI (P<0.001). Hemodynamic instability (P=0.014, OR 4.10,
Accepted: September 19, 2022 95%CI 1.33-12.66), higher blood urea nitrogen (BUN) (P=0.044), and lower albumin levels
(P=0.029) were associated with increased risk of ICU mortality. Conclusion: BSI in the
PICU is associated with increased mortality. Early identification and management of risk
factors independently associated with poor clinical outcomes in these patients should be
aimed to ensure improved survival.
Keywords: Hypoalbuminemia, Klebsiella spp, Mortality, Nosocomial infection.
B
loodstream infections (BSI) acquired in the PICU admissions, and facilities for respiratory and hemo-
pediatric intensive care unit (PICU) are the dynamic support, including extracorporeal membrane
leading cause of hospital morbidity and oxygenation. Cases were identified from monthly reports
mortality [1]. Mortality rates attributable to BSI of positive blood cultures. Clinical and laboratory data of
range from 11% to 81.8% [1-3]. A few studies have patients with positive blood cultures were obtained from
addressed the epidemiology of BSI in pediatric patients the case sheets. The study was approved by the local
admitted to PICU [1-5], but none of these studies have ethics committee.
examined the predictors of mortality. Recognition and
The Centers for Disease Control (CDC) guidelines
treatment of these predictors of mortality may lead to a
were used for classification of BSI [6]: PICU-acquired BSI:
reduction in the incidence, and consequently, the morbi-
BSI that occurred after the first 48 hours of hospital
dity and mortality of BSI.
admission, when no evidence of infection was present on
The aim of this study was to determine the admission; Primary BSI: BSI that was not due to infection
characteristics and outcome of BSI in the PICU, and to at another body site; Central line-associated BSI
identify predictors of mortality in these patients. (CLABSI): BSI in which a central venous catheter (CVC) is
present; Secondary BSI: BSI due to site-specific infection;
METHODS and, Mucosal barrier injury (MBI): BSI in neutropenic
patients or oncologic patients with diarrhea. Hemo-
We retrieved hospital records of children younger than 18 dynamic instability was defined as need for fluid resus-
years who were admitted to the PICU of Rambam Health citation and/or vasopressors, and respiratory deterio-
Care Campus between January, 2014 and December, 2019, ration was defined as worsening respiratory status. PICU
and had acquired BSI. This is a tertiary, university-affliated associated mortality was defined as mortality occurring
hospital with a 15-bed PICU with an average of 520 annual during the stay in PICU.

42 ACQUIRED BACTEREMIA IN PEDIATRIC INTENSIVE CARE UNIT
Coagulase-negative staphylococci (CoNS) and other Table I Characteristics of Children With Bloodstream
commensal bacteria were considered true pathogens only Infection in the Pediatric Intensive Care Unit (N=114)
if patients had at least two positive cultures or, Characteristic Number (%)
alternatively, clinical signs of sepsis and had received
targeted antibiotic treatment [6]. Age
0-28 d 22 (19.3)
Statistical analysis: Data were analyzed using SPSS 29 d - 1 y 36 (31.6)
software (version 26). Univariate analyses were performed 1-5 y 19 (16.7)
using chi square test for categorical variables and >5 y 37 (32.5)
independent t test for continuous variables. All tests were Jewish ethnicity 35 (30.7)
two-tailed, and P<0.05 was considered statistically signi- Diagnosis on admission
ficant. A binomial regression model was fitted for potential Medical 73 (64)
predictors of mortality during PICU stay. In this model, Surgical 25 (21.9)
only the last sepsis episode of each patient was Trauma/burns 15 (13.2)
considered. Variables were included if the P value in the Underlying condition
univariate analysis was <0.1; variables with P<0.05 were No underlying condition 25 (21.9)
retained. Cardiac 33 (28.9)
RESULTS Genetic/metabolic 15 (13.2)
Neurologic 11 (9.6)
Over the six-year study period, 114 patients [61 males; Oncologic/immune deficiency 11 (9.6)
median (IQR) age, 0.92 (0.12,11.53) years] were diagnosed Renal 6 (5.3)
with 136 episodes of BSI, with isolation of 152 pathogens Gastrointestinal 6 (5.3)
(Web Fig. 1). The BSI incidence rate in the PICU was 47.12 Prematurity 4 (3.5)
per thousand PICU admissions, and 7.95 per thousand Pulmonary 3 (2.6)
PICU hospitalization days (Fig. 1). Carriage of multidrug resistant organisms at time of BSIa
Extended spectrum beta-lactamases 45 (39.5)
About half of the patients with BSI were younger than
1 year, compared with 29.1% of all patients admitted to the Enterobacteriaceae
PICU during the study period (P<0.001). A CVC was Methicillin-resistant Staphylococcus aureus 8 (7)
documented in 99 (72.8%) cases, and 60 (60.6%) episodes Vancomycin resistant Enterococcus 3 (2.6)
of these were defined as CLABSI. Mean (SD) time from Clinical presentation
CVC insertion to BSI in patients with CLABSI was 14.45 Fever 99 (72.8)
(13.08) days (Table I). Hemodynamic instability 35 (25.7)
Respiratory deterioration 53 (39)
A total of 152 isolates were identified from blood Acute renal failure 20 (14.7)
cultures. Most, 114 (75%), were Gram-negative rods (GNR).
CVC type (>2 d)
No CVC 37 (27.2)
Subclavian 11 (8.1)
Femoral 30 (22.1)
Jugular 35 (25.7)
Multiple 23 (16.9)
Classification
CLABSI 60 (44.1)
Secondary BSI 42 (30.9)
Primary BSI 29 (21.3)
Mucosal barrier injury BSI 5 (3.7)
Secondary BSI
PVAP/PNEU 24 (57.1)
Surgical site infection 6 (14.3)
CAUTI/SUTI 8 (19)
Other sources 4 (9.6)
Values in no. (%) aOne child had carbapenem resistant Acinetobacter.
CVC-central venous catheter, CLABSI-central line associated blood stream
Fig. 1 Rates of bloodstream infections in children in a pediatric infection, BSI-bloodstream infection, PVAP/PNEU-ventilator associated
intensive care unit in Haifa, Israel (2014-2019). pneumonia, CAUTI/SUTI-catheter associated urinary tract infection.

DABAJA-YOUNIS, ET AL. 43
Table II Predictive Factors for Mortality in the Intensive Mortality occurred during stay at PICU was docu-
Care Unit (ICU) in Children With Bloodstream Infection mented in 25 (21.9%) patients with BSI compared with 94
Factors ICU survivors ICU non-sur- (3.1%) patients without BSI. Mean age, sex, and ethnicity
(n=89) vivors (n=25) were similar in survivors and non-survivors. Bacteria
group (GNR vs GPC) was not associated with higher
Age (y)a 4.82 (6.16) 5.43 (6.94)
mortality (P=0.557). Inappropriate empiric antibiotic
Male gender 50 (56.2) 11 (44) treatment administered within 2 hours of clinical or
Arab ethnicity 60 (67.4) 19 (76) laboratory evidence of bacteremia occurred in 12% of
Admission cause survivors and 11.6% of non-survivors (P=0.944) (Table II).
Medical 55 (62.5) 18 (72)
In univariate analysis, presence of serious comorbid
Surgical 20 (22.7) 5 (20.0)
Trauma/burns 13 (14.8) 2 (8.0) condition, hemodynamic instability, low albumin level and
Associated serious comorbid 65 (73.0) 23 (92.0) higher blood urea nitrogen (BUN) levels were significantly
conditionc more prevalent in non-survivors (P=0.046, 0.008, 0.035 and
Hemodynamically unstablec 19 (21.3) 12 (48.0) 0.010, respectively). These variables were included in the
Consciousness deterioration 6 (6.8) 2 (8) multivariate analysis in addition to carriage of ESBL
Acute kidney injury 12 (13.6) 6 (24) (P=0.056). In the multivariate analysis, hemodynamic
Laboratory instability resulted in a 4-fold increase in ICU mortality.
White blood count (109/L) a 14.07 (11.56) 15.96 (15.44) Each one-unit increase in BUN level was associated with a
Hemoglubin (g/dL) a 10.22 (2.69) 10.35 (2.26) 1.026-fold increase in ICU mortality, whereas each one-unit
Albumin (g/dL) a, c 2.75 (0.69) 2.43 (0.54) decrease in albumin level was associated with a 2.6-fold
CRP (mg/dL) a 0.53 (0.41) 0.74 (0.72) increase in ICU mortality (Table II). The logistic regression
Lactate (mmol/L) a 1.56 (0.64) 2.68 (1.41) model was statistically significant (P<0.001), and fitted the
Creatinine (mg/dL) a 0.53 (0.42) 0.74 (0.72) data well, as shown by Hosmer and Lemeshow test
BUN (mg/dL) a, c 17.9 (14.2) 34.87 (29.39)
(P=0.317).
Gram-positive organisms 23 (26.7) 5 (20.8)
CLABSI 38 (42.7) 12 (48.0) DISCUSSION
ICU stay before BSI (d) a 17.9 (15.42) 17.60 (17.26)
We found a high proportion of BSI among children in PICU,
ICU stay after BSI (d) a 25.1 (28.93) 21.08 (31.40)
comparable to rates of 56 and 63/1,000 PICU admissions
Carriage of resistant bacteriab 43 (48.3) 15 (60.0)
[2,3] and to 7 and 31.2/1,000 patient days [2,5]. During the
Carriage of ESBL 31 (34.8) 14 (56.0) study period, the incidence of BSI varied between 27 and
Inappropriate empiric antibiotics 13 (12) 5 (11.6) 70.7/1,000 PICU admissions. This change in incidence may
All values in no. (%) oramean bResistant
(SD). bacteria-ESBL, CRE, be related to the changing workload and intermittent
MRSA, VRE or CRAB. CLABSI-central line-associated bloodstream reinforcement of infection prevention measures taken to
infection, ESBL-extended-spectrum beta-lactamase Enterobacteria- reduce BSI in ICUs, such as reimplementation of CVC
ceae, CRE-carbapenem resistant enterobacteriaceae, MRSA-methi-
cillin resistant staphylococcus, VRE-vancomycin resistant entero-
insertion and maintenance policies, surveillance of BSI,
coccus, CRAB-carbapenem resistant Acinetobacter baumani. cP<0.05. and debriefing of BSI events. The significant proportion of
patients younger than one year and patients with
complicated underlying diseases may explain the broad use
Klebsiella spp. were most frequently identified in 37 of invasive devices, such as a CVC in this cohort.
(24.3%) cultures. Gram-positive cocci (GPC) were detected
in 33 (21.7%) cultures. Staphylococcus aureus was most The ICU mortality rate in patients who developed BSI
frequently isolated GPC in 13 (8.6%) cultures. was consistent with that reported by Gray, et al. [7], but
significantly lower than in previous studies (40.7 -55.9%)
Fifty-eight (50.9%) patients were carriers of multi-drug [2,3]. In the current study and in another Israeli study [3],
resistant organisms (MDRO) at the time of bacteremia, ICU mortality was 7-fold higher in patients with BSI than in
detected by screening or clinical specimens. ESBL patients without BSI. This difference in ICU mortality was
producing enterobacteriaceae were isolated from blood less pronounced in other studies worldwide [5,7].
cultures of 36 (31.6%) patients and MRSA was isolated
from blood cultures of 4 (3.5%) patients. Carbapenem- Hemodynamic instability, as also noted by Pillon, et al.
resistant enterobacteriaceae (CRE) were not detected [8], increased BUN, and decreased albumin levels were
during the study period. GNR resistance to amikacin was identified as predictors of PICU-associated mortality.
detected in 6 (5.8%), to piperacillin-tazobactam in 20 Diagnostic tools based on biomarkers such as albumin
(20.6%) and to ceftazidime in 36 (40.9%) patients (Table I). and urea have been successfully used to predict mortality

44 ACQUIRED BACTEREMIA IN PEDIATRIC INTENSIVE CARE UNIT

• Profile of bloodstream infections and associated factors of mortality in the pediatric intensive care unit are
presented.
[9,10]. Critical illness often results in altered cellular reviewed the manuscript; JBA,AH, YSM,TA: helped in
energy metabolism and protein catabolism. Whether gathering the data and revising the manuscript. All authors
albumin levels or nutritional status have a direct adverse approved the final version of manuscript, and are accountable for
effect on survival or reflect severe disease and catabolic all aspects related to the study.
Funding; None; Competing interests: None stated.
state remains to be determined [11]. The predictors of ICU
Note: Additional material related to this study is available with
mortality found in this study may reflect in some way the the online version at www.indianpediatrics.net
severity of illness at the onset of bacteremia and the
compromise to vital organs. REFERENCES
Similar to previous studies [2,3,5], GNR pathogens 1. Elella R, Najm H, Balkhy H, et al. Impact of bloodstream
were responsible for the majority of BSI events [2,3,5], but infection on the outcome of children undergoing cardiac
they were not associated with greater mortality. We found surgery. Pediatr Cardiol. 2010;31:483-9.
2. Jaballah N, Bouziri A, Mnif K, et al. Epidemiology of
a much lower rate of fungemia in this study, compared to
hospital-acquired bloodstream infections in a Tunisian
7.8-15% in previous studies [3,5]. pediatric intensive care unit: A 2-year prospective study.
The main limitation of the study was its retrospective Am J Infect Control. 2007;35:613-8.
design, which may affect the quality of the data and follow- 3. Grisaru-Soen G, Sweed Y, Lerner-Geva L, et al. Nosocomial
up. However, most of the data were collected as part of a bloodstream infections in a pediatric intensive care unit: 3-
year survey. Med Sci Monit. 2007;13:CR251-7.
national monthly surveillance of BSI in intensive care
4. Singhi S, Ray P, Mathew JL, et al. Nosocomial bloodstream
units in Israel, which masks this limitation. Although, a infection in a pediatric intensive care unit. Indian J Pediatr.
single study, it was conducted in a large referral center that 2008;75:25-30.
enrolls patients with complicated conditions, which may 5. Lakshmi KS, Jayashree M, Singhi S, et al. Study of
mitigate this limitation and even overestimate the mortality nosocomial primary bloodstream infections in a pediatric
rate. Although data on comorbidities and disease severity intensive care unit. J Trop Pediatr. 2007;53:87-92.
parameters were presented in the current study, no well- 6. Garner JS, Jarvis WR, Emori TG, et al. CDC Definitions for
known disease severity scores were used to standardize Nosocomial Infections, 1988. Am J Infect Control.
severity, and no severity data were collected from patients 1988;16:128-40.
7. Gray J, Gossain S, Morris K. Three-year survey of
who were admitted to the PICU but had not developed BSI,
bacteremia and fungemia in a pediatric intensive care unit.
making it difficult to determine whether patients with BSI Pediatr Infect Dis J. 2001;20:416-21.
had higher severity compared with patients without BSI. 8. Pillon M, Sperotto F, Zattarin E, et al. Predictors of
Moreover, the fact that low albumin levels were associated mortality after admission to pediatric intensive care unit in
with mortality makes it necessary to assess overall oncohematologic patients without history of hematopoietic
nutritional status in future studies. stem cell transplantation: A single-center experience. Pediatr
Blood Cancer. 2019;66:e27892.
In conclusion, the high incidence of BSI, the high 9. Zhang Y, Shi Q, Zhong G, et al. Biomarker-based score for
mortality in patients with BSI, and the uncontrolled factors predicting in-hospital mortality of children admitted to the
predicting mortality found in this study underscore the intensive care unit. J Investig Med. 2021;69:1458-63.
need for continuous surveillance and infection prevention 10. Loke YK, Kwok CS, Niruban A, et al. Value of severity
interventions to all patients to reduce the incidence of BSI. scales in predicting mortality from community-acquired
These predictors may indicate severe disease and pneumonia: systematic review and meta-analysis. Thorax.
catabolic state, and clinicians should be aware of these 2010;65:884-90.
predictors and provide optimal supportive and nutritional 11. Protti A, Singer M. Bench-to-bedside review: potential
strategies to protect or reverse mitochondrial dysfunction in
care.
sepsis-induced organ failure. Crit Care. 2006;10:228.
Ethics clearance: Local Ethics Committee; No.0053-19-RMB, 12. Shorr AF, Zilberberg MD, Micek ST, et al. Predictors of
dated Jan 24, 2019. hospital mortality among septic ICU patients with
Contributors: HDY,IK,KH: designed the study, analyzed the Acinetobacter spp. bacteremia: A cohort study. BMC Infect
data and edited the manuscript; MA,RDS: gathered the data and Dis. 2014;14:572.

DABAJA-YOUNIS, ET AL.
(a)
(b)
Web Fig. 1. (a) The total number of patients and blood cultures identified in the study. (b) Flowchart of patients, episodes and
pathogens included in the study.

RESEARCH PAPER
Evaluation of AIIMS Modified INCLEN Tool for Diagnosis of Epilepsy

PRIYANKA GOYAL, MONIKA SHARMA, VARUGHESE PV
From Department of Pediatrics, Christian Medical College, Ludhiana, Punjab.
Correspondence to: Objectives: To evaluate the AIIMS Modified INCLEN tool for the diagnosis of epilepsy.
Dr Priyanka Goyal, Methods: This cross-sectional study enrolled 250 children aged 1 month to 18 years
Department of Pediatrics, presenting with complaints of abnormal body movements to either the pediatric or neurology
Christian Medical College, outpatient departments in our institution between October 1, 2018 and June 30, 2020. The All
India Institute of Medical Sciences (AIIMS) modified International Clinical Epidemiology
Ludhiana, Punjab. Network (INCLEN) diagnostic tool for epilepsy (AIIMS modified INDT-EPI) was administered
Received: June 04, 2022; and a diagnosis was made, which was further verified by a pediatrician or a neurologist.
Initial review: July 31, 2022; Specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV)
Accepted: October 19, 2022. were calculated. Results: The study tool had a sensitivity of 87.6% and specificity of
84.0%. The PPV and NPV of the study tool were 86.8% and 84.9%, respectively.
Conclusion: The study tool has good psychometric properties for physician assessment
with regard to diagnosis of epilepsy.
Keywords: Diagnosis, Seizure, Sensitivity, Specificity.
E
pilepsy accounts for 0.5% of the global disease METHODS
burden [1]. The diagnosis of epilepsy is usually
This cross sectional study was conducted in the
made on the basis of clinical history supported
outpatient clinics of pediatric and neurology department in
by brain imaging and electroencephalography
a tertiary level healthcare institution in Northern India from
(EEG). Misdiagnosis may occur in nearly one third of
October 1, 2018 to June 30, 2020. Ethical approval was
cases, even when physicians are involved [2-5]. Multiple
obtained from the institutional ethics committee. A written
possible reasons for epilepsy misdiagnosis have pre-
informed consent was obtained from the primary care-
viously been reported [2,5,6]. Most health centers in our
giver, and written assent was obtained from children bet-
country do not have adequate resources or ready access
ween 12 and 18 years. Children aged one month to 18 years
to diagnostic facilities, which may contribute to
present-ing with abnormal body movements or seizures
misdiagnosis and increase in referral of several patients
were enrolled. Children with severe acute illness, which
[7,8]. Approximately 80% of specialist physicians are
required hospital admission, were excluded from the study.
practicing in urban India. In this scenario, primary health
center (PHC) based care can be essential to decrease Demographic details and pre-diagnosed comorbid
treatment gap [6]. neurodevelopmental disorders (NDDs) were recorded.
AIIMS Modified INDT-EPI 10-item questionnaire [11] was
Questionnaires that are inexpensive, freely available,
administered to primary caregivers, and the diagnosis of
and easy to use by a general pediatrician can aid in correct
“epilepsy”, “No epilepsy”, “single seizure” or “indetermi-
management of epilepsy in children. The International
nate” was made after assessing as per the scoring men-
Clinical Epidemiology Network (INCLEN) developed a
tioned in the INCLEN tool. The diagnosis of epilepsy was
simple questionnaire-based tool in multiple Indian
further verified by either a pediatrician or a neurologist
languages for epilepsy diagnosis in the community (INDT-
(labelled as ‘experts’), who were blinded to the scoring on
EPI), which had good psychometric properties [9]. This
the tool. Diagnosis of “epilepsy” or “No epilepsy” made
was subsequently modified as the AIIMS Modified
by the expert was considered as the gold standard.
INCLEN diagnostic tool for epilepsy (AIIMS Modified
INDT-EPI) [10]. This study was planned to evaluate the Statistical analysis: The sensitivity, specificity, positive
diagnostic accuracy of the AIIMS Modified INDT-EPI tool predictive value (PPV) and negative predictive value
for epilepsy. (NPV) were expressed as percentages with 95% CI. Cohen

46 MODIFIED INCLEN TOOL FOR EPILEPSY
Kappa test was used to compare diagnosis by study tool Table I Clinico-demographic Characteristics of Children
and the gold standard. The data of indeterminate category With Abnormal Movements Assessed for Epilepsy (N=250)
patients were excluded from statistical analysis while Characteristics Value
comparing the study tool with the experts’ diagnosis.
Males 161 (64.4)
RESULTS Age group
Clinico-demographic profile of the enrolled 250 children is 1 mo-2 y 70 (28)
illustrated in Table I. As per gold standard, 138 children 2 y-5 y 64 (25.6)
were diagnosed as epilepsy. Seizures were found 5-18 y 116 (46.4)
secondary to underlying etiologies in 80.3% (n=90) of Urban residence 194 (77.6)
children diagnosed with ‘No epilepsy’ and most common Comorbid NDDs 88 (35.2)
etiology was febrile seizures (n=44, 48.8%), followed by Intellectual disability 42 (47.7)
toxic and metabolic causes (n=21, 23.3%). As per the study Neuromotor disability 34 (38.6)
tool, 114 (45.6%) children had epilepsy, 93 (37.2%) children Behavioral disorder 12 (13.6)
did not have epilepsy and rest 43 (17.2%) children were Values in no. (%). NDDs-neurodevelopmental disorders.
classified as indeterminate.
There was substantial agreement between physician
The psychometric properties of a questionnaire will help
diagnosis and study tool diagnosis (κ=0.717, P<0.001).
qualify their usefulness as a diagnostic screening tool in
The sensitivity, specificity, PPV and NPV of the study tool
primary health care level where tertiary level diagnostic aids
were >80% (Table II). The study tool showed maximum
are not available. Earlier researchers have attempted to study
sensitivity and NPV among age group of 1 month-2 years,
the utility of questionnaire-based epilepsy diagnostic or
whereas maximum specificity and PPV was found among
screening tools. Most of the earlier screening questionnaires
age group of 2-5 years. However, this tool showed least
for epilepsy concentrated on diagnosis of only tonic clonic
accuracy with least specificity among age group of 5-18
seizures [14]. However, the AIIMS Modified INDT-EPI
years as compared to other age groups (Table II).
includes questions to detect various seizure types, including
DISCUSSION myoclonic seizures, epileptic spasms, atonic seizures,
absence seizures and focal seizures [10,11].
Utility of pediatric management protocols such as
Integrated management of neonatal and childhood illness Questionnaires for diagnosis of epilepsy used in the
(IMNCI) for management of common childhood illnesses earlier studies were designed based on experience of
have exemplified the importance and usefulness of simple experts rather than standard international definitions or
management tools that can help a primary care physician classification of seizures. AIIMS Modified INDT-EPI is
in the peripheral settings to manage patients satisfactorily based on ILAE classification, which could be possible
[12,13]. The present study demonstrates acceptable explanation for high sensitivity for this study tool as
psychometric properties of the AIIMS modified INDT-EPI compared to most of the previous studied tools [14,15].
tool for diagnosis of epilepsy in children. Second possible reason for high sensitivity in our study is
Table II Psychometric Properties of AIIMS Modified INDT-EPI in Various Age Groups (N=250)
Value 1 mo-18 y (overall) 1 mo-2 y (n=70) 2 - 5 y (n=64) 5-18 y (n=116)
Sensitivity 87.61% 94.44% 77.42% 90.62%
(80.09% to 93.06%) (72.71% to 99.86%) (58.90% to 90.41%) (80.70% to 96.48%)
Specificity 84.04% 85.71% 96.00% 70.37%
(75.05% to 90.78%) (71.46% to 94.57%) (79.65% to 99.90%) (49.82% to 86.25%)
Positive pre- 86.84% 73.91% 96.00% 87.88%
dictive value (80.50% to 91.34%) (57.25% to 85.70%) (77.70% to 99.40%) (80.13% to 92.87%)
Negative pre- 84.95% 97.30% 77.42% 76.0%
dictive value (77.42% to 90.28%) (84.22% to 99.59%) (64.00% to 86.86%) (58.72% to 87.57%)
Accuracy 85.99% 88.33% 85.71% 84.62%
(80.50% to 90.41%) (77.43% to 95.18%) (73.78% to 93.62%) (75.54% to 91.33%)
AIIMS modified INDT-EPI - All India Institute of Medical Sciences (AIIMS) modified International Clinical Epidemiology Network
(INCLEN) diagnostic tool for epilepsy.

GOYAL, ET AL. 47

• The AIIMS Modified INDT-EPI tool has a good sensitivity and specificity, and can be used in the outpatient
setting for a diagnosis of epilepsy or no epilepsy among children aged between 1 month and 18 years.
due to ability of our study tool to diagnose wide range of the usefulness of this questionnaire as a screening tool for
epileptic seizures as compared to earlier studies that diagnosis of abnormal body movements as possible
focused on specific seizure types only. Similarly, our study epilepsy or otherwise.
yielded high specificity as compared to previous studies To conclude, AIIMS modified INDT-EPI questionnaire
due to ability of the tool to diagnose more types of non- had a high diagnostic accuracy, and can be used in the
epileptic events like breath holding spells and syncope. A outpatient setting for a reliable diagnosis of seizure or
high specificity of study tool translates into high positive seizure-like events in children and young adults aged 1
predictive value and low false positive rates. month to 18 years.
We observed a lower sensitivity of study tool as Ethics clearance: Institutional Ethics Committee, CMCL; No:
compared to previous studies [10,16,17]. This can be 201812614/IECCMCL/PG Thesis-Paeds, dated Dec 14, 2018.
attributed to the different type of study population as Contributors: PG,MS: conceptualized the study design; PG: was
these studies enrolled children with higher risk of seizures. responsible for the data collection and analysis; MS,PV:
Parents of such children are more familiar with termino- supervised the data collection and analysis; PG: prepared the
logies which can increase chances of a positive response first draft of the study; MS: and PV: revised the manuscript. All
authors approved the final manuscript.
and thus higher sensitivity with a study questionnaire
Funding: None; Competing interests: None stated.
[10,16,17]. In our study, we enrolled children coming to the
general pediatric and neurology outpatient department REFERENCES
with history of any abnormal body movements. Similarly, 1. World Health Organization. Fact sheets: Epilepsy.
low specificity of diagnostic questionnaire in our study as Accessed June 1, 2022. Available from: https://www.who.int/
compared to some previous studies can be attributed to en/news-room/fact-sheets/detail/epilepsy
the different type of study population as unlike these 2. Udani V. Improving diagnosis of epilepsy in India–How
studies, our study did not include healthy children as difficult is it?. Indian Pediatr. 2014;51:535-6.
controls [14,16,17]. Specificity of a test usually increases 3. Chapman M, Iddon P, Atkinson K, et al. The misdiagnosis
of epilepsy in people with intellectual disabilities: A
with healthy controls.
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In subgroup analysis for age, in our study, AIIMS 4. Indrayan A. Diagnostic questionnaire and its validation.
Modified INDT-EPI tool showed highest utility in age Biostatistician’s perspective. Indian Pediatr. 2014;51:536-8.
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Child. 2006;91:206-9.
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6. Ganapathy K. Distribution of neurologists and neuro-
sensitivity (86.5%) and positive predictive value (88.4%) surgeons in India and its relevance to the adoption of
in age group of 1 month-2 years as compared to age >2 telemedicine. Neurol India. 2015;63:142-54.
years, and also demonstrated that the best diagnostic 7. Kumar R, Tripathy JP, Singh N, et al. Rapid assessment of
accuracy was found among age group of 2-9 years. A health services in Punjab using a mixed method approach.
higher sensitivity in children with comorbid NDDs could Indian J Comm Health. 2015;27:197-203.
possibly be because parents of children with comorbid 8. Singh T, Kankaria A, Bhatnagar N, et al. Assessment of
NDDs were more likely to understand the terminologies in functioning of public health facilities in a North Indian state.
the questionnaire. The original study [9] also demons- Int J Community Med Public Health. 2019;6:3358-63.
9. Konanki R, Mishra D, Gulati S, et al. INCLEN Diagnostic
trated the increase in sensitivity (97.4%) of diagnostic
Tool for Epilepsy (INDT-EPI) for primary care physicians:
questionnaire when administered to children with development and validation. Indian Pediatr. 2014;51:539-4.
comorbid NDDs, as also reported later [10]. 10. Gulati S, Patel H, Chakrabarty B, et al. Development and
The data of children with ‘indeterminate’ category on validation of AIIMS modified INCLEN diagnostic
instrument for epilepsy in children aged 1 month–18 years.
the tool was removed from analysis, which may have had a
Epilepsy Res. 2017;130:64-8.
modifying effect on the psychometric properties in this 11. Child Neurology division, AIIMS New Delhi. INDT-EPI
study. However, as the study setting was a general out- Module for epilepsy. Accessed June 1, 2022. Available
patient setting, it makes our findings more relatable to a from: http://pedneuroaiims.org/training_module_for_
peripheral health care setup. Thus, our findings support epilepsy.html

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12. Kaur S, Singh V, Dutta AK, et al. Validation of IMNCI 15. Patel AA, Ciccone O, Njau A, et al. A paediatrics epilepsy
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ADVERTISEMENT

RESEARCH PAPER
Antibiotic Susceptibility, Carrier State and Predictors of Outcome of

Staphylococcus aureus Infections in Hospitalized Children
KIRANPREET KAUR,1 SUMAIRA KHALIL,1 NP SINGH,2 POOJA DEWAN,1 PIYUSH GUPTA,1 DHEERAJ SHAH1
Departments of 1Pediatrics and 2Microbiology, University College of Medical Sciences (University of Delhi) and GTB Hospital,
Delhi.
Correspondence to: Objectives: To evaluate the antibiotic resistance pattern, clinical profile and predictors for
Dr Dheeraj Shah, Director-Professor, adverse outcomes in children hospitalized due to staphylococcal infection; and the
Department of Pediatrics, frequency of nasal and axillary carrier states in these children. Methods: This descriptive
University College of Medical Sciences study enrolled 100 symptomatic children (aged 1 month - 12 years) in whom S. aureus was
isolated from cultures of blood, pus or cerebrospinal fluid. All samples were processed as
& GTB Hospital, Delhi 110095. per the Clinical and Laboratory Standards Institute (CLSI) standards. Antimicrobial
dshah@ucms.ac.in susceptibility was tested using disc diffusion method; minimum inhibitory concentration (MIC)
Received: Sept 05, 2022; for vancomycin was measured using E strips. Predictors for poor recovery were
Initial review: Sept 28, 2022; determined by univariate and multivariable logistic regression analysis. Results: Skin and
Accepted: Nov 14, 2022. soft tissue infections were the most common (47%) followed by respiratory infections
(37%). Methicillin-resistant Staphylococcus aureus (MRSA) was detected in 62%, out of
which 63% (39/62) were multi-drug resistant. Carrier state was present in 49% (93%
MRSA); 80% were axillary carriers. High MIC (>1 µg/mL) for vancomycin was seen in 65% of
patients, and was the only factor associated with poor recovery [aOR (95%CI) 5.3
(1.6,18.5); P=0.008] on multivariable logistic regression analysis. Conclusion: MRSA is the
predominant strain in severe staphylococcal infections requiring hospitalization, and
majority of them are multidrug resistant. High MIC to vancomycin among S. aureus is an
emerging concern.
Keywords: Antimicrobial resistance, Methicillin-resistance, Treatment failure.
Published online: November 19, 2022; PII: S097475591600469
S
taphylococcus aureus is associated with METHODS
significant morbidity and mortality in children,
especially in low- and middle-income countries This observational study was conducted in the Depart-
(LMICs). Community-acquired MRSA (CA- ments of Pediatrics and Microbiology of a medical-college-
MRSA) infections have a fundamentally different affiliated public hospital, from November, 2017 to April,
epidemiology compared to hospital-acquired methicillin- 2019. We included children aged 1 month to 12 years with
resistant Staphylococcus aureus (MRSA) [1]. In India, the features of clinical sepsis such as fever, chills, deep
overall rate of MRSA in clinical specimens is reported to be abscesses, hypotension or oliguria, and where S. aureus
high (45-60%) [2]. was isolated from cultures of blood, pus or cerebrospinal
fluid (CSF). Culture isolate was considered a contaminant
Less is understood about community-acquired S. if the patient’s clinical features and laboratory test did not
aureus and predictors of adverse outcomes in children. suggest infection, follow up blood cultures were negative
There are conflicting data on whether higher vancomycin when the patient did not receive any antibiotic, patient
minimum inhibitory concentrations (MICs) adversely recovered without any anti-staphylococcal treatment, or
affects outcome in patients with S. aureus bacteremia [3]. there was a polymicrobial growth; such patients were
Moreover, there is paucity of recent data related to the excluded from the study. Informed consent was obtained
profile and resistance pattern of S. aureus infections in from parents or guardians of every participant. Assent was
children. Thus, we conducted this study to describe the obtained from children 7 years of age or older. An approval
antibiotic resistance pattern, clinical profile and predictors for from the institutional ethics committee was obtained.
adverse outcomes in children hospitalized due to staphy-
lococcal infection. We also aimed to study the frequency of A detailed history and physical examination were
nasal and axillary carrier states in these children. recorded for all participants. Complete hemogram and

50 DRUG RESISTANCE IN STAPHYLOCOCCAL INFECTIONS
blood culture were performed on all, pus and CSF cultures fever lasting more than 7 days, poor appetite for more than
were collected, wherever relevant. Other investigations 72 hours, hospitalization for more than 14 days, delayed
(ultrasonography, chest X-ray, echocardiography, com- microbiological clearance more than 72 hours, antibiotic
puted tomography (CT) scan) were guided by the clinical resistance, and complications (shock, encephalopathy,
symptoms and response to therapy. ventilatory support or death).
Peripheral venous blood (1-3 mL) was drawn by aseptic Using the proportion of 54% MRSA amongst total
method and inoculated in BACTEC 9120 bottles for staphylococcus infections in a previous study from India
culture. Samples for blood culture were collected at [7], we calculated a sample size of 96 participants with 10%
admission and every 48-72 hours till clearance. All the absolute precision at 95% confidence level and alpha error
clinical samples (blood, pus, CSF, and other body fluids) of 0.05. We planned to enrol 100 children with confirmed S.
were inoculated on 5% sheep blood agar and MacConkey aureus infection.
agar plates. After overnight incubation, isolates were Statistical analysis: The data were entered into Microsoft
identified by their colony characters, morphology and Excel and analyzed using SPSS 20. Descriptive statistics
staining characters. Antimicrobial susceptibility testing were performed for antibiotic resistance pattern, clinical
(AST) was done on Muller Hilton agar (MHA) by modified profile, nasal and axillary carrier rate, and outcome
Kirby Bauer disc diffusion and interpreted using Clinical parameters. For risk factors of poor recovery, various
and Laboratory Standards (CLSI) guidelines [4]. E-test was parameters were compared between children having poor
performed to determine the susceptibility to vancomycin recovery against those not having poor recovery. Student
and linezolid. Vancomycin MIC determination was t test was used to compare continuous variables, and chi-
performed by agar strip method, ATCC 29213 Staphylo- square test or Fischer exact test was used to compare
coccus aureus was used as control stain and the MIC’s for categorical variables. Logistic regression analysis was
the control strain were found within susceptible break- performed for risk factors with P value ≤0.25 on univariate
points. To determine the nasal carrier state, one sterile analysis to calculate adjusted odds ratio and 95%
cotton swab was inserted approximately 2 cm into both confidence interval for the outcomes of poor recovery.
nostrils and rotated against the anterior nasal mucosa for 3
seconds. Similarly, axillary swabs were obtained. RESULTS
All children were managed according to the National We enrolled 100 children (56 boys) with S. aureus
Centre for Disease Control guidelines [5]. Empirical infections with one-third (n=31) of them aged less than 6
therapy was started with amoxicillin-clavulanic acid or months and nearly half (n=51) were infants. Majority of the
cloxacillin (± gentamicin). In serious infections, vanco-
mycin was started by the treating physician at their Table I Clinical Diagnosis of Children With Staphylococcal
discretion. Antibiotics were changed as per the Infections Enrolled in the Study (N=100)
susceptibility pattern of the organisms. For uncomplicated Diagnosis No. (%)
infections, minimum duration of treatment was two weeks.
For complicated infections, liver abscess, empyema and Skin and soft tissue infections
Abscess 30 (30)
endocarditis, treatment duration varied from 21 to 42 days
upper limb 4 (4)
from negative blood cultures depending on their clinical lower limb 13 (13)
response [6]. both upper and lower limb 2 (2)
head and neck 6 (6)
The outcome was measured in terms of antibiotic
trunk and back 5 (5)
resistance pattern, type of infection, clinical recovery, and Pyoderma/cellulitis 9 (9)
nasal and axillary carriage of S. aureus. Isolates resistant Necrotizing soft tissue infection 8 (8)
to methicillin (cefoxitin) were labelled as MRSA [4] and Bone and joint infections
those resistant to vancomycin were labelled as
Septic arthritis 8 (8)
Vancomycin-resistant S. aureus (VRSA) [4]. MRSA
Osteomyelitis 2 (2)
isolates found to be resistant to three or more other Osteomyelitis and septic arthritis 2 (2)
antibiotics apart from beta-lactams were labelled as multi- Pneumonia 29 (29)
drug resistant (MDR) S. aureus [7]. Recovery was defined Pneumonia with complicationsa 8 (8)
in terms of duration of fever (from enrolment to beginning Acute meningitis 9 (9)
of an afebrile period of 72 hours), appetite, duration of Sepsis without focus 14 (14)
hospitalization and microbiological clearance (negative Total percentage exceeds 100 because of the presence of more than
blood culture at 48-72 hour). Poor recovery was defined by one diagnosis in some children. aempyema/pneumothorax.

KAUR, ET AL. 51
patients had acute complaints with mean (SD) duration of A carrier state was found in 49 patients, out of which 32
illness of 11.1 (20.3) days. Eighty-four children presented were axillary carriers, 10 were nasal carriers and 7 were both
with fever and one third (n=28) had associated chills and nasal and axillary carriers, leading to 56 S. aureus isolates.
rigors. Majority of participants were undernourished with Most (52, 93%) of these isolates were MRSA. In these 56
mean (SD) weight for age z-score (WAZ), height for age z- isolates, we compared their antibiotic susceptibility
score (HAZ) and weight for height z-score (WFHZ) as -2.9 pattern to S. aureus isolated from site of infection in the
(1.7), -2.1 (1.7) and -2.3 (1.5), respectively. Three-fourths same child. For 38 isolates, their methicillin (cefoxitin)
(77%) of the participants were anemic, and 50% had susceptibility/resistance status was same as that of S.
leukocytosis, predominantly neutrophilic leukocytosis. aureus isolated from site of infection. For 20 isolates, their
antibiotic susceptibility pattern (for all antibiotics) was
Table I depicts the sites of infection in study
similar to the S. aureus isolated from infection site.
participants. Majority (90%) of the cases did not have any
prior history (in last 30 days) of hospitalization or treatment Ninety-six participants were discharged from hospital,
in a healthcare facility. Skin and soft tissue infections three died and one left against medical advice. The mean
(SSTI) were the most common presentation (47%) followed (SD) duration of stay was 14.1 (5.5) days. The cause of
by respiratory infections (37%). Abscess was the most death in three patients was sepsis, severe pneumonia and
common manifestation of SSTI found in 64% (n=30). necrotizing fasciitis.
Necrotizing fasciitis, the most severe form of SSTI was
Poor recovery was present in 65 patients. On univariate
present in eight cases. Eight participants had complicated
analysis, severe stunting (HAZ score <-3 SD) (OR 4.54,
pneumonia. Septic arthritis (n=8) was more common than
95%CI 1.4,14.4) and high vancomycin MIC (OR 7.0, 95%CI
osteomyelitis (n=2).
Table II describes the antimicrobial susceptibility Table III Factors Associated with Poor Recovery in S. aureus
pattern of all isolates. Two-thirds of the isolates (n=62) Infection (N=100)
were MRSA. All the isolates were uniformly susceptible to
netilmicin, vancomycin and linezolid. There was no Factor OR (95%CI) aOR (95%CI)
significant difference in the clinical data, anthropometry Age <6 mo 0.60 (0.25, 1.45) 0.39 (0.12,1.24)
and biochemical parameters between MRSA and MSSA
Male gender 0.90 0.39, 2.05) -
infected children.
Presenting complaints
The MIC values for vancomycin ranged from 0.25 µg/ Fever 0.57 (0.17, 1.92) -
mL to 2 µg/mL. Two-third (65%) of the patients had high Chills 2.47 (0.89, 6.85) 2.38 (0.68,8.19)
(>1 µg/mL) vancomycin MIC values. The median (IQR) of Cough 0.92 (0.38,2.18)
vancomycin MIC of MRSA was higher as compared to History
MSSA [1 (1,1.5) µg/mL vs 1 (0.44,1) µg/mL, P<0.001). Trauma 0.30 (0.10, 0.92) 0.39 (0.90,1.75)
Prior hospitalization 1.29 (0.31, 5.32) -
Table II Antibiotic Susceptibility Pattern of Staphy- Prior antibiotics 1.50 (0.49, 4.62) -
locuccus aureus Isolates (N=100) Presence of abscess 0.57 (0.24,1.31) 0.65 (0.21,1.98)
Antibiotic MSSA(n=38) MRSA (n=62) BMI <-2SD 1.98 (0.85,4.60) 1.59 (0.54,4.69)
HFA z-score <-2SD 1.97 (0.85,4.58) 1.70 (0.61,4.73)
Cefoxitin, 38 (100) 0 Hemoglobin< 10 g/dL 1.60 (0.62,4.15) -
Clindamycinb 33 (86.8) 36 (58.1) TLC > 15×109 1.46 (0.63,3.35) -
Gentamicinc 37 (97.4) 34 (54.8) Vancomycin MIC 7.07 (2.24,22.30) 5.34(1.56,18.5)
>1 µ/mL
Ampicillinc 30 (78.9) 1 (1.61) MRSA 1.37 (0.59,3.17) -
Erythromycinc 19 (50) 3 (4.8) Focus of infection
Amikacinb 36 (94.7) 46 (74.2) Skin and soft tissue 0.66 (0.29,1.52) -
Netilmicin 38 (100) 62 (100) Bone and joint 0.72 (0.21,2.48) -
Ciprofloxacina 26 (68.4) 29 (46.8) Respiratory 1.45 (0.61,3.47) -
CNS 4.77 (0.57,39.82) 3.43 (0.33,34.4)
Cotrimoxazole 16 (42.1) 21 (33.9)
Sepsis without focus 1.41 (0.41,4.87) -
Vancomycin 38 (100) 62 (100)
Carrier state 0.51 (0.22,1.16) 0.47 (0.17,1.28)
Linezolid 38 (100) 62 (100)
BMI: body mass index, MRSA: methicillin resistant staphylococcal
Values in no. (%). MSSA-methicillin-sensitive S.aureus, MRSA- aureus, MIC: minimum inhibitory concentration, CNS: central
methicillin resistant S.aureus. aP<0.05; bP<0.01; cP<0.001. nervous system, TLC – Total leukocyte count, HFA – Height for age.

52 DRUG RESISTANCE IN STAPHYLOCOCCAL INFECTIONS
2.2,22.3) were associated with higher odds of poor associated with increased mortality and treatment failure.
recovery, whereas history of trauma preceding the illness However, Pradhan, et al. [18], in a meta-analysis including
was associated with lesser odds of poor recovery (OR=0.3, 2955 patients from 13 reports, concluded that vancomycin
95%CI 0.1,0.9) (Table III). On logistic regression analysis, MIC may not be the sole indicator of vanco-mycin treat-
only high vancomycin MIC was a significant risk factor for ment failure in MRSA and methodological differences,
poor recovery [aOR (95%CI) 5.3 (1.6,18.5); P=0.008]. heterogenous population and differences in methods for
estimation of drug susceptibility could be the other reasons.
DISCUSSION
Similar to this study, a high (42-82%) carrier state has
In this study enrolling 100 children with culture positive
also been reported in adults and children from other
staphylococcal infections, skin, soft tissue and respiratory
countries [19]. This may be of concern as colonized S.
tract were the most common sites of infection. MRSA was
aureus, may act as reservoirs for future clinical infection
isolated in 62% isolates; 63% of MRSA were MDR S.
and subsequent spread to the community. Lauderdale, et
aureus. Moreover, two-thirds (65%) of all S. aureus
al. [20] observed that only nasal culture is not a sensitive
isolates had high MIC (>1 µg/mL) for vancomycin. Carrier
marker of MRSA colonization, and if only nasal cultures are
state was present in almost half of the cases. High MIC for
used, MRSA colonized patients are underestimated.
vancomycin was associated with poor recovery.
Sending routine nasal and axillary swabs and eliminating
The global SENTRY surveillance program [8] carrier states may act as a step toward preventing
conducted in 45 countries from North America, Latin community spread of MRSA.
America, Europe and Asia-Pacific region collected
The limitations of our study were the absence of long-
nosocomial and CA-S. aureus isolates from 1997-2016 and
term follow up to determine any recurrence of infections,
revealed that MRSA proportion of S.aureus had peaked till
lack of molecular characterization including PVL gene, and
2008, and declined since 2009. This reduction was
lack of epidemiological typing of the isolates. Another
consistent with several other regional and national
limitation in our study was that vancomycin MIC were
surveillance programs during 2000-2010 [9]. This could be
determined by E-test which may provide 1-2 log dilutions
attributed to prioritizing MRSA infection prevention
higher MIC values than the reference broth microdilution
programs. However, in LMICs, the prevalence of MRSA
test (BMD), which is the gold standard. However, E strip
seems to be increasing. In India, prevalence of MRSA was
test is widely used as it is easy to perform and less
earlier reported to be 29-46% in hospital settings [10]. In
cumbersome as compared to BMD. Also, E strip test when
the year 2013, Eshwara, et al. [7] documented MRSA in 54%
used with ATCC25923 S. aureus standard susceptible
of S. aureus bacteremia in children and adults, hospitalized
strain, as done in present study, maybe better correlated
in a tertiary care hospital in India. There are other recent
than BMD [4]. We, also, did not compare proportionate
reports of high prevalence of MRSA from developing
carriage of S. aureus in healthy and diseased population as
countries [1,11]. Some of the possible reasons for high
we did not enrol any disease-free controls. The main
prevalence of MRSA in LMIC are irrational antibiotic
strength of our study was availability of clinical data of
prescription, socio-demographic factors like crowding and
patients till their discharge, which helped us to analyze the
poverty resulting in circulation of resistant bacteriological
significance of antimicrobial susceptibility in a better way.
strains in the community [12].
We used E strip to detect vancomycin MIC, which is a more
High MIC for vancomycin, a phenomenon referred to reliable method to determine the susceptibility of the
as ‘MIC creep,’ was first described in adults by Goldmann, organism to the glycopeptides.
et al. [13]; leading to concerns if vancomycin would be
appropriate to treat invasive staphylococcal infection in We conclude that MRSA is the predominant staphylo-
presence of high vancomycin resistance and its association coccal strain in children hospitalized due to staphylo-
with poor outcome [14]. An earlier study in adults from coccal infections in our setting, and majority of them are
North India documented that 50% of isolates from blood, multidrug resistant. Vancomycin may be used as a first line
skin and soft tissue infections had vanco-mycin MIC ≥1.5 empiric antibiotic for serious staphylococcal infections
µg/mL [15]. It has been seen that MIC creep phenomena is and in those with documented MRSA. Vancomycin
influenced by the type of S. aureus strain, type of patient susceptibility testing can help in monitoring treatment
population and storage of isolates [16]. especially in children with prolonged hospital stay or poor
recovery. A higher proportion of MRSA, MDR and high
We documented that high vancomycin MIC was signi- vancomycin MIC in our group of patients with S. aureus
ficantly associated with poor recovery. Earlier systematic infection is a serious concern with further risk of spread of
reviews [3,17] have also concluded that high MIC is resistant S. aureus infection in the community.

KAUR, ET AL. 53

• Methicillin-resistant Staphylococcus aureus (MRSA) was the predominant strain in children hospitalized due
to staphylococcal infection acquired in the community settings.
• High MIC to vancomycin was associated with a poor outcome among S. aureus infected children.
Ethics clearance: Institutional Ethics Committee of Human Forum Infect Dis. 2019;6: S47-53.
Research, UCMS; No. IEC-HR/2017/32/99, dated Oct 17, 2017. 9. Johnson AP, Davies J, Guy R, et al. Mandatory surveillance
Contributors: KK: Conducted the study, data collection, literature of methicillin-resistant Staphylococcus aureus (MRSA)
review and drafted the manuscript; SK: data analysis, data bacteremia in England: The first 10 years. J Antimicrob
interpretation, literature review, drafted and revising the Chemother. 2012; 67:802-9.
manuscript. NPS: study design, provided laboratory support, 10. Patel AK, Patel KK, Patel KR, et al. Time trends in the
supervised the study, provided critical inputs; PD: study design, epidemiology of microbial infections at a tertiary care center
supervised the study, literature review, provided critical inputs; in west India over last 5 years. J Assoc Physicians India. 2010;
PG: study design, supervised the study, literature review, provided 58:37-40.
critical inputs; DS: conceptualized the study, study design, 11. Dharmapalan D, Shet A, Yewale V, et al. High reported rates
literature review, data analysis, data interpretation, provided of antimicrobial resistance in Indian neonatal and pediatric
critical inputs. All authors approved the final manuscript. blood stream infections. J Pediatric Infect Dis Soc. 2017;
Funding: None; Competing interest: None stated. 6: e62-8.
12. Andreatos N, Shehadeh F, Pliakos EE, et al. The impact of
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meta-analysis. Clin Infect Dis. 2012;54:755-71. 15. Mewara A, Gautam V, Kaur H, et al. In vitro evaluation of
4. Clinical and Laboratory Standards Institute. Performance antibiotics for methicillin resistant Staphylococcus aureus
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M100-S26. Clinical and Laboratory Standards Institute. resistant staphylococcus aureus (MRSA) infections in
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characteristics, and carriage of the Panton-Valentine 20. Lauderdale, TL, Wang, JT, Lee, et al. Carriage rates of
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54 NOTICE
INDIAN ACADEMY OF PEDIATRICS

Kamdhenu Business Bay, 5th Floor, Plot No. 51, Sector 1,
(Near Juinagar Railway Station), Nerul, Navi Mumbai – 400706
NOTICE FOR ANNUAL GENERAL BODY MEETING OF INDIAN ACADEMY OF PEDIATRICS

Notice is hereby given that the Annual General Body Meeting of Indian Academy of Pediatrics for 2023 is scheduled
to be held on 21st February 2023, during 60th IAP Pedicon and 30th IPA congress 2023 at Mahatma Mandir Conven-
tion and Exhibition Centre, Salt Mount Rd, Sector 13C, Sector 13, Gandhinagar, Gujarat. 382016 from 4:30 pm
onwards to consider the following agenda.
Kindly make it convenient to attend the meeting.
With kind regards,
Sd/- Sd/-
DR UPENDRA KINJAWADEKAR DR VINEET K SAXENA
President, IAP 2023 Hon. Secretary General, IAP 2022 & 2023
Place: Navi Mumbai Date: 15 January, 2023
AGENDA:
1. Confirmation of the minutes of the Annual General Body Meeting held on 21st March 2022 at Noida.
2. Business arising out of the minutes.
3. Consideration and adoption of Annual Report of the Society.
4. Consideration and adoption of the audited Statement of Accounts for the year ended 31st March 2022 and the
Budget for the year 2023-2024.
5. Appointment of Auditors and fixing their remuneration for 2023-24.
6. Appointment of Honorary Legal Advisor for 2023-24.
7. Matters related to IAP Charity Activity.
8. Consideration of matters related to IAP Election for 2024.
9. Information of IAP Executive Board Members of the year 2023.
10. Matters related to 61st IAP Pedicon 2024.
11. Any other business, notice of which has been circulated with the agenda.
12. Any other business of which 30 days’ notice has been given to the Secretary General in writing.
13. Any other business with the permission of the chair.
Note:
(1) If there is no quorum within half an hour of time fixed for the meeting, the meeting shall be adjourned to a later
time on the same day and same place. No quorum is needed for the adjourned meeting.
(2) Kindly note that entry into the meeting hall will be permitted to only those members who give their Central IAP
membership number and who bring their personal photo ID (such as Driving License with photo / PAN Card /
Voter ID Card / Valid Passport / IAP Identity Card / Aadhar Card).
-oOo-

REVIEW ARTICLE
Management of Hepatitis C in Children – A New Paradigm

UJJAL PODDAR,1 DV UMESH REDDY2
1Departments of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh.
2Department of Pediatric Gastroenterology, Post Graduate Institute of Child Health Hospital, Noida, Uttar Pradesh.
Correspondence to: Dr Ujjal Poddar, Professor and Head, Department of Pediatric Gastroenterology, SGPGIMS, Raebareli Road,
Lucknow 226 014, Uttar Pradesh. ujjalpoddar@hotmail.com
Introduction: With the advent of direct-acting antivirals (DAAs), the past decade has seen a paradigm shift in the management of
hepatitis C (HCV) infection in children. In this review, we summarize the various treatment options for pediatric HCV infection, highlighting
the recent changes in the management.
Methods: A literature search was performed using the PubMed database with the relevant keywords. Filters included were human,
ages 0-18 years, and the English language.
Results: Initial phase of HCV treatment using conventional or pegylated interferon and ribavirin combination regimens yielded poor
outcomes in children, especially in genotypes 1 and 4, with an overall sustained virologic response of 58%. Also, treatment with
interferon and ribavirin combination was associated with significant side effects in up to 52% of those treated. Presently, various
combinations of direct-acting antivirals (DAAs) have been approved in children above three years of age with documented evidence of
high efficacy (SVR12 of 92% to 100%) and excellent safety, and the current standard of care.
Conclusion: With various DAA regimens now being approved for children above three years of age, the treatment of active HCV
infection (HCV-RNA positive) in children has become simple. Besides the effectiveness of DAA therapy, public awareness about HCV
transmission, better screening, and making the DAAs available at a subsidized price in the public sectors are necessary to eliminate
HCV infection in India.
Keywords: Direct-acting antivirals, Interferon, Outcome, Ribavirin.
H
epatitis C virus (HCV) is a primarily children and the breakthroughs in HCV management.
hepatotropic single-stranded RNA virus
HCV Prevalence - INDIAN SCENARIO
belonging to the Flaviviridae family. HCV is
classified into seven genotypes based on There is a scarcity of data on the prevalence of HCV
sequence variations. In India, genotype 3 is the most infection in Indian children. A hospital-based study from
predominant genotype, accounting for more than 80% of North India [4] documented HCV as the cause in 5% (3/60)
the cases [1]. HCV is mainly transmitted through the of Indian children presenting with cirrhosis. Schmelzer, et
parenteral route, sexual contact, and vertical transmission al. [5], in a modeling study, showed the global estimate for
from mother to baby. Of all infections, 75%-85% develop HCV viremic prevalence in children between 0–18 years of
chronic HCV (persistence of HCV for more than 6 months) age was 0.13%, corresponding to over 3 million children
[2]. However, the natural history of chronic HCV is relatively with HCV in 2018. The same study showed a 0.04% (0.03-
benign in children. It has been documented that HCV takes 0.08) HCV prevalence in Indian children; however, the
ten years to develop chronic hepatitis, 21 years for cirrhosis, results were by extrapolation using regression analysis
and 29 years for hepatocellular carcinoma (HCC) [3]. based on biological and epidemiological plausibility
Although morbidity in children is uncommon, a significant rather than by real epidemiological studies. Nevertheless,
proportion of the infected children grow into adulthood for various reasons, these reports likely underestimate
with the risk of severe liver disease, including cirrhosis and the true prevalence. Most children with HCV infection are
hepatocellular carcinoma. A substantial shift in the asymptomatic and, thus, are unaware of their status. Also,
treatment paradigm from interferon plus ribavirin-based a recent change in epidemiological patterns has been
therapy to all oral, safe and highly effective direct-acting reported, with an increased surge in the adolescent age
antivirals (DAAs) in the current era has revolutionized the group because of intravenous drug abuse and the opioid
treatment of hepatitis C. Major milestones have been epidemic. A high HCV disease burden in young adults is a
achieved from its initial report as a non-A, non-B virus in primary driver of an increased infection rate in pregnant
1975 to the present achievement of effective virological women and as a consequence, more children are born to
cure. This review collates the literature on HCV treatment in HCV-infected mothers (vertical transmission). In an adult

56 MANAGEMENT OF HEPATITIS C IN CHILDREN
study, Puri, et al. [6] estimated that the prevalence of HCV randomized control trials (RCTs) evaluating the efficacy
infection in India is between 0.5% and 1.5%. Similar of PEG-IFN (alfa-2a or alfa-2b) and ribavirin combination
results were documented by Goel, et al. [7] in a systematic therapy in children, reported an SVR of 58%, with a higher
review with a prevalence of 0.49% in the low-risk adult SVR for genotypes 2 and 3 (87% and 89%) than for
population. The only community-based study from India, genotypes 1 and 4 (61% and 52%). The most common side
Chowdhury, et al. [1] have shown the prevalence of HCV effects seen were leukopenia (52%), neutropenia (32%),
among children (<10 years) is 0.31%, and 0.83% among injection site erythema (27%), alopecia (13%), anemia
adolescents (10-19 years) [1]. Multi-transfused children (11%), pruritus (10%) and thrombocytopenia (5%)
are at a higher risk of having HCV infection (13-65%) [8]. leading to a discontinuation rate of 4% [12]. Therapy has
Though HCV screening has become mandatory since also been shown to negatively affect body weight, linear
2002, the serological tests used for screening cannot pick growth, and body composition, putting children at risk for
up cases in the window period. In developed countries, developmental blunting [13]. Neuropsychiatric distur-
with the use of NAT-based (nucleic acid technology) bances such as mood alteration, irritability, agitation, and
screening in blood banks, the risk of transfusion- aggressive behavior were reported in up to 30% of
transmitted infection has been reduced significantly. In children [13]. Ribavirin is also a known teratogenic agent
India, individual donation (ID) NAT testing is not yet (category X) in women of childbearing age.
compulsory and as a result of which HCV is still rampant
among multi-transfused children [9]. Further complicating the use of this combination
regimen was the prolonged duration of treatment (with a
MANAGEMENT OF HCV IN CHILDREN total of 48 weeks for genotypes 1 or 4 and 24 weeks for
genotypes 2 or 3), child-unfriendly formulation (sub-
The current era of DAA therapy has made a paradigm cutaneous injection), the need for intensive monitoring,
shift in the management of HCV infection in children, with and the known serious side effects profile. Ultimately, the
recently published guidelines suggesting that the treatment with PEG-IFN and ribavirin regimens, with their
regimen of pegylated-interferon (PEG-IFN) and ribavirin well-proven drawbacks, left pediatric gastroenterologists
(RBV) should not be utilized [10]. A review of historical searching for alternatives. This often resulted in the
antiviral therapeutic strategies, including PEG-IFN plus deferral of treatment in expectation of improved
ribavirin, is warranted to appreciate the degree of therapeutic options in the near future.
superiority of DAA therapy over previous older HCV
regimens. Present Status of HCV Treatment
Initial Phase of HCV Treatment The origin of the newer agents for HCV treatment in the
form of DAAs is based on the advanced understanding
The initial phase of HCV treatment was based on of HCV virology. HCV genome encodes for a 3011 amino
interferon (IFN) monotherapy starting from the early acid residue polyprotein which undergoes proteolysis to
1990s before advanced treatment in the form of long- yield ten individual proteins. Among them are three
acting pegylated interferon plus ribavirin was approved structural proteins (two envelope glycoproteins E1 and
in the late 2000s. The achievement and persistence of E2 and core protein) and seven non-structural (NS)
undetec-table HCV-RNA off treatment, defined as the proteins, which are p7, NS2, NS3, NS4A, NS4B, NS5A,
sustained virologic response (SVR) at 6 month of and NS5B (RNA polymerase activity), which participate in
stopping therapy is a satisfactory endpoint for a post-translational proteolytic processing and replication
virological cure. Jacobson, et al. [11] reviewed 19 trials of HCV genetic material. These drugs target specific non-
using IFN-alpha monotherapy for children with structural proteins of the virus and disrupt viral
HCV infection, documenting an overall SVR of 36%. replication and infection.
Most of the adverse events were mild and did not result in
any treatment discontinuation. As none of the studies Direct-acting Antivirals- A Boon for HCV Cure
systematically recorded these adverse events, only a
qualitative description of these events is available. DAAs are categorized into four classes based on their
The common adverse effects reported were influenza- mechanism of action and therapeutic target. The four
like symptoms, fever, weight loss (reportedly regained classes are non-structural proteins 3/4A (NS3/4A)
after the treatment), neutropenia, alopecia, allergic protease inhibitors (PIs), NS5B nucleoside polymerase
reactions, pruritus, thrombocytopenia, and febrile inhibitors (NPIs), NS5B non-nucleoside polymerase
convulsions [11]. inhibitors (NNPIs), and NS5A inhibitors (Fig.1).
Monotherapy with DAA should be avoided. Regimens
Druyts, et al. [12], in a metanalysis of eight should contain a combination of two different classes of

PODDAR, REDDY 57
Fig. 1 HCV genome with its encoded proteins as targets for direct-acting antiviral agents.
DAAs, as drugs from the same class share cross- comparable to those seen in adults [15,16]. Across the
resistance. Various combinations of DAA-regimens (with three studies, there were no serious adverse events with
a high genetic barrier to resistance) have been approved the most common side effects reported being headache
for children with HCV infection, showing high effective- (18% to 27%), fever (17% to 21%), vomiting (24%),
ness and excellent safety with an adverse event profile abdominal pain (15%), diarrhea (14%), and fatigue (13%)
comparable with placebo (Table I). [14,17,18]. Ledipasvir plus sofosbuvir was approved by
the Food and Drug Administration (FDA) in 2017, initially
Ledipasvir-sofosbuvir: The first pediatric study assessing
for children 12 to 17 years of age, with an extension to
the IFN-free treatment with DAAs was a phase 2,
those over three years of age in 2019. Ledipasvir plus
multicentric, open-label study which evaluated the
sofosbuvir is currently recommended for children aged ≥3
efficacy and safety of ledipasvir plus sofosbuvir in 100
years with genotypes 1, 4, 5, or 6 [10].
children between the age of 12 to 17 years with chronic
HCV genotype 1 infection [14]. Overall, 98% of patients Sofosbuvir-Velpatasvir: Jonas, et al. [19], in an open-label
reached SVR12 (at 12 weeks after stopping therapy), and study, evaluated the efficacy of sofosbuvir plus
no patient had a virologic failure. Two children who did velpatasvir for 12 weeks in children more than six years of
not achieve SVR12 were lost to follow up either during or age without cirrhosis or with compensated cirrhosis
after treatment [14]. The approval of ledipasvir plus having genotypes 1, 2, 3, 4 or 6 HCV infection. Most of the
sofosbuvir in the pediatric population aged 3 through 11 study participants (147/173; 85%) were treatment-naive,
years was supported by two clinical trials, which and the rest (26/173; 15%) were treatment-experienced.
demonstrated high SVR12 rates of 99% and 97%, Overall, SVR12 was ≥92%, with no treatment-related

Table I Studies on the Efficacy and Safety of DAA Regimens in the Treatment of HCV Infection in Children
DAA regimen Author, year, age group, Genotype SVR12(%) Common adverse events
number of study participants
Ledipasvir and sofosbuvir Balisteri, et al. [14], 2017; 1 98 Headache (18 -27%), fever (17-
combination 12-17 y, n=100 21%), vomiting (24%).
No serious adverse events.
Murray, et al. [17], 2018; 1 98 No reported drug discontinuation
6-11 y, n=90 due to serious adverse events
El Khayat, et al. [15], 2018; 1,4-6 99
12-17 y, n=144
Schwarz, et al. [16], 2019; 1 or 4 97
3-6 y, n=34
Sofosbuvir and velpatasvir Sokal, et al. [18], 2020; 1-4,6 92 Headache (20%), fatigue (17%),
combination 3-17 y, n=216 vomiting (15%), cough (12%),
nausea (10%)
Jonas, et al. [19], 2019; 1-4,6 >92 A severe adverse effect reported
6-17 y, n=173 was auditory hallucination (0.5%)
Glecaprevir and pibrentasvir Jonas et al. [20], 2020; 1-4 100 Nasopharyngitis (26%), upper
12-17 y, n=47 respiratory tract infection (19%),
headache (14-17%) etc.
Jonas, et al. [21], 2021; 1-4,6 98
3-12 y, n=81
DAA – direct-acting antivirals; SVR 12 – sustained virologic response 12.
severe adverse events or discontinuation [19]. erythematous rash [20]. Both the studies (DORA part 1
Sofosbuvir plus velpatasvir use in pediatric patients aged and DORA part 2) reported only mild to moderate side
3-17 years has been assessed by the phase-2 registration effects commonly as nasopharyngitis (26%), upper
trial (n=216), demonstrating high efficacy (SVR12 in 92% respiratory tract infection (20%), headache (14% to 17%),
cases, virological failure in <1%) [16]. Overall tolerability vomiting (14%), fatigue (11%), fever (11%), diarrhea
of the drug was good, with the common side effects (10%) etc. [20,21]. An added advantage of this
reported in the study were headache (20%), fatigue (17%), combination is its availability in the granule form
vomiting (15%), cough (12%), nausea (10%), etc. and (packaged as sachets) rather than as tablets aiding easier
serious adverse effects in the form of auditory administration, especially in younger children without the
hallucinations in one patient (0.5%) and treatment need to score the tablets. However, it is not yet available
discontinuation due to side effects in 1.3% [18]. Based on in the Indian market, unlike ledipasvir-sofosbuvir and
reports of experience in adults, coadministration with sofosbuvir-velpatasvir combinations. Glecaprevir plus
amiodarone is not recommended due to the risk for pibrentasvir was approved by FDA in 2019 as a pan-
symptomatic bradycardia. Sofosbuvir plus velpatasvir genotypic regimen initially for children above 12 years of
was approved by FDA in 2020 as a pan-genotypic regimen age, followed by an extension to three years or more in
initially for children above six years of age, followed by an 2021 [10].
extension to three years and more in 2021 [10].
Sofosbuvir-Daclatasvir: Abdel Ghaffar, et al. [22], in an
Glecaprevir-Pibrentasvir: Jonas, et al. [20] in part 1 of the open-label, prospective study evaluating the efficacy and
DORA study among 47 adolescents with chronic HCV safety of sofosbuvir-daclatasvir in 40 children (above
infection (genotype 1, 2, 3, 4, or 6) reported a high efficacy eight years of age or >17kg) with genotype 4 HCV
(SVR12 100%) with just eight weeks of treatment duration infection showed high efficacy with SVR12 of 97.5% and
and no serious adverse events or treatment-related no treatment-related serious adverse events or drug
discontinuation. Part 2 of the DORA study supported the discontinuation. The most commonly reported side
approval of glecaprevir plus pibrentasvir in the pediatric effects were cough (8%), fever (5%), and fatigue (5%).
population aged 3 to 11 years, achieving high SVR12 rates Similar results were reported by El-Shabrawi, et al. [23] in a
of 96% (77/80) with no serious adverse events [21]. One study of 10 children with HCV infection (pan-genotypic),
child (1.2%) discontinued the drug due to a non-serious documenting an SVR12 of 100% and no serious adverse

PODDAR, REDDY 59
events. The data to support the use of this combination in adolescents, showed a pooled proportion among those
younger children (above three years of age) was based on receiving all doses of treatment and reaching SVR12 of
modelled pharmacokinetic data in adolescents [24]. Based 100%. Reported side effects were mild, the most common
on this evidence, WHO has recommended using being headache (19.9%) and fatigue (13.9%), while
sofosbuvir plus daclatasvir in children above three years serious adverse events were uncommon, highlighting the
of age regardless of the genotype [25]. However, due to efficacy and safety of the various DAA regimens [26].
lack of well-powered studies and no direct study in
children less than 8 years of age, the combination is not Implications of DAAs for HCV in Children
yet approved by the FDA and is not currently
Although no direct studies are comparing DAAs with the
recommended by the American Association for the Study
older regimens (PEG-IFN and ribavirin), reported
of Liver Diseases (AASLD) and the Infectious Diseases
evidence suggests a high efficacy (92% to 100% vs 58%),
Society of America (IDSA) in the treatment of pediatric
mild or no serious side effects (discontinuation rate due
HCV infection [10].
to adverse effects <1.5% vs 4%) and very low risk of
Indolfi, et al. [26], in a systematic review and relapses (<1% vs 7%) for DAA based regimens over Peg-
metanalysis of 39 pediatric studies (1796 subjects) using IFN plus ribavirin [10,12,27], no need to do a liver biopsy
various combinations of DAA regimens in children and to document significant fibrosis in genotype 1. On the
Fig. 2 Timeline of advancements in HCV discovery and treatment. Colored boxes signify milestones related to the approval of DAA
therapy for children and adolescents.

basis of this well-documented evidence, updated Testing for HCV genotype should be considered for
recommendations paved the way for a completely IFN those in whom it may alter treatment recommendations
and ribavirin-free DAA-based treatment in children based on the age and availability of pan-genotypic
above three years of age irrespective of the genotype regimens. Screening for HBV infection (i.e., HBsAg, anti-
(Fig. 2) [10,25]. Also, therapy with DAAs is indicated for HBc, and anti-HBs) is recommended before initiating HCV
all children (>3 years) with active/current HCV infection DAA therapy due to the risk for HBV reactivation during
(HCV-RNA positive) even if they are asymptomatic or or after treatment.
have normal liver function tests; and liver biopsy is not
Treatment Regimens
necessary for starting treatment [10,28]. The rationale for
this recommendation comes from well-documented Simplified treatment regimens are recommended for
evidence of the high efficacy and safety of DAA combi- treatment-naive or interferon (± ribavirin) experienced
nation regimens in curing HCV infection thus preventing children without cirrhosis and with compensated
the risk of later development of complications like cirrhosis cirrhosis. Approved genotype-based and pan-genotypic
[10,28]. Additionally, curative DAA therapy during DAA regimens and the drug doses are summarized in
childhood or adolescence supports HCV treat-ment by Table II. Decompensated liver disease and recurrent HCV
preventing viral transmission, which is a major pillar in after liver transplantation is rare in children. DAA-
global/national preventive health strategies [10,28]. This experienced pediatric HCV patients are rarely
has led to a significant shift from the historical approach of encountered in clinical practice (Table III).
treatment deferment to a more aggressive strategy of
Treatment in Special Situations
initiating DAA therapy for all children (older than three
years of age) with HCV infection, irrespective of liver Recommendations for treatment of co-infection with HIV,
function tests, genotype, or degree of liver injury [10,28]. co-infection with Hepatitis B, decompensated cirrhosis,
and allograft recipients from HCV viremic donors are
CURRENT RECOMMENDATIONS given in Box I.
Whom and When to Treat CONCLUSION
All children diagnosed with active HCV infection (HCV- There is a paradigm shift in the management of HCV
RNA positive) who are above three years of age should infection in children with the approval of highly effective
be treated with a DAA-approved regimen regardless of and safe DAA therapy. Current guidelines recommend
disease severity, alanine aminotransferase (ALT) levels, only DAA-based combination regimens for treating HCV
genotype, history of treatment experience, and whether infection in children above three years, regardless of liver
the infection is acute or chronic [10]. A liver biopsy is not function test values, duration of infection (acute or
necessary to initiate treatment in children with HCV. chronic), and the genotype. Besides the effectiveness of
Table II Recommended DAA Regimens for Treatment-naive or Interferon-experienced Children and Adolescents Without
Cirrhosis or With Compensated Cirrhosis (Child-Pugh A)
Recommendation Duration of treatment Dose (weight based)
Combination of ledipasvir plus sofosbuvir 12 wk Once daily dose of ledipasvir/sofosbuvir
for children aged ≥3 y with genotype 1, 4, 5, or 6 < 17 kg= 33.75 mg/150 mg
17 to <35 kg = 45 mg/200 mg
≥35 kg=90 mg/400 mg
Combination of sofosbuvir plus velpatasvir 12 wk Once daily dose of sofosbuvir/velpatasvir
for children ≥3 y of age with any genotype < 17 kg= 150 mg/37.5 mg
17-<30 kg= 200 mg/50 mg
≥30 kg=400 mg/100 mg
Combination of glecaprevir plus pibrentasvir 8 wk Once daily dose of glecaprevir/pibrentasvir
for children aged ≥3 y with any genotype < 20 kg= 150 mg/60 mg
≥20 kg to <30 kg= 200 mg/80 mg
≥30 kg to <45 kg= 250 mg/100 mg
≥45 kg or ≥12 y=300 mg/120 mg
A longer duration of therapy (16 wk) may be needed for genotype 3 interferon-experienced patients.
Source: Reproduced from reference 10, with permission.

PODDAR, REDDY 61
Table III Recommended Treatment Regimens for DAA-experienced Children Without Cirrhosis or With Compensated
Cirrhosis (Child-Pugh A)
Recommendation Duration
Genotype 1: Ledipasvir plus sofosbuvir for children aged ≥3 years with prior exposure to interferon 12 wk (without cirrhosis)
(± ribavirin) plus an HCV protease inhibitor regimen 24 wk (with compensated
cirrhosis)
Genotype 4, 5, or 6: Ledipasvir plus sofosbuvir for children aged ≥3 years without cirrhosis or with 12 wk
compensated cirrhosis, having prior exposure to an interferon (± ribavirin) plus an HCV protease
inhibitor regimen
Genotype 1, 2, 4, 5, or 6: Glecaprevir (300 mg) plus pibrentasvir (120 mg) for adolescents aged ≥12 y 8 wk (without cirrhosis)
or weighing ≥45 kg having prior exposure to an interferon-based regimen (± ribavirin) and/or 12 wk (with compensated
sofosbuvir but no exposure to NS3/4A or NS5A protease inhibitors cirrhosis)
Genotype 3: Glecaprevir (300 mg) plus pibrentasvir (120 mg) for adolescents aged ≥12 y or weighing 16 wk
≥45 kg without cirrhosis or with compensated cirrhosis, having prior exposure to an interferon-based
regimen (± ribavirin) and/or sofosbuvir but no exposure to NS3/4A or NS5A protease inhibitors
Genotype 1: Glecaprevir (300 mg) plus pibrentasvir (120 mg) for adolescents aged ≥12 y or weighing 12 wk
≥45 kg without cirrhosis or with compensated cirrhosis, having prior exposure to NS3/4A protease
inhibitors but no NS5A inhibitor exposure
Genotype 1: Glecaprevir (300 mg) plus pibrentasvir (120 mg) for adolescents aged ≥12 years or 16 wk
weighing ≥45 kg without cirrhosis or with compensated cirrhosis, having prior exposure to an NS5A
inhibitor but no NS3/4A protease inhibitor exposure
Source: Reproduced from referemce 10, with permission. DAA-direct-acting antivirals; HCV-hepatitis C virus.
Box I Recommendations for the Management of Hepatitis C in Special Situations
Co-infection with HIV

• All HIV-positive children with HCV co-infection should be started on antiretroviral therapy (ART) irrespective of CD4 cell
count.
• HCV treatment with DAA should be initiated in the presence of HCV viremia.
• ART and DAA regimens should be selected with particular consideration for potential drug-drug interactions.
Co-infection with HBV
• HCV treatment is indicated for children with HCV viremia.
• Treatment of HCV with DAAs may cause reactivation of HBV. Children fulfilling the standard criteria for HBV treatment
should receive antiviral treatment.
• HBsAg-positive patients undergoing DAA therapy should be monitored for HBV DNA every 4 to 8 weeks during treatment
and for three months post-treatment for those who do not meet treatment criteria for HBV.
• Although HCV-positive children with occult HBV infection have a very low risk of HBV reactivation during DAA therapy,
they require close monitoring. Monitoring should be done with ALT levels at baseline, at the end of treatment, and on
follow-up, with HBV-DNA and HBsAg tested in whom ALT levels increase or fail to normalize during or post-treatment.
Decompensated cirrhosis (Rare in children)
• Regimens with extended duration (24 weeks) or the addition of low-dose ribavirin are used in these patients.
• Any protease inhibitor-containing (e.g., glecaprevir, grazoprevir, and voxilaprevir) or interferon-based regimens are
contraindicated.
Allograft recipients (HCV negative recipients from HCVviremic donors)
• Informed consent and formulation of treatment and follow-up strategies are necessary.
• Prophylactic (before HCV RNA results, immediately pre-transplant or day 0 post-transplant) or preemptive (day 0 to within
one-week post-transplant as clinically possible) DAA therapy with a pan-genotypic regimen is recommended.
• For recipients of liver grafts, early treatment within the first two weeks is recommended after a liver transplant.
Source: Reproduced from reference 10, with permission.
DAA therapy, increasing awareness about the mode of subsidized rate in the public sectors are necessary to
HCV spread, better screening (use of ID-NAT-based tests eliminate HCV infection from India without a preventive
in blood banks), and making the DAAs available at a vaccine.

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UPDATE
Management of Hyperbilirubinemia in Newborn Infants 35 or More Weeks

of Gestation: American Academy of Pediatrics, 2022
UMANG BHARDWAJ, VASUDHA KOHLI, ANU THUKRAL
From Division of Neonatology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi.
Correspondence to: Dr Anu Thukral, Associate Professor, Department of Pediatrics, WHO Collaborating Centre for Education and
Research in Newborn Care, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029. dranuthukral@gmail.com
Guidelines for management of hyperbilirubinemia in newborn babies 35 week or more have recently been updated by the American
Academy of Pediatrics (AAP). This article compares the two guidelines (previous guidelines in 2004 and new guidelines) and lists the
changes in diagnosis and management of hyperbilirubinemia proposed in the new guidelines along with implications for our setting.
N
eonatal hyperbilirubinemia is a common decreasing need for sampling. TSB should be done if TcB
problem faced by the pediatricians managing value is within 3mg/dL of phototherapy threshold or ≥15
newborns. It is the seventh most common of mg/dL. New guidelines also advise to consider the rate of
cause of neonatal mortality in first 7 days of rise of bilirubin if multiple values of TcB or TSB are
life worldwide and can lead to devastating long term available, terming rise of ≥0.3 mg/dL/h in first 24 hours
sequelae including kernicterus spectrum disorder (KSD) and ≥0.2 mg/dL/h thereafter as exceptional, indicating
[1]. American Academy of Pediatrics (AAP) recently hemolysis and need for direct antiglobulin test (DAT).
revised their previous guidelines on management of The increased focus on objective measurement by either
hyperbilirubinemia in newborns born at or above 35 TSB or TcB makes it difficult to follow the guidelines
weeks of gestation [2,3]. These guidelines have been strictly in LMICs. This is due to limited availability of TcB
designed primarily for developed countries where disease and even serum bilirubin estimation machines at primary
profile is different and proper facilities for follow-up care and secondary health care settings where infants are first
are available. Infants in developing countries have assessed for jaundice and where the visual inspection
different risk factors (prematurity, sepsis etc.), and (guided by Kramer’s chart) is relied upon for defining the
facilities for prompt detection and treatment are sparse. need for testing [5].
Even so, AAP guidelines have been widely used and
have been referred to in our national guidelines, primarily Among the risk factors for neurotoxicity, asphyxia,
for defining treatment thresholds [4]. Given their routine lethargy, temperature instability and acidosis in the 2004
use, it is important for pediatricians caring for neonates to guidelines have been replaced by the term ‘significant
be aware of the updated changes in these guidelines clinical instability’ in the preceding 24 hours, thereby
(Table I). broadening the scope, depending on the clinical
judgement. This along with sepsis, hypoalbuminemia (≤3
ASSESSMENT, MONITORING AND PREVENTION g/dL), hemolytic disease (including isoimmune, G6PD
OF HYPERBILIRUBINEMIA deficiency or other hemolytic conditions) and low
The new AAP guidelines 2022 re-emphasize the need for gestation age (<38 weeks) are the hyperbilirubinemia
visual assessment of jaundice every 12 hours after birth neurotoxicity risk factors, thereby lowering the threshold
and need to measure either transcutaneous bilirubin for treatment.
(TcB) or total serum bilirubin (TSB) if jaundice is present New guidelines have reinforced the importance of
in the first 24 hours of life. It is now recommended to providing support for breastfeeding and advice that oral
measure bilirubin (TcB or TSB) in all babies between 24 to supplementation with water or dextrose should not be
48 hours of life as visual inspection is deemed far too given to prevent jaundice.
inaccurate to assess the level of jaundice. Although TSB
should be used as the definitive test to guide the need for Blood group and DAT is recommended in all the
phototherapy or exchange transfusion, TcB values are babies born to Rh-negative mother whose antibody
valid for screening the need for TSB estimation and status is unknown; if positive, TSB is recommended 4

64 UPDATE
Table I Important Changes in 2022 Revision of American Academy of Pediatrics Guidelines on Hyperbilirubinemia
2004 Guidelines [2] 2022 Guidelines [3]
Antenatal maternal antibody screening
Maternal screening recommended. No specific or Maternal screening for anti-erythrocyte antibodies in Rh-negative
detailed recommendations for interpretation of DAT mothers, and if positive to test infant for blood group and DAT. A
following anti-Rh prophylaxis use in the mother. positive DAT may be ignored in cases when DAT is positive only for
anti-Rh, and mother turned positive only following anti-Rh prophylaxis.
Screening for jaundice
Universal screening by visual assessment every 8-12 h. Universal TSB or TcB screening is recommended between 24-48 h or
TSB or TcB measurement, if jaundice appears in first prior to discharge if it occurs earlier.
24 h or seems excessive.
Risk factors for significant hyperbilirubinemia
Include lower gestational age, jaundice in the first 24 h, TSB/TcB nearing
PT threshold or use of PT before discharge, hemolytic conditions,
– exclusive breastfed infant with suboptimal intake, scalp hematoma, and
history of PT in parents or siblings.
Additions: Down Syndrome
Omissions: Maternal age, male gender and East Asian race.
Hyperbilirubinemia neurotoxicity risk factors
Albumin <3g/dL, sepsis, isoimmune hemolytic disease, Gestational age <38 wk, albumin <3 g/dL, sepsis, hemolytic conditions
G6PD deficiency, acidosis, asphyxia, and significant and significant clinical instability in previous 24 h.
lethargy.
Breastfeeding jaundice
Formula or EBM supplementation recommended for Better described as Suboptimal intake hyperbilirubinemia. In infants
breast fed infants receiving phototherapy, in case of with TSB nearing the PT threshold, with history suggestive of
excessive weight loss or dehydration. suboptimal feeding and excess weight loss, supplementation with
formula can be considered.
Home-based PT for discharged newborns
Home-based PT may be used for newborns with TSB Home-based PT recommended to be used for discharged newborns who
2-3 mg/dL below the PT threshold, and not to be used meet the following criterion: Gestation ≥38 wk, age >48 h, adequately
in any infant with risk factors. feeding, no risk factors for neurotoxicity, no previous phototherapy,
TSB concentration no more than 1 mg/dL above the phototherapy
treatment threshold, an LED-based phototherapy device available, TSB
measured daily.
Discontinuation of PT
No standard for discontinuation. PT may be disconti- PT can be discontinued when TSB falls 2 mg/dL below the cut-off at
nued when TSB falls below 13-14 mg/dL. which PT was initiated. Longer duration recommended for those with
risk factors for rebound hyperbilirubinemia.
Rebound hyperbilirubinemia
Risk factors: No particular risk factors listed. Gestational age below 38 wk, PT initiation below 48 h,
and hemolytic disease.
Timing of measurement: Within 24 h after discharge, On the day after PT is stopped (at least 12 h, preferably 24 h).
if initiated early, discontinued before 3-4 d of life, and Earlier measurement (at 6-12 h) for those with aforementioned
in a newborn with hemolytic disease. risk factors.
Method: Not mentioned. TcB can be used if at least 24 h have elapsed since stopping PT.
Escalation of care threshold
Definition: No such threshold defined. 2 mg/dL below exchange threshold defined as “escalation of care”
threshold.
IVIG recommended in isoimmune hemolytic disease Treatment/monitoring: NICU admission, intravenous hydration and
TSB within 2-3 mg/dL of exchange threshold. intensive PT.
contd....

BHARDWAJ, ET AL. 65
Table I continued
2004 Guidelines [2] 2022 Guidelines [3]

Consider IVIG in isoimmune hemolytic disease. 2-hourly TSB
monitoring to be done till it falls below the threshold.
Workup: Measure total and direct bilirubin, albumin, blood chemistry,
blood group, send for cross match to arrange blood for ET, CBC, and
G6PD levels in all these infants.
Exchange transfusion (ET)
For readmitted infants, ET considered only if TSB Recommended for ABE or TSB at exchange cut-offs. Recommendations
remained above exchange threshold after 6 h of no longer vary for during birth hospitalization and readmissions in this
intensive PT (except for those infants who presented regard.
with features of ABE).
Hematocrit of blood: Not specified Recommend use of blood with 40% hematocrit for ET for the benefit of
increasing bilirubin clearance with additional albumin.
Risk assessment before discharge and subsequent follow up
Schedule based on Bhutani nomograms for risk stratifi- Schedule based on difference between pre-discharge TcB/TSB (measured
cation, based on pre-discharge bilirubin (TcB or TSB). at least 12 h after birth) and phototherapy cut-off.
ABE-acute bilirubin encephalopathy, CBC-complete blood count, DAT-direct antiglobulin test, EBM-expressed breast milk, ET-exchange
transfusion, G6PD-glucose-6-phospphate dehydrogenase, IVIG-Intravenous Immunoglobulin, PT-phototherapy, TcB-transcutaneous bilirubin,
TSB-total serum bilirubin.
hourly twice followed by 12 hourly, along with early Discontinuation of phototherapy, which was earlier
initiation of phototherapy. advised at TSB <13-14mg/dL, is now advised when TSB
falls 2mg/dL below the threshold at which it was started.
In case of prolonged jaundice persisting beyond 3-4
Further fall in TSB may be targeted if there is a substantial
weeks in breastfed and 2 weeks in formula-fed babies,
risk of rebound hyperbilirubinemia (as suggested by age
measurement of TSB with direct bilirubin is
<48 hours at start, gestational age <38 weeks or in setting
recommended, along with evaluation for hypothyroidism.
of hemolytic disease) [7]. In these cases, it is also advised
TREATMENT OF HYPERBILIRUBINEMIA to measure TSB 6-12 hours after stopping phototherapy.
In others, TSB is to be repeated the day after stopping
New guidelines have raised the threshold for initiation of
phototherapy. TcB can replace TSB if used at least 24
phototherapy and exchange transfusion at all gestations,
hours after stopping phototherapy [8].
recognizing that bilirubin neurotoxicity occurs well beyond
the threshold of 2004 guidelines [6]. While raising these Major additions to these guidelines are statements
thresholds, it is emphasized that these guidelines are about “escalation of care” when TSB approaches
applicable only to developed nations as they require strict exchange transfusion (ET) threshold (defined as 2 mg/dL
monitoring and follow-up post discharge and thus may not below ET threshold). Escalating care, described as a
be applicable if follow-up is uncertain, as is often the case in medical emergency, includes immediate admission to
resource-limited settings. To mitigate the issue of uncertain NICU with facility of ET, intensive phototherapy,
follow-up in LMICs, some experts advocate a lower intravenous hydration, blood tests for albumin, TSB,
threshold for initiation of treatment in secondary care direct bilirubin, and arranging blood for ET. It is followed
settings, while maintaining the same cut-offs in tertiary care by TSB measurement at two-hourly intervals till TSB falls
settings given that the follow up is certain and regular [5]. below escalation value.
In the new guidelines, hour-specific phototherapy Guidelines maintain previous stand of optional
and exchange transfusion thresholds have been provided treatment with intravenous immunoglobulin (IVIG; 0.5-
for each week of gestation age from 35 to 40 weeks in the 1g/kg)over 2 hours in patients with isoimmune hemolytic
low-risk group and 35 to ≥38 weeks for babies with disease which can be repeated after 12 hours if they
hyperbilirubinemia neurotoxicity risk factor group. New require escalation of care [9].
thresholds also consider the postmenstrual age of the
neonate and suggest that TSB should be measured within Any infants showing signs of advanced bilirubin
12 hours after starting phototherapy. encephalopathy (hypertonia, retrocollis, and apnea)

66 UPDATE
should receive ET irrespective of TSB. Blood with phototherapy may be initiated in the first few hours of life.
hematocrit of 40% is preferred for ET, with the rationale Another example is the recommendation to use blood
that it would provide additional albumin augmenting with hematocrit of 40% for ET. It will be interesting to see
binding of bilirubin. if there is an increase in the requirement of subsequent
packed RBC transfusion in these babies. So, it is prudent
Post-discharge follow up is now based on the
that the experience and practical issues faced with the
difference between TcB/TSB value at discharge and
new guidelines are reported and recommendations more
phototherapy threshold. Use of risk nomogram by
suitable to our setting can be formulated.
Bhutani, et al. [10] for this purpose is no longer advised as
they do not consider gestational age and risk factors. Contributors: UB, VK: drafted the manuscript; AT: reviewed and
edited the manuscript and provided important additional insights.
IMPLICATIONS FOR PRACTICE All authors approved the final version of manuscript, and are
accountable for all aspects related to the study.
The actual impact of new thresholds on number of babies Funding: None; Competing interests: None stated.
receiving phototherapy and exchange, and by extension,
on the healthcare system, will become clear in future. REFERENCES
Considering that the treatment threshold has been 1. Iskander I, Gamaleldin R. Acute bilirubin encephalopathy:
increased for all gestations, there is a probable potential Some lessons learned. Semin Perinatol. 2021;45:151353.
to decrease the treatment requirement and the duration of 2. Subcommittee on Hyperbilirubinemia. Management of
hospital stay. However, there is an invigorated emphasis Hyper- bilirubinemia in the Newborn Infant 35 or More
on monitoring and follow up, and a recommendation for Weeks of Gestation. Pediatrics. 2004;114:297-316.
rapid and timely escalation of care. This is aided by TcB 3. Kemper AR, Newman TB, Slaughter JL, et al. Clinical
machine facilitating rapid serial evaluation, which is still practice guideline revision: Management of hyperbili-
rubinemia in the newborn infant 35 or more weeks of
not readily available in our setting. Availability of TcB
gestation. Pediatrics. 2022;e2022058859.
machines at delivery centers or alternative like smart 4. Anand PS, Gopalakrishnan S, Sachdeva A, et al. Screening,
phone applications or newer point of care serum bilirubin prevention, and management of neonatal hyperbili-
machines along with structured follow-up schedule is rubinemia. J Neonat. 2020;34:153-69.
imperative for successful adoption of these guidelines. 5. Olusanya BO, Ogunlesi TA, Kumar P, et al. Management
Individual centers will need to devise an effective of late-preterm and term infants with hyperbilirubinaemia
machinery to provide optimal follow up services bearing in resource-constrained settings. BMC Pediatr. 2015;15:39.
in mind that increased treatment threshold carries a 6. Wu YW, Kuzniewicz MW, Wickremasinghe AC, et al. Risk
potential of devastating consequence of chronic bilirubin for cerebral palsy in infants with total serum bilirubin levels
at or above the exchange transfusion threshold: a
encephalopathy if follow up is inadequate. This can be
population-based study. JAMA Pediatr. 2015;169:239.
done by making the follow up for jaundice an essential 7. Chang PW, Kuzniewicz MW, McCulloch CE, Newman TB.
part of neonatal care and making the discharging unit A clinical prediction rule for rebound hyperbilirubinemia
responsible for follow up. Additionally, the risk factors following inpatient phototherapy. Pediatrics. 2017;139:
including infection are also different in LMICs. The e20162896.
contribution of infections to severe jaundice or 8. Grabenhenrich J, Grabenhenrich L, Buhrer C, Berns M.
kernicterus has been reported to vary from 14% in Africa Transcutaneous bilirubin after phototherapy in term and
to 31% in Asia, compared with 2% in major HICs [11]. preterm infants. Pediatrics. 2014;134:e1324-9.
Delays in delivering effective treatments, routinely 9. Slaughter JL, Kemper AR, Newman TB. Technical Report:
Diagnosis and management of hyperbilirubinemia in the
available in developed countries, continue to account for
newborn infant 35 or more weeks of gestation. Pediatrics.
the high burden of neonatal hyperbilirubinemia in LMICs. 2022;e2022058865.
Besides evaluation, it is evident that treatment 10. Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a
guidelines cannot be implemented in their entirety in our predischarge hour-specific serum bilirubin for subsequent
significant hyperbilirubinemia in healthy term and near-
settings. Home phototherapy would not be feasible in
term newborns. Pediatrics. 1999;103:6-14.
most cases. Additionally, the recommendation to stop 11. National Institute for Health and Care Excellence. Neonatal
phototherapy only after TSB is 2 mg/dL below the initial jaundice: Clinical guideline 98. May, 2010. Accessed
phototherapy threshold is impractical to be applied in November 10, 2022. Available from: https://www.nice.org.
case of isoimmune hemolytic anemia, where the uk/guidance/cg98

Reminiscences from Indian Pediatrics: A Tale of 50 Years
Lead Toxicity: The Unbeaten Menace

NIDHI BEDI
From the Department of Pediatrics, Faculty of Medical and Health Sciences, SGT University, Gurugram, Haryana.
Correspondence to: Dr Nidhi Bedi, Associate Professor, Department of Pediatrics, Faculty of Medical and Health Sciences,
SGT University, Gurugram, Haryana. drridhibedi@gmail.com
D
espite it being known for centuries that lead is encephalopathy group, respectively, showed raised lead
toxic to man, the uncontrolled hazard continues levels as against 3.3% children in control group. Abdominal
to affect millions of human pain in association with pica or
lives till date. As per Global encephalopathy was a significant factor.
burden of disease dataset 2019, nearly Urinary coproporphyrin levels showed
800 million children in world have unsafe no significant correlation with blood
levels of lead in body, more than 50% of lead levels. The most common sources
whom belong to South East Asia [1]. of lead cited were surma, sindoor, holi
Talking about India alone, we have almost colors and morning sample of drinking
a whopping 275 million kids with water from tap (lead pipes were used
elevated lead levels, highest among all then). Flaking paint as pica was more
countries [1]. Further, India accounts for prevalent in the West, as against mud or
26% of global deaths due to lead white washed walls in India during those
poisoning, 2,30,000 premature deaths times. Other sources quoted in various
recorded in the year 2017 alone [2]. An studies at that time included lead bottles,
increase of 53% and 30% in rates of lead containing medications (especially
deaths and disability due to lead skin and herbal), adulterated spices, lead
poisoning has been reported since 1996- foils and glazed pottery.
2000 [2]. Over the last five decades, the Industrialization was an upcoming cause
sources of lead in human life have changed, diagnosis has as an environmental lead contaminant.
evolved, and the management has refined but the menace
continues unabated. THE PRESENT
THE PAST Fifty years down the lane, a lot has changed but the
menace of lead toxicity continues. No lead levels are
The study by Sinclair, et al. [3] 50 years back, was considered safe but as one of the major revisions made by
conducted to measure blood lead levels in symptomatic World Health Organization (WHO) and Centre for
children and results compared with the control group. A Disease Control (CDC), blood levels >5 µg/dL has been
lead level of 60 µg/100 mL of blood was considered as labelled as unsafe [3]. In 2021, the Lead Exposure and
abnormally high. The study divided the children into three Prevention Advisory Committee (LEPAC) further
groups, group 1 of 50 children with history of pica with recommended CDC to use a blood reference value of 3.5
anemia or/and abdominal pain or/and neurological µg/dL to identify children with high blood lead levels [4].
abnormalities; group 2 of 25 children with acute
encephalopathy and group 3 of 30 children with diseases As per the United Nations Children Fund (UNICEF)
not associated to lead poisoning. The authors also checked and non-profit Pure Earth 2020, a third of the world’s
urinary coproporphyrin and X-ray of long bones in children children, nearly 800 million, are affected by lead
with high blood lead levels. The study results suggested a poisoning, of which India accounts for 275.5 million [1].
high mean blood lead level in children with pica (68.1 µg/ A loss of up to 5 IQ points has been noted with lead
100 mL) and encephalopathy (79.4 µg/100 mL) when poisoning [5]. Other associated features include reduced
compared to controls (28.7µg/100 mL). Of the total attention span, leaning disabilities, behavioral disorders,
children in each group, 46% and 36% children in pica and abdominal pain, anemia and encephalopathies.

68 TALE OF FIFTY YEARS
Multiple studies have since been done across India, paints and artificial jewelry, other sources of lead
including Delhi-NCR (National Capital Region) regions exposure include glazed pottery, fossil fuel burning and
to assess blood lead levels and its sources in children. In a some healthcare products including herbal medicines
study conducted in India by George foundation under [13-15].
‘Project Lead Free’ in late nineties, 22,000 children were
THE FUTURE
screened for high lead levels (>10 ìg/100 mL), 51% of
which were found to be positive [6]. In spite of phasing Pediatricians and health care workers should routinely
out of leaded gasoline, considered as one of the major assess the environmental exposure to lead in their OPD
causes of lead toxicity in nineties, children affected with practices. All children with symptoms suggestive of lead
lead toxicity continued to increase [2,7]. In a meta- levels or with history suggestive of high environmental
analysis published in 2018, 31 studies assessing blood exposure should be screened for blood lead levels. Those
lead levels in Indian population were included. The study found to have high levels should immediately be removed
showed mean BLL of 6.86 µg/dL (95% CI: 4.38-9.35) in from the source of contamination. Others should be
children, which is above the safe levels [8]. counselled on the sources of lead exposure and their
prevention. Those with iron deficiency should be treated
In a major study conducted in Delhi by the Energy with iron supplementation as lead absorption increases in
and Resources Institute (TERI) and UNICEF in 2012 [9], the presence of iron deficiency. Specific treatment in
23% of children living along the Yamuna river had lead terms of chelation therapy should only be initiated in high
levels more than 10 µg/dL. The most probable expla- lead exposure (>44 µg/dL), after consultation with an
nation given is contamination of water by dumping of expert and knowing the risks and benefits of the therapy
industrial wastes. The food grown in the nearby soil, [16].
especially green vegetables like spinach have high metal
content. Through this contaminated food and water, lead An urgent need of a government action plan is needed
enters the human body causing various health effects. In at state and national level to tackle the rising risk of lead
another study done in Delhi school children aged 4-6 poisoning. Joint efforts by policy makers and the people
years [10], it was found that nearly 18% children had of country can help us to curb this silent killer [17].
elevated lead levels (>10 µg/dL) [10]. The same author Funding: None; Competing interests: None stated.
conducted a similar study 10 years later in another subset
REFERENCES
of Delhi school students aged 6-10 years [11], and found
12% of children to have elevated lead levels (>10µg/dL), 1. Rees N, Fuller R. The toxic truth: children’s exposure to lead
giving a ray of hope, though the fall could be attributed to pollution undermines a generation of future potential.
many other reasons such as area of study, surrounding UNICEF and PURE EARTH; 2020. Accessed on Dec 16,
2022. Available from: http://www.unicer.org/media/
industry and less incidence of pica in this age group.
109361/ile/The%20toxic%20truth.pdf
With the phasing out of leaded gasoline, a fall in 2. GBD Compare. Institute for Health Metrics and Evaluation;
percentage of children with elevated blood lead levels 2020. Accessed on Dec 10, 2020. Available from: https://
www.healthdata.org/data-visualization/gbd-compare
was expected but the same did not happen, due to rapidly
3. Centre for Disease Control. Blood lead levels in children,
expanding industrialization. In the present scenario, CDC. Accessed on Dec 11, 2020. Available from: https://
industrialization and its effluents have become the major www.cdc.gov/nceh/lead/prevention/ blood-lead-levels.htm
source of lead contamination of environment. In 2009, a 4. Blood Lead Reference Value. Accessed on Dec 15, 2020.
study from Delhi measured the lead loading in household Available from: https://www.cdc.gov/nceh/lead/data/blood-
dusts [12]. The geometric mean of dust lead loading for lead-reference-value.htm
floor and interior window sill samples was found to be 5. A third of world’s children are poisoned by lead, says
19.7 μg/ft2 and 75.5 μg/ft2, respectively. This was much UNICEF report. Accessed on Dec 8, 2022. Available at
more than the geometric means of same samples checked https://www.downtoearth.org.in/news/health/a-third-of-
world-s-children-are-poisoned-by-lead-says-unicef-report-
in US in 2000 and recorded as 1.1 μg/ft2 and 9.4 μg/ft2 in
72560.
floor and windowsill samples, respectively [12]. 6. The George Foundation: Lead poisoning. Available at http:/
/tgfworld. org/lead.html. Accessed on 12th December 2022.
Among other causes of lead exposure, recent studies
7. Sharma S, Mitra P, Bhardwaj P, Sharma P. Blood lead level
have shown a very high level of lead found in paints in school going children of Jodhpur, Rajasthan, India. Turk J
(especially yellow paint), and artificial jewelry Biochem 2021; 46: 393-98.
(maximum in pink color), crossing the permissible limits 8. Ericson B, Dowling R, Dey S et al. A meta-analysis of blood
by almost 1000 times. Besides industrial waste lead levels in India and the attributable burden of disease.
(especially lead-based industrial products like batteries), Environ Int. 2018;121:461-70.

TALE OF FIFTY YEARS 69
9. Chauhan C. High lead found in 23% children living close to Delhi: NGO. Accessed on Dec 14, 2022. India Today; July 2,
Yamuna: Study. Hindustan Times; Feb 16, 2012. 2010.
10. Kalra V, Chitralekha KT, Dua T, Pandey RM, Gupta Y. 15. Jain NB, Hu H. Childhood correlates of blood lead levels in
Blood lead levels and risk factors for lead toxicity in children Mumbai and Delhi. Environ Health Perspect.
from schools and an urban slum in Delhi. J Trop Pediatr. 2006;114:466-70.
2003 Apr;49(2):121-3. 16. Pediatric Environmental health Specialty Units.
11. Kalra V, Sahu JK, Bedi P, Pandey RM. Blood lead levels Recommendations on Management of Childhood Lead
among school children after phasing-out of leaded petrol in Exposure A Resource for Clinicians; Updated Dec, 2021.
Delhi, India. Indian J Pediatr. 2013 Aug;80(8):636-40. Accessed on Dec 16, 2022. Available from: https://www.
12. Kumar A, Scott Clark C. Lead loadings in household dust in pehsu.net/_Library/facts/PEHSU_Fact_Sheet_Lead_
Delhi, India. Indoor Air. 2009;19:414-20. Management_Health_Professionals_9_2021.pdf
13. Singh P. Over 73 per cent of paints found to have excessive 17. ANI. Urgent State and National Level Action Plans needed
lead: Study. Times of India; Oct 30, 2015. to tackle lead poisoning in India: Experts. ANI; Oct 11,
14. PTI. Lead content high in children’s jewellery found in 2022.
ADVERTISEMENT

70 OBITUARY
OBITUARY
Dr. Natesan Janakiraman
(1 August, 1930 – 30 November, 2022)
Dr. Natesan Janakiraman passed away peacefully in Chicago on 30th November, 2022, after a brief illness, at
the age of 92.
Dr. Janakiraman was born on August 1, 1930 in Rangoon, Burma. His family fled to Madras by land to escape
the Japanese invasion of Burma during World War II. He completed his medical education in Madras and then
worked in small villages before migrating to the USA, where he joined Cook County Hospital in Chicago as an
Intern. He spent his entire professional career here. He set up the first PICU at Cook County Hospital. He also
became the Dean of the Chicago Medical School. In these capacities, he mentored an entire generation of
medical students and pediatric residents. Dr. Jay, as he was fondly called, was known for his clinical acumen
and humane approach to medicine.
In the early 1990s, Dr. Jay brought the Pediatric Advanced Life Support (PALS) course of the American Heart
Association to India and conducted India’s first PALS program in Madras. Subsequently, he conducted several
additional PALS courses all over India and was instrumental in setting up the PALS training program in India.
He was a known for his no nonsense approach and would not allow delegates to enter even if they were a few
minutes late. He did not hesitate to fail senior professors if they were not up to the mark.
Dr. Jay attended various Pediatric Intensive Care Conferences in India whenever he visited. He was known for
his humility and gentle powers of persuasion.
The entire Pediatric Intensive Community in India owes a huge debt of gratitude to Dr. Jay. He is survived by
his wife, Vatsala, two daughters and several grandchildren.

RESEARCH LETTERS
Multisystem Inflammatory Syndrome in Table I Characteristics of Patients With Multisystem

Inflammatory Syndrome in Children (MIS-C) Following
Children (MIS-C): Comparison of the the First and the Second Wave of Coronavirus Disease 2019
First and the Second Waves (COVID-19), Kolkata
Clinical presentations First wave Second wave
This study comparing the different parameters of children suffer- (n=75) (n=48)
ing from multisystem inflammatory syndrome in children (MIS-C) in
Kolkata, India, during the two waves (July, 2020-January, 2021 Age (y)a 5.66 (3,8) 4.62 (1.7,7)
and April-July, 2021) showed that the second wave had a higher History of SARS-CoV-2 positivity 32 (42.5) 33 (68.75)
propensity of Kawasaki disease (KD)-like presentation, cardiac
Rash 64 (86) 19 (39.5)
affection and pediatric intensive care unit admission, and in-
creased incidence of use of steroids for treatment. Abdominal symptoms 53 (70.6) 20 (41.6)
Keywords: Delta variant, Kawasaki disease, Steroids. Only febrile phenotype 3 (4) 13 (27.1)
Myocarditis 21 (28) 19 (39.5)
Coronary artery dilatations 22 (29.3) 23 (47.9)
Multisystem inflammatory syndrome in children (MIS-C) is PICU admission 34 (45.3) 28 (58.3)
a well described hyperinflammatory syndrome occurring 2-8
Death 0 3 (6.3)
weeks after symptomatic/asymptomatic severe acute
respiratory syndrome 2 (SARS-CoV-2) infection [1,2]. The Treatment
first MIS-C wave hit eastern India around July, 2020 and Intravenous immunoglobulin (IVIG) 29 (38.7) 0
lasted till January, 2021. The second wave of MIS-C started IVIG + steroids 43 (57.3) 32 (66.6)
Only steroids 4 (5.3) 14 (29.1)
in April, 2021 and went on till July, 2021. The second
Biologics (infliximab) 0 3 (6.3)
coronavirus disease 2019 (COVID-19) wave in India was
mainly of the Delta variant, and resulted in higher number of Data presented as no. (%) or amedian (IQR). SARS-CoV-2-severe acute
hospital admissions in adults and increased mortality [3]. respiratory syndrome coronavirus 2; PICU-pediatric intensive care unit.
The second wave of MIS-C that occurred in the aftermath of
this COVID wave was shorter lasting, but like the adult Delta significant during the second wave, presence of rashes and
wave, was more intense, affecting a higher number of abdominal symptoms were significant during the first wave.
children younger than 5 years.
The second wave also saw a paradigm shift in
This is a single-center study of MIS-C patients management, with an increased early use of steroids.
diagnosed by the World Health Organization (WHO) During the first wave, especially in the earlier months, there
criteria admitted at Institute of Child Health, Kolkata, a was a predominance of intravenous immuno-globulin (IVIG)
tertiary care pediatric hospital in eastern India. Hospital use. However, with passage of time and experience, use of
records of the clinical presentations, laboratory data, methylprednisolone increased with the result that none of
echocardiographic features, treatment protocols and the patients were treated by only IVIG during the second
outcomes of these patients were retrieved from hospital wave. On the contrary, many patients without myocarditis
records and analyzed. responded only to methylpre-dnisolone and did not require
IVIG. Use of early steroids increased, and only patients with
The comparative data between the two waves of MIS-C
myocarditis and KD-like presentation received IVIG.
are summarized in Table I. There was an appreciable change
Infliximab was used by us in three IVIG and steroid resistant
in the clinical picture with increased incidence of patients
KD-like patients, who also had coronary artery dilatations.
presenting with only fever without organ involvement,
and Kawasaki disease (KD)-like presentations. Majority of We had previously done a retrospective analysis on the
children during the first wave had abdominal symptoms and use of steroids in treating MIS-C [5]. We found that more
rashes, the numbers were much less during the second severe cases of myocarditis with reduced ejection fraction
wave; but there was a higher propensity of cardiac affection required steroids in addition to IVIG for treatment. During
and need for pediatric intensive care unit (PICU) admission. the second wave, we initiated treatment with
Statistical analysis of the results by the assumptions of the methylprednisolone in all and IVIG was added in patients
two sample z-proportion hypothesis test showed that with severe myocarditis presenting with shock. Patients
history of SARS-CoV-2 positivity was statistically presenting with features of myocarditis and shock were

72 RESEARCH LETTER
started on pulse methylprednisolone (10 to 30 mg/kg/day), REFERENCES

sicker children received higher doses, usually resulting in
1. Dhanalakshmi K, Venkataraman A, Balasubramanian S, et al.
clinical improvement by the next 2 to 3 days. Epidemiological and clinical profile of pediatric
There was no mortality during the first wave, whereas inflammatory multisystem syndrome-temporally associated
there were three deaths during the second wave; one due with SARS-CoV-2 (PIMS-TS) in Indian children. Indian
Pediatr. 2020;57: 1010-1014.
to refractory macrophage activation syndrome (MAS)
2. World Health Organization. Multisystem Inflammatory
and two with late referral, who succumbed to severe
Syndrome in Children and Adolescents Temporally Related
myocarditis and refractory hypotension. to COVID-19. WHO; 15 May, 2020. Accessed on Nov 31,
The antigenic shift of the virus led to differences in 2022. Available from: https://www.who.int/news-room/
severity and outcome between the two COVID waves. commentaries/detail/multisystem-inflammatory-syndrome-
in-children-and-adolescents-with-covid-19
This difference was also evident amongst the MIS-C
3. Kumar S. Second wave of COVID-19: emergency situation
patients with change in clinical presentations, the Delta in India. J Travel Med. 2021;28:aab082.
variant leading to a disease of increased severity and 4. Ganguly M, Nandi A, Banerjee P, et al. A comparative study
poorer outcome. of IL 6, CRP and NT proBNP levels in post COVID
Funding: None; Competing interests: None stated. multisystem inflammatory syndrome in children (MISC)
and Kawasaki disease patients. Int J Rheumat Dis.
MIMI GANGULY, PURBASHA GUPTA, DEBOPAMA BISWAS, 2022;25:27-31.
SUBHAJIT DEY SARKAR, PRIYANKAR PAL* 5. Pal P, Bathia JN, De H, et al. A retrospective analysis of the
Pediatric Rheumatology Unit, Institute of Child Health, need for methylprednisolone in addition to IVIG for treating
Kolkata, West Bengal. multisystem inflammatory syndrome in children. Rheuma-
*mailme.priyankar@gmail.com tology. 2022;61:e141-2.
Neonatologist-Performed Ultrasound- of cannulation failure as compared to conventional

approach [3]. Literature on neonatal USG-guided IJV
Guided Internal Jugular Vein cannulation is limited, and has been mainly described by
Cannulation anesthesiologists or pediatric surgeons [2,4-6].
We describe the success rate and complications of
neonatologist-performed USG-guided IJV cannulation
We retrieved data of ultrasound-guided neonatal internal jugular
vein (IJV) cannulations done between November, 2020 and
March, 2021. Of the 33 ultrasound-guided IJV cannulation in
neonates, 32 were successful with overall success rate of 97%.
Median (IQR) number of attempts per insertion was 2 (1,3.5).
There were no major complications observed during the inser-
tion of the catheter. In one instance, inadvertent carotid artery
puncture was encountered, without significant bleeding.
Key words: Central line, Percutaneous, Simulation, Training.
Trial registration: CTRI/2021/07/034944
Traditionally, cannulation of internal jugular vein (IJV) is

performed by a ‘blind’ technique based on anatomical
landmarks [1]. This technique; however, has a high failure
rate and may be associated with several complications
such as inadvertent carotid artery puncture, pneumo-
Fig. 1 Chicken breast simulator and its ultrasound image. Left
thorax or hemothorax, and formation of hematoma, side shows one chicken breast with dye filled tube. It is covered
particularly in young infants [1,2]. Ultrasound (USG)- with another breast on top and wrapped with a plastic cover.
guided IJV cannulation is a standard technique in Right side shows ultrasound image of model casting an acoustic
pediatric population and is reported to have reduced risk shadow resembling a large vein.

RESEARCH LETTER 73
from a tertiary care unit. The unit is a 32-bedded level 3B complications were routinely recorded on the patient’s
accredited neonatal intensive care unit. The unit has more case record. Maximum five attempts were made, following
than 1200 admissions per year, of which approximately which the procedure was abandoned. Cardiac tamponade
60% are extramural neonates; most being referred in was identified by sudden onset hypotension, muffled
critical condition such as hypoxic respiratory failure or heart sounds and enlarged cardiac silhouette on radio-
shock, without any reliable venous access. In this graph. Cardiac arrhythmia was defined as any change in
retrospective study, demographic and clinical details of the normal sequence of heart rhythms during or after
neonates who underwent IJV cannulation between catheterization and confirmed on electrocardiogram.
November, 2020 and March, 2021 were retrieved. Outcome Central line-associated blood stream infection was
measures were success of cannulation, number of attempts defined as positive blood culture not related to an
per cannulation, catheter dwell time, and complications infection at another site, when the jugular line was in
such as carotid artery puncture, pneumothorax, hematoma place at the time of or within 48 hours before the onset of
formation, cardiac tamponade, arrhythmia and central line- infection.
associated blood stream infection. The study was
During the study period, a total of 33 IJV cannulations
approved by institutional ethics committee and registered
were performed on 29 neonates. Of these, 32 (97%) were
with the Clinical Trial Registry of India. The neonato-
successful. Median (IQR) number of attempts per
logists acquired necessary training and expertise by first
insertion was 2 (1, 3.5). All IJV cannulation were
observing the cannulation performed by interventional
performed on extra-mural neonates, who had no access
radiologists, and then practicing puncturing at artificial
for umbilical or peripherally inserted central venous
targets in phantom models. This was followed by training
catheters. Majority (68.2%) of cannulations were
on a simulation model, prepared by placing a rubber tubing
performed on right IJV. The mean (SD) birth weight and
filled with fluid, tunnelled in between chicken breast pieces,
gestation of neonates were 2405 (860) g and 35.17 (4.2)
tightly wrapped in a plastic cover (Fig. 1) [7].
weeks, respectively. Nineteen neonates were mechani-
cally ventilated at the time of line insertion. Cumulative
All IJV cannulations were performed by one of the
success rate with first, second and third attempt was 39%,
two neonatologists, using Sonosite M Turbo machine
51.5% and 75.8%, respec-tively. Median (IQR) catheter
with 13-6 MHz linear probe. Informed consent was
dwell time was 13.5 (7.0, 17.5) days. There were no major
obtained from the parents before the procedure.
complications observed during insertion of catheter. In
Neonates were positioned in the Trendelenburg position
one neonate, who was extremely preterm, inadvertent
by placing a shoulder roll and head was tilted to the
carotid artery puncture occurred without significant
opposite side. We used short-axis, out-of-plane method,
bleeding. Attempt to cannulate was unsuccessful in
in which, USG probe was kept in a perpendicular manner,
another neonate, who was born at term gestation. In this
approximately at the base of Sedilot triangle to visualize
patient, cannulation was attempted without use of
IJV and surrounding structures in cross section. Internal
sedation, as there was no IV access available prior to
jugular vein was differentiated from carotid artery based
procedure. Central line associated blood stream infection
on its ellipsoid shape, larger size, presence of compressi-
was reported in three cases. All except three catheters
bility and absence of pulsatility. Venepuncture was
were removed once not required. One catheter was
performed under real time USG visualization with a 22-
removed on day 8 of insertion due to local extravasation,
gauge cannula, introduced just behind the mid-point of
while two were removed on day 15 and day 22 due to
the probe, at an angle 45-60% and directing it towards the
catheter occlusion.
ipsilateral nipple. Non-dominant hand was used to hold
the probe and dominant hand was used for needle Literature regarding feasibility and success rate of
puncture. Successful puncture was ascertained by free neonatologist-performed USG-guided IJV insertion is
flow of blood through the cannula, following which a limited. Goldstein, et al. [5] reported feasibility of USG-
guide-wire of calibre 0.46 mm was introduced through it. guided IJV cannulations in 20 neonates, which were
Subsequently, cannula was removed, while keeping guide performed by pediatric surgeons or anesthesiologists [5].
wire in place and a catheter of 22-gauge, 4 cm length Cannulations were performed successfully in all neonates
(leaderflex, Vygon) was threaded over the guide wire without any complication related to the procedure.
using Seldinger technique. Following this, guide-wire Similarly, Tapia, et al. [2], in a case series of USG-guided
was removed and line was secured, after ensuring free IJV cannulation performed on neonates by pediatric
flow of blood. Radiograph was done to confirm tip surgeons, observed a high success rate (94%) with
position and to evaluate for complications such as median (IQR) number of attempts 2 (1,8). Authors
pneumothorax or hemothorax. Number of attempts and reported procedure related complications in none of the

74 RESEARCH LETTER
neonates [2]. Oh C, et al. [4] reported serious complication ANUP THAKUR,* MANOJ MODI, NEELAM KLER,
in one out of 12 IJV cannulations performed by pediatric PANKAJ GARG
surgeons, in the form of hemoericardium [4]. Department of Neonatology, Institute of Child Health,
Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi
USG-guided cannulation of peripheral veins in *dr.thakuranup@gmail.com
neonates is technically challenging as these vessels have REFERENCES
a narrow lumen and small diameter. We performed IJV
cannulation in extramural neonates, in whom the umbilical 1. Troianos CA, Hartman GS, Glas KE, et al. Councils on
and peripheral veins were exhausted. Internal jugular vein Intraoperative Echocardiography and Vascular Ultrasound
of the American Society of Echocardiography. Guidelines
was preferred over femoral veins as it is a larger and more
for Performing Ultrasound Guided Vascular Cannulation:
easily accessible vein with a diameter that exceeds femoral
Reco-mmendations of the American Society of Echocardio-
vein by at least 50% [8]. We used single tube, chicken graphy and the Society of Cardiovascular Anesthesiologists.
breast simulation model for training. Further improvement J Am Soc Echocardiogr. 2011;24:1291-318.
of this model can be done by inserting another fluid-filled 2. Montes-Tapia F, Rodríguez-Taméz A, Cura-Esquivel I, et
tube to simulate carotid artery and therefore enhancing al. Efficacy and safety of ultrasound-guided internal jugular
skills to avoid carotid artery puncture. vein catheterization in low birth weight newborn. J Pediatr
Surg. 2016;51:1700-3.
To the best of our knowledge, this is the first 3. de Souza I, Brandao, MB, Nadal JH, Nogueira RJ.
feasibility report of neonatologist-performed USG-guided Ultrasound guidance for pediatric central venous catheteri-
IJV cannulation. Our findings suggest that neonato- zation: A meta-analysis. Pediatrics. 2018;142: e20181719.
logist-performed USG-guided IJV cannulation is feasible, 4. Oh C, Lee S, Seo JM, Lee SK. Ultrasound guided per-
with success and complication rates comparable to those cutaneous internal jugular vein access in neonatal intensive
reported with other interventional operators [2,4-6]. care unit patients. J Pediatr Surg. 2016;51:570-2.
Before contemplating the procedure on neonates, inten- 5. Goldstein SD, Pryor H, Salazar JH, et al. Ultrasound-guided
percutaneous central venous access in low birth weight
sivists should acquire adequate skills by undergoing
infants: Feasibility in the smallest of patients. J Laparo-
systematic training on simulation models. endosc Adv Surg Tech A. 2015;25:767-9.
Ethics clearance: EIC, Sir Ganga Ram Hospital, No. EC/04/21/ 6. Uzumcugil F, Yilbas AA, Akca B. Ultrasound-guided
1875, dated June 08, 2021. anatomical evaluation and percutaneous cannulation of the
Contributors: AT, MM: conceptualized the project; AT: wrote the right internal jugular vein in infants <4000 g. J Vasc Access.
protocol and had primary responsibility of patient screening, 2020; 21:92-7.
enrolment and data collection; AT: performed the statistical 7. Fürst RV, Polimanti C, Galego SJ, et al. Ultrasound-guided
analysis and wrote the first draft of the manuscript; MM: helped vascular access simulator for medical training: Proposal of a
in statistical analysis and manuscript writing; NK,PG: supervised simple, economic and effective model. World J Surg. 2017;
during enrolment, outcome assessment and manuscript writing. 41:681-6.
All authors approved the final version of manuscript, and are 8. Tailounie M, Mcadams LA, Frost KC, et al. Dimension and
accountable for all aspects related to the study. overlap of femoral and neck blood vessels in neonates.
Funding: None; Competing interests: None stated. Pediatr Crit Care Med. 2012;13:312-7.

CORRESPONDENCE
Effect of Favoritism on Junior and Mid- Table I Baseline Characteristics of the Respondents (N=93)
Level Faculty Characterstics Value

Age (y) 41 (4.83)
Qualification
Favoritism is defined as “showing of special favor or MBBS (graduation) 11 (11.8)
partiality and the state or fact of being a favorite” [1]. MBBS and MD/DNB (post graduation) 48 (51.6)
While it is human to connect better or feel more MBBS, MD/DNB and Super specialty training 34 (36.6)
comfortable with one individual compared to the others Specialty
but obvious display and/or conduct of favoritism by Pediatrics 31 (33.3)
those in administrative position has been shown to Medicine 18 (19.3)
hamper team work and organizational growth. At an Surgery 13 (14)
individual level, it appears to breed dissatisfaction in Orthopedics 11 (11.8)
those who are not the so called chosen ones and Other clinical specialities 9 (9.7)
negatively impact their overall performance [2,3]. As in Paraclinical specialities 11 (11.8)
other fields, medicine is also not untouched by favoritism. Professional level
There is limited data on its impact on professional Junior consultant 9 (9.6)
performance and satisfaction in the medical fraternity. Consultant 17 (18.2)
Therefore, we created an online survey to ascertain the Senior consultant 8 (8.6)
perceived prevalence of favoritism. Assistant professor 21 (22.6)
Associate professor 24 (25.8)
A survey was created on the SurveyMonkey- Professor 14 (15.0)
platform, and shared with assistant professors to
Values in no. (%) or amean (SD).
professors or junior and senior consultants in
government and private teaching hospitals, who had at
least one senior person supervising them directly (head silence or even cultural censorship. Such a work
of department, or unit head). environment is sure to promote cynicism adding to
The survey was shared with 100 medical personal stress in an already stressful environment. It
professionals among the author’s contacts, and 93 may also result in loss of quality and productivity as
responded Of these, 62 (66.7%) were women, and 58 reported in our survey, and also in previous studies [6].
(62.4%) were from government teaching hospitals. Nearly An obvious limitation of our study is that the survey
three-fourth (72.3%) participants were junior-to-middle participants answered queries regarding favoritism by
level medical professionals (Table I). their senior colleagues as perceived by them, and the
seniors’ viewpoint was not studied. The views of many
Among the respondents, 82 (88.5%) believed that they
others being considered to be favorites may be different,
had been at the receiving at the end of favoritism sometime
and not solicited. Another limitation may be the relatively
or the other. Thirty four (36.6%) participants reported that
small number of survey participants, and the highly
favoritism had impacted their professional satisfaction, 66
selective nature of the sample, which may lead to some
(71.2%) felt the impact of favoritism on their performance
skewing of results.
and that it influenced/ impacted their career. The results
are summarized in Web Table I. We feel that this small study raises important issues,
and further studies with larger number of faculty may give
Favoritism by leaders at any level creates an
a clearer picture.
environment of partiality and inequality, which is
detrimental to the performance outcomes and working of Note: Additional material related to this study is available with
any organization as a whole [2,3]. However, very little has the online version at www.indianpediatrics.net
been said about favoritism in medical institutes, SUPRITA KALRA
especially among faculty, and its impact on their career Department of Pediatrics,
progression, future choices and professional satisfaction Command Hospital, Pune, Maharashra.
[4,5]. This may possibly be a result of organizational kalrasuprita@gmail.com

76 CORRESPONDENCE
REFERENCES 2012;87:1555-88.
4. Karakose T. The Effects of nepotism, cronyism and
1. “Favoritism” Merriam-Webster.com Dictionary, political favoritism on the doctors working in public
Merriam-Webster. Accessed 20 Sep. 2022. Available from: hospitals. Studies on Ethno-Medicine.2014;8:3,245-50.
https://www.merriam-webster.com/dictionary/favoritism 5. De los Santos, JAA, Rosales, RA, Falguera, CC, et al.
2. Daskin M, Tezer M. Organizational politics and turnover: Impact of organizational silence and favoritism on nurse’s
An empirical research from hospitality industry. Tourism. work outcomes and psychological well-being. Nursing
2012;60:273-91. Forum. 2020;55:782-92.
3. Du F, Tang G, Young S. Influence activities and favoritism 6. Toytok EH, Uçar A. The effect of administrators’
in subjective performance evaluation: evidence from behaviors that involves favoritism on organizational
Chinese state owned enterprises. Account Rev. opposition. J Educ Training Stud. 2018;6:68-77.
Iron Overload in an Infant With Rh- hyperferritinemia in our case was similar to previous case
studies following multiple IUTs [1-3]. The possible
Isoimmunization differential diagnosis could be common causes of anemia
or either existing hemolysis due to Rh-isoimmunization, or
A late preterm (gestational age-36 wk) baby girl weighing suppression of erythropoiesis due to iron overload, or
2.1 kg was born to a 30-year-old, G4A2L1 mother excessive nadir of physiological anemia of infancy [2].
delivered through cesarean section. Mother had Rh-ve The burden of Rh-isoimmunization is more prevalent
blood group, had a living child with Rh+ve blood group in in developing countries like India. It causes hydrops
G1 pregnancy; and G2 and G3 were aborted in first fetalis and increases neonatal morbidity [4]. IUT is the
trimester. She did not receive anti-D prophylaxis during management option for severe fetal anemia, guided by
initial three pregnancies. In the current pregnancy (G4), antenatal middle cerebral artery Doppler. Currently, the
fetal hydrops fetalis was detected in 24-week antenatal facility for IUT is available only in few referral tertiary care
scan, indirect coombs test (ICT) was 1:256 titre positive. centers of India, and the infants are subsequently
She was managed with five intra uterine transfusions followed by pediatricians. We suggest that pedia-tricians
(IUT) between 25-34 weeks of pregnancy. Baby had should be cautious in prescribing iron supplementation
received phototherapy and exchange transfusion for to such infant, who have received multiple intrauterine
severe hyper-bilirubinemia during first postnatal week. transfusions.
At one-month of age, baby presented with moderate SANTOSH KUMAR PANDA,* CHINMAY JENA
anemia (hemoglobin - 8.3 gm/dL), without icterus and Department of Pediatrics,
organomegaly. She was afebrile, active, and with Kalinga Institute of Medical Sciences (KIMS),
appropriate weight gain. Her blood group was O positive KIIT DU, Bhubaneswar, Odisha.
(due to multiple IUTs). Her reticulocyte count was 3.5%, *doc.sant@yahoo.co.in
mean corpuscular volume MCV- 74 fL, negative direct REFERENCE
Coombs test (DCT) and microcytic normo-chromic red
blood cells (absence of hemolysis) found in peripheral 1. Sreenan C, Idikio HA, Osiovich H. Successful chelation
smear. She had hyperferritinemia (755, 655 ng/mL) with therapy in a case of neonatal iron overload following
raised serum iron (138,129 g/dL) and transferrin saturation intravascular intrauterine transfusion. J Perinatol. 2000;
20:509-12.
(76.7%, 56.6%) with low TIBC (180,228 mcg/dL) on day 29
2. DemircioÉglu F, Sözmen SC, Yilmaz S, et al. Severe iron over-
and 63 of age, respectively. On follow up at age of 3 month load and hyporegenerative anemia in a case with rhesus
and 6 month, she had only raised hyperferritinemia (322, hemo-lytic disease: therapeutic approach to rare
225 ng/mL), with normal hemoglobin (12 g/dL) at 6 month. complications. Turk J Haematol. 2010;27:204-8.
Baby was managed conservatively with routine 3. Yalaz M, Bilgin BS, KöroÃglu OA, et al. Desferrioxamine
supplementation of vitamin D, without any iron chelation treatment of iron overload secondary to RH isoimmuni-
therapy. zation and intrauterine transfusion in a newborn infant.
Eur J Pediatr. 2011;170:1457-60.
This neonate presented with asymptomatic anemia 4. Agarwal K, Rana A, Ravi, AK. Treatment and prevention
and was found to have iron overload. The presence of of Rh isoimmunization. J Fetal Med. 2014; 1:81-88.

CORRESPONDENCE
Web Table I Survey Findings on Impact of Favoritism (N=93)
Your position in your hospital/institute Junior consultant 9.6%

Consultant 18.2%
Senior consultant 8.60%
Assistant professor 22.58%
Associate professor 25.81%
Professor 15.05%
Are you involved in teaching and research Yes 83.70%
apart from your clinical work No 16.30%
Have you ever felt that your senior in the Always 21.51%
department or organization is Usually 37.63%
playing favorites Sometimes 30.11%
Rarely 3.23%
Never 7.53%
Have you been able to understand or figure Always 13.98%
out the reason why your Usually 36.56%
senior has been favoring someone Sometimes 33.33%
Rarely 8.60%
Never 7.53%
Has the reason for favoritism something Always .60%
that you feel you could Usually 7.53%
influence/change or generally in your Sometimes 16.13%
hands Rarely 49.46%
Never 18.28%
Do you think that the favoritism has Always 10.87% 10
impacted your performance at Usually 19.57% 18
work Sometimes 42.39% 39
Rarely 14.13% 13
Never 11.96% 11
1.09%
Has the favoritism influenced/impacted Yes 68.82%
your career in terms of No 31.18%
promotions/getting grants/better position in
your organization
How much would you say that favoritism A great deal 13.98%
has impacted your A lot 22.58%
professional satisfaction A moderate amount 24.73%
A little 27.96%
None at all 10.75%

NEWS IN BRIEF
Urban Green Space Cover and Mental Health A research team from George Washington University has
developed two newer mRNA vaccines to curb malaria
With the growing urbanization, more and more green areas infection and its transmission. The team evaluated the
have been replaced by massive human settlements and efficacy of experimental vaccine candidates targeting -
factories, causing many health problems in populations Pfs25 and PfCSP (Plasmodium falciparum circum-
living in these areas. Green cover not only reduces the air sporozoite protein) – interrupting the disease process of
pollution but it also attenuates the noise and heat levels in the parasite and its transmission. These vaccines were
the cities. Acknowledging the role of trees in mitigating the delivered as mRNA-Lipid Nano Particle (mRNA-LNP) in
climate crisis, governments, local organizations as well as mice. Researchers found that these vaccines induced a
corporates are now focusing on increasing the green powerful immune response regardless of whether they
cover in and around the cities to improve the ecosystems. were given individually or in combination. They also
Green spaces do not only include urban forests or parks, suggest that to achieve malaria elimination goals, a
but also the trees in the streets, gardens or roof tops. combination of vaccines targeting both the infection stage
Studies have shown that people living near urban green and sexual/midgut stages is expected to provide effective
spaces have fewer mental health problems, better cognitive ways to interrupt malaria transmission. With the advent of
function, mood, have healthier babies and longer life these vaccines, one of the oldest and most severe disease
expectancy compared to those living in areas without it. may be eliminated in the near future.
Availability of green spaces vary significantly between (npj vaccines 01 December, 2022)
different cities as well as even within cities. How much Vitamin B12 Supplementation for Plant-Based
green space is good for health? This question has been Diets
bothering urban planners for long time. In order to find the
answer to this question, a team of researchers from Spain Due to the efforts of the animal welfare organizations or
studied a population-based sample of 3145 individuals change in the dietary choices, globally more and more
aged 15–97 years in a cross-sectional study. Authors people are turning towards the plant-based diets. Also,
evaluated the relationship between 3-30-300 green space due to their anti-oxidant, anti-inflammatory, lipid-lowering,
rule (every citizen should be able to see at least three trees immunomodulatory effects, these diets are getting more
(of a decent size) from their home, have 30 percent tree attention. But every change comes with a cost, thus
canopy cover in their neighbourhood and not live further consuming plant-based diet only, increases the risk of
than 300 m away from the nearest park or green space) and deficiency of micronutrients like iron, calcium and vitamin
mental health status of the participants. Mental health was B12 etc. Vitamin B12 is essential for DNA synthesis, red
assessed using 12-item General Health Questionnaire blood cell production and nervous system. As plants
(GHQ-12) and medical history (use of tranquilizer/ cannot synthesize vitamin B12, consumption of plant-
sedatives or antidepressants and psy-chiatrist or based diets only increases the risk of development of
psychologist visits). After analyzing their findings, author cognitive deficits, depression, dyspnea, postural
concluded that participants meeting the 3-30-300 green hypotension, muscle weakness, as well as mental and
space rule had better mental health compared to the others, physical fatigue. In a recently published paper, authors
thus generating an evidence to guide the planning of suggest that vitamin B12 deficiency can manifest with
green cover in the urban areas. subtle neurological symptoms like fatigue, depression,
(Environmental Research 05 December, 2022) memory impairment even in the absence of hematological
manifestations. They recommend daily supplementation
mRNA Vaccines to Combat Malaria of vitamin B12 for individuals taking strict plant based
During October, 2021, World Health Organization diets, especially in the high risk groups like, pregnancy,
recommen-ded widespread use of first anti-malarial young infants of the mothers taking plant based diets and
vaccine - RTS, S/AS01 (RTS, S) malaria vaccine among age > 60 years. They also advocated the estimation of B12
children in areas with moderate to high P. levels, if no supplements were taken during the last 6
falciparum malaria transmission, resulting in the months.
significant reduction in the severe malaria cases. Despite (European Journal of Nutrition 05 December, 2022)
the extensive preventive efforts, globally there were ~247 RAJESH KUMAR MEENA
million cases of malaria and 6,19,000 malaria deaths in 2021. raj.mamc@gmail.com

CLIPPINGS
Neurodevelopmental outcomes at 1 year in infants of increase in lactose and citrate concentration and closure
mothers who tested positive for SARS-CoV-2 during of paracellular pathways leading to decrease in sodium,
pregnancy (JAMA Netw Open. 2022;5:e2215787) protein, and sodium-potassium ratio, and an increase in
potassium and lactose. This prospective, longitudinal
The likely association of COVID-19 infection of mother
descriptive study collected ante partum, D10, and day 60
with children neurodevelopment outcome is not yet
postpartum (D60) questionnaire data, and D10 milk
established. SARS-CoV-2 might enter the central nervous
samples. Protein, lactose, and citrate were analyzed with
system from the nasal mucosa, lamina cribrosa, and
enzymatic spectrophotometric assays. Sodium and
olfactory bulb or through retrograde axonal transport.The
potassium were analyzed with inductively coupled plasma
virus has neurovirulence, activating cytokine storms,
optical emission spectrophotometry. 92 mothers provided
affecting brain vasculature and blood–brain barrier .
a D10 breastmilk sample and completed D10
Studies have revealed that SARS-CoV-2 infection in
questionnaires, and D60 questionnaires were completed
pregnancy has adverse neurodevelopmental out-comes in
by 83. Mothers with impaired secretory activation sodium
progeny, like autism spectrum disorders, schizophrenia,
(>23.0 mM) on day 10, seemingly to report D10 insufficient
cerebral palsy, cognitive dysfunction, bipolar disorder,
milk supply perception; and less D10 feeding/pumping
and anxiety and depression. In this prospective cohort
frequency per day. They also had partial breastfeeding at
study, the neurodevelopmental status of 298 infants born
D60. Mothers with D10 impaired secretory activation
to SARS-CoV-2 infection positive mothers, was assessed
sodium to potassium ratio >0.8, were more presumable to
at 10-12 months post-discharge using the Ages and
partially breastfeed at D60. As, elevated milk sodium and
Stages Questionnaire, 3rd edition (ASQ-3). 90% infants
sodium to potassium ratios are biomarkers related to low
had favorable outcomes and only 10% exhibited
milk supply, so instantaneous milk testing can be useful in
developmental delays. Maximum women had SARS-CoV-2
recognizing lactation compromise and can help in
infection in their third trimester. The majority of
improving lactation duration.
developmental delays among infants was in those whose
mothers had SARS-CoV-2 infections during the first Quality improvement initiative to improve infant safe
(P=0.039) and second trimesters (P=0.001) than in those sleep practices in the newborn nursery (BMJ Open
whose mothers had SARS-CoV-2 infections during the Qual. 2022;11:e001834)
third trimester. Although the neurodevelopmental
American Academy of Pediatrics (AAP) safe sleep
outcomes of infants born to mothers with SARS-CoV-2
recommen-dations in 1992 and the initiation of the ‘Back to
infections appeared favorable, more studies with larger
Sleep’ campaign had led to a reduction in sudden infant
sample sizes and prolonged follow-up periods are
death syndrome (SIDS). Still a significant number of
essential.
deaths are attributed to SIDS. The practicing of safe sleep
Associations of secretory activation breast milk practices (SSP) within a hospital has shown to improve
biomarkers with breastfeeding outcome measures (J SSP at home. A prospective study was done with the use of
Pediatr. 2022:S0022-3476(22)00877-0) quality improve-ment (QI) methodology, to increase
adherence to infant safe sleep practices, with a goal to
The foremost cause for early discontinuation of
improve the proportion of infants having ‘perfect sleep’ to
breastfeeding is mother’s perception of inadequate milk
70% within a 1-year period. Multiple Plan-Do-Study-Act
supply. In the initial phase of postpartum, the transition of
cycles (7 cycles) were performed. Initial cycles targeted
mammary gland from secretory differentiation to activation
nurse and parental education, while later cycles focused
is depicted by bio-markers, along with the initiation of
on providing sleep sacks/wearable blankets for the infants.
copious milk production. In secretory activation, milk
The percentage of infants with ‘perfect sleep’ increased
composition changes occurs sequentially, which occurs
from a baseline of 41.9% to 67.3%.And even the
within 72 hours for healthy mothers. There occurs a
progresses were sustained over 12 months later.
decrease in protein and sodium concentrations, and
sodium-potassium ratio. Later milk synthesis occurs by BIJAYLAXMI BEHERA
upregulation of the trans cellular pathways), resulting in jollybubu2008@gmail.com

BOOK REVIEW
Hypoxic Ischemic Encephalopathy next reprint. In Chapter 1, a line stating that when the two-
thumb technique is used, the provider must stand at the
ANJALI KULKARNI, SANJAY WAZIR
head-end to allow space for the other person securing
Noble Vision (Medical Book
umbilical lines (potentially the next step in resuscitation)
Publishers), Delhi.
– as has been included in latest NRP guidelines. In the
Pages: 282; Price: Rs. 895/-
same chapter, the initial dose of IV epinephrine (0.02 mg/
kg) and endotracheal epinephrine (0.1 mg/kg) can be
incorporated. In Chapter 8, continuous low voltage has
The authors have edited an
been inadvertently described as both upper and lower
excellent book on hypoxic ischemic
margins <5. It should be changed to upper margin <10 and
encephalopathy (HIE), which will be useful for
lower margin <5. The editors can add the concept of
neonatology trainees and practicing neonatologists alike.
‘Expanded Apgar score’ as it has been advocated by both
Some of our general comments on the book are as follows:
AAP and ACOG since 2015. In Chapter 15, the editors can
The color plates provided by the editors at the start of mention that the dose of leviteracetam is loading dose of
the book give a good overall visual impression of the 40 mg/kg and maintenance with 40-60 mg/kg. This is
recent modalities used in field of HIE. They have covered according to the standard treatment workflow for
difficult topics like HIE in preterm neonates, and MRI in neonatal seizure given by ICMR. In Chapter 16, the cut-
HIE in a very lucid and clear manner, which makes it easy off value of FENa for pre-renal AKI can be modified to 2.5.
to understand. The highlights of this book are recent Many workers have suggested using 2.5 as FENa cut off
advances like NIRS in HIE, seizure detection and because FENa is inversely proportional to gestational
management in the context of HIE, and a lucid explanation age, and a few preterms may lose more urinary sodium in
of the ILAE 2021 position statement. The individual initial few days.
authors have also taken great efforts to include the latest
We suggest that Chapter 22 could include a few extra
evidence from clinical trials, and position papers for all
paragraphs on “Early stimulation” and “Principles of
chapters.
physiotherapy”. Chapter 23 summarizes all the metabolic
Our comments regarding specific chapters are as disorders which can masquerade as perinatal asphyxia.
follows: Chapter 1 and Chapter 3 emphasize all recent However, well-constructed algorithms may give a more
amend-ments in NRP like delayed cord clamping, initial FiO2 practical approach for the readers.
requirement, optimum use of pulse oximeter and ECG. The
Notwithstanding the minor changes suggested
relatively more recent concept of intact cord resuscitation
above, the book was a delightful read and a much needed
has been introduced to readers in a comprehensive way.
addition to the bookshelves of all those who practice
Chapter 2 summarizes all the modalities of antenatal fetal
neonatal care, especially those who are practicing in India
surveillance and provides useful recommendations on
and developing countries.
controversial topics like the choice of tests and the timing of
delivery based on these tests. Chapter 7 summarizes all the VENU KULKARNI, SOURABH DUTTA*
biomarkers of asphyxia. The well-constructed tables make it Neonatology unit, Department of Pediatrics,
easily digestible for readers. Postgraduate Institute of Medical Education
and Research (PGIMER),
There are a few minor points that the editors and the Chandigarh 160012.
respective chapter authors can consider revising in the *sourabhdutta1@gmail.com

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Printed and published by Dr Devendra Mishra on behalf of Indian Academy of Pediatrics and printed at
Cambridge Press, Kashmere Gate, Delhi-110006 and published at 115/4, Ground Floor,
Gautam Nagar, New Delhi 110 049. Editor: Dr Devendra Mishra

Indian Pediatrics January 2023 Issue

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INDIAN PEDIATRICS 3 VOLUME 60__JANUARY 15, 2023

INDIAN PEDIATRICS 4 VOLUME 60__JANUARY 15, 2023

January 2023 Volume 60 Number 1

Measuring Overnutrition in Children: Do We Know Enough?–SHIVANI A PATEL, NATALIA E POVEDA 11

Management of Hyperbilirubinemia in Newborn Infants 35 or More Weeks of Gestation: American Academy of

Lead Toxicity: The Unbeaten Menace–NIDHI BEDI 67

Neonatologist-Performed Ultrasound-Guided Internal Jugular Vein Cannulation–ANUP THAKUR, MANOJ MODI,

Iron Overload in an Infant With Rh-Isoimmunization–SANTOSH KUMAR PANDA, CHINMAY JENA 76

Impact Factor of Indian Pediatrics is 3.839

Editing the Academy’s Journal in the Peri-COVID Era –

INDIAN PEDIATRICS 7 VOLUME 60__JANUARY 15, 2023

INDIAN PEDIATRICS 8 VOLUME 60__JANUARY 15, 2023

Diamonds are Forever!

INDIAN PEDIATRICS 9 VOLUME 60__JANUARY 15, 2023

INDIAN PEDIATRICS 10 VOLUME 60__JANUARY 15, 2023

Measuring Overnutrition in Children: Do We Know Enough?

INDIAN PEDIATRICS 11 VOLUME 60__JANUARY 15, 2023

INDIAN PEDIATRICS 12 VOLUME 60__JANUARY 15, 2023

Effect of Kangaroo Mother Care on Cerebral Hemodynamics

INDIAN PEDIATRICS 13 VOLUME 60__JANUARY 15, 2023

INDIAN PEDIATRICS 14 VOLUME 60__JANUARY 15, 2023

Urgent Need of Research on Neurodevelopmental Outcome of Preterm/

INDIAN PEDIATRICS 15 VOLUME 60__JANUARY 15, 2023

REFERENCES literature. Paediatr Int Child Health. 2015;35:227-42.

INDIAN PEDIATRICS 16 VOLUME 60__JANUARY 15, 2023

Published online: Nov 19, 2022; PII: S097475591600470

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overweight (>2SD), but the overall prevalence

prevalence of possible risk of overweight with

The absolute differences in 0.5-5 years and

much higher in 0-0.5 years (53.9% vs 11.6% and

0.88 (37871); 0.94 (163858);

0.5-5 years (11.9% vs 18.2% and 8.1% vs 12.5%,

magnitude of overall prevalence and absolute

and 6-59 months and of a greater magnitude in

the stunted subjects (Web Fig.7).

age, weight for height, and BMI for age (z-

0.90 (41761); 0.94 (160553);

scores) of the CNNS dataset were 30.53 (16.8), -

1.15 (1.5), -0.72 (1.3), and -0.60 (1.3), respectively.

Boys comprised 52% of the sample. Patterns

overweight (>2SD) and the kernel density plots;

however, the magnitude of overall prevalence

Misclassification occurred in both

directions, being more evident in short

The reverse pattern was observed in 0.5-5

years, except for the Poland and Greenland

The Bland-Altman analyses varied with age

for the simulated short population. In the 0-6

months age group, thinner infants had lower

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