Iap Feb Issue
Iap Feb Issue
Iap Feb Issue
VOLUME 60
NUMBER 2
February 2023
CONTENTS
EDITORIAL BOARD 2023 91
PRESIDENT’S PAGE
Sankalp: Sampoorna Swasthya–UPENDRA KINJAWADEKAR 92
INVITED COMMENTARY
High Birth Weight and Risk of Childhood Obesity–MOSTAFA SALAMA, SEEMA KUMAR 94
Birthweight: An Early Beacon of Children’s Growth!–SOLVEIG ARGESEANU CUNNINGHAM, URVASHI MEHLAWAT 96
PERSPECTIVE
Congenital Heart Disease: Would It Be the Key Driver of Infant Survival During Amrit Kaal (2022-2047)?
–ARUN K BARANWAL, SHANKAR PRINJA, NAVPREET KAUR 98
RESEARCH PAPERS
Risk of Childhood Obesity in Children With High Birth Weight in a Rural Cohort of Northern India
–DINESH KUMAR, SEEMA SHARMA, SUNIL KUMAR RAINA 103
Effect of Obesity on the Recovery Profile After General Anesthesia in Children: A Prospective Cohort Study
–MEHMET SARGIN, EMINE ASLANLAR, FARUK ÇIÇEKCI, FATMA SARGIN, INCI KARA, JALE B CELIK 108
Neighborhood Walkability Index and Its Association With Indices of Childhood Obesity in Bengaluru, Karnataka
–DEEPA PUTTASWAMY, SANTU GHOSH, REBECCA KURIYAN 113
Risk Factors of Cooking-related Burn Injury Among Under-Four Children in Northwest Ethiopia:
A Community-Based Cross-Sectional Study–MESAFINT MOLLA ADANE, AMHA ADMASIE, TEBKEW SHIBABAW 119
Neonatal Outcomes in Pregnant Women With Repaired and Unrepaired Congenital Heart Disease in Zhejiang,
China–JIANG-LIN MA, FANG LUO, LINGLING YAN 123
Pattern of Psychiatric Emergencies in Children and Adolescents at a Tertiary Care Centre After Onset of
COVID-19 Pandemic–MAHADEV SINGH SEN, RAMAN DEEP, NISHTHA CHAWLA, RAJESH SAGAR, RAKESH KUMAR CHADDA 127
Sociodemographic and Clinical Characteristics of Child Sexual Abuse Reported to an Urban Public Hospital
in Southern India, 2019-22–KS KUMARAVEL, SS SUBHA, V ANUREKHA, P KUMAR, PR HARIPRIYA 133
Serum Occludin and Zonulin Levels in Children With Attention-Deficit/Hyperactivity Disorder and Healthy
Controls–ALI ÇAKIR, HICRAN DOGRU, ESRA LALOGLU 137
REMINISCENCES FROM INDIAN PEDIATRICS: A TALEOF 50 YEARS
Genetic Counselling for Global Developmental Delay/Intellectual Disability (GDD/ID) - Changing
Landscapes and Persisting Challenges–RANJANA MISHRA, SEEMA KAPOOR 142
89
CONTENTS (contd.)
RESEARCH LETTER
Effect of High Sodium Intake (5 mEq/kg/day) in Preterm Newborns (<35 Weeks Gestation) During the Initial 24
Hours of Life: A Non-Blinded Randomized Clinical Trial–CARLOS SÁNCHEZ, DENISSE CASTILLO,
BEN DAVID VALDÉS, FIDEL CASTAÑEDA 146
CLINICAL CASE LETTER
Successful Management of Systemic Pseudohypoaldosteronism Type 1 in an Infant–PAMALI MAHASWETA
NANDA, RAJNI SHARMA, VANDANA JAIN
CORRESPONDENCE
Tele-NICU: A Possible Solution for Bridging the ‘Gap’–ROHIT ARORA, R KISHORE KUMAR 151
Co-existing Iron Deficiency and Compliance Issues in Nutritional Macrocytic Anemia in Children
–SANJEEV KHERA, SANDEEP DHINGRA 152
Authors’ Reply–KRUTIKA RAHUL TANDON 153
Colistin Resistance in Gram Negative Bacteria in a Tertiary Care Neonatal Intensive Unit in Odisha
–SANTOSH KUMAR PANDA, RISHABH PUGALIA 154
REVIEWERS FOR 2022 155
NEWS IN BRIEF 157
CLIPPINGS 158
IMAGE 159
BOOK REVIEW 160
ADVERTISEMENTS 85-88,107,118,145,160-164
90
JOURNAL COMMITTEE AND ADVISORY BOARD FOR THE YEAR 2023
Editor-in-Chief: Devendra Mishra, Department of Pediatrics, Maulana Azad Medical College, Delhi.
Executive Editor: AP Dubey, New Delhi.
Managing Editor: Sharmila B Mukherjee, Department of Pediatrics, Lady Harding Medical College, Delhi.
Associate Editors
Rakesh Lodha, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Delhi.
Anup Mohta, Department of Pediatric Surgery, Lady Harding Medical College, Delhi.
Pooja Dewan, Department of Pediatrics, University College of Medical Sciences, Delhi.
Joseph L Mathews, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh.
Aashima Dabas, Department of Pediatrics, Maulana Azad Medical College, Delhi.
Abhijeet Saha, Department of Pediatrics, Lady Harding Medical College, Delhi.
Executive Members
Sunita Bijarnia-Mahay, Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi.
JS Kaushik, Department of Pediatrics, AIIMS, Guwahati, Assam.
Ujjal Poddar, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh.
Somshekhar Nimbalkar, Department of Neonatology, Bhaikaka University, Anand, Gujarat.
Ashish Jain, Department of Neonatology, Maulana Azad Medical College, Delhi.
Kana Ram Jat, Department of Pediatrics, AIIMS, Delhi.
Sumaira Khalil, Department of Pediatrics, University College of Medical Sciences, Delhi.
Romit Saxena, Department of Pediatrics, Maulana Azad Medical College, Delhi.
Amit Devgan, Department of Pediatrics, Army Hospital Research &Referral, Delhi.
Nidhi Sugandhi, Department of Pediatric Surgery, Vardhman Mahavir Medical College & Safdarjung Hospital, Delhi.
Rajesh Meena, Department of Pediatrics, University College of Medical Sciences, Delhi.
Nidhi Bedi, Department of Pediatrics, Shree Guru Gobind Singh Tricentenary Medical College Hospital & Research Institute,
Gurugram, Haryana.
NATIONAL ADVISORY BOARD
Central Zone: Mahima Mittal, Gorakhpur, Uttar Pradesh; R Ramakrishna Paramahamsa, Rajahmundry, Andhra Pradesh.
East Zone: Prasant Kumar Saboth, Bhubaneshwar, Odisha; Devajit K Sarma, Guwahati, Assam.
North Zone: Shiv K Gupta, Ludhiana, Punjab; Vidushi Mahajan, Chandigarh.
South Zone: Madhusudana C, Bengaluru, Karnataka; A Chenthil, Neyveli, Tamil Nadu.
West Zone: Arvind D’Almeida, Margao, Goa; Trupti Amol Joshi, Aurangabad, Maharashtra.
ADVISORS
Chief Advisor: Siddharth Ramji, Chennai, Tamil Nadu.
Central IAP Advisors (ex-officio)
Upendra S Kinjawadekar, President IAP, 2023.
GV Basavaraja, President-elect IAP, 2023.
TL Ratna Kumari, Editor-in-Chief, Indian Journal of Practical Pediatrics.
Vineet K Saxena, Hony. Secretary-General, IAP 2022-23.
Biostatistics: Amir M Khan, University College of Medical Sciences, Delhi.
Rajeev K Malhotra, All India Institute of Medical Sciences, Delhi.
Ethics: Jagdish Chinappa, Bengaluru, Karnataka.
Office Matters: AS Vasudev, Max Hospital, Patparganj, Delhi.
Peeyush Jain, Hindu Rao Hospital, Delhi.
Social Media: Arva Bhavnagarwala, Mumbai, Maharashtra.
Chandermohan Kumar, AIIMS, Patna, Bihar.
Amit Upadhyay, Nutema Hospital, Meerut, Uttar Pradesh.
Website: Sanjeev Goel, Meerut, Uttar Pradesh.
Samir R Shah, Vadodara, Gujarat.
C Vidyashankar, Ranchi, Jharkhand.
T
he advent of the 21st century brought several health trajectories, as well as the health of the next
notable changes to our lives. Precipitated by generation of children—by leveraging this crucial
the globalization of the 1990s, over the last two window of opportunity. Under the program, we are going
decades, our lifestyles have radically changed. to target five environmental and social drivers (nutrition,
Parents from my generation (myself included) are often physical activity, screen time, substance abuse, mental
telling children about how ‘eating out’ was a rarity in our health) that can have long-term repercussions on the
childhood, our options limited, and considered an health of the child.
occasional luxury. We did not carry a round-the-clock
There is a need to improve nutrition literacy amongst
connection with our friends in our pockets, and life was
children in India by explaining what exactly balanced diet
certainly not as sedentary as it is now. These oft-heard
is all about. With the number of low-cost, accessible
anecdotal lectures aside, over the past few years, I have
unhealthy options available in the market, it is crucial that
genuinely begun worrying for the short- and long-term
children are themselves intrinsically driven to not give in
health effects of these changing lifestyles on our children.
to temptation and choose wisely between what’s good
Studies have now shown the detrimental impact that
and bad for their health. There is a need to regulate screen
screen time, lack of physical activity, and deteriorating
exposure and to advice young children on how to
climatic conditions have on the physical and mental
consume the content that is hurled their way every day.
health of children. NFHS-5 data shows that obesity
Observational studies note that almost all young children
amongst children in India is on the rise. There is a plethora
seem to be exposed to screen-based media by 18 months
of cheap, tasty, unhealthy options that children have
of age in the urban setting, and the average screen time is
quick and easy access to. Rising academic pressures, and
over two hours. A population-based cross-sectional
a stressful environment inside and outside home are
study conducted in rural and urban health centers in
leading to unfortunate cases of high blood pressure,
Tamil Nadu showed that increased screen time amongst
diabetes and obesity amongst school-going adolescents.
under-five children was significantly associated with
Lifestyle disorders (also called non communicable
developmental delay, in particular, in the domains of
diseases) have reached epidemic proportions and are
language acquisition and communication. The concerns
increasing at alarming rates, more so in low- and middle-
about the excessive screen time among children and
income countries like India. Global healthcare agencies
adolescents also pertains to a reduction in time spent on
like WHO, and the Government of India, have already
physical activity, which further exacerbates mental and
identified NCDs as one of the foremost public health
physical health issues.
concerns, and have raised a call to action for the
prevention of NCDs. Reports suggest a rising threat of substance abuse
amongst younger sub-populations in India (both school
For the year 2023-24, the IAP will introduce a flagship going and out-of-school children), with 13% of the victims
program, ‘Sankalp: Sampoorna Swasthya’ — a drive of drug and substance abuse being under 20 years of age
towards comprehensive preventive healthcare for school [1]. Substance abuse, or even dependency, during the
going children. The program is led by the belief that formative years interferes with academic, social and life
healthy habits, cultivated early in life, are more likely to be skills development of a child, and can culminate into a
carried into adulthood. Childhood and adolescence are volatile and temperamental adulthood. Most individuals
critical life stages that are primed to absorb and process start their substance use during adolescence, but
new information. Hence, huge public health gains can be treatment is usually sought after a few years when health
realized – including improvements in the health of current or other psychosocial complications begin to emerge,
cohorts of children and adolescents, their future adult such that only 5% of treatment seekers are actually
adolescents [2]. The pattern suggests the importance of and the goal of accreditation, we will reach teachers,
preventive measures to avoid later-stage dependency educators and parents via school sessions, in-person
issues. There is also a need to address a rising number of counselling and culturally and contextually rooted
mental health stressors amongst children in India. This is videos. SSS is a unique program, in that it will not restrict
especially important as several people continue to be itself to training, but will also include follow-up support to
naysayers denying the reality and repercussions of students and parents, and strengthening of schools as
mental health issues. We are all well aware of the effective platforms to catalyse the adoption of the Indian
harrowing reality of student suicides in India. Clearly, our model of Health Promoting Schools as proposed by
children are overwhelmed with the internal and external NCDPA to meet the best of global standards [5]. In order
pressures of a highly competitive academic system. to achieve these objectives, SSS also intends to build
Additionally, grief, fear, uncertainty, social isolation, strong partnerships with other stakeholders including
increased screen time, and parental fatigue have government and NGOs and schools, to make the
negatively affected the mental health of children [3,4]. preventive services robust, sustainable, standards-
According to the Indian Journal of Psychiatry, even driven, and effective. In the past 60 years of its existence,
before the pandemic, at least 50 million children in India IAP has done tremendous work for the benefit of the
suffered from mental health issues. The incidence of children and adolescents of India, by continuously
social anxiety amongst children is further exacerbated by upgrading the knowledge and skills of pediatricians,
the flood of information through constant exposure to advising governments on critical issues and advocacy on
social media. This can drive body-image issues, and several fronts. Now, in its Diamond Jubilee year, it is only
amplify eating disorders or body dysmorphia, especially apt that through SSS, IAP is poised to take a big leap
amongst young girls. forward, by taking the benefits of the best of science,
directly to the community and doorstep of all school
As the apex organization committed to improvement going children of India, in an unprecedented manner.
of health and well-being of all children in India, Indian REFERENCES
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C
hildhood obesity has emerged as an important information on gender, years of schooling, diet and physical
global public health problem [1]. India has activity. The relative risk of elevated body mass index (≥2
also experienced an increase in prevalence of SD) between age 7-10 years was 5-fold higher in children
childhood overweight and obesity in the last with a birthweight of more than 3500 grams in comparison to
three decades [2]. Childhood obesity is associated with those with a birth weight of between 2500 and 2999 g, after
various metabolic disorders such as type 2 diabetes, adjustment for several confounding variables such as mean
dyslipidemia, hypertension, and fatty liver disease [3]. age, gender, mean years of schooling, dietary habits and
Additionally, cardiovascular events and mortality during physical activity. A major strength of the study by Kumar, et
adulthood are associated with obesity during childhood al. [7] is that it is community based and not hospital or clinic
[4]. Therefore it is imperative to identify modifiable based, as has been the case in previous longitudinal birth
factors during early life that play in role in development of cohorts in India. The rural setting in northern India is another
obesity in children [5]. strength as overweight/obesity are more prevalent than
Nutritional and environmental influences in the under nutrition in rural India [8]. Moreover, in a study that
intrauterine period affect weight gain and cardiometabolic pooled data from 52 studies conducted in 16 of the 28 states
risk factors in the offspring during childhood and adult life in India, the combined prevalence of childhood and
[6]. Epigenetic mechanisms that alter gene expression adolescent obesity was higher in northern India than in
without changing the DNA sequence in addition to genetic southern India [2]. Limitations of this study include the small
and environmental factors form the basis for the “metabolic sample size (379 children with birth weight between 2500
programming.’’ Higher maternal prepregnancy weight, and 2999 g and 377 children with birth weight of more than
excessive weight gain during pregnancy and gestational 3500 g) and lack of information on growth parameters during
diabetes mellitus are associated with weight gain in children early infancy such as catch-up growth and timing of adiposity
and adolescence. In addition, family history of obesity rebound. Additionally, the investigators did not adjust for
increases the predisposition for excess weight gain. These maternal characteristics that can affect obesity in offspring
factors account for intergenerational transmission of obesity such as age, prepregnancy body mass index, glycemic status,
and metabolic disorders. Nutrition during infancy and early and weight gain during pregnancy.
childhood also influences weight gain during later The findings of a positive association between birth
childhood. Breast feeding has a protective effect against weight and childhood overweight/obesity in children from
childhood obesity. In contrast, rapid weight gain during rural northern India are similar to those from previous studies
infancy and early adiposity rebound are associated with in other countries. In a 12-country study that included high
higher risk for subsequent development of obesity. income, middle income and low-income countries, birth
The increase in prevalence of childhood overweight and weight ≥3500 g was associated with a higher prevalence of
obesity in India has been noted not just in the higher obesity in children 9-11 years of age [9]. Most importantly,
socioeconomic groups but also in the lower income groups these associations have been stable during the development
[2]. In a study published in this issue of the journal, Kumar, et of the obesity epidemic as demonstrated by increased risk for
al. [7] conducted a retrospective birth cohort study among overweight between age 6 to 13 years in a population based
children 7 to 10 years of age in 22 villages in the state of Danish cohort study of children born between 1936 and 1983
Himachal Pradesh. Birth weight data was obtained from [10]. The increased risk for childhood overweight with
immunization cards of children born in year 2011-2012. higher birth weight is evident as early as 3 years of age as was
Specific questionnaires were administered to obtain shown in a Chinese birth cohort study [11]. The long-term
consequences of high birth weight on obesity extend beyond Engl J Med. 2016;374:2430-40.
childhood into adult life [12,13]. 5. Gillman MW, Ludwig DS. How early should obesity
prevention start? N Engl J Med. 2013; 369:2173-5.
The findings by Kumar, et al. [7] suggest an 6. Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark
association but do not imply a cause effect relationship. PM. Type 2 (non-insulin-dependent) diabetes mellitus,
Further longitudinal studies are warranted to determine if hypertension and hyperlipidaemia (syndrome X): relation to
targeting modifiable prenatal risk factors such as reduced fetal growth. Diabetologia. 1993;36:62-7.
optimizing maternal nutrition, pre-pregnancy body mass 7. Kumar D, Sharma S, Raina SK. Risk of childhood obesity in
index, gestational weight gain and glycemic status will children with high birth weight in a rural cohort of Northern
India. Indian Pediatr. 2023;60:103-7.
result in reduced risk of overweight and obesity in the
8. Premkumar S, Ramanan PV, Lakshmi JD. Rural childhood
offspring [5]. Given the crucial role played by obesity - an emerging health concern. Indian J Endocrinol
environmental factors in addition to genetic and epigenetic Metab. 2019;23:289-92.
factors, it would be important to utilize a multipronged 9. Qiao Y, Ma J, Wang Y, et al. Birth weight and childhood
approach including healthy nutrition and active lifestyle obesity: a 12-country study. Int J Obes Suppl. 2015;5(Suppl
during infancy and early childhood to effectively prevent 2):S74-9.
the development of childhood obesity. 10. Rugholm S, Baker JL, Olsen LW, Schack-Nielsen L, Bua J,
Sorensen TI. Stability of the association between birth weight
Funding: None; Competing interests: None stated. and childhood overweight during the development of the
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11. Ye R, Pei L, Ren A, Zhang Y, Zheng X, Liu JM. Birth weight,
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J Med. 2017;377:13-27. 12. Schellong K, Schulz S, Harder T, Plagemann A. Birth weight
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from early to late childhood and cardiometabolic measure- growth and relative weight gain during early life with adult
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*sargese@emory.edu
W
hat are the origins of obesity? How are the more so for the latter [4]. Research on contemporary child
causes related to genetic predispositions cohorts have reported linear associations between
and to environmental and behavioral birthweight and childhood weight, with weight status and
exposures, such as overeating and abdominal adiposity in childhood and adolescence
insufficient physical activity? With obesity being one of increasing steadily for children according to their weight at
the most impactful diseases experienced by contemporary birth, especially for girls [5]. A systematic review reported
cohorts in many places around the world, including India, that, across studies, children and adolescents who were
the answer to this question has major implications for small at birth are more likely than those who were large at
policies, programs, and recommendations aimed at birth to experience rapid growth during early childhood.
improving individual and population health. Though some However, children who were bigger at birth and who also
researchers have proposed that obesity has common- grew quickly had the highest odds of developing
sense solutions rooted in maintaining energy balance, it is overweight or obesity [6]. The same issue has also been
increasingly clear that obesity is a complex condition that addressed in a rural cohort in India by Kumar, et al. [7] in
develops and becomes entrenched over time. We are their study published in this issue of the journal.
becoming increasingly aware that at least some of the risk
To be able to understand these predispositions and
of obesity is set early in life.
apply the findings to obesity prevention, we must first
This early life risk may have origins even prior to birth, understand the underlying mechanisms. Some compo-
involving prenatal exposures and growth patterns [1]. nents of the observed predisposition to obesity are likely
Prenatal exposures are measured in terms of birthweight or genetic [8]. The likelihood of being obese is higher among
birthweight for gestational age. Clinically, birthweight of children with obese parents [9]. Still, the roles of genetic
under 1500 g is considered critically low; 1500-2500 g is predispositions, environmental exposures, and behavioral
considered low, and over 2500 g is considered normal [2]. patterns in intra-family similarities are difficult to
Recent studies have also started to raise concerns about disentangle. Twin studies have attempted to separate out
high birthweight, identifying high risks of later developing heritability from shared exposures and behaviors, and
some conditions for people with birthweight higher than have reported high heritability of BMI (body mass index)
3500 g. Birthweight is best considered in the context of ranging from 41% to 85%, with the association increasing
gestational age, as a child born prematurely with low with age [10].
birthweight has different health risks compared with a
In addition to genetic predisposition, contextual
child born at term of the same size, whose low birthweight
factors are also important, and can begin even prenatally.
may be an indicator of intrauterine growth retardation.
Indeed, genetic factors and environmental factors may
The relationship between birthweight and body size, interact, leading to different risks, even for children
including obesity, in childhood, and even in adulthood, growing up in the same environments. Mother’s health, for
has been an area of extensive research across example, suffering from obesity or diabetes, her nutritional
populations. Early studies, for example from the Nurses’ intake during pregnancy, and her exposure to stress, have
Health Study in the US, reported a U-shape relationship been shown to affect intrauterine growth and weight
between birthweight and body size in adulthood, with high status [11]. Mother’s health-related behaviors during
prevalence of obesity among people who had both low pregnancy are shaped by contextual factors and are also
and high birthweight [3]. Some recent studies have relevant to birthweight, for example smoking and drug
reported a J-shaped relationship, with the risks for obesity intake, eating behaviors, and activity levels [12].
being elevated for both low and high birthweight, but Contextual factors and maternal and family behaviors
Chandigarh.
Correspondence to: Prof Arun Kumar Baranwal, HDF Unit, Department of Pediatrics, Advanced Pediatrics Center, PGIMER,
Chandigarh 160 012. baranwal1970@gmail.com
Post-independence, we made significant strides in childhood survival. However, there is an abysmal improvement in survival due to
birth defects. Globally, India contributes the largest proportion of under-5 deaths, overall as well as due to birth defects. Congenital heart
disease (CHD) is the single most common cause of birth-defect related deaths, and is the 7th most common cause of infant deaths.
Scarcity of pediatric cardiac care professionals and pediatric cardiac centers has led to a huge demand-supply gap. Understanding the
burden of CHD and taking imperative steps at primary, secondary and tertiary levels are essential during Amrit Kaal (2022-2047). Cov-
erage of management of CHD under Janani Shishu Suraksha Karyakram, Rashtriya Bal Suraksha Karyakram and Ayushman Bharat
programs offers a huge promise, as shown by the experience from Hridayam program in Kerala.
Keywords: Birth defects, Infant mortality, Neonatal mortality, Under-5 deaths,
D
espite significant reduction in child mortality, General improvement in childhood survival during
India, a country with low-middle socio- 1990-2017 increased the proportional contribution of birth-
demographic index (SDI), contributes the defects to U5MR [2]. Concurrently, improving diagnostics
largest proportion of under-5 deaths to the and increasing awareness led to a steady rise in the
world statistics [1]. During 1990-2017, contribution of birth reported prevalence of CHD [7,8]. The two together moved
defects to child mortality has increased, with reducing CHD up from 8th to 7th most common cause of infant
neonatal mortality rate (NMR) and under-five mortality mortality [9]. With birth prevalence of CHD being 0.9%
rate (U5MR) [1,2]. We also contribute maximum to the (range, 0.8-1.2%), estimated annual birth prevalence
global under-5 deaths attributable to birth defects [2]. (EABP) in India is likely to be upwards of 2,40,000 [8]. EABP
Congenital heart diseases (CHD) contribute the most to of CHD in different regions are as follows– 84,000 in
birth defects (28%), and the single most common cause of Northern region (Jammu-Kashmir, Laddhakh, Punjab,
deaths due to them [3,4]. Here, we discuss the significance Himachal Pradesh, Uttarakhand, Punjab, Haryana,
if CHDs with respect to child mortality, our preparedness, Chandigarh), 52,000 in Eastern region (Bihar, Jharkhand,
and the way forward to deal with the situation during the Odisha, West Bengal), 38,000 in Southern region
‘Amrit Kaal’ of our independence (2022-2047). (Telangana, Andhra Pradesh, Tamil Nadu, Karnataka,
Kerala), 29,000 in Western region (Maharashtra, Gujrat),
CONGENITAL HEART DISEASE AND CHILD 23,000 in Central region (Madhya Pradesh, Uttar Pradesh,
MORTALITY Chhatisgarh, Rajasthan) and 12,500 in North-eastern
region (Assam, Sikkim, Meghalaya, Mizoram, Nagaland,
During the last three decades, child survival improved
Manipur, Arunachal Pradesh, Tripura) [8]. About 25% of
significantly due to improvement in antenatal and neonatal
these babies have critical CHD (i.e., requiring inter-
care, control of vaccine-preventable diseases, acute
ventions in the first year of life). Many of these babies
respiratory tract infections and diarrhea-dehydration, and
mimic sepsis and/or respiratory diseases during neonatal
nutritional programs. During 1990-2019, the NMR, infant
period, or get complicated with one.
mortality rate (IMR) and U5MR reduced significantly The
data from the Sample Registration System (SRS) revealed For the lack of timely surgery, children with CHD
birth defects moving up from the eighth to the fifth most consume healthcare resources unproductively for
common cause of infant deaths during the 12-years period repeated hospitalizations for congestive heart failure,
(2004-06 vs 2015-17) [5,6]. recurrent pneumonia, cardiovascular complications,
malnutrition and its associated problems. With passage of region (17%), Western region (28%), Southern region
time, surgical outcome would be compromised in many, (74%), while none get operated in the North-Eastern region
while many children would become inoperable. Thus, CHD [8,10]. Capacity, both infrastructure and human resource, is
is also an important cause of mortality and morbidity the prime limitation for the observed demand-supply gap,
during later childhood as well. In fact, birth defects (of especially in northern and eastern regions.
which CHD constitute the largest proportion) are
The Hridyam Program
estimated to contribute 8% of under-5 deaths in India [1].
Contribution is likely to be more in states with U5MR<25, IMR in Kerala was 16/1000 livebirths in 1991, and it
e.g., Kerala, Tamil Nadu, Maharashtra, Delhi, Manipur and stagnated around 10-12 for about a decade (2007-2017),
Nagaland. The same is likely to happen in most of other despite reduction in neonatal and infant deaths with
states as they are projected to achieve U5MR<25 by the improvement in perinatal care, infectious diseases and
year 2030, barring Uttar Pradesh, Madhya Pradesh, malnutrition— the so-called ‘low-lying fruits.’ Birth-
Chhatisgarh, Odisha, Rajasthan, Assam and Mizoram [1]. defects (of which CHD has the largest share) were found to
Another analysis revealed birth-defects to be the third be major contributor to infant death, and the second most
leading cause of early neonatal mortality in 17 states [2]. common cause of under-5 deaths [2,11]. A plan of
With persistently improving SDI, awareness, institutional ‘paediatric cardiac care continuum’ was worked out to
deliveries, neonatal, infant and under-5 survival, and lack address the issue of CHD, especially the critical ones. It
of healthcare infrastructure to manage CHD in majority of was implemented in August 2017 as ‘Hridyam’ program in
states, a fairly constant birth prevalence of CHD would public-private partnership. Children (aged 0-18 years) with
create a case of ‘perceptual explosion’ during the Amrit suspected CHD were registered to develop a life-time
Kaal. pathway instead of just providing one-time surgery.
Program created a state-wide network connecting primary
CURRENT STATUS
health centres to tertiary hospitals for timely and optimal
Care of Children With CHD management [11]. It led to fall in all-cause IMR to 6/1000
livebirths by the year 2019 (Fig. 1). Jammu-Kashmir,
Level of care available for children with CHD varies
Punjab, Himachal Pradesh, Delhi, West Bengal,
significantly between high income countries (HICs) and
Maharashtra, Goa, Tamil Nadu and all Union Territories
low- and middle- income countries (LMICs). In HICs, the
have already achieved an IMR of 20 or lesser, and more
vast majority reach adulthood owing to breakthroughs in
states are expected to join the league soon [1,12]. The CHD
diagnosis and management. This; however, is not the case
program may perceived to be expensive, cumbersome and
in LMICs. One fully equipped cardiac centre is estimated to
unyielding, experience and evidence from the ‘Hridayam’
serve a population of 1,20,000 in North America, while the
program; however, suggest this to be the only way to
same serves a population of 16 million in Asia. Similarly,
reduce IMR further in these states.
one cardiac surgeon serves a population of 3.5 million in
North America and Europe, while the figure in Asia is 1 per THE WAY FORWARD
25 million [8]. In India, a population of 141 crore is served
The Government of India is committed to achieve ‘single
by a handful of centers. We have very few trained
digit’ NMR by 2030 and U5MR of 23 by 2025 [13,14].
professionals in various disciplines of pediatric cardiac
Stagnating contribution of neonatal deaths to under-5
sciences and intensive care. Scarcity of facilities in public
deaths (i.e., ~55%) across states irrespective of their
sector hospitals is even more glaring. Even within the
U5MR and SDI [1] suggests the need to shift on to the
country, available pediatric cardiac facilities are unevenly
next paradigm of interventions. Birth-defect surveillance
distributed [8].
and management program is likely to reduce U5MR further,
Until recently, children with CHD were being managed especially in states with U5MR<25 [2]. Diagnosis and
through out-of-pocket expenditure. Thus, the majority management of CHD would be the most important aspect
were unable to afford timely surgery. Implementation of of this program.
flagship public healthcare schemes [e.g., Pradhan Mantri
Continuum of Care Through Ayushman Bharat
Jan Arogya Yojana (PM-JAY), Janani Shishu Suraksha
Karyakaram (JSSK) and Rashtriya Bal Swasthya Experience from countries with high SDI revealed that
Karyakram (RBSK)] is likely to become a game-changer. identification of newborns with CHD before discharge
Despite availability of funds through such schemes, from hospital, excellence in emergency care, and develop-
proportion of children with CHDs getting operated differs ments in pre-operative and post-operative intensive care,
substantially across different regions of the country — cardiopulmonary bypass and surgical techniques have
Central region (7.6%), Eastern region (12%), Northern dramatically improved survival of children with CHD [15].
Hridayam program provided a made-in-India model of patients’ choice. These person- and purpose-specific
community-based pediatric cardiac care continuum payment vouchers means public subsidy is provided only
(beginning from the antenatal period to the postnatal to the needy and only for the intended purpose. Early
evaluation, cardiac surgery and long term follow up), diagnosis, prompt referral, provision of affordable
which may be replicated in other parts of the country. The treatment, combined with better post-operative home-
experience gained may inform a national policy for children based care, would be a game-changer in bringing down the
with CHD, which may work to develop a similar approach attributable infant and child mortality.
integrating JSSK and RBSK with PM-JAY. As part of
Developing Pediatric Cardiac Care Services in
comprehensive primary health care, obstetricians and
the Public Sector
sonographers at Health and Well-being Centers (HWCs)
and district hospitals may be trained to detect CHD during Establishing at least one premier Center of Excellence
antenatal period. Inclusion of essential physical cardiac (CoE) in each region is an urgent need of the hour.
examination and pre-discharge screening by pulse Northern and eastern regions may be prioritised in view of
oximetry in the existing neonatal protocols would help to wider demand-supply gap; the former has lower U5MR as
detect CHD before discharge. Healthcare providers may be well. These centers should have five essential, distinct
trained to identify survivors of neglected CHD presenting and child-specific specialized clinical service verticals
to healthcare facilities or detected through school health working in horizontal collaboration– Pediatric (diagnostic
programs. Suspicion of CHD would prompt timely referral and interventional) Cardiology, Pediatric Cardiac Radio-
and transport of in utero baby, neonate or older child to a imaging, Pediatric Cardiac Intensive Care (to provide
designated tertiary care centre for detail assessment. specialized intensive care services before and after cardio-
Children with CHD thus identified may receive secondary logical intervention and cardiac surgery), Pediatric Cardiac
and tertiary healthcare under public-funded schemes. Surgery and Pediatric Cardiac Anaesthesia. Cardio-
Integration of HWCs with secondary and tertiary care pulmonary bypass, extracorporeal membrane oxygenation
centers may be enabled through care pathway linkages and pediatric cardiac critical care nursing services are
and information technology by creation of Ayushman essential component of the CHD program. Ancillary
Bharat Health Account (ABHA) ID, which would create a services should include Pediatric Cardiac Airway, Pediatric
longitudinal health record for babies with CHD. Recently, Cardiac Pulmonology and Cardiac Genetic services.
follow up packages has been added under PM-JAY to Creating CoEs in the established institutes of national
provide continuous support even after discharge from importance (INIs), as extension of their pediatric services,
hospital. National Health Authority introduced a digital is likely to be logistically and financially prudent. These
payment voucher, e-RUPI to ensure uninterrupted access CoEs would act as apex institutions, and would provide
to diagnostics and therapeutics from providers of training-learning opportunities, develop academic
Fig. 1 Effect of Hridayam program on the stagnating infant mortality rate in Kerala (1991-2019).
programs, help capacity-building and stimulate country- sciences in the new generation of tertiary healthcare
specific research and innovations [8]. institutions of national importance (e.g., the new All India
Institutes of Medical Sciences) and the autonomous
Strengthening behaviour change communication: Public
tertiary healthcare institutions under various state
awareness needs to be created about long-term survival of
governments would significantly improve the access
most of the CHD patients. It may improve health-seeking
across the country. They would also help create locally-
behavior within community. Emphasis on primary
relevant innovative approaches towards CHD program.
prevention by reducing consanguinity, immunization
These initiatives are likely to lead to development of a
against rubella, reducing risk factors like smoking, alcohol
comprehensive and sustainable India-made ecosystem to
intake during pregnancy, supplementing folic acid during
effectively deal with the epidemiological transition during
first trimester, and optimal control of diabetes should also
Amrit Kaal (2022-2047).
be on cards [16].
Deliverables
Human Resource Development
Improved childhood survival is likely to improve life
Management of CHD needs development of specialized
expectancy at birth and thus our Human Development
professionals in various disciplines of pediatric cardiac
Index [1]. Creation of a large public-funded healthcare
sciences as mentioned above. At present, we only have a
scheme would lead to new investments in healthcare,
post-doctoral (DM) program in Pediatric (diagnostic and
pharmaceutical, manufacturing and biomedical
interventional) Cardiology, and that too only at All India
engineering sectors. A relatively stable birth prevalence of
Institute of Medical Sciences-Delhi and Postgraduate
CHD, large population, huge demand-supply gap and
Institute of Medical Education & Research-Chandigarh.
locally relevant research/innovation would make the
There are no post-doctoral programs in the other four
indigenously developed CHD program self-sustainable,
essential disciplines. While establishing CoEs may be a
scalable and replicable. Shift of care of CHD from currently
long-term goal, post-doctoral programs need to be started
dominant private corporate hospitals to the public
immediately with horizontal integration of resources from
healthcare delivery system is likely to benefit domestic
Departments of Pediatrics, Cardiology, Cardiovascular
industry, as has been seen in the vaccine sector [17,18]. An
Surgery, Radiodiagnosis and Anesthesia in the
economically competitive CHD program could also foster
established INIs (Table I). The National Medical
medical tourism. All these would end up generating
Commission (NMC) and National Board for Examinations
employment for unskilled, skilled and highly skilled
in Medical Sciences (NBEMS) may find inclusion of these
personnel. In a nutshell, such a CHD program would fulfil
academic programs in their bouquet of post-doctoral
objectives of Atmanirbhar Bharat Abhiyaan, Heal-in-India
courses as visionary, and as need of country’s near future.
and Health-by-India programs, and would be an important
Training programs to create a pool of perfusionists,
component of roadmap to India@100.
pediatric cardiac critical care nurses and other
professionals required for in-hospital and out-of-hospital CONCLUSIONS
care of children with CHD may also be planned (Table I).
With reducing child mortality, CHD is becoming a key driver
Initiation of pediatric cardiac services and training
of childhood survival. Multilateral collaboration between
programs in various disciplines of pediatric cardiac
policy makers, administrators, public health delivery system, systematic review and meta-analysis. J Am Coll Cardiol.
private hospitals and pediatric cardiac professionals is 2011; 58:2241-47.
urgently needed. It would help in developing and 8. Saxena A. Congenital Heart Disease in India: A Status Report.
implementing pediatric cardiac care continuum across the Indian Pediatr. 2018;55: 1071082.
9. GBD 2017 congenital heart disease collaborators. global,
country. At least one CoE per region needs to be established,
regional, and national burden of congenital heart disease,
prioritizing the under-served regions. Professional training 1990-2017: A systematic analysis for the Global Burden of
programs may be initiated to create a sustainable ecosystem. Disease Study 2017. Lancet Child Adolesc Health.
An evidence-informed national policy may go a long way in 2020;4:185-200.
managing the imminent epidemic of CHD, improving HDI 10. Maheshwari S, Kiran VS. Cardiac care for the economically
ranking, and generating jobs in the run up to the centennial challenged: What are the options ? Ann Pediatr Cardiol.
celebrations of our independence in the year 2047. 2009;2:91-94.
11. Nair SM, Zheleva B, Dobrzycka A et al. A population health
Funding: None; Competing interests: None stated. approach to address the burden of congenital heart disease in
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Correspondence to: Dr Dinesh Kumar, Associate Professor, Department of Community Medicine, Dr Rajendra Prasad Government
Medical College, Kangra, Himachal Pradesh. dinesh9809@gmail.com
Received: May 07, 2022; Initial review: June 15, 2022; Accepted: November 28, 2022.
Objective: To compare the risk of early childhood obesity (BMI z- exposed and exposed group, respectively. Adjusted relative risk
score of ≥+2SD) among children of more than 7 years of age (aRR) between exposed and high BMI (>+2SD) was 4.9 (95%CI:
with a birth weight of more than 3500 g to a birth weight of 2500- 1.3-17.5) adjusted for mean age, gender, mean years of
2999 g. schooling, consumption of butter, fruits, vegetables, and indoor
playing.
Methods: Retrospective birth cohort study among children of 7
to 10 years of age in 22 villages of Himachal Pradesh with not- Conclusion: High birth weight (>3500 g) increases and normal
exposed (birth weight: 2500 to 2999 g) and exposed (> 3500 g) birth weight decreases the risk of childhood obesity up to five
group. times in rural India.
Results: A total of 379 and 377 participants were enrolled in not- Keywords: Body mass index, Catch-up growth, Outcome,
Overweight.
T
he nutrition in utero influences the risk of immediate vicinity of a metropolitan city [12,13]. Cultural
developing chronic diseases in adulthood like and dietary diversity has been observed in rural India for
obesity, metabolic syndrome, and heart preference of food items, ways of cooking food, and
diseases [1]. Maternal nutrition and health pattern of physical activity.
status affect in utero growth and development reflected by
This study was done to measure the relative risk for
birth weight as an outcome [2]. High birth weight (>3500 g)
early childhood obesity among children more than 7 years
is associated with morbidities later in life like obesity and
of age with a birth weight of more than 3500 g as compared
associated chronic diseases [3,4]. Adiposity during
to birth weight of 2500-2999 g in rural northern India.
childhood and adolescence was related to a high level of
blood glucose, insulin, and insulin resistance [5]. Apart from METHODS
in utero nutrition and health, postnatal dietary patterns are
A retrospective cohort study was conducted in 22 villages
also associated with chronic diseases in adulthood.
of a health block of district Una, Himachal Pradesh,
India observed a rising trend of overweight and covering a population of about 6.9 million with 1.4 million
obesity in both high and low socioeconomic groups [6]. households. The local census by the health administration
Childhood overweight and obesity warrants early showed that the health block had a population of 71,416
detection and appropriate intervention for the prevention with 14,107 households. The study was approved by the
of chronic diseases. Longitudinal studies and birth institutional ethics committee.
cohorts provide evidence for causal relationship between
risk factors and chronic diseases in adulthood during Invited Commentaries: Pages 94-97
antenatal and postnatal period. Indian birth cohorts have
Children with birth weights from 2500 to 2999 g were
been established and followed up to delineate risk factors
considered as not-exposed and more than 3500 g as an
associated with chronic diseases [7,8]. Similar data of birth
exposed group. The category of birth weight 3000-3499 g
cohort in rural areas of northern India are limited [9].
was not included to avoid overlap between high (exposed)
Likewise, other studies from India were hospital-based
and normal (not-exposed) birth weight. Inclusion criteria
[10,11], or were done in southern part of India around
for recruitment were children who possessed immunization
cards mentioning her/his birth weight, born in year 2011- test were used to compare for statistical significance for
12, a native resident of the village, and with an informed continuous and categorical variables between groups.
consent of parents. Participants with a known cause for The relative risk (RR) with a 95% confidence interval (95%
pathological obesity were excluded from the study. CI) was calculated to assess the strength of association
Recruitment was carried out in two phases: phase-I (2013- between birth weight and childhood obesity. Binary
14) and phase-II (2021-22). logistic regression analysis was done to observe unadjusted
RR and adjusted RR (aRR) of obesity and high birth weight
Data were collected by a trained field attendant using a for child age, gender, years of schooling, mean fraction of
pretested questionnaire containing information about time spent playing indoors, and consumption of fruits,
background characteristics like gender, socioeconomic vegetables, and Ghee/butter. Variables that were significantly
status, and schooling, followed by diet and physical different in descriptive analysis. The analysis was also
activity. Dietary assessment was done using interviewer- adjusted for potential confounders like the age of the mother
administered questionnaire where information regarding and socioeconomic status.
consumption of food items like fruits, vegetables, cooking
oil, additional butter/ghee while eating, salt while cooking RESULTS
were collected from parents of participants. For the study
A total of 399 (93 exposed, 306 non-exposed) participants
purpose, indoor physical activities were focused on
were enrolled in the first phase and 349 (284 exposed, 73
activities requiring mild exertion like carrom board, ludo,
non-exposed) in the second phase. The mothers were the
mobile games, playing with toys without physical exertion,
respondent for all participants.
etc. whereas, outdoor activities included moderate to
severe exertion like cricket, football, race, etc. Udai Pareek The sociodemographic characteristics and dietary
scale was used to measure socioeconomic status in both consumption patterns are shown in Table I. None of the
phases of surveys. Anthropometric assessment was done families in both groups were consuming salt more than 5
for body height (in meters) without shoes by Seca grams of salt per person per day. Fried food consumption
portable stadiometer (Seca Corporation) with participant’s was observed to be high but the difference was statisti-
head in the Frankfurt plane, and body weight (in kg) was cally indifferent (Table I). The physical activity assessment
measured by a portable Tanita SC-240 body composition and anthropometry compared between non-exposed and
analyzer (Tanita Corporation) with minimal light clothing exposed groups are shown in Table II.
and removal of heavy clothing, pocket items, and shoes.
Both height and weight were measured twice, and a third The risk ratio (RR) (95% CI) of high BMI ( ≥+2SD) high
time only if the difference in the two values of height and birth weight (>3500 g) was 7.0 (2.1-13.8; P=0.002), which
weight was more than 0.5 cm and 0.5 kg, respectively. The was statistically significant even when adjusted for age,
final value was an average of the two closest values. Body gender, years of schooling, consumption of butter, daily
fat (in percentage) was measured by Tanita SC-240 body consumption of fruits and vegetables, and proportion of
composition analyzer and two consecutive measurements time played indoor [aRR (95%CI) 4.9 (1.3-17.5); P=0.005].
were taken. If the difference between the two With high BMI, adjusted measures of association was
measurements was more than 2.0%, a third value was taken significant only for females [aRR (95%CI) 0.4 (0.1-0.9);
and an average of two closest values was considered for P=0.037]. Adjusted association was statistically signi-
analysis. Body mass index (BMI) was calculated for every ficant between low BMI ( ≤-2SD) and exposed group [aRR
child by dividing weight (in kilograms) by the square of (95%CI) 0.5 (0.4-0.7); P<0.001].
height (in meters). The BMI z-score was calculated using DISCUSSION
age- and sex-specific reference data as per the World
Health Organization (WHO) charts. Obesity was defined The current rural birth cohort study observed a significant
as BMI z-score more than 2 standard deviations (SD). association of high birth weight (more than 3500 g) than
normal birth weight (2500-2999 g) with obesity. The
Sample size assumptions were made with incidence of outdoor physical activity assessment was similar in
obesity of 11% in not-exposed and 15% in the exposed exposed and non-exposed group.
group with a relative risk (RR) of 1.7 [18]. The sample size
of 748 (374 in each group) was calculated at 5% level of The current study was a birth cohort with an adequate
significance and 80% study power. sample size in a rural setting. The non-inclusion of birth
weight category of 3000 to 3499 g in the sample avoided the
Statistical analysis: Data were entered in Microsoft Excel exposure ascertainment bias. Potential covariates like
and analyzed using the R studio software package mean fraction of time spent on indoor physical activity,
(version 3.3.1). Unpaired students t test and chi-square addition of extra ghee/butter, and frequency of healthy diet
Table I General Characteristics of Rural Cohort of Table II Physical Activity and Anthropometric Assessment
Himachal Pradesh of Rural Cohort of Himachal Pradesh
Characteristics Not exposed Exposed P value Characteristics Not exposed Exposed P value
(n=379) (n=377) (n=379) (n=377)
Respondent age (y)a 33.5 (4.2) 33.9 (4.2) 0.133 Physical activity
Birth weight (kg)a 2.6 (0.4) 3.7 (0.2) <0.001 Indoor playing 281 (74.1) 293 (77.7) 0.247
Age of child (y)a 8.6 (1.1) 9.0 (1.0) <0.001 Daily 252 (66.5) 280 (74.3) 0.018
Time (min/d) 123.9 (87.0) 138.9 (82.2) 0.015
Child age-group
Outdoor playing 377 (99.5) 372 (98.7) 0.244
7 68 (17.9) 33 (8.8) <0.001 Daily 335 (88.4) 334 (88.6) 0.931
8 120 (31.7) 89 (23.6) 0.012 Time (min/d)a 157.5 (62.0) 156.6 (51.9) 0.816
9 94 (24.8) 99 (26.3) 0.631 Physical sports at School 54 (14.2) 52 (13.8) 0.857
10 97 (25.6) 156 (41.4) <0.001 Time (min/d)a 30.4 (4.3) 31.7 (5.8) 0.539
Female 194 (51.2) 159 (42.2) 0.012 Fraction of time played 38.4 (24.3) 42.5 (24.2) 0.020
SES categories Indoor
Lower middle 28 (7.4) 16 (4.2) 0.060 Anthropometry,a
Middle 283 (74.7) 283 (75.1) 0.899 Height (cm) 118.8 (9.3) 123.7 (8.3) <0.001
Upper middle 68 (17.9) 78 (20.7) 0.329 Weight (kg) 20.3 (4.6) 23.9 (6.0) <0.001
School going 377 (99.5) 377 (100.0) 0.169 BMI (kg/m2) 14.1 (1.9) 15.3 (2.7) <0.001
Public school 293 (77.7) 276 (73.2) 0.150 Percent of body fat 8.5 (2.4) 10.0 (3.9) <0.001
Duration of education (y)a 2.7 (1.3) 3.2 (1.2) <0.001 BMI z-score
Breast fed 365 (96.3) 361 (95.8) 0.724
-3SD 98 (25.9) 69 (18.3) 0.011
Ghutti/honey 364 (96.0) 361 (95.8) 0.889
-2SD 133 (35.1) 106 (28.1) 0.023
Vegetarian 296 (78.1) 303 (80.4) 0.435
-1SD 96 (25.3) 98 (26.0) 0.825
Days in a week of fruits 6.3 (1.4) 6.4 (1.3) 0.342
At median 36 (9.5) 49 (13.0) 0.128
consumption
+1SD 13 (3.4) 35 (9.3) <0.001
Consumption of 1.0 (0.2) 1.1 (0.2) 0.032
+2SD 3 (0.8) 16 (4.2) <0.001
fruits/day
+3SD 0 (0.0) 4 (1.1) 0.040
Days in a week of vege- 6.9 (0.4) 7.0 (0.3) 0.029
tables consumption Data expressed as no. (%) or amean (SD). Exposed group: birth-
Consumption of vege- 1.5 (0.5) 1.8 (0.4) <0.001 weight>3500g; not exposed group: birthweight 2500-2999 g.
tables/day
Mustard oil as a 376 (99.2) 376 (99.7) 0.574
baked goods/biscuits, sugar-sweetened beverages, etc.
cooking oil could have been more informative. The education of the
Amount of cooking 11.6 (2.9) 11.7 (3.3) 0.599 mother could have been associated with BMI, but for the
oil a day (mL) study purpose, the socioeconomic status was assumed to
Amount of butter/ 14.2 (33.4) 4.7 (20.4) <0.001 be a more useful covariate for BMI after the age of six
ghee day (g)a years.
Amount of salt while 7.9 (2.2) 7.6 (2.1) 0.051
cooking/day (g)a In a hospital-based study [8], children with high mean
Salt > 5 g/d 326 (86.0) 315 (83.6) 0.358 birth weight had associated decline in physical growth in
Fried food consumption in a wk their first two years of life [8]. This was different from
One 251 (66.2) 250 (66.3) 0.976 current study that was community-based and observed
Two 114 (30.1) 114 (30.2) 0.976 children from 7 to 10 years of age. Factors like physical
Number of times fried 2.7 (1.3) 2.8 (1.3) 0.239 activity and nutrition in later part of childhood were
food/daya
potential confounders in this study. The risk of obesity
Data expressed as no. (%) or amean (SD). Exposed group: birth- stayed significant as a measure of association for birth
weight>3500g; not exposed group: birthweight 2500-2999 g. weight category and BMI after adjusting these covariates.
(vegetables and fruits) were included to assess adjusted The available evidence from India suggests that the
measures of association. This study had a few limitations large size at birth and high birth weight predict high fat and
as well like we relied on proxy measures like indoor and lean body mass at the age of 6 years [14], and a high post-
outdoor games as a measure of physical activity. Also, natal size at the age of 9 years [15]. Pooled analysis of five
failure to collect information on intrauterine growth and birth cohorts in low-and middle-income countries
maternal nutrition posed a limitation to the measurement of (LMICs) observed a positive significant association
association. Additional information on consumption of between high birth weight and BMI (OR 95% CI: 1.3; 1.2-
1.3) [16]. Similarly, a 12-country cross-sectional study on observing trend of risk factors with a specific focus on at-
children from 9-11 years of age observed a positive risk children. A population-based approach to inter-
association between birth weight and BMI. Multivariable ventions focusing on healthy foods and physical activity
adjusted odds (95%CI) for BMI ( ≥ +2SD) was observed to will have the potential to address both under- and over-
be 1.5 (1.1-1.9) and 2.1 (1.5-2.9) among children with birth nutrition.
weight 3500-3999 and >4000 g, respectively [4]. A Ethics clearance: IEC/135/2019 dated Aug 13, 2019.
population-based study among children of age from 6 to Contributors: DK conceived and wrote the manuscript along with
10 years observed that the risk of being overweight data analysis. SS and SKR assisted in data analysis and
increases with each unit increase in birth weight for both manuscript editing.
boys and girls [17]. Low birth weight was associated with a Funding: Indian Council of Medical Research (ICMR), No.
decreased risk for overweight [18], and high birth weight RBMNCH/Ad-hoc/74/2020-21; Competing interests: None
(>4000 g) with a higher risk (1.7-1.8) of childhood obesity stated.
[18,19]. However, a recent meta-analysis did not observe REFERENCES
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Correspondence to: Dr Mehmet Sargin, Selçuk University Faculty of Medicine, Department of Anesthesiology and Reanimation,
Konya, Turkey. mehmet21sargin@yahoo.com
Received: January 23, 2022; Initial review: August 08, 2022; Accepted: December 24, 2022.
Background: Obesity has become a serious problem not only in following parameters: time to spontaneous ventilation, laryngeal
adult patients but also in pediatric patients. mask airway removal time, time to open eyes, and post-
anesthesia care unit discharge time.
Aim: To evaluate whether obesity affects the recovery profile
after general anesthesia in children. Results: When the recovery profiles were compared, no
Participants: 40 children (aged 2–12 years) who underwent significant differences were found between the groups. Time to
surgery under general anesthesia and had an American Society spontaneous ventilation [mean difference (95% CI); 0.66 (0.09-
of Anesthesiologists (ASA) physical I and II. 1.42); P=0.085], laryngeal mask airway removal time [MD (95%
CI); 1.12 (0.06–2.22); P=0.057), time to open eyes [MD (95% CI)
Methods: This prospective cohort study was conducted over a 0.66 (0.40–1.74); P=0.217], and post-anesthesia care unit dis-
period of 3 months (January- April, 2021). The patients were charge time [MD (95% CI) 3.60 (0.59-7.25); P=0.054] were higher
divided into two groups according to body mass index (BMI): in Group II; however, these differences lacked both statistical
Group I comprised obese children (BMI ≥95th for age percentile) and clinical significance.
(n=20) and Group II comprised children with a normal BMI (25– Conclusion: The results suggest that obesity has no effect on
75th for-age percentile) (n=20). Anesthesia induction and the recovery profile after general anesthesia in children in our
maintenance were performed as per standard guidelines in both setting.
the groups.
Keywords: Adverse events, Body mass index, Outcome,
Outcome: The recovery profile was evaluated with the Sedation.
Trial registration: ClinicalTrials.gov; NCTO4652193. Published online: Jan 02, 2023; PII: S097475591600480
O
besity is having an increasing impact on adult Changes in body composition affect drug use; therefore, it
patients undergoing surgery worldwide. is important to know the weight scales required for dosing
Similar to this trend in adults, approximately in obese pediatric patients [10].
one-third of children admitted for surgery are
Although the perioperative care of obese adults has been
overweight or obese [1,2]. Childhood obesity is defined as
extensively studied, relatively few studies of this type have
a body mass index (BMI) above the 95th percentile for age
examined obese children. Similarly; although, there are pediatric
and gender, and the prevalence of childhood obesity is
studies on the recovery profile, there are no studies on this issue
upto 16.9% in some countries [3].
in obese children. The present study aimed to evaluate the
Obesity poses many difficulties for clinicians, as it is effect of obesity on the recovery profile of pediatric patients.
associated with pathophysiological changes affecting
METHODS
various organ systems [4,5]. Furthermore, obesity causes
an increase in perioperative and postoperative anesthesia After obtaining institutional ethics committee approval,
complications. Peripheral intravenous access difficulties written consent was obtained from the legal guardians of
caused by obesity and prolonged recovery profiles affect the children enrolled in the present study, which was also
the patient care process [6]. Moreover, the greatest registered at http://clinicaltrials.gov. Patients with
concern in anesthesia practice is the increasing adverse cerebrovascular disease and a history of drug use
airway and respiratory events [2,6,7]. In addition, obesity affecting the central nervous system, as well as patients
increases hospital costs, length of hospital stays, and transferred to the ward without visiting the recovery room,
unexpected hospitalization rates after surgery [8,9]. were excluded from the study.
Patients included in the study were divided into two they were evaluated according to the following criteria for
groups according to the body mass index (BMI): Group I discharge: consciousness, normal vital signs, no pain, and
comprised obese children (>95th BMI for age percentile), no nausea or vomiting. Discharge from the PACU of all
and Group II comprised children with a normal BMI (25– patients was performed by an anesthesiologist blinded to
75th BMI for age percentile). For this division, reference the study according to the standard guidelines in use in
values for Turkish children developed by Neyzi, et al. [11] the institution. For measuring postoperative pain, the
were used by a pediatrician, using preoperative measure- FLACC scale [13], which is based on a 0-10 score, was used
ments that were blind to intraoperative and postoperative in the PACU. According to the FLACC scale score, the
evaluations [11]. patients’ pain was evaluated as mild pain (0-3), moderate
pain (4-7), and severe pain (>7). Postoperative nausea and
All patients enrolled in the study complied with the
vomiting was evaluated with the Baxter Animated Retching
fasting periods specified by the ASA, and none of them
Faces (BARF) scale [14]. Surgical procedure duration,
received premedication. Standard monitoring was applied
anesthesia time, and PACU stay time were also recorded.
in the operating room. Anesthesia maintenance was per-
Anesthesia duration was evaluated as the time elapsed
formed with 1-2 minimum alveolar concentration (MAC) of
between induction of anesthesia and discontinuation of
sevoflurane in oxygen, which is the standard practice at
anesthetic agents. To evaluate the recovery profile, four
our clinic. All baseline measurements were recorded before
parameters were evaluated: i) time to spontaneous
anesthesia induction. After face mask inhalation induction
ventilation (time elapsed between discontinuation of
with 8% sevoflurane in oxygen in both groups, an intra-
sevoflurane and remifentanil and initiation of spontaneous
venous catheter was placed, and fentanyl (2 µg/kg,
ventilation of the patient); ii) LMA removal time (time
intravenous) was administered. After the establishment of
elapsed between discontinuation of sevoflurane and
intravenous access, 5% dextrose, 0.45% NaCl, and 5-10
remifentanil and removal of LMA); iii) time to open eyes
mL/kg/hour fluid infusion was initiated in accordance with
(time elapsed between discontinuation of sevoflurane and
our standard clinical practice. The sufficiency of anes-
remifentanil and eye-opening in response to a verbal or
thesia depth was evaluated considering the loss of eye-
painful stimulus); and iv) the length of stay in the PACU.
lash reflex and jaw opening. Then, airway patency was
The recovery profile was evaluated by two anesthetists
provided through the laryngeal mask airway (LMA).
experienced in pediatric anesthesia, and blinded to the
Volume-controlled mechanical ventilation was applied after
patients’ BMIs classification.
LMA insertion. Mechanical ventilation parameters were as
follows: tidal volume (6-8 mL/kg), respiratory rates were The current study was designed (1-β=90% and
adjusted to achieve an end-tidal carbon dioxide (EtCO2) of α=0.05) to detect a 25% change in the time to spontaneous
30-35 mm Hg, and positive end expiratory pressure was ventilation, as reported in a previous study [12]. We
not applied. Sevoflurane and remifentanil (0.25 µg/kg/min) calculated a sample size of 16 patients for each group.
was used for anesthesia maintenance. When there was a Thus, considering a 25% possible loss, it was planned to
decrease of more than 20% in mean blood pressure com- include 20 patients in each group.
pared to basal values, the crystalloid infusion rate was
increased. If this was not enough, the concentration of Statistical analysis: These were performed with SPSS 15.0
sevoflurane was decreased, and anesthesia maintenance software (SPSS Institute). Student t test was used in the
was continued. Paracetamol (10 mg/kg) was preferred for analysis of parametric data and results were presented as
postoperative analgesia. Heart rate, mean blood pressure, mean (SD) or mean (standard error of means). The analysis
and oxygen saturation (SpO2) values were constantly of categorical data was performed with the two-tailed
monitored and recorded at the following times: baseline, Pearson chi-square test and the results were expressed as
after induction of anesthesia, after successful LMA numbers. A P value less than 0.05 was considered
insertion, at the beginning of the surgical procedure, every statistically significant.
10 minutes during surgery, at the end of surgery, after LMA
removal, and during eye opening with stimuli (verbal RESULTS
stimulus and/or painful pinching). Anesthesia mainte-
A total of 40 patients were enrolled in this study between
nance stopped as the surgery neared conclusion. The
January, 2021 and April, 2021. All participants completed
LMA was removed when adequate depth of breathing was
the study and none were excluded. Patients demographics
reached (tidal volume >6 mL/kg, respiratory rate >16
are summarized in Table I. There were no significant
breaths per minute, and SpO2 greater than 98%) [12].
differences between the two groups in terms of
After removal of the LMA, the patients were demographic data except weight (P=0.004) and BMI
transferred to the post-anesthesia care unit (PACU), where (P<0.001), which were higher in Group II.
Table II Recovery Time, and Scores on the FLACC Scale and BARF Scale in the Two Groups
Obese children Non-obese children Mean difference P value
(n=20) (n=20) (95% CI)
Time to spontaneous ventilation (min) 3.57 (1.05) 4.24 (1.31) 0.66 (0.09-1.42) 0.085
LMA removal time (min) 4.82 (1.18) 5.94 (2.13) 1.12 (0.06-2.22) 0.057
Time to open eyes(min) 6.45 (1.40) 7.12 (1.91) 0.66 (0.40-1.74) 0.217
PACU stay time (min) 23.35 (5.66) 26.95 (5.76) 3.60 (0.59-7.25) 0.054
FLACC scale scores 3.45 (2.81) 4.85 (2.72) 1.40 (0.37-3.17) 0.118
BARF scale scores 1.90 (1.60) 2.30 (1.86) 0.40 (0.20-1.90) 0.248
Values are mean (SD). PACU: Post-anesthesia care unit; BARF: Baxter animated retching faces; LMA: Laryngeal mask airway.
study was performed in patients who underwent choice of anesthetic agent had an effect on the PACU
procedural sedation, and the recovery profile was not discharge times, and it was determined that the recovery
clearlydelineated [15]. In a study conducted in obese adult after desflurane was faster than after sevoflurane,
patients using sevoflurane for maintenance of anesthesia, isoflurane and propofol [21]. However, due to the nature of
it was shown that obesity did not affect the recovery times the present study, sevoflurane was preferred for anes-
[16]. In this study, recovery times were evaluated through thesia induction and maintenance in pediatric patients.
bispectral index monitoring. In the present study, the Although it is not clinically significant, we think that the
recovery profile was defined by clinical parameters but the high BARF score in Group II is the reason for prolonged
results were similar. PACU stay time in Group II. In a study conducted in adult
obese population, the effects of opioid type (remifentanil,
It has been shown that obesity causes a delay in the
fentanyl and alfentanil) added to propofol on recovery
response to verbal stimuli and is associated with a
profile were evaluated [22]. Spontaneous ventilation time
prolonged return time in airway reflexes [17]. The patients
and extubation times were found to be shorter in the
in this study were older and two different inhalation
remifentanil group compared to other opioids. In the
anesthetics (sevoflurane and desflurane) were used
present study, we preferred the use of remifentanil for
randomly for the maintenance of anesthesia of the
anesthesia maintenance. In a meta-analysis on this subject,
patients. In a retrospective study by Lee, et al. [18], in
the effects of desflurane and sevoflurane on the recovery
children aged 2-18 years, it was shown that obesity did not
profile of patients undergoing bariatric surgery were com-
affect the duration of anesthesia. Of the 9522 patients
pared, and it was stated that faster early recovery occurred
whose data were available for the study, 17.2% were
in patients who used desflurane for anesthesia mainte-
considered obese. In this study, the only independent
nance [23]. In another study comparing the effects of
predictor of both longer anesthesia and surgery durations
sevoflurane and desflurane on recovery profile in adult
was older age.
obese patients, no difference was found between the
In a study that included morbidly obese children and groups [24]. In our study, since our population consisted
adolescent patients undergoing laparoscopic surgery of pediatric patients, sevoflurane was preferred for the
under total intravenous anesthesia, it was stated that induction and maintenance of anesthesia.
excessive anesthetic administration was required and the
emergence was prolonged [19]. This prospective study There are some limitations of this study. Firstly,
had; however, only included morbidly obese patients aged anesthetists evaluating the recovery profile could have an
9-18 years, which could have been the reason for the idea about the BMI of the patients based on their physical
differences from this study. appearance; although, they were blind to the BMI
category of the children. Secondly, BIS monitoring was not
There are only limited number of studies evaluating used to monitor the depth of anesthesia of the patients.
PACU discharge time in the literature, and the results are However, this situation was eliminated by the use of the
different from the results of our study [20,21]. In a study same clinical application in the maintenance of anesthesia.
evaluating the effect of obesity degree on PACU discharge
In conclusion, based on the results of this study, we
times in a pediatric patient group, it was stated that
believe that obesity does not have any effect on the
although PACU stay time was prolonged in both moderately
clinical recovery profile of pediatric patients operated
and severely obese children who were operated under
under general anesthesia, and this information should
general anesthesia, there was no difference according to the
inform routine clinical practice.
obesity degree [20].
Ethics clearance: Selcuk University Faculty of Medicine Ethics
In a meta-analysis [21], it was shown that no difference Committee; No. 2019/51 dated Jan 30, 2019.
could be detected between obese and non-obese adult Contributors: All authors approved the final version of the
patients when PACU discharge times were evaluated. manuscript, and are accountable for all aspects related to the
These results are in parallel with the results of the present study.
study. It was also stated in this meta-analysis that the Funding: None; Competing interests; None stated.
Correspondence to: Dr Rebecca Kuriyan, Division of Nutrition, St John’s Research Institute, St John’s National Academy of Health
Sciences, Bengaluru 560 034, Karnataka. rebecca@sjri.res.in
Received: July 14, 2022; Initial review: August 20, 2022; Accepted: December 24, 2022.
Background: The prevalence of childhood obesity is increasing street connectivity and land-use mix environment variables.
in low-middle income countries like India. Built environment Results: The mean (SD) of age, body mass index (BMI), BMI z-
features such as walkability can influence weight-related score and percentage body fat (% Body fat) of 292 (50% boys)
outcomes but data from developing countries are scanty. children were 10.8 (2.9) year, 17.4 (3.3) kg/m2, -0.27 (1.35) and
Objective: To develop population level walkability index in urban 20.9% (8.8), respectively. The mean (SD) walkability index was
Bengaluru, and examine its association with indices of childhood 16.5, which was negatively associated with BMI (slope -0.25
obesity in school children. and -0.08) and percentage body fat (slope -0.47 and -0.21) for
age 5 and 10 years, respectively in children, but the effects
Study Design: Nested cross-sectional study based on a
decreased with increasing age.
cohort.
Participants: Normal healthy children aged 6 to 15 years from Conclusions: The findings of this pilot study suggest that the
urban schools in Bengaluru. The children were stratified into neighborhood walkability may be associated with the obesity
different land use classification such as residential, commercial indices in younger children. Future longitudinal studies are
and open space based on residential address. needed to understand how built environment affects health and
body composition of children in India and other low-middle income
Methods: Anthropometric data, body composition data, countries.
measured using air displacement plethysmography.
Keywords: Air displacement plethysmography, Body mass
Outcomes: Walkability index derived using residential density, index, Built environment, Physical activity.
T
he increasing prevalence of childhood obesity has shown to promote physical activity and prevent
is a major global public health challenge, steadily obesity [6]. Increased walkability characteristics have
affecting the urban population in India, with been associated with lower body mass index (BMI) z-score
combined prevalence of overweight and obesity in children [7], and in adults [8]. Walkability index, defined
of 5% in children aged 10-19 years [1]. In urban Bengaluru, as the extent to which the built environment is walking
13% of school-going children were overweight, while 5% friendly, can be derived by adopting spatial data obtained
were obese [2]. Multiple lifestyle factors, genetic, beha- from geographical information system (GIS), which has
vioral and environmental conditions contribute to the become popular to generate measures of specific attributes
etiology of obesity, also seen in Indian children [3]. The of the built environment, with its relative convenience,
barriers to physical activity in children include lack of smaller measurement error, higher reliability, and ease of
support/encouragement from parents, parental concerns translating to into health and planning policy [9-11].
with regard to safety, unsafe neighborhood, increased
The need for optimal urban planning and transport
traffic, risk of accidents, inadequate built environment,
policies to create and preserve built environments, with
and lack of recreational facilities [4]. Built environment can
supportive infrastructure for active commuting such as
influence weight-related outcomes through physical
walking and cycling has been highlighted by the World
activity, outdoor play, active transportation, dietary habits
Health Organization’s Global Action Plan for the
and sedentary behavior [5].
Prevention and Control of NCDs 2013–2020 [12]. India is
Neighborhood walkability, the capability to support faced with multiple problems such as lack of supportive
walking for multiple purposes such as availing transport, infrastructure, traffic congestion, overcrowded streets, air
shopping, recreation for children, commuting for school pollution and policies/ investments to promote active
commuting. There are limited Indian studies on American Neighbourhood Quality of Life Study (NQLS)
neighborhood walkability and body weight [13]. [9] walkability indexes. These walkability indexes are
constructed by four built environment variables-
Bengaluru is currently placed third among the top 10
residential density; street connectivity; land-use mix; and
fastest growing cities in the world [14]. The effect of
net retail area (a measure of pedestrian friendliness).
urbanization on the prevalence of overweight/obesity
However, retail area (which is the measure that calculates
among children is important. The primary aim of this
the retail floor area in relation to the total amount of land
exploratory study was to develop population level
area for retail use) information of Bengaluru city was not
walkability index for selected localities in Bengaluru city. The
available electronically in public domain. Therefore, we
secondary objective was to associate the walkability index
derived GIS based walkability index in the present study
with indices of childhood obesity such as BMI, body fat, and
using the other three components (Web Fig. 1).
waist to height ratio (WHtR) in a subset of school children.
METHODS The Global positioning system (GPS) coordinates of
residential addresses of 300 students were obtained by
The Pediatric Epidemiology and Child Health (PEACH) Google earth or Open street map from the street level
cohort was established by the Division of Nutrition, St. addresses. Further, these GPS coordinates were plotted on
John’s Research Institute, Bengaluru in 2011 [15], and the open street map to check the accuracy manually by street
children for the present study were recruited from this addresses of the residences and corrected accordingly in
cohort from the year 2011 to 2016 [2]. The study was case of discrepancy. A buffer of 1 km radius was drawn
approved by the institutional ethics committee. Normal over each of the residential coordinates within ArcGIS
healthy children aged 6 to 15 years were included into the platform [18].
study, while children with any chronic illness as reported
by the parents during the consenting process were Dwelling density, street connectivity and land-use mix
excluded. The schools were selected by using convenience were then derived for each of the buffer from ArcGIS tools.
sampling procedure for operational feasibility. The number of residential units were counted within each
buffer from the detailed map of Bengaluru city obtained
The children of the above cohort were stratified into 12 from the local municipality, over total residential area within
land use classification typologies by combination of the buffer. The dwelling density was derived by dividing
different degrees of land use of three basic patterns such number of residential units by total residential area within
as residential, commercial and open space based on each buffer. The street connectivity was measured by
children’s residential address. street intersection density. With the help of Bengaluru
The anthropometric measurements of body weight, map, the number of street intersections were counted
height and waist circumference were performed according within each of the buffer. Further, dividing the same by area
to standard techniques [16]. Children were weighed in light of each of the buffer provided intersection density as a
clothing using a calibrated digital scale (Salter), to the measure of connectivity.
nearest 0.1 kg. The height was measured to the nearest 0.1 Four different land use classifications that defined the
cm using mobile stadiometer (Seca 213). Waist variation of the land use such as residential, commercial,
circumference (WC) was measured with a non-stretchable park and open space area, and public and semi-public area
tape by trained nutritionists (exerting the same standard were measured. The sum of land area by the buffers was
pressure on the tape) at the midpoint of the lowest rib cage used to create an entropy score for each buffer, using the
and the iliac crest, to the nearest 0.1 cm, in a standing entropy equation [10]. The entropy equation results in a
position during end-tidal expiration. The body fat of the score of 0-1; 0 representing homogeneity and 1
children was measured using the BOD POD (Cosmed), representing heterogeneity.
with software version 5.2.0, which works on the principle of
air-displacement plethysmography (ADP) [17]. The BOD In order to create a standard measure, all the above
POD was placed inside a van and parked at a location measures were converted into 10-point scale, with scores
close to the measurement room in the school. The internal from 0 to 10 [10]. The walkability index was calculated by
CV of body fat by this method was 2.3% [2]. All the other summing up the scores of dwelling density, connectivity
measurements were performed at the schools in a room and land-use mix; the calculated index would be between 0
allotted for the study. and 30, with ‘0’ being the worst and ‘30’ being the best
walkability.
Two frequently used GIS based walkability indexes are
the South Australian Physical Activity in Localities and Sociodemographic details of selected school going
Community Environments (PLACE) study [10] and North children such as age, sex, BMI, income of parent, parental
BMI along with body composition of the children were Table I Demographic and Anthropometric Data (N=292)
extracted from the original cohort data base. Variable Mean (SD)
Statistical analysis: Data were analyzed using statistical Age (y) 10.84 (2.89)
software R version 4.1.0 (R core team, 2021). Distribution Body mass index (BMI) (kg/m2) 17.39 (3.26)
of health and demographics along with walkability index
BMI z-score -0.27 (1.35)
were summarized by descriptive statistics. Univariate
linear regression technique was applied to explore Waist-height ratio 0.44 (0.06)
univariate association between BMI, body fat /obesity % body fat 20.97 (8.78)
indicators and sociodemographic parameter. Unadjusted Body fat mass (kg) 7.89 (5.23)
associations between obesity indices and walkability were Paternal BMI (kg/m2), n=243 25.17 (3.62)
also examined prior to the estimation of adjusted effects of Maternal BMI (kg/m2), n=250 24.97 (4.76)
walkability on obesity indicators. Finally, a multivariate
Walkability index 16.54 (5.87)
linear mixed model with interaction was used to estimate
the effects of walkability on obesity indices adjusted for BMI: body mass index.
relevant confounders, effect modifiers and cluster effects
of school. 398) per month. The descriptive statistics are reported in
Table I. Web Fig. 2 depicts distribution of walkability
RESULTS
across households of the study participants.
The total cohort size was 9060 children (5172 boys). A
The univariate analysis exhibited significant
stratified random sample of 300 children was selected from
association between BMI and walkability index, age, sex of
the cohort as per the land use classification (Fig. 1).
the children and parental BMI. The walkability index
However, due to non-availability of body composition showed negative associations with percentage body fat
data of some of the selected children, the effective sample and waist height ratio (WHtR) but were not statistically
size was 292 (146 boys). Fifteen (5%) children were obese significant (Fig. 2). In the present analyses, sex was
while 44 (15%) were overweight based on BMI z-scores. considered as a confounder in the association of
Only 260 households had complete family income data walkability with BMI and percentage body fat. When the
with mean family income INR 26000 to 30000 (USD 345 to association of sex with walkability index was analyzed in
PEACH Cohort
2011 to 2012
n=9060
↓
Apparently healthy children
2011 to 2016 n=7425
A stratified random sample of 300 children were selected from the cohort. Out of 12, LCs, LC6 was excluded due to poor representation.
Children were equally stratified into 11 land use classification (27 in each. 3 additional children were selected from the 3 biggest strata.
LC=Land use classification
DISCUSSION
The present study developed population level walkability
index for selected localities in Bengaluru and examined its
association with indices of obesity in school going
children. Walkability index is a quantifiable index to study
health-promoting effects of the built environment that
was negatively associated with the BMI and percentage
body fat of children.
Studies from other countries have shown mixed results
in the associations between walkability and childhood
obesity [19-21], which could be due to difference in
analytical methods, measurement of study variables like
BMI, self-reporting of weight and height, and cross-
sectional nature of the studies. However, the concept of
an anti-obesogenic environment, including improved
Vertical dotted lines indicate the null hypothesis values. The error
bars that do not intersect dotted lines were considered statistically walkability is plausible. Additionally, the results from
significant. Western countries cannot be inferred for a LMIC like India,
where the built environment has distinct patterns of
Fig. 2 Univariate analysis between a) body mass index (BMI), b)
urbanization, density, and land use. With the rapid
% body fat and c) Weight-height ratio (WHtR) and walkability
index, age and sex of the children, parental BMI (the error bar increase in the prevalence of childhood overweight/
plots compare the unadjusted effects of different covariates and obesity and adult non-communicable diseases, it is
walkability on obesity indicators). important to understand the associations and develop
country-specific solutions for India.
the regression model by using sex as an interaction term, Walking is a significant mode of transport in India, but
we observed nonsignificant interaction coefficient, the difficulties faced by the pedestrians are lack of side-
suggesting that there was no effect modification by sex. walks, disappearing zebra crossings, traffic and ongoing
road constructions/repair work [22]. Only 38% of young
The multivariate linear mixed effects with age
adolescents and 17% of children in India were found to
interaction model that adjusted for sex, family income,
achieve the recommended 60-minutes/day of moderate-to-
parental BMI and cluster effects of schools showed a
vigorous intensity physical activity (MVPA) duration [3].
significant reduction in BMI with increase in walkability
Differences in physical activity between gender, socio-
index, but the impact decreased with age (Table II). The
economic status and type of school (public vs private)
slope of BMI as per age of a child was -0.415+0.033×age in
have also been observed in Indian children [23,24].
years. Similarly, the slope of percentage body fat with
respect to age was -0.723+0.051× age (years). The WHtR The present study observed the effects of walkability
did not show any significant associations in the index on BMI and percentage body fat to decrease with
multivariate analysis (Web Fig. 3). age. While the exact reason for this is not clear,
psychosocial factors like social support from peers Ethical committee; No. 177/2008, dated Feb 05, 2009.
affected the associations between the built environment Contributors: DP: data acquisition, preliminary analysis,
and active commute from schools (ACS) among adole- interpretation of data, writing original draft; SG: methodology,
scents [21]; adolescents chose the mode of transport to formal analysis, interpretation of data, writing-review and
editing; RK: conceptualization, supervision, analysis, interpre-
school based on ACS [21]. Younger children may not have
tation of data, writing – critical reviewing and editing.
the freedom for independent decision for walking plus Funding: None; Competing interests: None stated.
ACS. Additional postulated reasons could be time spent in Note: Additional material related to this article is available at
active games, academic pressure, increased mobile phone, www.indianpediatrics.net
screen and sedentary time duration and dietary habits,
which were not evaluated in this analysis. REFERENCES
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assessment of physical activity. The lack of information 2022. Available from: https://nhm.gov.in/ WriteReadData/
on the retail area of Bengaluru city in the public domain l892s/1405796031571201348.pdf
limited the inclusion of this parameter while calculating the 2. Kuriyan R, Selvan S, Thomas T, et al. Body composition
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Local foundation, Cooke Town, Bengaluru, India for extracting communities: Using geographic information systems to
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ADVERTISEMENT
[The multi-panel plot shows how the impact of walkability on obesity indicators decreases with increasing age. In the multivariate
regression, age was included as an interaction term with walkability index. The slopes at different age were estimated by regression
coefficient of walkability index and coefficient corresponding to interaction of age and walkability index by
; while were obtained from regression model specified in method section].
Web Fig. 3 Panel A shows the distribution of residential address and schools of PEACH cohort participants across Bengaluru
city. Panel B shows the distribution of the residential address and schools of the participants selected from the current study.
Correspondence to: Objective: To investigate the prevalence and risk factors of cooking-related child burn
Dr Mesafint Molla Adane, injury. Methods: A cross-sectional community-based study was conducted among a total
Department of Environmental Health, of 5830 children with their respective caretakers in randomly selected 100 clusters. Data
were collected through face-to-face interviews using a structured questionnaire. Logistic
School of Public Health,
regression was used to identify the risk factors and adjusted odds ratios were used as
College of Medicine and Health measures of effect. Results: The prevalence of cooking-related child burn injury was 6.2%
Sciences, Bahir Dar University, (95% CI: 5.5-6.8). This burden was linked with risk factors such as lower literacy of
Bahir Dar, Ethiopia. caretaker, family size, using traditional cook stove, long cooking time, and presence of extra
mesafintmolla@yahoo.com indoor burning events as well as lack of separate kitchen, child supervision, and injury
Received: June 1, 2022; prevention awareness. Conclusion: Children experience a high burden of burn injury.
Initial review: July 10, 2022; Thus, stakeholders should work to reduce this burden by controlling the aforementioned
Accepted: Sep 22, 2022. risk factors.
Keywords: Prevention, Scalds, Unintentional injury.
C
ooking-related burns create a major public The sample size was calculated assuming a 95%
health burden in low- and middle-income confidence level, a 3% acceptable margin of error, 13%
countries (LMICs), where over 95% of burn estimated population proportion of child burn injury in
deaths occur [1], and this type of injury carries Ethiopia, a design effect of 2 for cluster sampling, and an
greater long-term morbidity than burns of any other type addition of 5% to account for any unpredictable events.
[2]. The global burn registry report by the World Health The final sample size was estimated to be about 1017
Organization (WHO) shows that, burn injury incidence is children with their respective caretakers. Neverthe-less, to
excessively concentrated in LMICs [3,4]. Children, achieve the benefit of having a larger sample size, which
especially those under five years of age, are more vulnera- would increase the accuracy of estimations by decreasing
ble to experienc-ing pediatric burns [5], and several studies the sampling error, we included all the 5830 eligible children
have revealed that most pediatric burn injuries occur from the wider cookstove trial project [14].
below the age of 4 years [6-8].
From the total of 132 clusters in the study area, 100
In Ethiopia, burn injury is a common public health clusters were chosen randomly by the lottery method.
problem [9,10], and usually occurs in domestic kitchens Then, all eligible children with their respective caretakers
[8,11]. However, there is only little population-based were included in the study. However, when two or more
information in the East African region [12], with only a few eligible children were found living in the same household,
studies reporting on the determinants of child burn injuries only the youngest child was included. Also, in situations
in Ethiopia [13]. Therefore, this study aimed to investigate where there were two or more burn injury events on a
the prevalence and risk factors of cooking-related child single child, only the latest injury was considered, to
burn injury. reduce the possibility of recall bias.
METHODS
We defined cooking-related child burn injury as the
A cross-sectional study was conducted in Mecha District, occurrence of cooking-induced child burn injury related to
Northwest Ethiopia. The majority of the households in the the actual household cooking practice in the last 12
study localities primarily use an open three-stone months, as assessed by the local nurses through face-to-
traditional type cook-stoves for cooking on ground level. face interviews. Burn injury mechanism was classified as
Besides, improved cookstove types are alternatively used burns from hot liquids (scalds), burns from flames, burns
by the community in the study area [14,15]. from hot solid objects (contact burns), and others. Also,
the severity of the burn was defined as light (no scar), Table I Sociodemographic and Cooking-related Charac-
moderate (scar smaller than a coin), and serious (scar teristics of Study Participants (N=5830)
larger than a coin). Similarly, the predictor variables were Characteristic No. (%)
defined and assessed as fully mentioned in the attached Rural residence 4366 (74.9)
document (Web Appendix I). Female gender 2816 (48.3)
Data were collected from 1- 31 May, 2018 by 15 trained Age of child
local nurses through face-to-face interviews using a pre- 0-11 mo 1601 (27.5)
tested questionnaire. The occurrence of burn injury within 12-23 mo 1664 (28.5)
24-35 mo 1528 (26.2)
the last 12 months was assessed by asking the primary 36-47 mo 1037 (17.8)
caretakers whether the child had a burn injury related to the Literacy statusa
household cooking practice, as well as through examining Does read and write 4158 (71.3)
the injured child by trained nurses using the child burn Read & write only 452 (7.8)
management guideline [16]. Primary school (grade 1-8) 474 (8.1)
Secondary school (grade 9-12) 366 (6.3)
Statistical analysis: To evaluate the effect of possible Higher education 380 (6.5)
predictor variables on the occurrence of child burn injury, Occupational statusa
initially, univariate logistic regression analyses were Farmer 3893 (66.8)
carried out to observe the independent association of Merchant 839 (14.4)
child injury with each predictor variable independently. All Housewife 496 (8.5)
variables with a P value of 0.2 and below in the single model Employee 332 (5.7)
Daily laborer 234 (4.0)
analyses were entered into a multivariable logistic Student 36 (0.6)
regression analysis model to describe the associations Family size
between child injury and predictor variables. 2-5 3183 (54.6)
RESULTS 6-7 1784 (30.6)
8-9 746 (12.8)
A total of 5830 eligible study participants were included in ≥10 117 (2.0)
the study (Fig. 1). The majority (92.1%) of the household Rooms in the house
used a traditional type of household cook stove (Table I). One 1384 (23.7)
Two 3203 (55.5)
The prevalence of cooking-related child burn injury Three 1101 (18.9)
that occurred in the past 12 months was 6.2% (95% CI: 5.5- ≥4
Separate kitchen 3685 (63.2)
6.8). Its distribution by gender was 6% (95% CI: 5.1-6.9) for
Primary cookstove type
females and 6.3% (95% CI: 5.4-7.2) for males and an elevated
Traditional stove 5371 (92.1)
injury prevalence (12.5%) was observed in ages between Improved stove 459 (7.9)
36-47 months of life. More than one-third (37.6%) of the Meals cooked per day
injuries were moderate in severity and the common mecha- ≤1 meal 1090 (18.7)
nism of injury was burning from hot liquids (34.5%), and 2 meals 3366 (57.7)
occurred largely (46.2%) in the evening time (Web Table I). 3 meals 1008 (17.3)
≥4 meals 366 (6.3)
The burden of child burn was linked with various risk Time taken for cooking per day
factors such as lower literacy status of caretaker [AOR 1-2 h 1505 (25.8)
(95% CI) 2.21 (1.05-4.67)], high family size/overcrowding 3-4 h 3621 (62.1)
[AOR (95% CI) 2.35(1.25-4.43)], lack of separate kitchen ≥5h 704 (12.1)
[AOR (95% CI) 2.19 (1.56-3.07)], using traditional cook Cook stove extinguishing practice
stove [AOR (95% CI) (1.23-3.36)], lack of child supervision Extinguish each time 1625 (27.9)
[AOR (95% CI) 2.27 (1.63-3.17)], lack of injury prevention Extinguish only at night 2470 (42.4)
Do not extinguish at all 1735 (29.8)
awareness [AOR (95% CI) 1.65 (1.31-2.09)], and long Extra indoor burning events 5583 (95.8)
cooking time [AOR (95% CI) 1.99 (1.31-3.04)] (Table II). Estimated time/day
DISCUSSION 1-2 h 3622 (62.1)
3-4 h 544 (9.3)
The findings of this study reveal that 6.2% (95% CI: 5.5, 12 h 1214 (20.8)
6.8) children had suffered from cooking-related burn injury 24 h 203 (3.5)
in last one year. This finding is lower than the findings of Not aware of child injury preventiona 3009 (51.6)
two previous studies that reported a prevalence of 10% aprimary caretaker.
Table II Multivariate Analysis of Risk Factors Associated during cooking, which put them at greater risk of uninten-
With Cooking-related Child Burn Injury in North West tional burn injury exposure. The risk of burn injury was
Ethiopia, 2018 (N=5830) significantly elevated among children whose caretakers
Characteristics Crude OR (95% CI) AOR (95% CI) did not read and write. This finding is comparable to a
previous study, which found a positive association
Urban residence 0.55 (0.41,0.73) 0.80 (0.47,1.35)
between better educational level of caretakers and child
Female 0.95 (0.77,1.18) 0.94 (0.76,1.18) injury reduction [17].
Ageb
The risk of child burn was also increased among
1 year 2.236 (1.52,3.28) 2.13 (1.44,3.15)i
children living in households with a family size of 10 or
2 years 2.87 (1.97,4.17) 2.81 (1.91,4.12) i
3 years 5.74 (3.98,8.29) 5.87 (4.03,8.57) i more. This result can be explained by the fact that living in
overcrowded households may increase the risk of burn
Does not read and writea,c 3.14 (1.60,6.14) 2.21 (1.05,4.67) i
Occupational statusa,d injury among young children by creating a cluttered
Student 2.16 (0.61,7.66) 4.27 (1.06.17.21) i situation in the home. Also, overcrowded households
might not have adequate space for cooking and playing
Total family sizee
for toddlers. The risk of childhood burn injury was also
8-9 2.45 (1.67,3.59) i 1.79 (1.18,2.72)
increased among children living in households with a
≥10 4.30 (2.40,7.68) i 2.35 (1.25,4.43)
cooking area located inside the main living house. Corres-
No child supervision 1.29 (1.04,1.60) 2.27 (1.63,3.17)
pondingly, a separate kitchen is one of the most
by caretaker
recommended types of solutions to minimize the risk of fire
No awareness on 1.84 (1.47,2.30) 1.65 (1.31,2.09) hazards [18].
preventiona
Cooking area inside 1.30 (1.06,1.61) 2.19 (1.56,3.07) Among the behavioral factors, lack of child super-
living house vision by a caretaker was significantly linked with a greater
Traditional stove 1.57 (1.98,2.51) 2.04 (1.23,3.36) risk of child burn injury. This result is comparable with the
finding of a previous study [19], which reported that lack
Meals cooked per dayf
of caretaker supervision was the major determinant factor
3 meals 1.88 (1.31,2.69)* 1.91 (1.28,2.83) i
for burns among Ethiopian children.
≥4 meals 2.36 (1.52,3.66)* 1.98 (1.23,3.18) i
Length of time taken for cooking per dayg Recall and social desirability biases could be a
3-4 h 2.52 (1.82,3.48)* 1.98 (1.22,3.21) i potential limitation for a survey of this kind. This investi-
≥5 h 3.09 (2.07,4.62)* 1.99 (1.31,3.04) i gation could be also subjected to the limitations of a cross-
Do not extinguish 3.03 (2.18,4.20)* 1.60 (1.04, 2.46) i
sectional study design and cluster sampling method. The
cook stoveh results of this study, which underscored already well-
recognized risk factors of child burn injury in this region,
Child spends some 2.34 (1.43,3.84) 1.78 (1.05,3.03) i
time near cook stove will guide both the policy makers for interventions aimed at
addressing this common cause of childhood morbidity.
Extra indoor burning 3.28 (1.34,7.99) 2.68 (1.08,6.68) i
event Ethics clearance: Ethical Review Committee, College of
aprimary bcompared ccompared Medicine and Health Sciences at Bahir Dar University; No. 088/
caretaker; to <1-year-old; to higher
education; dcompared to housewife; ecompared to 2-3 member house-
18-04, dated April 4, 2018.
hold; fcompared to ≤1 meal/d; gcompared to 1-2 h/d; hcompared to Contributors: MMA: was the principal investigator of the study
extinguishing each time. iP<0.05. and took the leading responsibility, starting from the origin,
design, and supervising of the data collection process to the final
among children younger than 18 years in Northwest data analysis and preparation of the manuscript. AA, TS:
contributed, starting from the data analysis to the preparation of
Ethiopia [17], and a national prevalence of 13% among
the manuscript and reviewing the final document. All authors
children younger than 14 year in Ethiopia [11]. The approved the final manuscript.
possible justification for this disparity might be the Funding: Bahir Dar University through the research funding
difference in the age range of study participants, as the age scheme of MHDSS at Bahir Dar University in Ethiopia.
of our study participants was under four year. Competing interests: None stated.
Note: Additional material related to this study is available with
Concerning the risk factors, the risk of child burn injury the online version at www.indianpediatrics.net.
was significantly increased by more than five times
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Web Table I Severity, Cause, and Time of Child Burn Injury Across Age-groups in North West Ethiopia, 2018 (N=5830)
Web Appendix 1
Definitions, data sources, and methods of assessment for potential predictor variables
The potential predictor variables were broadly categorized into socio-demographic, environmental, and behavioral variables. These
variables were assessed through face-to-face interviews with the primary caretakers of the children by field nurses using questionnaires as
well as through observations as fully mentioned next:
i.Socio-demographic variables
─ Gender of child: The child’s gender was assessed by asking the respondent as female or male.
─ Age of child: The child’s age was assessed by asking the respondent by classifying it into four categories as i] < 1-Year-old; ii] 1-
Year-old; iii] 2 Years old, and iv] 3 Years old.
─ Literacy status of primary caretaker: Refers to the level of education achieved by the primary caretaker in child burn injury
reduction. To study the role of educational level in the occurrence of cooking-related child burn injury, primary caretakers were
asked about the level of education they accomplished as assessed by classifying them into five categories as i] do not read and
write; ii] read and write, iii] primary schooling completed, iv] secondary schooling completed, and v] higher education completed.
─ Occupational status of caretakers: The occupational status of the primary caretaker was assessed by asking the respondent by
classifying into six categories as i] Farmer, ii] Merchant, iii] Student, iv] Employee, v] Daily laborer, and vi] Housewife.
Correspondence to: Dr Jianglin Ma, Objective: To compare the neonatal outcomes in pregnant women with repaired vs
Department of Pediatrics, The First unrepaired congenital heart disease (CHD). Methods: Data on pregnant women with CHD
Affiliated Hospital, College of Medicine, was retrieved from our hospital records for the duration April, 2014 to December, 2021.
Pregnant women with CHD were divided into two groups: simple CHD and moderate-to-
Zhejiang University, Hangzhou,
complex CHD. Results: In simple CHD group, neonatal outcomes were similar in pregnant
Zhejiang, Province, China. women with repaired and unrepaired CHD. By contrast, in moderate-to-complex CHD group,
1515015@zju.edu.cn the offspring of women with unrepaired CHD had lower gestational age [mean (SD) 34.3
Received: May 10, 2022; (2.7) vs 36.8 (2.1) week; P=0.016] and lower birth weight [mean (SD) 2126.8 (711.9) vs
Initial review: June 20, 2022; 2720 (645.7); P=0.037] than those with repaired CHD. Infants of women with unrepaired
Accepted: November 28, 2022. moderate-to-complex CHD had a higher risk of premature delivery (87.5% vs 45.5%,
P=0.013), low birth weight (81.3% vs 36.4%, P=0.04) and neonatal intensive care unit
(NICU) admission (68.8% vs 27.3%, P=0.034). Conclusions: Surgical repair before
pregnancy in women with moderate-to-complex CHD significantly minimized the risks of
neonatal complications.
Keywords: Cardiac intervention, Pregnancy outcome, Severity, Surgical repair.
Published online: Jan 02, 2023; PII: S097475591600471
W
ith advances in surgical intervention and such as pregnancy induced hypertension (PIH), ante-
intensive care, more and more women with partum hemorrhage (APH), pre-eclampsia, maternal anemia,
congenital heart disease (CHD) are nephropathy, liver disease, pulmonary disease, connec-
surviving to childbearing age. Women tive tissue disease, and with induced abortion were
desirous of pregnancy might face various challenges excluded. Data were collected using medical records.
during pregnancy and child birth. For women with simple Information about mothers included age at inclusion, type
CHD, who are free of symptoms, pregnancy and delivery of heart defects, prior surgical procedures, severity of
could be well tolerated [1], but for women with complex disease as per New York Heart Association (NYHA) class,
CHD, pregnancy presents a challenge with numerous left ventricular eject fraction (LVEF), pulmonary artery
alterations in cardiovascular physiology [2]. Pregnancy pressure, oxygen saturation, gestational diabetes (GDM),
with CHD is associated with a high risk of premature thyroid function and drug exposures. Information about
delivery and small for gestational age (SGA) [3,4]. The neonatal outcome, as obtained from the medical records,
risks of adverse neonatal events are influenced by types included gestational age at birth, type of delivery, birth-
of cardiac defects and surgical repair. Women with complex weight, Apgar score and neonatal complications.
CHD who undergo cardiac surgery, seem to well tolerate
Based on guidelines from the European Society of
pregnancy, which may reduce the risks of neonatal
Cardiology, isolated atrial septal defect (ASD), ventricular
complications. Data on benefits of aggressive surgical
septal defect (VSD) and patent ductus arteriosus (PDA),
intervention before pregnancy with different severity of
were classified as simple CHD and other heart defects were
CHD are unknown. The present study was conducted to
considered as moderate-to-complex CHD [5]. Pulmonary
compare neonatal outcomes among women with cardiac
arterial hypertension (PAH) was defined hemodynamically
surgery for CHD before pregnancy.
by the presence of a mean pulmonary artery pressure of at
METHODS least 25 mmHg with a pulmonary capillary wedge pressure
This was a retrospective study that retrieved records of or left ventricular end diastolic pressure of up to 15 mm Hg.
women with CHD between April, 2014 and December, 2021 Patients were stratified by pulmonary artery systolic
at First Affiliated Hospital, College of Medicine. The pressure into three grades: 36-50 mm Hg, 50-70 mm Hg and
patients diagnosed with CHD and concurrent diseases >70 mm Hg [6]. Neonatal complications included: preterm
birth (<37 wk gestation), moderately preterm birth (32-36 Total pregnant women with CHD (n=102)
wk), very preterm birth (26-31wk), low birth weight (<2500
g), very low birth weight (<1500 g), extremely low birth Excluded (n=37)
weight (<1000 g), small for gestational age (below tenth Induced abortion (n=22)
percentile from the mean weight corrected for gestational Pre-eclampsia (n=6)
age and gender, SGA), cardiac birth defects and other birth → Antepartum hemorrhage (n=3)
Connective tissue disease
defects, necrotizing enterocolitis (NEC), intracranial
(n=4)
hemorrhage (ICH), and neonatal asphyxia. Maternal anemia (n=2)
Data analysis: Data were summarized by descriptive ↓
Enrolled (n=65)
statistics. Data were analyzed using SPSS V. 21. Mean (SD)
are presented for normally distributed continuous ↓
variables and were compared using Student t test. For non- ↓ ↓
normal continuous variables, Median (IQR) were computed Simple CHD Moderate-to-complex
and were compared using Mann-Whitney U test. Cate- (n=38) CHD (n=27)
gorical variables were expressed as proportions and ↓ ↓
compared using chi-square test or Fisher exact test. ↓ ↓ ↓ ↓
Multivariate logistic analysis was utilized to assess the Repaired Unrepaired Repaired Unrepaired
relationship between surgical repair and adverse neonatal CHD (n=12) CHD (n=26) CHD (n=11) CHD (n=16)
outcomes. Two-tailed probability values <0.05 were
CHD: congenital heart disease.
considered statistically significant.
Fig. 1 Flow of participants in the study.
RESULTS
Data of 65 pregnant women diagnosed with CHD was
women as per the type of CHD and surgical repair are
included (Fig.1); of which, 35 (58.5%) women had simple
shown in Table II.
CHD. In the simple CHD group, cardiac defects were
surgically repaired in 12 (31.6%) women. The obstetric Multivariate analysis demonstrated that pregnant
characteristics based on complexity of CHD and surgical women with unrepaired moderate-to-complex CHD had a
repair is shown in Table I. The neonatal outcomes of higher risk of premature delivery [OR (95%CI) 8.4 (1.26-
Table I Baseline Characteristics of Pregnant Women With Congenital Heart Disease (N=65)
Characteristics Simple CHD Moderate-to-complex CHD
Surgically repaired Unrepaired Surgically repaired Unrepaired
(n=12) (n=26) (n=11) (n=16)
Age (y)a 27.7 (3.2) 28.2 (4.8) 28.4 (3.5) 31.5 (7.1)
CHD diagnosis
Prior to pregnancyb 11 (91.6) 10 (38.5) 11 (100) 12 (75)
During pregnancy 1 (8.4) 16 (61.5) 0 4 (25)
LVEF (%)b 59.2 (7.5) 63.5 (5.5) 67.1 (4.8) 66.2 (5.6)
Oxygen saturation (%)a 98.7 (0.5) 98.1 (1.9) 98.5 (0.7) 94.5 (6.6)
PAH (mm Hg)
≥35-<50 2 (16.7) 6 (23.1) 0 2 (12.5)
≥50-<70 1 (8.3) 4 (15.4) 0 4 (25)
≥70 0 2 (7.7) 1 (9.1) 1 (6.3)
NYHA functional class
Class I-II 11 (91.7) 21 (80.8) 11 (100) 14 (87.5)
Class III-IV 1 (8.3) 5 (19.2) 0 2 (12.5)
Drug exposures
Corticosteroids 1 (8.3) 0 1 (9.1) 0
Warfarinb 0 0 6 (54.5) 0
Data provided as no (%). amean (SD). bP<0.05. CHD-congenital heart disease; LVEF: left ventricular eject fraction; PAH:pulmonary arterial
hypertension.
56.07); P=0.028], low birth weight [OR (95%CI) 7.58 (1.31- Women with an ASD were at an increased risk of SGA
41.92); P=0.024], and neonatal intensive care unit (NICU) and fetal mortality in comparison to women with a repaired
admission [OR (95%CI) 5.87 (1.08–32); P=0.041]. ASD in an earlier study [8]. Another study [9] showed that
women with repaired VSD had a higher risk of premature
DISCUSSION labor and SGA births in comparison to women with
The present study showed that women with simple unrepaired VSD. However, mechanism of a higher risk of
unrepaired CHD had similar neonatal outcomes as neonatal events in women with repaired VSD are not
compared to simple repaired CHD. In contrast, neonatal clearly understood. The present study reported a higher
outcomes were adverse in women with moderate-to- risk of premature delivery, low birth weight and NICU
complex CHD with unrepaired lesions than the repaired admission in women with unrepaired compared with
group. repaired moderate-to-complex CHD. The hemodynamic
changes in operated women with moderate-to-complex
Women with CHD experience longer life expectancy CHD are well tolerated and appear to be stable during
and improved general health with diagnostic and pregnancy. The risks of obstetric complications including
therapeutic advances in recent years. Consequently, more hypoxemia, heart failure, arrhythmia and pre-eclampsia,
and more women with CHD are reaching reproductive age and the risk of fetal and neonatal complications including
and are considering pregnancy. CHD increases the preterm birth and growth retardation were reported to
incidence of neonatal complications such as premature decrease [10]. Other studies [11,12] have likewise shown
delivery and SGA, in women without surgical repair of improvement in maternal, perinatal and neonatal
shunt lesions [7]. A few women with CHD were unaware of outcomes. Therefore, cardiac surgery could improve
their heart defects before pregnancy and had not received neonatal outcomes and should be performed before
any surgical repair but tolerated pregnancy and labor well. conception in CHD.
Other risk factors such as maternal PIH, APH, pre- congenital heart disease with pregnancy, maternal, and neonatal
eclampsia, connective tissue disease and other systematic outcomes. JAMA Network Open. 2019;2: e193667.
diseases were reported with adverse neonatal outcomes 4. Amanda O, Jie Y, Li-ZN, et al. Neonatal and maternal
[13-15]. The numbers of women with CHD and associated outcomes in pregnant women with cardiac disease. J Am
Heart Assoc. 2018;7:e009395.
comorbidity was very small in this study and were not
5. Regitz Zagrosek V, Jolien RH, Johann B, et al. 2018 ESC
included for analysis. The present study was also limited guidelines for the management of cardiovascular diseases
by the small sample size and retrospective design. during pregnancy. Euro Heart J. 2018;39:3165-241.
To conclude, the decision for corrective cardiac repair 6. Karen S, Iris MH, Werner B, et al. Pulmonary hypertension
and pregnancy outcomes: Data from the Registry of Preg-
should be individualized before pregnancy by weighing
nancy and Cardiac Disease (ROPAC) of the European Soc-
the risks and benefits. For women with simple CHD, iety of Cardiology. Euro J Heart Failure. 2016;18:1119-28.
surgical repair before pregnancy does not significantly 7. Katherine BS, Timothy BC. Pregnancy in women with
affect neonatal outcomes, unlike for women with moderate- adult congenital heart disease. Cardiol Clin. 2021;39:55-65.
to-complex CHD, where surgical repair before pregnancy 8. Yap SC, Drenthen W, Meijboom FJ, et al. Comparison of
minimizes the risks of neonatal complications. pregnancy outcomes in women with repaired versus
unrepaired atrial septal defect. BJOG. 2009;116:1593-601.
Ethics clearance: Clinical Research Ethics Committee of the First 9. Yap SC, Drenthen W, Pieper PG, et al. Pregnancy outcome
Affiliated Hospital, Zhejiang University School of Medicine; No. in women with repaired versus unrepaired isolated ventri-
IIT20220804A, dated August 9, 2022. cular septal defect. BJOG. 2010;117:683-9.
Contributors: JlM: carried out the retrospective review of all 10. Lia MP, Thais LP, Hanne BR, et al. Outcomes of pregnancy
cases, participated in the writing and organization of the in women with tetralogy of Fallot. Cardiol Young. 2008;18:
manuscript; FL, LlY: participated in the study’s design and the 423-9.
analysis of cases. All authors read and approved the final 11. Kana W, Jun-guo X, Xiao-dong W, et al. Pregnancy out-
manuscript. comes among 31 patients with tetralogy of Fallot, a
Funding: None; Competing interests: None stated. retrospective study. BMC Preg Childbirth. 2019;19:486.
REFERENCES 12. E Gelson, M Gatzoulis, P J Steer, et al. Tetralogy of Fallot:
maternal and neonatal outcomes. BJOG. 2008;115:398-402.
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women with complex congenital heart disease. A constant morbidity and mortality associated with anemia in pre-
challenge. Arquivos Brasileiros de Cardiologia. 2019; gnancy. Obstet Gynecol. 2019;134:1234-44.
113:1062-69. 15. Michelle P. Pregnancy and systemic lupus erythematosus.
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Correspondence to: Objective: To assess changes in profile of psychiatric emergencies in children and
Prof Rakesh Kumar Chadda, adolescents (aged <19 year) during the coronavirus disease 2019 (COVID-19) pandemic
Chief, NDDTC, Professor and Head, compared to pre-pandemic period. Methods: The psychiatric emergency records were
analyzed for the period of April, 2019 – September, 2021 to assess the pattern and profile of
Department of Psychiatry,
mental health emergencies in children and adolescents in the period before and after the
All India Institute of Medical Sciences, onset of the pandemic lockdown (i.e., 23 March, 2020). Results: 379 consecutive child and
Ansari Nagar, New Delhi 110 029. adolescent psychiatric emergencies were identified, of which 219 were seen after the
drrakeshchadda@gmail.com onset of pandemic. Commonest reason for referral in the pandemic group was attempted
Received: May 16, 2022; self-harm (44.3%). The ICD-10 neurotic, stress-related and somatoform disorders
Initial review: June 14, 2022; constituted the commonest diagnostic category, similar to pre-pandemic period. A
Accepted: October 26, 2022. significantly higher proportion (44% vs 28%) of children was prescribed benzodiazepines
in the pandemic period, compared to the pre-pandemic period. Conclusion: The average
monthly psychiatric emergencies in children and adolescents showed no increase during
the pandemic period. Self-harm was the commonest cause of psychiatric referral in
emergency services mental health crisis in the younger population.
Keywords: Benzodiazepine, Child and adolescent psychiatry, Mental health.
I
nternational literature indicates that there was a 26% In view of paucity of reports from India on child and
to 60% reduction in emergency visits immediately adolescent mental health emergencies with respect to
after the pandemic, especially during confinement COVID-19 pandemic, we aimed to assess the pattern and
periods [1-4]. Studies on mental health emergencies profile of psychiatric emergencies in younger age groups
during the peak pandemic months also demonstrated some after onset of COVID-19 pandemic with respect to pre-
decline in numbers of psychiatric emergency visits, though pandemic period, and explore for relationship, if any, with
that was proportionate to decline in overall emergency month-wise COVID-19 statistics in the country.
department visits. However, the pattern and profile of
METHODS
mental health issues showed some changes in the pan-
demic period. Some studies reported more suicidal attempts A retrospective review of psychiatric emergency records
or substance overdoses, while others found an increase of was carried out at Department of Psychiatry, All India
anxiety, stress- related or neurotic presentations [5-10]. Institute of Medical Sciences (AIIMS), New Delhi for the
period between April, 2019 and September, 2021. Institute
Literature on child and adolescent psychiatric Ethics Clearance was taken prior to study initiation.
emergencies is rather limited and somewhat conflicting.
The department maintains record of all individuals
Only one prior Indian study is available on psychiatric
visiting the emergency department and attended by
emergency department visits after COVID-19 pandemic;
psychiatry emergency team. After a psychiatric evaluation
however, most of the subjects were adults with no
of the patient, a plan is formulated, and treatment is
specific focus on younger age group [16]. The study
prescribed. Accordingly, patient is thereafter discharged
found that there was an overall decrease in total number
or kept for observation (usually up to 24 hours), or
of all-age emergency visits. In terms of diagnostic
admitted in the ward, if warranted.
distribution, there was an increase in patients for
schizophrenia and reduced representation of delirium, Consecutive child and adolescent patients [17],
while visits with self harm continued at similar rates in pre belonging to either gender, registered in the emergency
and post lockdown period. department of the Institute, and attended by the on-call
psychiatry emergency referral team during the study pandemic period) records were analyzed, which
period were included for the study. Unclear or incomplete constituted 16.7% of all-age psychiatric emergencies
case records or those with missing data were excluded. attendance in that period. The mean (SD) monthly child
Available demographic and clinical data, including and adolescent psychiatric emergency referrals in
diagnosis, comorbidities, referrals to other specialities, pandemic period was 6.6 (3.1), comparable to pre-pandemic
and treatment advice was noted. period [6.3 (3.9); P=0.798].
Statistical analysis: Statistical analysis was done using Table I shows the socio-demographic and clinical
SPSS 20.0. Descriptive analysis was done for socio- variables in pre-pandemic and pandemic groups. Both
demographic and clinical variables. Study groups prior and groups were comparable with respect to demographic
after onset of pandemic i.e., March 23, 2020, were compared variables. Nearly half of them had medico legal presen-
using chi-square and independent samples t-test. tations. The commonest reason for referral was assess-
ment for self-harm (46% vs 44%) in both groups. Compared
RESULTS
to pre-pandemic group, the pandemic group had
A total of 379 child and adolescent patient (160 in pre- significantly lower proportion with medical/neurological/
Table I Characteristics of Children with Referrals for Psychiatric Emergencies During the Pre-pandemic and Pandemic
Periods (N =379)
Characteristics Pre-pandemic period, Pandemic period, Mean difference (SD)/
n=160 n=219 OR (P value)
Agea 16.5 (2.5) 16.4 (2.5) 0.22 (0.8)
Male gender 86 (53.8) 124 (56.6) 0.308 (0.58)
Unmarriedb 156 (97.5) 210 (95.9) 0.723 (0.57)
Medico-legal cases 76 (47.5) 108 (49.3) 0.122 (0.73)
Carry-over cases from previous day 10 (6.3) 18 (8.2) 0.524 (0.47)
Past medical history 2.024 (0.57)
Medical 8 (5) 13 (5.9)
Neurological 15 (9.4) 16 (7.3)
Surgical 7 (4.4) 5 (2.3)
None 130 (81.3) 185 (84.5)
Past psychiatric history 32 (20) 54 (24.7) 1.143 (0.28)
Medication/s before presentation
Psychotropic 35 (21.9) 58 (26.5) 1.486 (0.48)
Other medication 12 (7.5) 12 (5.5)
None 113 (70.6) 149 (68)
Reasons for referral 2.114 (0.78)
Self-harm 74 (46.3) 97 (44.3)
Neglect 2 (1.3) 3 (1.4)
Harm to others 16 (10) 30 (13.7)
Diagnostic clarification 67 (41.9) 86 (39.3)
Psychiatric clearance 0 (0) 1 (0.5)
Others 1 (0.6) 2 (0.9)
Precipitating factor 3.921(0.14)
Biological 24 (15) 24 (11)
Psychosocial 42 (26.3) 77 (35.2)
None apparent 94 (58.8) 118 (53.9)
Comorbid medical diagnosis in emergency visitb 18.282 (<0.001)
Medical 23 (14.4) 12 (5.5)
Neurological 22 (13.8) 13 (5.9)
Surgical 3 (1) 2 (0.9)
None 112 (70) 192 (87)
All values are in frequency (%) except amean (SD). bP<0.01.
surgical diagnosis during emergency evaluation. On the with respect to COVID pandemic in India. The child and
other hand, while 88% has no known medical diagnosis in adolescent psychiatric emergencies had a clinical pre-
the pandemic group, same was 70% in pre pandemic group. valence of 16.7% among all-age psychiatric emergencies
attended at our center. The monthly average of child and
After onset of pandemic, the most common diagnostic
adolescent psychiatric emergency referrals in pandemic
category was neurotic, stress-related and somatoform
period was 6.6 (3.1). Overall monthly service utilization in
disorders (16.4%), followed by intentional self-harm with
the pandemic period remained comparable to pre-pandemic
no discernible psychiatric diagnosis (15.1%). There were;
group. There was, however, a short-term decline in months
however, no statistically significant differences between
coinciding with phases of active lockdown in the city with
the groups with respect to ICD-10 diagnostic categories.
limited transport facilities, consistent with available
Use of antidepressants, antipsychotics and other
literature [10,12-15]. In the context of COVID-19, travel and
psychotropic medications was equally prevalent. How-
visits to hospital casualties were avoided to the extent
ever, prescription of benzodiazepines significantly
possible due to fears of contracting infection in crowded
increased in the pandemic group (P=0.01; 42% vs 29%)
places. In spite of ongoing pandemic, the monthly
compared to pre-pandemic group. About 9% of children
average of child and adolescent psychiatric referrals in the
and adolescents attended in the pandemic period were
pandemic period has remained comparable to the year prior
advised psychiatric admission, compared to 15% in pre
to pandemic, which points to ongoing mental health
pandemic group (P<0.05%). Only 3.7% got admitted due to
service needs for younger patient population.
various reasons such as unwillingness/refusal, logistic
difficulty, or non-availability of beds. McAndrew and colleagues reported [11] decline in all-
age psychiatric emergency visits but found an increase of
DISCUSSION
visits by those less than 18 years. In a large retros-pective
The study adds to the findings from limited literature on study of emergency presentations in children <18 years of
child and adolescent psychiatric emergencies, specifically age, across ten countries, a reduction in psychiatric
Table II Characteristics of Children With Referrals for Psychiatric Emergencies in the Pre-pandemic and Pandemic Periods
(N =379)
Diagnosis/management Pre-pandemic, Pandemic, Mean difference (SD)/
n=160 n=219 OR (P value)
ICD F00-09 14 (8.8) 21 (9.6) 0.078 (0.78)
ICD F10-19 10 (6.3) 14 (6.4) 0.003 (0.96)
ICD F20-29 22 (13.8) 30 (13.7) 0 (0.99)
ICD F30-39 26 (16.3) 28 (12.8) 0.908 (0.34)
ICD F40-49 35 (21.9) 36 (16.4) 1.795 (0.18)
ICD F60-69 8 (5) 11 (5) 0 (0.99)
ICD F70-99a 2 (1.3) 8 (3.7) 2.078 (0.2)
ICD X60-84 (without F00-99) 22 (13.8) 33 (15.1) 0.129 (0.72)
Adverse effect of medication 2 (1.3) 4 (1.8) 0.197 (1)
Diagnosis deferred 29 (18.1) 36 (16.4) 0.185 (0.67)
Drugs – antipsychotic 22 (13.8) 43 (19.6) 2.253 (0.13)
Drugs – antidepressant 20 (12.5) 41 (18.7) 2.650 (0.1)
Drugs – mood stabilisera 4 (2.5) 5 (2.3) 0.019 (1)
Drugs – benzodiazepinea 46 (28.8) 92 (42) 7.02 (0.01)
Other drugs 11 (6.9) 17 (7.8) 0.661 (0.42)
Referral made (Any) 61 (38.1) 96 (43.8) 1.243 (0.26)
Advised psychiatric admission 24 (15) 20 (9.1) 3.102 (0.08)
Admitted under psychiatry 7 (4.4) 8 (3.7) 2.194 (0.33)
Referred to psychiatry OPD 111 (69.4) 146 (66.7) 0.311 (0.58)
All values in no. (%). ICD-10: International Classification of Diseases, 10th Edition; OPD: outpatient department. aP<0.01.
presentations was found, at least in first two months after increased from 50% in 2019 to 57% in 2020 but there was no
lockdown [12]. Leeb, et al. [13] found an initial reduction after difference in the proportion of those with severe self-harm
lockdown, followed by an increased proportion of younger [12]. In our study too, a little less than half of sample (44.3-
age group psychiatric emergencies in subsequent months. 46.3%) presented to casualty with self-harm.
The study by Davico, et al. [14] found a significant decline in
About 15% of records reflected only X code for
numbers of child and adolescent mental health emergencies
Intentional self-harm, with no assigned psychiatric
after onset of pandemic, but with no significant change in
diagnosis. About 16% had diagnosis deferred as per
hospitalization or in the prevalence distribution [14]. Cheek,
clinical records, though there may have been mental or
et al. [15] found 47.2% decrease in total presentations
behavioural issues at time of emergency evaluation. A
compared with year before, with a 35% increase in mental
provisional diagnosis is usually made to the extent
health diagnoses. Ferrando, et al. [10] found a decline in
possible, and management initiated accordingly. However,
pediatric psychiatric emergency numbers; however, child
those with unclear presentations or sub-syndromal
and adolescent patients had more new onset disorders and
presentations are subjected to psychological tests and
more likely to be admitted to inpatient care, but less likely to
detailed evaluations prior to assigning any psychiatric
present with suicide attempts, impulse control disorders and
diagnosis. In view of COVID-19 related mortality, issues
agitation/aggression.
pertaining to grief and loss were at the forefront especially
The ICD-10 neurotic, stress-related and somatoform during second wave, where younger population with still
disorders (16.4%) was the most common child/adolescent evolving coping skills are most vulnerable [19]. In the
psychiatric diagnostic category in the pandemic group, post-pandemic sample, one in three psychiatric emer-
followed by ICD-10 schizophrenia and other psychotic gencies reported a psychosocial precipitant, which was
disorders (13.7%) and ICD-10 mood disorders (12.8%). No similar to pre-pandemic period, though qualitatively
significant differences were; however, observed in fre- different. The nature of psychosocial precipitants, risk and
quency of ICD-10 diagnostic category across pre pandemic protective factors were not available in retrospectively
and pandemic group. This finding may contrast with findings assessed records.
from web-based surveys of community residing adolescents
Interestingly, it was seen that benzodiazepine
which have indicated a substantial rise in symptoms of
prescriptions increased significantly in the pandemic
depression and anxiety during the COVID-19 outbreak [18];
group (42% vs 28.8%), in contrast to the rates of other
however, those surveys have used screening instruments
psychotropic prescriptions which remained unchanged.
without diagnostic confirmation and must be viewed as a
Benzodiazepines may help in alleviation of milder, sub
measure of psychological distress in younger age groups
threshold or non-specific anxiety symptoms, for sleep
rather than a psychiatric diagnosis. In contrast, the current
related problems, or for sub-syndromal psychiatric
study focused only on those with a mental health crisis
symptoms, [20,21]. However, such symptoms could lead to
presenting to emergency and assessed by a trained
psychological distress and can become a matter of clinical
psychiatrist, rather than community-based adolescent
attention.
sample.
In contrast to a prior study [10], our study showed
Nearly 44% of emergency referrals in the pandemic
hospitalization rate of psychiatric emergencies was less
period were due to attempted self-harm in the pandemic
than pre-COVID period, which might be to promote
group, which was similar to the pre-pandemic sample. Self-
management of mental health issues at home. Further,
harm remained an important mental health crisis in child/
routine admissions were also restricted for few months
adolescent population irrespective of pandemic situation
after onset of pandemic, with institute policy permitting
in this study. A prior study by Ferrando, et al., found
only urgent admissions. Other similar studies on younger
suicidal ideation to be a presenting symptom in nearly
age group emergencies have reported either a decline
44%, self-injurious behaviour in 8.8% and suicidal
[6,22], or similar rates of hospitalizations before and after
attempts in nearly 5%, latter being less likely in post
onset of pandemic [14].
lockdown sample of that study [10]. Another similar study
found that the presentations with self-harm or suicidal There was a significant reduction in the proportion of
ideations remained same in adolescents, though there was referrals with known medical/surgical diagnosis after
a rise of anxiety disorders after COVID-related lockdown pandemic, compared to pre-COVID group. This may be
[11]. A large scale, retrospective cohort study from 23 due to decreased referrals for minor psychiatric symptoms,
hospital emergency departments in ten countries (N=2,073 as well as avoidance due to fear of poor prognosis of
visits) found that the proportion of children and getting hospitalized with COVID-19 with medical
adolescents presenting with self-harm significantly comorbidities [23].
The pandemic has not only led to increased rates of treatment. Since the psychological impact is likely to
acute stress or adjustment reactions but a wide spectrum continue for longer, it may be worthwhile to raise
of psychiatric diagnosis including anxiety, depression, etc awareness and identify ways to monitor the psychological
[24]. Social factors played an important role during both impact of COVID-19 on children and adolescents for timely
waves, however the age groups which were most affected identification and management.
by COVID-19 mortality differed somewhat in successive
Ethics clearance: Institute ethics committee, AIIMS, Delhi; No.
waves. In the first wave, it was seen that the focus was
IEC-658/03.09.2021, dated Sep 6, 2021.
more on geriatric age groups having pre-existing health Contributors: All authors contributed to study conceptualization
conditions who suffered more vulnerabilities in physical and methods. MSS, NC: data extraction and statistical analysis;
and mental health. During that wave, the children and MSS, NC, RD: manuscript drafting. All authors edited and
adolescents too were impacted due to closures of schools, approved the final draft.
playgrounds, parks and other such places of socialization Funding: None; Competing interests: None stated.
with peers. The perceived benefits for some children such
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Correspondence to: Dr P Kumar, Objective: To describe the profile of child sexual abuse (CSA) reported to a tertiary care
Assistant Professor, hospital. Methods: A retrospective analysis of CSA reported in children aged below 18
Department of Pediatrics, years from January, 2019 to June, 2022. Results: Out of the 231 cases of sexual abuse
reported, 115 (49.8%) were children below 18 years. Most of the victims were children from
Government Mohan
10 to 15 years (37.4%), and there were only two male victims. In 89.6%, the perpetrator
Kumaramangalam Medical College, was known to the victim. Revictimization was seen in 31%. The reported perpetrators
Salem, Tamil Nadu 636 030. were friends (27%), neighbors (34.8%), strangers (10.4%), or fathers (7.8%). Penetrative
pkumarramya@gmail.com abuse was seen in 58.3% of reports. External injuries were seen in 6.96%. Eight victims
Received: July 16, 2022; were pregnant and HIV screening was positive in one victim. Conclusion: Early
Initial review: Aug 15, 2022; identification of CSA is important to prevent revictimization. Children from all age groups can
Accepted: Nov 01, 2022. be victims of CSA. Perpetrators can hail from all walks of life of the children.
Keywords: Penetrative abuse, Revictimization, Sexual assault victim.
Published online: Jan 02, 2023; PII: S097475591600472
C
hild sexual abuse (CSA) is under reported in study hospital, with a history of sexual abuse during the
developing countries, due to cultural factors study period, were studied. The cases of elopements were
and social stigma [1]. Though many studies are excluded, as they represent a different social issue that is
available in the global literature, very few out of the scope of this study. Institutional ethics
studies have documented its prevalence in India. In the committee clearance was obtained. The name and
year 2012, the Government of India formulated ‘The identities of the victims were not disclosed. The guidelines
Protection of Children from Sexual Offences (POCSO) Act’ of the Ministry of Women and Child Development,
to more effectively address the rising sexual abuse in Government of India were used for case definitions and
children. The Ministry of Women and Child Development, management [1]. A standardized form was prepared to
Government of India has established a ‘One Stop Centre’ collect the data regarding the epidemiological and clinical
(OSC) for assisting survivors of gender violence [2], where characteristics of the abuse.
comprehensive services are provided under one roof.
Children, less than 18 years are treated under the Juvenile Statistical analysis: Statistical analysis was done using
Justice Act, 2011, and the POCSO Act, 2012 [1]. In a Statistical Package for Social Sciences, Version 25. All
systematic review of 51 studies from India, the prevalence categorical data were presented as frequency and
of CSA varied across the studies from 4 to 48% due to the percentages. To study the association of perpetrators with
heterogeneity of samples [3]. The authors reiterated the place, number and type of abuses, Kruskal-Wallis test was
need for a standardized tool for accurate measurement of applied. P value was considered significant at a 5% level of
CSA and also the need for more research regarding the significance for all comparisons.
social and psychological profile of the perpetrators of RESULTS
CSA. This study aims to describe the socio-demographic
and clinical characteristics of child sexual abuse, as The sociodemographic profile of the victims is presented
reported to an urban public hospital. in Table I. During the study period, after excluding 175
cases of elopements, there were 231 reported cases of
METHODS
sexual offenses. Out of these 231 cases, 115 (49.8%) were
This retrospective descriptive study was done in a cases of CSA. Nine children reported to the hospital with a
Government Medical College Hospital from January, 2019 parent or caretaker and 106 children were brought by the
to June, 2022. The case records of all the children and police. Most of the victims (37.4%) were in the age group
adolescents less than 18 years of age, reporting to the of 10 to 15 years. The youngest victim was a 75-day-old
Table I Sociodemographic Characteristics of Child Victims abdominal pain to the hospital. On examination, she was
and Perpetrators (N=115) found to be pregnant at 12 weeks of gestation. On
Characteristics No. (%) investigation by the police, she was found to have been
abused multiple times, and by multiple persons.
Child victims
Girls 113 (98.3) A significant number of incidents took place in a
neighbor’s house, when the perpetrator was a friend (P
Age
=0.013). When the perpetrator was either father or cousin,
0-5 y 3 (2.6)
the abuse occurred multiple times (P=0.005 and 0.007,
6-10 y 37 (32.2)
10-15 y 43 (37.4)
respectively). When the perpetrator was a friend,
16-18 y 32 (27.8) penetrative forms of CSA were common (P=0.028), and
when the perpetrator was a stranger, milder forms of CSA
Class of study
like fondling were common (P=0.004).
≤5th standard 39 (33.9)
6-10 standard 49 (42.6) DISCUSSION
≥11 standard 27 (23.5)
Rural residence 85 (73.9)
Child sexual abuse is an under-reported medico-social
Perpetrator
Identity known 103 (89.6) Table II Characteristics of Perpetrators and Victims of
Child Sexual Abuse (N=115)
Age
<18 y 11 (9.6) Characteristics No. (%)
19-30 y 44 (38.2) No. of perpetrators
31-60 y 40 (34.8)
One 105 (91.3)
>60 y 8 (7)
More than one 10 (8.7)
Not known 12 (10.4)
Place where abuse occurred
Rural residence 80 (69.6)
House of victim 46 (40)
Relationship with victima
House of perpetrator 11 (9.6)
Neighbor 40 (34.8) Relative/neighbor’s house 33 (28.7)
Friend 31 (27) Outdoor (field/farm/roadside) 15 (13.1)
Stranger 12 (10.4) Hostel 2 (1.7)
Father 9 (7.8) Lodge 2 (1.7)
Uncle 5 (4.3) School premises 5 (4.3)
Relative 4 (3.5) Unknown/multiple places 1 (0.9)
Father’s friend 3 (2.6)
Duration of abuse
Cousin 3 (2.6)
Teacher/caretaker 3 (2.6) Less than 30 d 99 (86.1)
Co-worker 2 (1.7) 1-12 mo 10 (8.7)
More than one year 6 (5.2)
aone each was stepfather, sibling and classmate.
Time of reporting the incident
infant girl and the perpetrator was her father. Two of the Same day 51 (44.4)
victims were boys. In 89.6%, the perpetrator was known to Within 1 wk 15 (13)
the victim. The oldest perpetrator was aged 70 years and After 1 week 49 (42.6)
the victim was a 16-year-old girl. Nature of abuse
Clinical details of the CSA (Table II) show that in 8.7% Kissing 10 (8.7)
of cases, more than one perpetrator was involved. The Fondling 35 (30.4)
Masturbation 2 (1.7)
house of the victim (40%) was the most common
Vaginal sex 67 (58.3)
occurrence of abuse. Re-victimization with more than one Oral sex 1 (0.9)
incident of CSA was seen at 31.3%. Penetrative abuse was Alcohol abusea 5 (4.4)
reported in 58.3% of victims. Alcohol abuse was seen in External injuries 8 (7)
4.3% of the perpetrators. The urine pregnancy test was Intact hymen 47 (40.9)
positive in eight victims, HIV screening being positive in HIV positiveb 1 (0.9)
one victim, while there were no reports of other sexually Positive urine pregnancy test 8 (7)
transmitted diseases. The HIV-positive victim was a 15- aNo history of any other intoxicant/drug abuse in the perpetrator;
year-old girl, residing in an orphanage, who presented with bvictim. HIV: human immunodeficiency virus.
Table III Association Between the Perpetrator and Place of Abuse (N=115)
Perpetrator Place of abuse
House of House of Hostel Lodge Outdoor Neighbor’s School Unknown P
victim perpetrator house house value
Classmate, n=1 0 0 0 0 0 0 1 0 0.001
Co-worker, n=2 1 0 0 0 1 0 0 0 0.851
Cousin, n=3 2 0 0 0 0 1 0 0 0.989
Father, n=9 8 1 0 0 0 0 0 0 0.111
Father’s friend, n=3 2 0 0 0 0 1 0 0 0.994
Friend, n=31 11 0 1 2 1 15 1 0 0.013
Teacher/ caretaker, n=3 0 0 1 0 0 0 2 0 0.002
Neighbor, n=40 13 1 0 0 3 22 1 0 0.109
Relative, n=3 3 0 0 0 0 0 0 0 0.961
Sibling, n=1 1 0 0 0 0 0 0 0 0.988
Stranger, n=13 0 1 0 0 10 1 0 1 0.001
Uncle, n=5 4 0 0 0 0 1 0 0 0.001
Stepfather, n=1 1 0 0 0 0 0 0 0 0.988
Total 46 3 2 2 15 41 5 1
Values in numbers.
problem. In our study, the prevalence of CSA was 49. 8% of other studies [4,6]. CSA usually happens in places familiar
all sexual offences reported over a period of 3.5 years. In a to the child victim, in contrast to adult incidents. In our
similar recent hospital-based study in Punjab, the study, many of the abuses occurred in the house of the
prevalence was 60% over a two-year period [4]. There has victim and neighbor/relative’s house; whereas a previous
been considerable heterogeneity in the incidence study [10] reported a higher occurrence of the abuses in
depending on the sample population [3]. Though many the perpetrator’s house or a private accommodation like a
studies have demonstrated an increase in reporting of CSA lodging house.
in recent years, the present study showed a sharp decline
Re-victimization was seen in 31.3% of reports. The
in the reports of CSA in the two years 2020 and 2021 due to
‘child sexual abuse accommodation syndrome’ that
the prevailing lockdown situation and closure of schools
describes the child’s reaction to CSA has five stages:
during the COVID-19 pandemic [4].
secrecy, helplessness, entrapment and accommodation,
In the present study, there were only two reported delayed and unconvincing disclosure of the abuse, and,
cases of boy victims. The lower prevalence among boys retraction of the complaint [11]. If uninterrupted, the
was observed in many other studies, which may be syndrome paves the way for further re-victimization. This
attributed to under-reporting, lack of adequate research, syndrome reiterates the need for early identification of
and social denial [5]. Depending on the study setting, there CSA to prevent further re-victimization. A study by
has been a wide variation in peak age groups for CSA [4,6]. Scoglio, et al. [12] reported that perceived parental care is
About 32.2% of the victims were in the age group of 6 to 10 the only preventive factor against re-victimization. In our
years and hence the educational programs for children study, nearly half the cases were reported after a week;
against CSA should ideally be targeted at this age group. whereas, Lal, et al. [6] found that 12% reported after a
month of abuse. The delay in reporting the incident is
In our study, perpetrator was known to the child victim
usually due to stigma, fear, and indecisiveness of the
in majority of cases, similar to that reported in other studies
parents. They need sufficient time to reconcile themselves
[7-9]. A study done in Imphal [10] reported 53.7% of
from the incident and brace themselves to report the
perpetrators to be boyfriends, which is much higher than
incident [10].
this study. The lesser reports of the friends as perpetrators
in our study could be attributed to the COVID-19 pandemic Penetrative sexual abuse is associated with serious
and the ensuing closure of schools, and/or regional psychological stress and physical problems like sexually
differences. The low proportion of the father, step-father, transmitted diseases and pregnancy. A previous study [13]
or sibling as a perpetrator in our study, was comparable to reported 37.9% incidence of pregnancies, as compared to
Correspondence to: Dr Hicran Doðru, Objective: To evaluate zonulin and occludin levels, potentially associated with
Department of Child and Adolescent immunological pathways in the gut-brain axis, in children with attention-deficit/hyperactivity
Psychiatry, Child Study Center, disorder (ADHD). Method: We examined the association between serum levels of zonulin
and occluding, and behavioral/emotional problems in children with ADHD. 40 medication-
One Park Avenue, 7th Floor
naïve children meeting Diagnostic and statistical (DSM-5) criteria for ADHD (11 females;
New York, NY 10016, USA. mean (SD) age 9.4 (1.6) years) and 39 healthy comparisons (12 females; mean (SD) age 9.3
hicran.dogru@nyulangone.org (1.9) years) were studied. Serum zonulin and occludin levels were measured by (ELISA).
Received: May 10, 2022; Result: We found higher mean (SD) serum zonulin levels [37.1 (28.2) vs 8.1 (4.5) ng/mL;
Initial review: June 20, 2022; P<0.001) and occludin levels [2.4 (1.6) vs 0.6 (0.4) ng/mL; P<0.001] in the ADHD group
Accepted: November 28, 2022. compared to control group. Serum zonulin levels had a positive correlation with weight
(r=0.452; P=0.003) and BMI (r=0.401; P=0.01) among children with ADHD. Serum zonulin and
occludin levels also had a positive correlation with Conners parent rating scale scores
(r=0.58; P<0.001), and Strengths and difficulties questionnaire scores (r=0.49; P<0.001).
Multiple linear regression analysis revealed that age, sex, weight, conduct problems and
oppositional sub-scores were significant predictors of increased serum zonulin levels.
Conclusion: These data confirm an association between ADHD, and serum zonulin and
occludin levels. Pathophysiological and clinical significance of these findings needs to be
elucidated.
Keywords: Behavioral symptoms, Brain-intestinal axis, Conduct problems, Conners
rating scale.
A
ttention-deficit/hyperactivity disorder [6]. Serum occludin level has been shown to increase
(ADHD) is a pervasive neurodevelopmental secondary to barrier disassembly [7]. A recent study
disorder, and has a worldwide prevalence of showed elevated concentrations of occludin, which was
5.9% [1]. Although, the pathophysiology is positively correlated with zonulin concentrations, in people
still unclear, emerging evidence has drawn attention to the with multiple sclerosis compared with healthy controls [8].
role of inflammation [2]. In recent years, the two-way This finding raises the question of whether occludin
communication between the brain and the gut (i.e., the gut- mediates the relationship between neuroinflammation and
brain axis) has become a focus of study across a wide range the gut-brain axis. Zonulin (pre-haptoglobulin-2), an
of psychiatric disorders, including ADHD [3]. Likely endogenous protein synthesized by the intestinal mucosa,
reflecting their common embryologic origins, tight has been identified as an important regulator of epithelial
junctions are essential components of both brain and gut. permeability of TJs [9]. Increased serum zonulin concen-
Increased leakiness of the blood-brain barrier has been trations have been reported in various psychiatric disorders
suggested to play a role in the inflammatory process [4]. On [10,11], as well as in chronic inflammatory diseases [12], but
the other hand, evidence for the possible role of inflammation only two studies have focused on ADHD [13,14].
in ADHD pathophysiology is also increasing [2].
We sought to measure serum zonulin and occludin
Tight junctions (TJ) are intercellular multiprotein levels in two groups: an independent sample of rigorously
junctional complexes that control intercellular permeability diagnosed medication-naïve children with ADHD and
in epithelium and endothelium [5]. Occludin, which is a healthy controls, and examine the association between
major component of TJs, plays a key role in maintaining TJ these proteins and behavioral/emotional problems and
integrity, stability and regulating paracellular permeability symptom severity of ADHD.
Table I Characteristics of the Enrolled Children Table II Multiple Stepwise Regression Analysis Showing
Variables Independently Associated With Changes in
Characteristics ADHD group Control group
Serum Zonulin and Occludin Levels
(n=40) (n=39)
Variables β SE B P value
Age (y) 9.4 (1.6) 9.3 (1.9)
Male gender 29 (72.5) 27 (69.2) Serum zonulin levels
Weight (kg) 35.0 (8.9) 32.5 (8.8) Occludin levels 4.215 1.414 0.004
Age -7.019 1.550 <.001
Height (cm) 133.3 (23.7) 133.4 (12.5)
Sex 9.784 4.189 0.022
BMI (kg/m2) 18.5 (2.6) 17.9 (2.6) Weight (kg) 1.839 0.311 <0.001
CPRS-R:Sa Conduct problemsa 3.188 1.557 0.044
Inattention 23.2 (6.1) 4.9 (3.4) Oppositionalb 1.604 0.642 0.015
Hyperactivity 9.0 (4.8) 2.1 (1.7) Peer relationshipsa -3.233 1.620 0.05
Oppositional 8.7 (4.4) 3.2 (2.3) Serum occludin levels
Cognitive problems 12.4 (3.4) 2.2 (1.7) Zonulin levels 0.019 0.006 0.003
Total CPRS-R:S score 48.1 (14.1) 11.7 (6.2) Cognitive problemsb 0.078 0.030 <0.010
SDQa Emotional problemsa 0.138 0.066 0.039
Emotional problems 3.3 (2.6) 1.6 (1.4) For zonulin; Occludin, age, sex, weight, height, BMI; CPRS-R:S
Conduct problems 2.8 (1.8) 1.1 (0.9) and SDQ scores were included in the original model. SE B:
Hyperactivity/Inattention 7.3 (1.9) 1.7 (1.2) standard error of the mean. For occludin; Zonulin, age, sex, weight,
Peer relationships problems 2.5 (1.3) 1.6 (1.0) height, BMI; CPRS-R:S and SDQ scores were included in the
Total SDQ score 15.9 (5.2) 6.2 (3.2) original model. aSDQ score; bCPRS – R:S score.
Fig.1 Serum zonulin levels in the ADHD and the control groups. Fig. 2 Serum occludin levels in the ADHD and the control groups.
Among the children with ADHD, we found analysis that shown an association between increased
statistically significant correlations between zonulin and plasma zonulin level and impaired intestinal barrier
weight (r= 0.452, P=0.003) and zonulin and BMI (r=0.401, function in children with a range of neurodevelopmental
P=0.01). No significant correlations were found between disorders [18]. We conclude that further studies of zonulin
occludin levels and these parameters. Across all children, in ADHD and neurodevelopmental disorders are
all CPRS-R:S sub-scores and some of the SDQ scores warranted, with greater focus on quantifying gastro-
(conduct problems, hyperactivity/inattention and total intestinal function in addition to standard behavioral
score) were significantly correlated with zonulin and ratings.
occludin levels (Web Table I). However, none of these
correlations remained significant within the ADHD group The number of studies investigating the sex
(P>0.05). Also, zonulin and occludin levels were not related differences in zonulin and occludin levels is limited. In
to ADHD presentation types or ADHD severity in children affective disorders, serum zonulin was found to be
with ADHD (P>0.05). significantly higher in women than in men, suggesting that
increased serum zonulin levels may represent a particularly
Finally, across the entire sample, zonulin and occludin heightened sensibility for depression [11]. In our study,
levels were significantly and positive correlated (r = 0.565, zonulin levels were considerably higher in females than
P <0.001). Aiming to control potential confounding males in ADHD group; although, none of the sex by
variables and identify which parameters are significantly diagnosis interactions reached significance. This
associated with zonulin in the whole sample, we selected suggests that there may be a sex difference in children with
age, sex, weight, height, BMI, occludin and all CPRS-R:S, ADHD in terms of zonulin levels. The number of females
and SDQ scale scores as independent variables and serum included in our study was relatively low. This issue can be
zonulin as a dependent variable in multiple stepwise re-analyzed in future studies, especially by paying
regression analysis (Table II). A multiple stepwise attention to the homogeneity of the distribution of the
regression analysis was conducted with the same males and females.
independent variables and zonulin for serum occludin
levels (Table II). Importantly, weight and BMI showed a significant
positive correlation with serum zonulin levels among
DISCUSSION ADHD group, conforming to previous studies [10,14]
This is the first study to evaluate serum zonulin (a marker showing a positive correlation with BMI. Moreover,
and modulator of TJ permeability) and occludin (a increased serum zonulin levels have been reported in
regulator of formation, maintenance, and function of TJ) obese children compared to healthy children [19],
levels in children with ADHD and age/sex-matched healthy therefore obesity was an exclusion criterion in our study.
comparison subjects. We found increased serum zonulin Despite this, serum zonulin levels showed a significant
and occludin levels in the ADHD group compared to positive association with weight and BMI.
health control. In addition, our data shows oppositional
This study has some limitations, including a relatively
and conduct problems to be associated with increased
small sample size and cross-section design. The most
zonulin levels.
important limitation is that our convenience control sample
The two prior studies on serum zonulin levels in differed from the ADHD sample in socio-economic status.
ADHD have produced conflicting results. An initial study The mentioned factors limit the generalizability of our
found elevated serum zonulin levels in children with findings.
ADHD than in health control, which were associated with
social dysfunction and ADHD symptom severity [13]. We In conclusion, we found significantly higher serum
confirmed increased serum zonulin levels in ADHD group, zonulin and occludin levels in children with ADHD than in
but in our sample, serum zonulin levels were associated sex- and age-matched healthy controls. Independent
with behavioral/emotional problems. replication of these preliminary results would motivate
further examination of intestinal permeability and possibly
Our results differ from those of a recent study [14], other components of TJs in the gut and/or brain. Future
which failed to find a difference in zonulin but instead research should focus on alterations in serum zonulin and
found elevation of claudin-5 (a TJ-forming protein occludin levels in diverse ADHD subgroups (for example,
functionally similar to occludin). We cannot resolve these after symptoms have been controlled with medication). In
inconsistencies, which could be secondary to any of addition, further studies comparing ADHD subgroups
several factors, including differences in analytic kits to enriched for oppositional defiant disorder and conduct
quantify levels. Our findings are consistent with a meta- disorder should be a priority.
Acknowledgments: Prof. Francisco X. Castellanos for editorial LM, Yong VW. Biomarkers of intestinal barrier function in
suggestions. multiple sclerosis are associated with disease activity. Multi
Ethics clearance: IEC, Ataturk University; No. B.30.2.ATA. Sclerosis J. 2019;26:1340-50.
0.01.00/2 dated Dec 17, 2020. 9. Fasano A. Zonulin, regulation of tight junctions, and
Contributors: AÇ: conceptualization, funding acquisition, autoimmune diseases. Ann NY Acad Sci. 2012;1258:25-33.
writing- original draft. HD: conceptualization, funding 10. Esnafoglu E, Cýrrýk S, Ayyýldýz SN, Erdil A, Ertürk EY,
acquisition, methodology, supervision, writing - review & Daglý A, Noyan T. Increased Serum Zonulin Levels as an
editing, EL: methodology, investigation. All authors approved Intestinal Permeability Marker in Autistic Subjects. J Pediatr.
the final version of manuscript, and are accountable for all aspects 2017;188:240-4.
related to the study. 11. Maget A, Dalkner N, Hamm C, et al. Sex differences in zonulin
Funding: Ataturk University, Scientific Research Projects in affective disorders and associations with current mood
coordination unit office (Registration Number TTU-2021-9001); symptoms. J Affect Disord. 2021;294:441-6.
Competing interests: None stated. 12. Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and
Note: Additional material related to this study is available with endothelial barrier functions, and its involvement in chronic
the online version at www.indianpediatrics.net inflammatory diseases. Tissue Barriers. 2016;4: e1251384.
13. Özyurt G, Öztürk Y, Appak YÇ, et al. Increased zonulin is
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children with attention deficit hyperactivity disorder.
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Federation of ADHD International Consensus Statement: 208 14. Aydoðan Avþar P, Iþýk Ü, Aktepe E, Kýlýç F, Doðuç DK,
Evidence-Based Conclusions About the Disorder. Neurosc Büyükbayram HÝ. Serum zonulin and claudin-5 levels in
Biobehav Rev. 2021;128:789-818. children with attention-deficit/hyperactivity disorder.
2. Anand D, Colpo GD, Zeni G, Zeni CP, Teixeira AL. Attention- International Journal of Psychiatry in Clinical Practice.
deficit/hyperactivity disorder and inflammation: what does 2020:1-7.
current knowledge tell us? A systematic review. Frontiers in 15. American Psychiatric Association. Diagnostic and statistical
Psychiatry. 2017;8. manual of mental disorders (DSM–5). 5th ed. American
3. Dam SA, Mostert JC, Szopinska-Tokov JW, Bloemendaal M, Psychiatric Association; 2013.
Amato M, Arias-Vasquez A. The role of the gut-brain axis in 16. Kaner S, Buyukozturk S, Iseri E. Conners parent rating scale-
attention-deficit/hyperactivity disorder. Gastro-enterol Clin revised short: Turkish standardization study. Arch Neuro-
North Amer. 2019;48:407-31. psych. 2013;50:100-10.
4. Kealy J, Greene C, Campbell M. Blood-brain barrier 17. Goodman R, Ford T, Richards H, Gatward R, Meltzer H. The
regulation in psychiatric disorders. Neurosc Lett. 2020;726: development and well-being assessment: description and
133664. initial validation of an integrated assessment of child and
5. Zihni C, Mills C, Matter K, Balda MS. Tight junctions: from adolescent psychopathology. J Child Psychol Psychiatry.
simple barriers to multifunctional molecular gates. Nature Revi 2000;41:645-55.
Mol Cell Bio. 2016;17:564-580. 18. Asbjornsdottir B, Snorradottir H, Andresdottir E, et al.
6. Feldman G, Mulllin J, Ryan M. Occludin: Structure, function Zonulin-dependent intestinal permeability in children
and regulation. Adv Drug Delivery Rev. 2005;57:883-917. diagnosed with mental disorders: a systematic review and
7. Yuan S, Li W, Hou C, et al. Serum occludin level combined with meta-analysis. Nutrients. 2020;12:1982.
NIHSS score predicts hemorrhage transformation in ischemic 19. Küme T, Acar S, Tuhan H, et al. The relationship between
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Web Table I Correlation between CPRS-R:S and SDQ Scores and Zonulin and Occludin Levels (N=79)
SDQ
Emotional problems 0.012 0.259c
Conduct problems 0.256c 0.302 a
a
Hyperactivity/inattention 0.455 0.541 a
Peer relationships problems 0.076 0.102
Total SDQ score 0.363a 0.498 a
C
hallenges in counselling the family of a child The article [1] focusses on parental counselling with
with mental retardation (sic) were highlighted specific reference to a child with mental retardation. Using
by Dr. Seeta Sinclair in the the correct terminology, utilizing changes
February, 1973 issue of in age-appropriate nomenclature has
Indian Pediatrics [1]. The article been emphasized in the article. The stress
stresses on the need for a family centric on utilization of appropriate tests to
approach, focusing not only on impro- comprehend the level of intellect has
ving the capabilities of a child with been delved in adequately. Confounding
mental retardation but also attempting factors like stressors, familiarity with
to resolve the issues in a holistic tests and the reduction in fear of the tests
manner. It also conveys the importance being administered are discussed to
of understanding comorbidities that change the interpretation of the tests
accompany these children, and address leading to overscoring in performance
them simultaneously for improvement [1]. Crnic, et al. [3] also reiterate the
in outcomes. Counselling of an index inconsistencies in the interpretation of
case with global developmental delay tests due to methodological issues, which
(GDD), currently the preferred term for focus on unidimensional variables with
children aged 5 years or intellectual unimodal measurements.
disability (ID) for children who have
attained the age of 5 years, still remains a difficult arena for Discussion on transmission of diagnosis in the presence
the physician, the genetic counsellor, and the social of both the parents is stressed upon, without alluding to
worker. genetic counselling. Concepts including guilt, blame,
disagreement and mutual discomfort of not revealing certain
THE PAST
issues between both parents are detailed. The knowledge of
Counselling is an American term coined by Carl Rogers, differential behavior adaptation of both parents has been a
who lacking a medical qualification, was prevented from major aspect in discussion related to the differentially abled
calling his work psychotherapy [2]. The concept of this child. The difference in the management of such an ordeal
important specialty started after the World War II. In its and later an adaptational or transformational journey that
evolution the term stems back to its initial use in tribal they embark is worth pondering upon [4]. It is even more
population and in essence can be traced back to the important to eliminate the concept of guilt, which
thoughts and dreams discussed in a common session of a accompanies this revelation. The authors remark that it may
meeting with senior members of the tribe. It subsequently be futile to discuss the fact if one parent is responsible for the
shifted with modernization, to the priests who would listen genetic transmission, as it serves no useful purpose [1]. In the
patiently and advise parsimonies. Counselling was initially era of internet, it may not be possible to conceal this piece of
imparted to help people navigate difficult situations such information. Nonetheless, counselling in X-linked and
as death of loved ones, divorce, natural disease, birth of a mitochondrial disorders is still a challenge, even to an
child with disability amongst other causes. The basic educated, computer savvy family. Thus, there is a paradigm
premise of counselling still remains the same as it intends shift on divulging the diagnosis and mode of transmission to
to direct life situations in the correct perspective, approach assure that the subsequent trauma can be avoided with
challenges and find feasible and practical solutions. medical termination of pregnancy, if the family so desires
after a concrete diagnosis is made and mode of inheritance in https://www.face2gene.com/) is a smart-phone based
the index case can be established. computerized facial dysmorphology analysis program that
analyses 2-dimensional facial images along with clinical
The authors [1] address the need for multidisciplinary characteristics to provide a list of candidate disorders. Others
health care assessments needed for holistic evaluation of a like Online Mendelian Inheritance in man (https://om
child with GDD/ID. Establishing a firm diagnosis is impor- im.org/), ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/)
tant before it is divulged to parents. The author has also are free databases that can also be relied upon.
brought to attention that simultaneous addressal of deficits in
speech, vision, hearing, management of spasticity are likely An underlying genetic etiology contributes to up to 50 %
to improve outcome in a holistic manner [1]. The basic tests of cases of GDD/ID [5]. The most recent published
for evaluating a child with GDD/ID include those easily guidelines on genetic evaluation of GDD/ID and ASD by the
available like radiological evaluation, urinary examination American Academy of Pediatrics (AAP) [6] and the
for inborn errors of metabolism and karyotype for those with American College of Medical Genetics and Genomics
a suggestive facial gestalt. Radiological evaluation, basic (ACMG) [7] respectively, unanimously recommend a tiered
urinary metabolites testing, and karyotyping on an approach to genetic testing. A similar stratified approach has
individualized basis were advised in the article along with also been alluded to in the Indian context [5,8]. A genome
delineation of dysmorphic features, if any. A skeletal survey wide chromosomal microarray (CMA) testing constitutes the
is still useful for evaluating skeletal dysplasias and storage first-tier genetic test for any patient with unexplained GDD,
disorders where characteristic changes can be appreciated. ID, and/or ASD. CMA detects sub-microscopic
Pharmacotherapy for hyperactivity and aggression are also chromosomal aberrations and has a diagnostic yield up to
elaborated upon. Though not mentioned as autism spectrum 10%, and higher (up to 15-20%) in patients with multiple
disorder (ASD), the use of specific medication has been congenital anomalies vis-à-vis karyotype, which has a
outlined [1]. diagnostic yield of 3% in such cases [9]. CMA has replaced a
conventional G-banded karyotype as a first-tier test unless
THE PRESENT
there are evident features of chromosomal aneuploidy (e.g.,
Scientific and technologic discoveries are constantly Down syndrome) or a history of recurrent miscarriages
transforming our understanding of genetic and genomic where karyotype still forms the basic test [9,10]. Neuro-
disorders including GDD/ID/ASD. Though, the social and imaging techniques like magnetic resonance imaging (MRI)
emotional stigma persists and the rehabilitative aspects of to magnetic resonance spectroscopy (MRS) and nuclear
these neurodevelopmental disorders are still in evolving magnetic resonance (NMR) are of proven value in unravell-
stage, there has been significant and expanding compre- ing a case with GDD/ID.
hension of the molecular etiology, and availability of multi-
tude of genetic, neurometabolic, and neuroimaging investi- Testing for single gene disorders like tuberous sclerosis
gations. Genetic counselling related to management, prog- and Lesch-Nyhan syndrome has become less labor intensive,
nosis and recurrence risk has also undergone significant cheaper and faster with the arrival of next generation
change. The cost of these genetic testing maybe forbidding in sequencing (NGS) technology. NGS is a high throughput
today’s date for the general public. However, as the testing sequencing technology enabling simultaneous sequencing of
evolves and becomes easily available, the price of the tests is multiple genes which can be done as a panel of GDD/ID/
likely to decline significantly. Thus, providing a genetic ASD specific genes or can include whole exome or whole
diagnosis to majority of patients with suspected genetic genome sequencing. Various studies have reported a high
etiology for GDD/ID/ASD, will soon become a reality. diagnostic yield of whole exome sequencing (WES) up to
40% in patients with ID [11-13], especially if a trio sample
An exhaustive clinical evaluation including pedigree (proband and parents) is tested. With further advancement of
charting, review of the antenatal and developmental history, exome sequencing technology in combination with robust
and deep phenotyping, still forms the foundation of accurate bioinformatic pipeline for assessment of copy number
diagnosis and likely successful outcome of genetic testing. variations, WES may soon become a dependable first tier
Easy accessibility of many online databases related to human analysis in non-specific GGD/ID/ASD. CMA and WES tests
genes and genetic phenotypes have refined clinical approach. being high throughput in nature, may identify variants which
With the advent of computer-learning algorithm in clinical may not have strong enough evidence to ascertain their
medicine, availability of artificial intelligence (AI) software clinical significance. Hence, pre-test and post-test counsel-
like “Face2Gene” has become a handy tool to the clinician ling which encompasses the advantages and limitations of
for enhancing their differential diagnosis and in improving these tests is an important facet of genetic counselling in
genomic data interpretation. Face2Gene (F2G, FDNA Inc, today’s era.
Screening for inborn errors of metabolism (IEMs) in Government support schemes and disease-specific support
individuals with GDD/ID/ASD has also witnessed a signi- groups. The Government of India has launched the National
ficant technological advancement like tandem mass Policy for Rare Diseases (NPRD), 2021 for the treatment of
spectrometry (TMS) and gas chromatography mass spectro- rare disease patients (https://main.mohfw. gov.in/sites/
metry (GC-MS) to screen for amino acid metabolism default/files/Final%20NPRD%2C%202021.pdf).Under
disorders, fatty acid oxidation defects and organic acidurias. this policy, rare diseases have been identified and there is a
Neurometabolic diseases account for 10% of cases of GDD/ provision for one-time financial support of up to Rs. 50 lakhs
ID [14] and this etiological group has a potential for either at one time or in a staggered manner to the patients
complete or near complete modification of phenotype. Apart suffering from any rare disease and for treatment in any of the
from dietary supplementation of the deficient metabolite like Centre of Excellence (CoE) mentioned in NPRD-2021,
pyridoxine or pyridoxal phosphate for pyridoxine responsive outside the umbrella scheme of Rashtriya Arogaya Nidhi.
epilepsy and creatine in creatine transporter deficiency, there Initially eight Centres of Excellence (CoEs) were identified
has been advancement in availability of metabolic-disease for diagnosis, prevention and treatment of rare diseases and
specific formulas like isoleucine, leucine and valine free diet this number has increased significantly over a short period of
in maple syrup urinary disease and phenylalanine and time. Five Nidan Kendras have been set up for genetic testing
tyrosine poor diets and drugs like nitisinone in tyrosinemia 1. and counselling services. These Government initiatives have
The ease of import regulations since 2017, by the country’s brought a ray of hope for parents with children with neuro-
regulatory authority – FSSAI (Food Safety and Standards developmental disorders. By virtue of social media, reaching
Authority of India) under the Diet4Life initiative, has made out to the various disease specific support groups and online
the import of these critical medical foods simpler and faster. resources have become feasible now for the parents. Accu-
Lysosomal storage disorders like mucopolysaccharidoses rate genetic diagnosis puts an end to the diagnostic odyssey,
types I and II, are another group of disorders associated with provides a natural history of the disease, facilitates enrolment
GDD/ID, which have become amenable to treatment by in clinical trials and provides basis for prenatal diagnosis.
enzyme replacement therapy (ERT). Currently, cost of ERT
THE FUTURE
is prohibitory and is mainly accessed through charitable
initiatives of manufacturers and clinical trials or are The inclusion of expanded newborn screening for disorders
occasionally provided to affected children of employees of of amino acid, fatty acid and organic acid metabolism in a
some central and state government organizations, which bear mandate or a national law will go a long way in preventing
the cost of treatment. GDD/ID before significant brain damage occurs. Precision
medicine in patients with GDD/ID/ASD will soon be
Discussion about risk of recurrence and appraisal about possible as the advances in genomic medicine continue.
the reproductive choices to the couple in subsequent Gene therapy and stem cell therapy will be options available
pregnancies forms an integral part of the counselling process. for a significant proportion of disorders. There is hope that
Various available options are prenatal diagnosis by means of the availability of cutting-edge diagnostic tools and multiple
chorionic villus sampling or amniocentesis and in vitro curative options will change the dynamics of counselling of
fertilization (IVF) with pre-implantation genetic diagnosis. the parents and would minimize the mental, social and
For disorders with mitochondrial inheritance, there is now emotional trauma inherent to dealing with a child with GDD/
the option of mitochondrial transfer also known as three- ID/ASD.
parent IVF, which involves genetic materials of three people
i.e., the nuclear DNA of the biological father and mother and Funding: None; Competing interests: None stated.
the mitochondrial DNA of a healthy egg donor. REFERENCES
Guidance about rehabilitation of children with GDD/ID/ 1. Sinclair S. Counselling of parents with mentally retarded
ASD is crucial to the counselling session. Current child children. Indian Pediatr. 1973;10:115-120.
development clinics and district early intervention centers, 2. Rogers CR. A counselling approach to human problems. Am J
apart from offering counselling imparted by the develop- Nurs. 1956;56:994-7.
3. Crnic KA, Friedrich WN, Greenberg TM. Adaptation of
mental pediatricians themselves, are equipped with a physio-
families with mentally retarded children: a model of stress,
therapist, a medical social worker, a speech therapist, and an coping, and family ecology. Am J Ment Defic. 1983;88:
occupational therapist. These one stop centers have been 125-38.
created to deliver the best possible outcomes in adaption of 4. Pelchat D. Levert MJ, Bourgeois-Guérin V. How do mothers
the family and the affected child. and fathers who have a child with a disability describe their
adaptation/ transformation process. J Child Health Care.
An important aspect of genetic counselling is also to 2009;13:239-5.
provide information about the available resources such as 5. Gupta N, Kabra M. Approach to the diagnosis of
developmental delay – The changing scenario. Indian J Med 10. De Vries B, Pfundt R, Leisink M, et al. Diagnostic genome
Res. 2014;139:4-6. profiling in mental retardation. Am J Hum Genet.
6. Moeschler JB, Shevell M; Committee on Genetics. 2005;77:606-16.
Comprehensive Evaluation of the Child With Intellectual 11. Lee H, Deignan JL, Dorrani N, et al. Clinical exome
Disability or Global Developmental Delays. Pediatrics. 2014; sequencing for genetic identification of rare Mendelian
134:e903–18. disorders. JAMA. 2014;312:1880-7.
7. Schaefer GB, Mendelsohn NJ; Professional Practice and 12. Srivastava S, Love-Nichols J, Dies K, et al. Meta-analysis and
Guidelines Committee. Clinical Genetics Evaluation in Multidisciplinary Consensus Statement: Exome Sequencing
Identifying the Etiology of Autism Spectrum Disorders: 2013 is a First-Tier Clinical Diagnostic Test for Individuals With
Guideline Revisions. Genet Med. 2013;15:399–407. Neurodevelopmental Disorders. Genet Med. 2019;21:
8. Jain S, Chowdhury V, Juneja M, et al. Intellectual disability in 2413-21.
Indian children: experience with a stratified approach for 13. Kuperberg M, Lev D, Blumkin L, et al. Utility of whole exome
etiological diagnosis. Indian Pediatr. 2013;50:1125-30. sequencing for genetic diagnosis of previously undiagnosed
9. Miller DT, Adam MP, Aradhya S, et al. Consensus Statement: pediatric neurology patients. J Child Neurol. 2016;31:1534-9.
Chromosomal Microarray is a First-Tier Clinical Diagnostic 14. Aggarwal S, Bogula VR, Mandal K, Kumar R, Phadke SR.
Test for Individuals With Developmental Disabilities or Aetiologic spectrum of mental retardation and development
Congenital Anomalies. Am J Hum Genet. 2010;86: 749-64. delay in India. Indian J Med Res. 2012;136:436-44.
FORM IV (Rule 8)
1. Place of publication : Delhi
2. Periodicity of its publication : Monthly
3. Printer’s name : Dr Devendra Mishra
Nationality Indian
Address 115/4, Ground Floor, Gautam Nagar, New Delhi 110 049
4. Publisher’s name : Dr Devendra Mishra
Nationality Indian
Address 115/4, Ground Floor, Gautam Nagar, New Delhi 110 049
5. Editor’s name : Dr Devendra Mishra
Nationality Indian
Address 115/4, Ground Floor, Gautam Nagar, New Delhi 110 049
6. Name and addresses of individuals who Indian Academy of Pediatrics
own the newspaper as partners and share Kamdhenu Business Bay,
holders holding more than 1 per cent of 5th Floor, Plot No. 51, Sector 1,
the total share : Juinagar East (Near Juinagar Railway Station),
Nerul, Navi Mumbai-400706
I, Dr Devendra Mishra, hereby declare that the particulars given above are true to the best of my knowledge and belief.
Sd/ Dr Devendra Mishra
Dated: February, 2023 Publisher
Effect of High Sodium Intake (5 mEq/kg/ [3,4]. The sodium delivered was calculated from the
sodium concentration and volume of fluid administered,
day) in Preterm Newborns (<35 Weeks including colloid, crystalloid, drugs, and flush volumes.
Gestation) During the Initial 24 Hours of The percentage of sodium in the fluids administered to
Life: A Non-Blinded Randomized Clinical each group of patients varied according to the needs of
Trial each participant, the solutions were prepared according
to the supervision of the investigators involved in this
The objective was to analyze effect of early sodium administra- protocol to assure the adequate delivery of sodium per kg
tion in preterm newborns <35 weeks of gestation. The develop-
according to the group. In average, the intervention
ment of hypo- and hyper-natremia, complications, and mortality
showed no difference between high sodium and low sodium group received maintenance fluids consisting of 0.25%
groups. The percentage of weight loss from birth to 48 hours sodium, and the control group received maintenance
(7.13% vs 4.08%) and 72 hours (9.02% vs 6.34%) was signifi- fluids containing 0.02% sodium.
cantly lower in the high sodium intake group (P=0.036). Early so-
dium implementation in preterm newborns may improve weight The intervention was initiated at 24 hours of life,
loss and decrease related complications. ending at 72 hours; all participants received standard care
Keywords: Complications, Hyponatremia, Weight loss. regarding fluid administration in different gestational
Trial registration: ClinicalTrials.gov; NTC 04035564
ages and sicknesses according to clinical practice guide-
lines. The intervention was discontinued if parents
withdrew consent midway, adverse effects attributable to
Electrolyte and fluid management is a challenge in the intervention were detected, or proto-col violation
premature newborns; up to 25% infants younger than 33 occurred.
weeks of gestational age develop serum sodium altera- The sample size was calculated using a bilateral test to
tions [1]. Preterm infants are at risk of hyponatremia due contrast a qualitative endpoint, with a 95% confidence level
to reduced glomerular filtration rate, limited kidney (1-α) and an 80% statistical power; the proportion of
sodium reabsorption, and increased arginine-vaso- patients with the primary endpoint in the control group and
pressin levels in response to illness; this impacts growth, the intervention group were selected according to previous
and occurrence of preterm-related compli-cations [1,2]. publications (50% and 20%, respectively) [2,4,5], resulting
We investigated the effect of early sodium adminis- tration in a sample size of 38 patients in each group.
on preterm newborns, by hypothesizing that early sodium
administration might impact growth and sodium The primary outcome measure was developing
imbalance, with no adverse effects. hyponatremia or hypernatremia (serum sodium < 130
mEq/L or >150 mEq/L) during the first 72 hours of life. The
A randomized clinical trial to analyze the impact of secondary outcome endpoints were the length of in-
sodium intake was conducted between March, 2018 and hospital stay, mortality, weight and sodium change
April, 2020 at our center. The hospital’s Ethics in Research through time, development of sepsis, necrotizing entero-
committee approved the protocol, and informed consent colitis, intraventricular hemorrhage, and bronchopul-
was obtained from parents or legal guardians of each monary dysplasia.
patient.
Serum sodium was measured using ion selective
Newborns with less than 35 weeks of gestation and electrode in the laboratory. The renal functions were
less than 24 hours of life were eligible to participate. followed by daily assessment of urine output and serum
Patients with major birth defects such as urinary tract creatinine, and calculation of the glomerular filtration rate.
malformations, abdominal wall defects, intestinal atresia The monitoring of adverse effects was conducted due to
or obstruction, and congenital heart defects were close monitoring of clinical and laboratory parameters.
excluded. The neonates were randomized using a random
number generator with a 1:1 allocation ratio to two groups Chi-square test, independent sample t test, and risk
viz., the control group (sodium intake <1 mEq/kg/day) and ratios were used to compare differences between groups.
the intervention group (sodium intake of 5 mEq/kg/day). The change in variables with time was evaluated using
There was no blinding done. The dose in the intervention repeatedmeasures analysis of variance. The intention-to-
group was selected according to previous publications treat analysis was not conducted as it may underestimate
Excluded (n=114)
Not meeting inclusion criteria (n=86)
Declined consent (n=28)
Randomized (n=52)
Not completed (n=4) Completed protrocol (n=23) Completed protocol (n=19) Not completed protrocol (n=6)
the actual intervention effect (type II error) and may loss of 7.13% (vs 4.08%) of weight, and from birth to 72
create heterogeneity in the sample. A P value <0.05 was hours, a loss of 9.02% (vs 6.34%) of weight (P= 0.036).
considered statistically significant. The statistical
analyses were performed using IBM SPSS Statistics for There was no increase in complications or adverse
Windows, Version 21.0 (IBM Corp). effects in our study due to increased sodium intake. The
relative risks (95% CI) for hypernatremia [1.21 (0.08, 8.0);
Of the 52 randomized patients, 42 completed the P=0.88] and hyponatremia [0.20 (0.02, 1.53); P=0.12] were
study. The reason for not completing was protocol not significant (Table I).
violations such as fluid and sodium administration and
delayed laboratory samples (n=3); no laboratory available Anecdotal publications mention that sodium intake
(n=4); and withdrawal of consent after enrollment (n=3). should be delayed until postnatal loss of body water, due to
Finally, 23 patients were enrolled in the control group and the risk of hypernatremia, fluid retention, and other
19 in the intervention group. Birth weight, sex, and complications [3]. Nonetheless, it has been demonstrated
gestational age showed no statistical difference between that sodium deficiency in preterm infants is a risk factor for
the groups (Fig.1). complications: Al-Dahhan, et al. [6] concluded that sodium
intake in premature infants might be optimized in the first
The mean (SD) sodium dose in the intervention group days of life to prevent side effects of hypo-natremia in
was 5.06 mEq/kg/day, and in the control group, 0.41 (0.2) growth and nervous system development. Other studies
mEq/kg/day. demonstrate that early sodium intake does not increase the
Mortality was slightly higher in the control group, frequency of complications and may be beneficial to
21.7%, against 10.5% in the intervention group; however, preterm newborns [4,7]. Vanpée, et al. [7] demonstrated that
no statistical significance was demonstrated (P=0.33). sodium supplementation in preterm newborns improved
The length of hospital stay, hypernatremia, and compli- weight gain and stabilized serum sodium value. Similarly,
cations related to prematurity showed no difference when studying preterm new-borns, Isemann, et al. [5]
between the groups. The development of hyponatremia reported improvement in growth and a decrease in the
accounted for six patients (26.1%) in the control group development of hyponatremia. In our study, the weight
against one patient (5.3%) in the intervention group; des- gain improved in the sodium-supplemented group, but we
pite the higher frequency in the control group, (P =0.071). did not find a statistically significant impact on
hyponatremia; however, we started sodium intake earlier
When analyzing the percentage of weight change than in the studies mentioned above.
through time; the difference from birth to 24 hours
showed no relevance between groups; nonetheless, the It is recommended to prescribe sodium to newborns
control group from birth to 48 hours presented a mean after weight loss has been achieved; although, some
Table I Characteristics and Outcomes of Preterm Newborns few reports of the literature to contrast with. Therefore,
(N=42) further updated studies are needed to implement an
Control group Intervention group P adequate recommendation regarding the dose and
(n=23) (n=19) value initiation of sodium supplementation.
Female 12 (52.2) 8 (42.1) 0.51 Ethics clearance: The study was approved by the Ethics in
Birth weight (g)a 1551 (447) 1609 (394) 0.66 Research Committee of Hospital del Niño “Dr. Federico Gomez
Santos” approved the protocol (01/03/18N01) and was
Gestational age (wk)a 32 (2.0) 32.05 (2.4) 0.94
registered at clinicaltrials.gov (NTC04035564). The study was
Hypernatremia 1 (4.3) 1 (5.3) 0.89 performed according to the Declaration of Helsinki. Informed
Hyponatremia 6 (26.1) 1 (5.3) 0.071 consent was obtained from all parents or legal guardians of each
patient.
IVH 6 (26.1) 4 (21.1) 0.70
Contributors: CS,DC,VDB,FC: contributed to the conception
BPD 1 (4.3) 2 (10.5) 0.43 and design of the research, collection, and analysis of data,
NEC 2 (8.7) 2 (10.5) 0.84 revision, and approval of the manuscript. Authors declare
responsibility for the entire manuscript.
Sepsis 8 (34.8) 5 (26.3) 0.55
Funding: None; Competing interests: None stated.
Mortality 5 (21.7) 2 (10.5) 0.33
Hospital stay (d)a 28.4 (16.2) 24 (18.3) 0.49
CARLOS SÁNCHEZ,* DENISSE CASTILLO,
BEN DAVID VALDÉS, FIDEL CASTAÑEDA
Weight changec
Hospital del Niño “Dr. Federico Gómez Santos”
24 hb -1.003 (0.54) -2.67 (0.8) 0.12 Saltillo, Coahuila, México.
48 hb -7.13 (0.79) -4.08 (0.75) 0.036 *sanchez.carlos8516@gmail.com
72 hb -9.02 (0.97) -6.34 (0.90) 0.036
REFERENCES
Serum sodium changed
1. Stritzke A, Thomas A, Amin H, et al. Renal consequences of
48 hb 3.18 (1.75) 5.94 (1.93) 0.29 preterm birth. Mol Cell Pediatr. 2017;4:2.
72 hb 1.92 (1.54) 5.71 (1.70) 0.10 2. Moritz ML, Ayus JC. Hyponatremia in preterm neonates: Not
a benign condition. Pediatrics. 2009;124:e1014-6.
Data presented as no. (%), amean (SD) or bmean (standard error). IVH-
3. Hartnoll G, Bétrémieux P, Mondi N. Randomised controlled
intraventricular hemorrhage; BPD-bronchopulmonary dysplasia;
trial of postnatal sodium supplementation on body composi-
NEC-necrotizing enterocolitis. cCompared to birth weight. dCompared
tion in 25 to 30 week gestational age infants. Arch Dis Child
to serum sodium at 24 h of life.
Fetal Neonatal Ed. 2000;82:F24-8.
4. Al-Dahhan J, Haycock GB, Nichol B, et al. Sodium homeostasis
authors have recommended sodium intake in preterm in term and preterm neonates. III. Effect of salt supple-
mentation. Arch Dis Child. 1984;59:945-50.
infants ranging from 1 to 3 mEq/kg/day during the first
5. Isemann B, Mueller EW, Narendran V, Akinbi H. Impact of
three days of life, this may be insufficient to maintain an early sodium supplementation on hyponatremia and growth in
adequate sodium balance [2,8]. Despite this, there is a lack premature infants: A randomized controlled trial. JPEN J
of consensus on whether or not and when to prescribe Parenter Enteral Nutr. 2016;40:342-9.
6. Al-Dahhan J, Jannoun L, Haycock GB. Effect of salt
sodium supplementation in preterm newborns. Segar, et
supplementation of newborn premature infants on neuro-
al. [9] stated that a targeted approach that identifies developmental outcome al 10-13 years of age. Arch Dis Child
sodium deficiency in premature infants and guides Fetal Neonatal Ed. 2002;86:F120-3.
sodium intake might be preferable [9]. Currently, study 7. Vanpée M, Herin P, Broberger U, Aperia A. Sodium
supplementation optimizes weight gain in preterm infants.
protocols are being developed to answer this unresolved
Acta Paediatr. 1995;84:1312-4.
question [10]. However, there is a limited number of 8. Bischoff AR, Tomlinson C, Belik J. Sodium Intake require-
publications about this issue. ments for preterm neonates: review and recommendations. J
Pediatr Gastroenterol Nutr. 2016;63:e123-9.
In conclusion, early sodium implementation in 9. Segar DE, Segar EK, Harshman LA, et al. Physiological
preterm newborns may be beneficial and safe; it may approach to sodium supplementation in preterm infants. Am
improve weight and decrease related complications. This J Perinatol. 2018;35:994-1000.
10. Chan W, Chua MYK, Teo E, et al. Higher versus lower sodium
study has limitations, such as a small sample size, the intake for preterm infants. Cochrane Database Syst Rev.
variability of the sodium concen-tration in fluids, and the 2017;2017:CD012642.
Successful Management of Systemic Genitalia was normal male phenotype and there was no
hyperpigmentation. The differential diagnosis consi-
Pseudohypoaldosteronism Type 1 in an dered were late-onset neonatal sepsis, CAH with adrenal
Infant crisis, aldosterone synthase deficiency, congenital
adrenal hypoplasia, and PHA. Laboratory evaluation
showed metabolic acidosis, sodium 114 mEq/L,
Pseudohypoaldosteronism (PHA) type 1 is characterized
potassium 6.5 mEq/L and normal renal function tests.
by end organ resistance to the action of mineralo-
Blood glucose was normal and sepsis screen was
corticoids and manifests as neonatal salt wasting [1]. The
negative. Ultrasonography showed normal renal and
autosomal dominant and less severe form, also known as
adrenal size. Hormonal profile revealed normal cortisol of
renal PHA type 1 (PHA 1a) is caused by mutation in
12 mg/dL, adrenocorticotrophic hormone (ACTH) level 15
mineralocorticoid receptor (MR) in the kidney, with
pg/mL, 17-hydroxyprogesterone level 17.27 ng/mL,
isolated renal salt wasting. Mutations in any of the three
DHEAS (dehydroepiandrosterone sulphate) 8.28 ng/mL,
subunits (alpha, beta or gamma) of the epithelial sodium
and elevated aldosterone levels >100 ng/mL and elevated
channel (ENaC) results in the autosomal recessive
PRA (plasma renin activity) >500 ng/mL/h (normal range
systemic PHA type 1 (PHA 1b). This form is characterized
2-35 ng/mL/h). Sweat chloride was elevated (148 mEq/L).
by sodium wasting in the kidneys, lungs, colon, sweat
Cultures of blood and urine were sterile. CAH was ruled
and saliva. In contrast to the renal form, patients have
out and a provisional diagnosis of systemic PHA type 1b
recurrent respiratory infections and a more severe disease
was considered. He required normal saline boluses, 3%
that requires lifelong therapy [2,3]. PHA type 2 (Gordon
hypertonic saline, oxygen support, intravenous fluids
syndrome) is a rare renal tubular defect that results from
(dextrose-normal saline at 1.5 times maintenance) and
mutation in WNK1 or 4, and is characterized by hyper-
intravenous antibiotics. Hyperkalemia was treated with
tension and hyperkalemic metabolic acidosis in the
sodium bicar-bonate, insulin-dextrose drip and per rectal
presence of low renin and aldosterone levels. Herein, we
potassium-exchange resin (calcium polystyrene sulfo-
report a neonate with systemic PHA type 1 who was
nate). Hydro-cortisone and fludrocortisone were tapered
managed successfully despite a tumultuous course.
and dis-continued. He was discharged after 2 weeks of
An 18-day-old baby boy was under treatment for poor hospital stay on sodium supplementation at a dose of 7.5
weight gain, electrolyte imbalance, metabolic acidosis mEq/kg/day (in the form of sodium bicarbonate
and sepsis. The baby was born as late preterm through suspension and 3% saline administered orally), and
non-consanguineous marriage with a birth weight of 2.5 potassium binders (4 g/kg/day).
kg and an uneventful perinatal period. He was sympto-
He was re-admitted at 7 months of age with pneu-
matic since day 8 of life in the form of lethargy and poor
monia, acute gastroenteritis and salt losing crisis. He was
feeding. There was no history of fever, cough, respiratory
managed with intravenous antibiotics and supportive
distress, vomiting, loose stools, skin lesions, seizures or
therapy. At discharge, sodium supplementation was
decreased urine output. He was managed with intra-
increased to 10 mEq/kg/day and potassium binders to 6 g/
venous fluids and antibiotics, and potassium lowering
kg/day. He subsequently had four hospitalizations with
measures (calcium gluconate, potassium binding resin
respiratory tract infections and mild metabolic decom-
and insulin infusion). The baby was resuscitated after an
pensation in the first two years of life, requiring high
episode of cardiac arrest on day 10 of life due to severe
doses of sodium (20-25 mEq/kg/day) and oral potassium
hyperkalemia (11.6 mEq/L). Peritoneal dialysis was
binders (up to 2.2 g/kg/day). Clinical exome sequencing
initiated and continued for 7 days in view of persistent
revealed two novel heterozygous variants in SCNN1A
hyperkalemia. He was started on hydrocortisone and
gene on chromosome 12. A heterozygous single base-pair
fludrocortisone for suspected classical congenital
duplication in exon 7 [c.1516dup (p.Tyr506LeufsTer13)]
adrenal hyperplasia (CAH). He was then referred to us for
and heterozygous single base-pair deletion in exon 3
further management.
[c.1041del. (pCys348AlafsTer42)] were identified. Both
At presentation, he was sick looking, lethargic and variants were novel and as they resulted in frameshift and
had dehydration and acidotic breathing. His weight was premature truncation of protein (alpha subunit of ENaC),
2.3 kg, length 52 cm and head circumference 34 cm. they were classified as pathogenic for PHA type 1b.
At present, the child is aged 5 years and has been which have been shown to directly activate the mutant
asymptomatic for past two years. His electrolytes have ENaC and hold promise for systemic PHA [6].
remained normal on sodium supplementation at 15-20
There is limited data on long-term follow up in
mEq/kg/day (table salt and oral sodium bicarbonate
patients with systemic PHA. Most patients continue to
suspension) and potassium binder (calcium polystyrene
require lifelong high dose salt supplementation [7]. The
sulphonate) 1g/kg/day. His blood pressure was normal
clinical course among patients is variable and associated
(50th-90th centile). His anthropometry and develop-
with the type of genetic mutation [8]. Patients with
mental milestones are age-appropriate. Biochemical
compound heterozygous mutations in genes encoding
profile at last follow up was normal (sodium 136 mEq/L,
ENaC had less severe disease, while those with homo-
potassium 4.5 mEq/L).
zygous mutations suffered frequent metabolic decom-
This presentation of systemic PHA type I can be pensations [4,7]. The favorable disease course in the
mistaken for salt-wasting CAH. Elevated aldosterone index case could be attributed to the presence of
levels and PRA with normal 17 OHP can help to establish compound heterozygous mutation; however, a longer
the diagnosis of PHA. Transtubular potassium gradient duration of follow up would be required.
(TTKG) is also useful in assessment of mineralo-corticoid
bioactivity in patients with hyperkalemia [2]. Cystic PAMALI MAHASWETA NANDA, RAJNI SHARMA,*
fibrosis (CF) is another close mimicker, as affected VANDANA JAIN
Division of Pediatric Endocrinology,
children may have recurrent wheezing and chest infec-
Department of Pediatrics,
tions with poor growth in presence of a positive sweat All India Institute of Medical Sciences, New Delhi.
test [3]. Secondary PHA can occur in the setting of *drrajnisharma@yahoo.com
urinary tract infections, renal dysplasia and reflux nephro-
pathy, mandating urine culture and renal ultrasound as a REFERENCES
part of work-up [3,4]. 1. Zennaro MC, Hubert EL, Fernandes-Rosa FL. Aldosterone
The management of systemic PHA remains sympto- resistance: Structural and functional considerations and new
perspectives. Molec Cell Endocrinol. 2012;350:206-15.
matic. Acute management includes intravenous fluids,
2. Choi MJ, Ziyadeh FN. The utility of the transtubular
sodium supplementation (using hypertonic saline and/or potassium gradient in the evaluation of hyperkalemia. J Am
sodium bicarbonate) and potassium lowering measures. Soc Nephrol. 2008;19:424-6.
Long-term therapy comprises of oral administration of 3. Amin N, Alvi NS, Barth JH, et al. Pseudohypo-aldostero-
sodium up to 10-40 mmol/kg/day (hypertonic saline, table nism type 1: Clinical features and management in infancy.
salt, oral sodium bicarbonate), along with kayexalate and Endocrinol Diabetes Metab Case Rep. 2013;2013: 130010.
low potassium diet [5]. Low potassium diets (0.5 mmol/kg/ 4. Tajima T, Morikawa S, Nakamura A. Clinical features and
day) can be difficult to achieve with commercial formulas molecular basis of pseudohypoaldosteronism type 1. Clin
which contain 15-20 mmol/L of potassium. Breast milk has Pediatr Endocrinol. 2017;26:109-17.
5. Sharma R, Pandey M, Kanwal SK, Zennaro MC. Pseudo-
low potassium content (10 mmol/L) and is ideal for
hypoaldosteronism type 1: management issues. Ind Pediatr.
feeding. High doses of potassium binders (up to 8 g/kg) 2013;50:331-3.
are often required but are poorly tolerated orally and may 6. Willam A, Aufy M, Tzotzos S, et al. Restoration of
result in rectal bleeding or prolapse when given as epithelial sodium channel function by synthetic peptides in
enemas [5]. Children who do not tolerate these therapies pseudohypoaldosteronism type 1B mutants. Front
may require gastrostomy tube placement. Fludrocorti- Pharmacol. 2017;8:85.
sone does not have a role in management because of 7. Edelheit O, Hanukoglu I, Gizewska M, et al. Novel muta-
target organ resistance to aldosterone action. Indo- tions in epithelial sodium channel (ENaC) subunit genes and
methacin, a potent inhibitor of prostaglandin synthesis, phenotypic expression of multisystem pseudo-hypo-
aldosteronism. Clin Endocrinol (Oxf). 2005;62:547-53.
has been used to reduce urine output and thereby urinary
8. Saxena A, Hanukoglu I, Saxena D, et al. Novel mutations
sodium losses [3]. However, its exact mechanism of action responsible for autosomal recessive multisystem pseudo-
is not clear and it seems to have limited role in manage- hypoaldosteronism and sequence variants in epithelial
ment of hyperkalemia [5]. Synthetic peptides, like sodium channel alpha-, beta-, and gamma-subunit genes. J
Solnatide and its congener, AP318 are novel agents, Clin Endo Metab. 2002;87:3344-50.
Tele-NICU: A Possible Solution for There is now enough evidence available to support
the utility of Tele- NICU services providing care at par at
Bridging the ‘Gap’ the ‘Spoke’ centers and improve outcomes [4,5]. A
recently published systematic review evaluating the
India has around 24 million live births per year, and 20 impact of telemedicine on clinical outcomes in pediatric
neonates out of every 1000 live births do not live beyond set-ups suggested that telemedicine in some form or the
neonatal period [1]. While there has been substantial other resulted in decreased rate of patient transfer to
improvement in NMR in last 2-3 decades, India still ranks higher centre (31-87.5%), shorter duration of stay (8.2 vs
at 121 as far as the global NMR rankings are concerned. 15.1 days), a reduction in complications and severity of
Preterm birth and its complications (43.7%), intrapartum- illness, and an overall lower mortality rate [6].
related events (19.2%) and sepsis (20.8%) constitute more
We surveyed some of the Tier- II cities where birthing
than 80% cases of neonatal deaths [2]. All of these causes
rates are high but there is lack of quality NICU services
are largely due to lack of immediate availability of skilled
leading to regular transfer of high risk neonates to nearby
resources (manpower/infrastructure/knowledge) to
major cities. We have started operations in three cities so
handle the high risk births. As per the Ministry of Health’s
far viz., Kanpur (Uttar Pradesh), Panipat and Sonipat
Rural Health Statistics, 2021 [3], there is an acute shortage
(both in Haryana), while plans for other cities are in this
of specialist doctors to the tune of 68% at the community
pipe-line. These NICUs are part of multi-specialty
health center level, all across the country. This means
hospitals in these cities, but now manned and run by our
transferring a lot of moderate/high risk pregnancies to
institution. The central command center (‘hub’) is located
higher centers with neonatal intensive care units
in Gurugram. Tele-rounds are conducted twice daily from
(NICUs), thus putting both mother and fetus at risk.
this center using a fully equipped audio/visual mobile cart
Similarly, newly born babies with delayed-transition/
with an Electronic Medical Record (EMR) software (ICCA
asphyxia/other issues are also referred to higher centers
Phillips India Inc.). Clinical rounds are carried out, and
thus, making them face transport related risks, apart from
cases discussed and treatment decided after reaching
the increased cost that comes with the transfer.
consensus in an evidence-based manner. In addition,
Fortunately, this distance and knowledge gap can troubleshooting is also available at odd hours, as
now be bridged by creating a Tele-NICU ecosystem using required. Regular neonatal resuscitation program (NRP) –
currently available technology. Thus, many peripheral based training sessions are conducted online for NICU
centers (‘Spokes’) can be connected with a tertiary center staff using simulation methodology. Outreach services to
(‘Hub’) through an internet-based network, and enable other NICUs/hospitals in the ‘spoke’ city are also pro-
evidence-based and standardized decision making and vided by our NICU team wherein, we attend high risk
knowledge-sharing. Virtual rounds can be conducted, deliveries at birth and then transfer to the nearby ‘spoke’
resuscitations attended and procedures can be guided NICU, as deemed necessary.
through use of two-way audio-visual communication.
Thus, high quality low cost NICU services are made
Also, data from devices such as monitors, ventilators,
available through this hub-and-spoke model of tele-
warmers etc can be captured from the ‘Spokes’, and used
NICU, without the need to transfer the baby to higher
for auditing and quality improvement purposes.
centers. Preliminary results are encouraging, and other
Tele-NICUs provides a platform wherein a trained institutions are encouraged to consider adopting similar
neonatologist can be made available at any given time on approaches.
short notice anywhere in the country be it rural, semi-rural ROHIT ARORA,* R KISHORE KUMAR
or semi-urban hospital. The neonatologist and pediatri- Division of Neonatology,
cians can interact in real time and take rounds together, Cloudnine Hospital, Gurugram, Haryana
discuss treatment options, plan investigations, do teach- *drrohitarora@cloudninecare.com
ings and establish protocols; thus, streamlining and REFERENCES
standardizing the management. Tele-NICU services can 1. Healthy Newborn Network (HNN). Numbers. Accessed
be used for a wide range of consults, including inter- Dec 2, 2022. Available from: https://www.healthynewborn
preting medical data and images, confirming diagnoses, network.org/numbers/
and conferring treatment plans in real time. 2. Sankar MJ, Neogi SB, Sharma J, et al. State of newborn
Co-existing Iron Deficiency and Only 10% of parenteral and 0.5-4% of oral dose of
administered vitamin B12 is absorbed [4]. Also,
Compliance Issues in Nutritional malabsorption is an important cause of B12 deficiency and
Macrocytic Anemia in Children was not excluded in study. Therefore, ensuring comp-
liance of oral preparation becomes vital. Authors have not
mentioned the measures taken to ensure compliance. The
oral group had high number of female children (75% vs
We read with interest the article by Tandon, et al. [1]. We 52%), who are more vulnerable to nutritional deprivation
compliment the authors for this relevant study comparing and poor compliance, emphasizing on the meticulous need
oral and parenteral vitamin B12 in macrocytic anaemia. We to check compliance [5].
would like to highlight certain aspects in the study, and Rise in serum B12 without monitoring of serum
request clarifications from the authors. methylmalonic acid (MMA) to determine treatment
The prevalence of dimorphic anemia in children <5 efficacy is a poor measure of primary outcome [3,4]. It
years in India is 50% [2]. It is recommended to give iron becomes more conspicuous once both the groups were
supplements during correction of nutritional B12 initially treated with one parenteral dose of B12. Time taken
deficiency (dimorphic anemia) as it may unmask iron for resolution of hematological and neurological findings
deficiency [3]. Authors have concluded that parenteral helps in better assessment and understanding of out-
route of vitamin B12 increases hemoglobin more compared comes of therapy in macrocytic anemia.
to the oral route in nutritional macrocytic anemia. A higher SANJEEV KHERA,* SANDEEP DHINGRA
proportion of children being given supplemental iron in Department of Pediatrics,
parenteral group compared to oral group (62% vs 27%), Army Hospital Research and Referral, Delhi.
especially when 45% of cohort revealed a dimorphic *kherakherakhera@gmail.com
peripheral blood picture, and a drop-out rate of 37.5% in
oral group [1], makes this conclusion unjustified. REFERENCES
Unexpected fall in platelet count and neutrophil count 1. Tandon R, Thacker J, Pandya U, et al. Parenteral vs oral
post-therapy, which ideally should increase, corroborate vitamin B12 in children with nutritional macrocytic anemia:
with above findings suggesting that correction of A randomized controlled trial. Indian Pediatr. 2022;59:
associated iron deficiency anemia (IDA) may have 683-7.
contributed to the same. Near normal median pretreatment 2. Sarna A, Porwal A, Ramesh S, et al. Characterisation of the
types of anaemia prevalent among children and adolescents
hemoglobin (11.3 g/dL) in oral group compared to 9.4 g/dL
aged 1-19 years in India: A population-based study. Lancet
in parenteral group also makes primary outcome of higher Child Adolesc Health. 2020;4:515-25.
rise of hemoglobin in parenteral group debatable. 3. Chandra J, Dewan P, Kumar P, et al. Diagnosis, Treatment
The cutoff for mean corpuscular volume (MCV) to and Prevention of Nutritional Anemia in Children:
Recommendations of the Joint Committee of Pediatric
define macrocytic anemia is 84+0.6×age (years) fL for
Hematology-Oncology Chapter and Pediatric and
children between 2-10 years and >90 fL for older children Adolescent Nutrition Society of the Indian Academy of
[3]. In this study [1], low median pre-treatment MCV (86 vs Pediatrics. Indian Pediatr. 2022;59:782-801.
84 fL) and unexpected low median fall of MCV in two 4. Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl
groups (8.2 vs 6.1 fL) post-therapy also indicate the J Med. 2013;368:49-60.
possibility of co-existing IDA in majority of studied 5. International Institute for Population Sciences (IIPS) and
subjects. ICF. 2021. National Family Health Survey-5, India, 2019-21.
AUTHORS’ REPLY receiving it as it was proven effective [4]. So, to avoid the
ethical dilemma, it was planned to give the first dose of
We thank the readers for their interest in our work [1]. As
vitamin B12 as an injection and immediate treatment was not
pointed out in the opening statement regarding the higher
put on hold until the confirmation of diagnosis, and informed
prevalence of dimorphic anemia [2], we also agree and, in our
written consent and randomization was done subsequently.
study, 45% (36 out of 80) had dimorphic picture in the
In fact, by giving first dose parenterally even in oral group, we
peripheral smear, and they also received additional iron
were expecting a better rise in laboratory parameters in the
supplements. Though, we had not stated this separately, 23
oral group. Even recent recommendations mention that there
in group A and 13 in group B had dimorphic anemia,
is little evidence on management of vitamin B12 and folic acid
respectively, and accordingly, they received additional iron
in children, and it is mostly from guidelines for the adult
supplementation (62% vs 27%). So, we do not agree with the
population [5], and so, what regimen to decide on was also a
possibility of unmasking of iron deficiency.
difficult task. Thus, giving the first dose as an injectable was
In this study [1], the primary objective was not to a pragmatic decision.
compare hemoglobin levels by giving vitamin B12 but to see
We agree that serum methylmalonic acid (MMA) is
a rise in vitamin B12 levels when given by different routes.
much more reliable for vitamin B12 deficiency, but the test
However, a rise in hemoglobin was found statistically better
was not readily available during this study. The guideline
in the parenteral group accepting the limitation of not
suggests that this test has a role when there is a normal or
ascertaining the other underlying etiology, but appropriate
borderline vitamin B12 and discordant laboratory and clinical
nutritional counseling and folic acid supplementation were
picture in a patient [5]. We had enrolled cases of vitamin B12
similar in both groups. In our study, both groups were
deficiency well below the deficient levels and not those with
advised regular out patient follow up at intervals as stated
borderline or normal levels. We agree that time taken for the
including repeating blood investigations 3 months post-
resolution of hematological and neurological findings helps
treatment. Still there was higher dropout (37.5%) in the oral
in better assessment and understanding of outcomes of
group, which might be explained by human behavior, i.e., not
therapy in macrocytic anemia, but that was a limitation of the
taking oral treatment seriously as compared to injectable
study as we wanted to avoid multiple pricks in children for
treatment.
repeated laboratory work up.
We agree with the comment emphasizing the meticulous KRUTIKA RAHUL TANDON
need to check compliance [3]. We also agree with the Department of Pediatrics,
possibility of coexisting iron deficiency as indicated by a fall Pramukhswami Medical College,
in platelet counts and neutrophil count but a comparatively Bhaikaka University, Karamsad,
low median fall in MCV post-therapy. Anand, Gujarat.
tandonkrutika72@gmail.com
We reviewed our data again regarding the underlying REFERENCES
peripheral smear picture, which suggested 36 dimorphic vs
1. Tandon R, Thacker J, Pandya U, et al. Parenteral vs oral
11 macrocytes/macro ovalocytes vs 33 normocytic red cells.
vitamin B12 in children with nutritional macrocytic anemia:
In the study, the median (IQR) of age were 11 (2.3,15) and 13 A randomized controlled trial. Indian Pediatr. 2022;59:683-7.
(8,16) years in group A and group B, respectively. Nearly 35- 2. Sarna A, Porwal A, Ramesh S, et al. Characterization of the
40% of children did not have clinically evident pallor at the types of anemia prevalent among children and adolescents
time of enrolment and the basis of enrolment was other aged 1-19 years in India: a population-based study. Lancet
clinical and laboratory parameters. Before enrolment, 62.5% Child Adolesc Health. 2020;4:515-25.
of group A and 75% of group B already received iron therapy 3. International Institute for Population Sciences (IIPS) and
from an outside consultation. All these reasons also might ICF. 2021. National Family Health Survey (NFHS-5), India,
have contributed to debatable hemoglobin changes as 2019-21.
4. De-Regil LM, Je erds MED, Sylvetsky AC, Dowswell T.
pointed out in this correspondence. We agree that mala-
Intermittent iron supplementation for improving nutrition and
bsorption is an important cause of vitamin B12 deficiency, development in children under 12 years of age. Cochrane
and it was mentioned in our study that we excluded children Database of Systematic Reviews 2011;12:CD009085.
with diseases other than nutritional anemia. However, as 5. Chandra J, Dewan P, Kumar P, et al. Diagnosis, Treatment and
mentioned earlier, extensive workup was not done to prove or Prevention of Nutritional Anemia in Children: Recommen-
to rule out conditions. dations of the Joint Committee of Pediatric Hematology-
Oncology Chapter and Pediatric and Adolescent Nutrition
When this trial was undertaken, it was not common Society of the Indian Academy of Pediatrics. Indian Pediatr.
practice to give oral therapy to children; though, adults were 2022;59: 782-801.
Colistin Resistance in Gram Negative The reported colistin resistance in this small sample is
alarming. However, three of the common pathogens
Bacteria in a Tertiary Care Neonatal Klebsiella spp, Acinetobacter spp. and E. coli were 93-
Intensive Unit in Odisha 100% colistin susceptible (including carbapenem resis-
tance pathogens), similar to the previous studies [1,4]. The
epidemiology of colistin-resistance among Acineto-bacter
spp. and Klebsiella spp. from different parts of the world
has been recently described [5]. Nine cases of colistin
Gram negative bacteria (GNB) like Klebsiella spp. and resistant Klebsiella spp. over twelve years were reported
Acinetobacter spp. are the leading microorganisms recently from neonatal sepsis in a neighboring state [6].
causing neonatal sepsis, and also reported to have high
We may face more cases of colistin resistant
rates of multidrug resistance (MDR) [1]. Clinicians have
enterobacterceae in near future due to over use of this
used colistimethate sodium (colistin) as last resort of
antibiotic. As a preventive strategy, colistin should be
treatment option for carbapenem-resistant pathogens
used as reserve antibiotics at proper drug dosing under
over the last two decades [2].
appropriate supervision for selective cases carbapenem
We conducted an audit of the microbiological data of resistance or MDR pathogens (antibiotic stewardship).
all blood culture-positive neonatal sepsis cases at our
Ethics clearance: IEC, Kalinga institute of Medical Sciences; No.
center between 01 January, 2017 and 30, September, 2022. KIIMS/KIIT/IEC/83/2017 dated Sept 15, 2017.
The organisms were identified from blood samples by BD
Bactec FX culture system (Becton Dickinson) and plating SANTOSH KUMAR PANDA,* RISHABH PUGALIA
in sheep blood agar and MacConkey agar media. Species Department of Pediatrics,
confirmation and antibiotic susceptibility were done with Kalinga Institute of Medical Sciences, KIIT DU,
Bhubaneswar, Odisha.
VITEK 2 Compact; and reported with the minimum
*doc.sant@yahoo.co.in
inhibitory concentration (MIC) value for different groups
REFERENCES
of antibiotics. For interpreting antibiotics sensitivity or
resistance, the guidelines of the Clinical and Laboratory 1. Investigators of the Delhi Neonatal Infection Study
Standards Institute (CLSI) were followed [3]. Multidrug (DeNIS) collaboration. Characterisation and antimicrobial
resistance was defined as GNB resistant to any three of resistance of sepsis pathogens in neonates born in tertiary
five antibiotic classes (extended-spectrum cephalo- care centres in Delhi, India: A cohort study. Lancet Glob
Health. 2016; 4:e752-60.
sporins, carbapenems, aminoglycosides, fluoroquino-
2. Kumar PP, Giri SR, Shaikh FA, et al. Safety and efficacy of
lones, and piperacillin-tazobactam). MIC value ≤2 mg/L intravenous colistin in children. Indian Pediatr. 2015;52:
and ≥4 mg/L were considered for labelling colistin 129-30.
susceptible and resistance, respectively. 3. Clinical Laboratory Standards Institute: Performance
standard for antimicrobial susceptibility testing. 23rd
During the study period, total 122 GNB were isolated
Information supplement. NCCLS Document M100S23.
from blood samples, including 34 (27.9%) Klebsiella spp., Clinical and Laboratory Standards Institute, 2013.
26 (21.3%) Acinetobacter spp., 16 (13.1%) Burkholderia 4. Jajoo M, Manchanda V, Chaurasia S, et al. Investigators of
spp., 15 (12.3%) E. coli, 9 (7.4%) Serratia spp., 7 (5.7%) the Delhi Neonatal Infection Study (DeNIS) collaboration,
each of Pseudomonas spp. and Enterobacter spp., and 8 New Delhi, India. Alarming rates of antimicrobial resistance
(6.5%) others. Among GNB pathogens, 30 (24.6%) were and fungal sepsis in outborn neonates in North India. PLoS
colistin resistant; Burkholderia spp. (15, 93.8%) and One. 2018;13:e0180705.
Serratia spp. (8, 88.9%) were the two most common 5. Kaye KS, Pogue JM, Tran TB, et al. Agents of last resort:
pathogens with high colistin resistance. Five isolates Polymyxin resistance. Infect Dis Clin North Am.
2016;30:391-414.
were colistin resistant (2, Acinetobacter spp., 1, E. coli, 1,
6. Naha S, Sands K, Mukherjee S, et al. A 12-year experience
Pseudomonas spp., 1, Enterobacter spp.). Among of colistin resistance in Klebsiella pneumoniae causing
isolated GNB, 48 (88.9%) out of 54 carbapenem resistant neonatal sepsis: Two-component systems, efflux pumps,
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INDIAN PEDIATRICS
Volume 59, January – December, 2022
The present status of this Journal is largely dependent on the expertise and selfless cooperation of the Reviewers,
whose help we gratefully acknowledge. We are indebted to them for this service.
- Journal Committee
Islet-autoantibody screening for childhood type 1 ratio (LMR) levels were significantly higher in patients who
diabetes (Lancet Diabetes Endocrinol. 2022;10:589-96) showed an insulin requirement of <0.5 IU/ kg/day at the third
month after diagnosis. The authors concluded that initial
Early prediction of childhood type 1 diabetes reduces
hematological parameters did not predict partial clinical remission
ketoacidosis at diagnosis and provides opportunities for disease
period in T1DM in children, however, a lower NLR and d-NLR,
prevention. The study was conducted with the aim to identify
or a higher LMR at the time of diagnosis can be used as an
efficient strategies for initial islet autoantibody screening in
indicator of a low daily insulin need at the 3rd month of T1DM.
children younger than 15 years. The data was harmonized from
five prospective cohorts from Finland (DIPP), Germany Pharmacological profile of lixisenatide in children and
(BABYDIAB), Sweden (DiPiS), and the USA (DAISY and adolescents with type 2 diabetes (Pediatr Diab.
DEW-IT) into the Type 1 Diabetes Intelligence (T1DI) cohort. 2022;23:641-8)
24, 662 children at high risk of diabetes enrolled before age 2
Lixisenatide, a glucagon-like peptide-1 receptor agonist has been
years were included and followed up for islet autoantibodies and
been found to be safe and efficacious as an add-on therapy in a
diabetes until age 15 years, or type 1 diabetes onset, whichever
variety of adult patient populations. The aim of this study was
occurred first. Islet autoantibodies measured included those
to investigate the pharmacokinetic, pharmacodynamic and safety
against glutamic acid decarboxylase, insulinoma antigen 2, and
profile for the treatment of type 2 diabetes (T2D) in pediatric
insulin. A total of 6722 were followed up to age 15 years or until
patients. In this Phase 1, multicenter, randomized, double-blind,
onset of type 1 diabetes. Type 1 diabetes developed by age 15
placebo-controlled, parallel-group, ascending repeated dose
years in 672 children, but did not develop in 6050 children.
study, participants aged 10-18 years were randomized 3:1 to
Optimal screening ages for two measurements were 2 years and 6
receive once-daily lixisenatide in 2-week increments of 5, 10, and
years, yielding sensitivity of 82% (95% CI 79–86) and PPV of
20 µg (n=18) or placebo (n=5) for 6 weeks. Improvements in
79% (95% CI 75–80) for diabetes by age 15 years. Autoantibody
fasting plasma glucose, post-prandial glucose, AUC0-4.5,
positivity at the beginning of each test age was highly predictive
HbA1c, and body weight were observed with lixisenatide.
of diagnosis in the subsequent 2–5·99 year or 6–15-year age
Overall, the safety profile was consistent with the known profile
intervals. Autoantibodies usually appeared before age 6 years
in adults, with no unexpected side effects and no treatment-
even in children diagnosed with diabetes much later in childhood.
emergent adverse events resulting in death or discontinuation.
Thus, initial screening for islet autoantibodies at two ages (2 y
The authors concluded that Lixisenatide was associated with
and 6 y) is sensitive and efficient for public health translation but
improved glycemic control, and a good safety profile.
might require adjustment by country on the basis of population-
specific disease characteristics. Artificial intelligence for predicting risk of overweight
or obesity in preschool-aged children (Endocrine.
Neutrophil-lymphocyte and lymphocyte-monocyte
2022;77:63-72)
ratios in type 1 diabetes for predicting future insulin
need (J Pediatr Endocrinol Metab. 2022;35:593-602) The authors adopted the machine-learning algorithms and deep-
learning sequential model to determine and optimize most
The exact mechanism of partial clinical remission in type 1
important factors for overweight and obesity in Chinese preschool-
diabetes mellitus (T1DM) has not been elucidated yet. The
aged children. A cross-sectional survey was conducted enrolling
severity of the inflammation at the time of diagnosis may affect
children aged 3-6 years using a stratified cluster random sampling
the occurrence or duration of this phase. The authors aimed to
strategy. A total of 9478 children were eligible for inclusion,
investigate the relationship between hematological inflammatory
including 1250 children with overweight or obesity. All children
parameters at the time of diagnosis in T1DM and daily insulin
were randomly divided into the training group and testing group at a
requirement during the follow-up, and the presence of partial
6:4 ratio. After comparison, support vector machine (SVM)
clinical remission period, which was determined according to
outperformed the other algorithms (accuracy: 0.9457), followed by
insulin dose-adjusted HbA1c levels. They conducted a single
gradient boosting machine (GBM) (accuracy: 0.9454). After
center retrospective study, including children who were
importance ranking, the top 5 factors seemed sufficient to obtain
diagnosed with T1DM, were positive for at least one
descent performance under GBM algorithm, including age, eating
autoantibody, and were followed up for one year in their clinic
speed, number of relatives with obesity, sweet drinking, and
between 2010 and 2020. 68 patients (56% female, 65% pre-
paternal education. The authors concluded that these five factors
pubertal) were included in the study. A total of 38 patients (56%)
can be fed to GBM algorithm to better differentiate children with
had partial clinical remission. None of the initial hematological
overweight or obesity from the general children.
indices were associated with the occurrence of partial remission.
Initial neutrophil/lymphocyte ratio (NLR) and derived-NLR (d- PINKY MEENA
NLR) levels were significantly lower and lymphocyte/monocyte pinkymeena189@gmail.com
Pediatric Endocrine Disorders clinical and laboratory diagnosis of the disorder. In addition,
Fourth Edition the inclusion of topics of current and future relevance to
MEENA P DESAI, PSN MENON, developing countries’ set-ups, such as the transition of care
VIJAYALAKSHMI BHATIA, and community pediatric endocrinology, is a welcome
ANJU SETH addition.
Orient BlackSwan Pvt. Ltd, The production quality of the book is good, and the text
Pages: 584; Price: Rs. 1,895/- is formatted in an easy-to-understand way. Future editions
may benefit from including more photographic illustrations,
Endocrine diseases in children often tables, and flow diagrams at suitable places in the chapters,
present as complex clinical which are devoid of these in the present edition.
situations for practicing pediatricians and endocrinologists. In all, the book will serve as a comprehensive guide for
With an emphasis on practical understanding as relevant to the diagnosis and management of pediatric endocrine
patient care, the just-released 4th edition of this book, edited disorders with special relevance to India and other
by eminent pediatric endocrinologists, aims to empower developing countries. I strongly recommend this book for
pediatricians, pediatric and adult endocrinologists, and practicing pediatricians, pediatric and adult endocrino-
trainees in pediatric endocrinology by providing a thorough logists, postgraduates in pediatrics, and allied healthcare
update on common as well as rare endocrine disorders in professionals such as endocrine and diabetes nurses.
children.
DEVI DAYAL
The book is well organized into 19 chapters written by Endocrinology and Diabetes Unit,
distinguished Indian and International academicians. Each Advanced Pediatrics Center, Postgraduate Institute of Medical
chapter provides an in-depth understanding of the topic, Education and Research, Chandigarh 160 012.
especially focusing on a stepwise and judicious approach to drdevidayal@gmail.com
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