I SSN: 0972-2408 Perinatology J o u r n a l o f P e r i n a t a l a n d N e o n a t a l C a r e Vol 24 • No. 1 May–Aug 2023 Indexed in EMBASE, CINAHL, and Scopus Scan to read the e-version of Perinatology
Indexed in EMBASE and CINAHL Dr Kamini A Rao, Bengaluru Dr Prathima Radhakrishnan, Bengaluru Dr DK Guha, Delhi Dr Uma Ram, Chennai Dr Hisham Mirghani, UAE Dr RS Prasad, UK Dr Ravi GP Krishnan, USA Dr David Ellwood, Australia Dr Meenakshi Bhat, Bengaluru Dr Arvind Shenoi, Bengaluru Dr MKC Nair, Trivandrum Dr Purnima Satoskar, Mumbai Dr Rajam S Ramamurthy, USA Dr Koravangattu Sankaran, Canada Dr Bhavani Sriram, Singapore Editor in chief Dr Ranjan Kumar Pejaver Bengaluru Editorial Board National Advisory Committee International Advisory Committee Managing Editor Dr Jayashree B Keshav Bengaluru EMBASE, CINAHL, and Scopus Perinatology J o u r n a l o f P e r i n a t a l a n d N e o n a t a l C a r e Vol 24 • No. 1 May–Aug 2023 From volume 24 and onward, the periodicity of Perinatology—Journal of Perinatal and Neonatal Care will change. The journal issues will be published triannually (3 issues per volume).
General Information II The Journal Perinatology (ISSN 0972-2408), one of the few journals dedicated to the emerging multidisciplinary field of perinatal medicine, is published and distributed triannually by Himalaya Wellness Company. The journal publishes original research articles, review articles, brief reports on clinical and laboratory observations, case reports, and clinical studies. The journal is indexed in the Excerpta Medica (EMBASE) database, Cumulative Index to Nursing and Allied Health Literature (CINAHL) database and print index, and Scopus. Information for Authors There are no page charges for Perinatology submissions. Please see the last section of the journal for guidelines to be followed while preparing and submitting a manuscript. Please submit your manuscripts online. Visit https://www.perinatology.in/submit-articles Subscription Information To subscribe to Perinatology, please visit the following weblink and fill in the requested details: https://www.perinatology.in/subscription Upon receipt of your request, subsequent issues of the journal will be sent to you on a regular basis, without any subscription charges. Copies of the journal are sent directly from the publisher’s address. It is illegal to acquire copies from any other source. If a copy is received for personal use, one cannot resell or give away the copy for commercial or library use. The copies of the journal are sent by ordinary post/courier. If a copy returns because of an incomplete, incorrect, or changed address of a subscriber on 2 consecutive occasions, the names of such members will be deleted from the mailing list of the journal. Hence, providing a complete, correct, and up-to-date address is the responsibility of the subscriber. Information regarding a change of address should be communicated to the publisher at perinatology@himalayawellness.com Feedback If you wish to share your views about the journal, please visit the following weblink or scan the QR code: https://tinyurl.com/ PerinatologyFeedbackForm or Copyright Copyright © 2023 Himalaya Wellness Company All content in this journal/publication is the property of Himalaya Wellness Company and is protected by Indian and international copyright laws. Any other use, including the reproduction, modification, distribution, transmission, republication, display or performance, of the content in this journal/ publication, without written permission from the owner, is strictly prohibited. For permission to reproduce articles/ information published in this journal, please write to perinatology@himalayawellness.com Address for Correspondence The Managing Editor—Perinatology Scientific Publications Division Himalaya Wellness Company Makali, Bengaluru 562162, Karnataka India E-mail: perinatology@himalayawellness.com Published by Scientific Publications Division Himalaya Wellness Company Makali, Bengaluru 562162, Karnataka India Printed at M/s Sri Sudhindra Offset Process #97, DT Street, 8th Cross, Malleshwaram Bengaluru 560003, Karnataka India Perinatology J o u r n a l o f P e r i n a t a l a n d N e o n a t a l C a r e Vol 24 • No. 1 • May–Aug 2023 Disclaimer: Perinatology is published by the Scientific Publications Division of Himalaya Wellness Company. The views and opinions expressed in the articles are of the authors and not of the journal’s publisher, editors, advisory board, and the editorial board. Perinatology does not guarantee directly or indirectly the quality or efficacy of any product, service, or advertisement featured in the journal. Readers are advised to verify any information they choose to rely on.
Contents III Perinatology J o u r n a l o f P e r i n a t a l a n d N e o n a t a l C a r e Vol 24 • No. 1 • May–Aug 2023 Research Articles Sociodemographic and Service Utilization Factors as Determinants of Severe Neonatal Jaundice: A Case–Control Study Datta M, Das I, Sharma K, Samanta S 1 The Need for Mandatory Newborn Screening in India: A Retrospective Analysis of 3-Year Data From a Multispecialty Private Hospital in Uttar Pradesh, India Gupta T, Gupta T, Yadav D, Gupta M 7 Cord Blood Lactate Level: A Predictor of Neonatal Mortality in Pregnancy-Induced Hypertension Kumar N, Malhotra P, Kaur S, Kaur G 15 Original Articles Assessment of Risk Factors of Intraventricular Hemorrhage Among Preterm Neonates: A Tertiary Care NICU Study Kulkarni PP, Vijayasree K, Konded KS, Kulkarni VK 21 Feasibility and Cost Analysis of Antenatal Screening and Diagnosis of Hemoglobinopathies: A Prospective Study Sampagar A, Patil NG, Mahantashetti NS, Patil H, Hukkeri M, Kangle R, Somannavar MS, Goudar S 26 The Association of Maternal and Obstetric Factors and Placental Weight With Neonatal Birth Weight: A Study From a Rural Tertiary Care Hospital Mohite RV 34 Review Article Improving Breastfeeding Rates in Working Mothers: Uncovering Barriers and Working Out Solutions in the Indian Scenario Mangla M, Kumar N 40 Brief Analysis Correlation Between Gestational Age Estimated Using Last Menstrual Period, Ultrasonogram, and the New Ballard Score Permatasari RD, Novina, Aziz MA, Gamayani U, Primadi A 46 Self-assessment Quiz 51 Picture Quiz 52 Clinical Audit A Perinatal Mortality Audit of a Tertiary Care Hospital Kanchan S, Pai M, Agrawal R, Machado N, Kyalakond K 54 Case Reports Respiratory Failure in a Term Neonate Due To a Novel Compound Heterozygous ABCA3 Mutation Mistri J, Patel A, Parikh R, Grover A 62 Meconium Peritonitis: Missed Opportunities and Diagnostic Challenges Alvarez Saenz MP, Martin DT, Otoya Castrillon JP, Quiroz CG, Medina EM, Alvarado Socarras JL 67
IV Dr Amitava Sen was a multifaceted personality. In addition to being a clinician, he was an avid academician. He served as a professor and head at the Calcutta National Medical College (Kolkata, West Bengal, India) and a senior consultant neonatologist at the Society for Applied Studies (Kolkata). He also served as the editor of the Bulletin of the National Neonatology Forum of India. He was a brilliant teacher and mentored several teachers. He was one of the pioneers of the Purulia model, a sick neonatal care unit (SNCU) that was set up in the Purulia district in West Bengal. This SNCU played a significant role in drastically reducing the high neonatal mortality rate in the district, and hence, went on to become a model SNCU to other states in India. Being a keen philatelist, he started the column Perinatology Through Medical Philately in Perinatology—Journal of Perinatal and Neonatal Care. He promptly sent his contributions (on different themes related to mothers and newborns) along with the photographs of the stamps in an impeccable manner. His write-ups were crisp and clear. This unique column was appreciated by the journal’s readers. He was a person with genuine appreciation for the journal and provided constructive criticism and encouraging inputs for over a decade. During the past several years, he had health issues and breathed his last on May 7, 2023. We will miss his valuable inputs and his presence, especially when the journal celebrates its silver jubilee next year. May his soul rest in eternal peace! Dr Ranjan Kumar Pejaver RESEARCH ARTICLES PERINATOLOGY • Vol. 13 • No. 4 • Jan–Mar 2013 153 Special Feature Perinatology Through Medical Philately Dame Kate Isabel Campbell and Retrolental Fibroplasia Amitava Sen* *Correspondence Dr Amitava Sen Senior Consultant, Neonatology Society for Applied Studies Kolkata, West Bengal India Email: amitavasen@vsnl.net Australian Post has honored 5 remarkable Australians with the release of new stamps titled “Medical Doctors– Legacy,” on April 10, 2012. One of these stamps honored Dame Kate Isabel Campbell (1899–1986), a pediatrician and the pioneer of neonatal intensive care (Figures 1 and 2). Kate Isabel Campbell was born on April 22, 1899 in Melbourne, Australia. Her parents had limited means. As a bright student at the primary school she was awarded scholarships to attend the College and then the medical school at the University of Melbourne. She obtained her MBBS degree in 1922 and MD in 1924. She graduated with the future luminaries, (Sir) Frank Macfarlane Burnet, (Dame) Jean McNamara, and others. As a student, she showed her power of clinical observation and sympathy with patients. After graduation she became one of the first female resident medical staff at the Children’s Hospital, Melbourne, and the first honorary pediatrician at the Women’s Hospital, Melbourne. Figure 1. Postage stamp of Dame Kate Isabel Campbell, Australia, 2012 (enlarged) Figure 2. Maxcard with a postage stamp of Dame Kate Isabel Campbell and First Day postmark, Australia, 2012 RESEARCH ARTICLES PERINATOLOGY • Vol. 14 • No. 1 • Apr–Jun 2013 20 Special Feature Perinatology Through Medical Philately Down Syndrome Awareness Amitava Sen* *Correspondence Dr Amitava Sen Senior Consultant, Neonatology Society for Applied Studies Kolkata E-mail: amitavasen@vsnl.net Down Syndrome Federation of India has defined Down syndrome (or Down’s syndrome) as a naturally occurring chromosomal arrangement that has always been a part of the human condition, being universally present across races, gender, or socioeconomic lines, and affects approximately 1 in 800 births worldwide, causing intellectual and physical disability, and associated medical issues.¹ Down Syndrome (DS) is the most common and readily identifiable chromosomal abnormality in humans. This condition is caused by the presence of all or part of a third copy of chromosome 21. DS can be identified in a baby at birth or even before birth by prenatal screening. It is typically associated with a delay in cognitive ability and physical growth, and a particular set of facial and physical characteristics. The average intelligence quotient (IQ) of young adults with DS is around 50% of the IQ of normal young adults without this condition. History DS is named after John Langdon Down (1828–1896), a British physician who described the syndrome in 1866.² The condition was clinically described even earlier by Figure 1. World Down Syndrome Day; Romania, 2011 Figure 2. World Down Syndrome Day; Mexico, 2012 Figure 3. 6th World Congress on Down Syndrome; Spain, 1997 RESEARCH ARTICLES PERINATOLOGY • Vol. 14 • No. 2 • Jul–Sep 2013 72 Special Feature Perinatology Through Medical Philately Fiona Juliet Stanley: A Living Legend Amitava Sen* *Correspondence Dr Amitava Sen Senior Consultant, Neonatology Society for Applied Studies Kolkata 700064, West Bengal E-mail: amitavasen@vsnl.net Professor Fiona Juliet Stanley¹ is an exceptional medical scientist who has been honored with a postage stamp (Figure 1) during her lifetime by her country (one of the 6 stamps showing eminent Australian medical scientists as Australian Legends, 2002). Professor Stanley is one of Australia’s best regarded pediatricians and epidemiologists and a major force behind improving health conditions in Australia’s Aboriginal maternal and child health. She was born on August 1, 1946 in Sydney, Australia. In 1956 her family moved to Perth, Western Australia (WA) as her father, a researcher on polio, was honored with the Foundation Chair of Microbiology, University of WA. In her childhood, she loved reading about scientists like Marie Curie. Education and Training She studied medicine and graduated from the University of WA in 1970. As part of her studies, she did a clinical post at the Aboriginal Clinic in Perth. The Figure 1. Fiona Juliet Stanley, Australia 2002 In loving memory of Professor Dr Amitava Sen A Revered Legendary Neonatologist
Perinatology Editorial Dear Friends, I am pleased to present this issue of Perinatology to you. Jaundice occurs in almost all neonates. Various aspects of this condition have been studied extensively. Datta et al’s study elucidates the sociodemographic and service utilization factors that pose as risks in the incidence of severe neonatal jaundice. Countries across the globe are taking several measures to reduce neonatal mortality. Gupta et al, in their study, substantiate the need for making newborn screening for some metabolic diseases mandatory in India, which is a crucial approach toward reducing neonatal mortality. Cord blood lactate level can help predict neonatal mortality in women with pregnancyinduced hypertension; Kumar et al shed light on the utility of this promising indicator. Hemoglobinopathies are still prevalent in various geographic belts. Sampagar et al demonstrate the feasibility of antenatal screening of hemoglobinopathies and recommend the implementation of carrier screening in routine antenatal investigations, in India, as the first step toward the prevention and elimination of this disorder. Many maternal and obstetric factors and placental weight determine the neonatal birth weight. Mohite’s study proposes that controlling and modifying these factors optimally can lead to the birth of normal-birth-weight neonates. Permatasari et al assess gestational age (GA) by various methods and show that a strong correlation exists between GA estimated based on the last menstrual period, ultrasonogram, and New Ballard Score. Working mothers face several barriers in breastfeeding their neonates. Mangla et al suggest ways to overcome these barriers to ensure adequate nutrition for neonates. Kanchan et al analyze the trends in perinatal mortality in a tertiary care center and recommend several measures to reduce perinatal mortality rate. With regular features and interesting case reports, the issue is comprehensive. I hope that you will benefit from reading this issue of Perinatology. With regards, V J o u r n a l o f P e r i n a t a l a n d N e o n a t a l C a r e Dr Ranjan Kumar Pejaver Editor in chief, Perinatology—Journal of Perinatal and Neonatal Care Editorial board member, Journal of Perinatal Medicine Editorial board member, The Journal of Maternal-Fetal & Neonatal Medicine E-mail: rpejaver@yahoo.com Vol 24 • No. 1 • May–Aug 2023
Theme VI Plastic waste has been largely burdening the environment. Here are some alarming facts about plastic production and use. • About 200 million tons of single-use plastic is produced every year. • Only a bare minimum (< 10%) of the plastic produced is recycled. • Mismanagement of plastic waste has resulted in 19 to 23 million tons of plastic landing in water bodies. • Microplastics are leaching into food, water, and air, proving to be detrimental. Accelerated and large-scale implementation of the solutions to prevent plastic pollution by all countries and a unified approach by businesses and individuals toward the sustainable use of plastic is crucial. World Environment Day is thus pivotal in mobilizing action from all parts of the world to tackle plastic pollution and help save the environment. Learning about the environment must happen at every home and every school in every village, town, and city. Remember, we need the environment to survive; the environment does not need us! The United Nations Theme for 2023: Beat Plastic Pollution Perinatology Vol 24 • No. 1 • May–Aug 2023 J o u r n a l o f P e r i n a t a l a n d N e o n a t a l C a r e JUNE 5
PERINATOLOGY • Vol 24 • No. 1 • May–Aug 2023 1 Research Article Sociodemographic and Service Utilization Factors as Determinants of Severe Neonatal Jaundice: A Case–Control Study Mousumi Datta, Indrani Das, Kundan Sharma, Sandip Samanta* Abstract Background: Severe neonatal jaundice can cause bilirubin encephalopathy. There is an incomplete understanding of the sociodemographic determinants of neonatal jaundice in India. Aims: To describe the cases and controls according to their demographic and disease profiles and to estimate the effect of added risk of adverse sociodemographic, maternal, perinatal, and poor service utilization factors on the incidence of severe jaundice in neonates at admission Materials and Methods: Data of neonates born between March 2019 and February 2020 were considered for this case–control study. The neonates with venous blood total serum bilirubin (TSB) ≥ 15 mg/dL at admission constituted the cases, and the neonates with TSB of 10 to 14.9 mg/dL constituted the controls. The mean TSB level and demographic, perinatal, and service utilization factors in cases and controls were statistically analyzed. Results: A total of 327 neonates were included, of which, 125 were cases and 202 were controls. The mean TSB of the cases was significantly higher than that of the controls (21.98 vs 12.2 mg/dL, respectively). In both the groups, the onset of jaundice was between days 2 and 7 of life. We found that the sociodemographic factors, including low maternal education and residence in rural areas, and the service utilization factors, including not availing the minimum recommended antenatal checkups and Matri Yan, delivering at home, and a delay of *Correspondence Dr Sandip Samanta Medical Superintendent and Vice Principal Associate Professor Department of Pediatric Medicine Dr BC Roy Post Graduate Institute of Pediatric Sciences 111, Narkeldanga Main Road Kolkata 700054, West Bengal India E-mail: drsandipsamanta@gmail.com
2 • PERINATOLOGY Vol 24 • No. 1 • May–Aug 2023 Research Article Datta M, et al. Determinants of Severe Neonatal Jaundice > 48 hours between the diagnosis of severe jaundice in the neonates and their hospital admission to be the factors responsible for an increased risk of severe jaundice. Conclusion: The delayed hospitalization of neonates with severe jaundice was found to be because of low maternal education and poor utilization of maternal and child health care services. The mothers’ ability to detect the signs of jaundice in their neonates early will aid in timely seeking of medical help. Key Words: Kernicterus, maternal education, antenatal care, total serum bilirubin, exchange transfusion, phototherapy Introduction Neonatal jaundice is defined as yellow discoloration of the skin and the sclera in the first 28 days of life due to hyperbilirubinemia. This condition occurs among 50% of term and 80% of preterm neonates, and it is a common cause of hospital readmission among neonates. Unconjugated bilirubin is potentially neurotoxic in neonates and can cause kernicterus or bilirubin encephalopathy.1 In developed countries, this condition has nearly disappeared; however, in developing countries, this preventable condition still causes considerable neonatal morbidity and mortality.2-4 Hence, it is necessary to explore the sociodemographic and mother–neonate health care service– related factors that act as barriers to the early detection of and intervention for neonatal jaundice in developing countries. The 2010 British National Institute for Health and Care Excellence guidelines stressed on the role of parents’ and caregivers’ education in the early detection of neonatal jaundice.5 The Integrated Management of Neonatal and Childhood Illness guidelines, implemented at the primary care level in India, also emphasize on the early detection of neonatal jaundice.6 However, the necessary awareness about this condition remains poor. A study conducted in India reports poor sensitivity and a low positive predictive value for the detection of neonatal jaundice by the mothers.7 As there is an incomplete understanding of the socio-demographic determinants of severe neonatal jaundice at presentation, in India, we conducted this case–control study. Aims • To describe the cases and controls according to their demographic and disease profiles • To estimate the added risk of adverse sociodemographic, maternal, perinatal, and poor service utilization factors on the incidence of severe neonatal jaundice at admission Materials and Methods Study design This case–control study was conducted at the Department of Pediatric Medicine, BC Roy Post Graduate Institute of Pediatric Sciences (Kolkata, West Bengal, India), a tertiary care center. The study was conducted between March 2019 and February 2020 and was compliant with the Helsinki declaration on bioethics policy and was approved by the institutional ethics committee. All the parents provided informed consent for their neonates to participate in the study. Data confidentiality and anonymity were maintained through all stages. The study population consisted of neonates born at gestational age ≥ 35 weeks, referred from peripheral health institutes, and admitted to the study center with a diagnosis of jaundice, during the data collection period. The neonates were categorized as cases and controls based on
PERINATOLOGY • Vol 24 • No. 1 • May–Aug 2023 • 3 Research Article Datta M, et al. Determinants of Severe Neonatal Jaundice their venous blood total serum bilirubin (TSB) level at admission. Inclusion and exclusion criteria Inclusion criterion for cases was TSB level ≥ 15 mg/dL at admission, and for controls, TSB level 10 to 14.9 mg/dL. Neonates with major congenital anomalies were excluded from the study. Sample size calculation Considering 34% delayed diagnosis of neonatal jaundice based on data from previous studies, type 1 error of 5%, and power of 75%, the minimum sample size was 125 cases.8,9 The hypothetical delayed diagnosis among controls was set at 20%. Cases and controls were enrolled at a ratio of 1:1.5. So, 189 controls were recruited by Fleiss’ continuity correction method of sample size calculation. The sample size was calculated using the OpenEpi software version 3.01.8 Thus, the target sample size was 125 cases and at least 189 controls. Study procedure Data were collected using a predesigned schedule. Variables assessed were mean TSB levels for both groups; demographic variables such as age at admission, sex, maternal age and education, and family income; perinatal factors such as parity, known maternal risk factors (obstetric or medical risks), mode of delivery, gestational age, birth weight, and early initiation of breastfeeding (EIBF); service utilization factors such as the number of antenatal care (ANC) visits, distance to the nearest public health facility, place of delivery, whether Matri Yan (a 24 × 7 transport facility run by the West Bengal government, that can be availed for care during pregnancy, delivery, and care of sick neonates) was availed; and the interval between the diagnosis of jaundice and the neonate’s admission and variables related to the severity of jaundice. A minimum of 5 ANC visits are mandated as per the current guidelines—registration, 3 visits across the second and third trimesters, and 1 additional visit as per the Pradhan Mantri Surakshit Matritva Abhiyan (an ANC program run by the Government of India).10 Bilirubin level was estimated using the Van den Bergh test. Venous blood bilirubin level of 15 mg/dL is the accepted cutoff level for categorizing the severity of neonatal jaundice; the high level of bilirubin is considered to be pathologic due to its association with kernicterus.11 However, this cutoff is not absolute, and therapeutic interventions such as phototherapy and exchange transfusion would be necessary to lower the bilirubin level, which depends on the gestational age, body weight, and known high-risk factors. EIBF was defined as the initiation of breastfeeding within 1 hour of vaginal delivery and 4 hours of cesarean delivery. Statistical analyses Mean and standard deviation were calculated for neonatal age at admission and TSB. For all the other variables, frequency and proportion of observations in the subcategories were calculated. Crude odds ratio (COR) and 95% confidence interval (CI) were calculated to estimate and compare the risks of jaundice in cases and controls. As COR is estimated for dichotomous categories, some variable categories were merged. SPSS version 19.0 for Windows (IBM Corp, Armonk, NY, USA) was used for all the statistical analyses. Results A total of 327 neonates were included in the study— 125 cases and 202 controls. The mean TSB level in cases was significantly higher than that in the controls (21.98 vs 12.2 mg/dL, respectively). The onset of jaundice was observed to be between days 2 and 7 of life, in most neonates in both the groups. Of the 327 neonates, home remedies and medications were tried in 187 (57.2%) neonates prior to hospital admission. There was a need for exchange transfusion in 64 (19.6%) neonates (Table 1). The median age at admission was 4 days for cases and 6 days for controls. Table 2 presents a comparison of the demographic and socioeconomic risk factors among the
4 • PERINATOLOGY Vol 24 • No. 1 • May–Aug 2023 cases and controls. The risk of severe jaundice (TSB ≥ 15 mg/dL) at admission was significantly high in neonates whose parents resided in rural areas and maternal education was low. Table 3 shows a comparison of the maternal and perinatal risk factors among the cases and controls. Low maternal age, primiparity, and neonatal birth weight < 2.5 kg were associated with a high risk of severe jaundice (TSB ≥ 15 mg/dL) at admission. In terms of service-related factors, the risk of jaundice (TSB ≥ 15 mg/dL) at admission was significantly high when the minimum recommended ANC visits, Matriyaan, and institutional delivery were not availed and when there was delay of ≥ 48 hours between the diagnosis of neonatal jaundice and hospital admission (Table 4). Table 1. Distribution of Cases and Controls According to the Disease Profile Variable Cases (n = 125), Frequency (%) Controls (n = 202), Frequency (%) TSB, Mean (SD) 21.98 (9.2) 12.2 (1.8) Age at Onset of Jaundice < 24 h 7 (5.6) 12.2 (1.8) 24 h to 7 d 102 (81.6) 0 (0) > 7 d 16 (12.8) 200 (99) Person Who First Detected Jaundice Mother 33 (26.4) 142 (70.3) Doctor 32 (25.6) 28 (13.9) Health Worker 60 (48.0) 32 (15.8) Neonates Who Received Home Remedies and Medications Yes 89 (71.2) 98 (48.5) No 36 (28.8) 104 (51.5) Neonates Who Required Exchange Transfusion Yes 63 (50.4) 1 (0.5) No 62 (49.6) 201 (99.5) Table 2. A Comparison of the Demographic and Socioeconomic Characteristics of the Cases and Controls Variable Cases (n = 125), Frequency (%) Controls (n = 202), Frequency (%) COR (95% CI) P Value Median Age of the Neonates, d 4 6 — Sex Male 75 (60) 117 (57.9) 1.08 (0.69–1.71) .71 Female 50 (40) 85 (42.1) Area of Residence Rural 60 (48) 60 (29.7) 2.18 (1.37–3.47)a .0009 Urban 65 (52) 142 (70.3) Maternal Educationb Lower than primary 33 (26.3) 21 (10.4) 3.09 (1.69–5.64)a .0002 Primary 88 (70.4) 166 (82.2) Secondary 4 (3.3) 15 (7.4) Average Monthly Family Incomeb ≤ 2000 59 (47.2) 90 (44.5) 1.11 (0.71–1.74) .64 2001–5000 30 (24.0) 32 (15.8) 5001–10000 31 (24.8) 69 (34.2) > 10,000 5 (4.0) 11 (5.5) aP < .01; bHigher categories (primary and secondary, 5001–10,000 and > 10,000) were clubbed for COR calculation. Research Article Datta M, et al. Determinants of Severe Neonatal Jaundice Table 3. A Comparison of the Maternal and Perinatal Factors in the Cases and Controls Variable Cases (n = 125), Frequency (%) Controls (n = 202), Frequency (%) COR (95% CI) Maternal Age, y < 25 87 (69.6) 103 (50.9) 2.20 (1.37–3.52)a .001 ≥ 25 38 (30.4) 99 (49) Parity Primiparous 98 (78.4) 102 (50.5) 3.54 (2.14–5.91)a .0001 Multiparous 27 (21.6) 100 (49.5) Known Maternal Risk Factor Yes 46 (36.8) 60 (29.7) 1.31 (0.85–2.21) .18 No 79 (63.2) 142 (70.3) Mode of Delivery Vaginal 90 (72) 131 (64.8) 1.39 (0.85–2.26) .18 Cesarean 35 (28) 71 (35.2) Gestational Age Term 112 (89.6) 172 (85.1) 1.50 (0.75–3.00) .24 Preterm 13 (10.4) 30 (14.9) Birth Weight, kg < 2.5 52 (41.6) 61 (30.2) 1.64 (1.03–2.62)b .03 ≥ 2.5 73 (58.4) 141 (69.8) EIBF Yes 119 (95.2) 188 (93.1) 1.47 (0.55–3.94) .4 No 6 (04.8) 14 (06.9) EIBF, early initiation of breastfeeding. aP < .01; bP < .05.
PERINATOLOGY • Vol 24 • No. 1 • May–Aug 2023 • 5 importance of recognizing jaundice early after the neonate’s discharge from the hospital. Jaundice is one of the most common reasons for hospital readmission among neonates.1 Hence, early detection of significant jaundice improves the prognosis, as therapy can be instituted at a lower bilirubin level, and the need for aggressive treatments such as exchange transfusion can be averted. On the other hand, home remedies cause unnecessary delay in seeking treatment. Studies report 5% to 11% of neonates in India develop significant jaundice; hence, mothers and community health workers should be made aware of this condition and advised to seek medical help immediately.14,15 In this study, the mothers detected physiologic jaundice in 70% of the cases and pathologic jaundice in 26% of the cases. Early detection may have been the reason for early care seeking in these cases. A study conducted in Nepal reports poor maternal knowledge about neonatal jaundice as a hindrance to seeking care.16 The results of this study and that of Ayeni et al’s17 study show that many families faced challenges in utilizing the available maternal and child health care services because of the lack of adequate education and geographic isolation. This makes neonates susceptible to adverse outcomes and adds to the pool of preventable neonatal morbidity and mortality.17 Creating community awareness, early detection, and availability of phototherapy at peripheral health centers can considerably reduce referrals to tertiary care centers, the need for exchange transfusion, and the burden of kernicterus. Limitations The study’s results cannot be generalized, as this was a hospital-based study with an unknown population denominator. The sociodemographic determinants were self-reported and were not verified by observation or other proxy measures. Conclusion Neonates with severe jaundice were presented late at the health care facility. Low maternal education and poor utilization of maternal and child health care services were the risk factors for the late presentation. The Table 4. A Comparison of the Service Utilization Factors Between the Cases and Controls Variable Cases (n = 125), Frequency (%) Controls (n = 125), Frequency (%) COR (95% CI) P Value Number of ANC Visits < 5 75 (60) 84 (41.6) 2.10 (1.33–3.31)a .001 ≥ 5 50 (40) 118 (58.4) Nearest Public Health Facility, kmb < 1 12 (9.6) 9 (4.5) 0.92 (0.59–1.46) .75 1–5 39 (31.2) 77 (38.1) > 5 74 (59.2) 116 (57.4) Place of Delivery Institutional 93 (74.4) 174 (86.1) 0.46 (0.26–0.82)a .008 Home 32 (25.6) 28 (13.9) Availed Matriyaan Yes 39 (31.2) 104 (51.5) 0.42 (0.26–0.68)a .0004 No 86 (68.8) 98 (48.5) Diagnosis of Jaundice to Admission Delay, h < 48 52 (41.6) 122 (60.4) 0.46 (0.29–0.73)a .001 ≥ 48 73 (58.4) 80 (39.6) ANC, antenatal care. aP < .01; b< 1 km and 1–5 km categories were clubbed for COR calculation. Discussion We found low maternal age, primiparity, neonatal birth weight < 2.5 kg, and poor utilization of maternal and child health care services as the factors that increased the risk of severe jaundice at admission, in neonates. In this study, the mean TSB was 21.98 mg/dL in the cases and 12.2 mg/dL in the controls. In a study conducted in Northern Ethiopia, the TSB ranged from 15 to 19.9 mg/dL in the cases, while the controls had a mean TSB of 10.66 mg/dL.12 In this study, the onset of jaundice was between days 2 and 7 of life in 94.5% of the neonates, including both cases and controls. This finding is in agreement with the finding of Nepal et al’s study.13 This emphasizes the Research Article Datta M, et al. Determinants of Severe Neonatal Jaundice
6 • PERINATOLOGY Vol 24 • No. 1 • May–Aug 2023 ability of mothers to detect jaundice will aid in early seeking of treatment. References 1. Woodgate P, Jardine LA. Neonatal jaundice. BMJ Clin Evid. 2011;2011:0319. 2. Amegan-Aho KH, et al. Neonatal jaundice: awareness, perception and preventive practices in expectant mothers. Ghana Med J. 2019;53(4):267–272. 3. Mwaniki MK, et al. An increase in the burden of neonatal admissions to a rural district hospital in Kenya over 19 years. BMC Public Health. 2010;10:591. 4. Manning D, et al. Prospective surveillance study of severe hyperbilirubinemia in the new born in the UK and Ireland. Arch Dis Child Fetal Neonatal Ed. 2007;92(5):F342–F346. 5. National Institute for Health and Care Excellence. Jaundice in newborn babies under 28 days. https://www.nice.org.uk/ guidance/cg98. Updated October 26, 2016. Accessed March 24, 2019. 6. Ministry of Health and Family Welfare, Government of India. Integrated management of neonatal and childhood illness. Training module of health workers. New Delhi: Ministry of Health and Family Welfare, Government of India; 2003. https://main.mohfw.gov.in/sites/default/ files/7091371954Mod%201%20INTRODUCTION%20R. pdf. Accessed July 18, 2020. 7. Yadav A, et al. Maternal ability to correctly detect significant jaundice in Indian neonates. Indian J Community Med. 2020;45(1):8–11. 8. Dean AG, Sullivan KM, Soe MM. OpenEpi: Open source epidemiologic statistics for public health. www.openepi.com/ SampleSize/SSCC.htm. Updated April 6, 2013. Accessed December 16, 2019. 9. Ogunlesi TA, Ogunlesi FB. Family socio-demographic factors and maternal obstetric factors influencing appropriate health-care seeking behaviours for newborn jaundice in Sagamu, Nigeria. Maternal Child Health J. 2012;16(3):677–684. 10. Maternal Health Division, Ministry of Health and Family Welfare, Government of India. Pradhan Mantri Surakshit Matritva Abhiyan. 2016. https://pmsma.mohfw.gov.in/ wp-content/uploads/2016/09/Pradhan_Mantri_Surakshit_ Matritva_Abhiyan.pdf. Accessed July 20, 2020. 11. Bhutani VK, Vilms RJ, Hamerman-Johnson L. Universal bilirubin screening for severe neonatal hyperbilirubinemia. J Perinatol. 2010;30(Suppl):S6–S15. 12. Asefa GG, et al. Determinants of neonatal jaundice among neonates admitted to neonatal intensive care unit in public general hospitals of Central Zone, Tigray, Northern Ethiopia, 2019: a case–control study. BioMed Res Int. 2020;2020:4743974. 13. Nepal D, et al. Neonatal hyperbilirubinaemia and its early outcome. J Institute Med Nepal. 2009;31(3):17–20. 14. Kaur N, et al. Maternal and neonatal risk factors for neonatal jaundice and readmission – an Indian perspective. Acta Medica Int. 2021;8(1):44–49. 15. Bedi N, Kumar CM, Singh S. A study of neonatal hyperbilirubinemia from a tertiary care hospital in northern India. Indian J Child Health. 2018;5(12):717–719. 16. Shrestha S, et al. Knowledge about neonatal jaundice among Nepalese mothers. J BP Koirala Institute Health Sci. 2019;2(1):34–42. 17. Ayeni VA, Ogunlesi TA, Ogunfowora OB. Factors associated with clinical outcomes among neonates admitted with acute bilirubin and hypoxic-ischaemic encephalopathies at a tertiary hospital in south-west Nigeria. South African Fam Pract. 2019;61(5):177–183. Authors’ Affiliations Dr Mousumi Datta, Associate Professor, Department of Community Medicine, RG Kar Medical College, 1, Ksudiram Bose Street, Kolkata 700004; Dr Indrani Das, Assistant Professor, Department of Obstetrics and Gynecology, Medical College Kolkata, 88, College Street, Kolkata 700073; Dr Sandip Samanta, Medical Superintendent and Vice Principal, Associate Professor; Dr Kundan Sharma, Resident, Department of Pediatric Medicine, Dr BC Roy Post Graduate Institute of Pediatric Sciences, 111, Narkeldanga Main Road, Kolkata 700054, West Bengal, India Research Article Datta M, et al. Determinants of Severe Neonatal Jaundice
PERINATOLOGY • Vol 24 • No. 1 • May–Aug 2023 • 7 Research Article The Need for Mandatory Newborn Screening in India: A Retrospective Analysis of 3-Year Data From a Multispecialty Private Hospital in Uttar Pradesh, India Tuhina Gupta*, Tanusree Gupta, Daksh Yadav, Mukulesh Gupta *Correspondence Dr Tuhina Gupta Consultant Obstetrician and Gynecologist Department of Obstetrics and Gynecology Udyaan Health Care Hospital 730, Udyaan 1, Eldeco, Near Bangla Bazar Lucknow 226002, Uttar Pradesh India E-mail: tuhinaemail@gmail.com Abstract Background and Aim: Newborn screening (NBS) is done in India but is not mandatory. As of now, the number of diseases in the list of screening is not standardized among hospitals and laboratories in India. The aim of this study was to find the prevalence of 4 commonly occurring inborn errors of metabolism (IEM) in neonates. Materials and Methods: This retrospective study enrolled 396 neonates (born between October 2018 and December 2021) aged up to 28 days, after obtaining their parents’ consent. The neonates were screened for 4 IEM—congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), glucose-6-phosphate dehydrogenase (G6PD) deficiency, and classical galactosemia (CG). Results: Among the 396 neonates, the prevalence of G6PD deficiency was more (2.27%) compared with that of the remaining 3 conditions. The prevalence of CAH and CH was only 0.25%, while the prevalence of CG was 0.51%. Conclusion: In summary, the current findings indicate that screening for all treatable and untreatable metabolic diseases should be made compulsory in all health care centers in India. It helps in the early diagnosis and treatment. Further,
8 • PERINATOLOGY Vol 24 • No. 1 • May–Aug 2023 Research Article Gupta T, et al. The Need for Mandatory Newborn Screening in India epidemiologic data gathered from this initiative can be used for further research. Key Words: Newborn screening, congenital hypothyroidism, congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase deficiency, classical galactosemia, metabolic diseases Introduction Newborn screening (NBS) is a minimally invasive, accurate, and efficient method that can help identify multiple presymptomatic metabolic disorders. It also helps gather knowledge about many rare diseases and prevent permanent disability that occurs due to undiagnosed or late-diagnosed disorders. NBS can be an effective reproductive and family planning tool. Although both parents have inborn errors of metabolism (IEM), both should not have the same metabolic disease, and if they do, prenatal screening and strict vigilance are necessary to prevent them from bearing a child affected severely with a genetic metabolic disease. Also, if a couple already has an affected child, they must undergo screening and prenatal testing in future pregnancies. The screening requires dried blood spots, developed from the blood sample collected through a heel prick.1 As a standard procedure, NBS has gained universal acceptance and has been deemed mandatory in many developed countries (eg, countries in North America and Europe).2 The Advisory Committee on Heritable Disorders in Newborns and Children recommends a uniform screening panel that is inclusive of 34 primary disorders and 26 secondary disorders.3 Though NBS has become an essential part of the health care system in many developed countries, India is still developing frameworks and infrastructure for making it an integral part of the childbirth services offered across the country. NBS, though available in India, is not mandatory. Some hospitals and laboratories list the disorders that are not standardized in the screening panel. The cost and number of conditions screened vary from laboratory to laboratory and city to city. Low-resource settings such as small cities, villages, and government colleges do not offer NBS because of the paucity of resources and time to counsel parents about the screening process and its advantages.4 Aim To find the prevalence of 4 commonly occurring IEM—congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), glucose-6-phosphate dehydrogenase (G6PD) deficiency, and classical galactosemia (CG)—in neonates Materials and Methods Study design This retrospective study was conducted at Udyaan Health Care Hospital (Lucknow, Uttar Pradesh, India). Data were aggregated from electronic health records of deliveries conducted from October 2018 to December 2021 (38 months). The institutional review board granted ethical clearance to conduct this study. Inclusion and exclusion criteria Neonates, aged up to 28 days, whose parents willingly provided their verbal consent were included in the study after being informed of the procedure prior to making any payments for the tests. Neonates of unwilling parents were excluded from the study. The WHO has issued guidelines and criteria for selecting disorders to include under the NBS program. Wilson and Jungner, in 1968, outlined the selection criteria for disorders to be included under the NBS program, which are as follows5: 1. The condition should be an important health problem.
PERINATOLOGY • Vol 24 • No. 1 • May–Aug 2023 • 9 Research Article Gupta T, et al. The Need for Mandatory Newborn Screening in India 2. The natural history of the condition should be well understood. 3. The condition should be detectable at an early age. 4. Treatment for the condition at an early stage should be beneficial. 5. A suitable test should be devised for early detection. 6. The test should be acceptable. 7. Intervals for repeating the test should be available. 8. Adequate health service provision should be made for the extra clinical workload from the screening. 9. The physical and psychological risks should be less than the benefits. 10. The cost should be balanced against the benefits. Study procedure Among the neonates that were born during the study period, 396 neonates were selected for screening. The blood samples were collected using the heel prick method. This method was chosen because it is a frequently used and accepted method of collecting blood from neonates and is much easier, safer, and less painful than an arterial puncture or venipuncture. The blood samples were tested for the 4 IEM using tandem mass spectrometry. While screening neonates, many parents expressed apprehension, regarding the method of blood collection. The problems faced by the clinicians while screening neonates included parents not understanding the importance of the screening activity and not wanting their neonate to be pricked even after informing about the safety and noninvasiveness of the procedure. Some parents did not find the procedure worthy in terms of cost, although the charges were minimal and reasonable. Another significant challenge was that as many metabolic errors did not manifest symptoms at birth, parents ignored or overlooked the importance of these tests. Because of strict protocols of COVID-19, the number of patients visiting the hospital decreased relatively, due to which the number of deliveries also reduced, which directly affected the rate of screening done at the hospital during this period. Statistical analyses Data were analyzed at an aggregate level using Python. Categorical data were represented in the form of frequencies and proportions, and continuous data were represented as mean and standard deviation. Results A total of 396 neonates were selected for the study. The demographic profile of the neonates enrolled in the study is shown in Table 1. Table 1. Demographic Profile of the Neonates Characteristic Value Sex, n (%) Male 210 (53) Female 185 (46.7) Ambiguous genitalia 1 (0.3) Birth Weight, kg Average birth weight, kg, mean (SD) 2.88 (0.47) 95% lower confidence interval for mean 2.83 95% upper confidence interval for mean 2.93 Gestation, wk Average gestation, wk, mean (SD) 37.48 (1.12) 95% lower confidence interval for mean 37.37 95% upper confidence interval for mean 37.59 Gestational Age of the Neonates at Birth, n (%) Preterm 45 (11.4) Term 351 (88.6) Single/Twin, n (%) Single 371 (93.7) Twin 25 (6.3) The neonates were screened for 4 major IEM—G6PD deficiency, CAH, CH, and CG. The screening results showed that in these neonates, G6PD deficiency was more prevalent (2.27%) than the remaining 3 disorders. The prevalence of CAH and CH was 0.25%, while that of CG was 0.51% (Figure 1). From October 2018 to December 2021 (38 mo), 724 neonates were delivered in our hospital, of which 396
10 • PERINATOLOGY Vol 24 • No. 1 • May–Aug 2023 range. Of the 396 neonates, 11.1% were preterm neonates, and 22.2% (of the 11.1%) were admitted to the NICU shortly after birth because of complications that may or may not have been related to the G6PD deficiency; 4 of these neonates were diagnosed positive for G6PD deficiency soon after. While neonates born with CH (n = 1) and CG (n = 2) were in the normal range regarding their birth weight and gestational term, 1 neonate screened positive for CAH weighed 4.4 kg at birth. Interestingly, the neonate with ambiguous genitalia did not screen positive for CAH, as was initially suspected (Table 2). Table 2. The Results of IEM Screening of Neonates Disorder No. of Patients Average Weight, kg Average Gestational Term, wk Additional Test Results G6PD Deficiency 9 2.79 37 3 had pathogenic variants present CH 1 2.8 37 TSH = 20 CG 2 2.9 39 0 CAH 1 4.4 39 Referred to an endocrinologist for testing CAH, congenital adrenal hyperplasia; CH, congenital hypothyroidism; CG, classical galactosemia; G6PD, glucose-6-phosphate dehydrogenase; TSH, thyroid-stimulating hormone. Research Article Gupta T, et al. The Need for Mandatory Newborn Screening in India neonates (55%) fulfilled the inclusion criteria and hence were enrolled in the study. Figure 2 depicts the monthly trend in the percentage of neonates tested. Of the 396 neonates, 13 neonates were found to be positive for the 4 conditions screened. Of these 13 neonates, the number of neonates who tested positive for G6PD deficiency was high compared with the remaining 3 conditions. The average birth weight of the neonates was 2.88 kg and the average gestational term was 37.48 weeks, which are considered to be in normal Figure 2. Month-wise Trend in Percentage of Neonates Tested 0 10 Oct 2018 Nov 2018 Dec 2018 Jan 2019 Feb 2019 Mar 2019 Apr 2019 May 2019 Jun 2019 Jul 2019 Aug 2019 Sep 2019 Oct 2019 Nov 2019 Dec 2019 Jan 2020 Feb 2020 Mar 2020 Apr 2020 May 2020 Jun 2020 Jul 2020 Aug 2020 Sep 2020 Oct 2020 Nov 2020 Dec 2020 Jan 2021 Feb 2021 Mar 2021 Apr 2021 May 2021 Jun 2021 Jul 2021 Aug 2021 Sep 2021 Oct 2021 Nov 2021 Dec 2021 20 30 40 50 60 70 64 92 77 81 67 58 69 74 75 72 50 50 55 58 81 92 72 64 63 70 57 62 78 56 54 67 41 60 61 71 13 6 47 31 13 12 13 0 0 80 90 100 Percentage of Neonates 0 0.25 CAH CH G6PD Galactosemia 0.25 0.51 2.27 0.50 1.00 1.50 2.00 2.50 Prevalence, % Figure 1. The Prevalence of CAH, CH, G6PD Deficiency, and CG CAH, congenital adrenal hyperplasia; CH, congenital hypothyroidism; CG, classical galactosemia; G6PD, glucose-6-phosphate dehydrogenase deficiency.
PERINATOLOGY • Vol 24 • No. 1 • May–Aug 2023 • 11 Discussion NBS is a universally accepted standard procedure in many countries across the world. The latest CDC data show that about 12,500 neonates, each year, are diagnosed with at least one of the core conditions from the recommended uniform screening panel, which could have been possible only through NBS.6-8 Many Asian developing countries, including India, have also developed programs for increasing NBS coverage, although they still lack the government policies and support necessary for sustaining the same. Dr Appaji Rao and Dr Radha Rama Devi initiated NBS in India.9 The Chandigarh Program (screened for CH and G6PD deficiency), Kerala State NBS Program,10 and Goa State NBS Program managed by Dr Rohit Cariappa11 were among the many state-level NBS programs that were launched in 2007. CH, CAH, and G6PD deficiency were proposed to be included in the screening panel under NBS in India by the National Neonatology Forum in 2011. A pilot, multicenter NBS program was started by the Indian Council of Medical Research (ICMR) in 2008 to screen 100,000 neonates for CH and CAH in 5 major cities.12 The West Bengal and Gujarat governments approved beginning a sizable NBS program in 2009 and 2011, respectively.9 However, the challenges for successful implementation of NBS in India include insufficient knowledge among health care workers and parents and poor access to neonatal units for middle- and lower-class population, as NICUs are usually not a part of primary health care centers. Family members turn a blind eye to the benefits of NBS policies, which limits the chances of neonates being screened.13,14 Given the prevalence of the illnesses and the significant cost implications of universal screening in a developing nation like India, a feasible approach will be to categorize the disorders as mentioned in Table 3. While a single test can screen up to 62 metabolic and genetic diseases, plans to start the screening with a more straightforward and cost-effective approach must be encouraged. Hence, screening for 11 conditions including, CH, G6PD deficiency, CAH, CG, cystic fibrosis, phenylketonuria [PKU], biotidinase deficiency, and hemoglobinopathies such as thalassemia, sickle cell, and hemoglobin traits can be conveniently recommended in all newborns. According to Indian data, the incidence of CAH ranges from 1:2600 to 1:16,000 live births, and India has a higher incidence than western countries.14,15 Our study showed an incidence of 0.25% in 396 neonates. According to research conducted by the ICMR Task Committee in 2018, the overall prevalence of CAH was 1:5762, with significant geographical variances in India.12 The incidence of CH was 1:722 neonates.12 There are conflicting reports about the incidence of CH in India. In our study, the incidence was 1:396 neonates, whereas Desai et al16 found a prevalence of 1:2804 after Table 3. Categories of Disorders Category Features Category A (All Newborns) • Screening for CH and hearing • Phase-wise screening for CH and G6PD deficiency • G6PD deficiency screening in the northern states of India • Screening for sickle cell disease and other hemoglobinopathies should be done in highincidence and high-risk groups and ethnicities Category B (Extended Screening and for High-Risk Population) • Conducted in the high-risk population (consanguinity, previous children with unexplained intellectual disability, seizure disorder, previous unexplained sibling deaths, critically ill neonates, neonates/ children with symptoms/signs/investigations suggestive of IEM) as well as for all newborns, irrespective of the cost • Mandatory in all tertiary care facilities, accessible to patients who can afford an additional INR 2000 to 3000 (USD 25 to 37) • Phenylketonuria, homocystinuria, alkaptonuria, galactosemia, and sickle cell anemia and other hemoglobinopathies • Cystic fibrosis, biotinidase deficiency, maple syrup urine disease, medium-chain acyl-CoA dehydrogenase deficiency, tyrosinemia, and fatty acid oxidation defects CH, congenital hypothyroidism; G6PD, glucose-6-phosphate dehydrogenase; IEM, inborn errors of metabolism. Research Article Gupta T, et al. The Need for Mandatory Newborn Screening in India
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