Complete genomic analysis of uncommon G12P[11] rotavirus causing a nosocomial outbreak of acute diarrhea in the newborns in New Delhi, India.

Rotaviruses (RVs) are the major causative agents of acute gastroenteritis in children, but in neonates, RV infections are generally nosocomial in origin and mostly asymptomatic. However, there have been infrequent reports of nosocomial outbreaks of clinical disease in this population. In this study, we describe uncommon RV genotype; G12P[11] associated with an outbreak of acute gastroenteritis in the neonatal ward and neonatal intensive care unit (NICU) in New Delhi, North India. Full-genome analyses of the pathogenic G12P[11] strain was carried out to map the genotype constellation and further to explore the variations in the antigenic epitopes on the immunodominant VP7 and VP4 proteins, the amino acid sequences were compared with neonatal strains; ROTAVAC® (G9P[11]) and asymptomatic G12P[11] and also other G/P-type matched strains. The study revealed G12-P[11]-I1-R1-C1-M1-A1-N1-T1-E1-H1 human Wa-like genotype constellation and highlights evidence of gene reassortment. No significant differences were observed in the sequences of structural (except VP3) and nonstructural encoding genes of G12P[11] strains recovered from symptomatic and asymptomatic neonates. Presence of additional N-linked glycosylation site was noted in the G12 strains, as a consequence of a change from Asp→Asn at amino acid position 238. Interestingly, only two and four amino acids substitution within the 7-1a and 8-1 antigenic epitope were observed, respectively, compared with asymptomatic G12P[11] strain. The study emphasizes the importance of close monitoring of RV outbreaks in neonates for early alarming of novel strain.

Flow Cytometry: An Important Diagnostic Tool in Critically Ill Preterm Neonates with Suspected Sepsis.

OBJECTIVE: Sepsis is a major cause of neonatal mortality. The gold standard for diagnosis is blood culture which suffers from low sensitivity and huge turn-around time. Flow cytometry has been extensively applied to malignant disorders and is an upcoming tool for diagnosis of nonmalignant disorders due to its rapidity and accuracy in detecting cells, cell products, and their functional states. The aim of this study was to investigate the utility of flow cytometric expression of neutrophil CD64, monocyte human leukocyte antigen (HLA-DR) and CD16 in diagnosis in suspected preterm neonates. STUDY DESIGN: In total, 100 preterm neonates with clinical signs of sepsis were enrolled in the study. Blood culture, C-reactive protein (CRP) and flow cytometry for nCD64, mHLA-DR, and mCD16 were performed. The neonates were divided into two groups: culture positive and culture negative and CRP and flow cytometric findings compared. ROC analysis was performed to determine the best cut-off for nCD64, mHLA-DR, and mCD16 values along with estimation of sensitivity, specificity, and predictive values. Probability of <0.05 was taken as significant. RESULTS: Out of the 100 enrolled neonates, 34 (34%) were culture positive. CRP was not found to be significantly different in the two groups. Expression of nCD64 (p = 0.03) was significantly upregulated in the blood culture positive cases with a cut-off mean fluorescence intensity (MFI) value = 4.72 and sensitivity of 92% and specificity of 52%. Expression of mCD16 (p = 0.02) was also upregulated in the blood culture positive cases with a cut-off MFI value = 4.9, with sensitivity of 41%, specificity of 83%. CONCLUSION: The study concluded that nCD64 and mCD16 can be potential biomarkers for early diagnosis of neonatal sepsis with a high sensitivity and specificity. KEY POINTS: · Neutrophil CD64 significantly upregulated in septic neonates.. · Monocyte CD16 significantly upregulated in septic neonates.. · C-reactive protein values were not significantly different in septic versus nonseptic neonates..

Evaluation of 75 g glucose load in non-fasting state [Diabetes in Pregnancy Study group of India (DIPSI) criteria] as a diagnostic test for gestational diabetes mellitus.

BACKGROUND & OBJECTIVES: There is no consensus regarding optimal standard for diagnosis of gestational diabetes mellitus (GDM). In this study, use of 75 g glucose load in non-fasting state [Diabetes in Pregnancy Study Group of India (DIPSI) criteria] as a diagnostic test for GDM in pregnant women was compared with different oral glucose tolerance tests (OGTTs). METHODS: This prospective study included 936 pregnant women, who underwent plasma glucose evaluation two hours after the challenge of 75 g glucose load irrespective of the timing of last meal (DIPSI criteria for GDM). After three days, standard 75 g OGTT was done in all women irrespective of previous plasma glucose value. Accuracy of the first result was compared to OGTT using cut-offs as per the World Health Organization (WHO) and International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria for the diagnosis of GDM. RESULTS: Of the total 936 pregnant women, 73 (7.8%) patients had plasma glucose value ≥140 mg/dl when measured two hours after glucose load. When comparing with the WHO and IADPSG criteria, the sensitivity values were 65.1 and 74.1 per cent, respectively, and the corresponding specificity values were 96.3 and 96.9 per cent, respectively. On comparing with the WHO OGTT, only 41 of the 73 (56.2%) were true positives, whereas when IADPSG criteria were used, true positives were 46 (63%). False negative cases were also present when classified by the WHO and IADPSG criteria though in lesser numbers than false positives. The positive predictive values (PPVs) for the WHO and IADPSG criteria were 56.1 and 63 per cent, respectively, and their corresponding negative predictive values were 97.7 and 97.9 per cent, respectively. INTERPRETATION & CONCLUSIONS: Our findings showed that when 75 g glucose load in non-fasting state was used as a diagnostic test for GDM, almost one quarter of patients with GDM escaped diagnosis as sensitivity values were low. On the other hand, some GDM cases were falsely labelled as normal as this test did not account for cases of fasting hyperglycaemia. In addition, comparison with other OGTTs showed low PPVs. Hence, use of DIPSI criteria for diagnosing GDM must be reconsidered till further validation.

Mutation Analyses in Selected Exons of the MUT Gene in Indian Patients with Methylmalonic Acidemia.

Deficiency or diminished activity of a cobalamin dependent enzyme methylmalonyl-CoA mutase causes inborn error of metabolism called methylmalonic acidemia (MMA). In this study we elucidated the spectrum of mutations in 21 Indian mut MMA patients by direct sequencing. Sequence analysis identified a total of 70 mutations in exon 2, 9, 11 and 12 of MUT gene. Out of which 26 mutations were predicted to be deleterious and rest were benign. The 23 novel mutations consist of four nonsense mutations (p.N6*, p.G539*, p.E609* and p.I671*), twelve missense mutations (p.K128I, p.N547T, p.D554Y, p.A558T, p.R559P, p.A631T, p.I647T, p.E656D, p.V657E, p.Q660H, p.K679N, and p.G696Y) and seven frame shift mutations (c.375_376insA, c.1642delA, c.1655delC, c.1825_1826insT, c.1957delGA, c.2014delA and c.2062_2063insGA). All of them are point mutations or micro rearrangements. Three of these mutations (p.K621N, p.G648D, p.G630E) have been previously reported; all of them are missense mutations. The mutations are distributed throughout the exon 2, 9, 11 and 12, 38.4 % mutation are located in exon 12.

Liquid-Liquid Extraction and Solid Phase Extraction for Urinary Organic Acids: A Comparative Study from a Resource Constraint Setting.

Pre analytical process of extraction for accurate detection of organic acids is a crucial step in diagnosis of organic acidemias by GCMS analysis. This process is accomplished either by solid phase extraction (SPE) or by liquid-liquid extraction (LLE). Both extraction procedures are used in different metabolic laboratories all over the world. In this study we compared these two extraction procedures in respect of precision, accuracy, percent recovery of metabolites, number of metabolites isolated, time and cost in a resource constraint setup. We observed that the mean recovery from SPE was 84.1 % and by LLE it was 77.4 % (p value <0.05). Moreover, the average number of metabolites isolated by SPE and LLE was 161.8 ± 18.6 and 140.1 ± 20.4 respectively. The processing cost of LLE was economical. In a cost constraint setting using LLE may be the practical option if used for organic acid analysis.

Chlorhexidine skin or cord care for prevention of mortality and infections in neonates.

BACKGROUND: Affordable, feasible and efficacious interventions to reduce neonatal infections and improve neonatal survival are needed. Chlorhexidine, a broad spectrum topical antiseptic agent, is active against aerobic and anaerobic organisms and reduces neonatal bacterial colonisation and may reduce infection. OBJECTIVES: To evaluate the efficacy of neonatal skin or cord care with chlorhexidine versus routine care or no treatment for prevention of infections in late preterm or term newborn infants in hospital and community settings. SEARCH METHODS: We searched CENTRAL, latest issue of The Cochrane Library, MEDLINE (1966 to November 2013), EMBASE (1980 to November 2013), and CINAHL (1982 to November 2013). Ongoing trials were detected by searching the following databases: www.clinicaltrials.gov and www.controlled-trials.com. SELECTION CRITERIA: Cluster and individual patient randomised controlled trials of chlorhexidine use (for skin care, or cord care, or both) in term or late preterm neonates in hospital and community settings were eligible for inclusion. Three authors independently screened and selected studies for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, and assessed study risk of bias. The quality of evidence for each outcome was assessed using GRADE. We calculated pooled risk ratios (RRs) and risk differences (RDs) with 95% confidence intervals (CIs), and presented results using GRADE 'Summary of findings' tables. MAIN RESULTS: We included 12 trials in this review. There were seven hospital-based and five community-based studies. In four studies maternal vaginal wash with chlorhexidine was done in addition to neonatal skin and cord care. Newborn skin or cord cleansing with chlorhexidine compared to usual care in hospitalsLow-quality evidence from one trial showed that chlorhexidine cord cleansing compared to dry cord care may lead to no difference in neonatal mortality (RR 0.11, 95% CI 0.01 to 2.04). Moderate-quality evidence from two trials showed that chlorhexidine cord cleansing compared to dry cord care probably reduces the risk of omphalitis/infections (RR 0.48, 95% CI 0.28 to 0.84).Low-quality evidence from two trials showed that chlorhexidine skin cleansing compared to dry cord care may lead to no difference in omphalitis/infections (RR 0.88, 95% CI 0.56 to 1.39). None of the studies in this comparison reported effects of the treatments on neonatal mortality. Newborn skin or cord cleansing with chlorhexidine compared to usual care in the communityHigh-quality evidence from three trials showed that chlorhexidine cord cleansing compared to dry cord care reduces neonatal mortality (RR 0.81, 95% CI 0.71 to 0.92) and omphalitis/infections (RR 0.48, 95% CI 0.40 to 0.57).High-quality evidence from one trial showed no difference between chlorhexidine skin cleansing and usual skin care on neonatal mortality (RR 1.03, 95% CI 0.87 to 1.23). None of the studies in this comparison reported effects of the treatments on omphalitis/infections. Maternal vaginal chlorhexidine in addition to total body cleansing compared to no intervention (sterile saline solution) in hospitalsModerate-quality evidence from one trial showed no difference between maternal vaginal chlorhexidine in addition to total body cleansing and no intervention on neonatal mortality (RR 0.98, 95% CI 0.67 to 1.42). High-quality evidence from two trials showed no difference between maternal vaginal chlorhexidine in addition to total body cleansing and no intervention on the risk of infections (RR 0.93, 95% CI 0.82 to 1.16).Findings from one trial showed that maternal vaginal cleansing in addition to total body cleansing results in increased risk of hypothermia (RR 1.33, 95% CI 1.19 to 1.49). Maternal vaginal chlorhexidine in addition to total body cleansing compared to no intervention (sterile saline solution) in the communityLow-quality evidence from one trial showed no difference between maternal vaginal chlorhexidine in addition to total body cleansing and no intervention on neonatal mortality (RR 0.20, 95% CI 0.01 to 4.03). Moderate-quality evidence from one trial showed that maternal vaginal chlorhexidine in addition to total body cleansing compared to no intervention probably reduces the risk of neonatal infections (RR 0.69, 95% CI 0.49 to 0.95). These studies did not report effect on omphalitis. AUTHORS' CONCLUSIONS: There is some uncertainty as to the effect of chlorhexidine applied to the umbilical cords of newborns in hospital settings on neonatal mortality. The quality of evidence for the effects on infection are moderate for cord application and low for application to skin. There is high-quality evidence that chlorhexidine skin or cord care in the community setting results in a 50% reduction in the incidence of omphalitis and a 12% reduction in neonatal mortality. Maternal vaginal chlorhexidine compared to usual care probably leads to no difference in neonatal mortality in hospital settings. Maternal vaginal chlorhexidine compared to usual care results in no difference in the risk of infections in hospital settings. The uncertainty over the effect of maternal vaginal chlorhexidine on mortality outcomes reflects small sample sizes and low event rates in the community settings.

Incidence of and risk factors for small vulnerable newborns in north India: a secondary analysis of a prospective pregnancy cohort.

BACKGROUND: Globally, recent estimates have shown there have been 3·6 million stillbirths and neonatal deaths in 2022, with nearly 60% occurring in low-income and middle-income countries. The Small Vulnerable Newborn Consortium has proposed a framework combining preterm birth (<37 weeks of gestation), small for gestational age (SGA) by INTERGROWTH-21st standard, and low birthweight (<2500 g) under the category small vulnerable newborns (SVN). Reliable data on SVN from sub-Saharan Africa, central Asia, and south Asia are sparse. We aimed to estimate the incidence of SVN and its types, and quantify risk factors, both overall and trimester-specific, from a pregnancy cohort in north India. METHODS: In the GARBH-Ini (Interdisciplinary Group for Advanced Research on Birth Outcomes-DBT India Initiative) pregnancy cohort, 8000 participants were enrolled with less than 20 weeks' gestation between May 11, 2015, and Aug 8, 2020, at a secondary-care hospital in north India. The cohort was followed up across the antenatal period for a detailed study on preterm birth. We conducted a secondary analysis of cohort data for the outcome of SVN, classified into its types: preterm-SGA, preterm-nonSGA, and term-SGA. We estimated the relative risk and population attributable fraction of candidate risk factors for SVN (modified Poisson regression) and its types (multinomial regression). FINDINGS: 7183 (89·9%) of 7990 participants completed the study. Among 6206 newborns included for analysis, the incidence of SVN was 48·4% (35·1% term-SGA newborns [n=2179], 9·7% preterm-nonSGA newborns [n=605], and 3·6% preterm-SGA newborns [n=222]). Compared with term-nonSGA newborns, proportions of stillbirths and neonatal deaths within 72 h of birth among SVN were three times and 2·5 times higher, respectively. Preterm-SGA newborns had the highest incidence of stillbirth (15 [6·8%] of 222) and neonatal deaths (six [4·2%] of 142). Low body-mass index (BMI <18·5 kg/m2) of participants at the start of pregnancy was associated with higher risk for preterm-SGA (adjusted relative risk [RR] 1·61 [95% CI 1·17-2·22]), preterm-nonSGA (1·35 [1·09-1·68]), and term-SGA (1·44 [1·27- 1·64]), with population attributable fraction ranging from 8·7% to 13·8%. Pre-eclampsia (adjusted RR 1·48 [95% CI 1·30-1·71]), short cervical length (1·15 [1·04-1·26]), and bacterial vaginosis (1·13 [0·88-1·45]) were other important antenatal risk factors. INTERPRETATION: In a comprehensive analysis of SVN and its types from north India, we identified risk factors to guide prioritisation of interventions. Complemented with risk-stratification tools, this focused approach will enhance antenatal care, and accelerate achievement of Sustainable Development Goals-namely, to end preventable deaths of newborns and children younger than 5 years by 2030 (target 3·2). FUNDING: Department of Biotechnology, Government of India and Grand Challenges India-Biotechnology Industry Research Assistance Council, Government of India. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Birth status, child growth, and adult outcomes in low- and middle-income countries.

OBJECTIVE: To assess the impact of being born preterm or small for gestational age (SGA) on several adult outcomes. STUDY DESIGN: We analyzed data for 4518 adult participants in 5 birth cohorts from Brazil, Guatemala, India, the Philippines, and South Africa. RESULTS: In the study population, 12.8% of males and 11.9% of females were born preterm, and 26.8% of males and 22.4% of females were born term but SGA. Adults born preterm were 1.11 cm shorter (95% CI, 0.57-1.65 cm), and those born term but SGA were 2.35 cm shorter (95% CI, 1.93-2.77 cm) compared with those born at term and appropriate size for gestational age. Blood pressure and blood glucose level did not differ by birth category. Compared with those born term and at appropriate size for gestational age, schooling attainment was 0.44 years lower (95% CI, 0.17-0.71 years) in those born preterm and 0.41 years lower (95% CI, 0.20-0.62 years) in those born term but SGA. CONCLUSION: Being born preterm or term but SGA is associated with persistent deficits in adult height and schooling, but is not related to blood pressure or blood glucose level in low- and middle-income settings. Increased postnatal growth is associated with gains in height and schooling regardless of birth status, but not with increases in blood pressure or blood glucose level.

Turning the Gaze from Survive to Thrive for Children in India: Learnings from Two Case Studies.

Despite significant efforts and progress made in newborn care programs in India, implementation gaps persist across the continuum of care. The present case studies of two districts in Himachal Pradesh revealed that pathways of care were often fragmented with inconsistent linkages between facility and community due to poor documentation, lack of tiered referral, health system weaknesses, low utilization of primary level institutions, and inadequate post-natal home visits by Accredited Social Health Activists (ASHAs). Involvement of healthcare providers (HCPs) and frontline health workers (FHWs) was low and uneven in generating awareness across the districts with limited participation in supporting care in the community. Ensuring functionality of health centers and first-level care facilities; strengthening referral systems; adequate/trained human resources; strengthening routine health management systems, discharge processes and community-based care with adequate integration with facilities are necessary in closing access gaps.

Screening for gestational diabetes mellitus: a prospective study in a tertiary care institution of North India.

AIM: The aim of this study was to determine the relevance of universal screening for gestational diabetes mellitus (GDM) in the patients attending the antenatal clinic of a tertiary institute of North India. MATERIAL AND METHODS: This was a prospective study conducted on 700 pregnant women attending the antenatal clinic of Lok Nayak Hospital, New Delhi at or before 24 weeks of gestation. All patients underwent screening with a 50-g 1-h glucose challenge test at 24-28 weeks of gestation. The women with an abnormal glucose challenge test subsequently underwent a diagnostic 3-h oral glucose tolerance test. All the patients were followed up till delivery. RESULTS: Out of 700, thirteen patients were lost to follow up and hence the final outcomes were measured on 687 patients. Out of 687, 613 patients (89.2%) had a normal glucose challenge test value, that is, <140 mg%, and 74 (10.8%) had a glucose challenge test value ≥140 mg%. On the subsequent oral glucose tolerance test, 64 (9.3%) had normal values and only 10 (1.5%) had an abnormal oral glucose tolerance test, that is, GDM. CONCLUSION: With such a low prevalence rate it appears to be unjustified to recommend universal screening for GDM. These findings may be considered as a basis for conducting larger, multicentric studies to establish the prevalence rate of GDM before deciding on a policy for screening.

Effect of zinc supplementation on growth in very low birth weight infants.

This was a randomized blinded placebo controlled trial undertaken to study the role of zinc supplementation on growth, primarily the linear growth velocity in very low birth weight (VLBW) infants at 3 months corrected age (CA). Out of 134 neonates with birth weight <1500 g, 101 babies were eligible. Due to lack of consent 10 were excluded. The remaining 91 neonates who were comparable for sex, gestational age, birth weight, APGAR and age at enrollment were randomized to receive either 1 ml of zinc sulfate (10 mg elemental zinc) (n = 46) or 1 ml placebo (n = 45) from enrollment to 60 days. The infants in the zinc group had significantly higher linear growth velocity (0.98 ± 0.12 cm week(-1)) compared to a placebo group (0.67 ± 0.15 cm week(-1)) (p < 0.001) at 3 months CA. We concluded that zinc supplementation at 10 mg day(-1) for 60 days in VLBW infants improves their linear growth during infancy.

Study Design: Observational Studies.

Observational study designs are those where the investigator/researcher just observes and does not carry out any intervention(s)/actions to alter the outcome. The three most common types of observational studies are cross-sectional, case control and cohort (or longitudinal). In cross-sectional studies, both the exposure/risk factor(s) and the outcome(s) are determined at a single time point. They can provide information on prevalence of a condition and snapshot of probable associations that can be used to generate hypothesis. Case-control studies are where subjects are selected based on presence/absence of outcome and the risk factors are determined during the study after enrolment of study subjects. The association between exposure and outcome is reported as odds ratio. These studies; however, have high risk of bias, which must be taken care of during study design. Cohort studies are prospective in nature, where subjects are selected based on presence/absence of exposure, and the outcome(s) is determined at the end of study. These studies can provide incidence of disease/outcome and the association between exposure and outcome is reported as relative risk. They are useful to ascertain causality. High dropouts of study participants and confounding can be problems encountered in these studies.

The Hearing Status of Preterm Infant's ≤ 34 Weeks as Revealed by Otoacoustic Emissions (OAE) Screening and Diagnostic Brainstem Evoked Response Audiometry (BERA): A Tertiary Center Experience.

To know the prevalence of hearing loss in preterm infants & to evaluate the sensitivity & specificity of otoacoustic emission (OAE) in detecting hearing loss in preterm infants ≤ 34 weeks. A total of 70 preterm babies from 28 to 34 weeks of gestational age were enrolled in the study. Detailed prenatal, perinatal, postnatal & family history and physical examination of the babies were carried out. First OAE was done at discharge or two weeks after birth, whichever was earlier and the second OAE assessment was done at 36-40 weeks of corrected age. Diagnostic brainstem evoked response audiometry (BERA) was done in all infants at 36-40 weeks of corrected age, at the time of second OAE. Neonates with hearing impairment were advised for early hearing aid amplification and were referred to the rehabilitation center for further management. The sensorineural hearing loss (SNHL) in either one of the ears was identified in 13 (18.57%) preterm babies. Bilateral profound SNHL was found in 5 (7.14%) babies. Auditory neuropathy profile was found in 7 (53.8%) out of 13 babies who had hearing loss. The sensitivity, specificity, positive and negative predictive values of second TEOAE compared with diagnostic BERA was 46.15%, 85.96%, 42.85%, and 87.5% respectively. Neonatal jaundice (p = 0.009) and history of exchange transfusion (p = 0.019) were found to be significant risk factors of hearing loss in our study. Other risk factors like mode of delivery, birth asphyxia, low APGAR score, meningitis, ototoxic drugs, and seizures were not associated with hearing loss. The prevalence of hearing loss in preterm infants < 34 weeks is very high. OAE alone is not an ideal screening test for high-risk neonates ≤ 34 weeks because of its low sensitivity. OAE combined with diagnostic BERA should be done in all high-risk infants preterm neonates ≤ 34 weeks to identify cases of auditory neuropathy spectrum disorders.

Growth Faltering Among Discharged Babies from Inpatient Newborn Care Facilities: Learnings from Two Districts of Himachal Pradesh.

OBJECTIVE: To determine the burden of early growth faltering and understand the care practices for small and sick babies discharged from newborn units in the district. STUDY DESIGN: Observational and follow-up study. PARTICIPANTS: 512 babies discharged from two Special Newborn Care Units (SNCUs) and four Newborn Stabilization Units (NBSUs) in two districts of Himachal Pradesh. METHODS: Anthropometric assessments, interview of mothers and Accredited Social Health Activists (ASHAs) conducted between August, 2018 and March, 2019. Change in weight-for-age z-score (DWAZ) of <-0.67SD between birth and assessment was used to define growth faltering. OUTCOMES: Proportion of growth faltering (or catch-down growth) in small and sick babies discharged from SNCUs and NBSUs, and infant care practices. RESULTS: Growth faltering was observed in a significant proportion of both term (30%) and preterm (52.6%) babies between 1 to 4 months of age. Among babies with growth faltering (n=180), 73.9% received a home visit by ASHA, and only 36.7% received a follow-up visit at a facility. There were 71.3% mothers counselled at discharge (mostly informed about breast feeding). Most (96.7%) mothers did not perceive inadequate weight gain in their babies post-discharge. During home visits, ASHAs weighed 61.6% of the infants with growth faltering. Amongst infants who had growth faltering, only 49.6% of mothers had been provided information about their infant's growth and 57.1% mothers had received breastfeeding counselling. CONCLUSION: Small and sick newborn infants (both term and preterm babies) discharged from special care newborn units are at increased risk of early growth faltering. Follow-up care provided to these infants is inadequate. There is a need to strengthen both facility-based and home-based follow up of small and sick newborn infants discharged from newborn care facilities.

Gestational weight gain trajectories in GARBH-Ini pregnancy cohort in North India and a comparative analysis with global references.

BACKGROUND: To describe the pattern of gestational weight gain (GWG), derive reference centiles for GWG specific to North Indian population, and to compare the weight gain across different periods of gestation with the INTERGROWTH-21st reference. METHODS: A prospective pregnancy (GARBH-Ini) cohort was initiated and followed between May 2015 and June 2019 in a district hospital, Gurguram, North India. GWG centile curves were modelled by Generalized Additive Models for Location, Scale and Shape method (n = 2844) and compared with INTERGROWTH-21st reference. The independent association of GWG with biological and social predictors was assessed using multivariable regression analysis. RESULTS: Percentiles (3rd, 10th, 50th, 90th and 97th) for each completed week from 18-40 weeks of gestation were derived from smoothed centile curves. The median GWG across pregnancy during specific antenatal visits was 1.29 at 18, 4.44 at 26, 5.8 at 30 and 9.06 kg at 40 weeks of gestation. Nearly 26% of participants had GWG < 10th centile at 18-20 weeks as per INTERGROWTH-21st reference and this increased to 45% at delivery. Significant predictors of GWG included maternal age, height, first trimester body mass index, parity, type of family, and use of clean fuel for cooking. CONCLUSION: These GWG percentiles will serve as a useful reference, particularly during the WHO recommended antenatal visit schedule for optimum pregnancy outcomes, for clinicians and researchers. Multiple independent biological and social predictors of GWG suggest that single interventions are unlikely to bridge the gap between general Indian population and international references.

Fetal scalp stimulation test: an adjunct to intermittent auscultation in non-reassuring fetal status during labor.

AIMS: To evaluate fetal scalp stimulation test (FSST) as an adjunct to intermittent auscultation in diagnosis of intrapartum fetal acidosis and associate result of FSST with cord blood pH and immediate neonatal outcome. MATERIAL & METHODS: This study was conducted at a tertiary hospital in India. Digital FSST was performed in seven hundred and fifty women in labor with singleton gestation ≥37 weeks, cephalic presentation and fetal heart abnormalities and/or thick meconium stained amniotic fluid. Intermittent auscultation was used for fetal monitoring during labor. The outcome measure was cord blood pH < 7.20 and neonatal morbidity. RESULTS: The non-reactive FSST is associated with lower umbilical cord blood pH, lower Apgar scores and higher asphyxia related neonatal morbidity (P-value < 0.001). The non-reactive FSST had 41% sensitivity and 84% specificity to detect pH < 7.20. The positive predictive value of FSST for fetal acidosis is 44% and negative predictive value is 83%. The likelihood ratio for acidosis with noncreative FSST is 2.57. CONCLUSIONS: Non-reactive FSST is associated with adverse neonatal outcomes. The positive and negative predictive values of FSST to diagnose fetal cord blood pH < 7.20 during labor are 44% & 83%, respectively.

Parental and professional perceptions of informed consent and participation in a time-critical neonatal trial: a mixed-methods study in India, Sri Lanka and Bangladesh.

INTRODUCTION: Time-critical neonatal trials in low-and-middle-income countries (LMICs) raise several ethical issues. Using a qualitative-dominant mixed-methods design, we explored informed consent process in Hypothermia for encephalopathy in low and middle-income countries (HELIX) trial conducted in India, Sri Lanka and Bangladesh. METHODS: Term infants with neonatal encephalopathy, aged less than 6 hours, were randomly allocated to cooling therapy or usual care, following informed parental consent. The consenting process was audio-video (A-V) recorded in all cases. We analysed A-V records of the consent process using a 5-point Likert scale on three parameters-empathy, information and autonomy. In addition, we used exploratory observation method to capture relevant aspects of consent process and discussions between parents and professionals. Finally, we conducted in-depth interviews with a subgroup of 20 parents and 15 healthcare professionals. A thematic analysis was performed on the observations of A-V records and on the interview transcripts. RESULTS: A total of 294 A-V records of the HELIX trial were analysed. Median (IQR) score for empathy, information and autonomy was 5 (0), 5 (1) and 5 (1), respectively. However, thematic analysis suggested that the consenting was a ceremonial process; and parental decision to participate was based on unreserved trust in the treating doctors, therapeutic misconception and access to an expensive treatment free of cost. Most parents did not understand the concept of a clinical trial nor the nature of the intervention. Professionals showed a strong bias towards cooling therapy and reported time constraints and explaining to multiple family members as key challenges. CONCLUSION: Despite rigorous research governance and consent process, parental decisions were heavily influenced by situational incapacity and a trust in doctors to make the right decision on their behalf. Further research is required to identify culturally and context-appropriate strategies for informed trial participation.

Indian Academy of Pediatrics Position Paper on Nurturing Care for Early Childhood Development.

Early childhood development (ECD) refers to the physical, motor, socio-emotional, cognitive, and linguistic development of a young child. The 'Countdown to 2030' global distribution of 'children at risk of poor development' indicates the need for urgent action and investment in ECD. Nurturing care enhances ECD, even in the presence of adversities. Strategic actions should exist at multiple levels: the family, community, health care providers and government. Previously, child health related policies and programs of the Government of India functioned in isolation, but have recently started demonstrating multi-sectoral collaboration. Nonetheless, the status of ECD in India is far from optimal. There is strong evidence that parenting programs improve outcomes related to ECD. This is dependent on key programmatic areas (timing, duration, frequency, intensity, modality, content, etc.), in addition to political will, funding, partnership, and plans for scaling up. Each country must implement its unique ECD program that is need-based and customized to their stakeholder community. Barriers like inadequate sensitization of the community and low competency of health care providers need to be overcome. IAP firmly believes that responsive parenting interventions revolving around nurturing care should be incorporated in office practice. This paper outlines IAP's position on ECD, and its recommendations for pediatricians and policy makers. It also presents the roadmap in partnership with other stakeholders in maternal, neonatal, and child health; Federation of Obstetric and Gynaecological Societies of India (FOGSI), National Neonatology Forum (NNF), World Health Organization (WHO), and United Nation Children Fund (UNICEF).