Child Neurodevelopment After Multidomain Interventions From Preconception Through Early Childhood: The WINGS Randomized Clinical Trial.

Importance: Multidomain interventions in pregnancy and early childhood have improved child neurodevelopment, but little is known about the effects of additional preconception interventions. Objective: To evaluate the effect of a multifaceted approach including health; nutrition; water, sanitation, and hygiene (WASH); and psychosocial support interventions delivered during the preconception period and/or during pregnancy and early childhood on child neurodevelopment. Design, Setting, and Participants: In this randomized trial involving low- and middle-income neighborhoods in Delhi, India, 13 500 participants were assigned to preconception interventions or routine care for the primary outcome of preterm births and childhood growth. Participants who became pregnant were randomized to pregnancy and early childhood interventions or routine care. Neurodevelopmental assessments, the trial's secondary outcome reported herein, were conducted in a subsample of children at age 24 months, including 509 with preconception, pregnancy, and early childhood interventions; 473 with preconception interventions alone; 380 with pregnancy and early childhood interventions alone; and 350 with routine care. This study was conducted from November 1, 2000, through February 25, 2022. Interventions: Health, nutrition, psychosocial care and support, and WASH interventions delivered during preconception, pregnancy, and early childhood periods. Main Outcomes and Measures: Cognitive, motor, language, and socioemotional performance at age 24 months, assessed using the Bayley Scales of Infant and Toddler Development 3 tool. Results: The mean age of participants at enrollment was 23.8 years (SD, 3.0 years). Compared with the controls at age 24 months, children in the preconception intervention groups had higher cognitive scores (mean difference [MD], 1.16; 98.3% CI, 0.18-2.13) but had similar language, motor, and socioemotional scores as controls. Those receiving pregnancy and early childhood interventions had higher cognitive (MD, 1.48; 98.3% CI, 0.49-2.46), language (MD, 2.29; 98.3% CI, 1.07-3.50), motor (MD, 1.53; 98.3% CI, 0.65-2.42), and socioemotional scores (MD, 4.15; 98.3% CI, 2.18-6.13) than did controls. The pregnancy and early childhood group also had lower incidence rate ratios (RRs) of moderate to severe delay in cognitive (incidence RR, 0.62; 98.3% CI, 0.40-0.96), language (incidence RR, 0.73; 98.3% CI, 0.57-0.93), and socioemotional (incidence RR, 0.49; 98.3% CI, 0.24-0.97) development than did those in the control group. Children in the preconception, pregnancy, and early childhood intervention group had higher cognitive (MD, 2.60; 98.3% CI, 1.08-4.12), language (MD, 3.46; 98.3% CI, 1.65-5.27), motor (MD, 2.31; 98.3% CI, 0.93-3.69), and socioemotional (MD, 5.55; 98.3% CI, 2.66-8.43) scores than did those in the control group. Conclusions and Relevance: Multidomain interventions during preconception, pregnancy and early childhood led to modest improvements in child neurodevelopment at 24 months. Such interventions for enhancing children's development warrant further evaluation. Trial Registration: Clinical Trials Registry-India CTRI/2017/06/008908.

Breastfeeding practices based on the gestational age and weight at birth in the first six months of life in a population-based cohort of infants from North India.

Background: Short and long term benefits of early Initiation of breastfeeding (EIBF) and exclusive breastfeeding (EBF) in the first six months of life are well established and recommended globally. However, reliable estimates of breastfeeding practices and impact of breastfeeding counselling interventions according to gestational age and weight at birth are not available in low and middle income countries. Objective: To assess the impact of breastfeeding counselling on EIBF and EBF during the first 6 months of life according to gestational age and weight at birth. Methods: We analysed the data collected from the Women and Infants Integrated Interventions for Growth Study (WINGS), an individually randomized factorial design trial. Mothers were counselled on EIBF during third trimester of pregnancy. They were supported throughout the first 6 months to continue EBF by early problem identification, frequent home visits and assistance in expressing breastmilk when direct breastfeeding was not possible. Breastfeeding practices were ascertained through 24 h recalls at infant ages 1, 3 and 5 months for both the intervention and control groups by an independent outcome ascertainment team. The World Health Organization (WHO) definitions were used for classification of infant breastfeeding practices. Generalized linear models of the Poisson family with a log-link function were used to estimate the effect of interventions on breastfeeding practices. The relative measures of effect on breastfeeding practices were estimated in term appropriate for gestational age (T-AGA), term small for gestational age (T-SGA), preterm AGA (PT-AGA), preterm SGA (PT-SGA) infants. Results: Amongst all infants irrespective of gestational age and weight at birth, EIBF was (51.7%) higher amongst the intervention group (IRR 1.38, 95% CI 1.28-1.48) compared with the control group. The proportion of exclusively breastfed infants at ages 1 month (IRR 1.37, 95% CI 1.28-1.48), 3 months (IRR 2.13, 95% CI 1.30-1.44) and 5 months (IRR 2.78, 95% CI 2.58-3.00) were higher in intervention group than control group. We identified significant interaction (p value for interaction <0.05) between intervention and infant size and gestation at birth on exclusive breastfeeding at 3 and 5 months of age. Subgroup analysis showed that the impact of the intervention was greater on exclusive breastfeeding in PT- SGA infants at 3 months (IRR 3.30, 95% CI 2.20-4.96) and 5 months of age (IRR 5.26, 95% CI 2.98-9.28). Conclusion: This is one of the first studies wherein impact of breastfeeding counselling interventions in the first 6 months of life was assessed according to infant size and gestation at birth wherein gestational age was reliably estimated. The impact of this intervention was higher in preterm and SGA babies compared to other infants. This finding is important as preterm and SGA infants have a higher burden of mortality and morbidity during early infancy. Intensive breastfeeding counselling to these vulnerable infants is likely to improve overall breastfeeding rates and reduce the adverse outcomes.Clinical Trial Registration: [http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339%26EncHid=%26userName=societyforappliedstudies], identifier [#CTRI/2017/06/008908].

Effects of kangaroo mother care on maternal and paternal health: systematic review and meta-analysis.

Objective: To investigate the effect of kangaroo mother care for low-birth-weight and preterm infants on parents' mental and physical health. Methods: The Cochrane Central Register of Controlled Trials, Cochrane Register of Studies Online, PubMed®, Web of Science, Scopus and EMBASE® databases were searched on 16 January 2023 for randomized and quasi-randomized trials on kangaroo mother care. Records identified were screened independently by two reviewers. Pooled relative risks (RRs) are reported for categorical variables, and standardized mean differences (SMDs) or mean differences are reported for continuous variables. Evidence quality was assessed using the GRADE approach. Findings: The search identified 30 studies involving 7719 preterm or low-birth-weight infants. There was high-certainty evidence that kangaroo mother care substantially reduced the risk of moderate-to-severe postpartum maternal depressive symptoms compared with no kangaroo mother care (RR: 0.76; 95% confidence interval, CI: 0.59 to 0.96). In addition, there was low-certainty evidence that kangaroo mother care reduced scores for maternal stress (SMD: -0.82; 95% CI: -1.32 to -0.32) and anxiety (SMD: -0.62; 95% CI: -1.01 to -0.23) and increased mother-infant attachment and bonding scores (SMD: 1.19; 95% CI: 0.27 to 2.10). Limited evidence indicated father-infant interactions may be improved, though no marked effect on paternal depression or stress was observed. No trial reported parental physical health outcomes. Conclusion: Kangaroo mother care for preterm and low-birth-weight infants was associated with less postpartum maternal depression, stress and anxiety and better mother-infant attachment and bonding. More research is required to evaluate effects on paternal health.

Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses - finding and creating similarities in variables and data collection.

BACKGROUND: Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. METHODS: We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. DISCUSSION: We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.

Government-led initiative increased the effective use of Kangaroo Mother Care in a region of North India.

AIM: To learn how to achieve high-quality, effective coverage of Kangaroo Mother Care (KMC), defined as 8 hours or more of skin-to-skin contact per day and exclusive breastfeeding in district Sonipat in North India, and to develop and evaluate an implementation model. METHODS: We conducted implementation research using a mixed-methods approach, including formative research, followed by repeated, rapid cycles of implementation, evaluation and refinement until a model with the potential for high and effective coverage was reached. Evaluation of this model was conducted over a 12-month period. RESULTS: Formative research findings informed the final implementation model. Programme learning was critical to achieve high coverage. The model included improving the identification of small babies, creating KMC wards, modification in hospitalisation criteria, private sector engagement and in-built programme learning to refine implementation progress. KMC was initiated in 87% of eligible babies. At discharge, 85% received skin-to-skin contact care, 60% effective KMC and 80% were exclusively breastfed. At home, 7-day post discharge, 81% received skin-to-skin care and 79% were exclusively breastfed in the previous 24 hours. CONCLUSION: Achieving high KMC coverage is feasible in the study setting using a model responsive to the local context and led by the Government.

Effect of kangaroo mother care initiated in community settings on financial risk protection of low-income households: a randomised controlled trial in Haryana, India.

INTRODUCTION: Many families in low-income and middle-income countries have high out-of-pocket expenditures (OOPE) for healthcare, and some face impoverishment. We aimed to assess the effect of Kangaroo Mother Care initiated in community setting (ciKMC) on financial risk protection estimated by healthcare OOPE, catastrophic healthcare expenditure (CHE) and impoverishment due to healthcare seeking for low birthweight infants, using a randomised controlled trial design. METHODS: We included 4475 low birthweight infants randomised to a ciKMC (2491 infants) and a control (1984 infants) arm, in a large trial conducted between 2017 and 2018 in Haryana, India. We used generalised linear models of the Gaussian family with an identity link to estimate the mean difference in healthcare OOPE, and Cox regression to estimate the HRs for CHE and impoverishment, between the trial arms. RESULTS: Overall, in the 8-week observation period, the mean healthcare OOPE per infant was lower (US$20.0) in the ciKMC arm compared with the control arm (US$25.6) that is, difference of -US$5.5, 95% CI -US$11.4 to US$0.3, p=0.06). Among infants who sought care it was US$8.5 (95% CI -US$17.0 to -US$0.03, p=0.03) lower in the ciKMC arm compared with the control arm. The HR for impoverishment due to healthcare seeking was 0.56 (95% CI 0.36 to 0.89, p=0.01) and it was 0.91 (95% CI 0.74 to 1.12, p=0.37) for CHE. CONCLUSION: ciKMC can substantially reduce the cost of care seeking and the risk of impoverishment for households. Our findings show that supporting mothers to provide KMC to low birthweight infants at home, in addition to reducing early infant mortality, may provide financial risk protection. TRIAL REGISTRATION NUMBER: CTRI/2017/10/010114.

Impact of a package of health, nutrition, psychosocial support, and WaSH interventions delivered during preconception, pregnancy, and early childhood periods on birth outcomes and on linear growth at 24 months of age: factorial, individually randomised controlled trial.

OBJECTIVE: To determine the effect of integrated and concurrent delivery of health, nutrition, water, sanitation and hygiene (WaSH), and psychosocial care interventions during the preconception period alone, during pregnancy and early childhood, and throughout preconception, pregnancy, and early childhood on birth outcomes and linear growth at 24 months of age compared with routine care. DESIGN: Individually randomised factorial trial. SETTING: Low and middle income neighbourhoods of Delhi, India. PARTICIPANTS: 13 500 women were randomised to receive preconception interventions (n=6722) or routine care (n=6778). 2652 and 2269 pregnant women were randomised again to receive pregnancy and early childhood interventions or routine care. The analysis of birth outcomes included 1290 live births for the preconception, pregnancy, and early childhood interventions (group A), 1276 for the preconception intervention (group B), 1093 for the pregnancy and early childhood interventions (group C), and 1093 for the control (group D). Children aged 24 months by 30 June 2021 were included in the 24 month outcome analysis (453 in group A, 439 in B, 293 in C, and 271 in D). INTERVENTIONS: Health, nutrition, psychosocial care and support, and WaSH interventions were delivered during preconception, pregnancy, and early childhood periods. MAIN OUTCOME MEASURES: The primary outcomes were low birth weight, small for gestational age, preterm, and mean birth weight. At 24 months, the outcomes were mean length-for-age z scores and proportion stunted. Three prespecified comparisons were made: preconception intervention groups (A+B) versus no preconception intervention groups (C+D); pregnancy and early childhood intervention groups (A+C) versus routine care during pregnancy and early childhood (B+D) and preconception, pregnancy, and early childhood interventions groups (A) versus control group (D). RESULTS: The proportion with low birth weight was lower in the preconception intervention groups (506/2235) than in the no preconception intervention groups (502/1889; incidence rate ratio 0.85, 98.3% confidence interval 0.75 to 0.97; absolute risk reduction -3.80%, 98.3% confidence interval -6.99% to -0.60%). The proportion with low birth weight was lower in the pregnancy intervention groups (502/2096) than in the no pregnancy intervention groups (506/2028) but the upper limit of the confidence interval crossed null effect (0.87, 0.76 to 1.01; -1.71%, -4.96% to 1.54%). There was a larger effect on proportion with low birth weight in the group that received interventions in the preconception and pregnancy periods (267/1141) compared with the control group (267/934; 0.76, 0.62 to 0.91; -5.59%, -10.32% to -0.85%). The proportion stunted at 24 months of age was substantially lower in the pregnancy and early childhood intervention groups (79/746) compared with the groups that did not receive these interventions (136/710; 0.51, 0.38 to 0.70; -8.32%, -12.31% to -4.32%), and in the group that received preconception, pregnancy, and early childhood interventions (47/453) compared with the control group (51/271; 0.49, 0.32 to 0.75; -7.98%, -14.24% to -1.71%). No effect on stunting at 24 months was observed in the preconception intervention groups (132/892) compared with the no preconception intervention groups (83/564). CONCLUSIONS: An intervention package delivered during preconception, pregnancy, and early childhood substantially reduced low birth weight and stunting at 24 months. Pregnancy and early childhood interventions alone had lower but important effects on birth outcomes and 24 month outcomes. Preconception interventions alone had an important effect on birth outcomes but not on 24 month outcomes. TRIAL REGISTRATION: Clinical Trial Registry-India CTRI/2017/06/008908.

Early child stimulation, linear growth and neurodevelopment in low birth weight infants.

BACKGROUND: Children with low birth weight (LBW) are at risk of linear growth faltering and developmental deficits. Evidence suggests that early child stimulation and care reflected as responsive caregiving and opportunities for learning can promote development. The current analysis aimed to measure the extent to which linear growth and early child stimulation modify each other's association with neurodevelopmental outcomes among LBW infants. METHODS: This is a secondary data analyses from a randomized controlled trial on the effect of community-initiated kangaroo mother care in LBW infants on their neurodevelopment at 12 months of corrected age. Bayley Scales of Infant and Toddler Development was used to assess cognitive, motor and language scores. Stimulation at home was assessed by the Pediatric Review of Children's Environmental Support and Stimulation (PROCESS) tool. PROCESS scores were categorized into three groups: < Mean-1SD (low stimulation); Mean ± 1 SD (moderate stimulation) and > mean + 1SD (high stimulation). RESULTS: A total of 516 infants were available for neurodevelopment assessments. Interactions were observed between length for age z-score (LAZ) and PROCESS score categories. In the low stimulation group, the adjusted regression coefficients for the association between LAZ and cognitive, motor and language scores were substantially higher than in the moderate and high stimulation group. Stimulation was positively associated with neurodevelopmental outcomes in both stunted and non-stunted infants; however, the association was twice as strong in stunted than in non-stunted. CONCLUSION: Moderate to high quality stimulation may alleviate the risk of sub-optimal development in LBW infants with linear growth deficits. CLINICAL TRIAL REGISTRATION: The primary trial whose data are analysed is registered at clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT02631343 ).

Effect of community-initiated kangaroo mother care on breastfeeding performance in low birthweight infants: A randomized clinical trial.

This individually randomized trial was conducted to estimate the effect of promoting community-initiated kangaroo mother care (ciKMC) in low birthweight (LBW) infants on infant breastfeeding performance. It was designed as a substudy within a larger primary trial on ciKMC and infant survival. Five hundred fifty stable LBW mother-infant dyads (1500-2250 g) who provided consent, were consecutively enroled for breastfeeding performance assessment. The ciKMC intervention included promotion and support of continuous skin-to-skin contact and exclusive breastfeeding (EBF) through home visits during the neonatal period. The primary outcome was effective breastfeeding performance indicated by an infant breastfeeding assessment tool score of ≥10 after the end of the neonatal period. As secondary outcomes, we reported maternal satisfaction related to infant breastfeeding, and EBF after the end of the neonatal period. We completed outcome assessments in 96% of participants. In the ciKMC arm, 92% of the infants showed effective breastfeeding performance against 81% in the control arm [adjusted prevalence ratio (aPR): 1.24, 95% confidence interval (CI): 1.16-1.32]. In the ciKMC arm, 65% of the mothers reported to be very satisfied with their infants' breastfeeding against 51% in the control arm (aPR: 1.22, 95% CI: 1.05-1.41). The proportion of infants practicing EBF was 89% in the ciKMC arm against 45% in the control arm (aPR: 1.62, 95% CI: 1.45-1.81). Our study findings suggest that promotion of ciKMC can improve effective breastfeeding, EBF and maternal satisfaction related to breastfeeding in LBW infants.

Enteral Calcium or Phosphorus Supplementation in Preterm or Low Birth Weight Infants: a Systematic Review and Meta-analysis.

OBJECTIVES: To assess effects of calcium or phosphorous supplementation compared with no supplementation in human milk-fed preterm or low birth weight infants. METHODS: Data sources include Cochrane Central Register of Controlled Trials, Medline and Embase. We included Randomized controlled trials (RCTs) and non-randomized trials (quasi-randomized). RESULTS: Three studies (4 reports; 162 infants) were included. At latest follow-up (38 weeks), there was reduction in osteopenia (3 studies, 159 participants, relative risk 0.68, 95% confidence interval [CI] 0.46-0.99). At latest follow-up (6 weeks), there was no effect on weight (1 study, 40 participants, mean difference [MD] 138.50 g, 95% CI -82.16 to 359.16); length (1 study, 40 participants, MD 0.77 cm, 95% CI -0.93 to 2.47); and head circumference (1 study, 40 participants, MD 0.33 cm, 95% CI -0.30 to 0.96). At latest follow-up, there was no effect on alkaline phosphatase (55 weeks) (2 studies, 122 participants, MD -126.11 IU/L, 95% CI -298.5 to 46.27, I2 = 73.4%); serum calcium (6 weeks) (1 study, 40 participants, MD 0.54 mg/dL, 95% CI -0.19 to 1.27); and serum phosphorus (6 weeks) (1 study, 40 participants, MD 0.07 mg/dL, 95% CI -0.22 to 0.36). The certainty of evidence ranged from very low to low. No studies reported on mortality and neurodevelopment outcomes. CONCLUSIONS: The evidence is insufficient to determine whether enteral supplementation with calcium or phosphorus for preterm or low birth weight infants who are fed mother's own milk or donor human milk is associated with benefit or harm.

Enteral Multiple Micronutrient Supplementation in Preterm and Low Birth Weight Infants: A Systematic Review and Meta-analysis.

OBJECTIVES: To assess effects of supplementation with 3 or more micronutrients (multiple micronutrients; MMN) compared to no MMN in human milk-fed preterm and low birth weight (LBW) infants. RESULTS: Data on a subgroup of 414 preterm or LBW infants from 2 randomized controlled trials (4 reports) were included. The certainty of evidence ranged from low to very low. For growth outcomes in the MMN compared to the non-MMN group, there was a small increase in weight-for-age (2 trials, 383 participants) and height-for-age z-scores (2 trials, 372 participants); a small decrease in wasting (2 trials, 398 participants); small increases in stunting (2 trials, 399 participants); and an increase in underweight (2 trials, 396 participants). For neurodevelopment outcomes at 78 weeks, we found small increases in Bayley Scales of Infant Development, Version III (BISD-III), scores (cognition, receptive language, expressive language, fine motor, gross motor) in the MMN compared to the non-MMN group (1 trial, 27 participants). There were no studies examining dose or timing of supplementation. CONCLUSIONS: Evidence is insufficient to determine whether enteral MMN supplementation to preterm or LBW infants who are fed mother's own milk is associated with benefit or harm. More trials are needed to generate evidence on mortality, morbidity, growth, and neurodevelopment.

Enteral Zinc Supplementation in Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Evidence on the effect of zinc supplementation on health outcomes in preterm or low birth weight (LBW) infants is unclear. We estimated the effect of enteral zinc versus no zinc supplementation in human milk fed preterm or LBW infants on mortality, growth, morbidities, and neurodevelopment. METHODS: Data sources include PubMed, Cochrane Central and Embase databases through March 24, 2021. Study selection was randomized or quazi-experimental trials. Two reviewers independently screened, extracted data, and assessed quality. We reported pooled relative risks (RR) for categorical outcomes, and mean differences (MD) for continuous outcomes. RESULTS: Fourteen trials with 9940 preterm or LBW infants were included. Moderate to low certainty evidence showed that enteral zinc supplementation had little or no effect on mortality (risk ratio 0.73, 95% confidence interval [CI] 0.46 to 1.16), but increased weight (MD 378.57, 95% CI 275.26 to 481.88), length (MD 2.92, 95% CI 1.53 to 4.31), head growth (MD 0.56, 95% CI 0.23 to 0.90), and decreased diarrhea (RR 0.81; 95% CI 0.68 to 0.97). There was no effect on acute respiratory infections, bacterial sepsis, and psychomotor development scores. The effect of zinc supplementation on mental development scores is inconclusive. There was no evidence of serious adverse events. Eight trials had some concerns or high risk of bias, small-sized studies, and high heterogeneity between trials led to moderate to very low certainty of evidence. CONCLUSIONS: Zinc supplementation in preterm or LBW infants have benefits on growth and diarrhea prevention. Further research is needed to generate better quality evidence.

Enteral Vitamin D Supplementation in Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Many preterm and low birth weight (LBW) infants have low vitamin D stores. The objective of this study was to assess effects of enteral vitamin D supplementation compared with no vitamin D supplementation in human milk fed preterm or LBW infants. METHODS: Data sources include Cochrane Central Register of Controlled Trials, Medline, and Embase from inception to March 16, 2021. The study selection included randomized trials. Data were extracted and pooled with fixed and random-effects models. RESULTS: We found 3 trials (2479 participants) that compared vitamin D to no vitamin D. At 6 months, there was increase in weight-for-age z-scores (mean difference 0.12, 95% confidence interval [CI] 0.01 to 0.22, 1 trial, 1273 participants), height-for-age z-scores (mean difference 0.12, 95% CI 0.02 to 0.21, 1 trial, 1258 participants); at 3 months there was decrease in vitamin D deficiency (risk ratio 0.58, 95% CI 0.49 to 0.68, I2=58%, 2 trials, 504 participants) in vitamin D supplementation groups. However, there was little or no effect on mortality, any serious morbidity, hospitalization, head circumference, growth to 6 years and neurodevelopment. The certainty of evidence ranged from very low to moderate. Fourteen trials (1969 participants) assessed dose and reported no effect on mortality, morbidity, growth, or neurodevelopment, except on parathyroid hormone and vitamin D status. No studies assessed timing. Limitations include heterogeneity and small sample size in included studies. CONCLUSIONS: Enteral vitamin D supplementation improves growth and vitamin D status in preterm and LBW infants.

Anthropometric Indicators as Predictors of Mortality in Early Life Among Low Birthweight Indian Infants.

Background: Low birthweight (LBW) babies (<2.5 kg) are at higher risk of mortality and weight for height z score is currently recommended for identifying infants at risk of mortality. Objective: To compare different anthropometric measures at 28-day of age in a cohort of LBW Indian infants for predicting mortality between 28-day and 180-day of age. Methods: We used data from an individually randomized controlled trial of LBW infants weighing between 1,500 and 2,250 g. Sensitivity, specificity, positive, and negative likelihood ratios, positive and negative predictive values, and area under receiver operating characteristics curves (AUC) were used to estimate the discrimination of mortality risk. The Cox regression was used to estimate hazard ratios and population attributable fraction for each anthropometric indicator. These estimates were calculated for individual as well as combinations of anthropometric indicators at the cut-off of -2 and -3 SD of the WHO 2006 growth standards. Results: Severe underweight (weight-for-age z-scores [WAZ] < -3) had a sensitivity of 75.0%, specificity of 68.0% with an AUC of 0.72. The risk of death was higher (HR 6.18; 95% CI 4.29-8.90) with a population attributable fraction of 0.63 (95% CI 0.52-0.72) for infants severely underweight at 28-day of age. Combination of different anthropometric measures did not perform better than individual measures. Conclusion: Severe underweight (WAZ < -3) better discriminated deaths among LBW infants < 6 months of age. It can be considered for diagnosis of nutritionally at-risk infants in this age group. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT02653534].

Linear Growth Trajectories, Catch-up Growth, and Its Predictors Among North Indian Small-for-Gestational Age Low Birthweight Infants: A Secondary Data Analysis.

Background: Low birthweight small-for-gestational-age (SGA-LBW) (birthweight below the 10th percentile for gestational age; SGA-LBW) infants are at an increased risk of poor postnatal growth outcomes. Linear growth trajectories of SGA-LBW infants are less studied in South Asian settings including India. Objectives: To describe the linear growth trajectories of the SGA-LBW infants compared with appropriate-for-gestational-age LBW (AGA-LBW) infants during the first 6 months of life. In addition, we estimated catch-up growth (ΔLAZ > 0.67) in SGA-LBW infants and their performance against the WHO linear growth velocity cut-offs. Additionally, we studied factors associated with poor catch-up growth in SGA-LBW infants. Methods: The data utilized came from an individually randomized controlled trial that included low birthweight (LBW) infants weighing 1,500-2,250 g at birth. A total of 8,360 LBW infants were included. For comparison between SGA-LBW and AGA-LBW infants, we presented unadjusted and adjusted estimates for mean differences (MDs) or risk ratios (RRs) for the outcomes of length, linear growth velocity, length for age z-score (LAZ) score, and stunting. We estimated the proportion of catch-up growth. Generalized linear models of the Poisson family with log links were used to identify factors associated with poor catch-up growth in SGA-LBW infants. Results: Low birthweight small-for-gestational-age infants had a higher risk of stunting, lower attained length, and a lower LAZ score throughout the first 6 months of life compared with AGA-LBW infants, with differences being maximum at 28 days and minimum at 6 months of age. The linear growth velocity in SGA-LBW infants compared with AGA-LBW infants was significantly lower during the birth-28 day period [MD -0.19, 95% confidence interval (CI): -0.28 to -0.10] and higher during the 3- to 6-month period (MD 0.17, 95% CI: 0.06-0.28). Among the SGA-LBW infants, 55% showed catch-up growth for length at 6 months of age. Lower wealth quintiles, high birth order, home birth, male child, term delivery, non-exclusive breastfeeding, and pneumonia were associated with the higher risk of poor catch-up in linear growth among SGA-LBW infants. Conclusion: Small for gestational age (SGA) status at birth, independent of gestational age, is a determinant of poor postnatal linear growth. Promotion of institutional deliveries, exclusive breastfeeding, and prevention and early treatment of pneumonia may be helpful to improve linear growth in SGA-LBW infants during early infancy. Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [NCT02653534].

Estimating the Impact of COVID-19 Pandemic Related Lockdown on Utilization of Maternal and Perinatal Health Services in an Urban Neighborhood in Delhi, India.

Objective: To estimate utilization of maternal, perinatal healthcare services after the lockdown was implemented in response to the COVID-19 pandemic compared to the period before. Methods: This study conducted in Dakshinpuri, an urban neighborhood in Delhi, reports data over a 13-month period which includes the period "before lockdown" i.e., October 1, 2019 to March 21, 2020 and "after lockdown" i.e., March 22 to November 5, 2020. The period "after lockdown" included the lockdown phase (March 22 to May 31, 2020) and unlock phase (June 1 to November 5, 2020). Mothers delivered during this period in the study area were interviewed using semi-structured questionnaires. In-depth interviews (IDIs) were conducted in a subsample to understand the experiences, challenges, and factors for underutilization of healthcare services. Findings: The survey covered a total population of 21,025 in 4,762 households; 199 eligible mothers (mean age 27.4 years) were interviewed. In women who delivered after lockdown against before lockdown, adjusted odds of having >2 antenatal care visits in the third trimester was 80% lower (aOR 0.2, 95% CI 0.1-0.5); proportion of institutional deliveries was lower (93 vs. 97%); exclusive breastfeeding during first 6 months of birth (64.5 vs. 75.7%) and health worker home visitation within 6 weeks of birth (median, 1 vs. 3 visits) were substantially lower. Fear of contracting COVID-19, poor quality of services, lack of transportation and financial constraints were key issues faced by mothers in accessing health care. More than three-fourth (81%) of the mothers reported feeling down, depressed or hopeless after lockdown. The major factors for stress during lockdown was financial reasons (70%), followed by health-related concerns. Conclusion: COVID-19 pandemic-related lockdown substantially affected maternal and perinatal healthcare utilization and service delivery.

Prevalence of reproductive tract infections including sexually transmitted infections among married women in urban and peri-urban mid to low socioeconomic neighbourhoods of Delhi, North India: an observational study protocol.

INTRODUCTION: The Global Health Sector Strategy on sexually transmitted infections (STIs), endorsed by the World Health Assembly in 2016 aims to end STIs as public health threat by 2030. WHO conducts global estimates of prevalence to monitor progress towards achieving the same. However, limited laboratory confirmed data exist of STIs and reproductive tract infections (RTIs) apart from few prevalence surveys among key populations and clinic-based reports, including in India. Syndromic approach is the cornerstone of RTI/STI management and to maximise the diagnostic accuracy, there is a need to determine the main aetiologies of vaginal discharge. This study aims to estimate the prevalence of common STIs and RTIs and their aetiological organisms in symptomatic and asymptomatic women living in the urban and peri-urban, mid to low socioeconomic neighbourhoods of Delhi, North India. METHODS AND ANALYSIS: A cross-sectional study will be conducted among 440 married women who participated in the 'Women and Infants Integrated Interventions for Growth Study (WINGS)'. Information on sociodemographic profile, sexual and reproductive health will be collected, followed by examination and collection of vaginal swabs for nucleic acid amplification tests to diagnose Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis and microscopy to identify bacterial vaginosis and Candida albicans. Treatment will be as per the syndromic approach recommendations in the Indian National Guidelines. Data will be analysed to estimate prevalence, presence of symptoms and signs associated with laboratory confirmed RTIs/STIs using STATA V.16.0 (StataCorp). ETHICS AND DISSEMINATION: This study protocol has been approved by the ethics review committees of the WHO and Society for Applied Studies (SAS/ERC/RHR-RTI/STI/2020). Approval has been obtained by the WINGS investigators from SAS ethics research committee to share the contact details of the participants with the investigators. The findings will be published in peer-reviewed journals and disseminated through scientific conferences. TRIAL REGISTRATION NUMBER: CTRI/2020/03/023954.

Characteristics, experiences and actions taken by women to address delayed conception: A mixed-methods cross-sectional study protocol.

BACKGROUND: The impact of infertility on mental, emotional, physical and sexual health is grave, particularly in a pronatalist society. Literature is replete with evidence of wide ranging psychosocial consequences of infertility in women, indicating the need for identifying the gaps and designing appropriate context specific interventions to improve access and utilization of services. Data that are accessible, primarily from infertility clinics and women visiting hospitals for infertility treatment; information from community settings is rare. This is a protocol paper for a study to understand women's experiences and actions taken by them to cope with delayed conception. METHODS: Mixed-methods cross-sectional design is used to obtain deep insights into the experiences of delayed conception, coping mechanisms, medical assistance and other help sought. Information is also being obtained on socio-demographic profile, fertility intentions, fertility quality of life, general medical history, obstetric, gynecological and sexual history, substance use and mental health status. A sample of 1530 women will be administered 4 modules of a quantitative survey. Focus group discussions, about four or till saturation point, will be conducted using purposive sampling. The study is recruiting from a population of women who previously participated in the 'Women and Infants Integrated Interventions for Growth Study (WINGS) and failed to conceive during 18 months follow up period. Data collected through questionnaire will be assembled, cleaned, analyzed and reported. The findings will be disseminated through reports with the ethics review committee, government entities, academic and research publications. DISCUSSION: This study will provide insights on the experiences and coping strategies of women with delayed conception in the study community. Results will assist in designing appropriate interventions to meet the holistic health and psychosocial needs of women with delayed conception and promote sexual and reproductive health within the broader framework of Sustainable Development Goals and Universal health coverage. TRIAL REGISTRATION: Trial registration number: CTRI/2020/03/023955.

Postpartum contraceptive practices among urban and peri-urban women in North India: a mixed-methods cohort study protocol.

BACKGROUND: Postpartum family planning (PPFP) helps women space childbirths, increase exclusive breastfeeding and prevent unintended pregnancies, leading to reduction in maternal, infant and child morbidities and mortality. Unmet need of family planning is highest among women in the postpartum period due to lack of knowledge, cultural and religious barriers, access barriers and low antenatal care service utilization. However, in spite of low prevalence of postpartum family planning practices, birth-to-birth interval is reportedly high in Delhi, India. This study explores the postpartum contraception practices and the relationship between use of postpartum contraception and subsequent child linear growth. METHODS: This is a mixed method cohort study on PPFP and is nested within an ongoing "Women and Infants Integrated Interventions for Growth Study" (WINGS). Married women aged 18-30 years who have delivered a live baby are recruited for quantitative interviews at 6 weeks, 6, 12, and 24 months postpartum. In-depth interviews are conducted with a randomly selected sub-sample of women at each of the four time points, 35 husbands and 20 local service providers to understand their perspectives on PPFP practices. DISCUSSION: The findings from the study will provide useful insights into couples' contraception preferences and choice of contraception, modern and traditional, initiation time and the effect of birth spacing and contraception use on subsequent linear growth of the child. This knowledge will be of significant public health relevance and will help in designing appropriate interventions for appropriate postpartum contraception use and delivery strategies. The study aims to work address the Sexual and Reproductive Health and Rights goal of promoting reproductive health, voluntary and safe sexual and reproductive choices for women. TRIAL REGISTRATION: Trial registration number: CTRI/2020/03/023954 .