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Objective This umbrella review synthesises evidence on the methods used to recruit and retain ethnically diverse participants and report and analyse variables related to ethnic diversity in randomised controlled trials.Design Umbrella review.Data sources Ovid MEDLINE, Ovid Embase, CINAHL, PsycINFO and Cochrane and Campbell Libraries for review papers published between 1 January 2010 and 13 May 2024.Eligibility criteria English language systematic reviews focusing on inclusion and reporting of ethnicity variables. Methodological quality was assessed using the AMSTAR 2 tool.Results Sixty-two systematic reviews were included. Findings point to limited representation and reporting of ethnic diversity in trials. Recruitment strategies commonly reported by the reviews were community engagement, advertisement, face-to-face recruitment, cultural targeting, clinical referral, community presentation, use of technology, incentives and research partnership with communities. Retention strategies highlighted by the reviews included frequent follow-ups on participants to check how they are doing in the study, provision of incentives, use of tailored approaches and culturally appropriate interventions. The findings point to a limited focus on the analysis of variables relevant to ethnic diversity in trials even when they are reported in trials.Conclusion Significant improvements are required in enhancing the recruitment and retention of ethnically diverse participants in trials as well as analysis and reporting of variables relating to diversity in clinical trials.PROSPERO registration number CRD42022325241.

IntroductionThe prevalence of underweight in women of reproductive age (WRA) in South Asia remains unacceptably high. Underweight women suffer from lowered immunity, infertility, and a risk of developing non-communicable diseases. In pregnancy, undernutrition results in poor neonatal and maternal outcomes. We present the findings and the management strategy of undernutrition in the preconception and pregnancy phase intervention group in the WING study in low- to lower-middle-income neighborhoods of North India.MethodsWe analyzed data from the Women and Infants Integrated Interventions for Growth Study (WINGS) intervention group. In this individually randomized factorial design trial, 13,500 women were enrolled from low to middle-income neighborhoods of Delhi: 6,722 women in the preconception group and 2,640 from the pregnancy group. Food supplements in the form of locally prepared snacks were given to provide necessary calories and protein requirements as per the Body mass index (BMI) during the preconception period and each trimester of pregnancy. The snacks (sweet or savory) and milk or egg as a source of high-quality protein were delivered at home, and intakes were observed. Individual tracking and close monthly monitoring were done for compliance, besides screening and treatment of infections.ResultsThe enrolled women's mean (SD) age was 24.2 (3.1) years. Approximately 35% of women had a height of < 150 cm, and 50% had schooling >12 years. 17% of women in preconception and 14 % in pregnancy intervention groups were Underweight. Approximately two-thirds of underweight women improved 9–12 months after management in the preconception group, and the same proportion improved 4 weeks after management during pregnancy. The proportion of women with inadequate weight gain (IWG) during pregnancy was higher in women who were underweight during preconception.DiscussionA comprehensive approach to managing undernutrition with high-quality energy-dense food supplementation substantially improved weight gain in women during preconception and pregnancy.Clinical trial registrationhttp://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339%26EncHid=%26userName=societyforappliedstudies, identifier: Clinical Trial Registry India #CTRI/2017/06/008908.

Abstract Background Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains—health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating. Methods An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata of 1300 preterm and 1300 term SGA infants each to receive the intervention package or routine care. Infants will be followed until 12 months of age. Outcome data will be collected by an independent outcome ascertainment team at infant ages 1, 3, 6, 9, and 12 months and at 2, 6, and 12 months after delivery for mothers. Discussion The findings of this study will indicate whether providing an intervention that addresses factors known to limit growth and neurodevelopment can offer substantial benefits to preterm or term SGA infants. The results from this study will increase our understanding of growth and development and guide the design of public health programs in low- and middle-income settings for vulnerable infants. Trial registration The trial has been registered prospectively in Clinical Trial Registry – India # CTRI/2021/11/037881, Registered on 08 November 2021.

Abstract Aim To synthesize available evidence on the association between change in linear growth (height for age z score, HAZ) beyond the first two years of life with later child neurodevelopment outcomes in Low- and middle-income countries (LMICs). Methods We searched PubMed, Web of Science, and EMBASE for cohort studies on the association between change in HAZ after age two and neurodevelopment outcomes in middle or late childhood. Data extraction was done independently by two reviewers. Results A total of 21 studies, that included 64,562 children from 13 LMICs were identified. Each unit increase in change in HAZ above two years is associated with a + 0.01 increase (N = 8 studies, 27,393 children) in the cognitive scores at 3.5 to 12 years of age and a + 0.05-standard deviation (SD) increase (95% CI 0.02 to 0.08, N = 3 studies, 17,830 children) in the language score at 5 to 15 years of age. No significant association of change in HAZ with motor (standardized mean difference (SMD) 0.04; 95% CI: -0.10, 0.18, N = 1 study, 966 children) or socio-emotional scores (SMD 0.00; 95% CI: -0.02, 0.01, N = 4 studies, 14,616 participants) was observed. Conclusion Changes in HAZ after the first two years of life appear to have a small or no association with child neurodevelopment outcomes in LMICs.

Background: The burden of wasting among under five children in India, has not reduced in the last decade. Objectives: We used child-level data from the latest nationally representative Comprehensive National Nutritional Survey (CNNS) to estimate the prevalence of wasting at the national and state level in India. Methods: We explored the association of wasting with maternal, child and household factors using multivariable logistic regression for the age group of 0-5, 6-23 and 24-59 months. Results: The overall prevalence of wasting was 17.3%, ranging from 5.8% to 29.1% across states, 23.3% in children 0-5 months, 19.6 % in children 6-23 months and 15.4 % in children 24-59 months of age. Higher birthweight i.e., every 100g increase (0-5 months aOR = 0.96, 6-23 months aOR = 0.94, 24-59 months aOR = 0.96), higher maternal BMI (0-5 months aOR = 0.51, 6-23 months aOR = 0.62, 24-59 months aOR = 0.67), increasing child age in months (0-5 months aOR = 0.84) and female sex of the child (24-59 months aOR = 0.82) was found to have significantly lower odds of wasting. The odds of wasting were significantly higher for poorest wealth quintile (0-5 months aOR = 1.99, 6-23 months aOR = 2.13), maternal unemployment (0-5 months aOR = 2.25), and lower levels of maternal education (6-23 months aOR = 1.74). Conclusions: Our analyses showed that burden of wasting continues to remain high in India. Preventive interventions must target reduction of low birthweight. Early identification and management of wasting should be done, especially during the first six months of life who are not part of current therapeutic feeding programme.

Abstract Objectives: To assess the impact of nutritional and multiple-micronutrient supplementation to lactating mothers on the micronutrient status of mother–infant dyad at 6 months of age postnatally. Design: This study was a trial that aimed to investigate the impact of maternal nutritional supplementation on infant growth. A secondary objective was to assess the effect on the micronutrient status of mother–infant pairs. The intervention group mothers received snacks with 600 kcal energy, 20 g protein and daily micronutrient tablets. Setting: Blood samples were collected from both mothers and infants at 6 months. Participants: The participants in this study were mother–infant pairs. The micronutrient status of these pairs was assessed through blood samples, focusing on vitamins A, D, B12, ferritin, Zn and folate. Results: Micronutrient analysis of serum samples from 600 mother–infant pairs showed that mothers in the intervention group had higher levels of serum ferritin (mean difference (MD) 14·7 ng/ml), retinol (MD 0·6 μmol/l), folate (MD 3·3 ng/ml) and vitamin D (1·03 ng/ml) at 6 months postpartum. Additionally, the supplementation was associated with a higher mean ± sd of serum ferritin (MD 8·9 ng/ml) and vitamin A (MD 0·2 μmol/l) levels in infants at 6 months. Conclusions: The study found that supplementing maternal nutrition with additional dietary and micronutrient intakes during lactation improved maternal micronutrient status and slightly increased ferritin and vitamin A levels in infants at 6 months. The findings highlight the importance of nutritional interventions for improving the micronutrient health of mother–infant pairs, with significant public health implications. Trial registered at www.clinicaltrials.gov (CTRI/2018/04/013095).

Abstract 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.

Abstract 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 ).

BackgroundShort 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.ObjectiveTo 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.MethodsWe 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.ResultsAmongst 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

Abstract Background The burden of gestational diabetes mellitus (GDM) appears to be increasing in India and may be related to the double burden of malnutrition. The population-based incidence and risk factors of GDM, particularly in lower socio-economic populations, are not known. We conducted analyses on data from a population-based cohort of pregnant women in South Delhi, India, to determine the incidence of GDM, its risk factors and association with adverse pregnancy outcomes (stillbirth, preterm birth, large for gestational age babies) and need for caesarean section. Methods We analyzed data from the intervention group of the Women and Infants Integrated Interventions for Growth Study (WINGS), an individually randomized factorial design trial. An oral glucose tolerance test (OGTT) was performed at the time of confirmation of pregnancy, and for those who had a normal test (≤140 mg), it was repeated at 24–28 and at 34–36 weeks. Logistic regression was performed to ascertain risk factors associated with GDM. Risk ratios (RR) were calculated to find association between GDM and adverse pregnancy outcomes and need for caesarean section. Results 19.2% (95% CI: 17.6 to 20.9) pregnant women who had at least one OGTT were diagnosed to have GDM. Women who had prediabetes at the time of confirmation of pregnancy had a significantly higher risk of developing GDM (RR 2.08, 95%CI 1.45 to 2.97). Other risk factors independently associated with GDM were woman’s age (adjusted OR (AOR) 1.10, 95% CI 1.06 to 1.15) and BMI (AOR 1.04, 95% CI 1.01 to 1.07). Higher maternal height was found to be protective factor for GDM (AOR 0.98, 95% CI 0.96 to 1.00). Women with GDM, received appropriate treatment did not have an increase in adverse outcomes and no increased need for caesarean section Conclusions A substantial proportion of pregnant women from a low to mid socio-economic population in Delhi had GDM, with older age, higher BMI and pre-diabetes as important risk factors. These findings highlight the need for interventions for prevention and provision of appropriate management of GDM in antenatal programmes. Clinical trial registration Clinical Trial Registry – India, #CTRI/2017/06/008908 ( http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies ).

Abstract Background Kangaroo mother care (KMC) can substantially enhance overall survival of low birthweight babies. In a large randomized controlled trial, we recently showed that supporting mothers to provide community initiated KMC (ciKMC) can reduce mortality among infants up to 180 days of life by 25% (hazard ratio (HR) 0.75). With the current analysis, we aimed to explore if ciKMC promotion leads to increased inequity in survival. Methods In the trial we randomized 8402 low birthweight babies to a ciKMC (4480 babies) and a control (3922 babies) arm, between 2015 and 2018 in Haryana, India. We estimated the difference in concentration indices, which measure inequality, between babies in the ciKMC and control arms for survival until 180 days of life. Further, we compared the effect of ciKMC promotion across subgroups defined by socioeconomic status, caste, maternal literacy, infant’s sex, and religion. Results Our intervention did not increase survival inequity, as the concentration index in the ciKMC arm of the trial was 0.05 (95% CI -0.07 to 0.17) lower than in the control arm. Survival impact was higher among those belonging to the lower two wealth quintiles, those born to illiterate mothers and those belonging to religions other than Hindu. Conclusions We found that ciKMC promotion did not increase inequity in survival associated with wealth. The beneficial impact of ciKMC tended to be larger among vulnerable groups. Supporting mothers to provide KMC at home to low birthweight babies will not increase and could indeed reduce inequities in infant survival. Trial registration ClinicalTrials.gov, NCT02653534 . Registered January 12, 2016—Retrospectively registered.

Hypothyroidism is the commonest endocrine disorder of pregnancy, with known adverse feto-maternal outcomes. There is limited data on population-based prevalence, risk factors and outcomes associated with treatment of hypothyroidism in early pregnancy. We conducted analysis on data from an urban and peri-urban low to mid socioeconomic population-based cohort of pregnant women in North Delhi, India to ascertain the burden, risk factors and impact of treatment, on adverse pregnancy outcomes- low birth weight, prematurity, small for gestational age and stillbirth. This is an observational study embedded within the intervention group of the Women and Infants Integrated Interventions for Growth Study, an individually randomized factorial design trial. Thyroid stimulating hormone was tested in 2317 women in early (9-13 weeks) pregnancy, and thyroxin replacement started hypothyroid (TSH ≥2.5mIU/mL). Univariable and multivariable generalized linear model with binomial family and log link were performed to ascertain risk factors associated with hypothyroidism and association between hypothyroidism and adverse pregnancy outcomes. Of 2317 women, 29.2% (95% CI: 27.4 to 31.1) had hypothyroidism and were started on thyroxin replacement with close monitoring. Overweight or obesity was associated with increased risk (adjusted RR 1.29, 95% CI 1.10 to 1.51), while higher hemoglobin concentration was associated with decreased risk (adjusted RR 0.93, 95% CI 0.88 to 0.98 for each g/dL) for hypothyroidism. Hypothyroid women received appropriate treatment with no increase in adverse pregnancy outcomes. Almost a third of women from low to mid socio-economic population had hypothyroidism in early pregnancy, more so if anemic and overweight or obese. With early screening and adequate replacement, adverse pregnancy outcomes may be avoided. These findings highlight the need in early pregnancy for universal TSH screening and adequate treatment of hypothyroidism; as well as for attempts to reduce pre and peri-conception overweight, obesity and anemia. Clinical trial registration: Clinical trial registration of Women and Infants Integrated Interventions for Growth Study Clinical Trial Registry-India, #CTRI/2017/06/008908; Registered on: 23/06/2017, (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies).

BackgroundThere is a paucity of studies which have examined associations between ultrasound based fetal anthropometric parameters and neurodevelopment in all infants. We examined the association between ultrasound based fetal anthropometric parameters and neurodevelopment in all infants through a secondary analysis of data collected in a large community based randomized controlled trial.MethodsA total of 1465 mother-child dyads were included. Ultrasound based fetal anthropometric parameters which included the head circumference (HC), abdominal circumference (AC), femur length (FL), biparietal diameter (BPD) and transcerebellar diameter (TCD) were collected at 26-28 weeks of gestation and their association with neurodevelopment at 24 months of age was examined.ResultsOnly the transcerebellar diameter z score was positively associated +0.54 units (95% CI: 0.15, 0.93) with motor composite score. When the neurodevelopment outcomes were analyzed as categorical, none of the fetal variables were associated with risk of moderate to severe neurodevelopment impairment.ConclusionThe findings suggest that transcerebellar diameter could be useful for early prediction of neurodevelopmental outcomes in childhood.Clinical trial registrationClinical trial registration of Women and Infants Integrated Interventions for Growth Study Clinical Trial Registry-India, #CTRI/2017/06/008908; Registered on: 23/06/2017, (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies).

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

Abstract 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.

Background Low birth weight (LBW), including preterm birth (PTB) and small for gestational age (SGA), contributes a significant global health burden. We aimed to summarise current evidence on the effect of preconception and periconception interventions on LBW, SGA and PTB.Methods In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library and WHO Global Index Medicus for randomised controlled trials and quasi-experimental studies published by 28 November 2020, which assessed interventions delivered in preconception and periconception or preconception and pregnancy. Primary outcomes were LBW, SGA and PTB. Studies were categorised by intervention type and delivery during preconception and periconception or during preconception and pregnancy. Estimates were pooled using fixed-effects or random-effects restricted maximum likelihood method meta-analyses. Quality of evidence for primary outcomes was assessed using the Grades of Recommendations, Assessment, Development and Evaluation approach.Results We included 58 studies. Twenty-eight studies examined nutrition interventions (primarily micronutrient or food supplementation). Thirty studies (including one reporting a nutrition intervention) provided health interventions (general preconception health, early adverse pregnancy outcome prevention, non-communicable disease and infectious disease prevention and management). One study assessed a social intervention (reproductive planning). Studies varied in terms of specific interventions, including delivery across preconception or pregnancy, resulting in few studies for any single comparison. Overall, the evidence was generally very uncertain regarding the impact of any intervention on LBW, SGA and PTB. Additionally, preconception and periconception nutritional supplementation containing folic acid was associated with reduced risk of birth defects (10 studies, N=3 13 312, risk ratio: 0.37 (95% CI: 0.24 to 0.55), I2: 74.33%).Conclusion We found a paucity of evidence regarding the impact of preconception and periconception interventions on LBW, SGA and PTB. Further research on a wider range of interventions is required to clearly ascertain their potential effectiveness.Trial registration number This review was prospectively registered with PROSPERO (CRD42020220915).

Abstract Background Weight for length z-score (WLZ)

BackgroundLow birthweight (LBW) babies (

BackgroundLow 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.ObjectivesTo 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.MethodsThe 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.ResultsLow 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.ConclusionSmall 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].

Abstract Background Faltering of growth in early life has been recognized as a public health challenge among Indian babies. A two-day consultation on growth faltering in early infancy was organized to examine the data and evidence on identification and management of early growth failure and to identify knowledge gaps and future areas of research. The consultation was supported by the Biotechnology Industry Research Assistance Council (BIRAC), the Indian Academy of Pediatrics (Nutrition Chapter), Vardhman Mahavir Medical College and Safdarjung Hospital, and the Society for Applied Studies. It brought together researchers, clinicians, policy makers and program managers.

Abstract Background In a randomized controlled trial (RCT) with 8402 stable low birthweight (LBW) infants, majority being late preterm or term small for gestational age, community-initiated KMC (ciKMC) showed a significant improvement in survival. However, the effect of ciKMC on neurodevelopment is unclear. This is important to elucidate as children born with low birth weight are at high risk of neurodevelopmental deficits. In the first 552 stable LBW infants enrolled in the above trial, we evaluated the effect of ciKMC on neurodevelopmental outcomes during infancy. Method This RCT was conducted among 552 stable LBW infants, majorly late preterm or term small for gestational age infants without any problems at birth and weighing 1500–2250 g at birth. The intervention comprised of promotion of skin-to-skin contact and exclusive breastfeeding by trained intervention delivery team through home visits. The intervention group mother-infant-dyads were supported to practice ciKMC till day 28 after birth or until the baby wriggled-out. All infants in the intervention and control groups received Home Based Post Natal Care (HBPNC) visits by government health workers. Cognitive, language, motor and socio-emotional outcomes were assessed at infant-ages 6- and 12-months using Bayley Scale of Infant Development (BSID-III). Other outcomes measured were infant temperament, maternal depression, maternal sense of competence, mother-infant bonding and home-environment. We performed post-hoc equivalence testing using two one-sided tests of equivalence (TOST) to provide evidence that ciKMC does not do harm in terms of neurodevelopment. Results In the intervention arm, the median (IQR) time to initiate ciKMC was 48 (48 to 72) hours after birth. The mean (SD) duration of skin-to-skin-contact was 27.9 (3.9) days with a mean (SD) of 8.7 (3.5) hours per day. We did not find significant effect of ciKMC on any of the child developmental outcomes during infancy. The TOST analysis demonstrated that composite scores for cognitive, language and motor domains at 12 months among the study arms were statistically equivalent. Conclusion Our study was unable to capture any effect of ciKMC on neurodevelopment during infancy in this sample of stable late preterm or term small for gestational age infants. Long term follow-up may provide meaningful insights. Trial registration The trial is registered at clinicaltrials.gov NCT02631343 dated February 17, 2016; Retrospectively registered.

Abstract Background Vitamin D is important for brain function and linear growth. Vitamin D deficiency during pregnancy has been linked with impaired neurodevelopment during early childhood. However, there is limited evidence from population-based studies on the long-term impact of vitamin D deficiency on cognitive development and linear growth. The objective of the current analysis is to examine whether vitamin D deficiency during infancy and early childhood is associated with cognitive development and linear growth measured in school age. Methods This is a follow-up study of a placebo-controlled trial among 1000 North Indian children 6–30 months of age. We measured growth and neurodevelopment in 791 of these children when they were 6–9 years old. Neurodevelopment was measured using the Wechsler Intelligence Scale for Children, 4th edition INDIA, the Crichton Verbal Scale, NEPSY-II subtests, and the BRIEF 2. We categorized vitamin D concentrations during infancy and early childhood according to the US Institute of Medicine’s recommendations; serum 25(OH)D 20 ng/ml as sufficient. In multivariable regression models, adjusting for relevant confounders, we estimated the association between vitamin D status, growth and neurodevelopmental outcomes. Results Among the 791 children, baseline vitamin D status was available for 716. Of these, 45.8% were vitamin D deficient, 32.7% were inadequate, and 21.5% were sufficient. Vitamin D status was not associated with any of the cognitive outcomes or linear growth [Adjusted β coefficient for height for age z-score between deficient and sufficient children was − 0.06 (95% CI − 0.24 to 0.11)] at follow up. Conclusion Our findings do not support the notion that poor vitamin D status in early childhood is an important limitation for cognitive development and linear growth. Trial Registration The trial was first registered at www.clinicaltrials.gov as NCT00717730 in July, 2008, and at CTRI/2010/091/001090 in August, 2010 and then as CTRI/2016/11/007494 in November 2016.

ObjectiveTo estimate utilization of maternal, perinatal healthcare services after the lockdown was implemented in response to the COVID-19 pandemic compared to the period before.MethodsThis 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.FindingsThe 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.ConclusionCOVID-19 pandemic-related lockdown substantially affected maternal and perinatal healthcare utilization and service delivery.

Abstract Despite the high prevalence of inadequate gestational weight gain (GWG) and adverse pregnancy outcomes, very few studies have addressed the association between GWG and pregnancy outcomes in South Asia. Our objectives were to estimate the prevalence of GWG during the second and third trimesters within, below and above the Institute of Medicine (IOM) guidelines, and to estimate the effect of the rate and adequacy of GWG on gestational age at the time of delivery, weight, length, length‐for‐age z‐score (LAZ), weight‐for‐length z‐score (WLZ) and adverse pregnancy outcomes, namely prematurity, small‐for‐gestational age (SGA), low birth weight (LBW), stunting and wasting at birth. We analysed data from the intervention group of the Women and Infants Integrated Interventions for Growth Study (WINGS), which is an ongoing individually randomized factorial design study. Of the 1332 women analysed, 40.2% [95% confidence interval (CI) 37.5 to 42.8] had GWG below the IOM guidelines. For every 100‐g/week increase in GWG, birth weight increased by 61 g, birth length by 0.16 cm, LAZ score by 0.08 SD, WLZ score by 0.14 SD, and gestational age at birth by 0.48 days. Women with GWG below the IOM guidelines had a higher relative risk of adverse pregnancy outcomes (44% for LBW, 27% for SGA, 32% for stunting and 42% for wasting at birth) than women who had GWG within the IOM guidelines, except for prematurity. The association between GWG and LAZ scores at birth was modified by early pregnancy body mass index (BMI). GWG is a strong predictor of newborn anthropometric outcomes and duration of gestation but not prematurity.

Objectives Kangaroo Mother Care (KMC), prolonged skin-to-skin care of the low birth weight baby with the mother plus exclusive breastfeeding reduces neonatal mortality. Global KMC coverage is low. This study was conducted to develop and evaluate context-adapted implementation models to achieve improved coverage.Design This study used mixed-methods applying implementation science to develop an adaptable strategy to improve implementation. Formative research informed the initial model which was refined in three iterative cycles. The models included three components: (1) maximising access to KMC-implementing facilities, (2) ensuring KMC initiation and maintenance in facilities and (3) supporting continuation at home postdischarge.Participants 3804 infants of birth weight under 2000 g who survived the first 3 days, were available in the study area and whose mother resided in the study area.Main outcome measures The primary outcomes were coverage of KMC during the 24 hours prior to discharge and at 7 days postdischarge.Results Key barriers and solutions were identified for scaling up KMC. The resulting implementation model achieved high population-based coverage. KMC initiation reached 68%–86% of infants in Ethiopian sites and 87% in Indian sites. At discharge, KMC was provided to 68% of infants in Ethiopia and 55% in India. At 7 days postdischarge, KMC was provided to 53%–65% of infants in all sites, except Oromia (38%) and Karnataka (36%).Conclusions This study shows how high coverage of KMC can be achieved using context-adapted models based on implementation science. They were supported by government leadership, health workers’ conviction that KMC is the standard of care, women’s and families’ acceptance of KMC, and changes in infrastructure, policy, skills and practice.Trial registration numbers ISRCTN12286667; CTRI/2017/07/008988; NCT03098069; NCT03419416; NCT03506698.

Introduction Young infants 7–59 days old with fast breathing pneumonia presented to a primary level health facility receive a 7-day course of amoxicillin as per the WHO guideline. However, community-level health workers (CLHW) are not allowed to treat these infants. This trial evaluated the community level treatment of non-hypoxaemic young infants with fast breathing pneumonia by CLHWs.Methods This cluster-randomised, open-label, non-inferiority trial was conducted in rural areas of Bangladesh, Ethiopia, India and Malawi. We randomly allocated clusters (first-level health facility) 1:1, stratified by the population size, to an intervention group (enhanced community case management) or control group (standard community case management). Infants aged 7–59 days with a respiratory rate of ≥60 breaths/min and oxygen saturation (SpO2) ≥90% were enrolled. In the intervention clusters, these infants were treated with a 7-day course of oral amoxicillin (according to WHO weight bands) and were regularly followed up by CLHWs. In the control clusters, CLHWs continued the standard management (assess and refer after pre-referral antibiotic dose) and followed up according to the national programme guideline. The primary outcome of treatment failure was assessed in both groups by independent outcome assessors on days 6 and 14 after enrolment. Secondary outcomes (accuracy and impact of pulse oximetry) were also assessed.Results Between September 2016 and December 2018, we enrolled 2334 infants (1168 in intervention and 1166 in control clusters) from 208 clusters (104 intervention and 104 control). Of 2334, 22 infants with fast breathing were excluded from analysis, leaving 2312 (1155 in intervention clusters and 1157 in control clusters) for intention-to-treat analysis. The proportion of treatment failure was 5.4% (63/1155) in intervention and 6.3% (73/1157) in the control clusters, including two deaths (0.2%) in each group. The adjusted risk difference for treatment failure between the two groups was −1.0% (95% CI −3.0% to 1.1%). The secondary outcome showed that CLHWs in the intervention clusters performed all recommended steps of pulse oximetry assessment in 94% (1050/1115) of enrolled patients.Conclusions The 7-day amoxicillin treatment for 7–59 days old non-hypoxaemic infants with fast breathing pneumonia by CLHWs was non-inferior to the currently recommended referral strategy.Trial registration numbers CTRI/2017/02/007761 and ACTRN12617000857303.

Abstract Background The period from conception to two years of life denotes a critical window of opportunity for promoting optimal growth and development of children. Poor nutrition and health in women of reproductive age and during pregnancy can negatively impact birth outcomes and subsequent infant survival, health and growth. Studies to improve birth outcomes and to achieve optimal growth and development in young children have usually tested the effect of standalone interventions in pregnancy and/or the postnatal period. It is not clearly known whether evidence-based interventions in the different domains such as health, nutrition, water sanitation and hygiene (WASH) and psychosocial care, when delivered together have a synergistic effect. Further, the effect of delivery of an intervention package in the pre and peri-conception period is not fully understood. This study was conceived with an aim to understand the impact of an integrated intervention package, delivered across the pre and peri-conception period, through pregnancy and till 24 months of child age on birth outcomes, growth and development in children. Methods An individually randomized controlled trial with factorial design is being conducted in urban and peri-urban low- to mid-socioeconomic neighbourhoods in South Delhi, India. 13,500 married women aged 18 to 30 years will be enrolled and randomized to receive either the pre and peri-conception intervention package or routine care (first randomization). Interventions will be delivered until women are confirmed to be pregnant or complete 18 months of follow up. Once pregnancy is confirmed, women are randomized again (second randomization) to receive either the intervention package for pregnancy and postnatal period or to routine care. Newborns will be followed up till 24 months of age. The interventions are delivered through different study teams. Outcome data are collected by an independent outcome ascertainment team. Discussion This study will demonstrate the improvement that can be achieved when key factors known to limit child growth and development are addressed together, throughout the continuum from pre and peri-conception until early childhood. The findings will increase our scientific understanding and provide guidance to nutrition programs in low- and middle-income settings. Trial registration Clinical Trial Registry – India #CTRI/2017/06/008908; Registered 23 June 2017, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies

Abstract Objectives We examined the utilisation, equity and determinants of full antenatal care (ANC), defined as 4 or more antenatal visits, at least one tetanus toxoid (TT) injection and consumption of iron folic acid (IFA) for a minimum of 100 days, in India. Methods We analysed a sample of 190,898 women from India’s National Family Health Survey 4. Concentration curves and concentration index were used to assess equity in full ANC utilisation. Multivariable logistic regression model was used to examine the factors associated with full ANC utilisation. Results In India, 21% of pregnant women utilised full ANC, ranging from 2.3–65.9% across states. Overall, 51.6% had 4 or more ANC visits, 30.8% consumed IFA for atleast 100 days, and 91.1% had one or more doses of tetanus toxoid. Full ANC utilisation was inequitable across place of residence, caste and maternal education. Registration of pregnancy, utilisation of government’s Integrated Child Development Services (ICDS) and health insurance coverage were associated with higher odds of full ANC utilisation. Lower maternal education, lower wealth quintile(s), lack of father’s participation during antenatal visits, higher birth order, teenage and unintended pregnancy were associated with lower odds of full ANC utilisation. Conclusions Full ANC utilisation in India was inadequate and inequitable. Although half of the women did not receive the minimum recommended ANC visits, the utilisation of TT immunisation was almost universal. The positive association of full ANC with ICDS utilisation and child’s father involvement may be leveraged for increasing the uptake of full ANC. Strategies to address the socio-demographic factors associated with low and inequitable utilisation of full ANC are imperative for strengthening India’s maternal health program.

Introduction The COVID-19 pandemic is disrupting health systems globally. Maternity care disruptions have been surveyed, but not those related to vulnerable small newborns. We aimed to survey reported disruptions to small and sick newborn care worldwide and undertake thematic analysis of healthcare providers’ experiences and proposed mitigation strategies.Methods Using a widely disseminated online survey in three languages, we reached out to neonatal healthcare providers. We collected data on COVID-19 preparedness, effects on health personnel and on newborn care services, including kangaroo mother care (KMC), as well as disruptors and solutions.Results We analysed 1120 responses from 62 countries, mainly low and middle-income countries (LMICs). Preparedness for COVID-19 was suboptimal in terms of guidelines and availability of personal protective equipment. One-third reported routine testing of all pregnant women, but 13% had no testing capacity at all. More than 85% of health personnel feared for their own health and 89% had increased stress. Newborn care practices were disrupted both due to reduced care-seeking and a compromised workforce. More than half reported that evidence-based interventions such as KMC were discontinued or discouraged. Separation of the mother–baby dyad was reported for both COVID-positive mothers (50%) and those with unknown status (16%). Follow-up care was disrupted primarily due to families’ fear of visiting hospitals (~73%).Conclusion Newborn care providers are stressed and there is lack clarity and guidelines regarding care of small newborns during the pandemic. There is an urgent need to protect life-saving interventions, such as KMC, threatened by the pandemic, and to be ready to recover and build back better.

BackgroundChildren born with low birth weight (LBW) tend to have lower neurodevelopmental scores compared to term normal birth weight children. It is important to determine factors that influence neurodevelopment in these low birth weight children especially in the first 2-3 years of life that represents a period of substantial brain development.MethodsThis secondary data analysis was conducted using data from LBW infants enrolled soon after birth in an individually randomized controlled trial (RCT) and followed up till end of 1st year. Neurodevelopmental assessment was done at 12 months of corrected age by trained psychologists using Bayley Scales of Infant and Toddler Development 3rd edition (Bayley-III). Factors influencing cognitive, motor and language scores were determined using multivariable linear regression model.ResultsLinear growth (i.e., length for age z score, LAZ) [cognitive: Standardized ẞ-coefficient = 2.19, 95% CI; 1.29, 3.10; motor: 2.41, 95% CI; 1.59, 3.23; language: 1.37, 95% CI; 0.70, 2.04], stimulation at home [cognitive: 0.21, 95% CI; 0.15, 0.27; motor: 0.12, 95% CI; 0.07, 0.17; language: 0.21, 95% CI; 0.16, 0.25] and number of diarrhoeal episodes [cognitive: -2.87, 95% CI; -4.34, -1.39; motor: -2.62, 95% CI; -3.93, -1.29; language: -2.25, 95% CI; -3.32, -1.17] influenced the composite scores in all three domains i.e., cognitive, language and motor. While increase in LAZ score and stimulation led to increase in composite scores; an increase in number of diarrhoeal episodes was associated with decrease in scores. Weight for height z scores (WHZ) were associated with motor and language but not with cognitive scores. Additionally, a negative association of birth order with cognitive and language scores was noted.ConclusionsThe findings indicate the possible importance of promoting nutrition and preventing diarrhoea as well as ensuring optimal stimulation and nurturance at home for enhancing child development in LBW infants.

Abstract Background South Asia contributes substantially to global low birth weight population (i.e. those with birth weight

Abstract Background Low and middle income countries (LMICs), including India, contribute to a major proportion of low birth weight (LBW) infants globally. These infants require special care. Kangaroo Mother Care (KMC) in hospitals is a cost effective and efficacious intervention. In institutional deliveries, the duration of facility stay is often short. In LMICs, a substantial proportion of deliveries still occur at home and access to health care services is limited. In these circumstances, a pragmatic choice may be to initiate KMC at home for LBW babies. However, evidence is lacking on benefits of community-initiated KMC (cKMC). Promoting KMC at home without an understanding of its acceptability may lead to limited success. Methods We conducted formative research to assess the feasibility, acceptability and adoption of cKMC with the aim of designing an intervention package for a randomised controlled trial in LBW infants in Haryana, India. Qualitative methods included 40 in-depth interviews with recently delivered women and 6 focus group discussions, two each with fathers and grandfathers, grandmothers, and community health workers. A prototype intervention package to promote cKMC was developed and tested in 28 mother-infant pairs (of them, one mother had twins), using Household (HH) trials. Results We found that most mothers in the community recognized that babies born small required special care. In spite of not being aware of the practice of KMC, respondents felt that creating awareness of KMC benefits will promote practice. They expressed concerns about doing KMC for long periods because mothers needed rest after delivery. However, the cultural practice of recently delivered women not expected to be doing household chores and availability of other family members were identified as enablers. HH trials provided an opportunity to test the intervention package and showed high acceptability for KMC. Most mothers perceived benefits such as weight gain and increased activity in the infant. Conclusions Community-initiated KMC is acceptable by mothers and adoption rates are high. Formative research is essential for developing a strategy for delivery of an intervention. Trial registration Trial registration number CTRI/2015/10/006267. Name of Registry: Clinical Trials Registry - India. URL of Registry: http://ctri.nic.in/Clinicaltrials/login.php Date of Registration: 15/10/2015. Date of enrolment of the first participant to the trial: 18/04/2015.

Abstract Background Vitamin-D deficiency has been linked with impaired development in animal studies; however, the evidence from human studies is scanty. Evidence as to whether vitamin-D deficiency during early childhood affects growth is also limited and conflicting. We examined the extent to which vitamin-D deficiency (

Abstract Background Around 70% neonatal deaths occur in low birth weight (LBW) babies. Globally, 15% of babies are born with LBW. Kangaroo Mother Care (KMC) appears to be an effective way to reduce mortality and morbidity among LBW babies. KMC comprises of early and continuous skin-to-skin contact between mother and baby as well as exclusive breastfeeding. Evidence derived from hospital-based studies shows that KMC results in a 40% relative reduction in mortality, a 58% relative reduction in the risk of nosocomial infections or sepsis, shorter hospital stay, and a lower risk of lower respiratory tract infections in babies with birth weight

BackgroundThere is a growing interest in the life course approach for the prevention, early detection and subsequent management of morbidity in women of reproductive age to ensure optimal health and nutrition when they enter pregnancy. Reliable estimates of such morbidities are lacking. We report the prevalence of health or nutrition-related morbidities, specifically, anemia, undernutrition, overweight and obesity, sexually transmitted infections (STIs) or reproductive tract infections (RTIs), diabetes or prediabetes, hypothyroidism, hypertension, and depressive symptoms, during the preconception period among women aged 18 to 30 years.MethodsA cross-sectional study was conducted among 2000 nonpregnant married women aged 18 to 30 years with no or one child who wished to have more children in two low- to middle-income urban neighborhoods in Delhi, India, in the context of a randomized controlled trial. STIs and RTIs were measured by symptoms and signs, blood pressure by a digital device, height by stadiometer and weight by a digital weighing scale. A blood specimen was taken to screen for anemia, diabetes, thyroid disorders and syphilis. Maternal depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression analysis was performed to identify sociodemographic factors associated with individual morbidity.ResultsOverall, 58.7% of women were anemic; 16.5%, undernourished; 26%, overweight or obese; 13.2%, hypothyroid; and 10.5% with both symptoms and signs of STIs/RTIs. There was an increased risk of RTI/STI symptoms and signs in undernourished women and an increased risk of diabetes or prediabetes in overweight or obese women. An increased risk of undernutrition was also observed in women from lower categories of wealth quintiles. A decreased risk of moderate to severe anemia was seen in overweight women and those who completed at least secondary education.ConclusionsOur findings show a high burden of undernutrition, anemia, RTIs, hypothyroidism and prediabetes among women in the study. This information will aid policymakers in planning special programs for women of reproductive age.

BackgroundGovernment of India and the World Health Organization have guidelines for outpatient management of young infants 0-59 days with signs of Possible Serious Bacterial Infection (PSBI), when referral is not feasible. Implementation research was conducted to identify facilitators and barriers to operationalizing these guidelines.MethodsHimachal Pradesh government implemented the guidelines in program settings supported by Centre for Health Research and Development, Society for Applied Studies. The strategy included community sensitization, skill enhancement of Accredited Social Health Activists (ASHA), Auxiliary Nurse Midwives (ANMs) and Medical Officers (MOs) to identify PSBI and treat when referral was not feasible. The research team collected information on facilitators and barriers. A technical support unit provided training and oversight.FindingsAmong 1997 live births from June 2017 to January 2019, we identified 160 cases of PSBI in young infants resulting in a coverage of 80%, assuming an incidence of 10%. Of these,29(18.1%) had signs of critical illness (CI), 92 (57.5%) had clinical severe infection (CSI), 5 (3.1%)had severe pneumonia (only fast breathing in young infants 0-6 days), while 34 (21%) had pneumonia (only fast breathing in young infants 7-59 days). Hospital referral was accepted by 48/160 (30%), whereas 112/160 (70%) were treated with the simplified treatment regimens at primary level facilities. Of the 29 infants with CI, 18 (62%) accepted referral; 26 (90%) recovered while 3 (10%) who had accepted referral, died. Of the 92 infants who had CSI, 86 (93%) recovered, 65 (71%) received simplified treatment and one infant who had accepted referral, died. All the five infants who had severe pneumonia, recovered; 3 (60%) had received simplified treatment. Of the 34 pneumonia cases, 33 received simplified treatment of which 5 (15%) failed treatment; two out of these 5 died. Overall, 6/160 infants died (case-fatality-rate 3.4%); 2 in the simplified treatment (case-fatality-rate 1.8%) and 4 in the hospital group (case-fatality-rate 8.3%). Delayed identification and care-seeking by families and health system weaknesses like manpower gaps and interrupted supplies were challenges in implementation.ConclusionsImplementation of the guidelines in program settings is possible and acceptable. Scaling up would require creating community awareness, early identification and appropriate care-seeking, strengthening ASHA home-visitation program, building skills and confidence of MOs and ANMs, uninterrupted supplies and a dependable referral system.

Introduction Kangaroo Mother Care (KMC) is the practice of early, continuous and prolonged skin-to-skin contact between the mother and the baby with exclusive breastfeeding. Despite clear evidence of impact in improving survival and health outcomes among low birth weight infants, KMC coverage has remained low and implementation has been limited. Consequently, only a small fraction of newborns that could benefit from KMC receive it.Methods and analysis This implementation research project aims to develop and evaluate district-level models for scaling up KMC in India and Ethiopia that can achieve high population coverage. The project includes formative research to identify barriers and contextual factors that affect implementation and utilisation of KMC and design scalable models to deliver KMC across the facility-community continuum. This will be followed by implementation and evaluation of these models in routine care settings, in an iterative fashion, with the aim of reaching a successful model for wider district, state and national-level scale-up. Implementation actions would happen at three levels: ‘pre-KMC facility’—to maximise the number of newborns getting to a facility that provides KMC; ‘KMC facility’—for initiation and maintenance of KMC; and ‘post-KMC facility’—for continuation of KMC at home. Stable infants with birth weight

Summary: Background: Modelled mortality estimates have been useful for health programmes in low-income and middle-income countries. However, these estimates are often based on sparse and low-quality data. We aimed to generate high quality data about the burden, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa. Methods: In this prospective cohort study done in 11 community-based research sites in south Asia and sub-Saharan Africa, between July, 2012, and February, 2016, we conducted population-based surveillance of women of reproductive age (15–49 years) to identify pregnancies, which were followed up to birth and 42 days post partum. We used standard operating procedures, data collection instruments, training, and standardisation to harmonise study implementation across sites. Verbal autopsies were done for deaths of all women of reproductive age, neonatal deaths, and stillbirths. Physicians used standardised methods for cause of death assignment. Site-specific rates and proportions were pooled at the regional level using a meta-analysis approach. Findings: We identified 278 186 pregnancies and 263 563 births across the study sites, with outcomes ascertained for 269 630 (96·9%) pregnancies, including 8761 (3·2%) that ended in miscarriage or abortion. Maternal mortality ratios in sub-Saharan Africa (351 per 100 000 livebirths, 95% CI 168–732) were similar to those in south Asia (336 per 100 000 livebirths, 247–458), with far greater variability within sites in sub-Saharan Africa. Stillbirth and neonatal mortality rates were approximately two times higher in sites in south Asia than in sub-Saharan Africa (stillbirths: 35·1 per 1000 births, 95% CI 28·5–43·1 vs 17·1 per 1000 births, 12·5–25·8; neonatal mortality: 43·0 per 1000 livebirths, 39·0–47·3 vs 20·1 per 1000 livebirths, 14·6–27·6). 40–45% of pregnancy-related deaths, stillbirths, and neonatal deaths occurred during labour, delivery, and the 24 h postpartum period in both regions. Obstetric haemorrhage, non-obstetric complications, hypertensive disorders of pregnancy, and pregnancy-related infections accounted for more than three-quarters of maternal deaths and stillbirths. The most common causes of neonatal deaths were perinatal asphyxia (40%, 95% CI 39–42, in south Asia; 34%, 32–36, in sub-Saharan Africa) and severe neonatal infections (35%, 34–36, in south Asia; 37%, 34–39 in sub-Saharan Africa), followed by complications of preterm birth (19%, 18–20, in south Asia; 24%, 22–26 in sub-Saharan Africa). Interpretation: These results will contribute to improved global estimates of rates, timing, and causes of maternal and newborn deaths and stillbirths. Our findings imply that programmes in sub-Saharan Africa and south Asia need to further intensify their efforts to reduce mortality rates, which continue to be high. The focus on improving the quality of maternal intrapartum care and immediate newborn care must be further enhanced. Efforts to address perinatal asphyxia and newborn infections, as well as preterm birth, are critical to achieving survival goals in the Sustainable Development Goals era. Funding: Bill & Melinda Gates Foundation.

OBJECTIVE:In this secondary analysis of data from an intervention trial, we assessed the performance of Mid Upper Arm Circumference (MUAC) as a predictor of mortality in children aged 6-59 months from Delhi, India, one year after their initial MUAC measurements were taken. Additionally, we assessed MUAC as an absolute value and MUAC z-scores as predictors of risk of mortality. METHODS:In the trial, children were screened using MUAC prior to referral to the study clinic. These children were revisited a year later to ascertain their vital status. Baseline MUAC and MUAC z-scores were used to categorize children as severely (MUAC

A phase III randomized double-blind placebo-controlled trial was conducted in the urban neighborhoods of Delhi to assess whether Oral Rotavirus Vaccine ROTAVAC® interferes with the immune response to childhood vaccines when coadministered. Infants aged 6 weeks were randomized to receive three doses of either ROTAVAC® or placebo along with childhood vaccines: Oral Polio Vaccine and vaccines against Diphtheria, Pertussis, Tetanus, Hepatitis B and Haemophilus influenza type b given as Pentavalent at 6, 10, 14 weeks of age. Blood specimens were collected from all infants at baseline and 4 weeks post dose 3 to assess the immune response to antigens in Oral Polio Vaccine, Pentavalent and ROTAVAC® vaccines. Non-inferiority of immune response to all vaccine components of the childhood vaccines when ROTAVAC® was administered concurrently was demonstrated. Non-inferior immune responses to childhood vaccines were evaluated based on the seroprotective levels of antibodies against polio types 1, 2, and 3, Diphtheria toxoid, Tetanus toxoid, Haemophilus influenza type b anti- polyribosyl ribitol phosphate antibodies and Hepatitis B antibodies; and the Geometric Mean Concentration for Pertussis. The proportion of infants who seroconverted (≥4 fold rise) was 38.6% in the ROTAVAC® group and 12.2% in the placebo group. The frequency and severity of immediate adverse events, adverse events and serious adverse events were similar in both groups. None of the five reported deaths were considered to be related to the ROTAVAC® and no case of intussusception meeting Brighton Diagnostic Certainty Level I criteria was reported.This study demonstrated that ROTAVAC® can be safely administered with childhood vaccines without interfering with the immune response to the antigens contained in these vaccines.

BACKGROUND:Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this paper, we examined the extent to which vitamin-D deficiency (

This paper aims to identify health research priorities that could improve the rate of progress in reducing global neonatal mortality from preterm birth and low birth weight (PB/LBW), as set out in the UN's Millennium Development Goal 4.

OBJECTIVE: To determine if educating caregivers in providing zinc supplements to infants < 6 months old with acute diarrhoea is effective in treating diarrhoea and preventing acute lower respiratory infections (ALRIs), and whether it leads to a decrease in the use of oral rehydration salts (ORS). METHODS: In this retrospective subgroup analysis of infants aged < 6 months, six clusters were randomly assigned to intervention or control sites. Care providers were trained to give zinc and ORS to children with acute diarrhoea at intervention sites, and only ORS at control sites. Surveys were conducted at 3 and 6 months to assess outcomes. Differences between intervention and control sites in episodes of diarrhoea and ALRI in the preceding 24 hours or 14 days and of hospitalizations in the preceding 3 months were analysed by logistic regression. FINDINGS: Compared with control sites, intervention sites had lower rates of acute diarrhoea in the preceding 14 days at 3 months (odds ratio, OR: 0.60; 95% confidence interval, CI: 0.43-0.84) and 6 months (OR: 0.72; 95% CI: 0.54-0.94); lower rates of acute diarrhoea in the preceding 24 hours at 3 months (0.66; 95% CI: 0.50-0.87) and of ALRI in the preceding 24 hours at 6 months (OR: 0.59; 95% CI: 0.37-0.93); and lower rates of hospitalization at 6 months for all causes (OR: 0.40; 95% CI: 0.34-0.49), diarrhoea (OR: 0.34; 0.18-0.63) and pasli chalna or pneumonia (OR: 0.36; 95% CI: 0.24-0.55). CONCLUSION: Educating caregivers in zinc supplementation and providing zinc to infants < 6 months old can reduce diarrhoea and ALRI. More studies are needed to confirm these findings as these data are from a subgroup analysis.

OBJECTIVE: To compare the estimated prevalence of malnutrition using the World Health Organization's (WHO) child growth standards versus the National Center for Health Statistics' (NCHS) growth reference, to examine the relationship between exclusive breastfeeding and malnutrition, and to determine the sensitivity and specificity of nutritional status indicators for predicting death during infancy. METHODS: A secondary analysis of data on 9424 mother-infant pairs in Ghana, India and Peru was conducted. Mothers and infants were enrolled in a trial of vitamin A supplementation during which the infants' weight, length and feeding practices were assessed regularly. Malnutrition indicators were determined using WHO and NCHS growth standards. FINDINGS: The prevalence of stunting, wasting and underweight in infants aged < 6 months was higher with WHO than NCHS standards. However, the prevalence of underweight in infants aged 6-12 months was much lower with WHO standards. The duration of exclusive breastfeeding was not associated with malnutrition in the first 6 months of life. In infants aged < 6 months, severe underweight at the first immunization visit as determined using WHO standards had the highest sensitivity (70.2%) and specificity (85.8%) for predicting mortality in India. No indicator was a good predictor in Ghana or Peru. In infants aged 6-12 months, underweight at 6 months had the highest sensitivity and specificity for predicting mortality in Ghana (37.0% and 82.2%, respectively) and Peru (33.3% and 97.9% respectively), while wasting was the best predictor in India (sensitivity: 54.6%; specificity: 85.5%). CONCLUSION: Malnutrition indicators determined using WHO standards were better predictors of mortality than those determined using NCHS standards. No association was found between breastfeeding duration and malnutrition at 6 months. Use of WHO child growth standards highlighted the importance of malnutrition in the first 6 months of life.

INTRODUCTION:Despite the evidence for preventing childhood morbidity and mortality, financial resources are cited as a constraint for Governments to scale up the key health interventions in some countries. We evaluate the cost effectiveness of implementing IMNCI program in India from a health system and societal perspective. METHODS:We parameterized a decision analytic model to assess incremental cost effectiveness of IMNCI program as against routine child health services for infant population at district level in India. Using a 15-years time horizon from 2007 to 2022, we populated the model using data on costs and effects as found from a cluster-randomized trial to assess effectiveness of IMNCI program in Haryana state. Effectiveness was estimated as reduction in infant illness episodes, deaths and disability adjusted life years (DALY). Incremental cost per DALY averted was used to estimate cost effectiveness of IMNCI. Future costs and effects were discounted at a rate of 3%. Probabilistic sensitivity analysis was undertaken to estimate the probability of IMNCI to be cost effective at varying willingness to pay thresholds. RESULTS:Implementation of IMNCI results in a cumulative reduction of 57,384 illness episodes, 2369 deaths and 76,158 DALYs among infants at district level from 2007 to 2022. Overall, from a health system perspective, IMNCI program incurs an incremental cost of USD 34.5 (INR 1554) per DALY averted, USD 34.5 (INR 1554) per life year gained, USD 1110 (INR 49,963) per infant death averted. There is 90% probability for ICER to be cost effective at INR 2300 willingness to pay, which is 5.5% of India's GDP per capita. From a societal perspective, IMNCI program incurs an additional cost of USD 24.1 (INR 1082) per DALY averted, USD 773 (INR 34799) per infant death averted and USD 26.3 (INR 1183) per illness averted in during infancy. CONCLUSION:IMNCI program in Indian context is very cost effective and should be scaled-up as a major child survival strategy.

Background: A trial to evaluate the Integrated Management of Neo-natal and Childhood Illness (IMNCI) strategy showed that the intervention resulted in lower infant mortality and improved infant care practices. In this paper, we present the results of a secondary analysis to examine the effect of the IMNCI strategy on inequities in health indicators. Methods: The trial was a cluster–randomized controlled trial in 18 primary health centre areas. For this analysis, the population was divided into subgroups by wealth status (using Principal Component Analysis), religion and caste, education of mother and sex of the infant. Multiple linear regression analysis was used to examine inequity gradients in neonatal and post–neonatal mortality, care practices and care seeking, and the differences in these gradients between intervention and control clusters. Findings: Inequity in post–neonatal infant mortality by wealth status was lower in the intervention as compared to control clusters (adjusted difference in gradients 2.2 per 1000, 95% confidence interval (CI) 0 to 4.4 per 1000, P=0.053). The intervention had no effect on inequities in neonatal mortality. The intervention resulted in a larger effect on breastfeeding within one hour of birth in poorer families (difference in inequity gradients 3.0%, CI 1.5 to 4.5, P

OBJECTIVE: To determine the association of different feeding patterns for infants (exclusive breastfeeding, predominant breastfeeding, partial breastfeeding and no breastfeeding) with mortality and hospital admissions during the first half of infancy. METHODS: This paper is based on a secondary analysis of data from a multicentre randomized controlled trial on immunization-linked vitamin A supplementation. Altogether, 9424 infants and their mothers (2919 in Ghana, 4000 in India and 2505 in Peru) were enrolled when infants were 18-42 days old in two urban slums in New Delhi, India, a periurban shanty town in Lima, Peru, and 37 villages in the Kintampo district of Ghana. Mother-infant pairs were visited at home every 4 weeks from the time the infant received the first dose of oral polio vaccine and diphtheria-pertussis-tetanus at the age of 6 weeks in Ghana and India and at the age of 10 weeks in Peru. At each visit, mothers were queried about what they had offered their infant to eat or drink during the past week. Information was also collected on hospital admissions and deaths occurring between the ages of 6 weeks and 6 months. The main outcome measures were all-cause mortality, diarrhoea-specific mortality, mortality caused by acute lower respiratory infections, and hospital admissions. FINDINGS: There was no significant difference in the risk of death between children who were exclusively breastfed and those who were predominantly breastfed (adjusted hazard ratio (HR) = 1.46; 95% confidence interval (CI) = 0.75-2.86). Non-breastfed infants had a higher risk of dying when compared with those who had been predominantly breastfed (HR = 10.5; 95% CI = 5.0-22.0; P < 0.001) as did partially breastfed infants (HR = 2.46; 95% CI = 1.44-4.18; P = 0.001). CONCLUSION: There are two major implications of these findings. First, the extremely high risks of infant mortality associated with not being breastfed need to be taken into account when informing HIV-infected mothers about options for feeding their infants. Second, our finding that the risks of death are similar for infants who are predominantly breastfed and those who are exclusively breastfed suggests that in settings where rates of predominant breastfeeding are already high, promotion efforts should focus on sustaining these high rates rather than on attempting to achieve a shift from predominant breastfeeding to exclusive breastfeeding.

ObjectivesDeficiencies of vitamin B12 and folate are associated with delayed development and neurological manifestations. The objective of this study was to measure the effect of daily supplementation of vitamin B12 and/or folic acid on development in young North Indian children.MethodsIn a randomized, double blind trial, children aged six to 30 months, received supplement with placebo or vitamin B12 and/or folic acid for six months. Children were allocated in a 1:1:1:1 ratio in a factorial design and in blocks of 16. We measured development in 422 children by the Ages and Stages Questionnaire 3rd ed. at the end of the intervention.ResultsCompared to placebo, children who received both vitamin B12 and folic acid had 0.45 (95% CI 0.19, 0.73) and 0.28 (95% CI 0.02, 0.54) higher SD-units in the domains of gross motor and problem solving functioning, respectively. The effect was highest in susceptible subgroups consisting of stunted children, those with high plasma homocysteine (> 10 μmol/L) or in those who were younger than 24 at end study. With the exception of a significant improvement on gross motor scores by vitamin B12 alone, supplementation of either vitamin alone had no effect on any of the outcomes.ConclusionOur findings suggest that supplementation of vitamin B12 and folic acid benefit development in North Indian Children.Trial registrationClinicalTrials.gov NCT00717730.

Background and objectiveInfants and young children in low to middle-income countries are at risk for adverse neurodevelopment due to multiple risk factors. In this study, we sought to identify stimulation and learning opportunities, growth, and burden of respiratory infections and diarrhea as predictors for neurodevelopment.MethodsWe visited 422 North Indian children 6 to 30 months old weekly for six months. Childhood illnesses were assessed biweekly. At end study, we assessed neurodevelopment using the Ages and Stages Questionnaire 3rd ed. (ASQ-3) and gathered information on stimulation and learning opportunities. We identified predictors for ASQ-3 scores in multiple linear and logistic regression models.ResultsWe were able to explain 30.5% of the variation in the total ASQ-3 score by the identified predictors. When adjusting for child characteristics and annual family income, stimulation and learning opportunities explained most of the variation by 25.1%. Height for age (standardized beta: 0.12, pConclusionOur results support the importance of early child stimulation and general nutrition for child development. Our study also suggests that diarrhea is an additional risk factor for adverse neurodevelopment in vulnerable children.