Impact of an integrated nutrition, health, water sanitation and hygiene, psychosocial care and support intervention package delivered during the pre- and peri-conception period and/or during pregnancy and early childhood on linear growth of infants in the first two years of life, birth outcomes and nutritional status of mothers: study protocol of a factorial, individually randomized controlled trial in India.

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.

Factors associated with the decline in under-five diarrhea mortality in India: a LiST analysis.

BACKGROUND: India has achieved 86% reduction in the number of under-five diarrheal deaths from 1980 to 2015. Nonetheless diarrhea is still among the leading causes of under-five deaths. The aim of this analysis was to study the contribution of factors that led to decline in diarrheal deaths in the country and the effect of scaling up of intervention packages to address the remaining diarrheal deaths. METHODS: We assessed the attribution of different factors and intervention packages such as direct diarrhea case management interventions, nutritional factors and WASH interventions which contributed to diarrhea specific under-five mortality reduction (DSMR) during 1980 to 2015 using the Lives Saved Tool (LiST). The potential impact of scaling up different packages of interventions to achieve universal coverage levels by year 2030 on reducing the number of remaining diarrheal deaths were estimated. RESULTS: The major factors associated with DSMR reduction in under-fives during 1980 to 2015, were increase in ORS use, reduction in stunting prevalence, improved sanitation, changes in age appropriate breastfeeding practices, increase in the vitamin-A supplementation and persistent diarrhea treatment. ORS use and reduction in stunting were the two key interventions, each accounting for around 32% of the lives saved during this period. Scaling up the direct diarrhea case management interventions from the current coverage levels in 2015 to achieve universal coverage levels by 2030 can save around 82 000 additional lives. If the universal targets for nutritional factors and WASH interventions can be achieved, an additional 23 675 lives can potentially be saved. CONCLUSIONS: While it is crucial to improve the coverage and equity in ORS use, an integrated approach to promote nutrition, WASH and direct diarrhea interventions is likely to yield the highest impact on reducing the remaining diarrheal deaths in under-five children.

Vitamin D deficiency and mild to moderate anemia in young North Indian children: A secondary data analysis.

OBJECTIVES: The aim of this study was to examine the association between vitamin D deficiency and anemia status among young children in the resource-poor setting of northern urban India. METHODS: We used data from a randomized controlled trial of daily supplementation with folic acid, vitamin B12, or both for 6 mo in children 6 to 30 mo of age conducted in Delhi, India. We measured serum vitamin D status, hemoglobin, plasma vitamin B12, folate, soluble transferrin receptor, and homocysteine levels at baseline. Children with severe anemia (hemoglobin [Hgb] <7 g/dL) were excluded from enrollment. Multivariable logistic and multinomial logistic regressions were used to examine the association between vitamin D and anemia status at baseline. RESULTS: 25-Hydroxyvitamin-D (25 OHD) concentration was measured for 960 (96%) children. Of the children, 331 (34.5%) were vitamin-D deficient (<10 ng/mL). Approximately 70% of the enrolled children were anemic, with ∼46% having moderate (Hgb 7-9.9 g/dL) and 24% mild (Hgb 10-10.9 g/dL) anemia. There was no association between vitamin D and anemia status after adjusting for confounders; however, the risk for moderate anemia was significantly higher among vitamin D-deficient children than those who were vitamin-D replete (relative risk, 1.58; 95% confidence interval, 1.09-2.31). CONCLUSIONS: Vitamin D deficiency was associated with moderate anemia among young children and the effect was independent of iron deficiency. The causal association of vitamin D deficiency with anemia risk remains debatable. The role of vitamin D in risk for anemia needs to be examined in further studies.

Risk of postneonatal mortality, hospitalisation and suboptimal breast feeding practices in low birthweight infants from rural Haryana, India: findings from a secondary data analysis.

OBJECTIVES: Low birth weight (LBW) is a risk factor for neonatal mortality and morbidity. It is important to examine whether this risk persists beyond neonatal period. The current secondary data analysis aimed to examine association of birth weight with mortality, hospitalisation and breast feeding practices during infancy. DESIGN: Data from a large randomised controlled trial of neonatal vitamin A supplementation (Neovita) trial were used. Log binomial model was applied to assess association between birth weight and mortality, hospitalisation and breast feeding practices. SETTING: Rural Haryana, North India. PARTICIPANTS: Newborns recruited in the primary intervention trial that aimed to evaluate the effect of single-dose oral vitamin A supplementation on mortality in the first 6 months of life. RESULTS: We recruited a total of 44 984 infants, of which 10 658 (23.7%) were born LBW, that is, birth weight less than 2500 g. In the neonatal period, LBW babies had four times higher risk of mortality (relative risk (RR) 3.92; 95% CI 3.33 to 4.66) compared with normal birthweight babies. In the postneonatal period, the risk was two times higher (RR 1.92; 95% CI 1.71 to 2.15); even higher in those with birth weight <2000 g (RR 3.38; 95% CI 2.71 to 4.12). The risk of hospitalisation in the neonatal period and postneonatal period was (RR 1.86; 95% CI 1.64 to 2.11) and (RR 1.13; 95% CI 1.05 to 1.21), respectively. LBWs were at increased risk of breast feeding initiation 24 hours after birth (RR 1.64; 95% CI 1.45 to 1.81), no breast feeding at 6 months (RR 1.34; 95% CI 1.23 to 1.46) and at 12 months of age (RR 1.24; 95% CI 1.18 to 1.30). CONCLUSIONS: LBW babies, especially those with birth weight of <2000 g, were at increased risk of mortality, hospitalisation and suboptimal breast feeding practices during entire infancy and therefore require additional care beyond the first 28 days of life. TRIAL REGISTRATION NUMBER: NCT01138449.

Vitamin-D status and neurodevelopment and growth in young north Indian children: a secondary data analysis.

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 (<10 ng/ml) is associated with neurodevelopment and physical growth in young children. METHODS: We used data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in children aged 6 to 30 months conducted in Delhi, India. We measured vitamin-D status and  neurodevelopment by the Ages and Stages Questionnaire-3 (ASQ-3) at 12 to 36 months of age. Multiple logistic and linear regressions were used to examine the association between vitamin-D deficiency at baseline and neurodevelopment and growth 6 months follow-up. RESULTS: 25-hydroxy-vitamin-D (25OHD) concentration was measured at baseline for 960 (96%) children. Of these, 331 (34.5%) children were vitamin-D deficient. The total and subscale (except for the Personal social scale) ASQ-3 scores, were not different between the vitamin-D deficient and non-deficient children. Vitamin-D deficiency was also not associated with physical growth at baseline and at follow -up. CONCLUSION: Our data do not support the hypothesis that vitamin-D deficiency is associated with poor growth and neurodevelopment. TRIAL REGISTRATION: NCT00717730 and CTRI/2010/091/001090 . Date of registration: 08 October, 2010.

Vitamin-D deficiency predicts infections in young north Indian children: A secondary data analysis.

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 (<10 ng/ml) predicts ALRI, clinical pneumonia and diarrhea among 6 to 30 months old children. METHODS: We used data from a randomized controlled trial (RCT) of daily folic acid and/or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Generalized estimating equations (GEE) were used to examine the associations between vitamin-D deficiency and episodes of ALRI, clinical pneumonia and diarrhea. RESULTS: Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status and season), that the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not associated with episodes of diarrhea or clinical pneumonia. CONCLUSION: Vitamin-D deficiency is common in young children in New Delhi and is associated with a higher risk of ALRI. The role of vitamin D in Indian children needs to be elucidated in further studies.

Immunization practices in low birth weight infants from rural Haryana, India: Findings from secondary data analysis.

BACKGROUND: Low birth weight (LBW) infants constitute a vulnerable subset of infants with impaired immunity in early life. In India, there is scarcity of studies that focus on immunization practices in such infants. This analysis aimed to examine immunization practices in LBW infants with the intention to identify areas requiring intervention. METHODS: Data on immunization status of LBW infants enrolled in an individually randomized, double-masked, placebo-controlled trial of neonatal vitamin A supplementation were analysed. Study outcomes were full immunization by one year of age and delayed vaccination with DPT1 and DPT3. Multivariable logistic regression was performed to identify factors associated with the outcome(s). FINDINGS: Out of 10 644 LBW infants enrolled in trial, immunization data were available for 10 517 (98.8%). Less than one-third (29.7%) were fully immunized by one year of age. Lowest wealth quintile (adjusted odds ratio (AOR) 0.39, 95% confidence interval (CI) 0.32-0.47), Muslim religion (AOR 0.41, 95% CI 0.35-0.48) and age of mother <20 years (AOR 0.62, 95% CI 0.52-0.73) were associated with decreased odds of full immunization. Proportion of infants with delayed vaccination for DPT1 and DPT3 were 52% and 81% respectively. Lowest wealth quintiles (AOR 1.51, 95% CI 1.25-1.82), Muslim religion (AOR 1.41, 95% CI 1.21-1.65), mother aged <20 years (AOR 1.31, 95% CI 1.11-1.53) and birth weight <2000 g (AOR 1.20, 95% CI 1.03-1.40) were associated with higher odds of delayed vaccination for DPT-1. Maternal education (≥12 years of schooling) was associated with high odds of full immunization (AOR 2.39, 95% CI 1.97-2.91) and low odds of delayed vaccination for both DPT-1 (AOR 0.59, 95% CI 0.49-0.73) and DPT-3 (AOR 0.57, 95% CI 0.43-0.76). CONCLUSION: In this population, LBW infants are at a risk of delayed and incomplete immunization and therefore need attention. The risks are even higher in identified subgroups that should specifically be targeted.

Effect of zinc supplementation on morbidity and growth in hospital-born, low-birth-weight infants.

BACKGROUND: Low-birth-weight infants may have impaired zinc status, but little is known about the effect of zinc supplementation. OBJECTIVE: The objective was to investigate the effect of daily zinc supplementation on morbidity and anthropometric status in hospital-born, low-birth-weight infants. DESIGN: In a double-blind, randomized, placebo-controlled trial, 2052 hospital-born term infants with a birth weight < or =2500 g were randomly assigned to receive zinc or placebo. The zinc group received elemental zinc: 5 mg/d for those infants between ages 2 wk and 6 mo and 10 mg/d for those infants aged >6 mo. All-cause hospitalizations, prevalence of diarrhea, acute lower respiratory tract infections, visits to health care providers, weights, and lengths were ascertained at 3, 6, 9, and 12 mo of age. RESULTS: The supplement was consumed for >85% of the follow-up period. Mean plasma zinc at 12 mo of age was higher in the zinc group (100.2 microg/dL) than in the control group (73.3 microg/dL) (difference in means: 26.9; 95% CI: 19.6, 34.2). The 24-h and 7-d prevalence of diarrhea and acute lower respiratory tract infections was similar at 3, 6, 9, and 12 mo. Care-seeking for illness was significantly lower in the zinc group (difference in proportions: -5.7; 95% CI: -9.9, -1.4; P < 0.05) at 9 mo. The numbers of hospitalizations, weights, and lengths were all similar at all 4 assessments. CONCLUSION: Hospital-born, term, low-birth-weight infants do not seem to benefit substantially from zinc supplementation that meets the Recommended Dietary Allowance for zinc in terms of morbidity or physical growth during infancy in this setting. This trial was registered at www.clinicaltrials.gov as NCT00272142.

Impact of zinc supplementation on mental and psychomotor scores of children aged 12 to 18 months: a randomized, double-blind trial.

OBJECTIVE: To evaluate the effect of zinc supplementation on mental and psychomotor scores in children aged 12 to 18 months. STUDY DESIGN: In this double-blind, randomized, placebo-controlled trial, children aged 6 to 30 months received daily elemental zinc (10 mg for infants and 20 mg for others) or placebo for 4 months. Bayley Scales of Infant Development II were used for development assessment in the 12- to 18-month subgroup at enrollment and the end of the study. RESULTS: At the end of the study, the adjusted mean mental ( P = .36) and psychomotor ( P = .28) index scores were similar in the intervention and control groups. In a multivariate model, the baseline mental development index score was positively associated with the mother's schooling, the child's height for age, packed cell volumes, hospital birth, and attendance at a day care center, and was negatively associated with the child's age. Breastfeeding, the child's weight for height, and packed cell volumes were positively associated with the baseline psychomotor index score. CONCLUSION: Zinc supplementation did not affect the mental or psychomotor development index scores in a setting in which zinc deficiency is common.