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 = 0.36) and psychomotor (P = 0.28) 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

Vitamin B12 and/or folic acid supplementation on linear growth; A 6 years follow-up study of a randomised controlled trial in early childhood in North India

Folate and vitamin B12 are essential for growth. Our objective was to estimate their long-term effects on linear growth in North Indian children. This is a follow-up study of a factorial designed, double-blind, randomised, placebo-controlled trial in 1000 young children. Starting at 6–30 months of age, we gave folic acid (approximately 2 RDA), vitamin B12 (approximately 2 RDA), both vitamins or a placebo daily for 6 months. Six years after the end of supplementation, we measured height in 791 children. We used the plasma concentrations of cobalamin, folate and total homocysteine to estimate vitamin status. The effect of the interventions, the association between height-for-age z-scores (HAZ) and baseline vitamin status, and the interactions between supplementation and baseline status were estimated in multiple regression models. Mean (SD) age at follow-up was 7·4 (0·7) years (range 6 to 9 years). There was a small, non-significant effect of vitamin B12 on linear growth and no effect of folic acid. We observed a subgroup effect of vitamin B12 supplementation in those with plasma cobalamin concentration < 200 pmol/l (Pfor interaction = 0·01). The effect of vitamin B12 supplementation in this group was 0·34 HAZ (95 % CI 0·11, 0·58). We found an association between cobalamin status and HAZ in children not given vitamin B12 (Pfor interaction = 0·001). In this group, each doubling of the cobalamin concentration was associated with 0·26 (95 % CI 0·15, 0·38) higher HAZ. Suboptimal vitamin B12 status in early childhood seemingly limits linear growth in North Indian children. © The Author(s), 2022. Published by Cambridge University Press on behalf of The Nutrition Society. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.Vitamin B12 and/or folic acid supplementation on linear growth; A 6 years follow-up study of a randomised controlled trial in early childhood in North IndiapublishedVersio

Effect of implementation of Integrated Management of Neonatal and Childhood Illness (IMNCI) programme on neonatal and infant mortality: cluster randomised controlled trial

Objective To evaluate the Indian Integrated Management of Neonatal and Childhood Illness (IMNCI) programme, which integrates improved treatment of illness for children with home visits for newborn care, to inform its scale-up

Impact on inequities in health indicators: effect of implementing the integrated management of neonatal and childhood illness programme in Haryana, India

Background: A trial to evaluate the Integrated Management of Neonatal 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 &#60; 0.001), in lower caste and minorities families, and in infants of mothers with fewer years of schooling. The intervention also reduced gender inequity in care seeking for severe neonatal illness from an appropriate provider (difference in inequity gradients 9.3%, CI 0.4 to 18.2, P = 0.042). Conclusions: Implementation of IMNCI reduced inequities in post-neonatal mortality, and newborn care practices (particularly starting breastfeeding within an hour of birth) and health care-seeking for severe illness. In spite of the intervention substantial inequities remained in the intervention group and therefore further efforts to ensure that health programs reach the vulnerable population subgroups are required

Vitamin B12, folate, and cognition in 6-to 9-year-olds: a randomized controlled trial

BACKGROUND AND OBJECTIVES: Vitamin B12 and folate are important for normal brain development. Our objective for this study was to measure the effects of 6-month supplementation of vitamin B12 and/or folic acid in early childhood on cognition when the children were 6 to 9 years old. METHODS: The study is a follow-up of a factorial randomized, double-blind, placebo-controlled trial in 1000 North Indian children. Children 6 to 30 months of age were randomly assigned to receive a placebo or 1.8 µg of vitamin B12, 150 mg of folic acid, or both daily for 6 months. After 6 years, we re-enrolled 791 of these children for cognitive assessments. We compared the scores of the main outcomes (the Wechsler Intelligence Scale for Children, Fourth Edition [India], the Crichton Verbal Scale, and subtests of the NEPSY-II) between the study groups. We also measured the associations between markers of the B vitamins (plasma cobalamin, folate, and total homocysteine concentrations) in early childhood and the cognitive outcomes. RESULTS: There were no differences between the intervention groups and the placebo group on the cognitive outcomes. Plasma cobalamin, folate, and total homocysteine concentrations in early childhood were associated with the cognitive outcomes at follow-up in the unadjusted models. These associations disappeared in models adjusted for relevant confounders. CONCLUSIONS: Our findings, from both an observational and a randomized design suggest that vitamin B12 and folate in children 6 to 36 months have limited public health relevance for long-term cognition.Thrasher Research Fund (grant 02827) and the Research Council of Norway (grants 172226 and 234495) provided financial support for the original and the follow-up study.AcceptedVersio

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 &#8804;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 &gt;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 &gt;85% of the follow-up period. Mean plasma zinc at 12 mo of age was higher in the zinc group (100.2 &#956;g/dL) than in the control group (73.3 &#956;g/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 &lt; 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

Adding zinc to supplemental iron and folic acid does not affect mortality and severe morbidity in young children

Studies have found a substantial reduction in diarrhea and respiratory morbidity in young children receiving zinc supplementation. The impact of daily zinc supplementation administered with iron plus folic acid (IFA) in young children on all-cause hospitalizations and mortality in comparison with IFA alone was evaluated. In a double blind cluster-randomized controlled trial, 94,359 subjects aged 1-23 mo were administered a daily dose of zinc plus IFA or IFA alone for a duration of 12 mo after enrollment. The intervention group tablet contained 10 mg of elemental zinc, 12.5 mg of iron, and 50 &#956;g of folic acid. The control group tablets were similar except that they contained a placebo for zinc. Infants aged &lt;6 mo were administered half a tablet, and those older received 1 tablet dissolved in breast milk or water. Hospitalizations were captured by trained study physicians through the surveillance of 8 hospitals. Deaths and hospitalizations were ascertained through visits to households by study supervisors once every 2 mo. The overall death rates did not differ significantly between the 2 groups when adjusted for cluster randomization (hazard ratio = 1.02, 95% CI 0.87, 1.19). Zinc and IFA supplementation compared with IFA alone did not affect adjusted hospitalization rates (overall rate ratio = 1.08, 95% CI 0.98, 1.19; diarrhea-specific rate ratio = 1.15, 95% CI 0.99, 1.34; or pneumonia-specific rate ratio = 1.09, 95% CI 0.94, 1.25). The lack of impact of zinc on mortality and hospitalization rates in this study may have been due to the use of lower daily zinc dosing than used in some of the morbidity prevention trials or from an interaction between zinc and iron, where the addition of iron may have adversely affected potential effects of zinc on immune function and morbidity. Future research should address iron and zinc interaction effects on important functional outcomes

Optimal breastfeeding practices and infant and child mortality: A systematic review and meta-analysis

Aim: To synthesise the evidence for effects of optimal breastfeeding on all-cause and infection-related mortality in infants and children aged 0–23 months. Methods: We conducted a systematic review to compare the effect of predominant, partial or nonbreastfeeding versus exclusive breastfeeding on mortality rates in the first six months of life and effect of no versus any breastfeeding on mortality rates between 6 and 23 months of age. A systematic literature search was conducted in PubMed, Cochrane CENTRAL and CABI. Results: The risk of all-cause mortality was higher in predominantly (RR 1.5), partially (RR 4.8) and nonbreastfed (RR14.4) infants compared to exclusively breastfed infants 0– 5 months of age. Children 6–11 and 12–23 months of age who were not breastfed had 1.8- and 2.0-fold higher risk of mortality, respectively, when compared to those who were breastfed. Risk of infection-related mortality in 0–5 months was higher in predominantly (RR 1.7), partially (RR 4.56) and nonbreastfed (RR 8.66) infants compared to exclusive breastfed infants. The risk was twofold higher in nonbreastfed children when compared to breastfed children aged 6–23 months. Conclusion: The findings underscore the importance of optimal breastfeeding practices during infancy and early childhood.publishedVersio

Daily Folic Acid and/or Vitamin B12 Supplementation Between 6 and 30 Months of Age and Cardiometabolic Risk Markers After 6–7 Years: A Follow-Up of a Randomized Controlled Trial

Background Deficiencies of vitamin B12 and folate are associated with elevated concentrations of metabolic markers related to CVDs. Objectives We investigated the effect of supplementation of vitamin B12 with or without folic acid for 6 mo in early childhood on cardiometabolic risk markers after 6–7 y. Methods This is a follow-up study of a 2 × 2 factorial, double-blind, randomized controlled trial of vitamin B12 and/or folic acid supplementation in 6–30-mo-old children. The supplement contained 1.8 μg of vitamin B12, 150 μg of folic acid, or both, constituting >1 AI or recommended daily allowances for a period of 6 mo. Enrolled children were contacted again after 6 y (September 2016–November 2017), and plasma concentrations of tHcy, leptin, high molecular weight adiponectin, and total adiponectin were measured (N = 791). Results At baseline, 32% of children had a deficiency of either vitamin B12 (<200 pmol/L) or folate (<7.5 nmol/L). Combined supplementation of vitamin B12 and folic acid resulted in 1.19 μmol/L (95% CI: 0.09; 2.30 μmol/L) lower tHcy concentration 6 y later compared to placebo. We also found that vitamin B12 supplementation was associated with a lower leptin–adiponectin ratio in subgroups based on their nutritional status. Conclusions Supplementation with vitamin B12 and folic acid in early childhood was associated with a decrease in plasma tHcy concentrations after 6 y. The results of our study provide some evidence of persistent beneficial metabolic effects of vitamin B12 and folic acid supplementation in impoverished populations.publishedVersio

Diagnostic measures for severe acute malnutrition in Indian infants under 6 months of age: a secondary data analysis

Background Weight for length z-score (WLZ) < − 3 is currently used to define severe acute malnutrition (SAM) among infants. However, this approach has important limitations for infants younger than 6 months of age as WLZ cannot be calculated using WHO growth standards if infant length is < 45 cm. Moreover, length for age z-score (LAZ) and weight for length z-score (WLZ) are least reliable measures, with high chances of variation, and less chances of detecting undernutrition in under 6 months infants. The objective of the current analysis was to compare WLZ with WAZ and LAZ in a cohort of Indian infants in predicting the deaths between 6 weeks and 6 months of age. Methods The data was from an individually randomized trial conducted in slums of Delhi, India in which infants’ weight and length were measured at 6 weeks of age (at the time of the first immunization visit). Vital status of the infants was documented from 6 weeks to 6 months of age. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated for WAZ < -3, WLZ < -3, and LAZ < -3 for deaths between 6 weeks and 6 months of age. The receiver operating characteristics curve was calculated for each of the above anthropometric indicators. Results For deaths occurring between 6 weeks to 6 months of age, the specificity ranged between 85.9–95.9% for all three anthropometric indicators. However, the sensitivity was considerably higher for WAZ; it was 64.6% for WAZ < -3, 39.1% for LAZ < -3, and 25.0% for WLZ < -3. WAZ < -3 had higher area under curve (0.75; 95% CI: 0.68, 0.82) and hence, better discriminated deaths between 6 weeks and 6 months of age than WLZ < -3. The adjusted relative risk (RR 10.6, 95% CI 5.9, 18.9) and the population attributable fraction (PAF 57.9, 95% CI 38.8, 71.0%) of mortality was highest for WAZ < -3. Conclusions We found WAZ < -3 at 6 weeks of age to be a better predictor of death in the 6 weeks to 6 months of life in comparison to WLZ < -3 and LAZ < -3 and propose that it should be considered to diagnose SAM in this age group.publishedVersio