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

Folic acid or vitamin B-12 supplementation did not reduce the burden of common childhood infections. In view of the increased risk of diarrhea, the safety of folic acid supplements in young children should be further assessed. This trial was registered at www.clinicaltrials.gov as NCT00717730 and at www.ctri.nic.in as CTRI/2010/091/001090.

BACKGROUND: Folate and vitamin B-12 are important for growth. Many children in low-and middle-income countries have inadequate intakes of these nutrients. METHODS:We undertook a randomized, placebo controlled double-blind trial in 1000 North Indian children, 6 to 35 months of age, providing twice the recommended daily allowance of folic acid and/or vitamin B-12, or placebo, daily for 6 months. By using a factorial design, we allocated children in a 1:1:1:1 ratio in blocks of 16. We measured the effect of giving vitamin B-12, folic acid, or the combination of both on linear and ponderal growth. We also identified predictors for growth in multiple linear regression models and effect modifiers for the effect of folic acid or vitamin B-12 supplementation on growth. RESULTS:The overall effect of either of the vitamins was significant only for weight; children who received vitamin B-12 increased their mean weight-for-age z scores by 0.07 (95% confidence interval: 0.01 to 0.13). Weight-for-age z scores and height-for-age z scores increased significantly after vitamin B-12 supplementation in wasted, underweight, and stunted children. These subgrouping variables significantly modified the effect of vitamin B-12 on growth. Vitamin B-12 status at baseline predicted linear and ponderal growth in children not receiving vitamin B-12 supplements but not in those who did (P-interaction , .001). CONCLUSIONS:We provide evidence that poor vitamin B-12 status contributes to poor growth. We recommend studies with larger doses and longer follow-up to confirm our findings. WHAT'S KNOWN ON THIS SUBJECT:Micronutrient deficiencies, including deficiencies of vitamin B-12 and folate, are common worldwide and may be a contributing factor to the estimated 165 million stunted children. WHAT THIS STUDY ADDS:Routine supplementation of vitamin B-12 improved linear and ponderal growth in subgroups of young Indian children. We provide evidence that vitamin B-12 deficiency is a contributor to poor growth in low-and middle-income countries.

Three administrations of vaccine doses of 1 X 10(4) ffu and 1 X 10(5) ffu were safe. The 1 X 10(5)-ffu dose of 116E demonstrated a robust immune response after 3 administrations. These favorable results warrant further development of the vaccine candidate and provide optimism that vaccinating infants in the developing world will prevent serious sequelae of rotavirus infection. Clinical trials registration. NCT00439660 and ISRCTN57452882 .

Objective and backgroundFor large epidemiological studies in low and middle-income countries, inexpensive and easily administered developmental assessment tools are called for. This report evaluates the feasibility of the assessment tool Ages and Stages Questionnaire 3.edition (ASQ-3) “home procedure” in a field trial in 422 North Indian young children.MethodsASQ-3 was translated and adjusted for a North Indian Hindi setting. Three examiners were trained by a clinical psychologist to perform the assessments. During the main study, ten % of the assessments were done by two examiners to estimate inter-observer agreement. During all sessions, the examiners recorded whether the scoring was based on observation of the skill during the session, or on caregiver’s report of the child’s skill. Intra class correlation coefficient was calculated to estimate the agreement between the raters and between the raters and a gold standard. Pearson product moment correlation coefficient and standardized alphas were calculated to measure internal consistency.Principal findingsInter-observer agreement was strong both during training exercises and during the main study. In the Motor subscales and the Problem Solving subscale most items could be observed during the session. The standardized alphas for the total ASQ-3 scale across all ages were strong, while the alpha values for the different subscales and age levels varied. The correlations between the total score and the subscale scores were consistently strong, while the correlations between subscale scores were moderate.Conclusions/significanceWe found that the translated and adjusted ASQ-3 “home procedure” was a feasible procedure for the collection of reliable data on the developmental status in infants and young children. Examiners were effectively trained over a short period of time, and the total ASQ scores showed adequate variability. However, further adjustments are needed to obtain satisfying alpha values in all subscales, and to ensure variability in all items when transferred to a North Indian cultural context.

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, p<.05) and weight for height z-scores (std. beta: 0.09, p<.05) were positively associated with the total ASQ-3 score, while number of days with diarrhea was negatively associated with these scores (std. beta: -0.13, p<0.01).ConclusionOur 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.

IntroductionAs many as 250 million children under the age of 5 may not be reaching their full developmental potential partly due to poor nutrition during pregnancy and the first 2 years of life. Micronutrients, including vitamin B12, are important for the development of brain structure and function; however, the timing, duration and severity of deficiencies may alter the impact on functional development outcomes. Consequently, to fully explore the effect of vitamin B12 on cognitive function, it is crucial to measure neurodevelopment at different ages, in different populations and with vitamin B12 supplementation at different times during the critical periods of neurodevelopment.Methods and analysisIn this project, we follow up children from four recently completed randomised placebo-controlled trials of oral vitamin B12 supplementation, two in India and two in Tanzania, to explore the long-term effects on neurodevelopmental outcomes and growth. All the included trials provided at least two recommended dietary allowances of oral vitamin B12 daily for at least 6 months. Vitamin B12 was supplemented either during pregnancy, early infancy or early childhood. Primary outcomes are neurodevelopmental status, cognitive function and growth later in childhood. We apply validated and culturally appropriate instruments to identify relevant developmental outcomes. All statistical analyses will be done according to intention-to-treat principles. The project provides an excellent opportunity to examine the effect of vitamin B12 supplementation in different periods during early life and measure the outcomes later in childhood.Ethics and disseminationThe study has received ethical approvals from all relevant authorities in Norway, USA, Tanzania and India and complies fully with ethical principles for medical research. Results will be presented at national and international research and policy meetings and published in peer-reviewed scientific journals, preferably open access.Trial registration numberNCT00641862 (Bangalore); NCT00717730, updated CTRI/2016/11/007494 (Delhi); NCT00197548 and NCT00421668 (Dar es Salaam).

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