Insights from global data for use of rotavirus vaccines in India

Rotavirus vaccines are being introduced in several low- and middle-income countries across the world with and without support from the GAVI Alliance. India has the highest disease burden of rotavirus based on morbidity and mortality estimates and several indigenous vaccine manufacturers are developing rotavirus vaccines. One candidate has undergone phase III testing and others have completed evaluation in phase II. Global data on licensed vaccine performance in terms of impact on disease, strain diversity, safety and cost-effectiveness has been reviewed to provide a framework for decision making in India

Does early vitamin B12 supplementation improve neurodevelopment and cognitive function in childhood and into school age: a study protocol for extended follow-ups from randomised controlled trials in India and Tanzania

Introduction: As 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 analysis In 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 dissemination The 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 number NCT00641862 (Bangalore); NCT00717730, updated CTRI/2016/11/007494 (Delhi); NCT00197548 and NCT00421668 (Dar es Salaam)

Diarrhea, Stimulation and Growth Predict Neurodevelopment in Young North Indian Children

Background and Objective. Infants 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. Methods. We 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. Results. We 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). Conclusion. Our 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

The assessment of developmental status using the Ages and Stages questionnaire-3 in nutritional research in north Indian young children

Objective and background: For 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. Methods: ASQ-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 findings: Inter-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/significance: We 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

Vitamin B12 and folic acid improve gross motor and problem-solving skills in young North Indian children: A randomized placebo-controlled trial

Objectives Deficiencies 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. Methods In 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. Results Compared 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. Conclusion Our findings suggest that supplementation of vitamin B12 and folic acid benefit development in North Indian Children. Trial Registration ClinicalTrials.gov NCT0071773

Vitamin B-12, folic acid, and growth in 6- to 30-month-old children: a randomized controlled trial

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 &#60;.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

Demographic and clinical characteristics of children in the cohort.

<p>^<i>1</i><i>Indian Rupees</i>,</p><p>^<i>2</i><i>One mother is deceased</i>,</p><p>^<i>3</i><i>Childcare center</i></p><p>Demographic and clinical characteristics of children in the cohort.</p

Demographic and clinical characteristics of children in the cohort.

<p>^<i>1</i><i>Indian Rupees</i>,</p><p>^<i>2</i><i>One mother is deceased</i>,</p><p>^<i>3</i><i>Childcare center</i></p><p>Demographic and clinical characteristics of children in the cohort.</p

Hierarchical Regression Analysis for variables predicting total ASQ-3 scores in North Indian children 12–36 months¹.

<p>*** p<.001,</p><p>** p<.01,</p><p>* p<.05,</p><p>¹ For the 422 assessed children, the mean total ASQ-3 score was 231.9 (SD = 50) with scores ranging from a minimum of 30 to a maximum of 300.</p><p>^<i>2</i> All models are adjusted for child characteristics (age, sex and breastfeeding status), and annual family income,</p><p>^<i>3</i> unstandardized Beta coefficient,</p><p>^<i>4</i> standardized regression coefficient, Beta values for model 7 only.</p><p>Hierarchical Regression Analysis for variables predicting total ASQ-3 scores in North Indian children 12–36 months<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121743#t002fn004" target="_blank">¹</a>.</p