Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring

Background:

The concept of fetal programming suggests that adverse intrauterine growth environment influences development of fetal organ structure and function, hence laying the basis for risk for chronic disease in later life with its consequent effects on human capital. One of the important factors determining intrauterine growth is maternal and fetal nutritional status. Micronutrients vitamin B12 and folic acid are essential determinants of one carbon metabolism and play an important role in DNA synthesis, methylation and epigenetic regulation of gene expression. The ongoing Pune Maternal Nutritional Study (PMNS) has demonstrated an association between low maternal vitamin B12 levels during pregnancy and impaired cognitive functioning in offspring at 9 and 12 years of age. This observation suggests that maternal micronutrient status during pregnancy can influence neurocognitive development and functioning in later life. Various other intervention studies conducted in Delhi and Bangladesh support that vitamin B12 and folic acid supplementation in children between 6-30 months of age can improve their motor and neurocognitive development. On this background the Diabetes unit of KEMHRC, Pune has been conducting the Pune Rural Intervention in Young Adolescents since last 3 years. Subjects of the PMNS cohort have been randomized as part of a controlled trial of nutritional intervention with vitamin B12 vs multiple micronutrient and milk protein vs placebo. This study aims to understand the intergenerational effects of vitamin B12 supplementation. 74 infants have been born in this trial since 2013. This presents a unique opportunity to study the effects of parental periconceptional vitamin B12 supplementation on infant neurocognitive development.

Objective and Hypothesis:

To compare group differences, in infant neurocognitive development scores assessed at 24 months of age between mothers who received either vitamin B12 alone, or MMN with milk protein or placebo.

Hypothesis: Infants born to mothers who received vitamin B12 would have favorable infant neurocognitive development scores as compared to placebo. And this effect would be enhanced in the group whose mothers received MMN with milk protein.