In The Pune Maternal Nutrition Study,
vitamin B12 deficiency was seen in 65% of pregnant women,
folate deficiency was rare. Maternal total
homocysteine concentrations were inversely associated with offspring
birthweight, and low
vitamin B12 and high
folate concentrations predicted higher offspring adiposity and
insulin resistance. These findings guided a nested pre-conceptional randomised controlled trial 'Pune Rural Intervention in Young Adolescents'. The interventions included: (1)
vitamin B12+multi-
micronutrients as per the United Nations International Multiple
Micronutrient Antenatal Preparation, and
proteins (B12+MMN), (2)
vitamin B12 (B12 alone), and (3) placebo. Intervention improved maternal pre-conceptional and in-pregnancy
micronutrient nutrition. Gene expression analysis in cord blood mononuclear cells in 88 pregnancies revealed 75 differentially expressed genes between the B12+MMN and placebo groups. The enriched biological processes included G2/M phase transition, chromosome segregation, and nuclear division. Enriched pathways included, mitotic spindle checkpoint and DNA damage response while enriched human phenotypes were sloping forehead and decreased head circumference.
Fructose-bisphosphatase 2 (FBP2) and Cell Division Cycle Associated 2 (CDCA2) genes were under-expressed in the B12 alone group. The latter, involved in chromosome segregation was under-expressed in both intervention groups. Based on the role of B-complex
vitamins in the synthesis of
nucleotides and S-adenosyl
methionine, and the roles of
vitamins A and D on gene expression, we propose that the multi-
micronutrient intervention epigenetically affected cell cycle dynamics. Neonates in the B12+MMN group had the highest ponderal index. Follow-up studies will reveal if the intervention and the altered biological processes influence offspring diabesity.