Fetal programming: maternal nutrition and role of one-carbon metabolism

India is world's capital for low birth weight (LBW), which is ascribed to intrauterine growth restriction (IUGR) rather than prematurity. An average Indian mother is short and thin and gives birth to a light and thin baby. Maternal undernutrition is thought to be a major factor in the aetiology of IUGR, and the undernutrition is usually thought to be a low macronutrient intake. The Pune Maternal Nutrition Study (PMNS) showed that the Indian babies were thin but fat (more adipose) compared to European babies, and that maternal intake of micronutrient-rich foods was a strong determinant of fetal size. Two thirds of the mothers had low vitamin B(12) concentrations, folate deficiency was rare, and high circulating concentrations of homocysteine predicted IUGR. Follow up of these children revealed that higher maternal folate in pregnancy predicted higher adiposity and insulin resistance at 6 years of age. The most insulin resistant children were born to mothers who were vitamin B(12) deficient and had high folate concentrations. Thus, PMNS suggests an important role for maternal one-carbon (1C) metabolism in fetal growth and programming of diabetes risk. This could be due to the role of 1C metabolism in synthesis of nucleic acids, genomic stability and the epigenetic regulation of gene function. In addition, methionine has important role in protein synthesis. These ideas are supported by animal studies. The next logical step in India will be to improve 1C metabolism in adolescents to effect intergenerational prevention of adiposity, diabetes and other related conditions.