Influence of Maternal Vitamin B<sub>12</sub> and Folate on Growth and Insulin Resistance in the Offspring

The burden of chronic noncommunicable diseases (NCDs) such as diabetes, obesity and cardiovascular disease is shifting rapidly to low- and middle-income countries. It calls for a review of the classic 'dogma' of genetic predisposition, precipitated by adult lifestyle. The paradigm of early life origins of chronic disease has focused attention on maternal health and nutrition as major determinants of the health of the offspring. India has high burden of maternal ill health and also of diabetes and cardiovascular disease, offering unique opportunities to study the links between the two. Pune studies showed that the Indian babies were thin but fat (more adipose) compared to European babies, and that maternal micronutrient status during pregnancy was a determinant of offspring size and body composition. Two thirds of the mothers had low vitamin B12 concentrations, while folate deficiency was rare. Higher circulating concentrations of homocysteine predicted smaller baby size. Follow-up studies revealed that higher maternal folate in pregnancy predicted higher adiposity and insulin resistance in the child at 6 years of age, and that low maternal vitamin B12 exaggerated the risk of insulin resistance. Low maternal vitamin B12 status is also associated with increased risk of neural tube defects and poor offspring cognitive functions. Our results suggest an important role for maternal one-carbon metabolism in offspring growth and programming of NCD risk. These ideas are supported by animal studies. Improvement of adolescent nutrition could effect intergenerational prevention of chronic diseases.