Elevated cord leptin from low B12 mothers predicts birth weight

Vitamin B12 (B12) insufficiency is common in pregnancy and independently predicts insulin resistance (IR) in the offspring. B12 is an important key nutrient for epigenetic programming through regulating DNA methylation. Such B12 DNA methylation may influence leptin, a strong candidate for methylation, which could impact both insulin resistance (IR) and associated neonatal metabolic risk. Therefore, we hypothesize that leptin can be programmed by maternal B12 which could influence metabolic risk in the offspring. To test this hypothesis, we investigated whether i) maternal B12 is associated with leptin in cord blood and ii) evaluated their association with birth weight. Paired maternal venous and cord blood samples (n=91) were collected at the time of elective caesarean section. Serum vitamin-B12 was determined by electro-chemiluminescent immunoassay. Leptin levels were measured by ELISA. B12 insufficiency (<150 pmol/l) was common (mothers-40%; and neonates-29%). Maternal B12 was inversely associated with neonatal leptin (r=−0.304; P=0.005). In regression analysis, adjusted for all likely confounders, maternal B12 independently predicted neonatal leptin (β=−0.647; P=0.005; R2=12.8%). There was no correlation between maternal and neonatal leptin levels. Cord leptin from mothers with low B12 correlated with birth weight (r=0.366; P=0.036). Regression analysis adjusted for maternal leptin and insulin showed that cord leptin from mothers with low B12 independently predicted birth weight (β=0.024; P=0.049; R2=14.5%). Our study highlights that maternal B12 insufficiency predicts elevated leptin in cord blood and is associated with higher birth weight. Since cord leptin is derived from neonatal adipose tissue and not mother, these findings suggest that maternal B12 might program leptin levels in-utero either directly through the satiety centre or mediated via inducing IR and adiposity in the offspring. Delineating the mechanistic relationship between cord leptin and maternal B12 might provide crucial answers in understanding the molecular mechanisms of adverse metabolic programming.