Associations of Early Pregnancy and Neonatal Circulating Folate, Vitamin B-12, and Homocysteine Concentrations with Cardiometabolic Risk Factors in Children at 10 y of Age

BACKGROUND: Higher circulating folate and vitamin B-12 concentrations and lower circulating homocysteine concentrations during pregnancy seem to be associated with fetal development. These micronutrients may also be associated with cardiometabolic health. OBJECTIVE: We examined the associations of circulating folate, vitamin B-12, and homocysteine concentrations during pregnancy and in neonates with childhood cardiometabolic outcomes. METHODS: This study was embedded in the Generation R Study, a population-based prospective cohort study from early pregnancy onward. We sampled blood in early pregnancy and cord blood. We measured cardiometabolic outcomes in the children at school age. Among 4449 children aged 10 y (median: 9.7; 95% range: 9.3, 10.7), we examined associations of plasma folate, serum vitamin B-12, and plasma homocysteine concentrations in early pregnancy and at birth with BMI, body fat distribution, heart rate, blood pressure, and insulin, glucose, and lipid concentrations, using linear regression models. Using logistic models, we examined the associations of these micronutrients with risks of overweight/obesity and clustering of cardiovascular risk factors. RESULTS: One standard deviation score (SDS) higher maternal plasma folate concentration was associated with lower BMI (−0.04 SDS; 95% CI: −0.08, −0.01), android-to-gynoid fat ratio (−0.04 SDS; 95% CI: −0.07, −0.01), systolic blood pressure (−0.06 SDS; 95% CI: −0.10, −0.03), risk of overweight (OR: 0.87; 95% CI: 0.78, 0.96), and clustering of cardiovascular risk factors (OR: 0.79; 95% CI: 0.68, 0.91). One SDS higher maternal serum total B-12 concentration was associated with lower glucose (−0.06 SDS; 95% CI: −0.10, −0.02) and higher HDL cholesterol concentrations (0.04 SDS; 95% CI: 0.00, 0.08). Cord blood folate, vitamin B-12, and homocysteine concentrations were not consistently associated with cardiometabolic outcomes. CONCLUSIONS: Subtle differences in circulating folate and vitamin B-12 concentrations in early pregnancy may be associated with child cardiometabolic health at age 10 y. The causality and mechanisms underlying these associations need further study.