Associations of maternal folic acid supplementation and folate concentrations during pregnancy with foetal and child head growth: the Generation R Study

Purpose Folic acid supplementation during pregnancy \nhas been associated with a reduced risk of common neurodevelopmental delays in the offspring. However, it is \nunclear whether low folate status has effects on the \ndeveloping brain. We evaluated the associations of \nmaternal folic acid supplementation and folate concentrations during pregnancy with repeatedly measured prenatal \nand postnatal head circumference in the offspring. \nMethods Within a population-based prospective cohort, \nwe measured maternal plasma folate concentrations at \napproximately 13 weeks of gestation (90 % range \n10.5\xe2\x80\x9317.2) and assessed folic acid supplementation by \nquestionnaire (2001\xe2\x80\x932005). Up to 11 repeated measures of \nhead circumference were obtained during foetal life (20 \nand 30 weeks of gestation) and childhood (between birth \nand age 6 years) in 5866 children (2002\xe2\x80\x932012). \nResults In unadjusted models, foetal head growth was \n0.006 SD (95 % CI 0.003; 0.009, P\\0.001) faster per \nweek per 1-SD higher maternal folate concentration. After \nadjustment for confounders, this association was attenuated \nto 0.004 SD per week (95 % CI 0.000; 0.007, P = 0.02; \nestimated absolute difference at birth of 2.7 mm). The \nassociation was independent of overall foetal growth. No \nassociations were found between maternal folate concentrations and child postnatal head growth. Preconceptional \nstart of folic acid supplementation was associated with \nlarger prenatal head size, but not with prenatal or postnatal \nhead growth. \nConclusions Our results suggest an independent, modest \nassociation between maternal folate concentrations in early \npregnancy and foetal head growth. More research is needed \nto identify whether specific brain regions are affected and \nwhether effects of folate on foetal head growth influence \nchildren\xe2\x80\x99s long-term functioning