Folic Acid and the Prevention of Neural Tube Defects

101 In 1991, a randomized trial funded by the Medical Research Council demonstrated that folic acid supplementation before pregnancy and during its early stages markedly reduced the risk of neural-tube defects in newborns.1This finding — which indicated that neural-tube defects may be considered to represent a vitamin-deficiency disorder — led to the recommendation that all women who are planning to become pregnant should take folic acid supplements beginning before pregnancy is recognized and continuing through its early stages. Once a pregnancy has been confirmed, it is probably too late for supplemental folic acid to be protective. In this issue of theJournal,Rothenberg and colleagues (pages 134–142) show that women who havehad a pregnancy complicated by a neural-tube defect haveautoantibodies to folate receptors. This observationsuggests a mechanism through which a folatedeficiency may cause neural-tube defects and how folic acid supplementation may prevent them. What is needed to guide public health policy is specification of the dose–response relation between extra folic acid and the reduction in the risk of neural-tube defects. What is the effect of different doses of folic acid on risk, and is there a dose that will prevent nearly all neural-tube defects? A two-stage dose–response model predicts the effects of a given amount of supplemental folic acid.2 The first part of the model specifies the relation between dietary folic acid and plasma folate, and the second part specifies the relation between the plasma folate level and the riskof a neural-tube defect. The first relation is additive: a given dose of folic acid adds a constant increment to a person’s plasma folate level, irrespective of dietary folate intake. The second relation isproportional: agiven percentage Folic Acid and the Prevention of Neural-Tube Defects