Epidemiology of neural tube defects

AbstractThe epidemiological investigation of the common open neural tube defects (NTDs), anencephaly, and spina bifida, has a long history. The most significant finding from these past studies of NTDs was the identification of the protective effect of maternal, periconceptional supplementation with folic acid. Fortuitously, the association between folic acid and NTDs became widely accepted in the early 1990s, at a time when genetic association studies of complex traits were becoming increasingly feasible. The confluence of these events has had a major impact on the direction of epidemiological, NTD research. Association studies to evaluate genes that may influence the risk of NTDs through their role in folate‐related processes, or through other metabolic or developmental pathways are now commonplace. Moreover, the study of genetic as well as non‐genetic, factors that may influence NTD risk through effects on the nutrient status of the mother or embryo has emerged as a major research focus. Research efforts over the past decade indicate that gene–gene, gene–environment, and higher‐order interactions, as well as maternal genetic effects influence NTD risk, highlighting the complexity