Epidemiology of neural tube defects

Neural tube defects (NTDs)-malformations secondary to abnormal neural tube closure between the third and fourth weeks of gestational age-have a complex and imperfectly understood etiology in which both genetic and environmental factors appear to be involved. A number of specific chromosomal or single-gene disorders, presumably not affected by environmental influences, are associated with the development of NTDs, but such syndromal cases account for a small proportion of NTDs in live-born infants. Analysis of recurrence patterns within families and of twin-concordance data provides evidence of a genetic influence in nonsyndromal cases, but factors such as socioeconomic status and geographic area (independent of race or ethnicity) are also associated with variations in the incidence of NTDs. The prevalence at birth of both anencephaly and spina bifida has decreased, but the advent of antenatal diagnosis and elective termination of affected pregnancies has undermined the reliability of birth prevalence rate as an estimate of incidence. Some occupational and other exposures, including maternal use of antiepileptic drugs (AEDs), are associated with increased risk for NTDs. Among women who have had an NTD-affected pregnancy, recurrence risk is markedly higher than the risk for a first NTD-affected pregnancy in the general population. There is strong evidence, overall, for a protective effect of adequate folate consumption. In some high-risk groups, however, such as women taking AEDs, folate supplementation has not been proven to reduce NTD risk.