Neural tube defects and maternal hyperthermia in early pregnancy: Epidemiology in a human embryo population

A causal relationship between neural tube defects and maternal febrile illness in early pregnancy was investigated retrospectively using human embryo data from Japan. The frequency of febrile illness was compared with corresponding data from normal controls, and holoprosencephalic and polydactylous embryos. Within the group of neural tube defects, the prevalence of maternal hyperthermia was significantly higher than in normal control and holoprosencephaly mothers. The association was constant and highly significant specifically for exencephaly, which is an embryonic forerunner of anencephaly. The correlation with myeloschisis (without exencephaly) was not significant. In eight out of the ten cases in which the timing of the fever was known, it occurred during the clinically determined critical period of neural tube closure in human embryos. These results support the hypothesis that maternal hyperthermia in early pregnancy can cause neural tube defects in man, especially anencephaly.