We present data from a case series in France of pregnant women who lost 2 to 14 kg during the first month after conception and whose fetuses developed neural tube defects (NTDs). Preliminary epidemiologic evidence from other data sets suggest that relative lack of weight gain during pregnancy may be associated with NTDs. The role of starvation, diabetes, and valproic acid in the etiology of NTDs is established. This etiologic information coupled with our data suggest an hypothesis that ketoacidosis induced by weight loss in early pregnancy is a risk factor for NTDs.