Maternal folate status is important in the prevention and pathogenesis of neural tube defects (NTDs) . It is, however, unclear which precise mechanisms are involved. Pregnant women are prone to develop a folate deficiency, probably due to their increased folate demands for the growing fetal and maternal tissues. Other factors provoking folate deficiency include a poor diet, the physiological haemodilution of pregnancy, increased plasma clearance and hormonal influences, Our hypothesis is that a subset of NTDs might be due to a disbalance in the maternal and/or embryonic homocysteine metabolism, partly genically determined, in which folate plays a particularly important role.
In 1952, Thiersch first suggested an association between NTDs and a maternal lack of folate, due to the prenatal use of folate antagonists. Hibbard 1964 reported a higher prevalence of birth defects in the offspring of folate-deficient mothers (3%), judged by an increased urinary excretion of FiGlu after histidine loading, compared to controls (1.6%). However, the difference was not statistically significant and the malformations did not include NTDs. In 1965, Hibbard and Smithells reported a possible link between folate deficiency and the development of human fetal malformations, in particular central nervous system malformations, including NTDs. Their results suggested the presence of an underlying defect of folate metabolism, such as a disturbance in folate absorption or turnover, possibly precipitated by the increased demands of folate during pregnancy. This has been supported by Yates et al. , who demonstrated an association between maternal folate levels and NTD births, which could not be entirely explained by a lower intake of folate. Because the red cell folate levels in particular were lowest in mothers who had three or four previous NTD pregnancies, they hypothesized that a maternal genetic disorder of folate metabolism was responsible for the development of NTDs. The data reported by Kirke et al. are in line with this. They found that maternal plasma folate and vitamin B12 levels, determined at the first antenatal visit, were independent risk factors for having a child with a NTD. The NTD prevalence in the products of spontaneous abortion is 10-fold increased as compared to the prevalence at birth.
Reference: Régine P. Steegers-Theunissen. Folate metabolism and neural tube defects: a review[J]. European Journal of Obstetrics & Gynecology & Reproductive Biology, 1995, 61(1):39-48.