Effects of folate deficiency on embryonic development.

While there is strong evidence that folate deficiency including the use of anti-folate drugs in early pregnancy is teratogenic and may lead to a range of serious abnormalities of the developing fetus including intrauterine death, the mechanism(s) for these effects have not yet been delineated. In neural tube defects, there is increasing evidence that marginal folate status exacerbates the effect of an underlying genetic defect in the mother, the fetus, or both. An abnormal relationship between the ingestion of folate and the folate levels in red blood cells has been found in women who have given birth to infants with neural tube defects. Periconceptional folate supplementation has been shown to give effective protection against the development of neural tube defects. The mechanism of the prevention is as yet unknown. However, folic acid will not prevent all cases of neural tube defect. Moreover, neither determinations of periconceptional vitamin profiles (Mooij et al, 1993) nor determinations of methylmalonic acid and homocysteine levels will detect all women at risk. Anencephaly and spina bifida can be identified prenatally by detection of excessive levels of alpha-fetoprotein in amniotic fluid and maternal serum and by ultrasonographic scanning (Wilson and Rudd, 1993). Both genetic counselling and prenatal diagnosis should be offered to women who are recognized to be at high risk. Research into the underlying biology of neural tube defects is of major importance. The identification of underlying genetic defects would allow for genetic testing and better counselling of families at risk for the occurrence of a neural tube defect.