Folic acid and neural tube defects: A review of the mechanisms of pathogenesis

Neural tube defects (NTDs) are common congenital problems in pediatric practice. Even though the epidemiologic link between maternal folate deficiency and fetal NTDs, and preventive role of folate supplementation on occurrence and recurrence of these defects is established, the causal mechanisms at cellular and molecular level remain undefined. Present paper reviews the embryology of neural tube closure in the light of recent molecular biologic advances, its regulation and role of abnormal folate metabolism in disturbing this process. Elevated levels of homocysteine probably represent the common pathway through which various errors of folate metabolism interfere with the process of neurulation. Various hypotheses which presently appear to be plausible in explaining this pathogenic link are discussed.