MATERNAL HYPERHOMOCYSTEINEMIA - A RISK FACTOR FOR NEURAL-TUBE DEFECTS

The maternal vitamin status, especially of folate, is involved in the pathogenesis of neural-tube defects (NTDs). Maternal folate administra tion can prevent these malformations. The precise metabolic mechanism of the beneficial effect of folate is unclear. In this study we focus on homocysteine accumulation, which may derive from abnormalities of m etabolism of folate, vitamin B-12, and vitamin B-6. We studied nonpreg nant women, 41 of whom had given birth to infants with NTDs and 50 con trol women who previously had normal offspring. The determinations inc luded the plasma total homocysteine both in the fasting state and 6 ho urs after the ingestion of a methionine load. In addition, we measured the fasting blood levels of folate, vitamin B-12, and vitamin b(6). T he mean values for both basal homocysteine and homocysteine following a methionine load were significantly increased in the group of women w ho previously had infants with NTDs. In nine of these subjects and two controls, the values after methionine ingestion exceeded the mean con trol by more than 2 standard deviations. Cystathionine synthase levels in skin fibroblasts derived from these methionine-intolerant women we re within the normal range. Our findings suggest a disorder in the rem ethylation of homocysteine to methionine due to an acquired (ie, nutri tional) or inherited derangement of folate or vitamin B-12 metabolism. Increased homocysteine levels can be normalized by administration of vitamin Bs or folate. Therefore, we suggest that the prevention of NTD s by periconceptional folate administration may effectively correct a mild to moderate hyperhomocysteinemia.