Mills J L, McPartlin J M, Kirke P N, Lee Y J, Conley M R, Weir D G, Scott J M
Pediatric Epidemiology Section, NICHD, NIH, Bethesda, MD 20892.
Lancet. 1995 Jan 21;345(8943):149-51. doi: 10.1016/s0140-6736(95)90165-5.
Folic acid taken around the time of conception can prevent many neural-tube defects. Women with low-normal vitamin B12 values may also be at increased risk. We considered whether homocysteine metabolism via the enzyme methionine synthase, which requires both folate and B12, could be the critical defect in folate-related neural tube defects. Blood was obtained during pregnancies that produced 81 infants with neural-tube defects and 323 normal children. Samples were assayed for homocysteine, methylmalonic acid, plasma folate, red-cell folate, and B12. Mothers of children with neural-tube defects had significantly higher homocysteine values (8.62 [SD 2.8] mumol/L) than did B12-matched controls (7.96 [2.5] mumol/L, p = 0.03). The difference was significant (p = 0.004) in the lower half of the B12 distribution after adjusting for plasma folate. Our study shows that an abnormality in homocysteine metabolism, apparently related to methionine synthase, is present in many women who give birth to children with neural-tube defects. Overcoming this abnormality is likely to be the mechanism by which folic acid prevents neural-tube defects. These findings suggest that the most effective periconceptional prophylaxis to prevent neural-tube defects may require B12 as well as folic acid.
受孕前后补充叶酸可预防许多神经管缺陷。维生素B12水平略低的女性患神经管缺陷的风险也可能增加。我们思考，通过蛋氨酸合酶进行的同型半胱氨酸代谢（该过程同时需要叶酸和B12）是否可能是叶酸相关神经管缺陷的关键缺陷。我们采集了81例患有神经管缺陷婴儿的孕妇以及323例正常儿童孕妇的血液样本，检测样本中的同型半胱氨酸、甲基丙二酸、血浆叶酸、红细胞叶酸和B12水平。患有神经管缺陷儿童的母亲的同型半胱氨酸值（8.62[标准差2.8]μmol/L）显著高于B12水平匹配的对照组（7.96[2.5]μmol/L，p = 0.03）。在对血浆叶酸进行校正后，B12分布下半部分的差异具有显著性（p = 0.004）。我们的研究表明，许多生育神经管缺陷患儿的女性存在同型半胱氨酸代谢异常，这显然与蛋氨酸合酶有关。克服这种异常可能是叶酸预防神经管缺陷的机制。这些发现表明，预防神经管缺陷最有效的孕前预防措施可能需要同时补充B12和叶酸。
