Hernández-Díaz S, Werler M M, Walker A M, Mitchell A A
Slone Epidemiology Unit, Boston University School of Public Health, Brookline, Mass 02446, USA.
N Engl J Med. 2000 Nov 30;343(22):1608-14. doi: 10.1056/NEJM200011303432204.
Multivitamin supplementation in pregnant women may reduce the risks of cardiovascular defects, oral clefts, and urinary tract defects in their infants. We evaluated whether the folic acid component of multivitamins is responsible for the reduction in risk by examining the associations between maternal use of folic acid antagonists and these congenital malformations.
We compared data on exposure to folic acid antagonists that act as dihydrofolate reductase inhibitors and to certain antiepileptic drugs for 3870 infants with cardiovascular defects, 1962 infants with oral clefts, and 1100 infants with urinary tract defects with data for 8387 control infants with malformations the risk of which is not reduced after vitamin supplementation. Mothers were interviewed within six months after delivery about their medication use.
The relative risks of cardiovascular defects and oral clefts in infants whose mothers were exposed to dihydrofolate reductase inhibitors during the second or third month after the last menstrual period, as compared with infants whose mothers had no such exposure, were 3.4 (95 percent confidence interval, 1.8 to 6.4) and 2.6 (95 percent confidence interval, 1.1 to 6.1), respectively. The relative risks of cardiovascular defects, oral clefts, and urinary tract defects after maternal exposure to antiepileptic drugs were 2.2 (95 percent confidence interval, 1.4 to 3.5), 2.5 (95 percent confidence interval, 1.5 to 4.2), and 2.5 (95 percent confidence interval, 1.2 to 5.0), respectively. Use of multivitamin supplements containing folic acid diminished the adverse effects of dihydrofolate reductase inhibitors, but not that of antiepileptic drugs.
Folic acid antagonists, which include such common drugs as trimethoprim, triamterene, carbamazepine, phenytoin, phenobarbital, and primidone, may increase the risk not only of neural-tube defects, but also of cardiovascular defects, oral clefts, and urinary tract defects. The folic acid component of multivitamins may reduce the risks of these defects.
孕妇补充多种维生素可能会降低其婴儿患心血管缺陷、唇腭裂和泌尿系统缺陷的风险。我们通过研究孕妇使用叶酸拮抗剂与这些先天性畸形之间的关联，来评估多种维生素中的叶酸成分是否是降低风险的原因。
我们将3870例患心血管缺陷的婴儿、1962例患唇腭裂的婴儿和1100例患泌尿系统缺陷的婴儿暴露于作为二氢叶酸还原酶抑制剂的叶酸拮抗剂及某些抗癫痫药物的数据，与8387例患畸形但补充维生素后风险未降低的对照婴儿的数据进行了比较。在分娩后6个月内对母亲进行访谈，了解她们的用药情况。
与母亲未暴露于此的婴儿相比，在末次月经后第二个或第三个月母亲暴露于二氢叶酸还原酶抑制剂的婴儿患心血管缺陷和唇腭裂的相对风险分别为3.4（95%置信区间为1.8至6.4）和2.6（95%置信区间为1.1至6.1）。母亲暴露于抗癫痫药物后患心血管缺陷、唇腭裂和泌尿系统缺陷的相对风险分别为2.2（95%置信区间为1.4至3.5）、2.5（95%置信区间为1.5至4.2）和2.5（95%置信区间为1.2至5.0）。使用含叶酸的多种维生素补充剂可减轻二氢叶酸还原酶抑制剂的不良影响，但不能减轻抗癫痫药物的不良影响。
叶酸拮抗剂，包括甲氧苄啶、氨苯蝶啶、卡马西平、苯妥英、苯巴比妥和扑米酮等常用药物，可能不仅会增加神经管缺陷的风险，还会增加心血管缺陷、唇腭裂和泌尿系统缺陷的风险。多种维生素中的叶酸成分可能会降低这些缺陷的风险。
