Shapiro S, Hartz S C, Siskind V, Mitchell A A, Slone D, Rosenberg L, Monson R R, Heinonen O P
Lancet. 1976 Feb 7;1(7954):272-5. doi: 10.1016/s0140-6736(76)91403-3.
The results of two studies, one in Finland and one in the U.S.A., raise the possibility that fetal damage previously attributed to phenytoin and other anticonvulsant drugs, principally phenobarbitone, may be due to epilepsy itself. In the U.S.A., drug-exposure information was collected before delivery in a cohort of 50 282 mother/child pairs. The total malformation rate in 305 children born to epileptic mothers was 10.5%, as against 6.4% in the remainder (p less than 0.01); corresponding rates for major malformations were 6.6% and 2.7%. When the fathers had epilepsy, the malformation-rates in their children were intermediate. The rates did not vary significantly according to maternal anticonvulsants therapy. Mental and motor scores as 8 months of age, and intelligence quotient scores at 4 years were lower in children of epileptic mothers, but not in children of epileptic fathers. The scores showed only random variation according to maternal anticonvulsant therapy. In Finland, 2784 children with craniofacial anomalies were compared with an equal number of normal children; 8 and 2 mothers, respectively, received anticonvulsants, while pregnant, for epilepsy. In that study, the separate effects of the disease and its treatmet could not be evaluated. Both studies did not find evidence of fetal damage when phenobarbitone was taken for indications other than epilepsy.
两项研究的结果,一项在芬兰进行,另一项在美国进行,这使得之前归因于苯妥英钠和其他抗惊厥药物(主要是苯巴比妥)的胎儿损伤可能是由癫痫本身导致的这一可能性增加。在美国,在一个由50282对母婴组成的队列中,在分娩前收集了药物暴露信息。癫痫母亲所生的305名儿童的总畸形率为10.5%,而其余儿童的畸形率为6.4%(p<0.01);主要畸形的相应发生率分别为6.6%和2.7%。当父亲患有癫痫时,其子女的畸形率处于中间水平。畸形率并未因母亲的抗惊厥治疗而有显著差异。癫痫母亲的孩子在8个月大时的智力和运动评分以及4岁时的智商评分较低,但癫痫父亲的孩子则不然。这些评分仅根据母亲的抗惊厥治疗显示出随机变化。在芬兰,将2784名患有颅面畸形的儿童与数量相等的正常儿童进行了比较;分别有8名和2名母亲在怀孕期间因癫痫接受了抗惊厥药物治疗。在该研究中,无法评估疾病及其治疗的单独影响。两项研究均未发现当苯巴比妥用于癫痫以外的适应症时存在胎儿损伤的证据。