In utero antiepileptic drug exposure - Fetal death and malformations
In utero antiepileptic drug exposure - Fetal death and malformations
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DOI：
10.1212/01.wnl.0000227919.81208.b2
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发表时间：
2006-08-08
期刊：
影响因子：
9.9
通讯作者：
Wolff, M. C.
中科院分区：
文献类型：
--
作者：
Meador, K. J.;Baker, G. A.;Wolff, M. C.
背景：子宫内暴露于抗癫痫药物(AED)后的妊娠结局是不确定的，这限制了一种基于证据的方法。目的：探讨宫内不同AED暴露对胎儿结局的影响。方法：这项正在进行的前瞻性观察研究涉及美国和英国的25个癫痫中心，从1999年10月至2004年2月招募了患有癫痫的孕妇，以确定四种最常用的抗癫痫药物是否存在不同的长期认知和行为神经发育影响。这份初步报告侧重于严重不良后果的发生率，包括严重的先天性畸形(可归因于AEDs)或胎儿死亡。总共对333对母子进行了单一药物暴露的分析：卡马西平(n=110)、拉莫三嗪(n=98)、苯妥英钠(n=56)和丙戊酸盐(n=69)。结果：各AED出现严重不良反应的妊娠反应频率分别为卡马西平8.2%、拉莫三嗪1.0%、苯妥英钠10.7%、丙戊酸盐20.3%。严重不良后果在AED中的分布差异很大，除了子宫内AED暴露外，不能用其他因素来解释。丙戊酸盐表现出剂量依赖效应。结论：与其他抗癫痫药物(AEDs)相比，宫内暴露丙戊酸盐的孕妇有更多的不良后果。这些结果结合最近的几项研究提供了强有力的证据，表明丙戊酸盐对胎儿的风险最高。对于未能通过其他AEDs并需要丙戊酸酯的女性，如果可能的话，剂量应该是有限的。
Background: Pregnancy outcomes following in utero exposure to antiepileptic drugs ( AEDs) are uncertain, limiting an evidenced-based approach. Objective: To determine if fetal outcomes vary as a function of different in utero AED exposures. Methods: This ongoing prospective observational study across 25 epilepsy centers in the USA and UK enrolled pregnant women with epilepsy from October 1999 to February 2004 to determine if differential long-term cognitive and behavioral neurodevelopmental effects exist across the four most commonly used AEDs. This initial report focuses on the incidence of serious adverse outcomes including major congenital malformations ( which could be attributable to AEDs) or fetal death. A total of 333 mother/child pairs were analyzed for monotherapy exposures: carbamazepine (n = 110), lamotrigine (n = 98), phenytoin (n = 56), and valproate (n = 69). Results: Response frequencies of pregnancies resulting in serious adverse outcomes for each AED were as follows: carbamazepine 8.2%, lamotrigine 1.0%, phenytoin 10.7%, and valproate 20.3%. Distribution of serious adverse outcomes differed significantly across AEDs and was not explained by factors other than in utero AED exposure. Valproate exhibited a dose-dependent effect. Conclusions: More adverse outcomes were observed in pregnancies with in utero valproate exposure vs the other antiepileptic drugs ( AEDs). These results combined with several recent studies provide strong evidence that valproate poses the highest risk to the fetus. For women who fail other AEDs and require valproate, the dose should be limited if possible.