Increased rate of major malformations in offspring exposed to valproate during pregnancy
Increased rate of major malformations in offspring exposed to valproate during pregnancy
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DOI：
10.1212/01.wnl.0000154516.43630.c5
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发表时间：
2005-03-22
期刊：
影响因子：
9.9
通讯作者：
Holmes, LB
中科院分区：
文献类型：
--
作者：
Wyszynski, DF;Nambisan, M;Holmes, LB
目的：了解在北美抗癫痫药物妊娠登记中心登记的母亲在妊娠前三个月服用丙戊酸（VPA）作为单药治疗的婴儿发生重大畸形的比率。方法：通过电话访谈从美国和加拿大的孕妇中收集数据。每位妇女在入组时、妊娠7个月时和产后均接受了访谈。在她的书面许可下，获得了每位母亲及其婴儿的医疗记录。表中列出的主要畸形是在5日龄或之前发现的畸形。将单一治疗暴露于vpa的妇女的后代先天性畸形的患病率与暴露于所有其他抗癫痫药物的妇女的婴儿（内部对照组）以及布里格姆妇女医院主动畸形监测项目的新生儿（外部对照组）进行比较。结果：在149名暴露于vpa的妇女中发现16例感染病例（比例：10.7%;95% CI: 6.3 ~ 16.9%）。内部对照组患病率为2.9% （95% CI: 2.0 ~ 4.1%；比值比：4.0,95% CI: 2.1 ~ 7.4; p < 0.001）。假设外部对照组的患病率为1.62%，VPA暴露妇女的后代受影响的相对风险为7.3 （95% CI: 4.4 ~ 12.2; p < 0.001）。结论：妊娠前三个月母体接触丙戊酸可显著增加重大畸形的发生风险。
Objective: To determine the rate of occurrence of major malformations in infants whose mothers had taken the drug valproic acid (VPA) as monotherapy during the first trimester of pregnancy and had enrolled in the North American Antiepileptic Drug Pregnancy Registry. Methods: Data were collected from pregnant women throughout the United States and Canada through telephone-based interviews. Each woman was interviewed at enrollment, at 7 months' gestation, and postpartum. With her written permission, the medical records of each mother and her infant were obtained. The major malformations tabulated were those identified at or before 5 days of age. The prevalence of congenital malformations among offspring of monotherapy VPA-exposed women was compared with that among infants of women exposed to all other antiepileptic drugs ( internal comparison group) and with that among newborns in the Active Malformations Surveillance Program at Brigham and Women's Hospital ( external comparison group). Results: Sixteen affected cases were identified among 149 VPA-exposed women ( proportion: 10.7%; 95% CI: 6.3 to 16.9%). The prevalence in the internal comparison group was 2.9% ( 95% CI: 2.0 to 4.1%; odds ratio: 4.0, 95% CI: 2.1 to 7.4; p < 0.001). Assuming a 1.62% prevalence in the external comparison group, the relative risk of having an affected offspring for VPA- exposed women was 7.3 ( 95% CI: 4.4 to 12.2; p < 0.001). Conclusion: Maternal exposure to valproic acid during the first trimester of pregnancy significantly increased the risk of major malformations.