Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
Neurology. 2012 May 22;78(21):1692-9. doi: 10.1212/WNL.0b013e3182574f39. Epub 2012 May 2.
To assess the safety of the newer antiepileptic drugs (AEDs) during pregnancy.
The study population was pregnant women who enrolled in the North American AED Pregnancy Registry between 1997 and 2011. Data on AED use and maternal characteristics were collected through phone interviews at enrollment, at 7 months' gestation, and postpartum. Malformations were confirmed by medical records. The risk of major malformations was calculated among infants exposed to specific AEDs in monotherapy during the first trimester of pregnancy and among an unexposed group. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated with logistic regression.
The risk of major malformations was 9.3% (30 of 323) for valproate, 5.5% (11 of 199) for phenobarbital, 4.2% (15 of 359) for topiramate, 3.0% (31 of 1.033) for carbamazepine, 2.9% (12 of 416) for phenytoin, 2.4% (11 of 450) for levetiracetam, and 2.0% (31 of 1,562) for lamotrigine. Compared with lamotrigine, the RR was 5.1 (95% CI 3.0-8.5) for valproate, 2.9 (1.4-5.8) for phenobarbital, and 2.2 (1.2-4.0) for topiramate. The proportion of women with epilepsy who had seizures during pregnancy ranged from 23% for valproate to 31% for lamotrigine. Valproate was associated with a higher risk of neural tube defects, hypospadias, cardiac defects, and oral clefts and phenobarbital with a higher risk of cardiac defects and oral clefts; 5 infants exposed to topiramate (1.4%) had a cleft lip.
AEDs such as valproate and phenobarbital were associated with a higher risk of major malformations than newer AEDs such as lamotrigine and levetiracetam. Topiramate was associated with an increased risk of cleft lip compared with that of a reference population.
评估新型抗癫痫药物（AEDs）在妊娠期间的安全性。
研究人群为 1997 年至 2011 年间参加北美 AED 妊娠登记处的孕妇。通过在入组时、妊娠 7 个月时和产后进行电话访谈，收集 AED 使用和产妇特征的数据。通过病历确认畸形。在妊娠早期单药暴露于特定 AED 的婴儿组和未暴露组中，计算主要畸形的风险。使用逻辑回归估计风险比（RR）和 95%置信区间（CI）。
丙戊酸的主要畸形风险为 9.3%（30/323），苯巴比妥为 5.5%（11/199），托吡酯为 4.2%（15/359），卡马西平为 3.0%（31/1033），苯妥英钠为 2.9%（12/416），左乙拉西坦为 2.4%（11/450），拉莫三嗪为 2.0%（31/1562）。与拉莫三嗪相比，丙戊酸的 RR 为 5.1（95%CI 3.0-8.5），苯巴比妥为 2.9（1.4-5.8），托吡酯为 2.2（1.2-4.0）。癫痫妇女在怀孕期间癫痫发作的比例从丙戊酸的 23%到拉莫三嗪的 31%不等。丙戊酸与神经管缺陷、尿道下裂、心脏缺陷和口腔裂的风险增加有关，苯巴比妥与心脏缺陷和口腔裂的风险增加有关；5 名暴露于托吡酯（1.4%）的婴儿有唇裂。
与新型 AED 如拉莫三嗪和左乙拉西坦相比，丙戊酸和苯巴比妥等 AED 与主要畸形风险增加相关。与参考人群相比，托吡酯与唇裂风险增加相关。
