Risks of 23 specific malformations associated with prenatal exposure to ten antiepileptic drugs

Objective: To assess the association between exposure to monotherapy with 10 different antiepileptic drugs (AED) during the first two months of pregnancy and the risk of 23 major congenital malformations (MCMs).
Methods: This nationwide cohort study, based on the French healthcare databases, included all pregnancies&[ge]20 weeks and ending between January 2011 and March 2015. Women were considered to be exposed when an AED had been dispensed between one month before and two months after the beginning of pregnancy. The reference group included pregnant women with no reimbursement for AEDs. MCMs were detected up to 12 months after birth (24 months for microcephaly, hypospadias and epispadias). Odds ratios were adjusted for potential confounders for MCMs with at least five cases. Otherwise, we calculated crude ORs with exact confidence intervals.
Results: The cohort included 1,886,825 pregnancies, 2,997 of which were exposed to lamotrigine, 1,671 to pregabalin, 980 to clonazepam, 913...

研究目的：评估妊娠首两个月暴露于10种不同抗癫痫药物（antiepileptic drugs, AED）单药治疗与23种重大先天性畸形（major congenital malformations, MCMs）发病风险之间的关联。
方法：本研究为基于法国医疗数据库的全国性队列研究，纳入2011年1月至2015年3月期间分娩孕周≥20周的所有妊娠病例。若女性在妊娠起始前1个月至妊娠起始后2个月内领取过抗癫痫药物调配，则判定为暴露；对照组为无抗癫痫药物报销记录的妊娠女性。重大先天性畸形的随访至出生后12个月，其中小头畸形、尿道下裂及尿道上裂的随访至出生后24个月。对于病例数≥5例的重大先天性畸形，采用校正潜在混杂因素的比值比（odds ratios, OR）进行分析；其余情况则计算未校正比值比及其精确置信区间。
结果：本队列共纳入1,886,825例妊娠病例，其中2,997例暴露于拉莫三嗪、1,671例暴露于普瑞巴林、980例暴露于氯硝西泮、913例……