College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.
British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
Br J Clin Pharmacol. 2024 Aug;90(8):1827-1837. doi: 10.1111/bcp.15752. Epub 2023 May 10.
We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy.
We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy.
We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW.
This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks.
我们旨在系统地综合目前已发表的关于抗癫痫药物(ASM)在妊娠期间使用与新生儿生长结局相关的文献。
我们检索了 7 个数据库,检索时间截至 2022 年 3 月 23 日。我们将小于胎龄儿(SGA)和低出生体重(LBW)作为主要结局,将出生体重、出生身高、头围指数作为次要结局进行研究。主要分析包括暴露于任何 ASM 的孕妇与未暴露于 ASM 的孕妇进行比较。亚组分析包括 ASM 类别分析、癫痫组内分析以及与单药治疗相比的多药治疗。
我们筛选了 15720 条引文,纳入了 65 项研究进行综述。暴露于 ASM 的孕妇发生 SGA 的相对风险(RR)显著增加(RR 1.33,95%CI 1.18 至 1.50,I²74%),LBW 的 RR 为 1.54(95%CI 1.33 至 1.77,I²67%),且出生体重平均差值(MD)为-118.87(95%CI -161.03 至 -76.71,I²42%)g。出生身高和头围的风险变化无统计学意义。在亚组分析中,ASM 多药治疗、癫痫内和 ASM 类别分析也与 SGA 和 LBW 的风险增加相关。
这项荟萃分析表明,与未暴露于 ASM 的孕妇相比,暴露于 ASM 的孕妇发生不良胎儿生长结局(包括 SGA 和 LBW)和出生体重降低的风险显著增加。与单药治疗相比,多药治疗与更高的风险相关。需要开展更多关于特定 ASM 风险的研究。