Shahriari Pouneh, Drouin Jérôme, Miranda Sara, Bougas Nicolas, Botton Jérémie, Dray-Spira Rosemary
EPI-PHARE Scientific Interest Group in Epidemiology of Health Products (French National Agency for the Safety of Medicines and Health Products [ANSM], French National Health Insurance [CNAM]), Saint-Denis, France.
Department of Social Epidemiology (ERES) of Pierre Louis Institute for Epidemiology and Public Health (IPLESP), French National Institute of Health and Medical Research (INSERM), Paris, France; and.
Neurology. 2025 Aug 26;105(4):e213933. doi: 10.1212/WNL.0000000000213933. Epub 2025 Jul 23.
Prenatal exposure to certain antiseizure medications (ASMs) is associated with established or suspected risks of congenital malformations and neurodevelopmental disorders. Large-scale, real-life data are essential to guide efforts to mitigate these risks. Our objective was to assess trends in prenatal exposure to ASMs over the past decade according to medication safety profiles.
This nationwide, population-based study is based on comprehensive data of the French National Mother-Child Register EPI-MERES. All ASM-exposed pregnancies ended between 2013 and 2021 were included. ASM-exposed pregnancies' frequency and characteristics (maternal sociodemographics and morbidities, pregnancy outcome, and ASM treatment modalities) were assessed considering 3 safety categories: (1) ASMs considered the safest (lamotrigine and levetiracetam); (2) ASMs with uncertain risk, including pregabalin, gabapentin, and newer ASMs (e.g., lacosamide and zonisamide); and (3) ASMs with acknowledged risk, including valproic acid, valpromide, carbamazepine, and topiramate.
Between 2013 and 2021, 55,801 pregnancies were exposed to ≥1 ASM. Pregnancies exposed to the safest ASMs increased by +30%. Meanwhile, prenatal exposure to valproic acid and valpromide dramatically decreased due to decreasing numbers of exposed pregnancies (-84% and -89%, respectively), increasing termination rate of exposed pregnancies (+23% and +28%, respectively), and among those ended in childbirth, decreasing numbers with multiple valproate dispensations (-86% and -93%, respectively) or sustained exposure throughout pregnancy (-91% and -96%, respectively). Prenatal exposure to carbamazepine and topiramate barely decreased, with almost 600 newborns still exposed to each of these ASMs in 2019-2021. Pregabalin and gabapentin became widely used during pregnancy, resulting in more and more newborns prenatally exposed (+28%), and for pregabalin increasingly with multiple dispensations (+65%) and sustained exposure throughout pregnancy (+171%). The numbers of pregnancies and newborns exposed to newer ASMs also sharply increased (+140% and +60%, respectively). Overall, prenatal exposure to ASMs with acknowledged or uncertain risk disproportionately concerned pregnant women with a low level of resources (18.5% and 17.9%, respectively, vs 13%-14% among pregnancies exposed to the safest ASMs or ASM-unexposed).
Despite a sharp shift from valproate to safer ASMs, prenatal exposure to other ASMs with acknowledged or uncertain risks has persisted or even increased, particularly among the most socially disadvantaged populations, requiring additional risk minimization measures.
孕期接触某些抗癫痫药物（ASM）与先天性畸形和神经发育障碍的既定或疑似风险相关。大规模的真实数据对于指导降低这些风险的努力至关重要。我们的目的是根据药物安全概况评估过去十年中孕期接触ASM的趋势。
这项基于全国人群的研究基于法国国家母婴登记册EPI-MERES的综合数据。纳入了2013年至2021年间所有以接触ASM告终的妊娠。考虑3种安全类别评估了接触ASM的妊娠的频率和特征（孕产妇社会人口统计学和发病率、妊娠结局以及ASM治疗方式）：（1）被认为最安全的ASM（拉莫三嗪和左乙拉西坦）；（2）风险不确定的ASM，包括普瑞巴林、加巴喷丁和新型ASM（如拉科酰胺和唑尼沙胺）；（3）有公认风险的ASM，包括丙戊酸、丙戊酰胺、卡马西平和托吡酯。
2013年至2021年间，55,801例妊娠接触了≥1种ASM。接触最安全ASM的妊娠增加了30%。与此同时，由于接触妊娠数量减少（分别减少84%和89%）、接触妊娠的终止率增加（分别增加23%和28%）以及在分娩的妊娠中，接受多次丙戊酸盐配药的数量减少（分别减少86%和93%）或整个孕期持续接触的数量减少（分别减少91%和96%），孕期接触丙戊酸和丙戊酰胺显著下降。孕期接触卡马西平和托吡酯几乎没有下降，2019 - 2021年每年仍有近600名新生儿接触这些ASM。普瑞巴林和加巴喷丁在孕期广泛使用，导致越来越多的新生儿在产前接触（增加28%），对于普瑞巴林，接受多次配药的情况越来越多（增加65%）且整个孕期持续接触的情况增加（增加171%）。接触新型ASM的妊娠和新生儿数量也急剧增加（分别增加140%和60%）。总体而言，接触有公认或不确定风险的ASM的情况在资源水平较低的孕妇中占比过高（分别为18.5%和17.9%，而接触最安全ASM或未接触ASM的妊娠中这一比例为13% - 14%）。
尽管从丙戊酸盐向更安全的ASM有明显转变，但孕期接触其他有公认或不确定风险的ASM的情况持续存在甚至增加，尤其是在社会经济最不利的人群中，这需要额外的风险最小化措施。
