Safety concerns of maternal antiseizure medications exposure on perinatal and offspring outcomes: a disproportionality analysis based on FDA adverse event reporting system.
{"title":"Safety concerns of maternal antiseizure medications exposure on perinatal and offspring outcomes: a disproportionality analysis based on FDA adverse event reporting system.","authors":"Yanbin Zeng, Wanlong Lin, Wei Zhuang","doi":"10.1007/s00415-025-13172-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Many women are exposed to antiseizure medications (ASMs) during pregnancy, raising concerns about pregnancy and offspring health risks. The current safety data remain insufficient, necessitating further investigation.</p><p><strong>Methods: </strong>Using data from the FDA Adverse Event Reporting System (2010-2023), this study employed both the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) for disproportionality analysis of pregnancy and offspring toxicity related to maternal ASM exposure. In addition, we performed signal adjustment by excluding polytherapy cases, and drug-drug interaction (DDI) signals of two ASMs were identified using Ω Shrinkage measures and Chi-square tests.</p><p><strong>Results: </strong>3,459 mothers were exposed to 23 ASMs, resulting in 10,910 adverse events. 59 malformation signals, 27 adverse perinatal outcome signals, and 35 dysplasia signals were identified. Among traditional ASMs, valproic acid (VPA) and carbamazepine (CBZ) exhibited the highest number of signals, while levetiracetam (LEV), lamotrigine (LTG), lacosamide, gabapentin, and topiramate (TPM) predominated among newer ASMs. Signals for cardiac malformations, adverse neurodevelopment, and adverse offspring growth outcomes were widespread, with the strongest signals for specific outcomes observed for zonisamide [ROR = 14.82, 95% CI: 5.43-40.41], gabapentin [ROR = 52.52, 95% CI: 15.68-175.95], and brivaracetam [ROR = 22.96, 95% CI: 8.42-62.61], respectively. Six DDI signals displayed ≥ 3, including LTG + LEV/VPA associated with malformation, CBZ + lacosamide/LTG, and VPA + clonazepam associated with fetal loss.</p><p><strong>Conclusions: </strong>The potential risks associated with LEV and LTG surpass expectations, warranting further evaluation, particularly in combination therapy. In addition, ASMs with widespread signals, such as VPA, CBZ, TPM, and lacosamide, warrant heightened attention.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"429"},"PeriodicalIF":4.8000,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00415-025-13172-3","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Many women are exposed to antiseizure medications (ASMs) during pregnancy, raising concerns about pregnancy and offspring health risks. The current safety data remain insufficient, necessitating further investigation.
Methods: Using data from the FDA Adverse Event Reporting System (2010-2023), this study employed both the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) for disproportionality analysis of pregnancy and offspring toxicity related to maternal ASM exposure. In addition, we performed signal adjustment by excluding polytherapy cases, and drug-drug interaction (DDI) signals of two ASMs were identified using Ω Shrinkage measures and Chi-square tests.
Results: 3,459 mothers were exposed to 23 ASMs, resulting in 10,910 adverse events. 59 malformation signals, 27 adverse perinatal outcome signals, and 35 dysplasia signals were identified. Among traditional ASMs, valproic acid (VPA) and carbamazepine (CBZ) exhibited the highest number of signals, while levetiracetam (LEV), lamotrigine (LTG), lacosamide, gabapentin, and topiramate (TPM) predominated among newer ASMs. Signals for cardiac malformations, adverse neurodevelopment, and adverse offspring growth outcomes were widespread, with the strongest signals for specific outcomes observed for zonisamide [ROR = 14.82, 95% CI: 5.43-40.41], gabapentin [ROR = 52.52, 95% CI: 15.68-175.95], and brivaracetam [ROR = 22.96, 95% CI: 8.42-62.61], respectively. Six DDI signals displayed ≥ 3, including LTG + LEV/VPA associated with malformation, CBZ + lacosamide/LTG, and VPA + clonazepam associated with fetal loss.
Conclusions: The potential risks associated with LEV and LTG surpass expectations, warranting further evaluation, particularly in combination therapy. In addition, ASMs with widespread signals, such as VPA, CBZ, TPM, and lacosamide, warrant heightened attention.
期刊介绍：
The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field.
In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials.
Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
