Association of prenatal exposure to antiseizure medication with risk of autism: a systematic review and meta-analysis

IF 2.7 3区医学 Q2 CLINICAL NEUROLOGY

Seizure-European Journal of Epilepsy Pub Date : 2025-05-03 DOI:10.1016/j.seizure.2025.05.003

Isabella Christina Amaral de Lara , Pedro Henrique de Souza Wagner , Gustavo Tadeu Freitas Uchôa Matheus , Lara Eduardo Campos , Celso de Almeida Souza Miranda , Maria Eduarda Cavalcanti Souza , Francisco Cezar Aquino de Moraes , Francinny Alves Kelly , Lilianne Rodrigues Fernandes

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Abstract

Background

Antiseizure medications (ASMs) can affect neurodevelopment and cause congenital malformations. Autism spectrum disorder (ASD) is characterized by challenges in communication, behavior, and learning. This study evaluated the association between prenatal ASM exposure and ASD development.

Methods

A systematic review and meta-analysis was conducted using PubMed, Scopus, Web of Science, and Cochrane databases to identify studies on fetal ASM exposure and ASD. Hazard ratio (HR) and risk ratio (RR) with 95 % confidence interval (CI) were pooled using a random-effects model. Heterogeneity was assessed using I² statistic. A p-value < 0.05 was considered significant.

Results

10 studies were included in our meta-analysis, comprising 54,747 patients exposed to ASM. Prenatal ASM exposure significantly increased the risk of ASD (HR 1.8082; 95 % CI 1.2616 to 2.5916; P = 0.001; RR 2.0401; 95 % CI 1.7588 to 2.3664; P < 0.0001). Subgroup analyses identified elevated risks with specific ASMs, including carbamazepine (HR 1.2213; 95 % CI 1.0047 to 1.4847; P = 0.045; I² = 0 %), valproate (HR 2.8306; 95 % CI 2.3881 to 3.3550; P < 0.001; I² = 0 %), and oxcarbazepine (HR 1.6141; 95 % CI 1.1500 to 2.2655; P = 0.006; I² = 27 %). Among women with epilepsy, prenatal ASM exposure increased ASD risk (RR 1.4174; 95 % CI 1.2345 to 1.6273; P < 0.0001; I² = 0 %).

Conclusions

This meta-analysis showed that prenatal exposure to antiseizures, particularly valproate, carbamazepine, and oxcarbazepine, significantly increases ASD risk. These findings emphasize the need for cautious ASM use during pregnancy.

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产前抗癫痫药物暴露与自闭症风险的关系：一项系统回顾和荟萃分析

背景：抗癫痫药物会影响神经发育并导致先天性畸形。自闭症谱系障碍（ASD）的特点是沟通、行为和学习方面的挑战。本研究评估了产前ASM暴露与ASD发展之间的关系。方法采用PubMed、Scopus、Web of Science、Cochrane等数据库，对胎儿ASM暴露与ASD的相关研究进行系统回顾和meta分析。采用随机效应模型合并95%置信区间的风险比（HR）和风险比（RR）。采用I²统计量评估异质性。p值<；0.05被认为是显著的。我们的荟萃分析纳入了10项研究，包括54,747例暴露于ASM的患者。产前ASM暴露显著增加ASD风险(HR 1.8082；95% CI 1.2616 - 2.5916；P = 0.001；RR 2.0401;95% CI 1.7588 - 2.3664；P & lt;0.0001)。亚组分析确定特定asm的风险升高，包括卡马西平(HR 1.2213；95% CI 1.0047 - 1.4847；P = 0.045；I²= 0%)，丙戊酸盐(HR 2.8306；95% CI 2.3881 - 3.3550；P & lt;0.001;I²= 0 %)和奥卡西平(HR 1.6141；95% CI 1.1500 - 2.2655；P = 0.006；I²= 27%)。在患有癫痫的女性中，产前ASM暴露会增加ASD风险(RR 1.4174；95% CI 1.2345 - 1.6273；P & lt;0.0001;I²= 0 %)。结论：本荟萃分析显示，产前暴露于抗癫痫药物，特别是丙戊酸、卡马西平和奥卡西平，显著增加ASD风险。这些发现强调了在怀孕期间谨慎使用ASM的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Seizure-European Journal of Epilepsy 医学-临床神经学

CiteScore

5.60

自引率

6.70%

发文量

231

审稿时长

34 days

期刊介绍： Seizure - European Journal of Epilepsy is an international journal owned by Epilepsy Action (the largest member led epilepsy organisation in the UK). It provides a forum for papers on all topics related to epilepsy and seizure disorders.