Xu Shan-Chun, Zhong Ying, Jiang Hai-Yin, Tang Jun
Department of General Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China.
Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China.
Front Neurol. 2024 Jul 22;15:1440145. doi: 10.3389/fneur.2024.1440145. eCollection 2024.
Evidence of an association between maternal use of anti-seizure medication (ASM) during pregnancy and the risk of autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) in children is conflicting. This systematic review and meta-analysis aimed to summarize the relationship between fetal exposure to ASM and the development of ASD or ADHD in offspring.
A comprehensive literature search was conducted in PubMed and other databases to identify relevant epidemiological studies published from inception until 1 March 2024.
Seven cohort studies were included in the meta-analysis. The results showed that maternal exposure to ASMs during pregnancy was associated with an increased risk of ASD [odds ratio (OR): 2.1, 95% confidence interval (CI): 1.63-2.71; < 0.001] in the general population. This association became weaker (ASD: OR: 1.38, 95% CI: 1.11-1.73; = 0.004) when the reference group was mothers with a psychiatric disorder or epilepsy not treated during pregnancy. Furthermore, an increased risk of ADHD was observed when the study data adjusted for drug indications were pooled (OR: 1.43, 95% CI: 1.07-1.92; = 0.015). In subgroup analyses based on individual ASM use, only exposure to valproate preconception was significantly associated with an increased risk of ASD or ADHD.
The significant association between maternal ASM use during pregnancy and ASD or ADHD in offspring may be partially explained by the drug indication or driven by valproate.
孕期母亲使用抗癫痫药物（ASM）与儿童患自闭症谱系障碍（ASD）或注意力缺陷多动障碍（ADHD）风险之间的关联证据存在矛盾。这项系统评价和荟萃分析旨在总结胎儿暴露于ASM与后代患ASD或ADHD之间的关系。
在PubMed和其他数据库中进行了全面的文献检索，以识别从开始到2024年3月1日发表的相关流行病学研究。
荟萃分析纳入了7项队列研究。结果显示，在一般人群中，孕期母亲接触ASM与ASD风险增加相关[比值比（OR）：2.1，95%置信区间（CI）：1.63 - 2.71；P < 0.001]。当参照组为孕期未接受治疗的精神疾病或癫痫母亲时，这种关联变弱（ASD：OR：1.38，95% CI：1.11 - 1.73；P = 0.004）。此外，当汇总针对药物适应症调整后的研究数据时，观察到ADHD风险增加（OR：1.43，95% CI：1.07 - 1.92；P = 0.015）。在基于个体ASM使用情况的亚组分析中，仅孕前接触丙戊酸盐与ASD或ADHD风险增加显著相关。
孕期母亲使用ASM与后代患ASD或ADHD之间的显著关联可能部分由药物适应症解释或由丙戊酸盐驱动。
