本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2309359

摘要内容如下：

背景

母亲在怀孕期间使用丙戊酸盐与儿童神经发育障碍的风险增加有关。尽管大多数关于其他抗癫痫药物的研究并未显示这些疾病的风险增加，但关于母亲使用托吡酯与自闭症谱系障碍风险相关的数据有限且相互矛盾。

方法

我们在美国的两个卫生保健利用数据库中确定了一个基于人群的孕妇及其子女队列，数据从2000年到2020年。特定抗癫痫药物的暴露量是根据从妊娠19周到分娩的处方药来定义的。在怀孕后半期暴露于托吡酯的儿童与在怀孕期间未暴露于任何抗癫痫药物的儿童在自闭症谱系障碍的风险方面进行比较。丙戊酸钠作为阳性对照，拉莫三嗪作为阴性对照。

结果

在未接触抗癫痫药物的全部儿童人群（4，199，796名儿童）中，估计8岁时自闭症谱系障碍的累积发病率为1.9%。仅限于患有癫痫的母亲所生的儿童，未接触抗癫痫药物的发生率为4.2%（8815名儿童），接触托吡酯的发生率为6.2%（1030名儿童），接触丙戊酸盐的发生率为10.5%（800名儿童），接触拉莫三嗪的发生率为4.1%（4205名儿童）。与未暴露于抗癫痫药物相比，暴露于托吡酯的倾向评分调整风险比为0.96（95%可信区间[CI]，0.56-1.65），暴露于丙戊酸盐的为2.67（95%CI，1.69-4.20），暴露于拉莫三嗪的为1.00（95%CI，0.69-1.46）。

结论

与普通人群相比，产前暴露于所研究的抗癫痫药物的儿童中自闭症谱系障碍的发病率更高。然而，在对适应症和其他混杂因素进行调整后，托吡酯和拉莫三嗪的相关性显著减弱，而丙戊酸盐的风险仍然增加。（由国家精神卫生研究所资助）。

英文原文如下：

Abstracts

BACKGROUND  Maternal use of valproate during pregnancy has been associated with an increased risk of neurodevelopmental disorders in children. Although most studies of other antiseizure medications have not shown increased risks of these disorders, there are limited and conflicting data regarding the risk of autism spectrum disorder associated with maternal topiramate use.

METHODS  We identified a population-based cohort of pregnant women and their children within two health care utilization databases in the United States, with data from 2000 through 2020. Exposure to specific antiseizure medications was defined on the basis of prescription fills from gestational week 19 until delivery. Children who had been exposed to topiramate during the second half of pregnancy were compared with those unexposed to any antiseizure medication during pregnancy with respect to the risk of autism spectrum disorder. Valproate was used as a positive control, and lamotrigine was used as a negative control.

RESULTS  The estimated cumulative incidence of autism spectrum disorder at 8 years of age was 1.9% for the full population of children who had not been exposed to antiseizure medication (4,199,796 children). With restriction to children born to mothers with epilepsy, the incidence was 4.2% with no exposure to antiseizure medication (8815 children), 6.2% with exposure to topiramate (1030 children), 10.5% with exposure to valproate (800 children), and 4.1% with exposure to lamotrigine (4205 children). Propensity score-adjusted hazard ratios in a comparison with no exposure to antiseizure medication were 0.96 (95% confidence interval [CI], 0.56 to 1.65) for exposure to topiramate, 2.67 (95% CI, 1.69 to 4.20) for exposure to valproate, and 1.00 (95% CI, 0.69 to 1.46) for exposure to lamotrigine.

CONCLUSIONS  The incidence of autism spectrum disorder was higher among children prenatally exposed to the studied antiseizure medications than in the general population. However, after adjustment for indication and other confounders, the association was substantially attenuated for topiramate and lamotrigine, whereas an increased risk remained for valproate. (Funded by the National Institute of Mental Health.).

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