Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
Nat Commun. 2024 Nov 15;15(1):9640. doi: 10.1038/s41467-024-53813-1.
The teratogenic potential of valproate in pregnancy is well established; however, evidence regarding the long-term safety of other antiseizure medications (ASMs) during pregnancy remains limited. Using routinely collected primary care data from the UK and nationwide Swedish registries to create a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in pregnancy, we show that those exposed to valproate were more likely to receive a diagnosis of autism, intellectual disability, and ADHD, when compared to children not exposed to ASMs. Additionally, children exposed to topiramate were 2.5 times more likely to be diagnosed with intellectual disability (95% CI: 1.23-4.98), and those exposed to carbamazepine were 1.25 times more likely to be diagnosed with autism (95% CI: 1.05-1.48) and 1.30 times more likely to be diagnosed with intellectual disability (95% CI: 1.01-1.69). There was little evidence that children exposed to lamotrigine in pregnancy were more likely to receive neurodevelopmental diagnoses. While further research is needed, these findings may support considering safer treatment alternatives well before conception when clinically appropriate.
在怀孕期间，丙戊酸的致畸潜力已得到充分证实；然而，关于怀孕期间其他抗癫痫药物（ASM）的长期安全性的证据仍然有限。本研究使用英国和全国性瑞典登记处常规收集的初级保健数据创建了一个 3182773 名儿童的队列，其中 17495 名儿童在怀孕期间暴露于 ASM，结果表明，与未暴露于 ASM 的儿童相比，暴露于丙戊酸的儿童更有可能被诊断为自闭症、智力残疾和 ADHD。此外，与未暴露于 ASM 的儿童相比，暴露于托吡酯的儿童被诊断为智力残疾的可能性高 2.5 倍（95%CI：1.23-4.98），暴露于卡马西平的儿童被诊断为自闭症的可能性高 1.25 倍（95%CI：1.05-1.48）和智力残疾的可能性高 1.30 倍（95%CI：1.01-1.69）。几乎没有证据表明在怀孕期间暴露于拉莫三嗪的儿童更有可能被诊断为神经发育障碍。虽然需要进一步研究，但这些发现可能支持在临床合适的情况下，在受孕前就考虑使用更安全的替代治疗方法。
