Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
Department of Obstetrics and Gynaecology, The University of British Columbia, Vancouver, British Columbia, Canada.
J Neurol Neurosurg Psychiatry. 2020 Sep;91(9):907-913. doi: 10.1136/jnnp-2020-323028. Epub 2020 Jul 10.
To investigate the association between paternal use of antiepileptic drugs (AEDs) and adverse neurodevelopmental outcomes and major congenital malformations (MCM) in the offspring.
Using nationwide Swedish registries, we included 1 144 795 births to 741 726 fathers without epilepsy and 4544 births to 2955 fathers with epilepsy. Of these, 2087 (45.9%) were born to fathers with epilepsy who had dispensed an AED during the conception period. Children who had both parents with epilepsy were excluded. The incidence rate of MCM, autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and intellectual disability in offspring was analysed.
Offspring of fathers exposed to AEDs did not show an increased risk of MCM (adjusted OR 0.9, 95% CI 0.7 to 1.2), autism (adjusted HR (aHR) 0.9, 95% CI 0.5 to 1.7), ADHD (aHR 1.1, 95% CI 0.7 to 1.9) or intellectual disability (aHR 1.3, 95% CI 0.6 to 2.8) compared with offspring of fathers with epilepsy not exposed to AEDs. Among offspring of fathers with epilepsy who used valproate in monotherapy during conception, rates of autism (2.9/1000 child-years) and intellectual disability (1.4/1000 child-years) were slightly higher compared with the offspring of fathers with epilepsy who did not use AEDs during conception (2.1/1000 child-years autism, 0.9/1000 child-years intellectual disability), but in the propensity-score adjusted analyses, no statistically significant increased risk of adverse outcomes was found.
Paternal AED use during conception is not associated with adverse outcomes in the offspring.
研究父亲使用抗癫痫药物（AEDs）与后代不良神经发育结局和主要先天性畸形（MCM）之间的关系。
利用全国性的瑞典登记处，我们纳入了 1144795 名出生于 741726 名无癫痫父亲和 4544 名出生于 2955 名癫痫父亲的子女。其中，2087 名（45.9%）父亲在受孕期间服用了 AED。排除同时患有癫痫的父母的子女。分析子女患 MCM、自闭症谱系障碍、注意缺陷多动障碍（ADHD）和智力残疾的发病率。
暴露于 AED 的父亲的子女，其 MCM（调整后的 OR 0.9，95%CI 0.7 至 1.2）、自闭症（调整后的 HR（aHR）0.9，95%CI 0.5 至 1.7）、ADHD（aHR 1.1，95%CI 0.7 至 1.9）或智力残疾（aHR 1.3，95%CI 0.6 至 2.8）的风险并未增加，与未暴露于 AED 的癫痫父亲的子女相比。在受孕期间接受单药丙戊酸钠治疗的癫痫父亲的子女中，自闭症（2.9/1000 儿童年）和智力残疾（1.4/1000 儿童年）的发生率略高于受孕期间未使用 AED 的癫痫父亲的子女（自闭症 2.1/1000 儿童年，智力残疾 0.9/1000 儿童年），但在倾向评分调整分析中，未发现不良结局风险有统计学意义的增加。
父亲在受孕期间使用 AED 与后代不良结局无关。
