Genetic susceptibility for neurodevelopmental disorders in children born to women with epilepsy

Children of women with epilepsy have higher rates of neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), than the general population. This likely reflects a complex gene-environment interplay, but the specific contribution of genetic susceptibility, independent of in utero antiseizure medication exposure, remains unclear. The objective of this study was to evaluate whether polygenic risk scores (PRSs) for ADHD and ASD are elevated in these children compared to the general population and to assess associations with childhood neurodevelopmental traits. We analysed genetic and questionnaire data from the Norwegian Mother, Father and Child Cohort Study (MoBa). We included children born to women with epilepsy (n = 422) and children of mothers without epilepsy (n = 73 300). The parent-reported neurodevelopmental traits hyperactivity, inattention, social difficulties, language difficulties, repetitive behaviour and motor difficulties were measured using z scores at ages 0.5, 1.5, 3, 5 and 8 years. The genetic susceptibility was calculated as PRSs for ADHD and ASD. Children born to women with epilepsy had higher PRSs for ADHD (mean difference = 0.09, P = 0.07), not ASD (mean difference = 0.014, P = 0.78), compared to those without epilepsy. In these children, we observed stronger associations between the ADHD PRSs and neurodevelopmental traits closely linked to ADHD, specifically hyperactivity and inattention for all ages examined with the strongest association at 8 years. For the ASD PRSs, we observed stronger associations with motor development and language difficulties particularly at 5 years in children born to women with epilepsy. Although these associations were in the same direction and statistically significant for all ages in the general population, they did not reach statistical significance in children born to women with epilepsy. Findings from this study show that the ADHD and ASD PRSs were more strongly associated with hyperactivity/inattention, and with language/motor difficulties respectively in children born to women with epilepsy, compared to the general population. However, statistical significance was not reached likely due to limited sample size. These findings underscore the importance of considering genetic predisposition when assessing neurodevelopmental risks in this population.