(300) Prenatal exposure to antiseizure medications and neurodevelopmental disorders: Children population-based cohort from the Quebec Pregnancy/Child Cohort

Background: Antiseizure medications (ASM) are the primary treatment for patients with epilepsy as well as for anxiety, bipolar disorders, migraine headache, and pain. Prenatal exposure to ASM is associated with increased risk of congenital malformations. However, there is limited data regarding the effects of prenatal exposure to ASM and the risk of neurodevelopmental teratogenicity.

Objectives: To quantify the association between prenatal exposure to ASM and the risk of neurodevelopmental disorders (NDDs) in children.

Methods: A birth cohort was put in place with data from the Quebec Pregnancy and Child Cohort, which encompasses all pregnancies of mothers insured by the Quebec provincial drug plan between 1998 and 2022. We included live-born children from a single pregnancy of mothers aged between 15 and 45 years old. Children were considered exposed to ASM if their mother had filled at least one prescription for any ASM within 60 days of delivery/birth. The main outcome was the combined NDDs including autism spectrum disorder, attention deficit hyperactivity disorder with or without hyperactivity , learning difficulty, speech/language disorder, intellectual disability, developmental coordination disorder, and behavioral disorder. Children were followed until the date of the first NDD diagnosis, or censored at end of the study period, termination of medication coverage plan, or date of death, whichever comes first. Cox proportional hazards regression models adjusted for ASM indications, maternal sociodemographic characteristics, maternal comorbidities, risk factors for NDD, were used to calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CIs).

Results: 188,236 singleton livebirths were eligible and considered in this study; 2,067 (1.1%) were exposed to ASM in the 60-days before delivery/birth. The majority (92.4%) of children were exposed to only one ASM in-utero. Among those exposed, the prevalence of NNDDs was 20.0% (392 children); among those unexposed to ASM before delivery, the prevalence of NDDs was 11.4% (21,239 children). In-utero exposure to ASM was associated with older maternal age and low education level, welfare status, multiple maternal comorbidities, obesity, tobacco use, and drugs and alcohol addiction. Adjusting for all potential confounders, late pregnancy exposure to ASMs was associated with a increased risk of NDDs (aHR 1.19 with 95% CI 1.07 to 1.33).

Conclusions: In this birth cohort, we observed a 19% increased risk of NDDs in children who were exposed to ASMs in-utero in the 60 days preceding birth. ASM prenatal exposure during late pregnancy requires careful evaluation to weigh their benefits and disadvantages.