Anti-seizure medication in pregnancy and pregnancy, baby, and child outcomes: a population-based cohort study

Background Evidence of the safety of some anti-seizure medicines (ASMs) during pregnancy remains uncertain. Methods We conducted a population-based cohort study of singleton pregnancies in Scotland conceived between 01/04/2010-02/07/2023. Exposure was ‘Any ASM’ dispensed 28 days prior to conception up to pregnancy end. Seven monotherapies were also examined: valproate, topiramate, carbamazepine, lamotrigine, levetiracetam, gabapentin, and pregabalin. Unexposed comparators were matched to the exposed on gestational age and year of conception. Pregnancy loss, congenital condition and child development outcomes were compared by exposure status using conditional logistic regression. Results Of 911,027 pregnancies, 11,011 (1.2%) were exposed to Any ASM. Pregnancy loss (3,175/11,011 pregnancies, 28.8% vs. 24,040/107,889 pregnancies, 22.3%), congenital conditions (230/8,370 babies, 2.7% vs. 1,693/82,085 babies, 2.1%) and developmental concerns (1,270/4,890 live births, 26.0% vs. 7,658/48,883 live births, 15.7%) were more common among Any ASM exposed vs. unexposed. Valproate was strongly associated with pregnancy loss (adjusted odds ratio (aOR): 1.92, 95% confidence interval (CI): 1.50–2.47), congenital conditions (aOR: 1.85, 95% CI: 1.06–3.21) and developmental concerns (aOR: 1.43, 95% CI: 1.01–2.03). Pregabalin, gabapentin and Any ASM were also associated with pregnancy loss and developmental concerns. Conclusions Our findings corroborate valproate teratogenicity, support the safety of lamotrigine and levetiracetam, and raise concerns regarding gabapentinoid use in pregnancy.