Pregnancy, baby, and childhood outcomes from using anti-seizure medication during pregnancy

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’ prescription issued 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 to account for the matched study design. Results: Here we show 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%) are more common following any ASM exposure in pregnancy compared with no ASM exposure in pregnancy. Valproate is 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 are also associated with pregnancy loss and developmental concerns. Conclusions: Our findings corroborate the associated risks of valproate use and embryo malformations, support the use of lamotrigine and levetiracetam in pregnancy, and raise concerns regarding gabapentinoid use in pregnancy.