Objective: To determine whether children born to women who use anti-seizure medications (ASMs) during pregnancy have higher risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) independent of confounding factors.

Methods: We used Swedish-register data (n=14,614 children born 1996-2011 and followed through 2013) to examine associations in children of women with epilepsy, using the largest sample to date and adjusting for a range of measured confounders. We examined maternal-reported first-trimester use of any ASM (22.7%); and the three most commonly reported individual drugs (valproic acid, 4.8%; lamotrigine, 6.8%; and carbamazepine, 9.7%). We identified ASD with ICD-10 diagnoses and ADHD with ICD-10 diagnoses or filled prescriptions of ADHD medication.

Results: Examination of individual drugs revealed that after adjustment for confounding, use of valproic acid was associated with ASD (Hazard Ratio=2.30, 95%CI=1.53-3.47) and ADHD (HR=1.74, 95%CI=1.28-2.38). Whereas a small, non-statistically significant association with ASD (HR=1.25, 95%CI=0.88-1.79) and ADHD (HR=1.18, 95%CI=0.91-1.52) remained for reported use of carbamazepine, confounding explained all of the associations with lamotrigine (HR_ASD=0.86, 95%CI=0.67-1.53; HR_ADHD=1.01, 95%CI=0.67-1.53).

Conclusions: We found no evidence of risk related to exposure to lamotrigine, whereas we observed elevated risk of ASD and ADHD related to maternal use of valproic acid. Associations with carbamazepine were weak and not statistically significant. Our findings add to a growing body of evidence that suggest that certain ASMs may be safer than others in pregnancy.