Maternal Use of Anti-Seizure Drugs, Risk of Autism and ADHD in Offspring

Maternal use of valproic acid during pregnancy may increase the risk for autism spectrum disorders (ASD) and attention-deficit and hyperactivity disorder (ADHD) in children, while lamotrigine did not present such risks, according to study results published in Neurology.

Previous studies reported an increased risk for adverse birth outcomes associated with anti-seizure medication use during pregnancy. The objective of the current study was to assess the risk for ASD and ADHD in children born to mothers who used anti-seizure medications during pregnancy.

Using data from the Swedish register-data, the study included 14,614 children born to women with epilepsy between January 1, 1996, and December 31, 2011. Study researchers followed children through December 31, 2013. A total of 3316 mothers reported use of any anti-seizure medication during the first trimester. The most commonly used medications were carbamazepine (n=1417, 9.7%), lamotrigine (n=996, 6.8%), and valproic acid (n=699, 4.8%).

The researchers considered diagnoses of ASD made by a specialist and those of ADHD made by a specialist or through filled prescriptions for stimulant medication. Regarding both, considered diagnoses were made only after 2 years of age.

Compared with children whose mothers reported no use of anti-seizure medication during pregnancy, children of mothers who were treated with valproic acid during pregnancy showed a 2.3-fold elevated risk for ASD (hazard ratio [HR], 2.30; 95% CI, 1.53-3.47) and 1.7-fold elevated risk for ADHD(HR, 1.74; 95% CI, 1.28-2.38).

After adjustment for important covariates, including parental psychiatric problems and seizure/epilepsy severity, maternal-reported use of lamotrigine during pregnancy was not associated with a significant increased risk for either ASD (HR, 0.86; 95% CI, 0.50-1.48) or ADHD (HR, 1.01; 95% CI, 0.67-1.53).

In unadjusted models, carbamazepine use was associated with increased risk for ASD and ADHD, but after adjustment for study variables, the associations were weaker and not statistically significant for both ASD (HR, 1.26; 95% CI, 0.88-1.79) and ADHD (HR, 1.18; 95% CI, 0.91-1.52).

The study had several limitations, including potential survival bias as the study researchers only considered children after 2 years of age, inability to adjust for parental diagnosis of ASD and ADHD, and the inability to investigate the impact of anti-seizure medication dose on the risk.

“Although we could not rule out all potential confounding factors, our findings add to a growing body of evidence that suggests that certain ASMs (i.e., lamotrigine) may be safer than others in pregnancy,” wrote the study researchers.

Reference

Wiggs KK, Rickert ME, Sujan AC, et al. Anti-seizure medication use during pregnancy and risk of ASD and ADHD in children. Neurology. Published online October 28, 2020.  doi:10.1212/WNL.0000000000010993