Some Seizure Medicine Combinations May Raise Birth Defect Risk

What was studied

This study looked at the risk of major congenital malformations in babies born to women who used common antiseizure medicine combinations during the first 12 weeks of pregnancy. The researchers used data from the North American AED Pregnancy Registry from 1997 to 2024.

The registry included 15,318 pregnant women who were taking an antiseizure medicine at conception. Of these, 2,348 used 2 or more medicines during the first trimester, and 796 polytherapy-exposed pregnancies were eligible for analysis. Most women in the analyzed polytherapy group were taking the medicines for epilepsy. The researchers compared these combinations with lamotrigine alone, which was the most common monotherapy.

Information on medicine use and maternal characteristics was collected by phone interviews during pregnancy and after birth. Major congenital malformations were confirmed from medical records and reviewed by a blinded teratologist.

What they found

In the lamotrigine-only comparison group, 2.0% of babies had a major congenital malformation. Compared with lamotrigine alone, the study findings suggest an increased risk with the lamotrigine-topiramate combination. For the other medicine combinations studied, the estimates were too imprecise to draw conclusions about risk.

Among babies exposed to any antiseizure medicine polytherapy, the most commonly reported major malformations were hypospadias, ventricular septal defect, and cleft lip or palate. All cleft lip or palate cases in the polytherapy group occurred with combinations that included topiramate or zonisamide.

Limits of the evidence

This was an observational registry study, so it cannot show that a medicine combination caused a birth defect. The study compared each combination with lamotrigine alone, not with no medicine use or with every other possible treatment.

Many of the two-drug combinations had small numbers of exposed pregnancies and few malformations, which made the risk estimates imprecise. Some confidence intervals were very wide, meaning the true risk could be lower or higher than the estimate suggests. The results mainly apply to the specific combinations studied and may not apply to less common combinations or to all pregnant people using antiseizure medicines.

For families and caregivers

For families, this study suggests that the choice of antiseizure medicines during pregnancy may matter, especially in the first trimester. It suggests that the combination of lamotrigine plus topiramate may be linked with a higher risk of major congenital malformations than lamotrigine alone.

At the same time, the study does not give clear answers for most other two-medicine combinations because the estimates were too imprecise. Treatment decisions during pregnancy often involve weighing potential medicine risks and the need for seizure control with a clinician.

What to watch next

Larger studies with more pregnancies in each specific medicine combination could help provide more precise risk estimates.

Terms in this summary

antiseizure medicine

A medicine used to prevent or reduce seizures; also called an anticonvulsant or ASM.

polytherapy

Using two or more medicines together.

first trimester

The first 12 weeks of pregnancy.

major congenital malformation

A major structural birth defect that develops before birth.

relative risk

A way to compare how often an outcome happens in one group versus another group.

confidence interval

A range that shows how uncertain an estimate is; a wide range means less certainty.

hypospadias

A birth defect in boys where the opening of the urethra is not in the usual place on the penis.

ventricular septal defect

A hole in the wall between the two lower chambers of the heart.