During pregnancy, are newer antiseizure medications safer than older drugs?

A new study that examined older and newer medications to treat seizures has found that using some medications during pregnancy is linked to an increased risk of malformations at birth, or birth defects. The study is published July 16, 2025, in Neurology®, the medical journal of the American Academy of Neurology.

“Seizures can lead to falls and other complications during pregnancy, so seizure control for those with epilepsy is crucial to protect the health of both the mother and child,” said study author Sonia Hernandez-Diaz, MD, DrPH, of Harvard T.H. Chan School of Public Health in Boston, Massachusetts. “While some older drugs are known to increase the risk of major malformations, less is known about the safety of newer ‘second generation’ medications. Our study looked at a number of drugs and provides valuable information for health care providers and people who may become pregnant to make more informed decisions about the use of these medications during pregnancy.”

For the study, researchers looked at 7,311 women who were taking an antiseizure medication during the first trimester of pregnancy. They were compared to 1,311 women who did not take antiseizure medications.

Participants completed phone interviews at the start of the study, at seven months pregnant, and within three months after delivery.

Researchers confirmed birth defects through medical records. These included cleft lip, larger-than-normal holes in the heart, neural tube defects where the spinal cord does not develop properly such as spina bifida, missing or underdeveloped limbs and other issues where parts of the body did not form correctly.

They then looked at the risk of these birth defects among infants exposed to specific antiseizure medications taken during the first trimester of pregnancy and compared them to infants exposed to lamotrigine, an antiseizure medication used as the reference group.

Researchers found that the risk of major birth defects varied among medications. Valproate posed the highest risk, with major birth defects occurring in 9% of infants exposed. Phenobarbital followed at 6%. Among newer drugs, birth defects occurred in 5% of those exposed to topiramate, while the group exposed to lamotrigine had malformations in 2% of births.

When compared to those who took lamotrigine, those who took valproate had more than five times the risk of birth defects, those who took phenobarbital had nearly three times the risk, and those taking topiramate had over twice the risk.

"Our results confirm that using valproate, phenobarbital or topiramate during early pregnancy is linked to a higher chance of major birth defects in the infants when compared to lamotrigine,” Hernandez-Diaz said. “On the other hand, our results did not show an increased risk with medications like levetiracetam, oxcarbazepine, gabapentin and zonisamide. For lacosamide and pregabalin, the data wasn’t clear enough to make solid conclusions, so more research is needed."

A limitation of the study was that participants were enrolled months after conception and in most cases early losses of pregnancy were not assessed for malformations, so the number of malformations overall may have been underestimated.

Reference:

Sonia Hernandez-Diaz, Use of Antiseizure Medications Early in Pregnancy and the Risk of Major Malformations in the Newborn,Neurology, doi/10.1212/WNL.0000000000213959.