Newer Antiseizure Medications Show Improved Safety Profile During Pregnancy
Key Insights
Second-generation antiseizure drugs including levetiracetam, oxcarbazepine, gabapentin and zonisamide demonstrated no increased risk for birth defects (search) in pregnant women.
Valproate showed the highest risk with birth defects (search) in 9% of exposed infants, while phenobarbital and topiramate also carried significant risks compared to lamotrigine.
A 30% increase in use of the safest antiseizure medications during pregnancy was observed, with an 80% decrease in valproic acid usage between 2013-2021.
A comprehensive study published in Neurology has revealed that several newer antiseizure medications appear significantly safer for pregnant women, offering hope for better maternal and fetal outcomes while maintaining essential seizure control.
The research, led by Dr. Sonia Hernandez-Diaz from Harvard T.H. Chan School of Public Health, tracked over 7,300 pregnancies in women taking antiseizure drugs and compared them to more than 1,300 women not on these medications. The study focused on major birth defects (search) including cleft lip (search), enlarged heart holes, spinal cord issues, and limb malformations.
Second-Generation Drugs Show Promise
The study found that second-generation antiseizure drugs including levetiracetam, oxcarbazepine, gabapentin and zonisamide did not show an increased risk for birth defects (search). "Our results did not show an increased risk with medications like levetiracetam, oxcarbazepine, gabapentin and zonisamide," Hernandez-Diaz stated.
These findings are particularly significant given the critical need for seizure control during pregnancy. "Seizures can lead to falls and other complications during pregnancy, so seizure control for those with epilepsy (search) is crucial to protect the health of both the mother and child," Hernandez-Diaz explained.
Older Medications Carry Higher Risks
The research confirmed substantial risks associated with older antiseizure medications. Women taking valproate faced more than five times the risk of birth defects (search) compared to those on lamotrigine, with birth defects occurring in 9% of infants exposed to valproate. Phenobarbital carried nearly three times the risk with a 6% birth defect rate, while topiramate showed over twice the risk with defects in 5% of exposed babies.
In contrast, lamotrigine, used as the reference drug, showed birth defects (search) in only 2% of exposed infants.
Shifting Treatment Patterns
A separate analysis of over 55,800 pregnancies in France between 2013 and 2021 revealed encouraging trends in prescribing practices. Dr. Rosemary Dray-Spira from the French National Agency for the Safety of Medicines and Health Products (search) reported a 30% increase in the use of the safest antiseizure drugs during pregnancy.
The study categorized medications into three safety groups: safest drugs (lamotrigine and levetiracetam), uncertain risk drugs (pregabalin, gabapentin, lacosamide and zonisamide), and known risk drugs (valproic acid, valpromide, carbamazepine and topiramate).
Clinical Implications and Ongoing Concerns
While the overall trend shows improvement, researchers noted persistent challenges. Use of valproic acid and valpromide decreased by more than 80%, but exposure to carbamazepine and topiramate remained largely unchanged. Additionally, there was a 28% increase in use of pregabalin and gabapentin despite their uncertain risk profiles.
"The good news is that use of the drugs with the greatest risks has decreased, and use of the safest drugs has increased, but we are concerned to still see use during pregnancy of some drugs with known risks and new drugs with uncertain risk," Dray-Spira noted.
For medications like lacosamide and pregabalin, the researchers acknowledged that "the data wasn't clear enough to make solid conclusions, so more research is needed."
Broader Treatment Context
These medications serve multiple therapeutic purposes beyond epilepsy (search), including treatment of mood disorders (search), chronic pain (search), and migraine (search). "These medications can be used for epilepsy, mood disorders, chronic pain and migraine, which often occur at young ages, and sometimes people are taking them before they realize that they are pregnant," Dray-Spira explained.
The research 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," according to Hernandez-Diaz, offering a foundation for evidence-based treatment decisions in this vulnerable population.