Controlling seizures during pregnancy is crucial for women with epilepsy, but the effects of newer antiseizure medications on children have long been unclear. While older drugs like valproate are known to cause congenital disabilities and cognitive issues such as lower IQ and autism, newer medications are generally considered safe. However, their potential impact on child cognition after fetal exposure remains largely unknown.
A new study examined the associations between fetal antiseizure medication (ASM) exposure and subsequent neuropsychological abilities of the child. This NIH-funded study clarifies the safety of two common ASMs, lamotrigine and levetiracetam.
It suggests that children of mothers who took certain antiseizure medications while pregnant do not have worse neurodevelopmental outcomes at age 6.
Adam Hartman, M.D., program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS), said, “One major component of this study was correlating the cognitive abilities of children with maternal blood levels of the drugs. This opens the door to future work and might inform better dosing strategies.”
In a study assessing language abilities in 387 children at age 6, including 298 born to women with epilepsy who took antiseizure medications, no differences were found in language scores between children whose mothers took the medications and those who didn’t. The children were tested on verbal skills, such as vocabulary and matching spoken words to pictures. Most of the women in the study were taking lamotrigine, levetiracetam, or a combination of both drugs during and after pregnancy.
Dr. Kimford Meador, the study’s co-lead investigator, highlighted that testing at age 6 is more sensitive than earlier assessments, providing a more precise prediction of school performance and adult cognitive abilities.
Finding the safest and most effective doses of antiseizure medications during pregnancy is challenging, as risks vary between different drugs. Previous studies have suggested that high doses of levetiracetam were linked to poorer cognitive outcomes at ages 2 and 3 and worse adaptive functioning at age 4.
However, overall outcomes for all ages were positive. The study emphasizes the importance of balancing the need for enough medication to prevent seizures in the mother and fetus without posing a risk to the child.
Additionally, the study found that folate use during the first trimester of pregnancy is associated with better cognitive and behavioral outcomes, even with higher doses of antiseizure medications. Folate, an essential nutrient, helps prevent congenital disabilities in the brain and spine.
This beneficial effect was seen in children of both women with and without epilepsy. High doses of folic acid (at or above 4 mg per day) did not have adverse effects, contrasting with previous studies that suggested long-term risks with high folic acid doses.
This report is part of the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, a long-term, prospective study examining antiseizure medications’ effects on pregnant women with epilepsy and their children from birth to age 6.
The study, led by Dr. Kimford Meador and Dr. Page Pennell, involved 20 medical centers across the United States. Additional analyses showed no adverse effects of antiseizure medications on breastfeeding.
However, the researchers emphasized the need for further studies to understand better the risks associated with high doses of folate and less common antiseizure medications, including newer drugs on the market.
Journal Reference:
- Meador KJ, et al. “Neuropsychological Outcomes in 6-Year-Old Children of Women With Epilepsy.” JAMA Neurology. November 25, 2024. DOI: 10.1001/jamaneurol.2024.3982