Newer epilepsy medications used during pregnancy do not affect neurological development in children

Children of mothers who took certain antiseizure medications while pregnant do not have worse neurodevelopmental outcomes at age six, according to a long-running study.

Treating epilepsy during pregnancy is challenging, as some antiseizure medications, primarily older drugs such as valproate, are known to cause serious birth defects and cognitive problems in children, including lower IQ and autism spectrum disorders.

Newer antiseizure drugs that are widely used today are generally considered safe, but little is known about whether they affect cognition in children after foetal exposure.

In the study, researchers assessed language abilities in 387 children at age 6 (298 were born to women with epilepsy who took antiseizure medications).

Children were tested on a variety of verbal abilities, including vocabulary and matching spoken words to pictures. There were no differences in language scores between children of women who took the medications and those who didn’t.

Most women were taking lamotrigine, levetiracetam, or a combination of both drugs during and after pregnancy.

“Controlling seizures during pregnancy is an important part of prenatal care for women with epilepsy, but for years, the effects of newer antiseizure medications on their children was unknown,” said Adam Hartman, programme director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS).

“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.”

“What makes this study meaningful is that when you assess a child at six, the tests are a lot more sensitive than at earlier ages, especially 2-year-olds. There’s measurable impact on school performance and results are more predictive of adult cognitive ability,” said Kimford Meador, co-lead investigator of the study at Stanford University.

Finding the most effective and safest doses during pregnancy is also a challenge, and risks tend to vary between antiseizure drugs. Prior studies from the same research team have shown that high doses of levetiracetam could lead to poorer cognitive outcomes at age two and three, and worse adaptive functioning at age four and a half, but the overall outcomes for all ages were positive.

“We need to balance making sure there is enough medicine on board to protect the mother and her developing foetus from seizures, but not too much where we’re creating risk for the child,” said Dr. Meador.

The study also found that folate use during the first 12 weeks of pregnancy was associated with better cognitive and behavioural outcomes, even at higher doses. Folate is an essential nutrient that can help prevent birth defects in the brain and spine of a developing foetus.

This held true for children of women with and without epilepsy. High doses at or above 4 mg per day did not have adverse effects, which contrasts with prior studies that found long-term risks associated with high doses of folic acid.

Additional analyses revealed no adverse effects of antiseizure medications on breastfeeding. Researchers point out that more studies need to be done to understand the risks of high doses of folate and less common antiseizure medications, including newer drugs on the market.