Children born to mothers who used specific anti-seizure medications during pregnancy showed no negative impacts on neurodevelopment at the age of 6, according to an extensive research project.
Children born to mothers who used certain anti-seizure medications during their pregnancies do not show worse neurodevelopmental outcomes by the time they reach age 6, based on findings from a long-term study supported by the National Institutes of Health (NIH). This study has been published in JAMA Neurology.
“Managing seizures during pregnancy is crucial for women with epilepsy, yet the implications of newer anti-seizure medications on their children have been uncertain for many years,” stated Adam Hartman, M.D., program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS). “A key aspect of this investigation involved linking the cognitive performance of children to the levels of medication present in their mothers’ blood. This paves the way for future research and might guide improved dosage recommendations.”
Addressing epilepsy during pregnancy can be tough since some older anti-seizure medications, like valproate, are known to result in serious birth defects and cognitive issues, such as reduced IQ and autism spectrum disorders. Although newer anti-seizure drugs that are widely prescribed today are generally thought to be safer, there is limited information on their impact on children’s cognitive development after exposure in the womb.
In the research, the language abilities of 387 six-year-olds were evaluated (298 of whom had mothers with epilepsy who took anti-seizure medications). The children underwent tests measuring various verbal skills, including vocabulary and the ability to match spoken words with images. The study found no significant differences in language scores between the children of mothers who used medications and those who did not. Most of the women in the study were taking lamotrigine, levetiracetam, or a combination of both during and after their pregnancies.
“The significance of this study lies in the assessment of children at the age of 6, where the tests used are much more discerning compared to earlier assessments, particularly for 2-year-olds. The outcomes can directly impact school performance and better predict future cognitive abilities,” noted Kimford Meador, M.D., co-lead investigator and professor of neurology at Stanford University.
Determining the safest and most effective dosages during pregnancy presents its own set of challenges, as the risks associated with various anti-seizure medications can differ. Previous research from the same team indicated that high doses of levetiracetam might lead to less favorable cognitive results at ages 2 and 3, along with poorer adaptive functioning by age 4 and a half, though overall outcomes at all ages remained positive.
“We must find a balance in ensuring adequate medication levels to protect both the mother and her developing fetus from seizures while avoiding excessive dosages that could pose risks for the child,” emphasized Dr. Meador.
The research also indicated that taking folate during the first 12 weeks of pregnancy was linked to improved cognitive and behavioral performance, even at higher doses. Folate is a vital nutrient that can aid in preventing brain and spinal birth defects. This finding was consistent for children of both mothers with and without epilepsy. High doses at 4 mg or more daily did not show negative effects, which contrasts with earlier studies that suggested long-term risks tied to high folic acid levels.
This information is part of the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, a long-term study investigating the effects of anti-seizure medications on pregnant women with epilepsy and their children from birth up to 6 years old. The study, led by Dr. Meador and Page Pennell, M.D., chair of neurology at the University of Pittsburgh, was conducted across 20 medical centers throughout the United States.
Further analyses found no negative effects of anti-seizure medications on breastfeeding. Researchers emphasize the need for additional studies to fully understand the risks tied to high folate dosages and less common anti-seizure medications, including newer drugs available today.
This study was made possible with support from the NINDS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01NS038455 and U01NS050659), and was part of the MONEAD study (NCT01730170).
