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Children of Women on Antiseizure Drugs Appear to Have Normal Neurodevelopment

The children of women who took antiseizure medication during pregnancy do not appear to have a different neurodevelopmental trajectory than do children from women who did not have epilepsy while they were pregnant, researchers reported at the 2021 virtual AAN annual meeting.

The findings came from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, a prospective, observational, multicenter investigation of pregnancy outcomes.

In his presentation at the meeting, Kimford Meador, MD, FAAN, professor of neurology and neurosciences at Stanford University, reported, “In these preliminary analyses, neurodevelopmental outcomes did not differ between children of women with epilepsy compared with healthy women, and exposure-dependent antiseizure medication effects were not seen."

The findings were adjusted for maternal IQ, education, and antiseizure medication group.

For the key outcome measure, the mean adjusted Verbal Index scores, there was essentially no statistically significant difference between 275 children born to women with epilepsy and 77 children whose mothers did not have epilepsy (the controls). The Verbal Index score was calculated by averaging the Differential Ability Scales-II (DAS-II) Naming Vocabulary and Verbal Comprehension subtests, Preschool Language Scale-5 Expressive Communication and Auditory Comprehension subscales, and Peabody Picture Vocabulary Test-4.

The research team enrolled women with epilepsy and healthy women who were pregnant.

At enrollment, most pregnant women with epilepsy were being treated with monotherapy. About 77 percent of the women were taking one medication. About 43 percent of the women were taking lamotrigine while another 37 percent were on levetiracetam. If the women were on combination treatment, Dr. Meador reported that treatment with lamotrigine plus levetiracetam was the most popular polytherapy.

In secondary analyses of DAS-II Non-Verbal Index and General Conceptual Ability scores, there was no difference in outcome between the children of women with epilepsy and children of healthy women.

In commenting on the study, Lia Ernst, MD, assistant professor of neurology at the Oregon Health Sciences University Comprehensive Epilepsy Center, told Neurology Today At the Meetings, “Overall the study is reassuring that most women with epilepsy are able to have healthy pregnancies and children of women with epilepsy have normal cognitive outcomes"

Dr. Ernst said that the current trial is a follow-up on the NEAD trial that was conducted from 1999-2004.“In the NEAD study, the antiseizure medications examined were lamotrigine, phenytoin, valproate, and carbamazepine," she said. “In the MONEAD study, most women were taking levetiracetam and/or lamotrigine. This likely represents a shift in practice, given the results of the NEAD study, which showed poorer cognitive outcomes in children of mothers taking valproate.

“Data from previous studies suggests that lamotrigine and levetiracetam are relatively safer medications. Given this shift, I am not surprised that cognitive outcomes appear better in this cohort than the NEAD cohort," Dr. Ernst said.

“The MONEAD study is well designed. “It was a multicenter, prospective study that used multiple outcome measures to determine cognitive outcomes of the children, Dr. Ernst said. “One caveat is that because the majority of women were taking lamotrigine and levetiracetam, the results may be less generalizable to women with epilepsy taking other antiseizure medications or combinations of multiple antiseizure medications."

Dr. Meador has received compensation for travel expenses from Eisai for serving as a lecturer for educational symposium at the European Paediatric Neurology Society. Dr. Ernst disclosed relationships with NeuroPace.

AAN Abstract S1.001: Meador K, Cohen M, Loring D, et al. Fetal antiseizure medication effects on neuropsychological outcomes at age 3 years in the MONEAD study.