Adaptive functioning scores did not differ between children of women with and without epilepsy, but a significant decrease in functioning was seen with increasing third-trimester levels of anti-seizure medications (ASMs), the observational cohort study MONEAD found.
No statistically significant difference emerged in adaptive functioning scores between 4.5-year-old children whose mothers had epilepsy and those whose mothers did not (parameter estimate [PE] 0.4, 95% CI -2.5 to 3.4, P=0.77), reported Morris Cohen, EdD, of Pediatric Neuropsychology International in Augusta, Georgia, and co-authors.
However, higher third-trimester ASM blood concentrations were associated with a significant decrease in adaptive functioning scores (adjusted PE −7.8, 95% CI −12.6 to −3.1, P=0.001), the researchers wrote in JAMA Neurology.
Fetal exposure to older ASMs like valproate (Depakote) has been linked to cognitive deficits, but cognitive and behavioral risks remain uncertain for many newer ASMs, Cohen and colleagues noted. Previous research from the MONEAD cohort showed that children with fetal exposure to newer ASMs showed no difference in verbal abilities at age 3 compared with unexposed children.
“The most important takeaway message is that the children of the persons with epilepsy on ASMs did not differ from the children of the control group with regard to any of these neurodevelopmental behavioral outcomes,” co-author Page Pennell, MD, of the University of Pittsburgh in Pennsylvania, told MedPage Today by email.
“These findings remind us to not increase doses carelessly beyond what is needed to maintain seizure control for the individual patient,” Pennell pointed out.
“We know from our prior studies that active adjustment of ASM doses during pregnancy is needed to maintain seizure stability,” she added. “The overall findings are extremely reassuring for adult persons with epilepsy who will need to continue their ASMs during pregnancy.”
Adaptive functioning scores were based on the Adaptive Behavior Assessment System, Third Edition, General Adaptive Composite (ABAS-3 GAC), a rating assessment with higher scores indicating higher functioning.
Parents completed the assessment for their child at ages 3 and 4.5 years, and GAC scores at age 4.5 were used as the study’s primary outcome. Parents also completed assessments of emotional or behavioral functioning, stress in the parent-child relationship, and autism spectrum disorder screening.
Participants were enrolled at U.S. epilepsy centers from 2012-2016. A total of 302 children of women with epilepsy (47.4% boys) and 84 children of women without epilepsy (53.6% boys) were included in the first primary analysis, which compared the groups’ GAC scores. The second primary analysis, which looked at third-trimester ASM blood concentrations and GAC scores, included 271 children of women with epilepsy.
The association between increasing third-trimester ASM blood concentration and decreasing adaptive functioning scores was seen for levetiracetam (Keppra) (PE -18.9, 95% CI-26.8 to -10.9, P
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