Antiepileptic drugs taken during pregnancy do not impact cognitive outcomes in children
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Children born to women with epilepsy who received antiepileptic drugs during pregnancy displayed similar neurodevelopmental outcomes as children born to healthy women, according to findings from a prospective study.
Additionally, the researchers — who presented their findings at the American Academy of Neurology annual meeting — which is being held virtually — observed no exposure-dependent effects of antiseizure medication.
“The original start of our Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study was in the late 1990s and was prompted by observations in animals that fetal exposure to older antiseizure medications could cause long lasting neurobehavioral deficits. The NEAD study gave us information on the danger of fetal exposure to valproate, but now women are taking newer antiseizure medications, for which we have information on only a small percentage of these medications,” Kimford J. Meador, MD, FAAN, FAES, FRCPE, professor in the department of neurology and neurological sciences at Stanford University School of Medicine, told Healio Neurology. “The present Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study extends our prior study by examining outcomes in both the mother and child in a new cohort of women taking the newer antiseizure medications.”
Previous studies have not controlled “for clearance changes during pregnancy” by looking at the link between blood levels and pregnancy outcomes, Meador continued. The study presented at AAN examined cognitive outcomes in children aged 3 years following in utero exposure to antiseizure medications, he said.
The researchers presented preliminary results from the prospective, observational, multicenter MONEAD study, in which women with epilepsy and healthy women were enrolled during pregnancy. They calculated a verbal index score as the primary outcome for children at aged 3 years, which was determined by averaging the Differential Ability-Scales II Naming Vocabulary and Verbal Comprehension subtests, the Preschool Language Scale-5 Expressive Communication and Auditory Comprehension subscales and the Peabody Picture Vocabulary Test-4.
Meador and colleagues calculated the primary outcome in children of women with epilepsy and healthy women and compared them using analysis of covariance, or ANCOVA. They also analyzed the relationship between this and maximum antiseizure medication levels in the blood during the third trimester with multiple linear regression. Models were adjusted for material IQ and education, as well as antiseizure medication group in the arm that had blood levels evaluated, according to the study results.
The study included 289 children born to women with epilepsy and 89 children born to healthy women, according to the data presented at AAN. More women were receiving monotherapy (78%) compared with polytherapy (22%) and the most commonly prescribed drug was lamotrigine (35%), followed by levetiracetam (28%).
The researchers observed no differences in the main outcome of language index score among children born to mothers with epilepsy compared with children born to healthy women, though “other factors” affected the child’s outcome, Meador said during his presentation, including the fact that the child’s outcome was better if the mother’s IQ was higher (P < .001) and worse for boys compared with girls (P < .001). Hispanic children scored lower on the verbal index score (P < .001), although Meador noted that English may have not been the primary language in the child’s household.
The study results demonstrated no relationship between verbal index scores at 3 years of age and antiseizure medication levels in the blood during the third trimester. A secondary analysis demonstrated “a level-dependent effect for levetiracetam, such that there may be risks at higher levels,” but additional research in children at older ages and in other cohorts are needed to confirm this result, Meador said.
“Our findings are encouraging for women with epilepsy and for the clinicians caring for them,” he told Healio Neurology. “The results suggests that children of women with epilepsy taking newer antiseizure medications are not at increased risk for cognitive problems, although the majority of our children were exposed to lamotrigine, levetiracetam or both. Additional studies are needed to confirm the safety of other new antiseizure medications.”