No effect of foetal antiseizure exposure on neurodevelopmental outcomes at age 3

Children of women who were on antiseizure medication during pregnancy did not show developmental deficits on neuropsychological outcomes at age 3. Prof. Kimford J. Meador (Stanford University, California, USA) presented the preliminary results of the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.

The prospective, observational, multi-centre MONEAD study evaluates the effects of antiepileptic drugs on pregnancy outcomes [1]. In the presented analysis, children of women with epilepsy (n=275) and children of healthy women (n=72) were compared on a Verbal Index score as primary outcome. This score was computed by averaging several verbal intelligence tests (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 model was adjusted for maternal IQ and maternal educational level. Children of women with epilepsy and those of healthy women did not differ on verbal index score (adjusted LS means: 103.4 vs 102.7).

A second model analysed if maximum antiseizure medication blood levels (ABLs) during the third trimester of pregnancy correlated with the Verbal Index score of the children. Prof. Meador mentioned that the third trimester was chosen because it is the most sensitive period to foetal alcohol syndrome exposure and this exposure resembles some of the effects of antiepileptic drugs in animals. This model adjusted additionally for antiseizure medication type. Monotherapy was the most commonly used antiseizure medication (74%); lamotrigine (LTG, 43%) and levetiracetam (LEV, 37%) were the most prevalent monotherapies. Women with epilepsy on polytherapy were primarily on a LTG plus LEV dual therapy (44%). Multiple linear regression analysis did not demonstrate an association between ABLs and Verbal Index score at age 3 (adjusted parameter estimate -1.2). Secondary analysis found similar results with DAS-II General Conceptual Ability scores as outcome measure: there was no difference in neuropsychological outcomes between children of women with epilepsy and healthy women. The only exception to this result was a secondary analysis of LEV blood levels, which showed a negative relation to both Verbal Index score and General Conceptual Ability scores. As it is a secondary analysis, these results should be interpreted with caution.

1. Meador KJ, et al. Fetal Antiseizure Medication Effects on Neuropschycological Outcomes at Age 3 Years in the MONEAD Study. S1.001, AAN 2021 Virtual Congress, 17-22 April.

Posted on 19 April 202117 June 2021