At age 3, similar neurodevelopmental outcomes are shown by children with fetal exposure to antiseizure medications compared with unexposed children, according to study findings published in the Lancet Neurology.
The neurodevelopmental risks and outcomes of fetal exposure to antiseizure medications remain largely unknown. Researchers sought to investigate the neuropsychological outcomes in children born to mothers with and without epilepsy.
The researchers conducted the prospective, observational cohort Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD; ClinicalTrials.gov Identifier: NCT0730170) study across 20 specialty epilepsy centers in the United States from 2012 to 2016. They compared cohorts of pregnant women between the ages of 14 to 45 years at a gestational age of 20 weeks or less with and without epilepsy, adjusting for education level and race to conserve similarity. The researchers excluded those with a major medical illness other than epilepsy, an estimated intelligence quotient (IQ) of less than 70, a history of psychogenic nonepileptic spells, and an antiseizure medication change during pregnancy.
For children at age 3, the researchers measured the primary outcome with a Verbal Index score, calculated from averaging the Naming Vocabulary and Verbal Comprehension subtests of Differential Ability Scales-II, the Expressive Communication and Auditory Comprehension subscales of Preschool Language Scale-5, and the Peabody Picture Vocabulary Test-4. The researchers chose verbal testing because prior studies suggest that verbal abilities may be particularly susceptible to fetal antiseizure medication exposure. They also assessed 13 additional secondary cognitive outcomes.
A total of 456 pregnant women (351 epileptic, 105 nonepileptic) participated in the study. A majority of women with epilepsy received antiseizure monotherapy (74%), with the most common prescriptions being lamotrigine (43%) and levetiracetam (35%). For those on polytherapy (22%), the most commonly prescribed combination therapy was lamotrigine with levetiracetam (41%).
Primary analysis found no significant differences in Verbal Index scores in children of women with epilepsy (unadjusted least squares mean, 102; 95% CI, 100.8-103.9) compared with those without epilepsy (unadjusted LS mean, 103.4; 95% CI, 100.6-106.2).
The researchers found several significant factors that influenced Verbal Index scores, including maternal IQ, education level, post-birth maternal anxiety, gestational age at enrollment, and child’s sex and ethnicity.
In an unadjusted analysis, the researchers found a negative association between Verbal Index score and the maximum ratio of antiseizure medication in the blood during the third trimester (parameter estimate, –7.5; 95% CI, –12.1 to –2·9; P =.0013). When adjusted for factors, this association was statistically insignificant (PE –2.9; 95% CI, –6.7 to 1.0; P =.15).
Study limitations included the researchers’ inability to randomly assign antiseizure medications to the cohort of pregnant women with epilepsy, confounding variables such as genetics and environmental exposure, and small sample sizes for the antiseizure medications.
“The findings of the MONEAD study showed that cognitive outcomes in children aged 3 years did not differ if their mother had epilepsy or did not have epilepsy,” the researchers concluded. “The teratogenic effects of most of antiseizure medications remain unknown, which is an important area for future research, along with delineation of genotypic risk factors for antiseizure medication teratogenicity.”
Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Meador KJ, Cohen MJ, Loring DW, et al. Cognitive outcomes at age 3 years in children with fetal exposure to antiseizure medications (MONEAD study) in the USA: a prospective, observational cohort study. Lancet Neurol. Published online July 19, 2023. doi:10.1016/S1474-4422(23)00199-0