Prenatal Exposure to Antiseizure Medications: Is Neurodevelopment Affected?

At age 4.5 years, there is no difference in creativity or executive functions in children who had prenatal exposure to antiseizure medications (ASMs) vs those without prenatal exposure, according to study findings published in Neurology.

Researchers conducted the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD; ClinicalTrials.gov Identifier: NCT01730170) study, an ongoing multicenter prospective observational parallel-group cohort study, to evaluate the effects of in utero ASM exposure on creativity and executive functions in 4.5-year-old children of mothers with and without epilepsy. Women aged 14 to 45 were eligible for inclusion. The primary outcome was the Torrance Test of Creative Thinking-Figural (TTCT-F) Creativity Index. Linear regression models were used in statistical analysis.

A total of 324 children were included in primary analysis 1, 251 of whom had mothers with epilepsy (boys, 44.6%; White, 81.3%; Hispanic/Latino, 20.7%) and 73 of whom had healthy mothers (boys, 52.1%; White, 67.1%; Hispanic/Latino, 23.3%). Primary analysis 2 comprised 228 children.

Monotherapy (72.5%) was the most prevalent third-trimester ASM regimen for women with epilepsy, followed by polytherapy (21.9%). Women not taking ASM during pregnancy were the minority (5.2%). The most common monotherapies were lamotrigine (44.5%) and levetiracetam (37.4%), while the most common polytherapy was lamotrigine plus levetiracetam (41.8%).

In primary analysis 1, no difference in the mean 4.5-year-old TTCT-F Creativity Index score was found between children of women with epilepsy (adjusted least squares mean [LSM], 90.5; 95% CI, 87.8-93.2) vs those of healthy women (adjusted LSM, 93.7; 95% CI, 88.6-98.8; P =.286). In the adjusted model, higher maternal IQ was significantly related to higher 4.5-year-old TTCT-F Creativity Index.

In primary analysis 2, no significant relationship was found between 4.5-year-old TTCT-F Creativity Index and mother’s third-trimester maximum observed ratio ASM concentration (adjusted parameter estimate, -2.6; 95% CI, -11.0 to 5.7; P =.530). In the adjusted model, higher maternal IQ was significantly associated with greater creativity.

In secondary analysis, fetal exposure-dependent effects for executive function in children of women with epilepsy were found (parameter estimate, 7.0; 95% CI, 2.9-11.2; P =.001), most prominently for levetiracetam (parameter estimate, 12.9; 95% CI, 4.2-21.6; P =.004).

Study limitations included the small sample size, reduced generalizability of results, potential unmeasured confounding, and possible selection bias.

“Our findings suggest that even for relatively safe ASMs, dosing needs to be adjusted to concentrations that prevent seizures, but balance risks to the fetus that high concentrations may pose,” the researchers concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.