Development of cerebral lateralization in children exposed to fetal antiseizure medications: A prospective cohort study at age 6 years
01/2026
Journal Article
Authors:
Li, Y.;
Loring, D. W.;
Cohen, M. J.;
Matthews, A. G.;
Birnbaum, A. K.;
Pennell, P. B.;
Meador, K. J.;
Maternal Outcomes Neurodevelopmental Effects of Antiepileptic Drugs Investigator Group
Journal:
Epilepsia
PMID:
41553327
URL:
https://www.ncbi.nlm.nih.gov/pubmed/41553327
Keywords:
antiseizure medications brain lateralization fetal folate handedness language
Abstract:
OBJECTIVE: We previously reported in a prior cohort that fetal exposure to antiseizure medications (ASMs), especially valproate, was associated with reduced right-handedness and poorer verbal versus nonverbal performance in children at age 6 years. Given changes in prescribing practices in epilepsy over the past 2 decades, we enrolled a new cohort of the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study to determine whether fetal exposure to newer generation ASMs is associated with altered cerebral lateralization in children at age 6 years and to assess exposure-dependent effects on handedness, manual dexterity, and verbal/nonverbal abilities. METHODS: The MONEAD multicenter prospective cohort study followed children of women with epilepsy (WWE) on ASMs and healthy women (HW) until age 6 years. We assessed handedness using the Edinburgh Handedness Inventory, manual dexterity through the Grooved Pegboard Test, and verbal/nonverbal abilities with the Differential Ability Scales-II. Outcomes were analyzed in relation to ASM exposure, controlling for confounders. RESULTS: Of 1123 screened pregnant women, 351 children born to WWE and 105 to HW were enrolled. The overall distribution of handedness and verbal/nonverbal scores did not differ between groups. However, subgroup analyses revealed that higher third-trimester levetiracetam concentrations were significantly associated with nondextrality (p = .03, 95% confidence interval [CI] = .03-.67). Across the WWE cohort, higher ASM concentrations correlated with poorer manual dexterity (coefficient = 6.76, 95% CI = .40-13.11, p = .037). Additionally, periconceptional folate supplementation was associated with better nonverbal outcomes (coefficient = 2.54, 95% CI = .93-4.15, p = .002) and parental stress was linked to poorer verbal scores (coefficient = -19.74, 95% CI = -28.48 to -11, p < .001). SIGNIFICANCE: This cohort reassuringly showed no overall difference in verbal/nonverbal abilities between WWE and HW. Fetal ASM exposure had exposure-dependent effects on manual dexterity. Modifiable factors, including folate supplementation and parental stress, significantly influenced developmental outcomes, underscoring the importance of proactive screening and providing intervention when appropriate.