Breastfeeding and Neurodevelopmental Outcomes in Children of Women Taking Antiseizure Medications

Importance Concerns regarding infant exposure to antiseizure medications (ASMs) via breast milk frequently discourage breastfeeding in women with epilepsy (WWE). Longitudinal neurodevelopmental data for breastfeeding while taking contemporary ASM regimens are essential for evidence-based management. Objective To evaluate the association between breastfeeding duration and neurodevelopmental outcomes at age 6 years in children exposed to contemporary ASM regimens. Design, Setting, and Participants The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a prospective, multicenter, cohort study. Pregnant WWE and healthy pregnant women were enrolled from December 2012 to October 2016, with children followed up to age 6 years. Children’s outcomes were analyzed between January 2023 and December 2024. Exposures Breastfeeding duration (none, <6 months, ≥6 months) and children’s exposure to contemporary ASMs (primarily levetiracetam and lamotrigine). Main Outcomes and Measures The primary outcomes at child age 6 years included verbal language (Verbal Index Score) and adaptive behavior (General Adaptive Composite score in Adaptive Behavior Assessment System Scale). Results A total of 273 children of WWE (median [range] maternal age, 31.0 [19.0-46.0] years; 127 [46.5%] male) and 84 children of healthy women (median maternal age, 31.0 [15.0-38.0] years; 47 [56.0%] male) were included, with 262 children of WWE and 80 children of healthy women in the language outcome sample and 261 children of WWE and 83 children of healthy women in the behavioral outcome set. Adjusted mean (SD) verbal language (107.93 [0.71] vs 107.18 [1.40]; difference, 0.75; 95% CI, −2.40 to 3.89; P = .64) and adaptive behavior (102.91 [0.75] vs 102.14 [1.46]; difference, 0.78; 95% CI, −2.52 to 4.07; P = .64) outcomes did not significantly differ between groups. Within the WWE cohort, breastfeeding for 6 months or longer was significantly associated with higher adaptive behavioral scores compared with no breastfeeding (estimate, 4.68; 95% CI, 1.34 to 8.03; P = .01), driven by practical and conceptual subdomains; whereas shorter durations (<6 months) did not differ. Neurodevelopmental outcomes were comparable within each specific ASM regimen—including levetiracetam, lamotrigine, other monotherapy, and polytherapy—regardless of breastfeeding duration. Notably, the benefit associated with breastfeeding for 6 months or longer remained significant in the pooled monotherapy group (difference, 5.88; 95% CI, 2.21 to 9.55; P = .001) but not in the polytherapy group. Conclusions and Relevance In this cohort study of children born to WWE, breastfeeding while taking contemporary ASM regimens was not associated with adverse neurodevelopmental outcomes at age 6 years. The observed improved adaptive behavioral outcome supports clinical recommendations for extended breastfeeding (≥6 months) in WWE.