Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?

This prospective cohort study within the Norwegian Mother, Father, and Child Cohort Study examined whether maternal genetic liability to folate deficiency modifies the association between prenatal antiseizure medication (ASM) exposure and child neurodevelopmental outcomes. Children of women with and without epilepsy were included with available genetic data. Polygenic risk scores for low folate concentrations and maternal rs1801133 genotype served as proxies for genetic liability. The polygenic risk score did not interact with ASM-associated risk of language impairment or autistic traits. ASM-exposed children had increased risk of language impairment at age 8 regardless of maternal rs1801133 genotype (aOR 2.88 for both CC and CT/TT genotypes). In children without epilepsy, maternal CT/TT genotype was associated with modestly increased language impairment risk at age 3 (aOR 1.18). Folic acid supplement use was widespread and may counteract genetic effects. Limitations include parent-reported outcomes via screening instruments rather than formal assessment, small subgroup sizes, and single measurement of folate concentrations.