Maternal folate receptor alpha autoantibodies and folate levels during pregnancy in relation to autism spectrum disorder: a pilot case-control study.

Background: Folate receptor alpha autoantibodies (FRAA) are reported to be associated with autism spectrum disorder (ASD) and are found more frequently in mothers of children with ASD. However, the relationship between maternal FRAA during pregnancy, folate status, and ASD risk in offspring remains unclear. Objective: In this exploratory pilot study, we compared maternal serum binding FRAA measured during pregnancy between high-folate ASD cases and childbirth-time-matched mothers of typically developing children. Methods: FRAA were retrospectively analyzed in serum samples collected between gestational weeks 7 and 18 from women whose children were later diagnosed with ASD (case subgroup, n = 10) and mothers of neurotypical children (control subgroup, n = 10). Case samples were selected based on previously measured elevated folate levels, while controls were selected to minimize differences in biobank storage duration. Results: FRAA were detected in 2 of 10 samples in each group, corresponding to a prevalence of 20%. Although based on limited statistical power, no significant difference in FRAA prevalence was observed. Conclusion: In this exploratory pilot study, no difference in binding FRAA prevalence was found between mothers of children with ASD, who were selected for elevated maternal folate levels, and mothers of neurotypical children. While this finding does not support a link between FRAA and elevated maternal folate levels, the small sample size and selection criteria limit interpretation. Limitations: The study was limited by the small sample size, differences in subgroup selection, uncertainty in gestational age at sampling, and the inability to assess blocking FRAA.