Rethinking Prenatal Folate Assessment: Maternal Folate Receptor Autoantibodies and Child Neurodevelopment

Abstract Folic acid supplementation during pregnancy is established for preventing neural tube defects, yet its broader neurodevelopmental benefits remain inconsistently observed. Folate receptor autoantibodies (FRAA) may disrupt folate transport, but population evidence is lacking. In a prospective cohort of 3,006 mother-child pairs from the Shanghai Birth Cohort, we precisely quantified maternal red blood cell 5-methyltetrahydrofolate (active folate) and FRAA levels in early pregnancy. We found that higher maternal folate was associated with better offspring cognitive performance, especially in executive function. This benefit was attenuated by elevated maternal FRAA (≥70th percentile). Notably, the attenuating effect of FRAA was specifically amplified among mothers with higher milk intake. Our findings highlight the importance of considering maternal immune status in prenatal folate assessment and support personalized nutritional strategies that consider immune context to optimize offspring neurodevelopment.