Leucovorin is a More Efficacious Folate Source in High-Risk Pregnancies

Abstract

Background: Folinic acid (leucovorin) supplementation in folate receptor alpha autoantibody (FRAA)-positive pregnancies offers a biologically targeted strategy to reduce autism spectrum disorder (ASD) risk and is proving superior to folic acid across a broader range of reproductive and neurodevelopmental outcomes. Observations: A pilot randomized trial by Giorlandino et al. (2026), together with emerging clinical data on infertility and preclinical evidence on a negative impact of excess folic acid, suggests that leucovorin may be the optimal choice of folate form for prenatal care. For at risk pregnancies with maternal FRAA present, standard folic acid supplementation resulted in 60% of births diagnosed as autistic within three years, while those on leucovorin resulted in 10% diagnosed autistic. Conclusion: This striking difference is evidence of the importance of choosing the appropriate form of folate for perinatal care, with leucovorin proving the safer choice, and perhaps the optimal choice when maternal FRAA is present.