Purpose of review To provide pediatric clinicians with an overview of current research on leucovorin use in children with autism spectrum disorder (ASD) and a guide to patient evaluation and treatment. Recent findings An association between cerebral folate deficiency (CFD) and ASD has been suggested in some studies. Autoantibodies that block folate entry into the brain are a cause of CFD and have been detected in 71% of patients with ASD. Leucovorin is a synthetic drug that increases folate concentrations in the brain despite the presence of autoantibodies. Certain studies have indicated reductions in communication deficits in nonverbal children with ASD, particularly those with these autoantibodies, following consistent leucovorin use. However, other studies have found no change in symptoms despite leucovorin intake. The American Academy of Pediatrics (AAP) currently does not recommend use of leucovorin in children with ASD. Summary Due to recent popularity among policymakers and on social media, many pediatricians have reported increased requests by families for leucovorin prescriptions to treat ASD in pediatric patients. This review provides clinicians with an overview of the biological rationale, clinical evidence, and potential benefits and limitations of leucovorin use in children with ASD.
Howard et al. (2026) studied this question.