The American Academy of Pediatrics (AAP) says it does not recommend the routine use of leucovorin in children with autism spectrum disorder (ASD), citing limited evidence in newly released interim guidance.
Leucovorin, a folate analog, is currently approved by the Food and Drug Administration (FDA) to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists. Its use in ASD gained momentum following the announcement by the Trump administration about a possible link between acetaminophen and autism risk.
During the meeting, the FDA’s Commissioner Dr Marty Makary stated that the FDA was working with GSK, the makers of Wellcovorin (a branded version of leucovorin calcium tablets) to broaden the labeling to include treatment of cerebral folate deficiency (CFD), a neurological disorder that affects folate transport to the brain.
Patients with CFD have been observed to have developmental delays with similar features to ASD including communication challenges, sensory processing, and repetitive behaviors. However, evidence for the use of leucovorin to treat autism symptoms is mainly limited to small studies and case reports in children with CFD. The FDA has acknowledged that additional studies are needed to assess the safety and efficacy of leucovorin in broader ASD pediatric populations.
“Medical decisions including emerging therapies like leucovorin must be thoroughly examined before we begin implementing them widely to ensure that children remain safe and healthy,” said Kristin Sohl, MD, FAAP, a member of the AAP Council on Children with Disabilities Executive Committee and immediate past chair of its Autism Subcommittee. “It is important that we take the necessary time to understand the evidence and equip pediatricians with accurate information to navigate these conversations in support of their patients.”
For clinicians who do prescribe leucovorin for a pediatric patient, the interim guidance states that “they should prioritize harm mitigation, closely monitor for adverse effects, and support families in navigating complex therapeutic decisions grounded in compassion, transparency, and scientific integrity.”
More information on leucovorin use in autism and CFD is available in the AAP’s accompanying Frequently Asked Questions section for pediatricians and other prescribing pediatric clinicians.
This article originally appeared on MPR
References:
American Academy of Pediatrics. Interim guidance from the American Academy of Pediatrics: use of leucovorin in autistic pediatric patients. October 31, 2025. https://www.aap.org/en/patient-care/autism/use-of-leucovorin-in-autistic-pediatric-patients/.
