Key takeaways:
- The American Academy of Pediatrics (AAP) issued new guidance advising against the routine use of leucovorin in children with autism, citing limited supporting evidence.
- The statement emphasizes shared decision-making, harm mitigation, and continued reliance on established autism therapies while research on leucovorin continues.
- The interim guidance follows FDA plans to update leucovorin labeling to include cerebral folate deficiency, which can present with developmental delay and autism-like features.
The American Academy of Pediatrics (AAP) has released a guidance statement saying it does not recommend the routine use of leucovorin in children with autism, citing limited evidence.1
In a press release sent on October 31, 2025, the AAP said the prescription form of folinic acid is typically used for the reduction of side effects associated with chemotherapy and to treat a specific kind of anemia caused by vitamin B12 and folate deficiencies.
“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, in a statement. Sohl is 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," added Sohl.
In the interim guidance, the AAP expressed support for continued research into promising therapies and provided recommendations for speaking with families about leucovorin.2
In the guidance, the AAP stated:3
"Pediatricians and prescribing pediatric care providers, including other physicians, physician assistants, and nurse practitioners, are encouraged to engage in shared decision-making with families who inquire about or request leucovorin, providing clear information about current evidence and potential risks. Autistic children, adolescents, and young adults benefit from access to robust supports and services based on their individual needs. Pediatricians and other pediatric care providers should work with families to optimize recommended services and emphasize continuation of well-established supports and therapies that are beneficial to the well-being of the child. The AAP does not have prescribing guidelines for leucovorin for the indication of autism. If a pediatrician or other physician, physician assistant, or nurse practitioner prescribes leucovorin for a pediatric patient, 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."
“The reason the AAP is not broadly recommending leucovorin is because we know that autistic children deserve the same level of evidence to support interventions for them as anyone else,” added Sohl.
Federal officials on leucovorin prompts guidance
The interim guidance comes after the FDA in September said it would begin the process of updating the label of leucovorin to include children and adults with cerebral folate deficiency (CFD), of which clinical findings of CFD may include developmental delay, autism, seizures, tone/movement abnormalities, acquired microcephaly, and myelination abnormalities on brain MRI.2
On September 23, AAP president Susan Kressly responded to federal health officials after claims that giving separate vaccines could reduce the rate of autism, stating at the time, "Today’s White House event on autism was filled with dangerous claims and misleading information that sends a confusing message to parents and expecting parents and does a disservice to autistic individuals."4
“We know parents are often looking to their pediatricians for support, for guidance, and we want to be there for them and need to be knowledgeable and informed so we can have these conversations,” said Sohl.
Aligning with this message, the AAP has published a frequently asked questions page for pediatricians and other pediatric clinicians regarding leucovorin use in autism and CFD.5
FAQs provided by the AAP regarding autism and leucovorin:
- What is leucovorin?
- What is leucovorin used for?
- Can I test for FRAAs in my autistic patients?
- What do the studies say about leucovorin in autism?
- Are there side effects to leucovorin?
For answers to these FAQs from the AAP, click here.
References:
- American Academy of Pediatrics Publishes Interim Guidance for Pediatricians on Supporting Parents in Conversations about the Drug Leucovorin. AAP. Press release. October 31, 2025. Accessed October 31, 2025.
- Jenco M. AAP: Evidence too limited to recommend leucovorin broadly for autistic children. AAP. October 31, 2025. Accessed October 31, 2025. https://publications.aap.org/aapnews/news/33649/AAP-Evidence-too-limited-to-recommend-leucovorin?searchresult=1
- Interim guidance from the American Academy of Pediatrics: Use of leucovorin in autistic pediatric patients. AAP. October 31, 2025. Accessed October 31, 2025. https://www.aap.org/en/patient-care/autism/use-of-leucovorin-in-autistic-pediatric-patients/?_gl=1*54aumt*_ga*ODQ2NDg4OTI4LjE3MjU4OTQ5MjA.*_ga_FD9D3XZVQQ*czE3NjE5MjAxOTkkbzQyNyRnMSR0MTc2MTkyMDE5OSRqNjAkbDAkaDA.
- Schering S. AAP: ‘Dangerous claims’ about causes of autism confuse parents, harm children. AAP. Published September 23, 2025. Accessed October 31, 2025. https://publications.aap.org/aapnews/news/33405/AAP-Dangerous-claims-about-causes-of-autism?autologincheck=redirected
- Frequently asked questions for pediatricians and other prescribing pediatric clinicians: leucovorin use in autism and cerebral folate deficiency. AAP. October 31, 2025. Accessed October 31, 2025. https://www.aap.org/en/patient-care/autism/use-of-leucovorin-in-autistic-pediatric-patients/frequently-asked-questions-faqs-for-pediatricians-and-other-prescribing-pediatric-clinicians/?_gl=1*1qs8o9s*_ga*ODQ2NDg4OTI4LjE3MjU4OTQ5MjA.*_ga_FD9D3XZVQQ*czE3NjE5MjAxOTkkbzQyNyRnMSR0MTc2MTkyMDIwNiRqNTMkbDAkaDA
