Highlights:
- The American Academy of Pediatrics (AAP) has issued new guidelines banning 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 treatments while research on leucovorin continues.
- The interim guidance follows the FDA’s plan to update leucovorin labeling to include cerebral folate deficiency, which may present with developmental delay and autism-like features.
The American Academy of Pediatrics (AAP) issued a guidance statement recommending against routine use of leucovorin in children with autism, citing limited evidence.1
In a press release sent on October 31, 2025, the AAP stated that prescribed folinic acid is commonly used to reduce side effects associated with chemotherapy and to treat certain types of anemia caused by vitamin B12 and folic acid deficiencies.
“Medical decisions involving new treatments like leucovorin should be thoroughly reviewed before widespread implementation to ensure children stay safe and healthy,” Kristin Sohl, MD, FAAP, said in a statement. Sohl is a member of the Executive Committee of the AAP Council on Children with Disabilities and Immediate Past Chair of the Autism Subcommittee. “It is important to take the time necessary to understand the evidence and navigate conversations that provide pediatricians with accurate information to support their patients,” Sohl added.
In the interim guidance, the AAP expressed support for continued research into promising treatments and provided recommendations for talking to families about leucovorin.2
In its 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 to provide clear information about the current evidence and potential risks. Children, adolescents, and young adults with autism benefit from access to robust supports and services tailored to their individual needs. Pediatricians and other pediatric care providers should work with families to optimize recommended services and emphasize continuation of robust supports,” the AAP states. There are no guidelines for leucovorin prescribing for any indication that pediatricians, physician assistants, or nurse practitioners should prioritize when prescribing leucovorin to pediatric patients. “We help families make complex treatment decisions through harm mitigation, close monitoring of side effects, and compassion, transparency, and scientific integrity.”
“The reason the AAP does not broadly recommend leucovorin is because we know that children with autism deserve the same level of evidence supporting the intervention as anyone else,” Sohl added.
Federal officials offer guidance on leucovorin
The interim guidance comes after the FDA announced in September that it would begin the process of updating leucovorin’s label to include children and adults with cerebral folate deficiency (CFD). Clinical findings of CFD may include developmental delay, autism, seizures, tone/motor abnormalities, acquired microcephaly, and myelin abnormalities on brain MRI.2
On September 23, AAP President Susan Kressley told federal health officials after claims that a separate vaccine could reduce autism rates: “Today’s White House event on autism was filled with dangerous claims and misleading information that sends confusing messages to parents and parents-to-be and harms people with autism.”4
“We know that parents often look to their pediatricians for support and guidance. We want to be there for them and we need to be knowledgeable and informed so we can have these conversations,” Sohl said.
In line with this message, the AAP has published a page of frequently asked questions for pediatricians and other pediatric clinicians regarding the use of leucovorin in autism and CFD.5
FAQs from the AAP about autism and leucovorin:
- What is leucovorin?
- What is leucovorin used for?
- Can FRAA be tested in people with autism?
- What does the research say about leucovorin in autism?
- Does leucovorin have any side effects?
References:
- The American Academy of Pediatrics issues interim guidance for pediatricians to support parents in conversations about the drug leucovorin. AAP. press release. October 31, 2025. Accessed October 31, 2025.
- Jenco M. AAP: Evidence is too limited to broadly recommend leucovorin for children with autism. 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 guidelines from the American Academy of Pediatrics: Use of leucovorin in pediatric patients with autism. 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 and 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.
