Nearly 50,000 American children received leucovorin prescriptions in 2025, highlighting rapid off-label use driven by public attention, despite limited evidence of effectiveness and safety concerns.
Nearly 50,000 American children filled a leucovorin prescription in 2025, according to research published in the New England Journal of Medicine, underscoring how quickly an unproven autism treatment has spread through paediatric care. The study, led by researchers at University of Michigan Health C.S. Mott Children’s Hospital, used the IQVIA Longitudinal Prescription Database and found 150,026 dispensings to 47,394 children over the year.
The rise was not gradual. Researchers said the weekly number of children receiving the drug climbed from 734 at the start of 2025 to 5,858 by the end of the year, with a sharp jump around a September 2025 federal press conference that described leucovorin as an effective autism treatment. In the week before that event, 4.6 children per 100,000 aged 0 to 17 filled a prescription; during the week of the briefing, that figure rose to 6.7 per 100,000, and by year-end it had reached about 8.0 per 100,000.
Kao-Ping Chua, the study’s lead author, said in a statement from Michigan Medicine that the increase is worrying because the drug’s effectiveness and long-term safety in autistic children remain uncertain. The biggest gains were among children aged 6 to 11 and in the southern United States. The authors also warned that greater off-label use could worsen shortages for cancer patients who rely on leucovorin in standard care.
Leucovorin, also known as folinic acid, is a long-established medicine used mainly to reduce the side effects of methotrexate in cancer and autoimmune disease treatment. Some small studies have suggested it may help certain children with autism, particularly those with folate-related abnormalities, but there has been no large randomised trial proving benefit for autism overall. The evidence base actually became shakier this year, after the largest randomised study of oral folinic acid in autistic children was retracted over data and statistical problems. The American Academy of Paediatrics does not recommend routine use of leucovorin for autism.
The regulatory picture is narrower than the public debate might suggest. On 10 March 2026, the Food and Drug Administration approved Wellcovorin, a leucovorin calcium tablet, for cerebral folate transport deficiency in adults and children with a confirmed variant in the folate receptor 1 gene. The condition is rare and can cause developmental delays and autistic features, but it is distinct from autism spectrum disorder, and the approval does not extend to autism. The FDA had already taken action in September 2025 to advance the treatment pathway for that rare disorder after reviewing published literature, case reports and mechanistic data.
For parents, the appeal of trying a cheap, familiar drug is easy to understand, especially when speech therapy and behavioural support are hard to access. But the known safety record for leucovorin comes from different patients, different doses and different time frames. A child taking it for months or longer for autism is not the population in which that record was built. Families already using it should not stop it abruptly without speaking to a clinician, and those considering it may want to ask whether their child has been assessed for cerebral folate transport deficiency, what change would count as a response and how long a trial should last.
The study also built on a separate analysis published in JAMA Network Open in May 2026, which found that prescribing had held steady for about two years before surging sharply in late 2025. Together, the findings suggest that a single high-profile announcement can move prescribing behaviour nationwide long before the underlying science changes.
Researchers said several trials are still under way, including a National Institutes of Health-funded study of leucovorin for language impairment in children with autism spectrum disorder. Until those results are published and independently reviewed, the current evidence supports a hypothesis, not a standard treatment.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
