A recent study reveals a sharp increase in leucovorin prescriptions for children following federal health messaging in 2025, raising concerns over evidence and safety outside approved uses.
A recent analysis in The New England Journal of Medicine has found that the number of American children filling leucovorin prescriptions rose steeply during 2025, with the sharpest weekly increase coinciding with a federal press event that promoted the drug as a potential autism treatment. The study, led by Kao-Ping Chua of the University of Michigan, used data from the IQVIA Longitudinal Prescription Database, which covers about 93% of prescriptions filled at US retail pharmacies.
According to the researchers, weekly dispensing among children increased from 734 at the start of the year to 5,858 by year-end. The pace quickened around the September 2025 announcement, with prescribing rising 46% in the week of the briefing itself. The increase was concentrated among children aged six to 11 and in the South, while adult prescribing did not show a similar surge. Chua told Michigan Medicine that the pattern illustrates how strongly federal messaging can shape medical practice, while also noting that the drug’s effectiveness and long-term safety for autistic children remain uncertain.
Leucovorin is a form of folinic acid that has long been used to reduce the toxic effects of methotrexate in cancer and autoimmune care. But the federal announcement in September 2025 went further, linking the drug to autism-related symptoms. The Food and Drug Administration later took a narrower step, approving Wellcovorin on 10 March 2026 for cerebral folate transport deficiency in patients with a confirmed FOLR1 gene variant, a rare genetic disorder that can cause developmental delays, seizures and movement problems. The agency did not approve the drug for autism spectrum disorder.
That distinction matters because the population with confirmed cerebral folate transport deficiency is very small, while the prescribing rise identified in the new analysis was broad and appeared to extend well beyond children with that diagnosis. Fact checkers at FactCheck.org noted that earlier suggestions of a wider autism approval did not match the FDA’s final decision. The FDA also listed possible side effects including rash, breathing difficulty and, in rare cases, anaphylaxis.
The evidence base has not strengthened alongside the rise in prescribing. If anything, it has weakened. The largest randomised trial often cited in support of leucovorin for autism, involving 77 children and published in 2024, was later retracted after statistical concerns could not be resolved. The Child Neurology Society says the three small randomised trials available so far do not allow firm conclusions about benefit, while the American Academy of Pediatrics continues to advise families to discuss the issue carefully with their own clinicians.
A separate study published in JAMA Network Open earlier this year found a similar pattern using electronic health record data: leucovorin prescribing for children with autism had been stable, then climbed rapidly after federal officials publicly highlighted it in September 2025. Advocates for autistic people have argued that the public promotion outpaced the science. Parents already using the medicine should not stop it abruptly, but they may want to ask which diagnosis it was intended to treat, whether any testing supported that choice, what improvement should be expected and how quickly, and whether the prescription could affect access or cost.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
