Pediatric Leucovorin Prescriptions Rose Sevenfold in 2025 After Federal Officials Touted It for Autism
核心洞察
Weekly counts of U.S. children filling a leucovorin prescription rose from 734 to 5,858 across 2025, a roughly 700% increase, according to a NEJM analysis.
A 46% single-week jump in pediatric dispensing coincided with a September 2025 federal press conference promoting leucovorin for autism.
The FDA approved leucovorin in March 2026 only for cerebral folate transport deficiency (搜索) tied to a FOLR1 (搜索) gene variant, not for autism spectrum disorder (搜索).
The number of American children filling a leucovorin prescription rose roughly sevenfold over the course of 2025, and a sharp single-week jump coincided with a federal press conference promoting the drug for autism, according to an analysis published in The New England Journal of Medicine.
The research, led by Kao-Ping Chua of the University of Michigan, drew on the IQVIA Longitudinal Prescription Database, which captures about 93 percent of prescriptions filled at United States retail pharmacies. Across 2025, the database recorded 150,026 leucovorin prescriptions dispensed to 47,394 children.
"Our findings suggest the press conference may have increased off-label prescribing of leucovorin to children with autism," said lead author Kao Ping Chua, M.D., Ph.D., a pediatrician and researcher at University of Michigan Health C.S. Mott Children's Hospital and director of the Susan B. Meister Child Health Evaluation and Research Center. "This increase is concerning because the effectiveness and long-term safety of leucovorin for children with autism is uncertain."
The Prescribing Curve Tracks the Announcement
The weekly number of children with a filled leucovorin prescription rose from 734 at the start of 2025 to 5,858 by the end of it, an increase of roughly 700 percent. Measured against the population, dispensing climbed from 1.0 per 100,000 children early in the year to 4.6 per 100,000 in the week before the September 2025 press conference.
During the week of the conference itself, the rate rose 46 percent, from 4.6 to 6.7 per 100,000 children. By the close of the study period, which ran through mid-December, it had reached 8.0 per 100,000. Dispensing to adults showed no comparable spike, which is the comparison that makes the pediatric pattern hard to explain by supply or coding changes.
The increases were concentrated among children ages 6 to 11 and in the southern United States. Michigan Medicine reported Chua as saying the findings "demonstrate the power of the federal government to influence medical practice," and that the increase is concerning because the effectiveness and long-term safety of leucovorin for children with autism is uncertain. The analysis also found dispensing was already rising before the press conference, a trend the authors suggest may have followed news coverage featuring individual patient stories.
A Narrow Approval and a Much Broader Use
Leucovorin is a prescription form of folinic acid that has been used for decades to counter the toxic effects of methotrexate in cancer and autoimmune treatment. The Department of Health and Human Services announced at the September 2025 event that it planned to update the drug's label to cover cerebral folate deficiency.
The approval that followed was considerably narrower than the announcement suggested. In March 2026, the Food and Drug Administration (搜索) approved leucovorin for cerebral folate transport deficiency (搜索), an ultra-rare genetic neurological condition tied to a confirmed variant in the FOLR1 (搜索) gene. The agency did not approve it for autism spectrum disorder (搜索).
That distinction is not academic. Cerebral folate transport deficiency (搜索) affects a very small number of children and requires specific genetic confirmation. The prescribing surge documented in the new analysis extends far beyond any population plausibly carrying that diagnosis, which means most of it represents off-label use for autism itself.
The Supporting Research Got Smaller, Not Larger
The clearest development since the announcement runs in the opposite direction from the prescribing curve. The largest randomized trial supporting leucovorin's use in autism, a study of 77 autistic children originally published in 2024, was retracted by the European Journal of Pediatrics early this year after a post publication statistical review confirmed concerns about the data and could not replicate the reported results. It was one of only a handful of randomized clinical trials ever conducted on leucovorin in autistic people.
Zoe Gross, director of advocacy at the Autistic Self Advocacy Network, told CIDRAP News that "When the administration made that recommendation, the evidence wasn't strong enough," and said the retraction left the evidence weaker still.
The American Academy of Pediatrics maintains guidance for clinicians on leucovorin use in autism that families can review with their own pediatrician. The Child Neurology Society position statement reviews the three small randomized trials of leucovorin as a treatment for idiopathic autism and concludes that their limitations preclude firm conclusions about effectiveness.
A separate electronic health record analysis from the University of California, San Diego, published in JAMA Network Open earlier this year, examined more than 11.9 million outpatient encounters involving 838,801 children with autism and found prescribing rates rose more than 2,000 percent from a stable baseline. The two studies use different denominators, but both point in the same direction.
Clinical and Safety Considerations
Chua says the rise in leucovorin use among children raises several concerns, including the potential to create false hope for families, displace evidence-based therapies and expose young children to a treatment whose effectiveness and long-term safety have not been established.
Other researchers have speculated that increased off-label prescribing of leucovorin may have contributed to ongoing drug shortages that have reduced access for cancer patients who depend on the medication.
The research letter measured prescribing behavior, not clinical outcomes. It does not establish that leucovorin is harmful, and it does not establish that it is ineffective for every child. What it establishes is that a large behavioral shift occurred without a matching shift in evidence, and that families deserve to know which side of that gap their own prescription sits on.
"Our findings demonstrate the power of the federal government to influence medical practice. Given this power, it is important that the government's messaging about medications is based on rigorous evidence," Chua said.