More leucovorin prescribed to kids after federal officials touted its unproven benefits for autism

Leucovorin prescriptions for children spiked after federal officials claimed the drug was an effective treatment for autism during a September 2025 press conference, according to a new Michigan Medicine-led study published in The New England Journal of Medicine.

During the highly publicized event, the United States Department of Health and Human Services announced a plan to update leucovorin’s label to include cerebral folate deficiency, a rare genetic condition that can sometimes include symptoms of autism.

At the same time, federal officials also touted leucovorin’s effectiveness for autism, despite limited evidence supporting that claim.

After the press conference, the number of children aged 0-17 with a filled leucovorin prescription increased 46%, from 4.6 children per 100,000 in the week before the conference to 6.7 per 100,000 during the week of the conference, according to the new research.

"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 authors analyzed a database representing nearly all prescriptions filled in U.S. retail pharmacies.

During 2025, the database included 150,026 leucovorin prescriptions dispensed to 47,394 children.

The weekly number of children with filled leucovorin prescriptions rose from 734 to 5,858 children between the beginning and end of 2025 – a 700% jump.

Much of this increase was driven by the spike in leucovorin dispensing after the press conference, and the largest increases were seen among children ages 6 to 11 and in the southern United States.

By comparison, leucovorin dispensing to adults did not spike after the press conference.

Leucovorin, a decades-old version of Vitamin B9, has mainly been used to counter side effects from methotrexate, a drug used in treating cancer and autoimmune conditions.

A handful of small studies have suggested that leucovorin can help improve some autism symptoms in children, but large randomized clinical trials have not been conducted.

By using a comprehensive national database, the new study builds on earlier research that used smaller databases to assess changes in leucovorin prescribing to children after the press conference.

Concerns about increased off-label use

The new research also showed that there was an increase in leucovorin dispensing to children even before the press conference.

The trend may have been driven by national news coverage featuring compelling patient stories that may have increased interest among some families.

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.

"Our findings demonstrate the power of the federal government to influence medical practice," Chua said.

"Given this power, it is important that the government’s messaging about medications is based on rigorous evidence.”

Additional authors: Sijia He, M.S. and Rena M. Conti, Ph.D.

Study Cited: "Leucovorin Dispensing to U.S. Children in 2025,” NEJM.