After President Donald Trump’s September 2025 unsupported claim that autism is linked to the use of acetaminophen (Tylenol) in pregnancy and that leucovorin may help autistic children, US Tylenol use fell among pregnant women, while leucovorin (folinic acid) prescriptions surged, Harvard and Brown University physician researchers suggested yesterday in The Lancet.
Despite the lack of new evidence, Trump made those statements at a White House briefing, where he called leucovorin “an exciting therapy that may benefit large numbers of children who have suffered from autism,” which was followed by a US Food and Drug Administration (FDA) label update listing it as a potential treatment for cerebral folate deficiency, a rare neurologic syndrome.
“The problem is that the best science does not suggest this linkage between acetaminophen use and later rates of autism,” first author Jeremy Faust, MD, of Harvard Medical School, wrote on his Inside Medicine Substack yesterday. “In the case of leucovorin, a drug that can treat a condition called cerebral folate deficiency, there is simply no good evidence to suggest that it will help most children with autism or related conditions.”
The authors caution that a causal relationship can’t be established with observational studies.
Models projected counterfactual scenarios
The researchers analyzed Epic electronic health record data up to November 2025 for Tylenol orders during emergency department (ED) visits and new leucovorin prescriptions in outpatient clinical visits. They also conducted an interrupted time-series analysis using weekly ED orders or outpatient clinic prescription counts from before Trump’s claims (June 30 to September 21, 2025).
The team then used the models to project counterfactual scenarios, predicting expected orders and prescription numbers for the post-policy period had the briefing not occurred. They also assessed orders for Tylenol, as well as opioids and lactated Ringer’s solution as control comparators. The analysis was repeated for non-pregnant women of the same age.
Children aged 5 to 17 years were used in the leucovorin analysis using new outpatient prescriptions for leucovorin, as well as aripiprazole, risperidone (the only other drugs with FDA-approved indications for use in autism spectrum disorder), folic acid preparations, and levoleucovorin (based on their similarity to leucovorin) as control comparators. The levoleucovorin analysis, however, was abandoned due to insufficient data.
Without evidence, politicians steer health behavior
From Sept 22, 2025, to November 2025, pregnant women aged 15 to 44 years made 88,857 ED visits, while non-pregnant women made 853,216 such visits, and children aged five to 17 years had more than 8.6 million outpatient visits.
The results show just how much political leaders can steer health behavior even when there has been no change in the evidence for these therapies.
Michael Barnett, MD
Tylenol orders for pregnant women visiting the ED fell 10% (observed-to-expected ratio [OER], 0.90), corresponding to an absolute rate change of 22.5 orders per 1,000 visits. During the initial study period, Tylenol orders plunged 16% (OER, 0.84), then reached the maximal change of 20% in the third week. No statistically significant change was noted in ED Tylenol use among non-pregnant women, nor among the comparators, regardless of pregnancy status.
“The White House briefing was an extremely unusual mechanism to communicate medical information and bypassed many standard checks on ensuring accurate messaging,” coauthor Michael Barnett, MD, of Brown University, said in a university news release. “The results show just how much political leaders can steer health behavior even when there has been no change in the evidence for these therapies.”
New outpatient leucovorin prescriptions for children rose 71% during the study period (OER, 1.71, corresponding to an absolute rate change of 17.5 prescriptions per 100,000 visits. Initially, a 93% increase (OER, 1.93) was noted, but the peak change was seen in the second week, when the prescription rate more than doubled (113% above expected values).
No statistically significant change was observed in outpatient folic acid prescriptions. Smaller increases in aripiprazole (OER, 1.14) and risperidone (OER, 1.13), which primarily occurred late in the study period.
“Although causal claims cannot be made, the observed associations are consistent with influence of new FDA recommendations on clinical decisions,” the authors wrote. “It is unknown whether the results reported reflect changes in patient demand or clinician decision making; nonetheless, they show the apparent power that public authority figures have to drive sudden changes in health-care practices.”
‘False expectations and unnecessary side-effects’
A similar effect was seen during the COVID-19 pandemic, wherein Trump’s statements, based on low-quality evidence, led to increased interest in drugs such as ivermectin, which is unproven for COVID-19.
There are multiple potential consequences from these changes.
The effects of these statements were rapid, although they seem to have faded for Tylenol. Explanations, the researchers said, “include fading salience of the press conference, which would be less likely for leucovorin as a long-term treatment, and messaging from trusted organisations refuting claims made at the briefing. Paracetamol [Tylenol] use also generally rises in late November due to the onset of cold and influenza season, and our model did not account for seasonality.”
The increase in aripiprazole and risperidone use, especially later in the study, could reflect spillover effects or searches for alternative therapies during the November 2025 US leucovorin shortage, they added.
“There are multiple potential consequences from these changes, including higher incidence of untreated fevers (a risk factor for neurological disorders) and use of antipyretic [fever-reducing] or analgesic [pain-relieving] medications that are less safe in pregnancy than paracetamol, which is safe to use during pregnancy,” they wrote.
“Recent additional evidence has identified no increased rates of autism disorders, attention-deficit hyperactivity disorder, or intellectual disability among the offspring of those who used paracetamol during pregnancy,” they concluded. “For leucovorin, an increase in prescribing outside the rare condition of cerebral folate deficiency might confer false expectations and unnecessary side-effects.”