Researchers found that orders of acetaminophen, the generic term for the drug in Tylenol, decreased by 10 percent among pregnant emergency room patients after President Donald Trump's remarks.
When President Donald Trump warned pregnant women against using Tylenol by tying it to autism without a proven link, the country listened, a study released Thursday suggests.
Orders of acetaminophen, the generic term for the drug in Tylenol, decreased by 10 percent among pregnant emergency room patients in the almost three months after Trump's comments in September compared to almost three months before, according to a peer-reviewed examination in the journal Lancet.
Researchers looked at U.S. data from Epic, an electronic health record system, comparing tens of thousands of ER visits at over 1,600 hospitals among pregnant female patients aged 15-44.
The findings show correlation rather than causation, the authors are careful to note. The study did not indicate whether the shift was because doctors were prescribing it less or women were declining to take it. Additionally, since this study only encompasses prescriptions for Tylenol in a hospital setting, usage patterns may differ among individuals who purchase it over the counter.
The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics say the science does not clearly tie Tylenol use in pregnancy to autism.
The study shows the president and his administration could have significant influence over people's personal medical decisions, said Jeremy Faust, one of the study's co-authors and an emergency room physician at Brigham and Women's Hospital in Boston and an assistant professor at Harvard Medical School.
"There are people who listen to our leaders, and they have an enormous responsibility to speak in a way that the science reflects," Faust said.
White House spokesman Kush Desai said the Trump administration does not believe that "simply popping more pills is the solution for better health outcomes."
"In light of evidence suggesting associative risks of autism with Tylenol use -- a fact that Tylenol executives have privately admitted to -- President Trump was right to express his common-sense opinion that Americans should use caution with all medications and adhere to FDA guidance," Desai said.
Meanwhile, outpatient prescriptions for leucovorin, a drug that Trump promoted as a potential autism treatment, rose 71 percent among children aged 5-17 during the same time period, according to the Epic data that looked at millions of outpatient encounters at 37,000 clinics.
The AAP does not recommend the routine use of leucovorin for children with autism. It does, however, stop short of opposing it outright, advising that pediatricians engage in shared decision-making with families who ask about the drug and offer clear information about the available evidence and its potential risks.
Faust and his co-author Michael L. Barnett, a public health professor at Brown University, noted the potential medical consequences tied to the trends involving Tylenol and leucovorin use. Backing off of using Tylenol could lead to a higher incidence of untreated fevers in those who are pregnant, which can put stress on the fetus.
Alycia Halladay, chief science officer for the Autism Science Foundation, said the study raises serious concerns.
"Having a fever during pregnancy has been shown to be more dangerous than having Tylenol," Halladay said.
"Pregnant women should consult with their health care provider about treatment options if they have a fever," said Andrew Nixon, a spokesman for the Department of Health and Human Services.
An increase in leucovorin use, the authors write, "might confer false expectations and unnecessary side effects."
The research points to a broader reality in a world of health misinformation and political spin: When leaders speak with confidence about science that isn't settled, people may change their behavior right away, while corrections and fuller explanations take longer to catch up.
"We are in a time when there's a lot of confusion and distrust around health messaging," said Megan Ranney, an emergency physician and dean of the Yale School of Public Health. "We've seen a dramatic decline in the public's trust in government health messaging over the last year, and that reflects confusion about whether what's coming out of the government is accurate or not."
Nixon pushed back on the critique: "This is the most pro-patient administration in American history, and delivering a message about a specific neurological risk for babies is another example of its commitment to telling the truth about public health -- something the Biden administration would not do."
'Don't take it'
"Don't take Tylenol, don't take it," Trump said in September. "Fight like hell not to take it." But in the days that followed, his health officials softened the administration's tone.
In a notice to physicians, Food and Drug Administration Commissioner Marty Makary advised doctors to "consider minimizing the use of acetaminophen during pregnancy for routine low-grade fevers," while also acknowledging that the drug remains the safest over-the-counter option for pregnant patients. By October, Health Secretary Robert F. Kennedy Jr. was describing the data as "very suggestive," but insufficient to say that acetaminophen "definitely causes autism."
Doctors described a disorienting aftermath to the Trump news conference -- a surge of urgent questions, alarm and families struggling to make sense of what they had just heard.
While Nixon pointed to the fact that there are not large randomized control trials for Tylenol for pregnant women -- the gold standard for proving cause and effect -- researchers don't embark on such studies due to ethical concerns over randomly assigning pregnant women to take or avoid a medication to test potential risks to a fetus. As a result, most research on a possible link between acetaminophen use during pregnancy and autism is observational, meaning it can identify associations but cannot definitively establish causation. That limitation helps explain the ongoing debate.
There have been more than 40 studies about maternal acetaminophen use (referred to as paracetamol in the United Kingdom) during pregnancy and autism in offspring, and some have found a link while others have not.
A meta-analysis, which looked at many of these studies together and was published in Environmental Health in August, concluded that there was a link. This paper was cited by the Trump administration in support of the president's remarks.
But in November, a new analysis in the BMJ, formerly the British Medical Journal, reached the opposite conclusion, finding no clear link between acetaminophen use during pregnancy and autism. And last month, a Lancet review reiterated the BMJ's findings after reviewing the evidence of more than three dozen studies and found no "clinically important increase in the likelihood of autism spectrum disorder, ADHD, or intellectual disability in children of pregnant individuals who use paracetamol as directed."
When asked about the newer findings, Nixon quoted part of the BMJ study that, when taken on its own, did not fully reflect the study's overall conclusion that no clear link was established.
Catherine Lord, a clinical psychologist at the University of California at Los Angeles, said the study from Faust and Barnett underscores how a single comment from a prominent leader can reverberate widely -- and change medical decision-making.
"That is important particularly if the level of science behind what they are saying is not strong" as in this case," she said.
Some parents who have children with autism, Lord said, were gripped by a sudden, misplaced guilt. They wondered whether taking Tylenol during pregnancy might now be to blame -- even as medical groups rushed to counter the claim, noting that no causal link has been established.
Leucovorin questions
Others parents asked about leucovorin, a folate-based medication that has circulated for years at the margins of autism treatment and was thrust, overnight, into wider view.
Leucovorin, or folinic acid, has long been used in cancer treatment. It has been shown to protect healthy cells from the toxic effects of one particular chemotherapy drug and to enhance the effectiveness of another one.
In the case of autism, researchers have theorized that some who are autistic have difficulty transporting folate -- a nutrient essential for neurodevelopment -- to the brain and think the medication may help deliver it more effectively.
Only a handful of randomized controlled trials have examined the drug in relation to autism, most involving no more than a few dozen participants. They have shown hopeful results but the largest of them was retracted by the European Journal of Pediatrics on Jan. 29. The editors wrote that, after publication, concerns were raised about the reported data and that the authors had subsequently identified "a number of errors in the reported results." The journal concluded that it "no longer has confidence in the validity of the results and conclusions reported in this article."
After the Trump administration touted leucovorin, hospitals have responded unevenly. Some systems have discouraged families from pursuing leucovorin outside of research settings. UCLA has taken a more permissive approach. Several physicians there are prescribing the drug, Lord said, and the hospital has generally advised families who are interested to consult a clinician with expertise in autism so that children can be monitored carefully.
In her own practice, Lord sees many patients who are taking leucovorin. (As a psychologist, she provides therapy but does not prescribe medication.) So far, the results have been underwhelming.
"I haven't seen even one minor change," she said.
In pledging to fast-track leucovorin for use in autism, the administration described a monitoring system that it said would generate data on how the drug performs in practice. But Lord and Halladay said they have heard nothing further about whether the system is actually being developed.
When asked for an update on the monitoring system, HHS did not provide new details,saying only that "when there are updates to share,we will."