For more than a decade, scientists have asked whether acetaminophen — the active ingredient in the painkiller Tylenol — could affect fetal brain development, causing problems in children like autism and A.D.H.D. Some studies have suggested that there is a link; others have found none.
Now the latest study, a scientific review by researchers at Harvard’s T.H. Chan School of Public Health and the Icahn School of Medicine at Mount Sinai, has been swept into a larger, politically fraught debate about the causes of autism, spurred in part by the views of Robert F. Kennedy Jr., the Health and Human Services secretary.
There has been speculation that Mr. Kennedy may cite Tylenol use during pregnancy, among other environmental factors, as a potential cause of autism in an upcoming report.
The review that began the latest round of controversy, which examined 46 existing studies, eight of them looking specifically at autism, found there was evidence for a connection between acetaminophen use during pregnancy and neurodevelopmental disorders.
But the researchers who conducted the review cautioned that their conclusion did not mean acetaminophen caused autism, which mainstream scientists overwhelmingly agree is a result of a complex mix of genetic and environmental factors.
And the findings, other experts said, would not alter the advice doctors routinely give pregnant patients about acetaminophen use.
The conclusion of the review “doesn’t change a thing,” said Dr. Nathaniel DeNicola, an OB-GYN who advises the American College of Obstetricians and Gynecologists on environmental issues.
“The conclusion of the paper is that Tylenol should be used judiciously in the lowest dose, least frequent interval,” he said, “which is exactly the current standard of care for Tylenol and for so many medications, and really so many things we may encounter in pregnancy counseling.”
Researchers cannot conduct randomized controlled trials on pregnant women to definitively answer whether the drug causes problems in the developing fetus, because it would be unethical. The studies they reviewed were observational, analyzing data on the women’s pregnancies and then looking at how their children did over time.
Still, the findings circulated widely on social media this week, igniting alarm among parents and autism activists.
The right-wing provocateur Laura Loomer urged “everyone who has ever taken Tylenol or knows someone with autism” to take note, and suggested the common pain reliever could be a culprit behind the rising prevalence of autism diagnoses among children in the United States.
Since he has been in office, Mr. Kennedy has repeatedly said that he thinks genetics play a minimal role in autism, an assertion that autism researchers have vehemently disputed. Instead, he has argued that vaccines and other environmental factors are driving the increased incidence of the disorder in children.
The new report on acetaminophen, published in the journal Environmental Health, came out two weeks before Mr. Kennedy announced at a cabinet meeting that later this month he would be revealing new research findings on “certain interventions” that are “almost certainly causing autism.”
On X, Ms. Loomer speculated that the announcement might include findings about acetaminophen. Children’s Health Defense, the anti-vaccine advocacy group founded by Mr. Kennedy, has raised questions about acetaminophen and neurological problems in children.
But multiple health authorities that have examined the question of acetaminophen use — including the Food and Drug Administration, the European Medicines Agency and the Society for Maternal-Fetal Medicine — have said that the findings are inconclusive, meaning that there is no established risk.
In December 2023, a federal judge ruled against plaintiffs in a class-action lawsuit against Johnson & Johnson and other manufacturers of acetaminophen, citing a lack of scientific evidence for the claim that use of the drug during pregnancy caused autism and A.D.H.D. One author of the new report was an expert witness for the plaintiffs in the case.
Tylenol is the most widely used drug in pregnancy, and given that pregnancy is a crucial window for infant brain development, it continues to be important for researchers to investigate the drug’s potential impacts.
In a statement, Kenvue, the parent company of Tylenol’s manufacturer, said: “Nothing is more important to us than the health and safety of the people who use our products. We have continuously evaluated the science and continue to believe there is no causal link between acetaminophen use during pregnancy and autism.”
The company added, “Acetaminophen is one of the most studied medications in history.” Shares of Kenvue dropped precipitously on Friday after a news report that Mr. Kennedy would link the pain reliever to autism in the forthcoming announcement.
The new study did not provide any new data on the question of what happens when pregnant women take acetaminophen. Instead, it weighed the risk of bias in the existing studies and tried to synthesize the results.
More than half of the studies included in the review found that women who took acetaminophen while pregnant were at higher risk for having children with autism, A.D.H.D. or other neurodevelopmental disorders.
But the study’s authors cautioned that the finding did not mean that acetaminophen was causing autism: The women who took acetaminophen during pregnancy may also have differed in important ways from the women who did not.
“We cannot answer the question about causation — that is very important to clarify,” said Dr. Diddier Prada, an epidemiologist at Mt. Sinai who conducted the study.
He offered an analogy. “Ice cream sales go up in the summer and also violent crime increases during summer — these are associated, but it doesn’t mean that the ice cream is causing violent crime,” he said. “Both increase because of the hot weather.”
In the same way, women typically take acetaminophen because of health issues during their pregnancies, including infections and fevers, and those problems might increase the risk of neurodevelopmental problems. While many of the studies tried to control for such factors, it is unclear what other variables might not have been accounted for.
One major study published last year tried to take an even deeper look at what hidden factors may be driving the link. The researchers in the study looked at electronic medical records from nearly 2.5 million children in Sweden, finding a small positive association between women who used acetaminophen and the incidence of autism, A.D.H.D. and intellectual disability.
The team did a subsequent analysis to control for the mother’s genetics or pre-existing health issues. Comparing siblings who were exposed to acetaminophen during the mother’s pregnancy to those who were not, the researchers found no difference in the incidence of neurodevelopmental problems.
“Especially in the context of highly heritable developmental conditions like autism and A.D.H.D., genetics is the big unobserved elephant in the room,” said Brian Lee, associate professor of epidemiology at Drexel University and lead investigator of the study.
One smaller study out of Norway also used sibling-matched controls but found differing results based on how long the women recalled having taken acetaminophen during their pregnancies.
Mothers who took the pain reliever for more than 28 days for one of their pregnancies saw a twofold increase in the risk that their baby would have A.D.H.D. But mothers who took the pain reliever for one to seven days during pregnancy actually saw a lowered risk of such problems in their babies compared with siblings who were not exposed to acetaminophen at all.
The researchers said this showed that taking Tylenol for short-term use was better for the baby than, for example, leaving a fever untreated. “It’s protective,” said Eivind Ystrom, a senior researcher at the Norwegian Institute of Public Health and an author of the study. But, he added, “Don’t take it 28 days or more.”
All of the researchers agreed that what was needed to better understand the issue was higher quality research that included robust data on genetics, the dosages and the frequency with which acetaminophen was taken, as well as information on how frequently the pain reliever was administered to infants after they were born.
But researchers also said studies needed to take into account the many factors that contribute to autism.
“To simplify it and boil it down to, ‘It’s just acetaminophen’ is disingenuous and misleading,” said Alycia Halladay, chief science officer at the Autism Science Foundation.
“We know that autism is incredibly complex: It’s the result of genetics and environmental factors that affect the way people respond to the world,” she said. “I think we need to move away from studies that simplify it down to one exposure without any other considerations.”
