acetaminophen

It’s not my habit to preface my columns with “trigger alerts,” so this is a first:

If talking about circumcision makes you cringe, feel free to move along.

If, on the other hand, you wish to understand what Robert F. Kennedy Jr. was talking about during a White House meeting Oct. 9 when he tried to connect circumcision with autism, follow along with me.

The offhand reference to circumcision’s possible role in autism by Kennedy, Trump’s secretary of Health and Human Services, is part and parcel of Kennedy’s documented assault on science-based medicine.

His campaign encompasses attacks on COVID-19 vaccines, which have been shown over the years to have saved millions of people from death, hospitalization or long-term disability; his firing members of professional advisory boards at his agency and replacing them with anti-vaccine activists; his promotion of unproven “cures” for vaccine-preventable diseases; and his inaction in the face of a nationwide surge in cases of measles, a disease that was declared eliminated in the U.S. in 2000.

Let’s pause for a few words about the broader consequences of the erosion of our public health infrastructure. It not only exposes Americans to more disease and more serious disease, but has profound economic effects.

That’s true worldwide, but especially in the U.S., which spends much more per capita on healthcare than other developed countries, for lower results. Undermining the existing system for partisan ends won’t make the picture look any lovelier.

“The U.S. health disadvantage threatens the country’s global competitiveness and national security, as well as the hopes and prospects of future generations,” according to a 2021 paper from the Department of Health and Human Services, the agency that Kennedy now leads.

“U.S. employers depend on a healthy workforce to maximize productivity and minimize healthcare costs,” the paper stated. “Population health also affects the consumer market, whereby the demand for nonessential products and services suffers when families are struggling with illnesses and much of their disposable income is required for medical expenses.”

The chaos imposed on our public health system under the Trump administration only intensifies the damage.

On Friday, hundreds of employees at Kennedy’s agency, including the Centers for Disease Control and Prevention, abruptly received layoff notices. Some were hastily informed that their firings were erroneous, but the experience rattled the CDC, an agency tasked with overseeing the national response to seasonal respiratory illnesses at a time when those illnesses typically spike.

“The damage is beyond repair,” Demetre Daskalakis, who resigned as director of the National Center for Immunization and Respiratory Diseases, a unit of the National Institutes of Health, over conflicts with Kennedy, told CNN. “Crippling CDC, even as a ploy to create political pressure to end the government shutdown, means America is even less prepared for outbreaks and infectious disease security threats.”

That brings us back to Kennedy’s preoccupation with autism. He has claimed that the autism rate is on the rise due to “environmental toxins” such as childhood vaccinations and the use of Tylenol — or acetaminophen, its generic name — by mothers during pregnancy.

As I’ve reported, however, the roots of the increase in reported autism rates in recent decades are well understood: They have much to do with a broader definition of autism, which is widely described today as “autism spectrum disorder,” and with improved access to screening and diagnostic services by formerly overlooked groups such as Blacks, Hispanics and other nonwhite cohorts.

Kennedy’s comment about circumcision came during a White House Cabinet meeting. At first, he and Trump traded misconceptions they had previously aired about Tylenol use by pregnant women — Trump asserting that “obviously,” the rise in autism rates is “artificially induced” and adding, “I would say don’t take Tylenol if you’re pregnant, and … when the baby is born don’t give it Tylenol.”

That advice dismayed physicians, who say that fevers during pregnancy are a greater risk for the unborn and that acetaminophen is safer than alternative fever-reducing medicines.

Kennedy then injected circumcision into the discussion. “There’s two studies that show children who were circumcised early have double the rate of autism,” he said. “It’s highly likely because they were given Tylenol.”

Unsurprisingly, Kennedy’s remark got extensive play in the news media, prompting him to try walking it back via a tweet on X. Rather than accept responsibility for his confusing words, he responded with Bondi-esque truculence, writing: “As usual, the mainstream media attacks me for something I didn’t say in order to distract from the truth of what I did say.”

He even took arms against the Murdoch-owned New York Post, which posted its story with the headline, “RFK Jr. says Tylenol after circumcisions linked to autism,” and proceeded to debunk the claim.

In trying to clarify his point, however, Kennedy dug himself a deeper hole. According to his tweet, the two studies he was referring to at the cabinet meeting were a Danish study from 2015 and a non-peer-reviewed preprint posted online in August, which refers to the Danish paper. Kennedy mischaracterizes both.

Contrary to Kennedy’s implication, the Danish study did not address the use of acetaminophen (called “paracetamol” in the paper) in connection with circumcision. The reason, its authors wrote, was that “we had no data available on analgesics or possible local anesthetics used during ritual circumcisions in our cohort, so we were unable to address the paracetamol hypothesis directly.”

They did note, however, that the acetaminophen theory had only “limited empirical support.” In other words, evidence was lacking. Anyway, the Danish study was criticized — in the same journal that had published it — for its reliance on a very small sample of children.

As for the preprint, contrary to Kennedy’s description, it did not identify the Danish paper as offering “the most compelling ‘standalone’ evidence” for an autism-acetaminophen link. That language referred to three studies, one of which was the Danish paper. Of the other papers, one was based on later interviews with parents. The other was a study of the effects of acetaminophen on 10-day-old mice, not human children.

I asked Kennedy’s agency to clarify his claim and to explain the discrepancies between his words and the papers themselves, but received no reply.

To summarize, Robert F. Kennedy Jr., the nation’s top federal healthcare official, conjured up a connection between circumcision and autism via a relationship between circumcision and Tylenol that is unsupported by the research he cited. Indeed, the Danish paper describes the idea that boys undergoing circumcision invariably are given acetaminophen for pain as “a questionable assumption.”

In searching for empirical support for the acetaminophen theory, moreover, the Danish paper cited a 2010 paper funded by NIH that cautioned: “No evidence is presented here that acetaminophen in any way causes autism. … This hypothesis is largely based on multiple lines of often weak evidence.” Anyway, the paper was focused on a possible link between acetaminophen use and asthma, not autism.

Sadly, this sort of mischaracterization of research described as “a rigorous scientific framework” (RFK Jr.’s words) isn’t surprising coming from today’s Department of Health and Human Services. This is the agency, it may be recalled, that in May issued an “assessment” of the health of America’s children that cited at least seven sources that did not exist.

Nothing can stop unwary parents from relying on the judgment of Donald Trump or Robert F. Kennedy Jr. to make healthcare decisions for their infants and children. But they should be warned: They do so at their own and their offsprings’ risk.

During this week’s White House press conference in which President Trump named the over-the-counter drug Tylenol as a possible cause of rising autism rates, he did not mince words, urging pregnant women to “fight like hell” not to take it.

But outside those remarks in the Roosevelt Room — during which Trump himself acknowledged “I’m not so careful with what I say” — the discussion on the common fever and pain reliever’s role during pregnancy is a lot more nuanced.

What the research on Tylenol use during pregnancy actually says

Physicians, researchers on the very studies cited in support of Trump’s position and even other members of the president’s administration are largely united on a few key facts: untreated fevers in pregnancy pose real risks to the fetus, acetaminophen (Tylenol’s active ingredient) remains the safest medication to treat them and any pregnant person seeking advice on the issue should consult their doctor.

“All that we should be asking of the medical profession [is] to actually weigh the risks and benefits for the women, with the women, and be cautious about chronic use of pain medications,” said Dr. Beate Ritz, a UCLA professor of epidemiology who co-authored a paper published last month that the White House cited as evidence for the link between Tylenol and autism.

Ritz said it has been misinterpreted.

The conclusion of the paper, which reviewed existing studies on the topic, was that the association between acetaminophen use in pregnancy and later diagnoses of neurodevelopmental disorders in kids was strong enough to merit doctors’ consideration when determining how to treat fever or pain in pregnancy. The group did not determine a causal relationship between the drug and autism, or suggest barring the drug altogether, she said.

“Looking at all of these studies, yes, there is a risk,” Ritz said. “It’s not very big, but it’s there, but the risk increases are more seen in regular users of Tylenol. This is not a woman who has a fever and takes three Tylenols.”

“There is always a weighing of the risks and the benefits, and fever in women is no good either. … Not having to take any pain medications when you are in severe pain or in chronic pain is also very cruel,” she said. “We all should have an interest in helping out here, making the right decisions without blaming the victim and putting it all on the individual woman.”

Her co-author, University of Massachusetts epidemiologist Ann Bauer, has made similar statements.

“What we recommend is judicious use — the lowest effective dose [for] the shortest duration of time under medical guidance and supervision, tailored to the individual,” Bauer told the news outlet Politico.

The administration’s confusing recommendations

Ultimately, that’s what the administration is recommending as well.

The letter that U.S. Food and Drug Administrator Dr. Marty Makary sent to physicians this week made clear that “a causal relationship” between autism and acetaminophen “has not been established and there are contrary studies in the scientific literature.”

It went on to recommend that clinicians consider limiting their use of acetaminophen for routine low-grade fevers during pregnancy, while noting that medical advice “should also be balanced with the fact that acetaminophen is the safest over-the-counter alternative in pregnancy among all analgesics and antipyretics.” (An analgesic is a pain reliever; an antipyretic reduces fever.)

Untreated fevers during pregnancy are associated with higher rates of birth defects, particularly those of the heart, brain and spinal cord; premature birth; low birth weight; neurodevelopmental disorders including autism; and fetal death, said Dr. E. Nicole Teal, an assistant professor of maternal-fetal medicine at UC San Diego.

“The FDA’s letter, while significantly more nuanced than the president’s comments on the issue, still gives too much weight to findings from poorly designed studies,” she said.

She said she will continue to prescribe acetaminophen to pregnant patients who need to treat fevers or severe pain, as it has the fewest known risks in pregnancy.

Are there other pain-relief and fever-reducing drugs that can be used during pregnancy?

Nonsteroidal anti-inflammatory drugs like ibuprofen (often sold as Advil) or naproxen (often sold as Aleve) are linked to problems with blood vessel and kidney development, as well as oligohydramnios, a condition in which there isn’t enough amniotic fluid to support a healthy pregnancy. Aspirin raises the risk of bleeding complications, and narcotics — which can relieve pain but not fever — pose addiction risks for the mother and infant alike, Teal said.

She referred to a statement from the American College of Obstetricians and Gynecologists noting that two decades of research on the question had failed to find a causal relationship between acetaminophen and autism.

“Acetaminophen is one of the few options available to pregnant patients to treat pain and fever, which can be harmful to pregnant people when left untreated,” American College of Obstetricians and Gynecologists president Dr. Steven J. Fleischman said in the statement.

The group also noted that reviews in 2015 and 2017 from the FDA and the Society for Maternal-Fetal Medicine respectively found no risks associated with appropriate usage of the drug in pregnancy.

How to navigate government communications around Tylenol use

Nonetheless, the mixed messaging from the Trump administration about Tylenol seems likely to continue.

The Department of Health and Human Services this week reposted a 2017 tweet from the Tylenol brand’s account that said, “We actually don’t recommend using any of our products while pregnant.”

A spokesperson for Kenvue, the company that owns Tylenol, said the post was taken out of context and incomplete.

“Consistent with regulations, our label states clearly ‘if pregnant or breast-feeding, ask a health professional before use,’ ” Melissa Witt said in an email. “We do not make recommendations on taking any medications in pregnancy because that is the job of a healthcare provider.”

Vice President JD Vance offered similar guidance this week.

“My guidance to pregnant women would be very simple, which is follow your doctor. Right?” Vance said in an interview with the outlet NewsNation after Trump’s press conference. “Talk to your doctor about these things.”

President Trump blamed the over-the-counter drug acetaminophen, commonly known by the brand name Tylenol, as a significant factor in the rise of U.S. autism diagnoses on Monday, at a news conference in which he offered often inaccurate medical advice for the nation’s children and pregnant women.

“Taking Tylenol is not good. I’ll say it. It’s not good,” Trump said, flanked by Health and Human Services Secretary Robert F. Kennedy Jr. and Centers for Medicare & Medicaid Services Administrator Dr. Mehmet Oz.

In a series of rambling, error-filled remarks that touched upon pain relievers, pregnancy, vaccines and the Amish — who he inaccurately said have no autism prevalence in their communities — Trump also said that the mumps, measles and rubella vaccine should be broken up into multiple shots and that children defer until age 12 the hepatitis B vaccine series now started at birth.

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“I’m just making these statements from me, I’m not making them from these doctors,” he said. “It’s too much liquid. Too many different things are going into that baby.”

The announcement was met with dismay from autism researchers and advocates who said that research thus far into causal links between acetaminophen and autism has turned up minimal evidence.

“Researchers have been studying the possible connections between acetaminophen and autism for more than a decade,” said Dr. David Mandell, a professor of psychiatry at the University of Pennsylvania Perelman School of Medicine. The Trump administration, he said, “has cherry-picked findings that are not in line with most of the research.”

Physicians and researchers also took issue with Trump’s insistence that there was “no downside” to women avoiding fever-reducing drugs in pregnancy. In fact, studies show that untreated fever in pregnancy is associated with higher risk of heart and facial birth defects, miscarriage and neurodevelopmental disorders — including autism.

The U.S. Food and Drug Administration will initiate a safety-label update for Tylenol and other acetaminophen products and send a letter to physicians about potential links between the drug’s use and autism, Kennedy said.

The actual text of the letter is much milder than Trump’s impassioned critique.

“In the spirit of patient safety and prudent medicine, clinicians should consider minimizing the use of acetaminophen during pregnancy for routine low-grade fevers. This consideration should also be balanced with the fact that acetaminophen is the safest over-the-counter alternative in pregnancy among all analgesics and antipyretics,” states the letter, signed by FDA Commissioner Dr. Marty Makary.

Monday’s announcement followed weeks of speculation that Kennedy planned to publicly link Tylenol usage to autism, which prompted multiple medical associations to release statements clarifying that any evidence of a causal relationship between the two is limited, and that the drug is safe to take during pregnancy with medical advice.

“All of us in the advocacy community, and all of us who have children with autism, had very high hopes that RFK and the President were serious when they said they wanted to find the causes of autism,” said Alison Singer, co-founder and president of the Autism Science Foundation. “The problem is that so far, what we’ve heard has not been gold-standard science.”

The administration also said it would fast-track the labeling of leucovorin, a generic drug currently used to reduce side effects of chemotherapy, as a treatment for autism-related speech deficits. Also known as folinic acid, leucovorin is a form of the B vitamin folate. Research into its effect on autistic children is still in its early stages, researchers said. The few studies that have been published had small sample sizes and found only minimal improvements in symptoms of concern, Mandell said.

“I want to see a large, rigorous, independent trial. In the absence of that, to tout this as a cure is reckless,” he said. “Families deserve better.”

Autism spectrum disorder is a complex neurological and developmental condition. Symptoms cluster around difficulties in communication, social interaction and sensory processing, and the condition can manifest in many different ways based on co-occurring disabilities and other factors.

Diagnoses in the U.S. have risen steadily since the Centers for Disease Control and Prevention began tracking data in 2000, thanks in large part to a broadening definition of the disorder and increased efforts to identify children with ASD.

Today one in 31 U.S. 8-year-olds has been identified as having autism spectrum disorder, according to the most recent CDC data, up from one in 150 in 2000.

Kennedy has long asserted that’s due to an external environmental cause, often using inaccurate statements to describe both the condition and the research around it.

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Most experts believe genetic links and changing diagnostic criteria play a significant role in the trend. In April, Kennedy dismissed such research and arguments as “epidemic denial.” He said he was certain an external factor was to blame.

“We know it’s an environmental exposure. It has to be,” Kennedy said. “Genes do not cause epidemics.” He said at the time that the administration would find an environmental cause by September.

Research into causal links between acetaminophen and autism have not found strong evidence.

Last year, a team of researchers from the U.S. and Europe reviewed records of 2.5 million babies born in Sweden between 1995 and 2019. At first glance, it did seem like children exposed to acetaminophen in the womb were 5% to 7% more likely to be diagnosed with autism than those who weren’t. But when the researchers compared those children to their siblings, they found that kids from the same parents were equally likely to be diagnosed with autism, whether their mother took acetaminophen during pregnancy or not.

“If you actually do an apples to apples comparison, you see absolutely zero effect. The association flatlines. In other words, there’s no real risk that’s attributable to acetaminophen,” said Brian K. Lee, a professor of epidemiology and biostatistics at Drexel University who was on the study team. “A large elephant in the room is being ignored, and that’s genetics.” Hundreds of studies over the years have explored the complex genetics of autism, with both inherited and spontaneous genes contributing to the condition.

The paper also noted that women who took acetaminophen while pregnant were, unsurprisingly, more likely to suffer from the kinds of ailments for which the medication is indicated, like fevers or chronic pain.

They were also more likely to have diagnoses of autism or other neurodevelopmental disorders, to have pre-existing mental health conditions or to be taking other prescribed medications, the team found. Their results were published in the Journal of the American Medical Association.

“People don’t take acetaminophen for fun. They are taking it for a health condition,” Lee said.

He compared the correlation between Tylenol exposure and autism to the correlation between ice cream sales and drownings. Both of those things tend to increase at the same time each year, he said, not because ice cream is deadly but because both rise during hot summer months. In other words, the underlying health causes that women are taking acetaminophen to treat could be more likely linked to autism than the pain reliever itself.

“This is just such a shame when there are so many things we could do to help autistic children and adults, and the negative consequences — making parents feel guilty about taking Tylenol during pregnancy and newly pregnant women afraid — are real,” said Catherine Lord, a clinical psychologist and autism researcher at UCLA. “Just sad all around.”