FDA Stayed Silent As Internal Reports About Potential Tylenol Risks Piled Up

The Food and Drug Administration (FDA) defied the advice of its own drug safety experts to warn pregnant women about Tylenol for nearly a decade, internal reports and presentations obtained by the Daily Caller News Foundation reveal.

FDA rank-and-file scientists repeatedly recommended the agency release information about Tylenol in pregnancy across three scientific reviews conducted in 2016, 2019, 2022 and two memos, one from the FDA’s maternal health division in 2016 and one from the FDA’s urological health division in 2017.

The scientific literature posits many plausible drivers of autism, the most well-established of which are genetic, and the FDA drug safety experts acknowledged that the research linking the condition to Tylenol is far from ironclad.

Still, as alarm bells rang within FDA headquarters and the boardrooms of Tylenol’s manufacturers, pregnant women heard nothing from either the government or the manufacturers about the potential risks until the September announcement by President Donald Trump and Health and Human Services Secretary Robert F. Kennedy Jr.

FDA leadership declined to update its webpage about over-the-counter painkillers in pregnancy, repeatedly falling back on language first issued in a January 2015. But that statement simply acknowledged that “FDA is aware of concerns” about Tylenol and attention deficit hyperactivity disorder (ADHD), citing just one scientific paper.

At the urging of Trump and Kennedy, FDA finally released a nuanced statement in September cautioning pregnant women about Tylenol while acknowledging that aspirin, ibuprofen and high fevers all pose their own risks. That move was first recommended by an FDA drug safety expert nine years earlier.

The DCNF obtained the FDA documents from the law firm Keller Postman LLC, which brought a class action lawsuit against Tylenol maker Kenvue, a legally independent spinoff of Johnson & Johnson. The personal injury law firm, which often brings class action lawsuits, obtained the documents from FDA via the Freedom of Information Act.

Tylenol, a brand name for acetaminophen, first received FDA approval in 1955 before modern drug laws tightened clinical trial requirements in 1962.

Some experts argue that neurological damage occurs due to a toxic byproduct of acetaminophen called NAPQI. Babies and children with autism may struggle to metabolize the drug, resulting in higher levels of NAPQI, which kills cells.

Warning Signs In 2014

An internal memo reveals that the agency first began examining acetaminophen in pregnancy 11 years ago, in May 2014, after an April 2014 study published in the Journal of the American Medical Association raised concerns about the drug and ADHD-like behaviors, prompting its sole statement on the issue for the next decade — an 2015 FDA webpage that acknowledging that “FDA is aware of concerns” and citing that single study.

Less than two years later, in October 2016, FDA Senior Medical Officer Andrew Mosholder had reviewed eight observational studies with seven showing an association between acetaminophen and issues including attention deficits, delayed motor development and autistic behaviors.

Mosholder’s 22-page report recommended that FDA issue a nuanced warning: Tylenol in pregnancy could cause neurological harm and the drug should be used sparingly, but other painkillers are associated with more definite risks and Tylenol will sometimes be necessary to reduce fever. The report also recommended more toxicology studies — laboratory studies designed to uncover the potential toxicity of a drug.

Mosholder declined to comment.

Both the FDA Division of Pediatric and Maternal Health and FDA Division of Bone, Reproductive, and Urologic Products recommended issuing nuanced communications to the public in 2016-2017.

In January 2018, an FDA decision-making committee led by longtime Center for Drug Evaluation and Research Director (CDER) Janet Woodcock heard a presentation by Mosholder and Valerie Pratt, who oversaw the safety of over-the-counter drugs, according to the meeting minutes. By this time the scientists had reviewed 21 studies, three-fourths of which indicated a risk of Tylenol in pregnancy, the slides show.

FDA had preemptively ruled out a drug label change, but Woodcock and other FDA officials also nixed Mosholder’s proposed public statement, instead postponing a decision by six months and calling for yet more studies, the meeting minutes show.

Woodcock oversaw CDER during other controversial decisions over her lengthy tenure, including the approval of OxyContin in 1996, government records show, and defended the approval as following “all applicable statutes and regulations” in a 2020 Senate letter. She also delayed a clinical warning about the risk of heart issues and the COVID-19 mRNA vaccines in 2021, according to a Senate investigation.

CDER under Woodcock had downplayed a warning flagged by Mosholder before when he warned in a Dec. 2003 report that antidepressants increased suicide rates in children, a report superiors sought to suppress.

Requests for comment from the DCNF sent to two nonprofits for which Woodcock serves on the board of directors did not receive a reply.

‘Precautionary Measure’

In October 2018, at the follow-up meeting FDA officials had called for six months earlier, the FDA’s toxicology division shared their hypothesis that Tylenol could impede blood flow to the growing infant. Other details have been largely redacted in the documents obtained by the DCNF.

The European equivalent of the FDA, the European Medicines Agency (EMA), briefed the agency on its decision to inform patients the next month.

A 2019 epidemiological review concluded an association also existed between Tylenol in pregnancy and defects in the urinary tract or the reproductive tract, such as one or both of a baby’s testicles having not moved into the proper position, a condition that can sometimes require surgery.

“These findings, like the data on neurodevelopmental outcomes, suggest that [ acetaminophen or Tylenol] use during pregnancy is not necessarily free of risk,” Mosholder wrote. “It would be desirable for the agency to communicate this message.”

The first sentence of the conclusion of an epidemiological review in 2022 states that “the functional neurobehavioral outcome studies examined in this review along with the reviewed meta-analyses suggest a consistent association between [acetaminophen] or long durations of prenatal [acetaminophen] exposure and ADHD.”

It noted studies were limited by crude measurements of Tylenol exposure, unclear clinical meaning of findings, the use of inconsistent questionnaires across studies; and the possibility of unmeasured confounding variables.

Coauthored by Mosholder and another FDA senior medical advisor, it noted that the existing 2015 FDA statement included no discussion of the amount of Tylenol pregnant women should use and recommended that the FDA change that.

“It may be prudent, as a precautionary measure, to issue a communication emphasizing that [acetaminophen or Tylenol] use in pregnancy should be judicious,” the review concluded, while noting that fever can also pose risks in pregnancy.

A final 2023 review — which did not include Mosholder — stated that “the three studies reviewed here are limited and do not change [FDA’s] conclusions from its most recent review.”

But the 2023 epidemiological review departed from prior reviews in that it included no “recommendations” section at all.

Court Controversy

Perhaps the most consequential review of the evidence outside the FDA will occur in November before the Court of Appeals for the Second Circuit, where law firm Keller Postman will bring an appeal in its class action suit against Tylenol maker Kenvue. Lead attorney for the plaintiffs Ashley Keller told NPR the firm had received roughly 1,000 phone calls the week of Trump’s announcement.

In a lower court ruling for Kenvue, District Judge Denise Cote strongly rejected a causal link between Tylenol and autism and tossed the testimony of the firm’s experts. The litigation could leave women without access to Tylenol at all, Cote and some medical experts worry.

FDA officials did not go as far as the firm’s experts, saying that while the association between Tylenol and autism appeared consistent, the evidence had not surmounted the threshold of causality, citing study limitations like non-standardized methodologies across the papers in how autism is diagnosed.

Five of six FDA internal reports say pregnant women receiving communication from FDA about the potential for risks or the agency’s ongoing review of the literature would be “needed,” “important,” or “desirable.” In a letter to the court, Biden’s Department of Justice quoted only the sixth report, the most recent FDA review in 2023 without Mosholder and without a recommendations section.