Study Finds No Link Between Prenatal Acetaminophen Use and Autism, ADHD

A large population-based study published in JAMA Internal Medicine found no evidence that prenatal exposure to acetaminophen (Tylenol) increases the risk of autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) in children after accounting for unmeasured familial factors.¹

The findings arrive as pharmacists continue to field questions from pregnant patients following high-profile public claims linking the common analgesic to neurodevelopmental harm.

Study Design and Population

Investigators at the University of Hong Kong used a sibling-matched cohort design, drawing on electronic health records from the Hong Kong Hospital Authority covering births from January 1, 2001, to December 31, 2023. From an initial cohort of 708,020 mother-child pairs—approximately 43.3% with prenatal acetaminophen exposure—they constructed 2 outcome-specific cohorts, including 124,333 children for ASD analysis and 97,285 for ADHD analysis.

In each cohort, only families with discordant prenatal exposure, defined as at least 1 exposed sibling and 1 unexposed sibling from the same mother, were included, allowing within-family comparisons that control for shared genetic and environmental factors.¹

The study used prospectively recorded electronic prescription records—identified via the British National Formulary, section 4.7.1—to capture detailed exposure data including drug strength, dosage, frequency, and timing by trimester. Outcomes were incident diagnoses of ASD (ICD-9-CM code 299) or ADHD (ICD-9-CM code 314) or a filled prescription for a licensed ADHD medication (methylphenidate, atomoxetine, or lisdexamfetamine).¹

No Association After Controlling for Family Factors

In the primary sibling-matched analysis, prenatal acetaminophen exposure was not associated with ASD (adjusted hazard ratio [aHR], 1.00; 95% CI, 0.91-1.11) or ADHD (aHR, 1.01; 95% CI, 0.93-1.08). Null findings held across every exposure subgroup were examined, including first, second, and third trimester use; sporadic, intermittent, and persistent use patterns; and low, medium, and high mean daily dose categories. No dose-response relationship emerged for either outcome. Subgroup analyses by child sex, birth era, and maternal age showed no evidence of effect modification.¹

These findings stand in sharp contrast to results from conventional cohort analyses conducted within the same dataset, which—like earlier published studies—showed positive associations for both ASD (HR, 1.17; 95% CI, 1.13-1.20) and ADHD (HR, 1.23; 95% CI, 1.20-1.27). Propensity score-matched and inverse probability of treatment-weighted models produced similar positive findings.

Debates on Acetaminophen Grows

The new study enters a debate that intensified significantly following a September 2025 press conference in which President Donald Trump claimed a link between Tylenol use during pregnancy and autism, prompting initiatives across the National Institutes of Health (NIH), the FDA, and the Center for Medicare & Medicaid Services. At that press conference, NIH launched the Autism Data Science Initiative with an additional $50 million in funding.²

In response, regulatory bodies including the Medicines and Healthcare Products Regulatory Agency and the World Health Organization reaffirmed acetaminophen's safety profile for use during pregnancy.¹

Mark Garofoli, PharmD, BCGP, CPE, CTTS, a clinical assistant professor at the West Virginia University School of Pharmacy and a pain management expert, questioned the evidentiary basis for the administration's position when the controversy first emerged.

"The largest study included in the respective review article involved 2.5 million [Swedish] babies born from 1995 to 2019...Unlike previous studies, this study compared siblings within the same family to remove genetic and familial bias—and poof, the risk disappeared," Garofoli told Drug Topics.³ "In other words, acetaminophen [was] not guilty."

Garofoli also raised concerns about the broader quality of the evidence base.

"There is a publication or 3 for every single point of view," he said.³ "It is not enough to say that one single study (or even a handful of small studies) makes something correct or not at the time; rather, substantiated studies endorsed by reputable professional organizations can lead the way."

Implications for Pharmacist Counseling

Pharmacists have found themselves at the center of this controversy, often serving as the first point of contact for pregnant patients encountering contradictory information. Garofoli warned that the public discourse risks creating unintended clinical consequences for patients who avoid a medication they may legitimately need during pregnancy.

"To think that a pregnant mother would be shamed into not treating her own incredible needs (fever, pain) is not only deeply concerning on a compassionate level, yet clinically concerning, as the resultant tachycardia, hypertension, anxiety, [and] stress—amongst other sequelae—can literally be detrimental to both the pregnant mother and child," Garofoli told Drug Topics.⁴

He also expressed concern about the long-term toll this debate will exact on health care professionals.

"We just walked into a scenario where, for the next few decades, us health care professionals will spend an incredible amount of time and energy refuting the acetaminophen claims," Garofoli said.⁴ "Sound familiar? [Do] immunizations come to mind? Just so unfortunate.”

Both the new JAMA Internal Medicine study and the prior 2024 JAMA sibling-controlled analysis of 2.5 million Swedish children align in their null findings, further strengthening the evidentiary case that observed associations in conventional observational designs reflect familial confounding rather than drug toxicity.^1,2 For pharmacists counseling pregnant patients about analgesic and antipyretic options, the accumulating body of sibling-controlled evidence supports continuing to recommend acetaminophen as the first-line choice when pain or fever management is clinically indicated.

REFERENCES

1. Luo S, Gong Q, Ai Y, et al. Prenatal acetaminophen (paracetamol) use and the risk of autism and/or attention-deficit/hyperactivity disorder among sibling-matched cohorts. JAMA Intern Med. Published online June 29, 2026. doi:10.1001/jamainternmed.2026.2215

2. Gallagher A. Trump administration claims link between autism and acetaminophen use in pregnancy. Drug Topics. September 23, 2025. Accessed June 29, 2026. https://www.drugtopics.com/view/trump-administration-claims-link-between-autism-and-acetaminophen-use-in-pregnancy

3. Nowosielski B, Garofoli M. Q&A: Acetaminophen-autism link highlights issues of confounding evidence. Drug Topics. September 26, 2025. Accessed June 29, 2026. https://www.drugtopics.com/view/acetaminophen-autism-link-highlights-issues-of-confounding-evidence

4. Nowosielski B, Garofoli M. Q&A: How acetaminophen-autism link creates concerns in clinical decision-making. Drug Topics. September 27, 2025. Accessed June 29, 2026. https://www.drugtopics.com/view/how-acetaminophen-autism-link-creates-concerns-in-clinical-decision-making