No Clear Evidence of Tylenol-Autism Link, Major Review Shows

There is no clear evidence that acetaminophen use during pregnancy causes autism spectrum disorder or attention-deficit/hyperactivity disorder (ADHD) in children, a comprehensive review of existing research has concluded.

The findings, drawn from nine systematic reviews covering 40 studies, suggested that any apparent association observed in earlier research may be explained by shared genetic and environmental factors within families rather than by the analgesic itself.

“Given that alternative classes of drugs for relief of pain and fever, such as nonsteroidal anti- inflammatory drugs, are known to adversely affect the fetal vascular system and can cause complications such as oligohydramnios and premature closure of the ductus arteriosus, and considering the harmful effects of pyrexia on pregnancy, women should be advised to take paracetamol when needed to treat pain and pyrexia in pregnancy,” the investigators, led by Jameela Sheikh, MBChB, with University of Liverpool, England, wrote.

The study was published online on November 10 in the BMJ.

Unfounded Concerns

Acetaminophen, which is also known as paracetamol in the UK, remains the most commonly used pain and fever medication during pregnancy and is widely recommended by health agencies worldwide.

Concerns over its use during pregnancy intensified in September 2025, when the US government officials publicly advised against in pregnant people, citing autism risks — a claim that sparked global anxiety among expectant mothers and parents of children with autism. In response, regulators in the UK, EU, and Australia reaffirmed that paracetamol remains safe for use in pregnancy.

Previous systematic reviews and observational studies offered inconsistent findings on whether prenatal exposure to the analgesic increases the risk for autism or ADHD. Many lacked proper adjustment for confounding factors such as maternal health, genetics, and environmental influences — all known to shape neurodevelopmental outcomes.

To investigate further, the researchers conducted an umbrella review of nine systematic reviews of randomized trials and observational studies reporting maternal acetaminophen use during pregnancy and diagnoses of autism or ADHD in offspring.

All nine reviews reported some degree of positive association between maternal paracetamol use and neurodevelopmental outcomes. However, the authors of seven reviews cautioned against inferring causation, citing a lack of data, bias in the primary studies, and unmeasured or inadequately controlled confounders.

In the four reviews that included meta-analyses, pooled estimates for ADHD ranged from 1.2 to 1.4, with smaller but still positive associations for autism. Authors of two analyses cautioned, however, that bias and unmeasured confounding in the primary studies likely influenced these results.

In the single review that incorporated two sibling-comparison studies accounting for shared familial and genetic factors — by comparing exposed and unexposed children within the same families — the observed associations weakened and approached a null effect.

For autism, the hazard ratio for ever use of acetaminophen in pregnancy dropped from 1.05 in the general cohort to 0.98 among siblings. Likewise, for ADHD, it declined from 1.07 to 0.98 in one study and from 2.02 to 1.06 in the other.

These findings suggest that “shared family factors, such as parental mental health, genetic predisposition, and socioenvironmental background, explain much of the observed risk,” the authors wrote.

Methodologically, the overlap of primary studies included in the reviews was “very high” (23% corrected covered area), suggesting that many reviews drew on the same core studies, the investigators noted. Overall, confidence in the results was rated as “critically low” in seven of the reviews and “low” in the remaining two reviews.

The investigators noted that, to date, no well-established biological mechanism in humans links prenatal exposure to acetaminophen with autism or ADHD in childhood. A review of animal studies likewise “found no consistent evidence that developmental exposure to paracetamol at therapeutic or nontoxic doses results in neurodevelopmental harm.”

A Welcome, High-Quality Analysis

Outside experts praised the quality of this review in a statement from the UK nonprofit Science Media Centre.

“This paper is a welcome and careful assessment which rightly concludes the evidence does not clearly link use of paracetamol in pregnancy with autism of ADHD in the offspring,” said Gráinne McAlonan, MBBS, PhD, professor of translational neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, England.

“The methods are robust and clearly laid out. The emphasis on the importance of family history in increasing the likelihood of outcomes like autism and ADHD is appropriate,” McAlonan added.

“The high-quality methodology used in this new umbrella review confirms what experts around the globe have been saying,” added Dimitrios Siassakos, professor of obstetrics and gynecology, University College London, England.

“The evidence that links paracetamol use in pregnancy to autism is tenuous and those studies which do report an association are confounded by the association of autism or ADHD with factors shared by families such as genetics, lifestyle etc.,” Siassakos said.

Note: This article originally appeared on Medscape.