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A new analysis of research on acetaminophen use during pregnancy finds little evidence that the common pain reliever causes autism or attention-deficit/hyperactivity disorder in children. Earlier reviews had reported small increases in risk, but these associations shrank when the researchers focused on the highest-quality evidence, though small associations remained in some analyses. The study was published in Developmental Medicine & Child Neurology.
Acetaminophen, also known as paracetamol and sold under brand names such as Tylenol, is a widely available medication used to treat pain and reduce fever. Because it does not carry the same risks of birth defects as many other pain relievers, it has become the standard first-line treatment for pain and fever during pregnancy. Estimates suggest that more than half of pregnant women globally use the medication at some point during gestation.
Over the past decade, conflicting studies have fueled a debate about the safety of prenatal acetaminophen exposure. A 2019 meta-analysis, for instance, pooled early observational research and found that prenatal exposure to the drug was associated with higher rates of ADHD in children. Regulatory bodies and medical professionals debated whether this risk was genuine or the result of flawed research methods.
Soon after, scientists began to question whether these risks were actually caused by the drug itself. A 2021 study comparing brothers and sisters suggested that family background and genetics, rather than acetaminophen use, likely explained the apparent link to ADHD.
Further support came from a 2024 study of nearly 2.5 million Swedish children. When its authors compared siblings, taking acetaminophen during pregnancy was not linked to a higher risk of autism or ADHD.
The debate took a political turn in September 2025, when U.S. President Donald Trump advised against acetaminophen use during pregnancy, citing a possible autism risk, and the Food and Drug Administration began updating the drug’s label to note a possible association. The next day, the European Medicines Agency said it had found no evidence that the drug causes autism, a position echoed by regulators in the U.K. and Australia. The conflicting nature of these past studies and public health messages created confusion for both expectant mothers and healthcare providers.
The new study, led by Hoda Tayebi-Hillali of the University of Santiago de Compostela in Spain, set out to determine whether the reported risks hold up once methodologically weaker studies are set aside. “Previous systematic reviews had reached discordant conclusions, and many counted the same primary studies several times without acknowledging it,” Tayebi-Hillali told PsyPost.
“We set out to settle this debate rigorously: we quantified the overlap between reviews, appraised their quality, and reanalyzed the underlying primary studies according to their risk of bias,” she said. “Our goal was to give clinicians, pregnant women, and health authorities an answer grounded in the best available evidence, not in headlines.”
The researchers conducted an umbrella review, which is a large-scale analysis that gathers and synthesizes data from previously published meta-analyses. They searched six major scientific databases for studies published up to November 2025. In total, they included seven meta-analyses that together encompassed more than three million participants.
Initially, the researchers pooled the results of all the meta-analyses regardless of quality (three examined autism, and all seven examined ADHD). In this unrestricted analysis, they found small positive associations. The pooled risk ratio was 1.17 for autism and 1.29 for ADHD, meaning children exposed before birth had about a 17 percent and 29 percent higher relative risk of a diagnosis than unexposed children.
Next, the team rated the quality of each meta-analysis using a standard checklist. Most were judged to be of low quality, often because they did not report how much acetaminophen women took or did not list the studies they had excluded. Dropping only the weakest reviews barely changed the results (1.17 for autism and 1.28 for ADHD). Only one meta-analysis, published in 2025, earned a high-confidence rating, and it reported smaller risk ratios of 1.10 for autism, a result that was not statistically significant, and 1.16 for ADHD.
Because many of the meta-analyses relied on the same primary studies, the researchers went a step further and analyzed the individual primary studies themselves. They rated each for risk of bias using a standard tool that weighs problems such as unaccounted-for confounding factors, how exposure was measured, and how participants were selected.
When the analysis was limited to primary studies with a low risk of bias, the risk ratios fell to 1.05 for autism, based on two large studies from Sweden and Japan, and 1.17 for ADHD, based on three studies. Both estimates remained slightly above 1, meaning a small association persisted, and the results of the ADHD studies varied considerably.
“One of the most striking findings was how much the estimates changed once we took the quality of the evidence into account,” Tayebi-Hillali explained. “Associations that initially appeared consistent were substantially attenuated when we excluded lower-quality reviews and primary studies at higher risk of bias. It was also particularly telling that some sibling-comparison studies, which help control for the genetic and environmental factors shared within a family, did not find the associations originally reported. This underscores the importance of distinguishing between a statistical signal and a possible causal relationship.”
Given the baseline global prevalence of autism (about 1 in 117 children) and ADHD (about 1 in 60 children), the actual absolute increase in risk would be expected to be modest even if the remaining association were genuine. “Even taking the figures at face value, the impact would be very small,” Tayebi-Hillali noted. “Moreover, in observational studies, a risk ratio this small can readily be explained by bias, without the drug playing any role at all. The size of the effect, therefore, does not justify alarm.”
The findings are in line with research covered by PsyPost in 2026, which found that prenatal exposure to acetaminophen was not tied to autism or ADHD in sibling-matched analyses. Both suggest that previously observed links largely reflect confounding and other biases rather than the medication itself.
The findings stand in tension with a 2025 review covered by PsyPost, which reported that the associations were strongest in the more rigorous studies, particularly those that measured the drug in biological samples. The authors of the new review, by contrast, regarded biomarker measurements taken from umbilical cord blood, meconium, or maternal blood as being of uncertain validity.
The findings also contrast with a 2022 study and a 2016 study previously covered by PsyPost, which linked prenatal acetaminophen to attention and behavior problems in children. Those studies measured parent-reported symptoms rather than formal diagnoses, and although both were among the primary studies the new review examined, neither met its strictest risk-of-bias standards.
As with all research, there are a few things to keep in mind. “The main misinterpretation to avoid is the claim that our study proves paracetamol causes autism or ADHD; equally, it would be wrong to conclude that we have shown any exposure, regardless of dose or duration, to be entirely free of risk,” Tayebi-Hillali cautioned. “Our work is a synthesis of observational studies and therefore cannot establish causality on its own.”
A major consideration is “confounding by indication.” Pregnant women usually take acetaminophen to treat fevers, infections, pain, or inflammation. These underlying health issues can sometimes influence fetal brain development, making it difficult for scientists to separate the effects of the drug from the effects of the illness it was being used to treat. In addition, many studies relied on self-reported questionnaires, which can mislabel who was actually exposed, as people may not accurately recall exactly when or how often they took an over-the-counter medication.
The most rigorous estimates also rest on a small number of studies: a single high-quality meta-analysis and two or three primary studies. The researchers did not formally assess publication bias, the tendency for studies with positive results to be more likely to get published. The review also could not evaluate how much acetaminophen women took, for how long, or when in pregnancy; some earlier studies reported higher risks with use lasting more than 28 days, but most did not report timing at all.
“The next step should be to improve the quality of the observational studies available, with a more precise characterization of the dose, frequency, duration, and timing in pregnancy of paracetamol use, as well as of the clinical indication that prompts it,” Tayebi-Hillali added. “Designs that better control for familial, genetic, and environmental factors, such as sibling-comparison studies, are especially important, together with rigorous assessments of risk of bias.”
Animal studies have suggested that acetaminophen might interfere with hormones involved in development, but the authors note that this experimental evidence is not enough to show the drug alters human fetal brain development. Given the well-documented harms of untreated fever and pain during pregnancy, they conclude that acetaminophen remains an appropriate first-line treatment when medically needed, at the lowest effective dose and for the shortest necessary time.
“Headlines that present an association as if it were proven causation can convey an alarm that the evidence does not warrant. At the same time, it is essential to acknowledge uncertainty and to keep investigating,” Tayebi-Hillali said. “We should also remember that untreated fever and pain during pregnancy can have consequences, so avoiding a clinically necessary medication without consulting a healthcare professional is not a risk-free decision either.”
The study, “Prenatal exposure to paracetamol and the risk of autism and attention-deficit/hyperactivity disorder: An umbrella review and meta-meta-analysis,” was authored by Hoda Tayebi-Hillali, María Blanco-Suárez, Berta Rivas-Mundiña, Jacobo Limeres-Posse, Márcio Diniz-Freitas, and Pedro Diz-Dios.