Meta-Analysis Offers Reassurance That Pregnant Women Can Safely Use Acetaminophen

A rigorous systematic review of the present state of knowledge on the use of acetaminophen during pregnancy and the risk of specific neurodevelopmental disorders (NDDs), such as autism and ADHD, offers reassurance that acetaminophen does not increase the risk of NDDs. The studyopens in new tab/window in the Journal of the American Academy of Child & Adolescent Psychiatryopens in new tab/window (JAACAP), published by Elsevier, points to methodological inadequacies in previous reviews and studies. It offers reassurance for pregnant women, public health agencies, and healthcare providers in alignment with recommendations from the Centers for Disease Control and Prevention (CDC), American College of Obstetricians and Gynecologists (ACOG), and The Society of Obstetricians and Gynecologists of Canada (SOGC).

Acetaminophen (paracetamol) is the most commonly used over-the-counter pain reliever during pregnancy, taken in an estimated 70% of all pregnancies. In 2021, a commentary about a possible increased risk of NDDs in children exposed to acetaminophen in utero was published, leading to substantial concerns in the general population and among prescribers. However, this publication—as well as a subsequent narrative review by the same group of researchers—was met with criticism of its methodology, choice and quality of studies considered, and lack of mechanistic data.

Acetaminophen exposure during pregnancy is difficult to assess in epidemiological studies because it is available over the counter without a prescription and is used as needed. Hence, there is inconsistency between studies regarding the risk of NDDs associated with its use in pregnancy.

“Given the significant methodological challenges in this area, additional individual studies will inevitably suffer the same limitations as are already present in published studies,” explains lead author of the current systematic review and meta-analysis Anick Bérard, PhD, University of Montreal and CHU Sainte-Justine, Montréal, Quebec, Canada. “An integrative approach, summarizing the present state of knowledge and quantifying specific methodological areas of biases, as our study does, is needed in order to have a significant impact in future studies performed as well as on the causal effect of acetaminophen use during pregnancy on the risk of specific NDDs.”

Dr. Bérard and an international group of experts in the field conducted a comprehensive search of major bibliographic databases and grey literature to identify human studies evaluating the association between prenatal acetaminophen exposure and the risk of NDDs in offspring. Sixteen studies retrieved met eligibility criteria. In the resulting novel systematic review and meta-analysis, the investigators applied rigorous systematic review methodologies to determine the extent to which current data can support an association between prenatal exposure to acetaminophen and the risk of NDDs in children. They also used quantitative bias analysis to provide an estimate of the direction, magnitude, and uncertainty arising from systematic errors when assessing acetaminophen use during pregnancy and the risk of ADHD in children and performed sensitivity analyses.

Dr. Bérard notes that while a modest but significant association between acetaminophen use during pregnancy and ADHD in children was initially observed, concerns about its reliability remain. She explains, "This association is unlikely to be explained by possible confounding factors that were assessed but were not seen when sibling controls (considered to be the most reliable study design for assessing this risk) were used."

The authors conclude that the observed increase in ADHD risk is likely not causal and can be explained by inherent biases and underlying genetic factors. They recommend further studies to examine this association more robustly.

Commenting on the study, noted expert in the field David Coghill, MD, Financial Markets Foundation Chair of Developmental Mental Health in the Departments of Paediatrics and Psychiatry at the University of Melbourne, observes, “This is a landmark study that highlights the importance of good science and strong methods. The findings of no association between acetaminophen use during pregnancy and the risk of autism and ADHD in the child are not unexpected. These new findings support the position of professional organizations and regulatory bodies around the world that women should continue to use acetaminophen during pregnancy and do so without fear. The fact that they contradict the recent announcements by the US government must be acknowledged and acted on.”

Notes for editors

The article is “Systematic Review and Meta-Analysis: Acetaminophen Use During Pregnancy and the Risk of Neurodevelopmental Disorders in Childhood,” by Anick Bérard, PhD, Judith Cottin, PharmD, Lisiane F. Leal, ScD, Cyndie Picot, PhD, Justine Pleau, MA, Jan M. Friedman, MD, PhD, Per Damkier, PhD, Michel Cucherat, MD, PhD, Sura Alwan, PhD, Lucie Jurek, MD, PhD, Louise M. Winn, PhD, Bruce C. Carleton, PharmD, Andréa D. Bertoldi, ScD, Sonia M. Grandi, PhD, Reem Masarwa, PharmD, PhD, Philippe Dodin, MA, Michael Ceulemans, PharmD, PhD, Robert W. Platt, PhD, Mikail Nourredine, MD, MSc, Erika Björkström Gram, MD, Areti Angeliki Veroniki, PhD, Jérôme Massardier, MD, MSc, and Andrea C. Tricco, PhD, MSc (https://doi.org/10.1016/j.jaac.2025.09.031opens in new tab/window). The article appears online in advance of volume 65, issue 4 (April 2026) of the Journal of the American Academy of Child & Adolescent Psychiatry, published by Elsevier.

The article is openly available at https://www.jaacap.org/article/S0890-8567(25)02106-9/fulltextopens in new tab/window.

Full text of the article is also available to credentialed journalists upon request. Contact Mary Billingsley at [email protected]opens in new tab/window or Elsevier Health & Medical Sciences at [email protected]opens in new tab/window to request a PDF of the article or more information. Journalists wishing to interview the authors should contact Anick Bérard, PhD, at [email protected]opens in new tab/window. David Coghill, MD, may be reached for comment at [email protected]opens in new tab/window.

This research was funded by the Center for Truth in Science. The funder was not involved in the design, analyses, and interpretation of findings. The study adheres to PRISMA guidelines.

About the Journal of the American Academy of Child & Adolescent Psychiatry

The Journal of the American Academy of Child & Adolescent Psychiatry is the flagship journal of the American Academy of Child and Adolescent Psychiatryopens in new tab/window and is the leading journal focusing exclusively on today's psychiatric research and treatment of the child and adolescent. Published twelve times per year, each issue is committed to its mission of advancing the science of pediatric mental health and promoting the care of youth and their families. jaacap.orgopens in new tab/window

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