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Acetaminophen use during pregnancy: is there a problem?

Pediatric Research (2024)Cite this article

Acetaminophen (paracetamol) is a very common over-the-counter medication primarily used for pain management.1 It exerts an anti-inflammatory effect by inhibition of the cyclooxygenase pathway in the central nervous system, which ultimately inhibits the synthesis of prostaglandins.1 While the exact mechanisms for the analgesic properties of acetaminophen are not completely understood, it has been linked to: (1) inhibition of prostaglandin synthesis, (2) stimulation of the descending pathways of the serotonergic system, and (3) activation the endogenous cannabinoid systems.1 Acetaminophen does cross the placenta (detected in cord blood and meconium), thereby exposing the fetus to its effects.2,3 Furthermore, alterations in the metabolism of acetaminophen can occur during pregnancy which can increase the risk of toxicity in pregnant persons.3

Acetaminophen is the only pain medication that has historically been thought to be safe for use during pregnancy and is recommended as a first-line agent by both the American College of Obstetrics and Gynecology and the Society for Maternal Fetal Medicine.4 Approximately 50–65% of pregnant persons have reported the use of acetaminophen at least once during pregnancy.3 Despite the ubiquity of acetaminophen use and its recommendations as a first-line agent for the treatment of pain or fever, there is limited safety data available for review.3 The Food and Drug Administration has labeled acetaminophen as a class “B” drug indicating a lack of known toxicity seen in animal models and a relative lack of data from pregnant persons who have been exposed to acetaminophen.2 However, in 2021 a consensus statement called for greater caution among pregnant persons using acetaminophen and encouraged additional restrictions including taking the drug only after a medical consultation and using the lowest and least frequent dose possible.3 Meta-analyses of intrauterine acetaminophen exposure have demonstrated possible associations of acetaminophen use on behavior, specifically attention deficit disorders.5 Other observational studies have linked intrauterine acetaminophen exposure to autism, reduced intellect, challenges with executive function, conduct disorder, oppositional defiant disorder, language delays, and cerebral palsy.3 A study from Sweden demonstrated potential delays in language development in children exposed to acetaminophen in early pregnancy.6 Data from Norway also demonstrated diminished language scores on the Ages and Stages Questionnaire at 18 and 30 months for children exposed to acetaminophen in utero.7,8 However, concerns about these data include confounding from acetaminophen reporting (self-report after the pregnancy was over, potential recall bias, errors in timing of exposure), lack of biologic plausibility directly linking acetaminophen to the specific findings, and unclear outcomes from parental reports.3

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Acknowledgements

The authors want to thank Dr. Lynne Yao from the US Food and Drug Administration for her thoughtful comments.

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Authors and Affiliations

  1. Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Paige Terrien Church

  2. Department of Pediatrics, Tufts Medical Center, Boston, MA, USA

    Paige Terrien Church & Jonathan M. Davis

  3. Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA, USA

    Erika Werner

  4. The Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA, USA

    Jonathan M. Davis

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  1. Paige Terrien Church
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All authors contributed to drafting the Commentary, reviewing the manuscript, and making any final edits.

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Correspondence to Jonathan M. Davis.

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Northeastern University is a partner institution of the Tufts Clinical and Translational Science Institute.

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Church, P.T., Werner, E. & Davis, J.M. Acetaminophen use during pregnancy: is there a problem?. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03050-5

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