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. 2021 Sep 23;17(12):757–766. doi: 10.1038/s41574-021-00553-7

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Human observational studies suggest prenatal N-acetyl-p-aminophenol (APAP) exposure might be associated with both reproductive and neurobehavioural abnormalities in both sexes. APAP exposure during pregnancy might increase risk of male urogenital and reproductive tract abnormalities, as studies have found an elevated risk of undescended testicles (cryptorchidism) and reduced distance between the anus and the base of the penis, a measure known as the anogenital distance (AGD). Both reduced AGD and cryptorchidism are indicators of disturbed masculinization and risk factors for reproductive disorders in later life. Prenatal APAP exposure has also been associated with earlier female pubertal development. Additionally, epidemiological studies consistently suggest prenatal APAP exposure might increase the risk of adverse neurodevelopmental and behavioural outcomes, such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, language delay (in girls) and decreased intelligence quotient. Collectively, the studies suggest that the timing and duration of maternal APAP use are critical factors.