A 2021 consensus statement by an international group of scientists and clinicians (Bauer et al.) recommended that pregnant individuals “forego [acetaminophen] unless its use is medically indicated,” due to the potential risk of developmental disorders such as autism and attention-deficit/hyperactivity disorder (ADHD).
A mostly Swedish research team, collaborating with a U.S. researcher, nevertheless noted that previous studies have been limited by:
- Confounding by indication, because acetaminophen is taken for infection, fever, and pain (including pain from autoimmune disease), which are themselves risk factors for neurodevelopmental disorders such as ADHD.
- Confounding by parental health and genetics, because neurodevelopmental disorders are highly heritable.
Sweden has a single-payer health insurance system that includes virtually its entire population, and national registers that enable tracking the health history of mothers and their children, including their children’s siblings.
The team used the Swedish registers to identify the roughly two-and-a-half million children born in Sweden from mid-1995 through 2019. They were also able to identify all siblings to be able to control for otherwise unmeasured familial and genetic confounding.
Almost 186,000 of these children were exposed to acetaminophen during pregnancy.
After adjusting for available known confounders, including (but not limited to) child sex and birthdate, mother’s age and medical history, use of any other painkillers, use of any psychoactive medications, country of birth, residential region, smoking status, highest household education, and disposable income, children exposed to acetaminophen during pregnancy were 7% more likely to be diagnosed with ADHD subsequently than those who were not exposed.
However, roughly the same results were found for other painkillers, including aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and antimigraine medication. High doses of acetaminophen did not produce any stronger association with subsequent ADHD than low dosage.
Moreover, when confining results to siblings – 8,526 children who were exposed versus 87,679 who were unexposed – the association between acetaminophen use during pregnancy and subsequent offspring ADHD vanished altogether (and, again, at every dose level). The associations similarly vanished with every other painkiller medication.
The Swedish team concluded, “Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in models without sibling control may have been attributable to confounding.”
Viktor H. Ahlqvist, Hugo Sjöqvist, Christina Dalman, Håkan Karlsson, Olof Stephansson, Stefan Johansson, Cecilia Magnusson, Renee M. Gardner, and Brian K. Lee, “Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability,” JAMA (2024), 331(14):1205-1214, https://doi.org/10.1001/jama.2024.3172.
Ann Z. Bauer, Shanna H. Swan, David Kriebel, Zeyan Liew, Hugh S. Taylor, Carl-Gustaf Bornehag, Anderson M. Andrade, Jørn Olsen, Rigmor H. Jensen, Rod T. Mitchell, Niels E. Skakkebaek, Bernard Jégou, and David M. Kristensen, “Consensus Statement: Paracetamol use during pregnancy — a call for precautionary action,” Nature Reviews Endocrinology (2021), 17, 757-766, https://doi.org/10.1038/s41574-021-00553-7.
Brandlistuen, R. E., Ystrom, E., Nulman, I., Koren, G. & Nordeng, H. (2013). Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study. Int J Epidemiol 42, 1702-13.
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