Maternal Use of Acetaminophen (Paracetamol) During Pregnancy and Neurodevelopmental Disorders in Offspring: A Reasoned Evaluation of Risk

J Clin Psychiatry. 2025 Nov 10;86(4):25f16187. doi: 10.4088/JCP.25f16187.

Abstract

The US Administration has moved to declare gestational exposure to acetaminophen (paracetamol) a risk factor for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in children. This article examines the science on the subject. Studies suggest that about half of women use acetaminophen during pregnancy; nevertheless, there is no epidemic of neurodevelopmental disorders (NDDs) in offspring. Two large population-based studies, one Swedish and the other Japanese, found that maternal use of acetaminophen during pregnancy was associated with an increased risk of ASD, ADHD, and intellectual disability (ID) in children. However, the risks were very small in fully adjusted analyses; hazard ratios (HRs) were mostly in the 1.05-1.07 range. Importantly, maternal use of aspirin, other NSAIDs, opioids, or antimigraine drugs during pregnancy was also associated with an increased risk of ASD and ADHD (but not ID). Most importantly, in sibling analyses, gestational exposure to acetaminophen, aspirin, and other analgesic drug categories was not associated with an increased risk of NDDs. There are many key points. Acetaminophen has a safety profile that is better than that of alternative treatments. The magnitude of increase in absolute risk for NDDs is very small (eg, by 0.09% at age 10, for ASD). There are many unmeasured confounds that, evenif weak, could nullify the relationship between acetaminophen and NDDs. Sibling analyses suggest that shared genetic and shared environment risk factors (rather than acetaminophen exposure) may explain the NDD risk. Analyses of other analgesic drug groups suggest that pain and inflammation, rather than drug exposure, may also explain the NDD risk. Finally, for reasons that are explained, making acetaminophen unavailable during pregnancy does not mean that the NDD risk will reduce. These points need to be discussed with women in a shared decision-making process that is both equitable and free from guilting.

Publication types

  • Review

MeSH terms

  • Acetaminophen* / adverse effects
  • Analgesics, Non-Narcotic* / adverse effects
  • Attention Deficit Disorder with Hyperactivity* / chemically induced
  • Attention Deficit Disorder with Hyperactivity* / epidemiology
  • Autism Spectrum Disorder* / chemically induced
  • Autism Spectrum Disorder* / epidemiology
  • Child
  • Female
  • Humans
  • Intellectual Disability / chemically induced
  • Intellectual Disability / epidemiology
  • Neurodevelopmental Disorders* / chemically induced
  • Neurodevelopmental Disorders* / epidemiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / chemically induced
  • Prenatal Exposure Delayed Effects* / epidemiology
  • Risk Factors

Substances

  • Acetaminophen
  • Analgesics, Non-Narcotic