Is acetaminophen (paracetamol) use during pregnancy associated with an increased risk of autism spectrum disorder in children?

Acetaminophen Use During Pregnancy and Autism Risk

Based on the most recent and highest quality evidence, acetaminophen use during pregnancy is not associated with an increased risk of autism spectrum disorder in children when familial confounding factors are properly controlled for in sibling analyses. 1

Current Evidence and Guidelines

The Society for Maternal-Fetal Medicine (SMFM) and the American College of Obstetricians and Gynecologists (ACOG) continue to recommend acetaminophen as a reasonable and appropriate medication choice for pain and fever relief during pregnancy, while emphasizing judicious use 2. This recommendation is supported by the most recent high-quality research evidence.

Key Research Findings

• The most recent and comprehensive study (JAMA, 2024) examined 2.48 million children born between 1995-2019 in Sweden with follow-up through 2021 1:

  • Initial analysis showed marginally increased risks (HR 1.05) for autism with acetaminophen exposure
  • However, when using sibling control analyses to account for familial confounding, no association was found between prenatal acetaminophen use and autism (HR 0.98,95% CI 0.93-1.04)
  • No dose-response relationship was observed in sibling analyses

• Earlier studies had suggested potential associations:

  • A Danish national birth cohort study (2016) found an association between acetaminophen use and ASD with hyperkinetic symptoms (HR 1.51,95% CI 1.19-1.92), particularly with longer duration of use 3
  • However, this study did not control for familial confounding factors as thoroughly as the 2024 JAMA study

Clinical Implications

Healthcare providers should consider the following when counseling pregnant patients:

1. Acetaminophen remains the preferred medication for pain and fever management during pregnancy 2
2. Use the lowest effective dose for the shortest possible duration 2
3. Consider non-pharmacological approaches for mild to moderate pain when appropriate 2
4. Avoid prolonged use without periodic evaluation of continued need 2

Important Considerations

• Untreated pain or fever during pregnancy may pose greater risks than judicious acetaminophen use 2
• The conditions requiring acetaminophen (fever, inflammation) may themselves contribute to neurodevelopmental outcomes 2
• While some studies suggest associations between acetaminophen and neurodevelopmental disorders 4, the highest quality evidence using sibling controls does not support this association 1

Common Pitfalls to Avoid

1. Overinterpretation of observational data: Many earlier studies failed to adequately control for familial confounding factors
2. Ignoring indication bias: The conditions requiring acetaminophen may themselves affect neurodevelopmental outcomes
3. Creating unnecessary anxiety: Pregnant patients should be reassured that when properly used, acetaminophen remains a safe option for managing pain and fever during pregnancy

When discussing this topic with patients, emphasize that the most recent and methodologically robust evidence does not support an association between prenatal acetaminophen use and autism when familial factors are properly controlled for.