Is acetaminophen (paracetamol) safe to use during pregnancy?

Acetaminophen Use During Pregnancy: Safety Considerations for Autism Risk

Acetaminophen remains a reasonable and appropriate medication choice for pain and fever during pregnancy, but should be used at the lowest effective dose for the shortest possible duration due to inconclusive evidence regarding potential neurodevelopmental effects. 1, 2

Current Evidence on Acetaminophen and Neurodevelopmental Outcomes

• Recent observational studies have suggested associations between prenatal acetaminophen exposure and neurodevelopmental outcomes in children, including:

  • Increased risk of ADHD symptoms (12.2-25% increased risk) 2, 3
  • Potential association with autism spectrum disorder (ASD) with hyperkinetic disorder (hazard ratio 1.51; 95% CI 1.19-1.92) 1
  • Higher odds of conduct problems (RR 1.42) and hyperactivity symptoms (RR 1.31) 1, 3

• The risk appears to be dose-dependent, with stronger associations observed with:

  • Use in more than one trimester 3
  • Longer duration of exposure (>28 days) 3
  • Higher frequency of use during gestation 3

Limitations of Current Evidence

• The Society for Maternal-Fetal Medicine (SMFM) and FDA have evaluated these studies and determined that "the weight of evidence is inconclusive regarding a possible causal relationship between acetaminophen use and neurobehavioral disorders in the offspring" 1, 2

• Significant methodological limitations in existing studies include:

  • Maternal self-reporting of acetaminophen use (potential for recall bias) 1
  • Lack of quantification of doses and duration 1
  • Outcome measurement using parental surveys rather than clinical assessment 1
  • Inability to control for all potential confounders 1, 2
  • Failure to adjust for multiple testing 2

Clinical Recommendations

• Acetaminophen should be used during pregnancy only when medically necessary 2, 3

  • Use the lowest effective dose for the shortest possible duration 2, 3
  • Avoid excessive or prolonged use 2, 3

• Communication regarding risks versus benefits should occur between patient and provider 1, 2

  • The FDA label advises pregnant women to consult a healthcare professional before use 4

• For pain management during pregnancy, acetaminophen remains the safest analgesic option compared to alternatives like NSAIDs 2, 3

  • NSAIDs should be avoided, particularly after 28 weeks of gestation, due to risks of premature closure of the fetal ductus arteriosus 2

Common Pitfalls and Caveats

• Overreaction to preliminary evidence may lead to inadequate pain or fever management during pregnancy 5

  • Untreated fever during pregnancy may pose greater risks to fetal development than acetaminophen use 5

• There is currently no alternative medication with the same safety profile as acetaminophen for pain and fever during pregnancy 5

• Recent studies on language development suggest that higher acetaminophen use during the second and third trimesters may be associated with poorer language development outcomes, particularly in male children 6

• While concerns exist, acetaminophen should not be withheld when clinically indicated, as there are no safer alternatives for pain or fever relief during pregnancy 5