Is acetaminophen (Tylenol) safe to use during pregnancy for pain and fever relief?

Acetaminophen Use During Pregnancy

Acetaminophen remains a reasonable and appropriate medication choice for the treatment of pain and/or fever during pregnancy when medically necessary, but should be used at the lowest effective dose for the shortest possible duration. 1

Safety Profile and Recommendations

• The Society for Maternal-Fetal Medicine (SMFM) Publications Committee continues to advise that acetaminophen be considered a reasonable and appropriate medication choice for the treatment of pain and/or fever during pregnancy. 1

• Acetaminophen is the most widely used medication during pregnancy, with 40-65% of pregnant women using it at some point, primarily for headache and fever. 1

• Acetaminophen crosses the placenta relatively easily and has been detected in umbilical cord blood after maternal administration. 1

• The FDA drug label for acetaminophen recommends consulting a healthcare professional before use during pregnancy or breastfeeding. 2

Evidence on Potential Risks

• 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) 1
  • Increased risk of autism spectrum disorder (12.9% increased risk) 1
  • Higher risk with longer duration of exposure (>28 days) 1

• Several systematic reviews have found associations between prenatal acetaminophen exposure and neurodevelopmental disorders:

  • Masarwa et al. (2018) found 20-30% increased risk of ADHD and ASD outcomes 1
  • Gou et al. (2019) found 25% increased risk of ADHD outcomes 1
  • Alemany et al. (2021) found 12.2% increased risk of ADHD symptoms and 12.9% increased risk of autism spectrum conditions 1

Limitations of Current Evidence

• The FDA and SMFM 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

• Most studies have significant methodological and design limitations, including:

  • Inability to determine or control for all potential confounders 1
  • Recall bias and interview bias 1
  • Failure to adjust for multiple testing 1
  • Self-reported acetaminophen use 1
  • Lack of information on dosage and duration of exposure 1

• Correlating exposures during pregnancy with childhood neurobehavioral disorders is especially difficult because:

  • The definition and diagnosis of these illnesses, especially ADHD, continues to evolve 1
  • The cause or causes of ADHD are unknown 1
  • There are potential prenatal and postnatal confounders, such as environmental exposures and genetic predisposition 1

Clinical Guidance for Healthcare Providers

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

  • Use the lowest effective dose for the shortest possible duration 1, 3
  • Avoid excessive or prolonged use 1

• Communication regarding the risks versus the benefits of acetaminophen use should occur between patient and provider 1

• Pregnant women who use acetaminophen should be closely monitored across all trimesters of pregnancy 1

• For fever and pain during pregnancy, acetaminophen remains the safest analgesic and antipyretic option 3, 4

Important Considerations and Caveats

• There is no alternative medication with the same safety profile as acetaminophen for pain and fever relief during pregnancy 4

• Untreated fever during pregnancy may itself be associated with adverse gestational outcomes 5

• The potential risks of acetaminophen must be balanced against the risks of untreated pain or fever 5, 4

• When deciding to use acetaminophen during pregnancy, consider:

  • The medical necessity of treatment 3
  • The potential risks of not treating the condition 5
  • The duration of treatment needed 1
  • Alternative non-pharmacological approaches when appropriate 4