Is acetaminophen (Tylenol) a cause of autism?

Tylenol (Acetaminophen) and Autism Risk

Current evidence does not conclusively support a causal relationship between acetaminophen use during pregnancy and autism spectrum disorder (ASD) in offspring. 1, 2

Evidence Assessment

• The FDA and Society for Maternal-Fetal Medicine (SMFM) have evaluated studies on this topic and determined that "the weight of evidence is inconclusive regarding a possible connection between acetaminophen use in pregnancy and neurodevelopmental disorders" 1, 2
• Existing studies have significant methodological limitations, including:
  • Self-reported acetaminophen use with potential for recall bias 2
  • Inability to determine or control for all potential confounders 1
  • Retrospective study designs with inherent limitations 1
  • Lack of quantification of doses in many studies 2

Specific Findings on Acetaminophen and ASD

• Some systematic reviews have found associations between prenatal acetaminophen exposure and ASD outcomes with risk ratios ranging from 1.093 to 1.19 2
• The Danish National Birth Cohort study found that prenatal acetaminophen use was associated with an increased risk specifically for ASD with hyperkinetic disorder (hazard ratio 1.51; 95% CI 1.19-1.92), but not for ASD without hyperkinetic disorder (hazard ratio 1.07; 95% CI 0.92-1.24) 3
• The risk appears to be dose-dependent, with stronger associations observed with longer duration of exposure (≥28 days) 2, 3
• The third trimester may present the highest risk period for potential neurodevelopmental effects 2

Potential Mechanisms

• Hypothesized mechanisms include acetaminophen indirectly activating:
  • The maternal immune system 2
  • Fetal endocannabinoid system, which has been implicated in both ASD and ADHD etiology 2
• Animal studies have found links between acetaminophen exposure and alterations in brain development, including:
  • Lower levels of brain-derived neurotrophic factor (BDNF) in the striatum 2
  • Alterations in dopamine metabolism 2

Clinical Recommendations

• The SMFM continues to advise that acetaminophen be considered a reasonable and appropriate medication choice for the treatment of pain and/or fever during pregnancy 1
• When used during pregnancy, acetaminophen should be used at the lowest effective dose for the shortest possible duration 2
• Communication regarding the risks versus benefits of acetaminophen use should occur between patient and provider 1, 2

Important Caveats

• While some ecological studies have suggested population-level trends between acetaminophen use and autism prevalence 4, these designs cannot establish causation
• The evidence suggesting acetaminophen exposure early in life (rather than prenatally) may be associated with autism lacks robust clinical evidence 5
• Most studies showing associations have significant methodological limitations that prevent firm conclusions 1, 2
• The definition and diagnosis of neurodevelopmental disorders, especially ADHD and ASD, continues to evolve, making retrospective studies challenging 1