Does acetaminophen (Tylenol) use during pregnancy increase the risk of autism?

Acetaminophen During Pregnancy and Risk of Autism

Current evidence suggests that acetaminophen use during pregnancy may be associated with a small increased risk of neurodevelopmental disorders including autism spectrum disorder, particularly with prolonged use exceeding 28 days or use during the third trimester. 1

Evidence Overview

The relationship between prenatal acetaminophen exposure and autism risk has been examined in multiple studies with varying conclusions:

• Most recent high-quality evidence: A 2024 study published in JAMA found no link between acetaminophen use during pregnancy and autism, ADHD, or intellectual disability in offspring 2

• Previous evidence: Multiple meta-analyses and cohort studies had suggested associations between prenatal acetaminophen exposure and neurodevelopmental disorders:

  • Risk ratios for autism spectrum disorder ranging from 1.09-1.19 3, 1
  • Higher risk with prolonged use (>28 days) with risk ratio of 1.63 3, 1
  • Specific association with autism accompanied by hyperkinetic symptoms (HR = 1.51) 4

Mechanism of Potential Risk

Several potential mechanisms have been proposed:

• Acetaminophen crosses the placenta easily 1
• May activate maternal immune system and fetal endocannabinoid system 3
• Animal studies show links to decreased brain-derived neurotrophic factor (BDNF) and altered dopamine metabolism 3
• May affect frontoparietal brain connectivity in developing brains 3

Risk Factors and Timing

• Duration: Risk appears dose-dependent, with higher risk when used for >28 consecutive days 3, 1
• Trimester: Third trimester exposure may carry higher risk (RR = 1.26) 3
• Gender differences: Some studies suggest slightly higher risk for males, but effect sizes are too small for firm conclusions 3

Clinical Recommendations

• Benefit-risk assessment: Acetaminophen remains the safest analgesic and antipyretic option during pregnancy 1, 5
• Use guidelines:
  • Use lowest effective dose for shortest duration possible 1
  • Maximum 4g daily (preferably limit to 3g) 1
  • Consider non-pharmacological approaches for mild to moderate pain when appropriate 1
  • Do not withhold when clinically indicated for pain or fever 5

Important Caveats

• Most studies showing associations are observational and cannot establish causality 6
• Significant heterogeneity exists between studies in exposure measurement and outcome assessment 3
• Confounding factors may influence results, including:
  • Reason for medication use (fever/infection itself may affect neurodevelopment)
  • Maternal factors (age, psychiatric illness, etc.)
  • Recall bias in self-reported medication use

Bottom Line

While some evidence suggests a potential small increased risk of neurodevelopmental disorders with prenatal acetaminophen exposure, the most recent high-quality study shows no association. When acetaminophen is clinically indicated during pregnancy, it should be used at the lowest effective dose for the shortest duration possible, as it remains the safest option for pain and fever management during pregnancy.