Is Tylenol (acetaminophen) use during pregnancy associated with an increased risk of autism spectrum disorder in the fetus?

Acetaminophen Use During Pregnancy and Autism Risk

The weight of evidence is inconclusive regarding a possible causal relationship between acetaminophen use during pregnancy and autism spectrum disorder in offspring, though some studies suggest an association, particularly with prolonged use. 1, 2

Current Evidence on Acetaminophen and Neurodevelopmental Outcomes

The Society for Maternal-Fetal Medicine (SMFM) and FDA have reviewed the available evidence and determined that studies examining the link between prenatal acetaminophen exposure and neurodevelopmental disorders, including autism spectrum disorder (ASD), have significant methodological limitations 1, 2:

• Reliance on maternal self-reported acetaminophen use
• Lack of quantification of doses and duration
• Inability to control for all potential confounders (maternal fever, pain, inflammation)
• Recall bias in retrospective studies
• Limited assessment of outcomes

Specific Findings on Autism Risk

Some observational studies have reported associations between prenatal acetaminophen use and autism:

• Danish National Birth Cohort study found prenatal acetaminophen was associated with increased risk for ASD with hyperkinetic disorder (hazard ratio = 1.51; 95% CI, 1.19-1.92), but not ASD without hyperkinetic disorder (hazard ratio = 1.07; 95% CI, 0.92-1.24) 1, 3
• Longer duration of use (>20 weeks in gestation) may increase the risk of ASD with hyperkinetic symptoms almost twofold 2, 3
• Risk appears to be dose-dependent, with stronger associations observed with more frequent or prolonged use 2, 4

Risk Factors and Considerations

Several important factors should be considered when evaluating the potential risk:

• Duration of exposure: Longer exposure (≥28 days or >20 weeks gestation) shows stronger associations with neurodevelopmental outcomes 2, 3
• Timing of exposure: Third trimester exposure may present higher risk for ADHD-related outcomes 2
• Frequency of use: More frequent use shows stronger associations in some studies 4
• Confounding factors: Maternal fever, pain, or inflammation may independently affect neurodevelopment 2

Clinical Recommendations

Based on current evidence and guidelines:

1. Use acetaminophen at the lowest effective dose for the shortest duration possible when clinically indicated during pregnancy 2

2. Do not withhold acetaminophen when clinically necessary for treating pain or fever during pregnancy, as untreated fever or pain may pose risks to both mother and fetus 2, 5

3. Consider non-pharmacological approaches for mild to moderate pain when appropriate 2

4. Exercise particular caution with prolonged use, especially in second and third trimesters 2

Important Caveats

• Despite concerns raised by some studies, acetaminophen remains the safest medication option for necessary pain or fever relief during pregnancy 5
• The SMFM considers acetaminophen a reasonable and appropriate medication choice for treating pain and/or fever during pregnancy 1, 2
• The potential risks of untreated pain or fever during pregnancy may outweigh the theoretical risks associated with acetaminophen use 2
• Most studies showing associations have significant methodological limitations that prevent establishing causality 1, 2, 6

While some evidence suggests a possible link between prenatal acetaminophen exposure and neurodevelopmental outcomes including autism, current guidelines emphasize that the evidence is inconclusive and does not warrant avoiding this medication when clinically indicated during pregnancy.