Is there a link between acetaminophen (paracetamol) and autism spectrum disorder?

Acetaminophen and Autism: Examining the Evidence

The current evidence suggests a possible association between prenatal acetaminophen exposure and autism spectrum disorder (ASD), particularly when combined with hyperkinetic symptoms, but the relationship is not definitively causal and must be weighed against the risks of untreated pain or fever during pregnancy. 1

Current Evidence on the Association

The relationship between acetaminophen use during pregnancy and autism has been examined in several studies with mixed results:

• A 2022 umbrella review found associations between prenatal acetaminophen exposure and increased risk of neurodevelopmental disorders, including ASD 2
• Longer duration of acetaminophen use (>20 weeks in gestation) may increase the risk of ASD with hyperkinetic disorder almost twofold 1, 3
• A Danish national birth cohort study found that maternal acetaminophen use was specifically associated with ASD accompanied by hyperkinetic symptoms (HR = 1.51,95% CI 1.19-1.92), but not with other ASD cases (HR = 1.06,95% CI 0.92-1.24) 3
• The Society for Maternal-Fetal Medicine (SMFM) and the American College of Obstetricians and Gynecologists (ACOG) have stated that the weight of evidence is inconclusive regarding a possible causal relationship between acetaminophen use and neurodevelopmental disorders 1

Strength of Evidence and Limitations

The evidence linking acetaminophen to autism has important limitations:

• Many studies fail to adequately control for the conditions requiring acetaminophen (fever, inflammation), which may themselves contribute to neurodevelopmental outcomes 1
• The American College of Obstetricians and Gynecologists notes that the evidence for a causal relationship is inconclusive 1
• While recent research using the Navigation Guide methodology reported associations between prenatal acetaminophen exposure and neurodevelopmental disorders 4, this must be interpreted cautiously in light of guideline statements

Potential Mechanisms

Some proposed mechanisms for how acetaminophen might affect neurodevelopment include:

• Effects on the maternal immune system and fetal endocannabinoid system 1, 5
• Influence on inflammatory and immunologic mechanisms 6
• Potential to induce oxidative stress that could compromise neurodevelopment 6

Clinical Recommendations

Based on the current evidence:

1. Acetaminophen remains the safest medication option for necessary pain or fever relief during pregnancy 1, 7
2. Use acetaminophen at the lowest effective dosage and for the shortest time possible 1, 7
3. Avoid prolonged use (>28 days) without periodic evaluation of continued need 1
4. Exercise particular caution with prolonged use in the second and third trimesters 1
5. Consider non-pharmacological approaches for mild to moderate pain when appropriate 1

Important Caveats

• Untreated pain or fever during pregnancy may pose greater risks than judicious acetaminophen use 1
• The conditions requiring acetaminophen treatment may themselves contribute to neurodevelopmental outcomes 1
• Acetaminophen should not be withheld when medically necessary due to concerns about potential neurodevelopmental effects 7
• The association appears stronger for ASD with hyperkinetic symptoms rather than ASD alone, suggesting the predisposition may be toward hyperkinetic syndrome rather than autism specifically 6, 3

The relationship between acetaminophen use during pregnancy and autism remains an area of ongoing research, with current guidelines recommending judicious use while acknowledging the limitations of existing evidence.