Is acetaminophen (paracetamol) associated with an increased risk of autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD)?

Acetaminophen and Risk of Autism/ADHD in Pregnancy

Current evidence does not support withholding acetaminophen during pregnancy due to concerns about autism or ADHD risk, as the most recent high-quality research using sibling control analysis found no association between prenatal acetaminophen use and neurodevelopmental disorders. 1

Evidence Analysis and Recommendations

Current Guidelines and Position Statements

The Society for Maternal-Fetal Medicine (SMFM) and the American College of Obstetricians and Gynecologists (ACOG) continue to recommend acetaminophen as a reasonable and appropriate medication choice for pain and fever relief during pregnancy 2. These organizations emphasize that:

• The evidence on acetaminophen's association with neurodevelopmental disorders is inconclusive and has significant limitations
• Untreated pain or fever may pose greater risks to pregnancy than judicious acetaminophen use
• Non-pharmacological approaches should be considered for mild to moderate pain when appropriate

Research Evidence Evaluation

The most recent and methodologically rigorous evidence comes from a 2024 nationwide cohort study published in JAMA that included 2,480,797 children born between 1995-2019 in Sweden 1. This study:

• Used sibling control analysis to address unobserved confounding
• Found no evidence that acetaminophen use during pregnancy was associated with:
  • Autism (HR 0.98,95% CI 0.93-1.04)
  • ADHD (HR 0.98,95% CI 0.94-1.02)
  • Intellectual disability (HR 1.01,95% CI 0.92-1.10)
• Found no dose-response relationship in sibling control analyses

Earlier studies and meta-analyses had suggested potential associations:

• A 2022 umbrella review reported significant associations between maternal prenatal acetaminophen use and ADHD outcomes (risk ratio range: 1.08–1.34) 3
• A Danish national birth cohort study found an association with ASD accompanied by hyperkinetic symptoms (HR = 1.51,95% CI 1.19-1.92) but not with other ASD cases 4

However, these earlier studies had important limitations in controlling for familial confounding factors that the 2024 JAMA study specifically addressed.

Clinical Guidance for Acetaminophen Use in Pregnancy

When acetaminophen is needed during pregnancy:

• Use the lowest effective dose for the shortest possible time 2
• Adhere to recommended dosing guidelines (maximum 4g daily, though limiting to 3g or less may be preferable) 2
• Avoid prolonged use without periodic evaluation of continued need, particularly in the second and third trimesters 2
• Be vigilant about total daily dose, especially when using combination products 2

Common Pitfalls to Avoid

1. Overreacting to observational studies: Many earlier studies showing associations failed to adequately control for genetic and environmental confounders that the sibling-controlled analysis addressed.

2. Undertreating fever or pain: Untreated fever or significant pain during pregnancy may pose greater risks than judicious acetaminophen use.

3. Extended use without reassessment: While short-term use appears safe, prolonged use should be periodically reevaluated.

4. Overlooking combination products: Be aware of acetaminophen in combination medications to avoid exceeding safe dosages.

Counseling Pregnant Patients

When discussing acetaminophen use with pregnant patients:

• Explain that it remains the preferred analgesic and antipyretic during pregnancy 2, 5
• Acknowledge that while some studies have suggested associations with neurodevelopmental disorders, the highest quality evidence does not support these concerns 1
• Emphasize the importance of using the lowest effective dose for the shortest duration
• Discuss non-pharmacological pain management strategies when appropriate

The evidence supports continued judicious use of acetaminophen during pregnancy when clinically indicated, without undue concern about autism or ADHD risk.