What is the significance of the Mount Sinai study linking autism to acetaminophen (Tylenol) use during pregnancy?

The Mount Sinai Study on Acetaminophen Use During Pregnancy and Autism Risk

The Mount Sinai study refers to research that found prenatal acetaminophen exposure is associated with an increased risk of autism spectrum disorder (ASD) with hyperkinetic symptoms, with a hazard ratio of 1.51 (95% CI 1.19-1.92), particularly with longer duration of use (>20 weeks). 1, 2

Key Findings of the Danish National Birth Cohort Study

This landmark study, often referred to as the Mount Sinai study due to researcher affiliations, followed 64,322 mother-child pairs in Denmark for an average of 12.7 years and found:

• Prenatal acetaminophen use was specifically associated with ASD accompanied by hyperkinetic symptoms (HR = 1.51,95% CI 1.19-1.92) 2
• No significant association was found with other ASD cases without hyperkinetic features (HR = 1.06,95% CI 0.92-1.24) 2
• Longer duration of use (>20 weeks during pregnancy) nearly doubled the risk of ASD with hyperkinetic symptoms 2
• 31% of ASD cases (26% of infantile autism) were also diagnosed with hyperkinetic disorders 2

Clinical Significance and Current Guidelines

The Society for Maternal-Fetal Medicine (SMFM) and American College of Obstetricians and Gynecologists (ACOG) continue to recommend acetaminophen as a reasonable medication choice for pain and fever during pregnancy, but emphasize judicious use 1. This recommendation is based on:

• The evidence on acetaminophen's association with neurodevelopmental disorders remains inconclusive and has significant limitations 1
• Untreated pain or fever during pregnancy may pose greater risks than acetaminophen use 1

Subsequent Research and Meta-Analyses

Following the Mount Sinai study, additional research has supported potential associations:

• A 2018 meta-analysis found pooled risk ratios of 1.34 (95% CI: 1.21,1.47) for ADHD and 1.19 (95% CI: 1.14,1.25) for ASD with prenatal acetaminophen exposure 3
• A 2025 systematic review using the Navigation Guide methodology found that higher-quality studies were more likely to show positive associations between prenatal acetaminophen use and neurodevelopmental disorders 4

Clinical Recommendations

For healthcare providers discussing acetaminophen use with pregnant patients:

• Advise using the lowest effective dose for the shortest possible time 1
• Consider non-pharmacological approaches for mild to moderate pain when appropriate 1
• Limit acetaminophen to 325mg per dosage unit in prescription products 1
• Avoid exceeding 4g daily, with 3g or less being preferable to reduce hepatic toxicity risk 1
• Inform patients that acetaminophen is widely used during pregnancy, but evidence regarding neurodevelopmental risks is still evolving 1

Limitations and Caveats

• Most studies on this topic are observational and cannot establish causality 5
• There is significant heterogeneity in exposure assessment and outcome measures across studies 3
• The specific mechanism by which acetaminophen might affect neurodevelopment remains unclear, though hypotheses include effects on inflammatory processes, immunologic mechanisms, and oxidative stress 5
• The association appears stronger for ASD with hyperkinetic features, suggesting the predisposition may be toward hyperkinetic syndrome rather than autism itself 5

The Mount Sinai study represents an important contribution to our understanding of potential risks associated with prenatal acetaminophen exposure, but current clinical guidelines still support judicious use when medically indicated during pregnancy.