Acetaminophen Use During Pregnancy and Autism Risk
Acetaminophen remains a reasonable and appropriate medication choice for treating pain and fever during pregnancy, but should be used at the lowest effective dose for the shortest duration possible due to inconclusive evidence regarding its association with neurodevelopmental disorders including autism spectrum disorder (ASD). 1, 2
Current Evidence on Acetaminophen and Neurodevelopmental Outcomes
Association with ASD and ADHD
- Multiple studies have found associations between prenatal acetaminophen exposure and neurodevelopmental outcomes:
- Danish National Birth Cohort study found prenatal acetaminophen use was associated with increased risk of ASD with hyperkinetic symptoms (HR = 1.51,95% CI 1.19-1.92), but not with other ASD cases (HR = 1.07,95% CI 0.92-1.24) 3
- Longer duration of use (>20 weeks in gestation) increased risk of ASD with hyperkinetic symptoms almost twofold 3
- Meta-analyses have found risk ratios of 1.19-1.34 for ADHD outcomes and 1.09-1.19 for ASD outcomes 1
Dose-Response and Timing Considerations
- Evidence suggests a possible dose-dependent relationship 1, 2:
- Longer duration of use (≥28 days) associated with higher risk (RR = 1.63) 1
- Third trimester exposure may present higher risk for ADHD outcomes 1, 4
- Recent research suggests higher acetaminophen use during second and third trimesters may be associated with poorer language development, particularly in male children 4
Limitations of Current Research
Most studies have significant methodological limitations 1, 2:
- Reliance on maternal self-report of acetaminophen use
- Lack of quantification of doses and duration
- Inability to control for all potential confounders (maternal fever, pain, inflammation)
- Recall bias and interview bias
- Failure to adjust for multiple testing
The Society for Maternal-Fetal Medicine (SMFM) and FDA have both stated that the weight of evidence is inconclusive regarding a possible causal relationship between acetaminophen use and neurodevelopmental disorders 1
Clinical Recommendations
Use acetaminophen only when medically necessary for pain or fever during pregnancy 1, 2
Administer at the lowest effective dose for the shortest duration possible 2
Consider non-pharmacological approaches for mild to moderate pain when appropriate 2
Exercise particular caution with prolonged use, especially in second and third trimesters 1, 2, 4
Discuss risks versus benefits with pregnant patients, acknowledging the limitations of current evidence 2
Important Caveats
Acetaminophen remains the safest medication option for necessary pain or fever relief during pregnancy 5
Untreated fever or pain during pregnancy may pose risks to both mother and fetus 1, 5
There is no alternative medication with better safety data for pain relief during pregnancy 5
Acetaminophen should not be withheld when clinically indicated due to fear of potential neurodevelopmental effects 5
The SMFM Publications Committee continues to advise that acetaminophen be considered a reasonable and appropriate medication choice for the treatment of pain and/or fever during pregnancy, while emphasizing judicious use 1.