Prenatal exposure to paracetamol and risk of autism spectrum disorder: systematic review and meta-analysis of observational studies
Abstract
Abstract Objective: This meta-analysis aimed to assess the ASD risk in offspring exposed to prenatal acetaminophen compared to non-exposed offspring. Methods: A systematic search was conducted across PubMed, Embase, and Cochrane Central Register of Controlled Trials databases up to October 2025. Studies were included if they involved pregnant women, compared exposed versus non-exposed groups, were RCTs or cohort studies, and reported ASD outcomes. Data was extracted independently by two authors, with discrepancies resolved by consensus. Statistical analyses used odds ratios (ORs) with 95% confidence intervals, Cochran Q, and I² statistics with a random-effects model. Study quality was appraised using the ROBINS-E tool. Results: Eight studies, involving 2,560,208 patients, were included. Pooled results showed an 18% increased risk of ASD diagnosis (p <0.0001) and a non-significant 16% increase for ASD symptoms (p=0.1719). Dose-response relationships and gender-specific effects were reported by studies, while familial confounding and "some concerns" to "high" risk of bias were identified. Conclusion: A consistent, albeit modest, association was found. These findings emphasize the necessity for careful benefit-risk assessments and informed dialogue with expectant mothers regarding pain and fever management during pregnancy. PROSPERO: CRD420251160888
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 2,560,208 participants or records.
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