Testing Claimed Associations of Prenatal Acetaminophen with Neurodevelopmental Disorders: Re-analysis Using Bias-Correction Methods
TL;DR
The claim of "strong evidence" for an acetaminophen-neurodevelopmental-disorder association was not supported by this reanalysis, as a modest ADHD association persisted, while ASD and other-NDD estimates moved toward the null.
Abstract
Background: A 2025 systematic review concluded there was "strong evidence of a likely relationship" between prenatal acetaminophen exposure and neurodevelopmental disorders, informing a federal health advisory, based on qualitative synthesis without quantitative pooling or bias correction. We reanalysed the same studies to test whether this association withstands standard meta-analytic and bias-correction methods. Methods: We used 24 of 46 studies from a 2025 Navigation Guide systematic review (PubMed search through 25 February 2025) that reported a ratio measure (hazard ratio, odds ratio, relative risk, or incidence rate ratio). Estimates were collapsed to one per study, outcome group, and design, yielding 30 study-level estimates (sample sizes, 307-2,480,797) for attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and other neurodevelopmental disorders. We applied random-effects meta-analysis, eight publication-bias-correction methods, a credibility-ceiling sensitivity analysis, and five quality-filtered subsets, then repeated all analyses after harmonising odds and hazard ratios onto a common risk-ratio scale. Results: The ASD association attenuated from 1.14 (95% CI, 1.01-1.28) to 1.08 (95% CI, 0.97-1.19; P=.17) once each study was weighted once rather than by its number of sub-analyses, before any bias correction. The ADHD association remained positive under most bias-correction methods (range, 1.02-1.31), but its 95% CI crossed 1.00 under a 15% credibility ceiling. The other-NDD association reversed direction under one method (ratio, 0.98; 95% CI, 0.65-1.19) and showed no right-skew on p-curve testing (P=.71). Conclusions: The claim of "strong evidence" for an acetaminophen-neurodevelopmental-disorder association was not supported by this reanalysis. A modest ADHD association persisted, while ASD and other-NDD estimates moved toward the null.