(B-210) Acetaminophen Use During Pregnancy and the Risk of Childhood Attention-Deficit/Hyperactivity Disorder (ADHD): A Quantitative Bias Analysis
Monday, August 25, 2025
11:30 AM - 1:00 PM ET
Background: Acetaminophen, an over-the counter (OTC) medication commonly used during pregnancy, has been reported to be associated with attention-deficit/hyperactivity disorder (ADHD) in children. However, available evidence does not consider different assumptions regarding exposure and outcome misclassification.
Objectives: To provide a quantitative estimate of the direction, magnitude, and uncertainty arising from systematic errors when assessing acetaminophen use during pregnancy and the risk of ADHD in children.
Methods: We performed a probabilistic bias analysis (PBA) for each of the etiologic studies identified from a systematic literature search that assessed the association of acetaminophen use during pregnancy and the risk of ADHD in children. A search of the currently available literature was performed to retrieve validation studies providing estimates on sensitivity and specificity measures of acetaminophen use and ADHD outcomes to inform our bias parameters. A beta distribution was used to calculate α and β parameters to inform the PBA. Bias parameters were varied considering non-differential and differential misclassification scenarios. We estimated non-corrected pooled odds ratios (ORpooled) and bias-corrected pooled odds ratios (bcORpooled). Summary-level data were used to obtain bias-corrected estimates. The web-based tool apisensr was used to perform PBA analyses, while bcORpooled was estimated using R 4.4.2 software.
Results: Our meta-analysis of 6 included studies found that acetaminophen use during pregnancy was associated with an increased risk of ADHD (ORpooled=1.17; 95%CI 1.08-1.27). Non-differential misclassification of exposure and outcome resulted in a bias towards the null (bcORpooled=1.26, 95%CI 1.21-1.32, and bcORpooled=1.24, 95%CI 1.12-1.36, respectively). Differential misclassification of exposure, assuming higher sensitivity among children with ADHD exposed to acetaminophen, changed the direction of the estimates, moving away from the null (bcORpooled 0.91; 95%CI 0.41-2.01). A similar result was observed when assessing differential outcome misclassification with outcome specificity higher among children without ADHD whose mothers were exposed to acetaminophen (bcORpooled=1.03, 95%CI 0.82-1.28).
Conclusions: Exposure and outcome misclassification may play an important role when quantifying the risk of ADHD associated with acetaminophen exposure during pregnancy. The direction and magnitude of the bias depends on whether the misclassification is assumed to be differential or non-differential for both exposure and outcome measures. This study highlights the need to assess the potential impact of misclassification when studying OTC medications and cognitive outcomes, such as ADHD.