Association of Prenatal Acetaminophen Measured in Meconium with Attention-Deficit Hyperactivity Disorder

Abstract

Background Multiple studies have shown an association between prenatal acetaminophen exposure and attention-deficit hyperactivity disorder (ADHD), but questions remain due to a paucity of quantifiable dose-response estimates and poor understanding of fetal exposure to acetaminophen and its toxic metabolites. To address this gap, we examined the association between prenatal acetaminophen concentrations measured in meconium and ADHD diagnosis in children aged 6-7 years. Methods Acetaminophen was measured in meconium with ultraperformance liquid chromatography mass spectrometry and ADHD diagnosis was determined at a scheduled cohort follow-up when children were 6-7 years old or from medical records for 345 children in the Gestation and the Environment prospective observational pregnancy cohort in Sherbrooke, Quebec, Canada. We modeled the associations of both binary (detected versus not detected) and continuous meconium acetaminophen with ADHD using logistic regressions. We compared continuous linear and non-linear models with a likelihood ratio test. We employed inverse probability weighting with propensity scores to account for potential confounders, including child sex, familial income, and maternal age, education, pre-pregnancy BMI, smoking during pregnancy, alcohol during pregnancy, and maternal self-reported ADHD. Results Acetaminophen was detected in 199 meconium samples (58%) and ADHD was diagnosed in 33 children (10%). Compared to no acetaminophen, detection of acetaminophen in meconium was associated with more than double the odds of ADHD (odds ratio = 2.44 [1.41, 4.22]). There was a linear dose response relationship: each doubling of exposure increased the odds of ADHD by 10% (OR = 1.10 [1.02, 1.19]). Conclusions and Relevance Together with the multitude of other cohort studies showing adverse neurodevelopment associated with prenatal acetaminophen, this work suggests caution should be used in administering acetaminophen during pregnancy. Research into alternative pain management strategies for pregnant women could be beneficial.