18.2 ASSOCIATION OF PRENATAL ACETAMINOPHEN WITH CHILD ADHD IS MEDIATED BY FUNCTIONAL BRAIN CONNECTIVITY BUT NOT BIRTH OUTCOMES

Abstract

This presentation aims to evaluate associations of prenatal acetaminophen exposure measured in meconium with child ADHD, and to test birth outcomes and functional brain connectivity as potential mediators. Mothers were enrolled into this birth cohort study in Sherbrooke, Québec, Canada at their first prenatal care visit or delivery. Acetaminophen was measured in the meconium. A physician diagnosis of ADHD was determined at follow-up when children were 6 to 7 years old or from medical records. When children were 9 to 11 years old, resting-state brain connectivity was assessed with MRI, and attention problems and hyperactivity were assessed with the Behavioral Assessment System for Children Parent Report Scale. Associations between the meconium, acetaminophen, and outcomes were estimated with linear, logistic, and cox proportional hazards models. Birth outcomes and resting-state brain connectivity were tested as mediators of the association between prenatal acetaminophen exposure and ADHD. Among 345 children included in the analysis, acetaminophen was detected in 199 meconium samples (57.7%), and ADHD was diagnosed in 33 children (9.6%). Detection of acetaminophen in meconium was associated with increased odds of ADHD (OR = 2.43; 95% CI, 1.41-4.21). Prenatal acetaminophen was associated with negative connectivity between frontoparietal and default mode network nodes to clusters in the sensorimotor cortices, which mediated an indirect effect on increased child hyperactivity (14% mediation; 95% CI, 1-26). Although prenatal acetaminophen exposure was associated with decreased birthweight by 128 grams (β = –128; 95% CI, –221 to –36), and 22% increased weekly hazard of delivery (hazard ratio = 1.22; 95% CI, 1.06-1.40), birth outcomes did not mediate an effect on ADHD. Although unobserved confounding and confounding by indication are possible, these results warrant further investigation into adverse perinatal effects of prenatal acetaminophen exposure.