THE IMPACT OF PRENATAL ORGANOPHOSPHATE ESTERS ON ATTENTION-DEFICIT/HYPERACTIVITY DISORDER AND EXECUTIVE FUNCTION IN PRESCHOOLERS

Background: Organophosphate esters (OPEs) are increasingly prevalent chemicals that have been linked to adverse neurodevelopment. However, no studies have assessed prenatal OPE exposure on ADHD or executive function (EF) in preschoolers. To address this gap, we evaluated prenatal OPE exposures on ADHD (AIM 1) and EF (AIM 2) in preschoolers. Methods: For this dissertation, we used the ADHD Substudy nested within the Norwegian Mother, Father, and Child Cohort Study. Di-n-butyl-phosphate (DnBP), diphenyl-phosphate (DPhP), bis(2-butoxyethyl) phosphate (BBOEP), and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were measured in maternal urine samples collected at 17 weeks’ gestation. For AIM 1, 260 preschool ADHD children, determined from the Preschool Age Psychiatric Assessment (PAPA), were compared to 549 birth-year stratified cases. For AIM 2, The Behavior Rating Inventory of Executive Functioning-Preschool (BRIEF-P) and subtests from the Stanford Binet fifth edition (SB-5) were used to measure EF in 340 preschoolers (262 ADHD, 78 typically-developing controls). We utilized logistic- (AIM 1) and inverse-probability-of-selection-weighted linear- (AIM 2) regression to estimate exposure-outcome associations as well as modification by sex. Results: Mothers with higher DnBP exposure were generally more likely to have a child with ADHD (3rd vs. 1st quartile OR: 1.71 95%CI: 1.13, 2.58) and worse EF compared to mothers with lower exposure. Higher DPhP was associated with adverse SB-5 verbal working memory (β = 0.49, 95%CI: 0.12, 0.87) and worse parent-reported BRIEF-P measures among boys but not girls (p-interaction for all: <0.01). Mothers with BDCIPP exposure ≥ limit of detection (LOD) but <limit of quantification had 1.39 times the odds of having a child with ADHD compared to those with BDCIPP <LOD (95%CI: 0.83, 2.31). Similarly, higher BDCIPP was associated with adverse SB-5 verbal working memory (β = 0.53, 95%CI: 0.08, 1.02). Girls had lower odds of ADHD with increasing BBOEP exposure (log10 OR: 0.55 (95%CI: 0.37, 0.93), however boys had a weakly increased odds [log10 OR: 1.25 (95%CI: 0.74, 2.11) p-interaction=0.01]. Additionally, higher BBOEP was associated with worse teacher-rated inhibition (β = 0.34, 95%CI: 0.01, 0.63). Conclusions: Overall, there was some evidence of associations between prenatal OPE exposures with ADHD and EF in preschoolers and variation in association by sex.