Identifying associations and key early life exposure windows for organophosphate esters and adolescent brain morphometry in the HOME study

BACKGROUND: Organophosphate esters (OPEs) can be used as flame retardants and plasticizers in consumer products. Early life exposure may disrupt brain development by modifying brain structure and neurochemistry. OBJECTIVES: To evaluate the associations between gestational and childhood OPE metabolite urinary concentrations and their mixtures with neurobehavioral outcomes, explore the potential mediation of brain structure and neurochemistry, and identify potential windows of susceptibility. METHODS: We employed quantile-based g-computation models to investigate the mixture associations of OPE metabolite concentrations with three distinct categories of outcomes within the HOME Study at age 12 years: 1) magnetic resonance imaging (MRI)-based morphometric measurements; 2) magnetic resonance spectroscopy (MRS)-derived neurochemical concentrations; and 3) neurobehavioral outcomes across four non-overlapping exposure windows: 1) gestational, 2) birth, 3) ages 1-3 years, and 4) ages 5-8 years. We identified outcomes associated with OPE metabolite concentrations. We conducted analyses to evaluate the potential mediation of changes in brain structure and neurochemistry. RESULTS: Urinary concentrations of the mixture of OPE metabolites were primarily associated with morphometric measurements compared to neurobehavioral outcomes and were seen across all windows investigated before adjusting for multiple comparisons. The OPE metabolite mixture in the 5-8 year window was associated with reduced cortical volume of the pars triangularis, which mediated 27% of the increase in dominant hand drops on the grooved pegboard test before adjusting for multiple comparisons. DISCUSSION: Cortical volume of the pars triangularis may mediate the adverse relationship between OPE metabolite mixture concentrations and adolescent visual motor function during the 5-8-year window.