aDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, United StatesbDepartment of Statistical Science and Global Health Institute, Duke University, United StatescDepartment of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, United StatesdDepartment of Psychology and Neuroscience & FPG Child Development Institute, University of North Carolina at Chapel Hill, United StateseDepartment of Environmental Medicine and Public Health, Mount Sinai School of Medicine, United StatesfDepartment of Genetics and Genomic Sciences, Mount Sinai School of Medicine, United StatesgDepartment of Environmental Health, Rollins School of Public Health, Emory University, United States
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Prenatal exposure to organophosphorus pesticides (OPs) has been associated with different neurodevelopmental outcomes across different cohorts. A phenotypic approach may address some of these differences by incorporating information across scales and accounting for the complex correlational structure of neurodevelopmental outcomes. Additionally, Bayesian hierarchical modeling can account for confounding by collinear co-exposures. We use this framework to examine associations between prenatal exposure to OPs and behavior, executive functioning, and IQ assessed at age 6–9 years in a cohort of 404 mother/infant pairs recruited during pregnancy. We derived phenotypes of neurodevelopment with a factor analysis, and estimated associations between OP metabolites and these phenotypes in Bayesian hierarchical models for exposure mixtures. We report seven factors: 1) Impulsivity and Externalizing, 2) Executive Functioning, 3) Internalizing, 4) Perceptual Reasoning, 5) Adaptability, 6) Processing Speed, and 7) Verbal Intelligence. These, along with the Working Memory Index, were standardized and scaled so that positive values reflected positive attributes and negative values represented adverse outcomes. Standardized dimethylphosphate metabolites were negatively associated with Internalizing factor scores (Symbol − 0.13, 95% CI − 0.26, 0.00) but positively associated with Executive Functioning factor scores (Symbol 0.18, 95% CI 0.04, 0.31). Standardized diethylphosphate metabolites were negatively associated with the Working Memory Index (Symbol − 0.17, 95% CI − 0.33, − 0.03). Associations with factor scores were generally stronger and more precise than associations with individual instrument-specific items. Factor analysis of outcomes may provide some advantages in etiological studies of childhood neurodevelopment by incorporating information across scales to reduce dimensionality and improve precision.HighlightsWe investigated longitudinal associations between prenatal OPs and neurodevelopment.We identified 7 phenotypes that characterized neurodevelopment.Prenatal ΣDMPs were associated with a worse Internalizing phenotype in childhood.Prenatal ΣDEPs were associated with worse Working Memory in childhood.