Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes

Abstract

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 ( trueβ^−0.13, 95% CI − 0.26, 0.00) but positively associated with Executive Functioning factor scores ( trueβ^0.2em0.18, 95% CI 0.04, 0.31). Standardized diethylphosphate metabolites were negatively associated with the Working Memory Index ( trueβ^−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.

Relationship between Autism Spectrum Disorder and Pesticides: A Systematic Review of Human and Preclinical Models

“…Additionally, Zhang et al [ 79 ] and Mora et al [ 80 ] used Carbofuranphenol and Mancozeb compounds to assess CM exposure, whereas Keil et al [ 81 ] assessed Imidacloprid exposure, a NN pesticide. Finally, 9 out of 45 (20.0%) studies [ 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ] reported exposure to a common mix of different types of pesticides. From all these studies, 37 out of 45 (82.2%) followed a longitudinal design, while only 8 (17.8%) were case-control studies.…”

“…Concerning the quality of the preclinical studies, three out of the 16 were labeled as H (18.8%) [ 30 , 37 , 38 ], 10 as MH (62.5%) [ 31 , 32 , 33 , 34 , 35 , 36 , 40 , 43 , 44 , 45 ], and the remaining three as ML-quality (18.8%) [ 39 , 41 , 42 ]. In a similar vein, 37 out of 45 human studies were classified as VH (82.2%) [ 46 , 48 , 49 , 50 , 51 , 52 , 53 , 56 , 57 , 58 , 59 , 61 , 63 , 64 , 65 , 66 , 67 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 80 , 81 , 82 , 83 , 84 , 85 , 87 , 88 , 89 , 90 , 91 ], 7 as H (15.6%) [ 47 , …”

“…The remaining articles, specifically 12 out of 45 (26.7%), studied the effects of exposure to a common mix of pesticides and other toxicants or several types of pesticides. All of these studies were classified as VH [ 46 , 80 , 81 , 82 , 83 , 84 , 85 , 87 , 88 , 89 , 90 , 91 ]. Eight out of 12 studies assessed only prenatal exposure, three out of 12 (25.0%, [ 46 , 83 , 88 ]) assessed both prenatal and postnatal exposure, whereas only one study [ 87 ] evaluated postnatal exposure.…”

Impaired innate and conditioned social behavior in adult C57Bl6/J mice prenatally exposed to chlorpyrifos

“…Lower IQ scores and impaired working memory were reported in different longitudinal studies at 7 years [3, 12, 42]. In contrast, a more recent study found a positive association between maternal DMP during pregnancy and maternal-reported measures of executive function in children aged 6–9 [15].…”

Co-expression network of long non-coding RNA and mRNA reveals molecular phenotype changes in kidney development of prenatal chlorpyrifos exposure in a mouse model

“…Organophosphorus pesticides (OPs) are widely studied chemicals that can be absorbed by humans (3). Researchers have confirmed that prenatal exposure to OPs leads to neurodevelopmental disabilities and impairments (4)(5)(6). Chlorpyrifos (CPF) is one of the most widely used OPs in the world (7).…”