The Role of Early Life Pesticide Exposure, Genetic Susceptibility, and Thyroid Function in Childhood Neurodevelopment.

Abstract

Globally, organophosphate (OP) pesticide usage and exposure is widespread. Studies have found that fetuses and infants are more sensitive than adults to environmental toxicants and that prenatal exposure to low levels of OPs has been associated with an Attention Deficit Hyperactivity Disorder-like phenotype (ADHD-LP). ADHD is the most commonly studied and diagnosed cognitive and behavioral disorder in school-age children. The etiology of ADHD is unclear, but genetic and environmental factors, such as pesticide exposure, have been hypothesized. Numerous animal studies have demonstrated that in utero exposure to OP pesticides adversely affects neurodevelopment, but human studies remain limited. Using a prospective cohort study design, this research investigates the relationship between in utero exposure to chlorpyrifos and ADHD-LP in low to middle income, school-age, children from a Mexican birth cohort. Maternal, third trimester, second-morning void urine samples were analyzed for 3, 5, 6-trichloro-2-pyridinol (TCPY), a urinary metabolite of chlorpyrifos and chlorpyrifos-methyl. Maternal and child Paraoxonase 1 (PON1) polymorphisms, PON1G192R and PON1L55M were analyzed to explore their relationship with ADHD-LP and as a modifying factor in the relationship between chlorpyrifos (or chlorpyrifos-methyl) exposure and ADHD-LP. We assessed ADHD-LP for children 6-13 years old using subscales of Conners’ Parental Rating Scales-Revised, Conners’ Continuous Performance Test, and the parental scores for Behavior Assessment System for Children-2. Lastly, we assessed whether urinary concentrations of TCPY were associated with circulating thyroid hormone (TH) levels as a potential non-cholinergic mechanism of action of OP neurotoxicity using publicly available data from the National Health and Nutrition Examination Survey (NHANES). Results of this work suggest fetal exposure to chlorpyrifos, chlorpyrifos-methyl, or TCPY and maternal PON1 polymorphisms may influence the display of ADHD characteristics in childhood. We also found that urinary TCPY concentrations altered THs. Considering the continued widespread agricultural and possible residential use of chlorpyrifos and chlorpyrifos-methyl in Mexico, this research has added to the current knowledge on environmental predictors of child neurodevelopment and behavior, and provided additional insights into proposed biological mechanisms, susceptibility factors, and biomarker utility.