Organophosphate pesticide exposure, PON1, and neurodevelopment in school-age children from the CHAMACOS study.

INTRODUCTION Organophosphate (OP) pesticides remain widely used in agriculture. Previously, we reported that PON1 genotype was directly associated with neurodevelopment at age two, and that PON1 genotype may increase susceptibility to OP exposure. OBJECTIVES We examined the relationships of maternal and child PON1 genotype and enzyme activity levels and neurodevelopment at school age and examined their interaction with maternal dialkyl phosphate (DAP) metabolite levels to investigate differential susceptibility to OP-related neurotoxicity. METHODS Participants were from the CHAMACOS longitudinal birth cohort of Latino families in an agricultural region of California. We measured DAP metabolites of OP pesticides in maternal and child urine samples, and analyzed PON1192 and PON1-108 genotypes and enzyme activity [arylesterase (ARYase), paraoxonase (POase)] in maternal and child blood. We examined their association with children׳s performance on the Conners׳ Kiddie Continuous Performance Test (K-CPT) at 5 years (n=296) and the Wechsler Intelligence Scale for Children (WISC-IV) at 7 years (n=327). RESULTS Maternal and child PON1 genotype was not related to performance on K-CPT or WISC, although WISC scores tended to be lowest in children and children of mothers who carried the PON-108TT genotype. Pregnancy ARYase levels were positively associated with all WISC subscales (e.g., 4.0 point increase in Full Scale IQ per standard deviation increase in ARYase, 95% CI=1.6, 6.4), while pregnancy POase levels were positively associated with WISC Processing Speed only. Maternal PON1-108 weakly modified the relationship of maternal DAPS and K-CPT scores (pinteraction=0.21) and WISC verbal IQ (pinteraction=0.71). The association between DAPs and Full-Scale IQ was strongest for children of mothers with lowest-tertile ARYase levels (pinteraction=0.27). This relationship held for both diethyl and dimethyl DAPs and for all subscales of the WISC. CONCLUSIONS We extend our previous findings that PON1 genotype and enzyme levels may be directly related to performance on certain domains of neurodevelopment in school-age children. Lower maternal PON1 enzyme levels during pregnancy may also increase susceptibility of children to neurotoxicity from OP pesticide exposure.