Organophosphate pesticide metabolite concentrations in urine during pregnancy and offspring brain structural alterations

Abstract

OPS 55: Pesticides and neurological outcomes, Room 412, Floor 4, August 26, 2019, 1:30 PM - 3:00 PM Background: Prenatal exposure to organophosphate pesticides (OPs) is associated with neurodevelopment in humans and animal models. However, only few studies investigated the effect of prenatal exposure of OPs on brain structure and function. The aim of this study was to investigate whether prenatal OPs exposure was associated with brain structural alterations in children at 9-12 years old. Method Data came from 441 mother–child pairs participating in the Generation R study, a population-based birth cohort in Rotterdam, the Netherlands. Maternal urine concentrations of six dialkylphosphates (DAPs), collected at <18, 18–25, and >25 weeks of gestation, were determined. Structural magnetic resonance imaging in children (age 9-12 years) was used to investigate brain morphology using volumetric indices and whole-brain analyses (n=441); diffusion tensor imaging was used to assess white matter microstructure (n=398). Large fiber tracts of white matter integrity were combined to create global measures. Linear regression models were fit for each of the three collection phases separately, the three collection phases jointly, and for the averaged concentrations of exposure across pregnancy. Results: Overall, DAP concentrations were not associated with volumetric brain indices. However, early- and mid-pregnancy, and averaged DAP concentrations across pregnancy were inversely associated with lower fractional anisotropy (e.g. -1.05 (95%CI: -1.92, -0.18) per 10-fold increase in averaged DAP concentrations across pregnancy). Next, mid-pregnancy and averaged DAP concentrations across pregnancy were positively associated with higher mean diffusivity (e.g. 0.11 (95%CI: 0.02, 0.20) per 10-fold increase in averaged DAP concentrations across pregnancy). Conclusions: In this study of maternal urinary DAP concentrations during pregnancy, we did not observe associations with brain volumes. However, there was some evidence for an association of early and mid-pregnancy urinary DAP metabolite with lower fractional anisotropy and some evidence for a association between mid-pregnancy urinary DAP concentrations with higher mean diffusivity, which are generally considered indicators for atypical white matter microstructure.