产前暴露于有机磷农药与青少年前脑形态和白质微观结构。
Prenatal exposure to organophosphate pesticides and brain morphology and white matter microstructure in preadolescents.
机构信息
Erasmus MC, University Medical Center Rotterdam, Department of Child and Adolescent Psychiatry, Rotterdam, 3015 CN, the Netherlands; Erasmus MC, University Medical Center Rotterdam, The Generation R Study Group, Rotterdam, 3015 CN, the Netherlands.
Erasmus MC, University Medical Center Rotterdam, The Generation R Study Group, Rotterdam, 3015 CN, the Netherlands; Erasmus MC, University Medical Center Rotterdam, Department of Epidemiology, Rotterdam, 3015 CN, the Netherlands; Erasmus MC, University Medical Center Rotterdam, Department of Clinical Genetics, Rotterdam, 3015 CN, the Netherlands.
出版信息
Environ Res. 2020 Dec;191:110047. doi: 10.1016/j.envres.2020.110047. Epub 2020 Aug 14.
BACKGROUND
Prenatal exposure to organophosphate (OP) pesticides associate with impaired neurodevelopment in humans and animal models. However, much uncertainty exists about the brain structural alterations underlying these associations. The objective of this study was to determine whether maternal OP pesticide metabolite concentrations in urine repeatedly measured during gestation are associated with brain morphology and white matter microstructure in 518 preadolescents aged 9-12 years.
METHOD
Data came from 518 mother-child pairs participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands. Maternal urine concentrations were determined for 6 dialkylphosphates (DAPs) including 3 dimethyl (DM) and 3 diethyl (DE) alkyl phosphate metabolites, collected at early, mid, and late pregnancy. At child's age 9-12 years, magnetic resonance imaging was performed to obtain T1-weighted images for brain volumes and surface-based cortical thickness and cortical surface area, and diffusion tensor imaging was used to measure white matter microstructure through fractional anisotropy (FA) and mean diffusivity (MD). Linear regression models were fit for the averaged prenatal exposure across pregnancy.
RESULTS
DM and DE metabolite concentrations were not associated with brain volumes, cortical thickness, and cortical surface area. However, a 10-fold increase in averaged DM metabolite concentrations across pregnancy was associated with lower FA (B = -1.00, 95%CI = -1.80, -0.20) and higher MD (B = 0.13, 95%CI = 0.04, 0.21). Similar associations were observed for DE concentrations.
CONCLUSIONS
This study provides the first evidence that OP pesticides may alter normal white matter microstructure in children, which could have consequences for normal neurodevelopment. No associations were observed with structural brain morphology, including brain volumes, cortical thickness, and cortical surface area.
背景
产前接触有机磷 (OP) 农药与人类和动物模型的神经发育受损有关。然而，这些关联背后的大脑结构变化存在很大的不确定性。本研究的目的是确定在 518 名 9-12 岁的青春期前儿童中，反复测量的妊娠期间母体 OP 农药代谢物浓度是否与大脑形态和白质微观结构有关。
方法
数据来自荷兰鹿特丹的一项基于人群的出生队列研究——Generation R 研究中的 518 对母婴对。在妊娠早期、中期和晚期采集 6 种二烷基磷酸酯 (DAP) 的母体尿液浓度，包括 3 种二甲基 (DM) 和 3 种二乙基 (DE) 烷基磷酸盐代谢物。在儿童 9-12 岁时，进行磁共振成像以获得大脑容积和基于表面的皮质厚度和皮质表面积，并使用扩散张量成像测量白质微观结构，通过分数各向异性 (FA) 和平均扩散系数 (MD)。线性回归模型用于拟合整个妊娠期间的平均产前暴露。
结果
DM 和 DE 代谢物浓度与大脑容积、皮质厚度和皮质表面积无关。然而，妊娠期间 DM 代谢物浓度增加 10 倍与 FA 降低相关（B = -1.00，95%CI = -1.80，-0.20）和 MD 升高（B = 0.13，95%CI = 0.04，0.21）。DE 浓度也观察到类似的关联。
结论
本研究首次提供了证据表明 OP 农药可能会改变儿童正常的白质微观结构，这可能对正常的神经发育产生影响。没有观察到与结构脑形态有关的关联，包括大脑容积、皮质厚度和皮质表面积。
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