Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Durham, NC, United States.
The Generation R Study Group, Erasmus Medical Center, University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus Medical Center, University Medical Center, Rotterdam, the Netherlands.
Environ Int. 2024 Nov;193:109082. doi: 10.1016/j.envint.2024.109082. Epub 2024 Oct 19.
The general population is chronically exposed to organophosphate pesticides through various routes including ingestion, hand-to-mouth contact, inhalation, and dermal contact. Exposure to organophosphate pesticides during pregnancy impairs fetal development, but the potential long-term effects of gestational organophosphate pesticide exposure are less well understood.
We investigated associations between gestational organophosphate pesticide exposure and cardiovascular outcomes in 643 children in the Generation R Study, a prospective pregnancy cohort based in Rotterdam, The Netherlands. Urinary organophosphate pesticide metabolites (dimethyl [∑DMAP], diethyl [∑DEAP], and total dialkyl phosphate [∑DAP] metabolites) were quantified in three urine samples collected from pregnant participants, and their children were followed until age 10 years at which time cardiac magnetic resonance imaging, ultrasonography, blood pressure, and serum biomarkers assessed cardiovascular health. Linear regression models estimated associations (β and 95 % confidence interval [CI]) between a one-interquartile range (IQR) increase in averaged gestational exposure biomarker concentrations and z-scored pediatric cardiovascular outcomes. We investigated effect modification of associations by PON1 genotype.
Carotid intima-media thickness z-score was lower (β: -0.14 [95 % CI: -0.25, -0.02]) and HDL cholesterol z-score was higher (β: 0.14 [95 % CI: 0.02, 0.25]) for increases in ∑DEAP concentrations. Carotid intima-media distensibility z-score was lower (β: -0.08 [95 % CI: -0.19, 0.03]) for increases in ∑DMAP concentrations, and systolic blood pressure z-score was higher (β: 0.10 [95 % CI: -0.01, 0.21]) for increases in ∑DMAP and ∑DAP. Among those with PON1-161CC and PON1-L55MTT genotypes, higher organophosphate pesticide concentrations conferred an excess risk of adverse vascular and glycemic outcomes, respectively.
We observed heterogenous associations between gestational organophosphate pesticide exposure and pediatric cardiovascular health: an anti-atherogenic profile was observed for increases in ∑DEAP concentrations, and impairments in multiple aspects of cardiovascular health was observed for increases in ∑DMAP concentrations. PON1-161 and PON1-L55M single nucleotide polymorphisms modified associations for vascular and glycemic outcomes, respectively.
一般人群通过摄入、手口接触、吸入和皮肤接触等多种途径长期接触有机磷农药。孕妇接触有机磷农药会损害胎儿发育，但孕期接触有机磷农药的潜在长期影响知之甚少。
我们调查了在荷兰鹿特丹的一项前瞻性妊娠队列研究——“生育队列研究”（Generation R Study）中的 643 名儿童中，妊娠期间接触有机磷农药与心血管结局之间的关系。从孕妇采集的 3 份尿液样本中定量检测了尿有机磷农药代谢物（二甲基[∑DMAP]、二乙基[∑DEAP]和总二烷基磷酸盐[∑DAP]代谢物），并对其儿童进行了随访，直至 10 岁，此时通过心脏磁共振成像、超声检查、血压和血清生物标志物评估心血管健康。线性回归模型估计了一个 IQR 增加的平均妊娠暴露生物标志物浓度与儿科心血管结局 z 评分之间的关系（β 和 95%置信区间[CI]）。我们研究了 PON1 基因型对关联的修饰作用。
∑DEAP 浓度升高，颈动脉内膜中层厚度 z 评分降低（β：-0.14 [95%CI：-0.25，-0.02]），高密度脂蛋白胆固醇 z 评分升高（β：0.14 [95%CI：0.02，0.25]）。∑DMAP 浓度升高，颈动脉内中膜扩张性 z 评分降低（β：-0.08 [95%CI：-0.19，0.03]），∑DMAP 和∑DAP 浓度升高，收缩压 z 评分升高（β：0.10 [95%CI：-0.01，0.21]）。PON1-161CC 和 PON1-L55MTT 基因型的个体中，有机磷农药浓度升高分别与血管和血糖不良结局的风险增加相关。
我们观察到妊娠期间接触有机磷农药与儿科心血管健康之间存在异质关联：∑DEAP 浓度升高呈现出抗动脉粥样硬化特征，∑DMAP 浓度升高则对心血管健康的多个方面产生损害。PON1-161 和 PON1-L55M 单核苷酸多态性分别修饰了血管和血糖结局的关联。
