Predictors and reproducibility of urinary organophosphate ester metabolite concentrations during pregnancy and associations with birth outcomes in an urban population
Predictors and reproducibility of urinary organophosphate ester metabolite concentrations during pregnancy and associations with birth outcomes in an urban population
复制标题
DOI：
10.1186/s12940-020-00610-0
复制
发表时间：
2020-05-24
影响因子：
6
通讯作者：
Buckley, Jessie P.
中科院分区：
文献类型：
--
作者：
Kuiper, Jordan R.;Stapleton, Heather M.;Buckley, Jessie P.
背景有机磷酸酯 (OPE) 是一种合成化学品，在多种产品中用作阻燃剂和增塑剂。尽管人类普遍存在 OPE 暴露，且实验室证据表明产前 OPE 暴露可能会扰乱后代的新陈代谢，但对 OPE 健康影响的围产期研究仍然有限。本研究的目的是：1) 确定妊娠期间尿 OPE 生物标志物浓度的预测因子和重现性，2) 估计产前 OPE 暴露与出生结果以及脐带血脂肪因子和胰岛素浓度的关系。方法 我们分析了 2017 年至 2019 年马里兰州巴尔的摩儿童健康与发展复原力 (ORCHARD) 妊娠队列中登记的 90 名妇女在怀孕期间最多 3 次就诊时收集的尿液样本中的 5 种 OPE 代谢物。为了量化怀孕期间代谢物浓度的变异性，我们使用混合效应回归模型计算了每种代谢物的组内相关系数 (ICC)。使用妊娠期间收集的自我报告问卷数据，我们使用广义估计方程评估了每种 OPE 代谢物可能的社会人口统计学和环境/行为预测因子，以解释重复暴露测量。我们根据病历确定了 76 名后代的出生结果，包括胎龄体重、身长、体重指数和胎龄。我们测量了 37 名婴儿的脐带血中瘦素、脂联素和胰岛素的浓度。为了考虑重复暴露测量，我们使用线性结构方程模型来评估产前 OPE 代谢因子评分的标准差 (SD) 增加与连续出生结果和脐带血生物标志物浓度的关系。结果 ICC 范围为磷酸异丙基苯基-苯基酯 (ip-PPP) 的 0.09 到磷酸二(1,3-二氯-2-丙基)酯 (BDCIPP) 的 0.59。我们观察到 OPE 暴露的环境或行为预测因素几乎没有一致性，尽管与其他季节相比，下午收集的样本浓度通常低于早晨和冬季。在调整后的分析中，BDCIPP浓度的SD增加与0.06 g/cm(3) (95% CI: 0.00, 0.12)更大的重量指数相关。 BDCIPP 的 SD 增加与胰岛素浓度降低 0.37 (95% CI: - 0.62, - 0.13) SD 和瘦素浓度降低 0.24 (95% CI: - 0.39, - 0.08) SD 相关。其他 OPE 与婴儿结局无关。结论 这些发现表明一些 OPE 可能是代谢干扰物，值得在更大规模的研究中进行调查。
Background Organophosphate esters (OPEs) are synthetic chemicals used as flame retardants and plasticizers in a variety of goods. Despite ubiquitous human exposures and laboratory evidence that prenatal OPE exposures may disrupt offspring metabolism, perinatal studies of OPE health effects are limited. The objectives of this study were to: 1) Determine predictors and reproducibility of urinary OPE biomarker concentrations during pregnancy, and 2) Estimate the relation of prenatal OPE exposures with birth outcomes and cord blood adipokine and insulin concentrations. Methods We analyzed five OPE metabolites in urine samples collected at up to three visits during pregnancy from 90 women enrolled in the ORigins of Child Health And Resilience in Development (ORCHARD) pregnancy cohort in Baltimore, MD from 2017 to 2019. To quantify the variability of metabolite concentrations during pregnancy, we calculated intraclass correlation coefficients (ICCs) for each metabolite using mixed effects regression models. Using self-reported questionnaire data collected during gestation, we assessed possible sociodemographic and environmental/behavioral predictors of each OPE metabolite using generalized estimating equations to account for repeated exposure measures. We ascertained birth outcomes of 76 offspring from medical records, including weight-for-gestational age, length, ponderal index, and gestational age. In a subset of 37 infants, we measured cord blood concentrations of leptin, adiponectin, and insulin. To account for repeated exposure measures, we used linear structural equation models to assess the relations of standard deviation (SD) increases in prenatal OPE metabolite factor scores with continuous birth outcomes and cord blood biomarker concentrations. Results ICCs ranged from 0.09 for isopropylphenyl-phenyl phosphate (ip-PPP) to 0.59 for bis(1,3-dichloro-2-propyl) phosphate (BDCIPP). We observed little consistency in environmental or behavioral predictors of OPE exposures, although concentrations were generally lower for samples collected in the afternoon compared to morning and winter compared to other seasons. In adjusted analyses, a SD increase in BDCIPP concentration was associated with a 0.06 g/cm(3) (95% CI: 0.00, 0.12) greater ponderal index. A SD increase in BDCIPP was associated with a 0.37 (95% CI: - 0.62, - 0.13) SD lower insulin concentration and 0.24 (95% CI: - 0.39, - 0.08) SD lower leptin concentration. Other OPEs were not associated with infant outcomes. Conclusions These findings suggest some OPEs may be metabolic disruptors warranting investigation in larger studies.