Background

A few endocrine disrupting chemicals (EDCs) have been associated with pregnancy loss often as reported by women, though there has been no study of EDC mixtures and pregnancy loss in keeping with the nature of human exposure.

Objectives

To investigate preconception exposure to a mixture of EDCs to identify important drivers and inform multi-pollutant models of EDCs in relation to incident human gonadrophin chorionic (hCG) pregnancy loss.

Methods

A cohort of 501 couples were recruited from the general population and prospectively followed until a hCG-confirmed pregnancy or 12 months of trying to become pregnant. Pregnant (n = 344; 69%) women were followed daily through seven weeks post-conception then monthly until delivery. Loss was defined as conversion to negative pregnancy test or a clinical diagnosis. Preconception exposure assessment of EDCs included sixty-three serum chemicals and three blood metals. EDCs were measured using isotope dilution gas chromatography-high resolution mass spectrometry or high-performance liquid chromatography-tandem mass spectrometry, and inductively coupled plasma-mass spectrometry, respectively. Using elastic net variable selection to identify important factors from the exposure mixture, EDC levels and covariates were then included in Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of time-to-pregnancy loss in multi-pollutant models.

Results

Incidence of hCG pregnancy loss was 28%. Nine EDCs of the sixty-six chemical mixture were associated with pregnancy loss; HRs were elevated for polychlorinated biphenyl 194, 2-(N-methyl-perfluorooctane sulfonamido) acetate, polybrominated diphenyl ether 28, and cadmium, even in sensitivity models adjusting for male partners’ EDC concentrations. In final multivariable multi-pollutant Cox proportional hazard models, female partners’polybrominated diphenyl ether 28 (aHR = 1.16, 95% CI: 1.02, 1.31) and cadmium (aHR = 1.23, 95% CI: 1.07, 1.40) remained associated with hCG pregnancy loss. Female partners’ preconception serum polychlorinated biphenyl 194 and 2-(N-methyl-perfluorooctane sulfonamido) acetate concentrations were consistently inversely associated with loss [(aHR = 0.72, 95% CI: 0.56, 0.92) and (aHR = 0.79, 95% CI: 0.65, 0.95), respectively].

Conclusion

Assessing exposure to a mixture of 66 persistent EDCs, females’ preconception concentrations of polybrominated diphenyl ether 28 and cadmium were positively associated with incident hCG pregnancy loss in a cohort of couples from the general population trying for pregnancy.

中文翻译：

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对孕前持续内分泌干扰化学物质和意外流产的多污染物评估

背景

一些内分泌干扰化学物质 (EDC) 经常与女性报告的流产有关，尽管没有与人类暴露的性质保持一致的 EDC 混合物和流产的研究。

目标

调查孕前暴露于混合 EDCs 以确定重要驱动因素，并告知与事件人类促性腺激素绒毛膜 (hCG) 妊娠丢失相关的 EDCs 多污染物模型。

方法

从一般人群中招募了 501 对夫妇，并进行了前瞻性随访，直到 hCG 确认怀孕或尝试怀孕 12 个月。怀孕（n = 344；69%）妇女在受孕后 7 周内每天接受随访，然后每月随访直至分娩。丢失被定义为转换为阴性妊娠试验或临床诊断。EDCs 的孕前暴露评估包括 63 种血清化学物质和三种血液金属。分别使用同位素稀释气相色谱-高分辨质谱或高效液相色谱-串联质谱和电感耦合等离子体质谱测量 EDC。使用弹性净变量选择来识别暴露混合物中的重要因素，

结果

hCG 流产的发生率为 28%。66 种化学混合物中的 9 种 EDC 与流产有关；多氯联苯 194、2-（N-甲基-全氟辛烷磺酰胺）乙酸酯、多溴联苯醚 28 和镉的 HR 升高，即使在针对男性伴侣的 EDC 浓度进行调整的敏感性模型中也是如此。在最终的多变量多污染物 Cox 比例风险模型中，女性伴侣的多溴二苯醚 28 (aHR = 1.16, 95% CI: 1.02, 1.31) 和镉 (aHR = 1.23, 95% CI: 1.07, 1.40) 仍与 hCG 相关妊娠丢失。女性伴侣的孕前血清多氯联苯 194 和 2-（N-甲基-全氟辛烷磺酰胺）醋酸盐浓度始终与丢失呈负相关 [(aHR = 0.72, 95% CI: 0.56, 0.92) 和 (aHR = 0.79, 95% CI) : 0.65, 0.95), 分别]。

结论

评估暴露于 66 种持久性 EDC 的混合物中，女性的多溴二苯醚 28 和镉的孕前浓度与尝试怀孕的普通人群中的一组夫妇中发生的 hCG 妊娠丢失呈正相关。