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孕期母体尿液邻苯二甲酸代谢物与母血和脐血甲状腺激素浓度:HOME 研究。

Maternal urinary phthalate metabolites during pregnancy and thyroid hormone concentrations in maternal and cord sera: The HOME Study.

机构信息

Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA; Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA.

Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA.

出版信息

Int J Hyg Environ Health. 2018 May;221(4):623-631. doi: 10.1016/j.ijheh.2018.03.010. Epub 2018 Mar 23.

Abstract

BACKGROUND

Phthalates, endocrine-disrupting chemicals that are commonly found in consumer products, may adversely affect thyroid hormones, but findings from prior epidemiologic studies are inconsistent.

OBJECTIVES

In a prospective cohort study, we investigated whether maternal urinary phthalate metabolite concentrations and phthalate mixtures measured during pregnancy were associated with thyroid hormones among pregnant women and newborns.

METHODS

We measured nine phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate, mono-isobutyl phthalate, monobenzyl phthalate (MBzP), and four monoesthers of di(2-ethylhexyl) phthalate] in urine collected at approximately 16 and 26 weeks' gestation among women in the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, Ohio). Thyroid stimulating hormone (TSH) and free and total thyroxine and triiodothyronine were measured in maternal serum at 16 weeks' gestation (n = 202) and cord serum at delivery (n = 276). We used multivariable linear regression to assess associations between individual urinary phthalate metabolites and concentrations of maternal or cord serum thyroid hormones. We used weighted quantile sum regression (WQS) to create a phthalate index describing combined concentrations of phthalate metabolites and to investigate associations of the phthalate index with individual thyroid hormones.

RESULTS

With each 10-fold increase in 16-week maternal urinary MEP, maternal serum total thyroxine (TT) decreased by 0.52 μg/dL (95% CI: -1.01, -0.03). For each 10-fold increase in average (16- and 26-week) maternal urinary MBzP, cord serum TSH decreased by 19% (95% CI: -33.1, -1.9). Among mothers, the phthalate index was inversely associated with maternal serum TT (WQS beta = -0.60; 95% CI: -1.01, -0.18). Among newborns, the phthalate index was inversely associated with both cord serum TSH (WQS beta = -0.11; 95% CI: -0.20, -0.03) and TT (WQS beta = -0.53; 95% CI: -0.90, -0.16).

CONCLUSION

Our results suggest that co-exposure to multiple phthalates was inversely associated with certain thyroid hormones (TT in pregnant women and newborns, and TSH in newborns) in this birth cohort. These findings highlight the need to study chemical mixtures in environmental epidemiology.

摘要

背景

邻苯二甲酸酯是一种常见于消费产品中的内分泌干扰化学物质,可能会对甲状腺激素产生不良影响,但先前的流行病学研究结果并不一致。

目的

在一项前瞻性队列研究中,我们调查了孕妇尿液中妊娠期间测量的邻苯二甲酸代谢物浓度和邻苯二甲酸混合物是否与孕妇和新生儿的甲状腺激素有关。

方法

我们在 2003-2006 年(俄亥俄州辛辛那提)的健康结果和环境测量研究(Health Outcomes and Measures of the Environment Study)中测量了 9 种邻苯二甲酸代谢物[邻苯二甲酸单乙酯(MEP)、单正丁基邻苯二甲酸酯、单异丁基邻苯二甲酸酯、单苄基邻苯二甲酸酯(MBzP)和二(2-乙基己基)邻苯二甲酸酯的四种单酯],这些代谢物是在女性妊娠 16 周和 26 周时收集的尿液中测量的。在 16 周妊娠时(n=202)和分娩时(n=276)测量了母亲血清中的促甲状腺激素(TSH)和游离及总甲状腺素和三碘甲状腺原氨酸。我们使用多变量线性回归来评估个体尿液邻苯二甲酸代谢物浓度与母血清或脐带血清甲状腺激素之间的关系。我们使用加权分位数总和回归(weighted quantile sum regression,WQS)来创建一个描述邻苯二甲酸代谢物综合浓度的邻苯二甲酸指数,并研究邻苯二甲酸指数与个体甲状腺激素之间的关系。

结果

与 16 周时母体尿液中 MEP 每增加 10 倍相比,母体血清总甲状腺素(TT)降低 0.52μg/dL(95%置信区间:-1.01,-0.03)。与平均(16-26 周)母体尿液中 MBzP 每增加 10 倍相比,脐带血清 TSH 降低 19%(95%置信区间:-33.1,-1.9)。在母亲中,邻苯二甲酸指数与母体血清 TT 呈负相关(WQS 贝塔系数=-0.60;95%置信区间:-1.01,-0.18)。在新生儿中,邻苯二甲酸指数与脐带血清 TSH(WQS 贝塔系数=-0.11;95%置信区间:-0.20,-0.03)和 TT(WQS 贝塔系数=-0.53;95%置信区间:-0.90,-0.16)均呈负相关。

结论

我们的研究结果表明,在这个出生队列中,多种邻苯二甲酸同时暴露与某些甲状腺激素(孕妇和新生儿的 TT,以及新生儿的 TSH)呈负相关。这些发现突出表明需要在环境流行病学中研究化学混合物。

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