State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, Hubei 430030, China; Hospital Management Institute of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, PR China.
State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, Hubei 430030, China.
Environ Int. 2021 Nov;156:106640. doi: 10.1016/j.envint.2021.106640. Epub 2021 May 18.
Increasing animal studies have indicated that organophosphate esters (OPEs) have endocrine-disruptive potential. However, human epidemiological evidence is limited, especially in susceptible populations, such as pregnant women and neonates. The purpose of this present study was to examine the trimester-specific relationships of prenatal exposure to OPEs with neonatal thyroid-stimulating hormone (TSH).
A total of 102 mother-newborn pairs were recruited from a birth cohort study between April 2015 and September 2016 in Wuhan, China. Eight OPE metabolites were detectable in urine samples from pregnant women across the different three trimesters. Neonatal TSH levels were measured using time-resolved immunofluorescence assay. The associations between maternal urinary OPE metabolites and neonatal TSH and the critical exposure windows of fetal vulnerability were estimated using multiple informant models.
Seven OPE metabolites with detection frequency > 50% (52.9%-98.0%) were detected in repeated urine samples from different three trimesters, and the urinary OPE metabolites across pregnancy was of high variability (ICCs: 0.09-0.26). After adjusted for confounders (e.g., maternal age, prepregnancy BMI, passive smoking during pregnancy), some suggestive associations were observed between maternal urinary OPE metabolites and neonatal TSH in different trimesters. A doubling of second trimester di-o-cresyl phosphate & di-p-cresyl phosphate (DoCP & DpCP) was associated with a 7.82% increase in neonatal TSH level (95% CI: -0.70%, 17.06%, p-value = 0.07), a doubling of third trimester diphenyl phosphate (DPHP) was associated with a 4.71% decrease in neonatal TSH level (95% CI: -9.80%, 0.67%, p-value = 0.09), and a doubling of third trimester bis(2-butoxyethyl) phosphate (BBOEP) was associated with a 6.38% increase in neonatal TSH level (95% CI: -0.12%, 13.31%, p = 0.05). However, such associations did not differ materially across trimesters. When performing stratified analysis by infant sex, the associations were statistically significant and were sex-dependent.In females, maternal urinary DoCP & DpCP concentrations in each trimester were associated with increased neonatal TSH levels, and urinary DPHP concentration in the third trimester was associated with decreased neonatal TSH level. In males, maternal urinary BBOEP concentration in the first trimester was positively related to neonatal TSH level.
This prospective study demonstrated that prenatal exposure to OPEs can lead to a sex-dependent change in neonatal TSH levels. Although the sex-selective effect was differed among various urinary OPE metabolites, more evidence was supported that OPE exposure was related to increased TSH levels for both males and females.
越来越多的动物研究表明，有机磷酸酯 (OPEs) 具有内分泌干扰潜力。然而，人类流行病学证据有限，特别是在孕妇和新生儿等易感人群中。本研究的目的是检查产前暴露于 OPEs 与新生儿促甲状腺激素 (TSH) 之间的特定孕期关系。
本研究共招募了 102 对母婴，来自中国武汉 2015 年 4 月至 2016 年 9 月期间的一项出生队列研究。在不同的三个孕期中，8 种 OPE 代谢物可在孕妇尿液样本中检测到。采用时间分辨免疫荧光分析法测量新生儿 TSH 水平。使用多信息模型估计母体尿液 OPE 代谢物与新生儿 TSH 之间的关联以及胎儿易感性的关键暴露窗口。
在不同的三个孕期中，在重复尿液样本中检测到 7 种具有检测频率>50%（52.9%-98.0%）的 OPE 代谢物，并且整个孕期的尿液 OPE 代谢物具有高度可变性（ICC：0.09-0.26）。调整混杂因素（例如，母亲年龄、孕前 BMI、孕期被动吸烟）后，在不同孕期观察到母体尿液 OPE 代谢物与新生儿 TSH 之间存在一些提示性关联。第二孕期中二-o-邻苯基磷酸酯和二-p-邻苯基磷酸酯（DoCP 和 DpCP）的浓度加倍与新生儿 TSH 水平增加 7.82%（95%CI：-0.70%，17.06%，p 值=0.07）有关，第三孕期中 diphenyl phosphate（DPHP）的浓度加倍与新生儿 TSH 水平降低 4.71%（95%CI：-9.80%，0.67%，p 值=0.09）有关，第三孕期中 bis(2-butoxyethyl) phosphate（BBOEP）的浓度加倍与新生儿 TSH 水平升高 6.38%（95%CI：-0.12%，13.31%，p=0.05）有关。然而，这些关联在不同孕期之间没有明显差异。当按婴儿性别进行分层分析时，关联具有统计学意义且具有性别依赖性。在女性中，每个孕期母体尿液中的 DoCP 和 DpCP 浓度与新生儿 TSH 水平升高有关，第三孕期母体尿液中的 DPHP 浓度与新生儿 TSH 水平降低有关。在男性中，第一孕期母体尿液中的 BBOEP 浓度与新生儿 TSH 水平呈正相关。
这项前瞻性研究表明，产前接触 OPEs 会导致新生儿 TSH 水平的性别依赖性变化。尽管各种尿液 OPE 代谢物的性别选择性效应不同，但更多的证据表明 OPE 暴露与男性和女性的 TSH 水平升高有关。
