Associations of public water system trihalomethane exposure during pregnancy with spontaneous preterm birth and the cervicovaginal microbial-immune state.

Associations of public water system trihalomethane exposure during pregnancy with spontaneous preterm birth and the cervicovaginal microbial-immune state.
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DOI:
10.1016/j.envres.2021.111288
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发表时间:
2021-08
影响因子:
8.3
通讯作者:
Burris HH
Burris HH
中科院分区:
环境科学与生态学2区
文献类型:
--
作者:
Lewis A;McKeon TP;De Roos AJ;Ravel J;Elovitz MA;Burris HH

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水总三卤甲烷(TTHM)是城市供水中发现的消毒副产品。TTHM暴露与癌症有关,并可能与不良生殖结果有关。非最佳宫颈阴道微生物群和低宫颈阴道β-防御素-2水平与自发性早产风险增加相关。TTHM暴露是否会增加自发性早产的风险或改变宫颈阴道微生物或免疫状态尚不清楚。在一个完整的、多样化的城市妊娠队列中调查水TTHM水平与自发性早产、非最佳宫颈阴道微生物群和β-防御素-2水平的相关性。我们假设较高的TTHM水平与自发性早产、非最佳宫颈阴道微生物群和较低的β-防御素-2水平相关。这是对Motherhood & Microbiome(M&M)研究(n=2000)中的参与者(n=474)进行的二次分析,这些参与者居住在费城,并对宫颈阴道微生物群组成和β-防御素-2水平进行了宫颈阴道样本分析。微生物群被分为社区状态类型(CST)。CST IV(非最佳微生物群)的特征是缺乏乳酸菌物种和广泛的厌氧菌。每月从费城16个地点获得市政水TTHM水平,以确定每个参与者在妊娠前4个月的平均住宅供水水平(在妊娠16-20周的阴道拭子采集之前)。使用多变量逻辑回归分析水TTHM水平与自发性早产和非最佳宫颈阴道微生物群分娩的关联。多变量线性回归用于模拟水TTHM水平与对数转换的宫颈阴道β-防御素-2水平的关联。由于水的TTHM水平随季节而变化,并且β-防御素-2水平已被证明因种族而异,因此利用了温暖季节(4月至9月)和寒冷季节(10月至3月)以及自我确定的种族的分层模型。参与者的供水TTHM水平(平均μg/L [SD])在温暖季节(53.5 [9.4])高于寒冷季节(33.4 [7.5])(p<0.0001)。黑人参与者的TTHM水平非显著高于非黑人参与者(44.8[13.5] vs. 41.8[11.8],p=0.07)。未检测到TTHM与自发性早产(TTHM每SD增量,aOR 0.94,95%CI:0.66,1.34)或CST IV(aOR 0.94,95%CI:0.86,1.16)之间的相关性。与我们的假设相反,我们在未调整的模型中观察到水TTHM与对数转换的宫颈阴道β-防御素-2水平呈正相关(β 0.20 [95%CI:0.02,0.39]/TTHM的SD增量),但在调整季节后,相关性为零。然而,在调整了包括季节在内的协变量并按种族分层的模型中,TTHM与非黑人参与者中较低的β-防御素-2水平显著相关(β-0.75 [95%CI:-1.43,-0.08]),但与黑人参与者无关(β 0.17 [95%CI:-0.15,0.49]),相互作用p=0.013)。我们没有检测到水TTHM水平与自发性早产或宫颈阴道微生物群结构的相关性。然而,TTHM和种族之间的β-防御素-2水平的显着相互作用的发现表明,环境暴露可能有助于生殖道先天免疫功能的种族差异。未来的研究,以描绘环境的贡献,宫颈阴道微生物免疫状态,一个潜在的重要的生物学基础早产,是必要的。
Water total trihalomethanes (TTHMs) are disinfectant byproducts found in municipal water supplies. TTHM exposure has been linked to cancer and may be associated with adverse reproductive outcomes. A non-optimal cervicovaginal microbiota and low cervicovaginal beta-defensin-2 levels are associated with increased risk of spontaneous preterm birth. Whether TTHM exposure increases the risk of spontaneous preterm birth or alters the cervicovaginal microbial or immune state is unknown. Investigate associations of water TTHM levels with spontaneous preterm birth, a non-optimal cervicovaginal microbiota, and beta-defensin-2 levels in a completed, diverse, urban pregnancy cohort. We hypothesized that higher TTHM levels would be associated with spontaneous preterm birth, a non-optimal cervicovaginal microbiota, and lower beta-defensin-2 levels. This was a secondary analysis of participants (n=474) in the Motherhood & Microbiome (M&M) study (n=2000), who lived in Philadelphia and had cervicovaginal samples analyzed for cervicovaginal microbiota composition and beta-defensin-2 levels. The microbiota was classified into community state types (CSTs). CST IV (non-optimal microbiota) is characterized by a paucity of Lactobacillus species and wide array of anaerobes. Municipal water TTHM levels were obtained from 16 sites monthly across the city of Philadelphia to establish mean residential water supply levels for each participant for the first four months of pregnancy (prior to vaginal swab collection at 16-20 weeks’ gestation). Associations of water TTHM levels with spontaneous preterm birth and a non-optimal cervicovaginal microbiota birth were analyzed using multivariable logistic regression. Multivariable linear regression was used to model associations of water TTHM levels with log-transformed cervicovaginal beta-defensin-2 levels. Since water TTHM levels vary by season and Beta-defensin-2 levels have been shown to differ by race, stratified models by warm (April-September) and cold (October-March) seasons as well as by self-identified race were utilized. Participants’ water supply TTHM levels (mean μg/L [SD]) were higher in the warm (53.5 [9.4]) than cold (33.4 [7.5]) season (p<0.0001). TTHM levels were non-significantly higher among Black participants than non-Black participants (44.8[13.5] vs. 41.8[11.8], p=0.07). No associations were detected between TTHM with spontaneous preterm birth (per SD increment of TTHM, aOR 0.94, 95%CI: 0.66, 1.34) or with CST IV (aOR 0.94, 95%CI: 0.86, 1.16). Counter to our hypothesis, we observed positive associations of water TTHM with log-transformed cervicovaginal beta-defensin-2 levels in unadjusted models (β 0.20 [95%CI: 0.02, 0.39)] per SD increment of TTHM), but the association was null after adjustment for season. However, in models adjusted for covariates including season and stratified by race, TTHM was significantly associated with lower beta-defensin-2 levels among non-Black participants (β −0.75 [95%CI: −1.43, −0.08]) but not among Black participants (β 0.17 [95%CI: −0.15, 0.49]), interaction p=0.013). We did not detect associations of water TTHM levels with spontaneous preterm birth or the structure of the cervicovaginal microbiota. However, the finding of a significant interaction between TTHM and race on beta-defensin-2 levels suggest that environmental exposures may contribute to differences in reproductive tract innate immune function by race. Future studies to delineate environmental contributions to the cervicovaginal microbial-immune state, a potentially important biologic underpinning for preterm birth, are warranted.
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发表时间: 2005-07-01
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