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孕早期和孕中期对羟基苯甲酸酯的尿液浓度与妊娠期糖尿病:PETALS队列中的一项巢式病例对照研究。

Urinary concentrations of early and mid-pregnancy parabens and gestational diabetes: A nested case-control study within the PETALS cohort.

作者信息

Peterson Alicia K, Zhu Yeyi, Feng Juanran, Calafat Antonia M, Hedderson Monique M, Alexeeff Stacey E, Ferrara Assiamira

机构信息

Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, United States of America; Center for Upstream Prevention of Adiposity and Diabetes Mellitus (UPSTREAM), Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, United States of America.

Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, United States of America; Center for Upstream Prevention of Adiposity and Diabetes Mellitus (UPSTREAM), Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, United States of America.

出版信息

Sci Total Environ. 2025 Apr 25;974:179253. doi: 10.1016/j.scitotenv.2025.179253. Epub 2025 Mar 27.

Abstract

Parabens are widely used preservatives with endocrine-disrupting properties, but their role in glucose metabolism during pregnancy is unclear. This study examines prospective associations between urinary concentrations of four parabens in early and mid-pregnancy and gestational diabetes (GDM). A matched case-control study nested within a diverse longitudinal pregnancy cohort (PETALS) with universal GDM screening matched GDM cases to two controls (111 cases; 222 controls). Urine samples collected 2015-2017 in early (14 ± 2.3 weeks) and mid-pregnancy (20 ± 2.4 weeks) were analyzed for paraben concentrations with mass spectrometry. Area-under-the-time-concentration-curve (AUC) assessed cumulative exposure. Conditional logistic regression models evaluated associations between paraben concentrations and GDM, adjusting for covariates. We a priori examined effect modification by Asian/Pacific Islander (A/PI) race/ethnicity due to the case-control matching and GDM prevalence highest among A/PI. Participants were 31 ± 5 years old and 40 % A/PI, 33 % Hispanic, 14 % White and 9 % Black. Methylparaben and propylparaben had >94 % detection, while ethylparaben and butylparaben ranged from 22 %-51 %. Paraben exposure was not associated with GDM overall. Among A/PI, higher methylparaben concentrations exhibited higher odds of GDM: early-pregnancy OR 1.14 per IQR (95 % CI: 0.89,1.45) and AUC 1.07 (0.89,1.30) compared to non-A/PI (early-pregnancy 0.81 [0.62,1.06] and AUC 0.70 [0.44,1.12]; P = 0.01 and 0.03, respectively). A/PI mid-pregnancy ethylparaben exposure (detectable vs non-detectable) was linked to higher GDM odds (2.00 [0.84,4.76] vs. non-A/PI 0.47 [0.17,1.27]; P = 0.04) as was mid-pregnancy propylparaben exposure (Tertile 2 vs. 1: 3.67 [1.21,11.1] vs. non-A/PI 0.70 [0.22, 2.25]; P = 0.04). Although overall paraben exposure was not associated with GDM, interactions by A/PI race/ethnicity suggested potential increased odds of GDM related to propylparaben, methylparaben, and ethylparaben exposure. Future studies should explore paraben exposure in diverse populations.

摘要

对羟基苯甲酸酯是具有内分泌干扰特性的广泛使用的防腐剂,但其在孕期葡萄糖代谢中的作用尚不清楚。本研究调查了孕早期和孕中期尿液中四种对羟基苯甲酸酯浓度与妊娠期糖尿病(GDM)之间的前瞻性关联。一项匹配病例对照研究嵌套在一个多样化的纵向妊娠队列(PETALS)中,该队列进行了普遍的GDM筛查,将GDM病例与两名对照进行匹配(111例病例;222名对照)。收集了2015 - 2017年孕早期(14±2.3周)和孕中期(20±2.4周)的尿液样本,用质谱法分析对羟基苯甲酸酯浓度。时间浓度曲线下面积(AUC)评估累积暴露量。条件逻辑回归模型评估对羟基苯甲酸酯浓度与GDM之间的关联,并对协变量进行调整。由于病例对照匹配以及A/PI中GDM患病率最高,我们预先检验了亚洲/太平洋岛民(A/PI)种族/族裔的效应修正。参与者年龄为31±5岁,40%为A/PI,33%为西班牙裔,14%为白人,9%为黑人。对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的检出率>94%,而对羟基苯甲酸乙酯和对羟基苯甲酸丁酯的检出率在22% - 51%之间。总体而言,对羟基苯甲酸酯暴露与GDM无关。在A/PI中,较高的对羟基苯甲酸甲酯浓度显示出患GDM的几率更高:与非A/PI相比,孕早期每IQR的比值比为1.14(95%CI:0.89,1.45),AUC为1.07(0.89,1.30)(孕早期非A/PI为0.81[0.62,1.06],AUC为0.70[0.44,1.12];P分别为0.01和0.03)。A/PI孕中期对羟基苯甲酸乙酯暴露(可检测与不可检测)与较高的GDM几率相关(2.00[0.84,4.76]与非A/PI的0.47[0.17,1.27];P = 0.04),孕中期对羟基苯甲酸丙酯暴露也是如此(第二三分位数与第一三分位数相比:3.67[1.21,11.1]与非A/PI的0.70[0.22,2.25];P = 0.04)。尽管总体对羟基苯甲酸酯暴露与GDM无关,但A/PI种族/族裔的相互作用表明,与对羟基苯甲酸丙酯、对羟基苯甲酸甲酯和对羟基苯甲酸乙酯暴露相关的GDM几率可能增加。未来的研究应探索不同人群中的对羟基苯甲酸酯暴露情况。

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Parabens exposure in early pregnancy and gestational diabetes mellitus.孕期接触防腐剂与妊娠糖尿病。
Environ Int. 2019 May;126:468-475. doi: 10.1016/j.envint.2019.02.040. Epub 2019 Mar 4.

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