背景:全氟烷基和多氟烷基物质(PFAS)是持久性合成化学物质,常见于日常用品中。PFAS与破坏葡萄糖稳态有关,然而,它们是否与妊娠期糖尿病(GDM)风险相关尚无定论.我们研究了妊娠期两次测量的PFAS浓度与GDM风险的前瞻性关联。
方法:在PETALS妊娠队列中,我们进行了一项巢式病例对照研究,包括41例GDM病例和87例对照.在妊娠早期和中期收集的血清中测量PFAS分析物(平均值[SD]:13.9[2.2]和20.2[2.2]孕周,分别),通过曲线下面积(AUC)计算累积暴露量,以整合PFAS浓度和暴露时间。个体调整加权非条件逻辑回归模型检查了7个与GDM风险相关的PFAS。使用错误发现率(FDR)校正P值。用贝叶斯核机回归(BKMR)分析混合模型。
结果:PFDA,在妊娠早期,PFNA和PFOA分别与每四分位数范围(IQR)较高的GDM风险相关(OR[95%CI]:1.23[1.09,1.38]),1.40[1.24、1.58]),和1.15[1.04,1.27],分别),怀孕中期(1.28[1.15,1.43],1.16[1.05,1.28],和1.20[1.09,1.33],分别),和累积暴露(1.23[1.09,1.38],1.21[1.07,1.37],和1.19[1.09,1.31],分别)。妊娠中期和累积暴露的全氟辛烷磺酸与GDM风险增加相关(1.41[1.17,1.71]和1.33[1.06,1.58],分别)。妊娠早期PFUnDA与较低的GDM风险相关(0.79[0.64,0.98]),而妊娠中期水平与较高风险相关(1.49[1.18,1.89]).PFHxS与妊娠早期和中期GDM风险降低相关(0.48[0.38,0.60]和0.48[0.37,0.63],分别)和累积暴露(0.49[0.38,0.63])。PFPeA与GDM无关。在BKMR模型中观察到类似的结论;然而,这些模型的总体关联无统计学意义.
结论:始终观察到与PFDA相关的GDM风险较高,PFNA,和PFOA暴露在妊娠早期和中期。结果应在更大的基于人群的队列中得到证实,育龄个体应潜在地避免PFAS的已知来源。
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals and are commonly found in everyday items. PFAS have been linked to disrupting glucose homeostasis, however, whether they are associated with gestational diabetes mellitus (GDM) risk remains inconclusive. We examined prospective associations of PFAS concentrations measured twice in pregnancy with GDM risk.
METHODS: In the PETALS pregnancy cohort, a nested
case-control study which included 41 GDM cases and 87 controls was conducted. PFAS analytes were measured in blood serum collected in both early and mid-pregnancy (mean [SD]: 13.9 [2.2] and 20.2 [2.2] gestational weeks, respectively), with cumulative exposure calculated by the area-under-the-curve (AUC) to integrate both the PFAS concentration and the timing of the exposure. Individual adjusted weighted unconditional logistic regression models examined seven PFAS in association with GDM risk. P-values were corrected using the false-discovery-rate (FDR). Mixture models were analyzed with Bayesian kernel machine regression (
BKMR).
RESULTS: PFDA, PFNA and PFOA were individually associated with higher GDM risk per interquartile range (IQR) in early pregnancy (OR [95% CI]: 1.23 [1.09, 1.38]), 1.40 [1.24, 1.58]), and 1.15 [1.04, 1.27], respectively), mid-pregnancy (1.28 [1.15, 1.43], 1.16 [1.05, 1.28], and 1.20 [1.09, 1.33], respectively), and with cumulative exposure (1.23 [1.09, 1.38], 1.21 [1.07, 1.37], and 1.19 [1.09, 1.31], respectively). PFOS in mid-pregnancy and with cumulative exposure was associated with increased GDM risk (1.41 [1.17, 1.71] and 1.33 [1.06, 1.58], respectively). PFUnDA in early pregnancy was associated with lower GDM risk (0.79 [0.64, 0.98]), whereas mid-pregnancy levels were associated with higher risk (1.49 [1.18, 1.89]). PFHxS was associated with decreased GDM risk in early and mid-pregnancy (0.48 [0.38, 0.60] and 0.48 [0.37, 0.63], respectively) and with cumulative exposure (0.49 [0.38,0.63]). PFPeA was not associated with GDM. Similar conclusions were observed in
BKMR models; however, overall associations in these models were not statistically significant.
CONCLUSIONS: Higher risk of GDM was consistently observed in association with PFDA, PFNA, and PFOA exposure in both early and mid-pregnancy. Results should be corroborated in larger population-based cohorts and individuals of reproductive age should potentially avoid known sources of PFAS.