BACKGROUND Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity. OBJECTIVES Our aim was to quantify the association of serum PFAS with placental hCG, measured as an intact molecule (hCG), as free alpha-(hCGα) and beta-subunits (hCGβ), and as a hyperglycosylated form (h-hCG), and evaluate effect measure modification by social determinants and by fetal sex. METHODS Data were collected from 326 pregnant women enrolled from 2015 to 2019 in the UPSIDE study in Rochester, New York. hCG forms were normalized for gestational age at the time of blood draw in the first trimester [multiple of the median (MoM)]. Seven PFAS were measured in second-trimester maternal serum. Multivariate imputation by chained equations and inverse probability weighting were used to evaluate robustness of linear associations. PFAS mixture effects were estimated by Bayesian kernel machine regression. RESULTS Perfluorohexane sulfonic acid (PFHxS) [hCGβ: 0.29 log MoM units per log PFHxS; 95% confidence interval (CI): 0.08, 0.51] and perfluorodecanoic acid (PFDA) (hCG: -0.09; 95% CI: -0.16, -0.02) were associated with hCG in the single chemical and mixture analyses. The PFAS mixture was negatively associated with hCGα and positively with hCGβ. Subgroup analyses revealed that PFAS associations with hCG differed by maternal race/ethnicity and education. Perfluoropentanoic acid (PFPeA) was associated with hCGβ only in Black participants (-0.23; 95% CI: -0.37, -0.09) and in participants with high school education or less (-0.14; 95% CI: -0.26, -0.02); conversely, perfluorononanoic acid (PFNA) was negatively associated with hCGα only in White participants (-0.15; 95% CI: -0.27, -0.03) and with hCGβ only in participants with a college education or greater (-0.19; 95% CI: -0.36, -0.01). These findings were robust to testing for selection bias, confounding bias, and left truncation bias where PFAS detection frequency was <100%. Two associations were negative in male (and null in female) pregnancies: Perfluoroundecanoic acid (PFUnDA) with hCGα, and PFNA with h-hCG. CONCLUSIONS Evidence was strongest for the association between PFHxS and PFDA with hCG in all participants and for PFPeA and PFNA within subgroups defined by social determinants and fetal sex. PFAS mixture associations with hCGα and hCGβ differed, suggesting subunit-specific types of toxicity and/or regulation. Future studies will evaluate the biological, clinical and public health significance of these findings. https://doi.org/10.1289/EHP12950.

中文翻译：

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纽约州罗彻斯特的 UPSIDE 研究测量了妊娠早期血清全氟烷基物质与胎盘人绒毛膜促性腺激素的关联。


背景全氟烷基物质和多氟烷基物质（PFAS）在孕妇中广泛检测到，并与胎盘功能受损相关的不良后果相关。人绒毛膜促性腺激素 (hCG) 是一种二聚体糖蛋白激素，可指示胎盘毒性。目的 我们的目的是量化血清 PFAS 与胎盘 hCG 的关联，以完整分子 (hCG)、游离 α-(hCGα) 和 β-亚基 (hCGβ) 以及高糖基化形式 (h-hCG) 进行测量。并评估社会决定因素和胎儿性别对影响措施的修改。方法 收集了 2015 年至 2019 年纽约州罗彻斯特 UPSIDE 研究中招募的 326 名孕妇的数据。 hCG 形式根据妊娠早期抽血时的胎龄进行标准化[中位数的倍数 (MoM)]。在妊娠中期母体血清中检测到了 7 种 PFAS。使用链式方程和逆概率加权进行多元插补来评估线性关联的稳健性。 PFAS 混合效应通过贝叶斯核机回归进行估计。结果 全氟己烷磺酸 (PFHxS) [hCGβ：每 log PFHxS 0.29 log MoM 单位；在单一化学分析和混合物分析中，95% 置信区间 (CI)：0.08，0.51] 和全氟癸酸 (PFDA)（hCG：-0.09；95% CI：-0.16，-0.02）与 hCG 相关。 PFAS 混合物与 hCGα 呈负相关，与 hCGβ 呈正相关。亚组分析显示，PFAS 与 hCG 的关联因母亲种族/民族和教育程度而异。全氟戊酸 (PFP​​eA) 仅在黑人参与者 (-0.23; 95% CI: -0.37, -0.09) 和高中及以下教育程度的参与者 (-0.14; 95% CI: -0.26, -0.09) 中与 hCGβ 相关。02);相反，全氟壬酸（PFNA）仅在白人参与者中与 hCGα 呈负相关（-0.15；95% CI：-0.27，-0.03），仅在受过大学或以上教育的参与者中与 hCGβ 呈负相关（-0.19；95% CI： -0.36，-0.01）。这些发现对于测试选择偏倚、混杂偏倚和左截断偏倚（其中 PFAS 检测频率 <100%）来说是稳健的。男性（女性）妊娠中有两种呈阴性关联：全氟十一烷酸 (PFUnDA) 与 hCGα 的关联，以及 PFNA 与 h-hCG 的关联。结论 在所有参与者中，PFHxS 和 PFDA 与 hCG 之间的关联性以及由社会决定因素和胎儿性别定义的亚组中的 PFPeA 和 PFNA 之间的关联性证据最强。 PFAS 混合物与 hCGα 和 hCGβ 的关联不同，表明亚基特异性类型的毒性和/或调节。未来的研究将评估这些发现的生物学、临床和公共卫生意义。 https://doi.org/10.1289/EHP12950。