内分沁激素对全氟和多氟烷基物质暴露与出生体重之间关联的中介作用：来自射阳母婴队列研究的结果。
Mediating effect of endocrine hormones on association between per- and polyfluoroalkyl substances exposure and birth size: Findings from sheyang mini birth cohort study.
机构信息
School of Public Health/ MOE Key Laboratory of Public Health Safety/ NHC Key Lab of Health Technology Assessment, Fudan University, No.130 Dong'an Road, Shanghai, 200032, China.
School of Public Health/ MOE Key Laboratory of Public Health Safety/ NHC Key Lab of Health Technology Assessment, Fudan University, No.130 Dong'an Road, Shanghai, 200032, China.
出版信息
Environ Res. 2023 Jun 1;226:115658. doi: 10.1016/j.envres.2023.115658. Epub 2023 Mar 8.
BACKGROUND
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to affect fetus growth, but current results were inconsistent and their mechanism remained unclear.
OBJECTIVES
We aimed to evaluate the associations of prenatal exposure to single and/or multiple PFAS with birth size and to elucidate whether thyroid hormones and reproductive hormones mediate these associations.
METHODS
A total of 1087 mother-newborn pairs from Sheyang Mini Birth Cohort Study were included in the present cross-sectional analysis. 12 PFAS, 5 thyroid hormones and 2 reproductive hormones were measured in cord serum. Multiple linear regression models and Bayesian kernel machine regression (BKMR) models were used to examine the associations of PFAS with either birth size or endocrine hormones. One-at-a-time pairwise mediating effect analysis was applied to estimate the mediating effect of single hormone in the association between individual chemical and birth size. High-dimensional mediation approach including elastic net regularization and Bayesian shrinkage estimation were further performed to reduce exposure dimension and figure out the global mediation effects of joint endocrine hormones.
RESULTS
Perfluorononanoic acid (PFNA) exposure was positively associated to weight for length z score [WLZ, per log10-unit: regression coefficient (β) = 0.26, 95% confidence intervals (CI): 0.04, 0.47] and ponderal index (PI, β = 0.56, 95% CI: 0.09, 1.02), and PFAS mixture results fit by BKMR model showed consistent consequences. High-dimensional mediating analyses revealed that thyroid stimulating hormone (TSH) explained 6.7% of the positive association between PFAS mixtures exposure and PI [Total effect (TE) = 1.499 (0.565, 2.405); Indirect effect (IE) = 0.105 (0.015, 0.231)]. Besides, 7.3% of the PI variance was indirectly explained by 7 endocrine hormones jointly [TE = 0.810 (0.802, 0.819); IE = 0.040 (0.038, 0.041)].
CONCLUSIONS
Prenatal PFAS mixtures exposure, especially PFNA, was positively associated to birth size. Such associations were partly mediated by cord serum TSH.
背景
已有研究报道，围孕期多氟和全氟烷基物质（PFAS）暴露会影响胎儿生长，但目前的结果并不一致，其作用机制尚不清楚。
目的
本研究旨在评估孕期单一和/或多种 PFAS 暴露与出生体重的关系，并阐明甲状腺激素和生殖激素是否介导了这些关联。
方法
本研究纳入射阳母婴队列研究中的 1087 对母婴。采用液相色谱-串联质谱法检测脐带血清中 12 种 PFAS、5 种甲状腺激素和 2 种生殖激素。采用多元线性回归模型和贝叶斯核机器回归（BKMR）模型评估 PFAS 与出生体重或内分泌激素之间的关系。采用逐步单因素中介效应分析方法估计单个激素在个体化学物质与出生体重之间关联中的中介效应。进一步采用高维中介分析方法，包括弹性网络正则化和贝叶斯收缩估计，以减少暴露维度并确定联合内分泌激素的全局中介效应。
结果
全氟壬酸（PFNA）暴露与体重长度 Z 评分（WLZ）呈正相关[每 log10 单位的回归系数（β）= 0.26，95%置信区间（CI）：0.04，0.47]和体质量指数（PI，β= 0.56，95% CI：0.09，1.02），且 BKMR 模型拟合的 PFAS 混合物结果显示出一致的结果。高维中介分析显示，促甲状腺激素（TSH）解释了 PFAS 混合物暴露与 PI 之间正相关的 6.7%[总效应（TE）= 1.499（0.565，2.405）；间接效应（IE）= 0.105（0.015，0.231）]。此外，7 种内分泌激素联合解释了 PI 变异的 7.3%[TE = 0.810（0.802，0.819）；IE = 0.040（0.038，0.041）]。
结论
围孕期 PFAS 混合物暴露，尤其是 PFNA，与出生体重呈正相关。这种关联部分是由脐带血清 TSH 介导的。
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