在三项儿童健康结果环境影响（ECHO）队列研究中，产前母亲体内的全氟和多氟烷基物质与生物活性脂质之间的横断面关联。
Cross-sectional associations between prenatal maternal per- and poly-fluoroalkyl substances and bioactive lipids in three Environmental influences on Child Health Outcomes (ECHO) cohorts.
作者信息
Suthar Himal, Manea Tomás, Pak Dominic, Woodbury Megan, Eick Stephanie M, Cathey Amber, Watkins Deborah J, Strakovsky Rita S, Ryva Brad A, Pennathur Subramaniam, Zeng Lixia, Weller David, Park June-Soo, Smith Sabrina, DeMicco Erin, Padula Amy, Fry Rebecca C, Mukherjee Bhramar, Aguiar Andrea, Dee Geiger Sarah, Ng Shukhan, Huerta-Montanez Gredia, Vélez-Vega Carmen, Rosario Zaira, Cordero Jose F, Zimmerman Emily, Woodruff Tracey J, Morello-Frosch Rachel, Schantz Susan L, Meeker John D, Alshawabkeh Akram, Aung Max T
机构信息
Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
Department of Civil and Environmental Engineering, Northeastern University, Boston, MA, USA.
出版信息
medRxiv. 2023 Nov 7:2023.11.03.23297930. doi: 10.1101/2023.11.03.23297930.
BACKGROUND
Per- and poly-fluoroalkyl substances (PFAS) exposure can occur through ingestion of contaminated food and water, and inhalation of indoor air contaminated with these chemicals from consumer and industrial products. Prenatal PFAS exposures may confer risk for pregnancy-related outcomes such as hypertensive and metabolic disorders, preterm birth, and impaired fetal development through intermediate metabolic and inflammation pathways.
OBJECTIVE
Estimate associations between maternal pregnancy PFAS exposure (individually and as a mixture) and bioactive lipids.
METHODS
Our study included pregnant women in the Environmental influences on Child Health Outcomes Program: Chemicals in our Bodies cohort (CiOB, n=73), Illinois Kids Developmental Study (IKIDS, n=287), and the ECHO-PROTECT cohort (n=54). We measured twelve PFAS in serum and 50 plasma bioactive lipids (parent fatty acids and eicosanoids derived from cytochrome p450, lipoxygenase, and cyclooxygenase) during pregnancy (median 17 gestational weeks). Pairwise associations across cohorts were estimated using linear mixed models and meta-analysis. Associations between the PFAS mixture and individual bioactive lipids were estimated using quantile g-computation.
RESULTS
PFDeA, PFOA, and PFUdA were associated (<0.05) with changes in bioactive lipid levels in all three enzymatic pathways (cyclooxygenase [n=6 signatures]; cytochrome p450 [n=5 signatures]; lipoxygenase [n=7 signatures]) in at least one combined cohort analysis. The strongest signature indicated that a doubling in PFOA corresponded with a 24.3% increase (95% CI [7.3%, 43.9%]) in PGD2 (cyclooxygenase pathway) in the combined cohort. In the mixtures analysis, we observed nine positive signals across all pathways associated with the PFAS mixture. The strongest signature indicated that a quartile increase in the PFAS mixture was associated with a 34% increase in PGD2 (95% CI [8%, 66%]), with PFOS contributing most to the increase.
CONCLUSIONS
Bioactive lipids were revealed as biomarkers of PFAS exposure and could provide mechanistic insights into PFAS' influence on pregnancy outcomes, informing more precise risk estimation and prevention strategies.
背景
全氟和多氟烷基物质（PFAS）暴露可通过摄入受污染的食物和水，以及吸入受这些来自消费品和工业产品的化学物质污染的室内空气而发生。产前PFAS暴露可能通过中间代谢和炎症途径导致与妊娠相关的不良后果，如高血压和代谢紊乱、早产以及胎儿发育受损。
目的
评估孕妇孕期PFAS暴露（单独及混合暴露）与生物活性脂质之间的关联。
方法
我们的研究纳入了参与“环境对儿童健康结果的影响计划”的孕妇：“我们体内的化学物质”队列研究（CiOB，n = 73）、伊利诺伊州儿童发育研究（IKIDS，n = 287）以及ECHO - PROTECT队列研究（n = 54）。我们在孕期（妊娠周数中位数为17周）测量了血清中的12种PFAS以及50种血浆生物活性脂质（母体脂肪酸和源自细胞色素p450、脂氧合酶和环氧化酶的类花生酸）。使用线性混合模型和荟萃分析估计各队列之间的成对关联。使用分位数g计算估计PFAS混合物与个体生物活性脂质之间的关联。
结果
在至少一项合并队列分析中，全氟癸酸（PFDeA）、全氟辛酸（PFOA）和全氟十一烷酸（PFUdA）与所有三种酶促途径（环氧化酶[n = 6种特征]；细胞色素p450[n = 5种特征]；脂氧合酶[n = 7种特征]）中的生物活性脂质水平变化相关（P<0.05）。最强的特征表明，在合并队列中，PFOA浓度翻倍与前列腺素D2（PGD2，环氧化酶途径）增加24.3%（95%置信区间[7.3%，43.9%]）相对应。在混合物分析中，我们在与PFAS混合物相关的所有途径中观察到9个阳性信号。最强的特征表明，PFAS混合物四分位数增加与PGD2增加34%（95%置信区间[8%，66%]）相关，其中全氟辛烷磺酸（PFOS）对该增加的贡献最大。
结论
生物活性脂质被揭示为PFAS暴露的生物标志物，并可为PFAS对妊娠结局的影响提供机制性见解，从而为更精确的风险评估和预防策略提供依据。
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