Jones Laura E, Ghassabian Akhgar, Yeung Edwina, Mendola Pauline, Kannan Kurunthachalam, Bell Erin M
Center for Biostatistics, Bassett Research Institute, 1 Atwell Rd. Cooperstown NY USA.
Department of Pediatrics, New York University Grossman School of Medicine NY USA; Department of Population Health, New York University Grossman School of Medicine NY USA.
Environ Int. 2025 Feb;196:109288. doi: 10.1016/j.envint.2025.109288. Epub 2025 Jan 16.
There is growing concern that exposure to per/polyfluoroalkyl substances (PFAS), persistent chemicals used widely to make consumer products water- or grease-proof, may alter immune function, leading to reduced vaccine response or greater susceptibility to infections. We investigated associations between two legacy PFAS (PFOA and PFOS) and infant cytokine levels measured in newborn dried bloodspots (NDBS) from a large population-based birth cohort in Upstate New York, to determine whether exposure to legacy PFAS is associated with variability in cytokine profiles in newborns. We performed adjusted mixed effects regressions for each cytokine against PFOS and PFOA followed by exploratory factor analysis (EFA) on specific cytokine subsets selected via the prior regressions. Among 3448 neonates (2280 singletons and 1168 twins), significant cytokines were dominated by cytokines negatively associated with the given PFAS. Adjusted single-pollutant models with continuous log-transformed PFOA showed significant negative associations with IL-16 (-0.07, 95% CI: -0.3, -0.1), IL-5 (-0.05, 95%CI: -0.09, -0.02), IL-6 (-0.06, 95%CI: -0.1, -0.02), 6-Ckine (0.06, 95% CI: -0.10, -0.02) and significant positive associations with IL-1α (0.066, 95%CI: 0.03, 0.11), MCP-1 (0.06, 95%CI: 0.03, 0.10). Estimates for PFOS were slightly larger than estimates for PFOA but only significant for 6-Ckine (-0.21, 95%CI: -0.09, -0.33) after correction for multiplicity. Our data consistently suggest that legacy PFAS exposures are associated with disrupted, typically reduced, cytokine levels in neonates, with PFOA exposure resulting in more significant differences in individual cytokines and cytokine groupings than PFOS. Regression by PFAS quartile shows evidence of nonlinear dose-response relationships for most cytokines and cytokine groupings.
全氟/多氟烷基物质（PFAS）是一类广泛用于使消费品具有防水或防油性能的持久性化学物质。人们越来越担心接触PFAS可能会改变免疫功能，导致疫苗反应降低或更易感染。我们调查了纽约州北部一个大型人群出生队列中，两种遗留PFAS（全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS））与新生儿干血斑（NDBS）中测量的婴儿细胞因子水平之间的关联，以确定接触遗留PFAS是否与新生儿细胞因子谱的变异性有关。我们针对每种细胞因子对PFOS和PFOA进行了调整后的混合效应回归，然后对通过先前回归选择的特定细胞因子子集进行探索性因子分析（EFA）。在3448名新生儿（2280名单胎和1168名双胞胎）中，显著的细胞因子主要是与给定PFAS呈负相关的细胞因子。采用连续对数转换的PFOA的调整单污染物模型显示，与白细胞介素-16（IL-16）（-0.07，95%置信区间：-0.3，-0.1）、IL-5（-0.05，95%置信区间：-0.09，-0.02）、IL-6（-0.06，95%置信区间：-0.1，-0.02）、6-Ckine（0.06，95%置信区间：-0.10，-0.02）呈显著负相关，与IL-1α（0.066，95%置信区间：0.03，0.11）、单核细胞趋化蛋白-1（MCP-1）（0.06，95%置信区间：0.03，0.10）呈显著正相关。PFOS的估计值略大于PFOA的估计值，但在进行多重校正后，仅对6-Ckine（-0.21，95%置信区间：-0.09，-0.33）具有显著性。我们的数据一致表明，遗留PFAS暴露与新生儿细胞因子水平的紊乱（通常降低）有关，与PFOS相比，PFOA暴露导致个体细胞因子和细胞因子分组的差异更显著。按PFAS四分位数进行的回归显示，大多数细胞因子和细胞因子分组存在非线性剂量反应关系。
