Hull Sidsel Dan, Ferguson Kelly K, London Stephanie J, Hougaard Karin Sørig, Lindh Christian, Petersen Kajsa Ugelvig, Flachs Esben Meulengracht, Wise Lauren A, Wilcox Allen J, Liew Zeyan, Ramlau-Hansen Cecilia Høst, Toft Gunnar, Bonde Jens Peter, Tøttenborg Sandra Søgaard
Department of Occupational and Environmental Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Denmark.
Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, USA.
Environ Res. 2025 Sep 2;286(Pt 1):122746. doi: 10.1016/j.envres.2025.122746.
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may influence lung and immune system development, but previous epidemiological studies are inconclusive and have not extended into young adulthood.
To examine associations between prenatal exposure to a mixture of PFAS and respiratory and immune-related outcomes in a cohort of males.
We studied 866 males with maternal pregnancy plasma measured for 15 PFAS, triclosan, and 10 phthalate metabolites used as a proxy for prenatal exposure. Spirometry was measured at approximately age 19 years. Asthma in young adulthood was reported in questionnaires at age 18 years. Asthma, hay fever, and eczema at 7 and 11 years of age were based on parental reports. We estimated the difference in spirometry measures and odds ratios (ORs) for questionnaire outcomes per one-interquartile range (IQR) increase in a mixture of seven well-detected PFAS using quantile g-computation models. Subsequently, we examined a mixture of seven PFAS, two phthalate metabolites and triclosan, and ran single-pollutant analyses.
A one-IQR increase in the PFAS mixture was associated with lower forced expiratory volume in 1 second (FEV) and forced vital capacity (FVC) (milliliter difference [95 % CI]: 85 [-160;-9], -88 [-173;-3], respectively), but not FEV/FVC. Higher concentration of the PFAS mixture was also associated with lower odds of a history of and current hay fever (OR [95 % CI]: 0.52 [0.34; 0.80], 0.49 [0.30; 0.81], respectively), but not asthma or eczema. Associations did not change substantially when including phthalate metabolites and triclosan to the PFAS mixture and single-pollutant analyses were overall consistent with the mixture analyses.
Prenatal PFAS exposure was associated with lower FEV and FVC in a cohort of young adult males, suggesting an impact on lung development. Associations with reduced hay fever in childhood may suggest influences on immune maturation. Potential sex-specific effects should be addressed in future studies.
孕期暴露于全氟和多氟烷基物质（PFAS）可能会影响肺部和免疫系统发育，但先前的流行病学研究尚无定论，且未延伸至青年期。
研究男性队列中孕期暴露于PFAS混合物与呼吸及免疫相关结局之间的关联。
我们对866名男性进行了研究，测量其母亲孕期血浆中的15种PFAS、三氯生以及10种邻苯二甲酸酯代谢物，以此作为孕期暴露的替代指标。在约19岁时进行肺活量测定。18岁时通过问卷报告青年期哮喘情况。7岁和11岁时的哮喘、花粉症和湿疹情况基于父母报告。我们使用分位数g计算模型，估计七种检测良好的PFAS混合物每增加一个四分位数间距（IQR），肺活量测定指标的差异以及问卷结局的比值比（OR）。随后，我们研究了七种PFAS、两种邻苯二甲酸酯代谢物和三氯生的混合物，并进行了单污染物分析。
PFAS混合物每增加一个IQR，与1秒用力呼气量（FEV）和用力肺活量（FVC）降低相关（毫升差异[95%CI]：分别为85[-160;-9]，-88[-173;-3]），但与FEV/FVC无关。PFAS混合物浓度较高还与既往和当前花粉症的较低几率相关（OR[95%CI]：分别为0.52[0.34;0.80]，0.49[0.30;0.81]），但与哮喘或湿疹无关。当将邻苯二甲酸酯代谢物和三氯生纳入PFAS混合物时，关联无实质性变化，单污染物分析总体上与混合物分析一致。
在青年男性队列中，孕期PFAS暴露与较低的FEV和FVC相关，提示对肺部发育有影响。与儿童期花粉症减少的关联可能提示对免疫成熟有影响。未来研究应探讨潜在的性别特异性影响。
