Prenatal exposure to a mixture of per- and polyfluoroalkyl substances (PFAS) and lung function and immune-related outcomes among males in childhood and young adulthood

By Sidsel Dan Hull, Kelly K Ferguson, Stephanie J London, Karin Sørig Hougaard, Christian Lindh, Kajsa Ugelvig Petersen, Esben Meulengracht Flachs, Lauren A Wise, Allen J Wilcox, Zeyan Liew, Cecilia Høst Ramlau-Hansen, Gunnar Toft, Jens Peter Bonde, and Sandra Søgaard Tøttenborg
Environ Res
September 2, 2025
DOI: 10.1016/j.envres.2025.122746

Background

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.

Objective

To examine associations between prenatal exposure to a mixture of PFAS and respiratory and immune-related outcomes in a cohort of males.

Methods

We studied 866 males with maternal pregnancy plasma measured for 15 PFAS, triclosan, and nine 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.

Results

A one-IQR increase in the PFAS mixture was associated with lower forced expiratory volume in one 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 mixture analyses.

Conclusion

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.

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