Per- and polyfluoroalkyl substances exposure is associated with sleep problems in children: Multi-omics evidence

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants that may pose health risks to children. Sleep is essential for children's physical, cognitive, and behavioral development, yet the environmental determinants of sleep problems remain poorly understood. Despite widespread PFAS exposure, evidence regarding their association with sleep disorders and the underlying mechanisms remains limited. This study aimed to investigate the association between PFAS mixture exposure and sleep disorders in children and to identify PFAS-associated molecular signatures and potential biological pathways through integrated proteomic and lipidomic analyses. A total of 135 children were included, and a quartile-based scoring approach was used to construct a PFAS mixture index. Multivariable linear regression was performed to evaluate associations between PFAS exposure and sleep disorders, with the total score of the Children's Sleep Habits Questionnaire (CSHQ) as the primary outcome. Serum PFAS concentrations were measured using liquid chromatography-mass spectrometry, and proteomic and lipidomic profiling were conducted using ultra-high-performance liquid chromatography coupled with mass spectrometry. Higher PFAS exposure was associated with increased CSHQ scores (β = 0.243, 95%CI: 0.012, 0.474, P = 0.040). Multi-omics analysis identified 270 PFAS-associated proteins and 139 PFAS-associated lipids (P < 0.05). The Antigen processing and presentation pathways emerged as a potential mediator, while sphingolipid metabolism was significantly enriched among the PFAS-associated lipids. These findings suggest that PFAS exposure is associated with sleep disorders in children and may be linked to alterations in immune-related pathways and lipid metabolism, offering preliminary insights into the potential biological pathways underlying this association.