Pattern-based environmental antibiotic exposure associated with elevated cardiovascular risk and lipidomic disruption in children: a dual-center study.

Abstract

Childhood exposure to environmental antibiotics, particularly those related to veterinary use, may contribute to health risks, but evidence on the association between mixture patterns and childhood cardiovascular risk and underlying pathways remains limited. We aimed to identify reproducible urinary antibiotic exposure patterns in children, evaluate their associations with cardiovascular phenotypes, and explore potential lipidomic pathways. We analyzed data from two cohorts, the CBPEFC cohort (n = 584) and the 4C cohort (baseline, n = 686). Twenty-four urinary antibiotics were quantified by HPLC-MS/MS. Exposure patterns were derived using an integrated unsupervised clustering framework. Associations were assessed using generalized estimating equations (GEEs) and generalized linear models. Lipidomics was conducted in a small longitudinal subset and analyzed using multilevel PLS-DA, GEEs, LION enrichment, and mediation analysis. Two reproducible exposure patterns were identified: an azithromycin-high peak (AHP, 23.3-25.7%) and a ciprofloxacin-high peak (CHP, 74.3-76.7%). Compared with AHP, the CHP pattern was associated with higher SBP Z-score (β = 0.145, 95% CI: 0.074 to 0.216), DBP Z-score (β = 0.126, 95% CI: 0.025 to 0.228), and elevated blood pressure (EBP, OR = 1.512, 95% CI: 1.009 to 2.266). The CHP pattern was also associated with higher end-systolic volume (β = 0.998, 95% CI: 0.085 to 1.911). Lipid dysregulation in the CHP group involved enrichment on glycerolipids, lipid droplets and lipid storage pathways, which were also implicated among blood pressure-associated lipids. Several glycerophospholipids showed evidence of potential indirect association though these did not remain statistically significant after multiple corrections. These findings suggest that the ciprofloxacin dominant pattern may represent a more adverse environmental exposure signature associated with cardiovascular health in children.