Urinary bisphenol A analogues and metabolically unhealthy obesity in school-age children

Childhood obesity manifests metabolic heterogeneity, and differentiating metabolically unhealthy obesity (MUO) from metabolically healthy obesity (MHO) provides a refined framework for early cardiometabolic risk stratification than obesity status alone. However, the effects of multiple bisphenol A (BPA) analogues exposure on MUO in obese children remained understudied. This study investigated the associations between multiple urinary BPA analogues and metabolic obesity phenotypes in 290 obese Chinese children aged 6-7 years. Individual analogue associations were evaluated using logistic regression, while joint exposure effects were characterized using weighted quantile sum regression (WQS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR). Urinary trace elements underwent principal components reduction and were incorporated into sensitivity analyses to address co-exposure confounding. Continuous metabolic phenotypes and selected pairwise interaction patterns were additionally examined as complementary analyses. In single-pollutant models, BPAF was identified as the most consistent positive association signal for MUO, maintaining directional stability following batch adjustment and trace-element principal component correction. Although the mixture models did not demonstrate a robust overall joint effect, component-weight and contribution analyses consistently highlighted BPAF as a leading positive contributor, with several analogues exhibiting weaker or antagonistic effects. Phenome-wide analyses showed modest, exploratory signals mainly for blood pressure- and adiposity-related traits. Overall, these findings establish BPAF as a higher-priority candidate exposure for pediatric metabolic dysfunction and indicate that BPA analogue co-exposure manifests through heterogeneous component-specific contributions rather than uniform cumulative effects.