Associations between Serum Metal Mixtures and Systemic Inflammation Indices Among Chinese Early Adolescents: A Prospective Cohort Study

Abstract

Research has demonstrated a link between metal exposure and inflammation. However, little is known about this relationship among adolescents, especially in prospective cohort studies. The aim of this study was to investigate the relationship between serum metal exposure and inflammatory status in Chinese early adolescents. In this study, 12 serum metals were detected at baseline in 1,551 participants from the Chinese Early Adolescents Cohort. The participants' inflammatory status was assessed via three systemic inflammation indices (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)) at both baseline and follow-up. Generalized linear mixed models and restricted cubic splines regression were used to examine the linear and nonlinear relationships between single metal concentrations and systemic inflammation indices. Multiple mixture models were implemented to assess the relationships of mixed metals with systemic inflammation indices. Additionally, sex subgroup analyses were conducted to explore the sex-specific associations between serum metals and inflammatory status. Single-exposure analysis revealed that exposure to multiple serum metals, such as chromium, cobalt, copper and lead, was positively associated with the NLR and SII, whereas iron was negatively correlated with the three systemic inflammation indices (PFDR<0.05). Additionally, inverted U-shaped associations were observed between vanadium, manganese and systemic inflammation indices. In the mixture models, high levels of the serum metal mixture were positively correlated with NLR and SII levels. Cobalt had the highest positive weight in the mixed samples, whereas iron had the greatest negative weight in the serum-metal mixtures. Subgroup analyses revealed that serum exposure to the metal mixture had a more significant effect on systemic inflammation markers in females than in males. This study reveals the impact of real-world mixed metal exposure on adolescents’ inflammatory levels, which is of primary significance for protecting the healthy development of early adolescents.

Keywords: Metal mixtures, Systemic inflammation indices, Iron, Cobalt, Combined effect, Early adolescents