Sex-specific associations of a ferroalloy metal mixture with motor function in Italian adolescents

Background:Motor function is critical for children's health, yet remains an understudied neurodevelopmental domain. Exposure to metals has been linked with motor function, but no study has examined the joint effects of metal mixtures.Methods:We evaluated cross-sectional associations between a metal mixture and motor function among 569 adolescents (10-14 years old) living near the ferroalloy industry. Concentrations of blood lead, hair manganese, hair copper, and hair chromium were quantified using inductively coupled plasma mass spectrometry. Neuropsychologists administered multiple fine motor function assessments: pursuit aiming, finger tapping, visual reaction time (VRT), and subtests from the Luria Nebraska battery. We estimated associations between motor function and the metal mixture using quantile-based g-computation and multivariable linear regression, adjusting for child age, sex, and socioeconomic status. We explored sex-specific associations in stratified models.Results:Associations between the metal mixture and motor function were mostly null but were modified by sex. We observed a beneficial association among females: a quartile increase in all metals in the mixture was associated with a 2.6% faster average response time on the VRT (95% confidence interval [CI] = -4.7%, -0.5%), driven by Cu and Cr. In contrast, this association was adverse among males (ss = 1.5% slower response time [95% CI = -0.7%, 3.9%]), driven by Cu and Mn.Conclusions:Results suggest that males may be more susceptible to the adverse effects of metal exposure on motor function during adolescence than females. Future studies, particularly prospective study designs, are warranted to further understand the associations of metal mixtures with motor function.