Exposure to metal mixture and growth indicators at 4-5 years. A study in the INMA-Asturias cohort

Background: Exposure to toxic and non-toxic metals impacts childhood growth and development, but limited data exists on exposure to metal mixtures. Here, we investigated the effects of exposure to individual metals and a mixture of barium, cadmium, cobalt, lead, molybdenum, zinc, and arsenic on growth indicators in children 4-5 years of age. Methods: We used urine metal concentrations as biomarkers of exposure in 328 children enrolled in the Spanish INMA-Asturias cohort. Anthropometric measurements (arm, head, and waist circumferences, standing height, and body mass index) and parental sociodemographic variables were collected through face-to-face interviews by trained study staff. Linear regressions were used to estimate the independent effects and were adjusted for each metal in the mixture. We applied Bayesian kernel machine regression to examine non-linear associations and potential interactions. Results: In linear regression, urinary levels of cadmium were associated with reduced arm circumference (beta adjusted = -0.44, 95% confidence interval [CI]: -0.73, -0.15), waist circumference (beta adjusted = -1.29, 95% CI: -2.10, -0.48), and standing height (beta adjusted = -1.09, 95% CI: -1.82, -0.35). Lead and cobalt concentrations were associated with reduced standing height (beta adjusted = -0.64, 95% CI: -1.20, -0.07) and smaller head circumference (beta adjusted = -0.29, 95% CI: -0.49, -0.09), respectively. However, molybdenum was positively associated with head circumference (beta adjusted = 0.22, 95% CI: 0.01, 0.43). BKMR analyses showed strong linear negative associations of cadmium with arm and head circumference and standing height. BKMR analyses also found lead and cobalt in the metal mixture were related to reduce standing height and head circumference, and consistently found molybdenum was related to increased head circumference. Conclusion: Our findings suggest that exposure to metal mixtures impacts growth indicators in children.