Latent Childhood Exposure to Mixtures of Metals and Neurodevelopmental Outcomes in 4-5-Year-Old Children Living in Spain

Neurodevelopmental disorders are increasing globally, and metal exposure may play a significant role as an environmental factor. This cross-sectional study aimed to identify metal mixture patterns and assess their impact on children's neurodevelopment. Data from 962 children (aged 4-5 years) participating in the Spanish INMA cohort study were analysed. Urinary metal concentrations (cobalt (Co), copper (Cu), molybdenum (Mo), selenium (Se), lead (Pb), zinc (Zn), and arsenic speciation) were used as exposure biomarkers. Principal component analysis (PCA) revealed four latent exposure variables representing uncorrelated metal mixture patterns. Linear regression analyses examined the associations between these variables and children's neuropsychological functions assessed through the McCarthy Scales of Children's Abilities. The first latent exposure variable (Cu, Se, Pb, Zn) and the second (inorganic arsenic, monomethylarsonic acid) showed negative associations with verbal executive function (beta = - 1.88, 95% confidence interval (CI) = - 3.17 to - 0.59) and gross motor function (beta = - 1.41, 95% CI = - 2.36 to - 0.46), respectively. Conversely, the third variable (Mo, Co) and the fourth (arsenobetaine) exhibited positive associations with visual and verbal span functions (beta = 1.14, 95% CI = 0.16 to 2.12) and fine motor function (beta = 1.01, 95% CI = 0.11 to 1.92), respectively. This study suggests that even relatively low levels of metal latent exposures, notably inorganic arsenic and a mixture of metals including Pb, adversely affect children's neuropsychological development function scores, while exposure to arsenobetaine and a mixture of Co and Mo has a positive impact.