Effects of co-exposure to multiple metals on children's behavior problems in China

Exposure to single metals have been linked to childhood behavior problems, But little is known about the effects of metals mixtures on children. We aimed to evaluate associations of multiple metals exposures in urine with childhood behavior in China. For this population-based study, the children eligible for inclusion provided urine samples and their parents agreed to take in-person interview. A total of 831 children were remained from three cities for the final analysis. Urinary metals concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). The childhood behavior scores was calculated by the Conners' Parent Rating Scale (CPRS). Variable selection was achieved by the least absolute shrinkage and selection operator (LASSO) regularization and stepwise regression to for all metals in the study. Linear regression models and Bayesian kernel machine regression (BKMR) were applied to estimate the associations of urinary metals concentrations with children's behavior. In BKMR models, the overall effect of mixture was significantly associated with conduct problems, learning problems and hyperactive index when urinary metals concentrations were all above the 50th percentile compared to all of them at their medians. The models also suggested marginally significant interaction effects of Se and Fe as well as Se and Sb (P_Se∗Fe = 0.063; P_Se∗Sb = 0.061), with a decline in estimate of Se on learning problems when Sb/Fe levels were relatively high. The concentrations of 22 metals in boys were higher than girls. In summary, multiple metals are associated with an increased risk of childhood behavioral problems in China. Potential interaction effects of Se and Fe as well as Se and Sb on childhood behavior should be taken into consideration.