Exposure to a Mixture of Arsenic Species and Growth Indicators in 6-12-Year-Old Children from the Cycles 2007-2020 Nhanes

Abstract

Background: Exposure to arsenic (As) and its metabolites can affect normal growth in children, but the combine effects at simultaneous low-level exposures, remain uncertain. Hence, this study aims to analyze how the combined effects of As  and its metabolites can impact growth indicators in 1,792 US children aged 6-12 years, from the NHANES.Methods: Levels of As species in urine were measured during the 2007-2020 cycles of NHANES. Sum of urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) was used as a biomarker of internal iAs exposure (∑As). As methylation efficiency was measured by primary and secondary methylation index (PMI, SMI). Linear regression and Bayesian Kernel Machine Regression (BKMR) models were used to identify adverse effect, nonlinear-associations, interactions, and combine effects.Results: Median concentrations of MMA, DMA, iAs, and ∑(As) were 0.56 μg/L, 4.07 μg/L, 1.33 μg/L, and 6.40 μg/L, respectively. In the linear regression analyses, DMA and ∑As were inversely associated with arm circumference, and DMA was inversely associated with height. Additionally, MMA was inversely associated with BMI, waist circumference, and weight. BKMR analyses showed strong linear associations of MMA with a reduction in arm circumference and BMI. Conversely, iAs concentrations were associated with an increase in arm circumference and BMI. Furthermore, ∑As was positively associated with BMI and arm circumference in the lower percentiles of the mixture. In the sex-stratified BKMR analyses, exposure to DMA, when the concentrations of other metabolites were low in the mixture, was positively associated with BMI, waist circumference, and weight in males. No statistically significant relationship between anthropometric measures and arsenic methylation efficiency was found.Conclusion: Childhood exposure to a mixture of inorganic arsenic species was negatively associated with growth indicators in children. Our findings suggest that even low levels of arsenic exposure can adversely affect physical development.

Keywords: Inorganic arsenic, children, BKMR, As methylation, mixture.