Association between prenatal exposure to metal mixtures and early childhood allergic diseases.

The association between prenatal exposure to the metal mixture and allergic diseases is poorly understood. We aimed to explore the individual effect and the combined effect of prenatal exposure to vanadium (V), chromium (Cr), nickel (Ni), arsenic (As), cadmium (Cd), thallium (Tl), and lead (Pb) on early childhood allergic diseases based on a birth cohort study that included 628 mother-infant pairs. Metals were measured in maternal urine samples collected in the first, second, and third trimesters. Children were prospectively followed up at age 4 years to collect information on allergic rhinitis, wheeze, and eczema status. By applying logistic regression models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR), the different statistical analyses revealed urinary metals were only associated with early childhood allergic rhinitis. The averaged prenatal As exposure was significantly associated with an increased OR for allergic rhinitis in both single-metal (OR = 2.04, 95% CI: 1.35, 3.07) and multiple-metal logistic regression models (OR = 1.78, 95% CI: 1.15, 2.78). The WQS index of mixed metal exposure was positively associated with allergic rhinitis (OR = 1.66, 95% CI: 1.26, 2.19), and As and Tl had the largest weights in the WQS index (weighted 0.51 and 0.29, respectively). The BKMR analysis also showed the overall effect of the metal mixture was significantly associated with allergic rhinitis when all the metals were at their 55th percentile or above, compared to their 50th percentile. The effect of As and Tl on the risk of allergic rhinitis was significant when all of the other metals were fixed at the specific percentiles. Our findings suggest that prenatal co-exposure to higher levels of the seven metals increases the risk of allergic rhinitis in children, and As and Tl may contribute most to the combined risk.