Prenatal Metal Mixtures and Birth Weight for Gestational Age in A Lower Income Predominately Hispanic Pregnancy Cohort

Abstract

Background/Aim: Reduced fetal growth increases risk for adverse health outcomes. Growing evidence indicates that metal exposures contribute to reduced fetal growth, but little is known about the impacts of complex metal mixtures. The objective of this study was to investigate the impact of prenatal exposure to a complex mixture of metals on birth weight for gestational age (BW for GA) in the MADRES study, a predominately lower income Hispanic pregnancy cohort in Los Angeles, California. Methods: Cadmium, cobalt, mercury, nickel, lead, and thallium were measured by ICP-MS in urine samples collected in early pregnancy (median: 13.1 weeks gestation). Speciated urinary arsenic (inorganic+monomethyl+dimethyl) was measured by HPLC coupled to ICP-MS. The impact of these seven elements on BW for GA z-scores was evaluated using covariate-adjusted Bayesian Kernel Machine Regression (N=262). A novel method (Bayesian semiparametric regression and sparsity inducing priors) was also used to formally investigate pairwise interactions between elements.Results: Among the seven elements evaluated, mercury and nickel ranked most highly in importance for predicting BW for GA. Setting other metals to their median, an interquartile increase in mercury was associated with a -0.021 (95% CI: -0.027, -0.015) standard deviation difference in BW for GA. A non-linear association was observed for nickel, where a positive association was seen at low-to-moderate, but not high levels of this element. There was also evidence of an interaction between mercury and nickel, such that the positive association between nickel and BW for GA was attenuated in a dose-dependent manner at higher levels of mercury. This interaction was confirmed using Bayesian semiparametric regression and sparsity inducing priors.Conclusions: In a mostly lower income Hispanic pregnancy cohort in Los Angeles, we identified a possible antagonism between mercury and nickel, which suggests that at low-to-moderate levels nickel may promote fetal growth while mercury may counteract this effect.