Urinary Trace Metals Individually and in Mixtures in Association with Preterm Birth

Abstract

Preterm birth (PTB), birth <37 weeks gestation, affects 1 in 10 births in the United States. Though some risk factors have been identified, most causes remain unknown. Exposure to high levels of metals has been linked to higher risk of PTB, but consequences of lower levels of exposure, less studied metals, and combinations of these factors are unclear. In collaboration with the Children’s Health Exposure Analysis Resource, we examined the association between 17 urinary trace metals and PTB. The LIFECODES birth cohort enrolled pregnant women at <15 weeks gestation at Brigham and Women’s Hospital in Boston. Women participated in 4 study visits. We selected cases of PTB (n=99) and unmatched controls (n=291) and analyzed urine samples from visit 3 (median: 26 weeks) using mass spectrometry. We used logistic regression models to calculate odds ratios (OR) for PTB, controlling for maternal age, race, education, pre-pregnancy body mass index (BMI), specific gravity, and gestational age at time of urine collection. We used elastic net (ENET) regularization methods to determine which metals were driving the association with PTB and whether there were any meaningful interactions between exposures. We observed increased odds of PTB (OR: 1.88, 95% CI: 1.24, 2.86) associated with an interquartile range difference of copper (Cu). We also observed an elevated OR for selenium (OR: 1.92, 95% CI 0.95, 3.87). In addition, we observed small differences in associations with individual metals by presentation of PTB. The ENET methods selected Cu as the primary driver in the association with PTB. ENET also selected interactions between Cu and several other metals, including cadmium, molybdenum, selenium, and zinc. Our results suggested that Cu concentration in mothers at the 3rd trimester was associated with increased risk of PTB, despite Cu being an essential nutrient.