Urinary trace metals, maternal circulating angiogenic biomarkers, and preeclampsia: a single-contaminant and mixture-based approach.

Background: Exposures to toxic metals and deficiencies in essential metals disrupt placentation and may contribute to preeclampsia. However, effects of exposure to combinations of metals remain unknown.

Objective: We investigated the relationship between urinary trace metals, circulating angiogenic biomarkers, and preeclampsia using the LIFECODES birth cohort.

Methods: Urine samples collected during pregnancy were analyzed for 17 trace metals and plasma samples were analyzed for soluble fms-like tyrosine-1 (sFlt-1) and placental growth factor (PlGF). Cox proportional hazard models were used to estimate the hazard ratios (HR) of preeclampsia associated with urinary trace metals. Linear regression models were used to estimate the relationship between urinary trace metals and angiogenic biomarkers. Principal components analysis (PCA) was used to identify groups of metals and interactions between principal components (PCs) loaded by toxic and essential metals were examined.

Results: In single-contaminant models, several toxic and essential metals were associated with lower PlGF and higher sFlt-1/PlGF ratio. Detection of urinary chromium was associated with preeclampsia: HR (95% Confidence Interval [CI]) = 3.48 (1.02, 11.8) and an IQR-increase in urinary selenium was associated with reduced risk of preeclampsia (HR: 0.28, 95% CI: 0.08, 0.94). Using PCA, 3 PCs were identified, characterized by essential metals (PC1), toxic metals (PC2), and seafood-associated metals (PC3). PC1 and PC2 were associated with lower PlGF levels, but not preeclampsia risk in the overall cohort.

Conclusions: Trace urinary metals may be associated with adverse profiles of angiogenic biomarkers and preeclampsia.