Non-essential and essential trace element mixtures and kidney function in early pregnancy - A cross-sectional analysis in project viva

Abstract

Some trace elements are established nephrotoxicants, yet their associations with kidney function remain understudied in the context of pregnancy, a time of substantial change in kidney physiology and function. We aimed to estimate the individual and joint associations of trace element mixtures with maternal kidney function during the 1st trimester of pregnancy (mean 9.7 gestational weeks). 1040 women from Project Viva contributed blood samples which were assessed for erythrocyte non-essential [arsenic (As), cadmium (Cd), cesium (Cs), mercury (Hg), lead (Pb)] and essential [barium (Ba), magnesium (Mg), manganese (Mn), selenium (Se), and Zinc (Zn)] trace elements, and plasma creatinine for kidney function. We estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration (eGFR_CKD-EPI) equation without race-adjustment factors. We examined associations of eGFR_CKD-EPI with individual trace elements using multivariable linear regression and their mixtures using quantile-based g-computation, adjusting for sociodemographics, pregnancy characteristics, and diet. Participants in our study were predominantly White (75%), college graduates (72%), and had household income >$70,000/year (63%). After adjusting for covariates, higher Pb (β -3.51 ml/min/1.73 m²; 95% CI -5.83, -1.18) concentrations were associated with lower eGFR_CKD-EPI, while higher Mg (β 10.53 ml/min/1.73 m²; 95% CI 5.35, 15.71), Se (β 5.56 ml/min/1.73 m²; 95% CI 0.82, 10.31), and Zn (β 5.88 ml/min/1.73 m²; 95% CI 0.51, 11.26) concentrations were associated with higher eGFR_CKD-EPI. In mixture analyses, higher non-essential trace elements mixture concentration was associated with reduced eGFR_CKD-EPI (Ψ -1.03 ml/min/1.73 m²; 95% CI: 1.92, -0.14). Conversely, higher essential trace elements mixture concentration was associated with higher eGFR (Ψ 1.42; 95% CI: 0.48, 2.37). Exposure to trace elements in early pregnancy may influence women's kidney function although reverse causation cannot be eliminated in this cross-sectional analysis. These findings have important implications for long-term cardiovascular and postpartum kidney health that warrant additional studies.

Keywords: Kidney function; Pregnancy; Trace elements; eGFR.

Figure 1.

Spearman correlations of first trimester erythrocyte trace element concentrations among Project Viva mothers (N=1040)

Figure 2.

Associations of log₂ transformed 1^st trimester trace elements with 1^st trimester eGFR_CKD-EPI. All associations were adjusted for maternal age, pre-pregnancy BMI, race/ethnicity, education level, household income, parity, pregnancy smoking status, hematocrit level, gestational age at blood draw, and DASH score.