Urinary Trace Metals Research Articles

Semiparametric analysis of a generalized linear model withmultiple covariates subject to detection limits.

Studies on the health effects of environmental mixtures face the challenge of limit of detection (LOD) in multiple correlated exposure measurements. Conventional approaches to deal with covariates subject to LOD, including complete-case analysis, substitution methods, and parametric modeling of covariate distribution, are feasible but may result in efficiency loss or bias. With a single covariate subject to LOD, a flexible semiparametric accelerated failure time (AFT) model to accommodate censored measurements has been proposed. We generalize this approach by considering a multivariate AFT model for the multiple correlated covariates subject to LOD and a generalized linear model for the outcome. A two-stage procedure based on semiparametric pseudo-likelihood is proposed for estimating the effects of these covariates on health outcome. Consistency and asymptotic normality of the estimators are derived for an arbitrary fixed dimension of covariates. Simulations studies demonstrate good large sample performance of the proposed methods vs conventional methods in realistic scenarios. We illustrate the practical utility of the proposed method with the LIFECODES birth cohort data, where we compare our approach to existing approaches in an analysis of multiple urinary trace metals in association with oxidative stress in pregnant women.

Trend analysis of the association of urinary metals and obesity in children and adolescents

Based on data from the United States National Health and Nutrition Examination Survey (NHANES), this study investigated whether the association between urinary trace metals and obesity changes with age. A multinomial logistic regression was used to explore the association between metals and obesity. We built models based on rolling window data with a seven-year time interval to investigate the trend of odd ratios (ORs) in metals. Finally, an application was built to show the trend of the ORs of metals with age. We found that obesity was positively associated with barium but negatively associated with cobalt, cadmium, and lead among children and adolescents. The trend analysis shows that different metals have different trends. Both barium and cobalt showed an age-related trend, and the younger the age, the greater the effect; the former and the latter were positively and negatively correlated with obesity, respectively. Lead showed no trend. The length of the confidence interval of barium's ORs decreased with age, whereas the confidence interval lengths for cobalt's OR values did not show significant changes across age groups. Our results indicate that: 1. The body mass index (BMI) of younger children is more susceptible to certain metals. 2. Barium's effect on young children is highly volatile. 3. The effects of cobalt on children of different ages are less volatile.

Urinary Trace Elements Are Biomarkers for Early Detection of Acute Kidney Injury

IntroductionAcute kidney injury (AKI) is common in hospitalized patients and associated with poor outcomes. Current methods for identifying AKI (rise in serum creatinine [sCr] or fall in urine output [UO]) are inadequate and delay detection. Early detection of AKI with easily measurable biomarkers might improve outcomes by facilitating early implementation of AKI care pathways.MethodsFrom a porcine model of AKI, we identified trace elements (TEs) in urine that were associated with subsequent development of AKI. We tested these putative biomarkers in 2 observational cohort studies of patients at high risk of AKI: 151 patients undergoing cardiac surgery and 150 patients admitted to a general adult intensive care unit (ICU).ResultsIn adults admitted to the ICU, urinary cadmium (Cd) (adjusted for urinary creatinine) had area under the receiver operating characteristic curve (AUROC) 0.70 and negative predictive value (NPV) 89%; copper (Cu) had AUROC 0.76 and NPV 91%. In humans (but not pigs), urinary zinc (Zn) was also associated with AKI and, in the ICU study, had AUROC 0.67 and NPV 80%. In patients undergoing cardiac surgery, Zn had AUROC 0.77 and NPV 91%; urinary Cd and Cu had poor AUROC but NPV of 93% and 95%, respectively. In control studies, we found that the urinary biomarkers are stable at room temperature for at least 14 days and are not affected by other confounding factors, such as chronic kidney disease (CKD).ConclusionUrinary Cd, Cu, and Zn are novel biomarkers for early detection of AKI. Urinary trace metals have advantages over proteins as AKI biomarkers because they are stable at room temperature and have potential for cheap point-of-care testing using electrochemistry.

Respiratory Health and Urinary Trace Metals among Artisanal Stone-Crushers: A Cross-Sectional Study in Lubumbashi, DR Congo.

Background: Thousands of artisanal workers are exposed to mineral dusts from various origins in the African Copperbelt. We determined the prevalence of respiratory symptoms, pulmonary function, and urinary metals among artisanal stone-crushers in Lubumbashi. Methods: We conducted a cross-sectional study of 48 male artisanal stone-crushers and 50 male taxi-drivers using a standardized questionnaire and spirometry. Concentrations of trace metals were measured by Inductively Coupled - Plasma Mass Spectrometry (ICP-MS) in urine spot samples. Results: Urinary Co, Ni, As, and Se were higher in stone-crushers than in control participants. Wheezing was more prevalent (p = 0.021) among stone-crushers (23%) than among taxi-drivers (6%). In multiple logistic regression analysis, the job of a stone-crusher was associated to wheezing (adjusted Odds Ratio 4.45, 95% Confidence Interval 1.09–18.24). Stone-crushers had higher values (% predicted) than taxi-drivers for Forced Vital Capacity (105.4 ± 15.9 vs. 92.2 ± 17.8, p = 0.048), Forced Expiratory Volume in 1 Second (104.4 ± 13.7 vs. 88.0 ± 19.6, p = 0.052), and Maximum Expiratory Flow at 25% of the Forced Vital Capacity (79.0.1 ± 20.7 vs. 55.7 ± 30.1, p = 0.078). Conclusion: Stone-crushers were more heavily exposed to mineral dust and various trace elements than taxi-drivers, and they had a fourfold increased risk of reporting wheezing, but they did not have evidence of more respiratory impairment than taxi-drivers.

Urinary trace metals in association with fetal ultrasound measures during pregnancy.

Toxic metals have been associated with lower birth weight while essential metals have been associated with higher birth weight. Evidence for other metals is either inconsistent or limited in terms of number of studies. This study analyzed 17 urinary metals, individually and as a mixture, and their association with measures of fetal growth in the LIFECODES birth cohort. Ultrasound was used to measure abdominal circumference, head circumference, and femur length and measures were used to calculate estimated fetal weight at ~26 and ~35 weeks. We calculated the z-score based on gestational age at scan, and estimated fetal weight (EFW) was combined with birth weight for longitudinal analyses. Metals were measured in samples collected at ~26 weeks. We used linear mixed effects models to examine associations between metals and repeated measures of each outcome, controlling for covariates. Principal components analysis reduced the biomarkers to predictors that may share some commonality. We found that an interquartile range increase in selenium was inversely associated with femur length z-score as well as other growth outcomes. Other essential metals, however, were associated with an increase in growth. Finally, the PCA component comprised of arsenic, mercury, and tin was associated with decreased head circumference z-score (-0.14 [95% CI: -0.23, -0.05]).

Manganese is associated with increased plasma interleukin-1β during pregnancy, within a mixtures analysis framework of urinary trace metals

Exposure to trace metals may impact reproductive health outcomes through perturbations in maternal immune signaling molecules. We conducted a cross-sectional study of 390 pregnant women from the LIFECODES birth cohort and investigated the associations between 17 urinary metals and five immune biomarkers measured in the 3rd trimester (median 26 weeks gestation). We used linear regression to estimate pair-wise associations and applied elastic net and Bayesian kernel machine regression to identify important contributing exposures analytes as well as non-linear effects. Maternal urinary manganese, nickel, and barium were positively associated with maternal plasma interleukin-1β (IL-1β). Elastic net and Bayesian kernel machine regression identified manganese as the dominant trace metal in association with IL-1β. An interquartile range difference in manganese (0.6 μg/L) was associated with a 29 % increase in IL-1β (95 % CI: 12.4–48.2). In conclusion, trace metal exposures were associated with biomarkers of immune perturbations, and this warrants further investigation.

Exposure to 17 trace metals in pregnancy and associations with urinary oxidative stress biomarkers

BackgroundExposure to some toxic metals, such as lead and cadmium, has been associated with increased oxidative stress. However less is known about other metals and metal mixtures, especially in pregnant women who are a vulnerable population. MethodsTo study the relationship between exposure to trace metals and oxidative stress, we analyzed a panel of 17 metals and two oxidative stress biomarkers (8-isoprostane and 8-hydroxydeoxyguanosine [8-OHdG]) in urine samples collected at ~26 weeks gestation from pregnant women in Boston (n = 380). We used linear regression models to calculate percent differences and 95% confidence intervals (CI) in oxidative stress markers for an interquartile range (IQR) increase in each urinary metal with adjustment for other metals. In addition, we applied principal components analysis (PCA) and Bayesian kernel machine regression (BKMR), to examine cumulative effects (within correlated groups of exposures as well as overall) and interactions. ResultsWe estimated 109% (95% CI: 47, 198) higher 8-isoprostane and 71% (95% CI: 45, 102) higher 8-OHdG with an IQR increase in urinary selenium (Se). We also estimated higher 8-isoprostane (47%, 95% CI: 20.5, 79.4) and 8-OHdG (15.3%, 95% CI: 5.09, 26.5) in association with urinary copper (Cu). In our PCA, we observed higher 8-isoprostane levels in association with the “essential” PC (highly loaded by Cu, Se, and Zinc). In BKMR analyses, we also estimated higher levels of both oxidative stress biomarkers with increasing Se and Cu as well as increasing levels of both oxidative stress biomarkers in association with cumulative concentrations of urinary trace metals. ConclusionWe observed higher 8-isoprostane and 8-OHdG levels in association with urinary trace metals and elements, particularly Se and Cu, in linear models and using mixtures approaches. Additionally, increasing cumulative exposure to urinary trace metals was associated with higher levels of both oxidative stress biomarkers. The beneficial effects of these compounds should be carefully questioned.

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

BackgroundExposures 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.ObjectiveWe investigated the relationship between urinary trace metals, circulating angiogenic biomarkers, and preeclampsia using the LIFECODES birth cohort.MethodsUrine 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.ResultsIn 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.ConclusionsTrace urinary metals may be associated with adverse profiles of angiogenic biomarkers and preeclampsia.

Urinary trace metals individually and in mixtures in association with preterm birth

One in ten infants born in the United States is born preterm, or prior to 37 weeks gestation. Exposure to elevated levels of metals, such as lead and arsenic, has been linked to higher risk of preterm birth (PTB), but consequences of lower levels of exposure and less studied metals are unclear. We examined the associations between 17 urinary trace metals individually and in mixtures in relation to PTB. The LIFECODES birth cohort enrolled pregnant women at <15 weeks gestation at Brigham and Women's Hospital in Boston. We selected cases of PTB (n = 99) and unmatched controls (n = 291) and analyzed urine samples for a panel of trace metals (median: 26 weeks gestation). We used logistic regression models to calculate the odds ratio (OR) for PTB and subtypes of PTB based on presentation at delivery. Subtypes included spontaneous and placental PTB. We used elastic net (ENET) regularization to identify individual metals or pairwise interactions that had the strongest associations with PTB, and principal components analysis (PCA) to identify classes of exposures associated with the outcome. We observed increased odds of PTB (OR: 1.41, 95% Confidence Interval [CI]: 1.12, 1.78) in association with an interquartile range difference in urinary copper (Cu). We also observed an increased OR for selenium (OR: 1.33, 95% CI: 0.98, 1.81). ENET selected Cu as the most important trace metal associated with PTB. PCA identified 3 principal components (PCs) that roughly reflected exposure to toxic metals, essential metals, and metals with seafood as a common source of exposure. PCs reflecting essential metals were associated with increased odds of overall and spontaneous PTB. Maternal urinary copper in the third trimester was associated with increased risk of PTB, and statistical analyses for mixtures indicated that after accounting for correlation this metal was the most important statistical predictor of the outcome.

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

Preterm birth (PTB), birth &amp;lt;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&amp;#8217;s Health Exposure Analysis Resource, we examined the association between 17 urinary trace metals and PTB. The LIFECODES birth cohort enrolled pregnant women at &amp;lt;15 weeks gestation at Brigham and Women&amp;#8217;s Hospital in Boston. Women participated in 4 study visits. We selected cases of PTB (n&amp;#61;99) and unmatched controls (n&amp;#61;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.

The Relationships between Maternal Urinary Trace Metals and Plasma Immune Biomarkers during Pregnancy

Background: Environmental exposure to metals is widespread and may pose a risk for adverse birth outcomes. Metals may impact these outcomes through immunotoxic mechanisms via perturbations in mater...

Urinary trace metals and breast cancer: a prospective Danish cohort study

Urinary trace metals and breast cancer: a prospective Danish cohort study