Gestational exposure to organochlorine compounds and metals and infant birth weight: effect modification by maternal hardships.

BACKGROUND: Gestational exposure to toxic environmental chemicals and maternal social hardships are individually associated with impaired fetal growth, but it is unclear whether the effects of environmental chemical exposure on infant birth weight are modified by maternal hardships. METHODS: We used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1982 pregnant females enrolled between 2008 and 2011. We quantified eleven environmental chemical concentrations from two chemical classes - six organochlorine compounds (OCs) and five metals - that were detected in ≥ 70% of blood samples collected during the first trimester. We examined fetal growth using birth weight adjusted for gestational age and assessed nine maternal hardships by questionnaire. Each maternal hardship variable was dichotomized to indicate whether the females experienced the hardship. In our analysis, we used elastic net to select the environmental chemicals, maternal hardships, and 2-way interactions between maternal hardships and environmental chemicals that were most predictive of birth weight. Next, we obtained effect estimates using multiple linear regression, and plotted the relationships by hardship status for visual interpretation. RESULTS: Elastic net selected trans-nonachlor, lead, low educational status, racially minoritized background, and low supplemental folic acid intake. All were inversely associated with birth weight. Elastic net also selected interaction terms. Among those with increasing environmental chemical exposures and reported hardships, we observed stronger negative associations and a few positive associations. For example, every two-fold increase in lead concentrations was more strongly associated with reduced infant birth weight among participants with low educational status (ß = -100 g (g); 95% confidence interval (CI): -215, 16), than those with higher educational status (ß = -34 g; 95% CI: -63, -3). In contrast, every two-fold increase in mercury concentrations was associated with slightly higher birth weight among participants with low educational status (ß = 23 g; 95% CI: -25, 71) compared to those with higher educational status (ß = -9 g; 95% CI: -24, 6). CONCLUSIONS: Our findings suggest that maternal hardships can modify the associations of gestational exposure to some OCs and metals with infant birth weight.

Blood levels of metallic chemical element exposure patterns and associated factors in a population living in an Industrial District in Brazil.

AIM: to estimate the level of metallic chemical elements in the population living in the Steel company vicinity in Santa Cruz, Rio de Janeiro, Brazil; and estimate the association between exposure to the Steel company and the blood metals concentrations patterns. METHOD: A cross-sectional study was carried out on 463 individuals aged 18+ years old residing 1+ years in the Steel company vicinity. Mg, Be, Co, Ba, Ni, Cd, Al, and Pb were assessed in blood by DRC-ICP-MS. Metallic chemical element concentration patterns were obtained by exploratory factor analysis in the studied population. Exposure was set as the distance (Km) from each participant's residence to the Steel company in Santa Cruz, georeferenced by GPS. The outcome was set as the positive factor loadings in the factor analysis, including Mg and Be (Factor-1), Co, Ba, and Ni (Factor-2), Cd, Al, and Pb (Factor-4). Crude and adjusted OR, and their respective 95 %CI, were estimated to explore associations between independent variables and the exposures to metallic elements positively associated with the factors using polychotomous logistic regression. RESULTS: A reduction of 19 % was found between each km distance from the residence and the Steel company and P50 concentration of Cd, Al, and Pb (ORP50=0.81; 95 %CI:0.67-0.97), after adjusting by age, sex, and smoking. No statistically significant associations were observed for the distance from residences and the Steel company, after adjusting for age, gender, having a domestic vegetable garden and chewing gum for Mg and Be concentrations (Factor-1) (ORP50=0.84; 95 %CI:0.70-1.01; ORP75=1.10; 95 %CI:0.91-1.34); nor for Co, Ba and Ni (Factor-2) blood concentrations(ORP50=1.10; 95 %CI:0.91-1.33; ORP75=1.03; 95 %CI:0.84-1.26), in the adjusted analysis. CONCLUSIONS: For each Km distance from residences to the Steel company, a 19 % reduction in the risk of Cd, Al, and Pb blood concentration was observed in the population living in Santa Cruz, Rio de Janeiro, Brazil.

Metal exposure in the Greenlandic ACCEPT cohort: follow-up and comparison with other Arctic populations.

Humans are exposed to metals through diet and lifestyle e.g. smoking. Some metals are essential for physiologically body functions, while others are non-essential and can be toxic to humans. This study follows up on metal concentrations in the Greenlandic ACCEPT birth-cohort (mothers and fathers) and compares with other Arctic populations. The data from 2019 to 2020 include blood metal concentrations, lifestyle and food frequency questionnaires from 101 mothers and 76 fathers, 24-55 years, living in Nuuk, Sisimiut, and Ilulissat. A high percentage (25-45%) exceeded international guidance values for Hg. For the mothers, the metal concentrations changed significantly from inclusion at pregnancy to this follow-up 3-5 years after birth; some increased and others decreased. Most metals differed significantly between mothers and fathers, while few also differed between residential towns. Several metals correlated significantly with marine food intake and socio-economic factors, but the direction of the correlations varied. Traditional marine food intake was associated positively with Se, As and Hg. To the best of our knowledge, this study provides the most recent data on metal exposure of both men and women in Greenland, elucidating metal exposure sources among Arctic populations, and documents the need for continuing biomonitoring to follow the exceeding of guidance values for Hg. [Figure: see text].

A prospective cohort study of multimetal exposure and risk of gestational diabetes mellitus.

The relationship between co-exposure to multiple metals and gestational diabetes mellitus (GDM) and the mechanisms involved are poorly understood. In this nested case-control study, 228 GDM cases and 456 matched controls were recruited, and biological samples were collected at 12-14 gestational weeks. The urinary concentrations of 10 metals and 8-hydroxydeoxyguanosine (8-OHdG) as well as the serum levels of malondialdehyde (MDA) and advanced glycation end products (AGEs) were determined to assess the association of metals with GDM risk and the mediating effects of oxidative stress. Urinary Ti concentration was significantly and positively associated with the risk of GDM (odds ratio [OR]:1.45, 95 % confidence interval [CI]: 1.12, 1.88), while Mn and Fe were negatively associated with GDM risk (OR: 0.67, 95 % CI: 0.50, 0.91 or OR: 0.61, 95 % CI: 0.47, 0.80, respectively). A significant negative association was observed between Mo and GDM risk, specifically in overweight and obese pregnant women. Bayesian kernel machine regression showed a significant negative joint effect of the mixture of 10 metals on GDM risk. The adjusted restricted cubic spline showed a protective role of Mn and Fe in GDM risk (P < 0.05). A significant negative association was observed between essential metals and GDM risk in quantile g-computation analysis (P < 0.05). Mediation analyses showed a mediating effect of MDA on the association between Ti and GDM risk, with a proportion of 8.7 % (P < 0.05), and significant direct and total effects on Ti, Mn, and Fe. This study identified Ti as a potential risk factor and Mn, Fe, and Mo as potential protective factors against GDM, as well as the mediating effect of lipid oxidation.

Association of exposure to multiple metals with hemoglobin levels in Chinese children and adolescents.

BACKGROUND: Previous studies have linked single metal to hemoglobin levels in children and adolescents; however, studies with regards to metal mixtures are still limited. OBJECTIVE: We aimed to investigate the associations of single metal and metal mixtures with hemoglobin levels in children and adolescents. METHODS: We conducted a cross-sectional study of 2064 children and adolescents aged 6 to 19 years in Liuzhou, China in 2018. The concentrations of 15 metals in urine were determined by inductively coupled plasma mass spectrometry. Generalized linear regression and weighted quantile sum (WQS) regression were used to estimate the associations of single metal and metal mixtures with hemoglobin levels, respectively. RESULTS: The multivariable-adjusted ß-values for the highest versus the first quartiles of urinary metal concentrations were - 1.57 (95 % confidence interval [CI]: -3.01, -0.13) for chromium, -2.47 (95 % CI: -3.90, -1.05) for nickel and 1.88 (95 % CI: 0.49, 3.28) for copper. In addition, we found a significant negative association between the WQS index and hemoglobin levels (adjusted ß = -0.93, 95 % CI: -1.69, -0.19), with nickel contributing the most to the WQS index at 59.0 %. Subgroup analyses showed that exposure to urinary nickel or metal mixtures were associated with decreased hemoglobin levels in adolescents, but not in children (all Pinteration < 0.001). CONCLUSION: Among children and adolescents, urinary chromium and nickel concentrations were associated with decreased hemoglobin levels, while copper showed a positive relationship. Moreover, a negative association was observed between exposure to metal mixtures and hemoglobin levels. These findings need to be further validated in prospective studies.

Associations of mixed metal exposure with chronic kidney disease from NHANES 2011-2018.

Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear. We assessed the urine and whole blood levels of cadmium (Cd), manganese (Mn), lead (Pb), mercury (Hg), and renal function in 3080 adults from National Health and Nutrition Survey (NHANES) (2011-2018) to explore the effect of mixed metal exposure on CKD especially in people with type 2 diabetes mellitus (T2DM). Weighted quantile sum regression model and Bayesian Kernel Machine Regression model were used to evaluate the overall exposure impact of metal mixture and potential interaction between metals. The results showed that the exposure to mixed metals was significantly associated with an increased risk of CKD in blood glucose stratification, with the risk of CKD being 1.58 (1.26,1.99) times in urine and 1.67 (1.19,2.34) times in whole blood higher in individuals exposed to high concentrations of the metal mixture compared to those exposed to low concentrations. The effect of urine metal mixture was elevated magnitude in stratified analysis. There were interactions between urine Pb and Cd, Pb and Mn, Pb and Hg, Cd and Mn, Cd and Hg, and blood Pb and Hg, Mn and Cd, Mn and Pb, Mn and Hg on the risk of CKD in patients with T2DM and no significant interaction between metals was observed in non-diabetics. In summary, mixed metal exposure increased the risk of CKD in patients with T2DM, and there were complex interactions between metals. More in-depth studies are needed to explore the mechanism and demonstrate the causal relationship.

Association of metals and bisphenols exposure with lipid profiles and dyslipidemia in Chinese adults: Independent, combined and interactive effects.

BACKGROUND: Although studies have assessed the association of metals and bisphenols with lipid metabolism, the observed results have been controversial, and limited knowledge exists about the combined and interactive effects of metals and bisphenols exposure on lipid metabolism. METHODS: Plasma metals and serum bisphenols concentrations were evaluated in 888 participants. Multiple linear regression and logistic regression models were conducted to assess individual associations of 18 metals and 3 bisphenols with 5 lipid profiles and dyslipidemia risk, respectively. The dose-response relationships of targeted contaminants with lipid profiles and dyslipidemia risk were captured by applying a restriction cubic spline (RCS) function. The bayesian kernel machine regression (BKMR) model was used to assess the overall effects of metals and bisphenols mixture on lipid profiles and dyslipidemia risk. The interactive effects of targeted contaminants on interested outcomes were explored by constructing an interaction model. RESULTS: Single-contaminant analyses revealed that exposure to iron (Fe), nickel (Ni), copper (Cu), arsenic (As), selenium (Se), strontium (Sr), and tin (Sn) was associated with elevated lipid levels. Cobalt (Co) showed a negative association with high density lipoprotein cholesterol (HDL-C). Bisphenol A (BPA) and bisphenol AF (BPAF) were associated with decreased HDL-C levels, with nonlinear associations observed. Vanadium (V), lead (Pb), and silver (Ag) displayed U-shaped dose-response relationships with most lipid profiles. Multi-contaminant analyses indicated positive trends between contaminants mixture and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C). The interaction analyses showed that Se-Fe exhibited synergistic effects on LDL-C and non-HDL-C, and Se-Sn showed a synergistic effect on HDL-C. CONCLUSIONS: Our study suggested that exposure to metals and bisphenols was associated with changes in lipid levels, and demonstrated their combined and interactive effects.

Plasma metals, genetic risk, and rapid kidney function decline among type 2 diabetes.

BACKGROUND: Rapid kidney function decline (RKFD) is a main clinical feature of early chronic kidney disease (CKD) in type 2 diabetes (T2D). Environmental and genetic factors influencing RKFD remain inadequately elucidated. OBJECTIVES: This study aimed to examine the associations of metals with RKFD among T2D and to further investigate the effect of metal mixtures on RKFD with the modifying effect of genetic susceptibility. METHODS: This study included 2209 people with T2D (1942 had genotyping data) free of CKD at baseline from the Dongfeng-Tongji cohort. We used inductively coupled plasma-mass spectrometry (ICP-MS) to measure 23 metals in baseline plasma. Using elastic net (ENET), multivariate logistic regression, and Bayesian kernel machine regression (BKMR) model, we examined independent associations of multiple metals with RKFD. We calculated the environmental risk score (ERS) to assess the effects of metal mixtures on RKFD and the genetic risk score (GRS) to assess genetic susceptibility. RKFD was defined as estimated glomerular filtration rate (eGFR) loss > 3 mL/min/1.73 m2/year. RESULTS: During a median of 9.8 years follow-up, 262 participants developed RKFD. Aluminum, vanadium, zinc, selenium, rubidium, tin, barium, and tungsten were screened from ENET. In multivariate logistic models, vanadium, selenium, and tungsten were negatively associated with RKFD, while zinc, tin, and rubidium were positively associated. The BKMR showed a nonlinear association of vanadium and rubidium with RKFD and interactions between metals (barium­vanadium, barium­rubidium). The ERS was positive associated with RKFD (per SD increase in ERS, OR = 1.94, 95% CI: 1.66, 2.27). No significant interaction between ERS and GRS was observed on RKFD, however, participants in the highest ERS and GRS group had the highest RKFD risk. CONCLUSION: Vanadium and rubidium were associated with RKFD in T2D. Metal mixtures was associated with an increased risk of RKFD in T2D, particularly in those at high genetic risk.

Associations of toxic metals and their mixture with hyperuricemia in Chinese rural older adults.

Previous studies have related single toxic metals (TMs) to hyperuricemia (HUA) among the general population, however, the association of the TM mixture with HUA, especially in older adults, remains poorly understood. We aimed to examine the relationships between individual TMs and their mixture and HUA in Chinese rural older adults. This study consisted of 2075 rural older adults aged 60 years or over. Blood concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), gallium (Ga), mercury (Hg), lead (Pb), thallium (Tl), and uranium (U) were detected using inductively coupled plasma mass spectrometry. The associations of single TMs with HUA were assessed using logistic regression and restricted cubic spline (RCS) models, and the association of TM mixture with HUA was explored using the elastic net with environmental risk score (ENET-ERS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR) models, respectively. Adjusted logistic regression model showed that Cs (OR = 1.65, 95% CI 1.37-1.99) and Pb (OR = 1.46, 95% CI 1.28-1.67) were positively related to HUA, and RCS model exhibited a positive linear association of Cs and Pb with HUA. ENET-ERS and QGC models quantified a positive correlation between the TM mixture and the odds of HUA, with estimated ORs of 1.15 (95% CI 1.11-1.19) and 1.84 (95% CI 1.37-2.47), respectively, and Cs and Pb had the most weight. BKMR model demonstrated a significant linear association between the TM mixture and increased odds of HUA, with the posterior inclusion probabilities (PIPs) of both Cs and Pb being 1.00. Moreover, we observed a positive interaction between Cs and Pb on HUA. The TM mixture is associated with increased odds of HUA in rural older adults, which may mainly be driven by Cs and Pb. Subsequent studies are warranted to confirm these findings and clarify the mechanisms linking multiple TMs with HUA.

Metal exposure and blood lipid biomarkers in early pregnancy: A cross-sectional study.

Recognizing the risk factors for dyslipidemia during pregnancy is crucial for safeguarding the health of both the mothers and the offspring. Growing evidence emerged and suggested links between environmental factors, including metals, and alteration in lipid levels or dyslipidemia in general populations. However, knowledge of the associations during pregnancy remains extremely lacking. Herein, we aimed to explore whether elevated metal exposure constitutes a risk factor for dyslipidemia in pregnant women. Based on the Tongji-Shuangliu Birth Cohort (TSBC), a total of 663 pregnant women were recruited and their urinary levels of 17 metals and blood lipid biomarkers in early pregnancy were measured, namely triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). The multivariable linear regression models revealed that exposure to selected metals during early pregnancy was significantly associated with some important biomarkers. In particular, after natural log-transformed for the levels of lipid biomarkers and metals, copper (Cu) exposure was positively associated with HDL-C (ß = 0.024, 95% CI: 0.001, 0.046), while zinc (Zn) was associated with TG (ß = 0.062, 95% CI: 0.013, 0.110) and selenium with TC (ß = 0.028, 95% CI: 0.004, 0.054). Exposure to rubidium (Rb) was positively associated with multiple lipid biomarkers, including HDL-C (ß = 0.020, 95% CI: 0.002, 0.037) and LDL-C (ß = 0.022, 95% CI: 0.001, 0.042). Mixture exposure analysis further identified significant associations between Cu and HDL-C, Zn and TG, Rb and HDL-C, when multiple metal exposures were considered in the Bayesian kernel machine regression model simultaneously. Our findings showed that exposure to several metals during early pregnancy was associated with an increased prevalence of blood lipid abnormalities in pregnant women. These findings underscore the potential impact of metal combinations on lipid metabolism and increase our understanding of the risk factors associated with abnormal lipid metabolism during pregnancy.

Associations between maternal exposure to multiple metals and metalloids and blood pressure in preschool children: A mixture-based approach.

BACKGROUND: Exposure to metals during pregnancy can potentially influence blood pressure (BP) in children, but few studies have examined the mixed effects of prenatal metal exposure on childhood BP. We aimed to assess the individual and combined effects of prenatal metal and metalloid exposure on BP in preschool children. METHODS: A total of 217 mother-child pairs were selected from the Zhuang Birth Cohort in Guangxi, China. The maternal plasma concentrations of 20 metals [e.g. lead (Pb), rubidium (Rb), cesium (Cs), and zinc (Zn)] in early pregnancy were measured by inductively coupled plasmamass spectrometry. Childhood BP was measured in August 2021. The effects of prenatal metal exposure on childhood BP were explored by generalized linear models, restricted cubic spline and Bayesian kernel machine regression (BKMR) models. RESULTS: In total children, each unit increase in the log10-transformed maternal Rb concentration was associated with a 10.82-mmHg decrease (95% CI: -19.40, -2.24) in childhood diastolic BP (DBP), and each unit increase in the log10-transformed maternal Cs and Zn concentrations was associated with a 9.67-mmHg (95% CI: -16.72, -2.61) and 4.37-mmHg (95% CI: -8.68, -0.062) decrease in childhood pulse pressure (PP), respectively. The log10-transformed Rb and Cs concentrations were linearly related to DBP (P nonlinear=0.603) and PP (P nonlinear=0.962), respectively. Furthermore, an inverse association was observed between the log10-transformed Cs concentration and PP (ß =-12.18; 95% CI: -22.82, -1.54) in girls, and between the log10-transformed Rb concentration and DBP (ß =-12.54; 95% CI: -23.87, -1.21) in boys, while there was an increasing association between the log10-transformed Pb concentration and DBP there was an increasing in boys (ß =6.06; 95% CI: 0.36, 11.77). Additionally, a U-shaped relationship was observed between the log10-transformed Pb concentration and SBP (P nonlinear=0.015) and DBP (P nonlinear=0.041) in boys. Although there was no statistically signiffcant difference, there was an inverse trend in the combined effect of maternal metal mixture exposure on childhood BP among both the total children and girls in BKMR. CONCLUSIONS: Prenatal exposure to both individual and mixtures of metals and metalloids influences BP in preschool children, potentially leading to nonlinear and sex-specific effects.

Associations between seminal plasma metals/metalloids and semen quality: A cross-sectional study.

Exposure to metals/metalloids is reported to potentially influence semen quality. While most studies have focused on single metal impacts, the link between exposure to multiple metals and semen quality has remained less explored. The study aimed to investigate the effects of both individual and mixed metal/metalloid exposure on semen quality. A total of 330 men were recruited from three reproductive centers in eastern China. Seminal plasma levels of 25 metals/metalloids and sperm parameters were determined. We used the Generalized Linear Model (GLM) and Restricted Cubic Spline (RCS) to assess the relationships between single metals/metalloids and semen quality. The weighted quantile sum (WQS) models were then applied to evaluate the combined effect of all these metals/metalloids. We observed positive associations of exposure to lithium (Li), zinc (Zn), and magnesium (Mg) with an increased risk of below reference values for progressive motility and total motility using a logistic regression model (P < 0.05). Additionally, our results also revealed a significant inverse relationship between aluminum (Al) and both sperm concentration and count, while cobalt (Co) demonstrated a positive association with sperm concentration (P < 0.05). Notably, the WQS model indicated a significant positive association between exposure to metal/metalloid mixtures and the risk of abnormal progressive motility (OR: 1.57; 95%CI: 1.10, 2.24) and abnormal total motility (OR: 1.53; 95%CI: 1.06, 2.19), with this association primarily driven by Li, Mg, and Zn. In summary, our findings indicate that exposure to metal/metalloid mixtures might have an adverse effect on semen quality.

Association of serum metal levels with type 2 diabetes: A prospective cohort and mediating effects of metabolites analysis in Chinese population.

Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10-5). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D.

Association between plasma metal exposure and health span in very elderly adults: a prospective cohort study with mixture statistical approach.

BACKGROUND: Metals have been linked to a diverse spectrum of age-related diseases; however, the effects of metal exposure on health span remains largely unknown. This cohort study aims to determine the association between plasma metal and health span in elder adults aged ≥ 90 years. METHODS: The plasma concentrations of seven metals were measured at baseline in 300 elder adults. The end of the health span (EHS) was identified as the occurrence of one of eight major morbidities or mortality events. We used Cox regression to assess hazard ratios (HR). The combined effects of multiple metal mixtures were estimated using grouped-weighted quantile sum (GWQS), quantile g-computation (Q-gcomp), and Bayesian kernel machine regression (BKMR) methods. RESULTS: The estimated HR for EHS with an inter-quartile range (IQR) increment for selenium (Se) was 0.826 (95% confidence interval [CI]: 0.737-0.926); magnesium (Mg), 0.806 (95% CI: 0.691-0.941); iron (Fe), 0.756 (95% CI: 0.623-0.917), and copper (Cu), 0.856 (95% CI: 0.750-0.976). The P for trend of Se, Mg, and Fe were all < 0.05. In the mixture analyses, Q-gcomp showed a negative correlation with EHS (P = 0.904), with the sum of the negative coefficients being -0.211. CONCLUSION: Higher plasma Se, Mg, and Fe reduced the risk of premature end of health span, suggesting that essential metal elements played a role in health maintenance in elder adults.

Comparative mathematical modeling of causal association between metal exposure and development of chronic kidney disease.

Background: Previous studies have identified several genetic and environmental risk factors for chronic kidney disease (CKD). However, little is known about the relationship between serum metals and CKD risk. Methods: We investigated associations between serum metals levels and CKD risk among 100 medical examiners and 443 CKD patients in the medical center of the First Hospital Affiliated to China Medical University. Serum metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). We analyzed factors influencing CKD, including abnormalities in Creatine and Cystatin C, using univariate and multiple analysis such as Lasso and Logistic regression. Metal levels among CKD patients at different stages were also explored. The study utilized machine learning and Bayesian Kernel Machine Regression (BKMR) to assess associations and predict CKD risk based on serum metals. A chained mediation model was applied to investigate how interventions with different heavy metals influence renal function indicators (creatinine and cystatin C) and their impact on diagnosing and treating renal impairment. Results: Serum potassium (K), sodium (Na), and calcium (Ca) showed positive trends with CKD, while selenium (Se) and molybdenum (Mo) showed negative trends. Metal mixtures had a significant negative effect on CKD when concentrations were all from 30th to 45th percentiles compared to the median, but the opposite was observed for the 55th to 60th percentiles. For example, a change in serum K concentration from the 25th to the 75th percentile was associated with a significant increase in CKD risk of 5.15(1.77,8.53), 13.62(8.91,18.33) and 31.81(14.03,49.58) when other metals were fixed at the 25th, 50th and 75th percentiles, respectively. Conclusions: Cumulative metal exposures, especially double-exposure to serum K and Se may impact CKD risk. Machine learning methods validated the external relevance of the metal factors. Our study highlights the importance of employing diverse methodologies to evaluate health effects of metal mixtures.

Associations among neighborhood walkability, metal exposure, and sex steroid hormone levels: Results from Hangzhou Birth Cohort Study â ¡.

BACKGROUND: Neighborhood walkability may influence maternal-fetal exposure to environmental hazards and maternal-fetal health (e.g., fetal growth restriction, reproductive toxicity). However, few studies have explored the association between neighborhood walkability and hormones in pregnant women. METHODS: We included 533 pregnant women from the Hangzhou Birth Cohort Study II (HBCS-II) with testosterone (TTE) and estradiol (E2) measured for analysis. Neighborhood walkability was evaluated by calculating a walkability index based on geo-coded addresses. Placental metals were measured using inductively coupled plasma mass spectrometry (ICP-MS). TTE and E2 levels in umbilical cord blood were measured using chemiluminescence microparticle immunoassay (CMIA). Linear regression model was used to estimate the relationship between the walkability index, placental metals, and sex steroid hormones. Effect modification was also assessed to estimate the effect of placental metals on the associations of neighborhood walkability with TTE and E2. RESULTS: Neighborhood walkability was significantly linked to increased E2 levels (P trend=0.023). Compared with participants at the first quintile (Q1) of walkability index, those at the third quintiles (Q3) had lower chromium (Cr) levels (ß = -0.212, 95% CI = -0.421 to -0.003). Arsenic (As), cobalt (Co), manganese (Mn), molybdenum (Mo), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), tin (Sn), and vanadium (V) were linked to decreased TTE levels, and cadmium (Cd) was linked to increased TTE levels. No metal was significantly associated with E2 levels in trend analysis. In the analysis of effect modification, the associations of neighborhood walkability with TTE and E2 were significantly modified by Mn (P = 0.005) and Cu (P = 0.049) respectively. CONCLUSION: Neighborhood walkability could be a favorable factor for E2 production during pregnancy, which may be inhibited by maternal exposure to heavy metals.

Association of individual and combined exposures of 10 metals with periodontitis: Results from a large population-based study.

AIMS: To systematically investigate the association between individual and combined metal exposure and periodontitis. METHODS: Data encompassing complete periodontal examinations and metal detection in blood and urine samples were procured from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Three statistical methods, namely weighted logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression, were used to evaluate the independent and combined associations between metals and periodontitis. RESULTS: Elevated concentrations of blood cadmium (odds ratio [OR]: 1.73, 95% confidence interval [CI]: 1.15-2.61) and blood lead (OR: 1.17, 95 %CI: 1.02-1.34) exhibited a positive association with periodontitis, even after adjusting for potential confounding factors. The BKMR and WQS regression suggested that the co-exposure of metals was also positively associated with periodontitis. Moreover, estradiol and albumin were identified as potential mediators in the relationship between the WQS index of the 10 metals in blood and periodontitis explaining 25.36% and 2.02% of the relationship, respectively. Furthermore, generally consistent patterns of associations between metals and periodontitis and mediating roles of estrogen and albumin were observed after a series of sensitivity analyses. CONCLUSION: This study provides evidence of positive associations between elevated levels of cadmium, lead or metal mixture and periodontitis, which may be partially mediated by sex hormones and oxidative stress indicators.

Effects of multiple metals exposure on abnormal liver function: The mediating role of low-density lipoprotein cholesterol.

Equilibration of metal metabolism is critical for normal liver function. Most epidemiological studies have only concentrated on the influence of limited metals. However, the single and synergistic impact of multiple-metal exposures on abnormal liver function (ALF) are still unknown. A cross-sectional study involving 1493 Chinese adults residing in Shenzhen was conducted. Plasma concentrations of 13 metals, including essential metals (calcium, copper, cobalt, iron, magnesium, manganese, molybdenum, zinc, and selenium) and toxic metals (aluminum, cadmium, arsenic, and thallium) were detected by the inductively coupled plasma spectrometry (ICP-MS). ALF was ascertained as any observed abnormality from albumin, alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase, and direct bilirubin. Diverse statistical methods were used to evaluate the single and mixture effect of metals, as well as the dose-response relationships with ALF risk, respectively. Mediation analysis was conducted to evaluate the role of blood lipids in the relation of metal exposure with ALF. The average age of subjects was 59.7 years, and 56.7 % were females. Logistic regression and the least absolute shrinkage and selection operator (LASSO) penalized regression model consistently suggested that increased levels of arsenic, aluminum, manganese, and cadmium were related to elevated risk of ALF; while magnesium and zinc showed protective effects on ALF (all p-trend < 0.05). The grouped weighted quantile sum (GWQS) regression revealed that the WQS index of essential metals and toxic metals showed significantly negative or positive relationship with ALF, respectively. Aluminum, arsenic, cadmium, and manganese showed linear whilst magnesium and zinc showed non-linear dose-response relationships with ALF risk. Mediation analysis showed that LDL-c mediated 4.41 % and 14.74 % of the relationship of plasma cadmium and manganese with ALF, respectively. In summary, plasma aluminum, arsenic, manganese, cadmium, magnesium, and zinc related with ALF, and LDL-c might underlie the pathogenesis of ALF associated with cadmium and manganese exposure. This study may provide critical public health significances in liver injury prevention and scientific evidence for the establishment of environmental standard.

Associations of maternal blood metal concentrations with plasma eicosanoids among pregnant women in Puerto Rico.

BACKGROUND/AIM: Heavy metals are known to induce oxidative stress and inflammation, and the association between metal exposure and adverse birth outcomes is well established. However, there lacks research on biomarker profiles linking metal exposures and adverse birth outcomes. Eicosanoids are lipid molecules that regulate inflammation in the body, and there is growing evidence that suggests associations between plasma eicosanoids and pregnancy outcomes. Eicosanoids may aid our understanding of etiologic birth pathways. Here, we assessed associations between maternal blood metal concentrations with eicosanoid profiles among 654 pregnant women in the Puerto Rico PROTECT birth cohort. METHODS: We measured concentrations of 11 metals in whole blood collected at median 18 and 26 weeks of pregnancy, and eicosanoid profiles measured in plasma collected at median 26 weeks. Multivariable linear models were used to regress eicosanoids on metals concentrations. Effect modification by infant sex was explored using interaction terms. RESULTS: A total of 55 eicosanoids were profiled. Notably, 12-oxoeicosatetraenoic acid (12-oxoETE) and 15-oxoeicosatetraenoic acid (15-oxoETE), both of which exert inflammatory activities, had the greatest number of significant associations with metal concentrations. These eicosanoids were associated with increased concentrations of Cu, Mn, and Zn, and decreased concentrations of Cd, Co, Ni, and Pb, with the strongest effect sizes observed for 12-oxoETE and Pb (ß:-33.5,95 %CI:-42.9,-22.6) and 15-oxoETE and Sn (ß:43.2,95 %CI:11.4,84.1). Also, we observed differences in metals-eicosanoid associations by infant sex. Particularly, Cs and Mn had the most infant sex-specific significant associations with eicosanoids, which were primarily driven by female fetuses. All significant sex-specific associations with Cs were inverse among females, while significant sex-specific associations with Mn among females were positive within the cyclooxygenase group but inverse among the lipoxygenase group. CONCLUSION: Certain metals were significantly associated with eicosanoids that are responsible for regulating inflammatory responses. Eicosanoid-metal associations may suggest a role for eicosanoids in mediating metal-induced adverse birth outcomes.

Elevated blood metal ion levels in patients undergoing instrumented spinal surgery: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Elevated blood metal levels have been reported in patients after spinal surgery using metallic implants. Although some studies have suggested an association between heightened blood metal concentrations and potential adverse effects, estimates of the incidence of abnormal metal levels after spinal surgery have been inconsistent. PURPOSE: The aims of this systematic review and meta-analysis were to assess: (1) mean differences in blood metal ion levels between patients undergoing spinal fusion surgery and healthy controls, (2) odds of elevated blood metal ion levels after surgery compared to presurgery levels, and (3) pooled incidence of elevated blood metal ions overall and by metal type. STUDY DESIGN: Systematic review and meta-analysis. PATIENTS SAMPLE: The patient sample included 613 patients from 11 studies who underwent spinal surgery instrumentation. OUTCOME MEASURES: Blood metal ion concentrations and the incidence of patients with elevated metal levels compared with in those the control group. METHODS: A comprehensive search was conducted in PubMed, EMBASE, Scopus, and Cochrane Library to identify studies reporting blood metal ion levels after spinal fusion surgery. Mean differences (MD), odds ratios (OR), and incidence rates were pooled using random effects models. Heterogeneity was assessed using I2 statistics, and fixed-effects models were used if no heterogeneity was detected. Detailed statistical analysis was performed using the Review Manager version 5.4 software. RESULTS: The analysis included 11 studies, with a total of 613 patients. Mean blood metal ion levels were significantly higher after spinal fusion surgery (MD 0.56, 95% CI 0.17-0.96; I2=86%). Specifically, titanium levels were significantly elevated (MD 0.81, 95% CI 0.32-1.30; I2=47%). The odds of elevated blood metal ions were higher after surgery (OR 8.17, 95% CI 3.38-19.72; I2=41%), primarily driven by chromium (OR 23.50, 95% CI 5.56-99.31; I2=30%). The incidence of elevated chromium levels was found to be 66.98% (95% CI 42.31-91.65). CONCLUSION: In conclusion, blood metal ion levels, particularly titanium and chromium, were significantly increased after spinal fusion surgery compared to presurgery levels and healthy controls. Approximately 70% of the patients exhibited elevated blood levels of chromium and titanium.