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Associations between exposure to heavy metals and the risk of chronic kidney disease: a systematic review and meta-analysis.
Jalili, C, Kazemi, M, Cheng, H, Mohammadi, H, Babaei, A, Taheri, E, Moradi, S
Critical reviews in toxicology. 2021;(2):165-182
Abstract
We performed a systematic review and meta-analysis to examine the relationship between heavy metals (HMs) exposure and the risk of chronic kidney disease (CKD). Databases of Web of Science, Embase, MEDLINE, and Scopus were searched through June 2020 to identify studies assessing the relationships between exposure to HMs (i.e. cadmium, lead, arsenic, mercury) and the risk of CKD, evaluated by decreased estimated glomerular filtration rate (eGFR) and/or increased proteinuria risks in adults (≥18 years). Data were pooled by random-effects models and expressed as weighted mean differences and 95% confidence intervals. The risk of bias was assessed by the Newcastle-Ottawa scale (NOS). Twenty-eight eligible articles (n = 107,539 participants) were included. Unlike eGFR risk (p = 0.10), Cadmium exposure was associated with an increased proteinuria risk (OR = 1.35; 95% CI: 1.13, 1.61; p < 0.001; I2 = 79.7%). Lead exposure was associated with decreased eGFR (OR = 1.12; 95%CI: 1.03, 1.22; p = 0.008; I2 = 87.8%) and increased proteinuria (OR = 1.25; 95% CI: 1.04, 1.49; p = 0.02; I2 = 79.6) risks. Further, arsenic exposure was linked to a decreased eGFR risk (OR = 1.55; 95% CI: 1.05, 2.28; p = 0.03; I2 = 89.1%) in contrast to mercury exposure (p = 0.89). Only two studies reported the link between arsenic exposure and proteinuria risk, while no study reported the link between mercury exposure and proteinuria risk. Exposure to cadmium, lead, and arsenic may increase CKD risk in adults, albeit studies were heterogeneous, warranting further investigations. Our observations support the consideration of these associations for preventative, diagnostic, monitoring, and management practices of CKD.
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Per- and polyfluoroalkyl substances exposure during pregnancy and adverse pregnancy and birth outcomes: A systematic review and meta-analysis.
Gao, X, Ni, W, Zhu, S, Wu, Y, Cui, Y, Ma, J, Liu, Y, Qiao, J, Ye, Y, Yang, P, et al
Environmental research. 2021;:111632
Abstract
BACKGROUND Exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy has been suggested to be associated with adverse pregnancy and birth outcomes; however, the findings have been inconsistent. We aimed to conduct a systematic review and meta-analysis to provide an overview of these associations. METHODS The online databases PubMed, EMBASE and Web of Science were searched comprehensively for eligible studies from inception to February 2021. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random- or fixed-effects models, and dose-response meta-analyses were also conducted when possible. FINDINGS A total of 29 studies (32,905 participants) were included. The pooled results demonstrated that perfluorooctane sulfonate (PFOS) exposure during pregnancy was linearly associated with increased preterm birth risk (pooled OR per 1-ng/ml increase: 1.01, 95% CIs: 1.00-1.02, P = 0.009) and perfluorononanoate (PFNA) and perfluorooctanoate (PFOA) exposure showed inverted U-shaped associations with preterm birth risk (P values for the nonlinear trend: 0.025 and 0.030). Positive associations were also observed for exposure to perfluorodecanoate (PFDA) and miscarriage (pooled OR per 1-ng/ml increase: 1.87, 95% CIs: 1.15-3.03) and PFOS and preeclampsia (pooled OR per 1-log increase: 1.27, 95% CIs: 1.06-1.51), whereas exposure to perfluoroundecanoate (PFUnDA) was inversely associated with preeclampsia risk (pooled OR per 1-log increase: 0.81, 95% CIs: 0.71-0.93). Based on individual evidence, detrimental effects were observed between PFDA exposure and small for gestational age and between PFOA and PFOS and intrauterine growth restriction. No significant associations were found between pregnancy PFAS exposure and other adverse pregnancy outcomes (i.e., gestational diabetes mellitus, pregnancy-induced hypertension, low birth weight, and large and small for gestational age). INTERPRETATION Our findings indicated that PFOS, PFOA and PFNA exposure during pregnancy might be associated with increased preterm birth risk and that PFAS exposure might be associated with the risk of miscarriage and preeclampsia. Due to the limited evidence obtained for most associations, additional studies are required to confirm these findings.
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Early Life Exposure to Perfluoroalkyl Substances (PFAS) and ADHD: A Meta-Analysis of Nine European Population-Based Studies.
Forns, J, Verner, MA, Iszatt, N, Nowack, N, Bach, CC, Vrijheid, M, Costa, O, Andiarena, A, Sovcikova, E, Høyer, BB, et al
Environmental health perspectives. 2020;(5):57002
Abstract
INTRODUCTION To date, the evidence for an association between perfluoroalkyl substances (PFAS) exposure and attention deficit and hyperactivity disorder (ADHD) is inconclusive. OBJECTIVE We investigated the association between early life exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), and ADHD in a collaborative study including nine European population-based studies, encompassing 4,826 mother-child pairs. METHODS Concentrations of PFOS and PFOA were measured in maternal serum/plasma during pregnancy, or in breast milk, with different timing of sample collection in each cohort. We used a validated pharmacokinetic model of pregnancy and lactation to estimate concentrations of PFOS and PFOA in children at birth and at 3, 6, 12, and 24 months of age. We classified ADHD using recommended cutoff points for each instrument used to derive symptoms scores. We used multiple imputation for missing covariates, logistic regression to model the association between PFAS exposure and ADHD in each study, and combined all adjusted study-specific effect estimates using random-effects meta-analysis. RESULTS A total of 399 children were classified as having ADHD, with a prevalence ranging from 2.3% to 7.3% in the studies. Early life exposure to PFOS or PFOA was not associated with ADHD during childhood [odds ratios (ORs) ranging from 0.96 (95% CI: 0.87, 1.06) to 1.02 (95% CI: 0.93, 1.11)]. Results from stratified models suggest potential differential effects of PFAS related to child sex and maternal education. CONCLUSION We did not identify an increased prevalence of ADHD in association with early life exposure to PFOS and PFOA. However, stratified analyses suggest that there may be an increased prevalence of ADHD in association with PFAS exposure in girls, in children from nulliparous women, and in children from low-educated mothers, all of which warrant further exploration. https://doi.org/10.1289/EHP5444.
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Biomarkers of environmental manganese exposure and associations with childhood neurodevelopment: a systematic review and meta-analysis.
Liu, W, Xin, Y, Li, Q, Shang, Y, Ping, Z, Min, J, Cahill, CM, Rogers, JT, Wang, F
Environmental health : a global access science source. 2020;(1):104
Abstract
BACKGROUND Although prior studies showed a correlation between environmental manganese (Mn) exposure and neurodevelopmental disorders in children, the results have been inconclusive. There has yet been no consistent biomarker of environmental Mn exposure. Here, we summarized studies that investigated associations between manganese in biomarkers and childhood neurodevelopment and suggest a reliable biomarker. METHODS We searched PubMed and Web of Science for potentially relevant articles published until December 31th 2019 in English. We also conducted a meta-analysis to quantify the effects of manganese exposure on Intelligence Quotient (IQ) and the correlations of manganese in different indicators. RESULTS Of 1754 citations identified, 55 studies with 13,388 subjects were included. Evidence from cohort studies found that higher manganese exposure had a negative effect on neurodevelopment, mostly influencing cognitive and motor skills in children under 6 years of age, as indicated by various metrics. Results from cross-sectional studies revealed that elevated Mn in hair (H-Mn) and drinking water (W-Mn), but not blood (B-Mn) or teeth (T-Mn), were associated with poorer cognitive and behavioral performance in children aged 6-18 years old. Of these cross-sectional studies, most papers reported that the mean of H-Mn was more than 0.55 μg/g. The meta-analysis concerning H-Mn suggested that a 10-fold increase in hair manganese was associated with a decrease of 2.51 points (95% confidence interval (CI), - 4.58, - 0.45) in Full Scale IQ, while the meta-analysis of B-Mn and W-Mn generated no such significant effects. The pooled correlation analysis revealed that H-Mn showed a more consistent correlation with W-Mn than B-Mn. Results regarding sex differences of manganese associations were inconsistent, although the preliminary meta-analysis found that higher W-Mn was associated with better Performance IQ only in boys, at a relatively low water manganese concentrations (most below 50 μg/L). CONCLUSIONS Higher manganese exposure is adversely associated with childhood neurodevelopment. Hair is the most reliable indicator of manganese exposure for children at 6-18 years of age. Analysis of the publications demonstrated sex differences in neurodevelopment upon manganese exposure, although a clear pattern has not yet been elucidated for this facet of our study.
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The role of exposure to phthalates in variations of anogenital distance: A systematic review and meta-analysis.
Zarean, M, Keikha, M, Feizi, A, Kazemitabaee, M, Kelishadi, R
Environmental pollution (Barking, Essex : 1987). 2019;:172-179
Abstract
Environmental chemicals such as phthalate esters may have adverse effects on anogenital distance (AGD), but the evidence in both genders has not been reviewed systematically. The objective of the present study is to conduct a systematic review and meta-analysis of studies that analyzed the relationship between exposure to phthalates and AGD. English papers published up to March 2018 were searched in PubMed, Scopus, Clarivate-Web of Science, and Google scholar. We applied fixed-effects models to calculate pooled beta coefficient [β]. In the case of heterogeneity, random-effects models were used. Using the comprehensive search strategies, 313 papers were identified and after screening, 10 of them were included in this study. In primary analyses, we found that exposure to phthalates was not associated with short AGD (β = -0.11; 95% CI, -0.27, 0.06; I2 = 0%). However, results of subgroup analyses indicated that in boys, the sum of di-2-ethylhexyl phthalate (∑DEHP) metabolites had significant association with the risk of shortened anopenile distance (AGDAP) (β = -0.915, 95% CI: 1.629, -0.2) and anoscrotal distance (AGDAS) (β = -0.857, 95% CI: 1.455, -0.26). In addition, urinary monobutyl phthalate (MBP), monoethyl phthalate (MEP), and monoisobutyl phthalate (MiBP) were associated with short AGDAP. We also observed significant association between monobenzylphthalate (MBzP) and anofourchette distance (AGDAF) in girls. Our study provided findings on significant association of exposure to ∑DEHP metabolites, MBP, MEP, and MiBP with shortened AGDAP in boys. The mechanisms of phthalates effect on AGD may involve receptors and enzymes involved in steroidgenesis, negative influence on Leydig cells, cell proliferation, gonocyte cell numbers, and testosterone production.
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Environmental toxic metal contaminants and risk of cardiovascular disease: systematic review and meta-analysis.
Chowdhury, R, Ramond, A, O'Keeffe, LM, Shahzad, S, Kunutsor, SK, Muka, T, Gregson, J, Willeit, P, Warnakula, S, Khan, H, et al
BMJ (Clinical research ed.). 2018;:k3310
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Abstract
OBJECTIVE To conduct a systematic review and meta-analysis of epidemiological studies investigating the association of arsenic, lead, cadmium, mercury, and copper with cardiovascular disease. DESIGN Systematic review and meta-analysis. DATA SOURCES PubMed, Embase, and Web of Science searched up to December 2017. REVIEW METHODS Studies reporting risk estimates for total cardiovascular disease, coronary heart disease, and stroke for levels of arsenic, lead, cadmium, mercury, or copper were included. Two investigators independently extracted information on study characteristics and outcomes in accordance with PRISMA and MOOSE guidelines. Relative risks were standardised to a common scale and pooled across studies for each marker using random effects meta-analyses. RESULTS The review identified 37 unique studies comprising 348 259 non-overlapping participants, with 13 033 coronary heart disease, 4205 stroke, and 15 274 cardiovascular disease outcomes in aggregate. Comparing top versus bottom thirds of baseline levels, pooled relative risks for arsenic and lead were 1.30 (95% confidence interval 1.04 to 1.63) and 1.43 (1.16 to 1.76) for cardiovascular disease, 1.23 (1.04 to 1.45) and 1.85 (1.27 to 2.69) for coronary heart disease, and 1.15 (0.92 to 1.43) and 1.63 (1.14 to 2.34) for stroke. Relative risks for cadmium and copper were 1.33 (1.09 to 1.64) and 1.81 (1.05 to 3.11) for cardiovascular disease, 1.29 (0.98 to 1.71) and 2.22 (1.31 to 3.74) for coronary heart disease, and 1.72 (1.29 to 2.28) and 1.29 (0.77 to 2.17) for stroke. Mercury had no distinctive association with cardiovascular outcomes. There was a linear dose-response relation for arsenic, lead, and cadmium with cardiovascular disease outcomes. CONCLUSION Exposure to arsenic, lead, cadmium, and copper is associated with an increased risk of cardiovascular disease and coronary heart disease. Mercury is not associated with cardiovascular risk. These findings reinforce the importance of environmental toxic metals in cardiovascular risk, beyond the roles of conventional behavioural risk factors.
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Association Between Cd Exposure and Risk of Prostate Cancer: A PRISMA-Compliant Systematic Review and Meta-Analysis.
Ju-Kun, S, Yuan, DB, Rao, HF, Chen, TF, Luan, BS, Xu, XM, Jiang, FN, Zhong, WD, Zhu, JG
Medicine. 2016;(6):e2708
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Several observational studies on the association between Cd exposure and risk of prostate cancer have yielded inconsistent results. To address this issue, we conducted a meta-analysis to evaluate the correlation between Cd exposure and risk of prostate cancer.Relevant studies in PubMed and Embase databases were retrieved until October 2015. We compared the highest and lowest meta-analyses to quantitatively evaluate the relationship between Cd exposure and risk of prostate cancer. Summary estimates were obtained using a random-effects model.In the general population, high Cd exposure was not associated with increased prostate cancer (OR 1.21; 95% CI 0.91-1.64), whereas the combined standardized mortality ratio of the association between Cd exposure and risk of prostate cancer was 1.66 (95% CI 1.10-2.50) in populations exposed to occupational Cd. In addition, high D-Cd intake (OR 1.07; 95% CI 0.96-1.20) and U-Cd concentration (OR 0.86; 95% CI 0.48-1.55) among the general population was not related to the increased risk of prostate cancer. In the dose analysis, the summary relative risk was 1.07 (95% CI 0.73-1.57) for each 0.5 μg/g creatinine increase in U-Cd and 1.02 (95% CI 0.99-1.06) for each 10 μg/day increase of dietary Cd intake. However, compared with nonoccupational exposure, high occupational Cd exposure may be associated with the increased risk of prostate cancer.This meta-analysis suggests high Cd exposure as a risk factor for prostate cancer in occupational rather than nonoccupational populations. However, these results should be carefully interpreted because of the significant heterogeneity among studies. Additional large-scale and high-quality prospective studies are needed to confirm the association between Cd exposure and risk of prostate cancer.
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Persistent organic pollutants and type 2 diabetes: a prospective analysis in the nurses' health study and meta-analysis.
Wu, H, Bertrand, KA, Choi, AL, Hu, FB, Laden, F, Grandjean, P, Sun, Q
Environmental health perspectives. 2013;(2):153-61
Abstract
BACKGROUND Prospective data regarding persistent organic pollutants (POPs) and risk of type 2 diabetes (T2D) are limited, and the results for individual POPs are not entirely consistent across studies. OBJECTIVES We prospectively examined plasma POP concentrations in relation to incident T2D and summarized existing evidence in a meta-analysis. METHODS Plasma polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and hexachlorobenzene (HCB) concentrations were measured in 1,095 women who were free of diabetes at blood draw in 1989-1990 and participated in two case-control studies in the Nurses' Health Study. We identified 48 incident T2D cases through 30 June 2008. We conducted a literature search in PubMed and EMBASE through December 2011 to identify prospective studies on POPs in relation to diabetes. We used a fixed-effects model to summarize results. RESULTS After multivariable adjustment, plasma HCB concentration was positively associated with incident T2D [pooled odds ratio (OR) 3.59 (95% CI: 1.49, 8.64, ptrend = 0.003) comparing extreme tertiles]. Other POPs were not significantly associated with diabetes. After pooling our results with those of six published prospective studies that included 842 diabetes cases in total, we found that HCB and total PCBs both were associated with diabetes: the pooled ORs were 2.00 (95% CI: 1.13, 3.53; I2 = 21.4%, pheterogeneity = 0.28) and 1.70 (95% CI: 1.28, 2.27; I2 = 16.3%, pheterogeneity = 0.30) for HCB and total PCBs, respectively. CONCLUSIONS These findings support an association between POP exposure and the risk of T2D.