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      Blood cadmium is elevated in iron deficient U.S. children: a cross-sectional study

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          Abstract

          Background

          Cadmium (Cd), a widespread environmental contaminant, and iron deficiency (ID), the most common nutrient deficiency in the world, are known risk factors for neurodevelopmental delays, as well as other disorders, in infants and children. Studies assessing the cumulative effects of these factors are lacking in children, despite concerns of increased uptake of metals in the presence of ID. Here we sought to determine if blood and urine Cd levels were elevated in ID children compared to non-ID children.

          Methods

          Data for 5224 children, aged 3–19 years, were obtained from the 1999–2002 NHANES. ID was defined as ≥2 of 3 abnormal iron indicators (low serum ferritin [SF], high free erythrocyte protoporphyrin [FEP], low % transferrin saturation [TSAT]); ID anemia (IDA) was defined as ID plus low hemoglobin (Hgb). Logistic regression was used to evaluate associations between ID, IDA, and abnormal iron indicators and categories of blood and urine Cd.

          Results

          Adjusted odds of ID, IDA, low SF, and low TSAT were associated with increasing category of blood Cd but not urine Cd. Adjusted ORs (95% CI) for blood Cd ≥0.5 μg/L versus < LOD were = 1.74 (1.30-2.34), 4.02 (1.92-8.41), 4.08 (2.36-5.89) and 1.78 (1.32-2.39), for ID, IDA, low SF, and low TSAT, respectively. Age and sex specific analyses of blood Cd and ID/abnormal iron indicators revealed that the observed associations were strongest in females aged 16–19 years.

          Conclusions

          Given their shared neurotoxic effects in children, and that many people live in areas with high burdens of both ID and Cd, more research into the complex relationships between nutrient deficiencies and environmental toxicants is vital.

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          Most cited references43

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          Iron deficiency and brain development.

          Iron deficiency (ID) is common in pregnant women and infants worldwide. Rodent models show that ID during gestation/lactation alters neurometabolism, neurotransmitters, myelination, and gene/protein profiles before and after iron repletion at weaning. Human infants with iron deficiency anemia test lower in cognitive, motor, social-emotional, and neurophysiologic development than comparison group infants. Iron therapy does not consistently improve developmental outcome, with long-term differences observed. Poorer outcome has also been shown in human and monkey infants with fetal/neonatal ID. Recent randomized trials of infant iron supplementation show benefits, indicating that adverse effects can be prevented and/or reversed with iron earlier in development or before ID becomes severe or chronic. This body of research emphasizes the importance of protecting the developing brain from ID.
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            Adverse Health Effects of Chronic Exposure to Low-Level Cadmium in Foodstuffs and Cigarette Smoke

            Cadmium is a cumulative nephrotoxicant that is absorbed into the body from dietary sources and cigarette smoking. The levels of Cd in organs such as liver and kidney cortex increase with age because of the lack of an active biochemical process for its elimination coupled with renal reabsorption. Recent research has provided evidence linking Cd-related kidney dysfunction and decreases in bone mineral density in nonoccupationally exposed populations who showed no signs of nutritional deficiency. This challenges the previous view that the concurrent kidney and bone damage seen in Japanese itai-itai disease patients was the result of Cd toxicity in combination with nutritional deficiencies, notably, of zinc and calcium. Further, such Cd-linked bone and kidney toxicities were observed in people whose dietary Cd intakes were well within the provisional tolerable weekly intake (PTWI) set by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives of 1 μg/kg body weight/day or 70 μg/day. This evidence points to the much-needed revision of the current PTWI for Cd. Also, evidence for the carcinogenic risk of chronic Cd exposure is accumulating and Cd effects on reproductive outcomes have begun to emerge.
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              Heavy metal poisoning: the effects of cadmium on the kidney.

              The heavy metal cadmium (Cd) is known to be a widespread environmental contaminant and a potential toxin that may adversely affect human health. Exposure is largely via the respiratory or gastrointestinal tracts; important non-industrial sources of exposure are cigarette smoke and food (from contaminated soil and water). The kidney is the main organ affected by chronic Cd exposure and toxicity. Cd accumulates in the kidney as a result of its preferential uptake by receptor-mediated endocytosis of freely filtered and metallothionein bound Cd (Cd-MT) in the renal proximal tubule. Internalised Cd-MT is degraded in endosomes and lysosomes, releasing free Cd(2+) into the cytosol, where it can generate reactive oxygen species (ROS) and activate cell death pathways. An early and sensitive manifestation of chronic Cd renal toxicity, which can be useful in individual and population screening, is impaired reabsorption of low molecular weight proteins (LMWP) (also a receptor-mediated process in the proximal tubule) such as retinol binding protein (RBP). This so-called 'tubular proteinuria' is a good index of proximal tubular damage, but it is not usually detected by routine clinical dipstick testing for proteinuria. Continued and heavy Cd exposure can progress to the clinical renal Fanconi syndrome, and ultimately to renal failure. Environmental Cd exposure may be a significant contributory factor to the development of chronic kidney disease, especially in the presence of other co-morbidities such as diabetes or hypertension; therefore, the sources and environmental impact of Cd, and efforts to limit Cd exposure, justify more attention.
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                Author and article information

                Journal
                Environ Health
                Environ Health
                Environmental Health
                BioMed Central
                1476-069X
                2013
                30 December 2013
                : 12
                : 117
                Affiliations
                [1 ]Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
                [2 ]Center for Human Growth and Development, University of Michigan, Ann Arbor, Michigan, USA
                Article
                1476-069X-12-117
                10.1186/1476-069X-12-117
                3883480
                24373608
                2de20c2d-1612-40f7-9015-c402c71b26b4
                Copyright © 2013 Silver et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 November 2013
                : 18 December 2013
                Categories
                Research

                Public health
                cadmium,iron deficiency,serum ferritin,free erythrocyte protoporphyrin,transferrin saturation,anemia,nhanes,cdc

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