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      Early exposure to toxic metals has a limited effect on blood pressure or kidney function in later childhood, rural Bangladesh

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          Abstract

          Background Chronic exposure to toxic metals such as arsenic and cadmium has been implicated in the development of kidney and cardiovascular diseases but few studies have directly measured exposure during inutero and early child development.

          Methods We investigated the impact of exposure to arsenic (mainly in drinking water) and cadmium (mainly in rice) during pregnancy on blood pressure and kidney function at 4.5 years of age in rural Bangladesh. The effect of arsenic exposure in infancy was also assessed.

          Results Within a cohort of 1887 children recruited into the MINIMat study, exposure to arsenic (maternal urinary arsenic, U-As), but not cadmium, during in utero development was associated with a minimal increase in blood pressure at 4.5 years. Each 1 mg/l increase in pregnancy U-As was associated with 3.69 mmHg (95% CI: 0.74, 6.63; P: 0.01) increase in child systolic and a 2.91 mmHg (95% CI: 0.41, 5.42; P: 0.02) increase in child diastolic blood pressure. Similarly, a 1 mg/l increase in child U-As at 18 months of age was associated with a 8.25 mmHg (95% CI: 1.37, 15.1; P: 0.02) increase in systolic blood pressure at 4.5 years. There was also a marginal inverse association between infancy U-As and glomerular filtration rate at 4.5 years (−33.4 ml/min/1.72 m 2; 95% CI: −70.2, 3.34; P: 0.08). No association was observed between early arsenic or cadmium exposure and kidney volume at 4.5 years assessed by ultrasound.

          Conclusions These modest effect sizes provide some evidence that arsenic exposure in early life has long-term consequences for blood pressure and maybe kidney function.

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          Most cited references49

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          Current status of cadmium as an environmental health problem.

          Cadmium is a toxic metal occurring in the environment naturally and as a pollutant emanating from industrial and agricultural sources. Food is the main source of cadmium intake in the non-smoking population. The bioavailability, retention and toxicity are affected by several factors including nutritional status such as low iron status. Cadmium is efficiently retained in the kidney (half-time 10-30 years) and the concentration is proportional to that in urine (U-Cd). Cadmium is nephrotoxic, initially causing kidney tubular damage. Cadmium can also cause bone damage, either via a direct effect on bone tissue or indirectly as a result of renal dysfunction. After prolonged and/or high exposure the tubular injury may progress to glomerular damage with decreased glomerular filtration rate, and eventually to renal failure. Furthermore, recent data also suggest increased cancer risks and increased mortality in environmentally exposed populations. Dose-response assessment using a variety of early markers of kidney damage has identified U-Cd points of departure for early kidney effects between 0.5 and 3 microg Cd/g creatinine, similar to the points of departure for effects on bone. It can be anticipated that a considerable proportion of the non-smoking adult population has urinary cadmium concentrations of 0.5 microg/g creatinine or higher in non-exposed areas. For smokers this proportion is considerably higher. This implies no margin of safety between the point of departure and the exposure levels in the general population. Therefore, measures should be put in place to reduce exposure to a minimum, and the tolerably daily intake should be set in accordance with recent findings.
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            Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study.

            Millions of people worldwide are chronically exposed to arsenic through drinking water, including 35-77 million people in Bangladesh. The association between arsenic exposure and mortality rate has not been prospectively investigated by use of individual-level data. We therefore prospectively assessed whether chronic and recent changes in arsenic exposure are associated with all-cause and chronic-disease mortalities in a Bangladeshi population. In the prospective cohort Health Effects of Arsenic Longitudinal Study (HEALS), trained physicians unaware of arsenic exposure interviewed in person and clinically assessed 11 746 population-based participants (aged 18-75 years) from Araihazar, Bangladesh. Participants were recruited from October, 2000, to May, 2002, and followed-up biennially. Data for mortality rates were available throughout February, 2009. We used Cox proportional hazards model to estimate hazard ratios (HRs) of mortality, with adjustment for potential confounders, at different doses of arsenic exposure. 407 deaths were ascertained between October, 2000, and February, 2009. Multivariate adjusted HRs for all-cause mortality in a comparison of arsenic at concentrations of 10.1-50.0 microg/L, 50.1-150.0 microg/L, and 150.1-864.0 microg/L with at least 10.0 microg/L in well water were 1.34 (95% CI 0.99-1.82), 1.09 (0.81-1.47), and 1.68 (1.26-2.23), respectively. Results were similar with daily arsenic dose and total arsenic concentration in urine. Recent change in exposure, measurement of total arsenic concentrations in urine repeated biennially, did not have much effect on the mortality rate. Chronic arsenic exposure through drinking water was associated with an increase in the mortality rate. Follow-up data from this cohort will be used to assess the long-term effects of arsenic exposure and how they might be affected by changes in exposure. However, solutions and resources are urgently needed to mitigate the resulting health effects of arsenic exposure. US National Institutes of Health. Copyright 2010 Elsevier Ltd. All rights reserved.
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              Is low birth weight an antecedent of CKD in later life? A systematic review of observational studies.

              There has been considerable interest in the hypothesis that low birth weight may be a marker of impaired nephrogenesis and that this is causally related to chronic kidney disease (CKD). Systematic review and meta-analysis of observational studies. Studies of the relationship between birth weight and CKD published before February 1, 2008, were identified by using electronic searches. All studies that had collected data for birth weight and kidney function at greater than 12 months of age were eligible for inclusion, except for studies of extremely low-birth-weight infants, very premature infants, or toxic exposure in utero. STUDY FACTOR: Birth weight. CKD defined as albuminuria, low estimated glomerular filtration rate (<60 mL/min/1.73 m(2) or < 10th centile for age/sex), or end-stage renal disease. We analyzed 31 relevant cohort or case-control studies with data for 49,376 individuals and data for 2,183,317 individuals from a single record-linkage study. Overall, 16 studies reported a significant association between low birth weight and risk of CKD and 16 observed a null result. The combination of weighted estimates from the 18 studies for which risk estimates were available (n = 46,249 plus 2,183,317 from the record linkage study) gave an overall odds ratio (OR) of 1.73 (95% confidence interval [CI], 1.44 to 2.08). Combined ORs were consistent in magnitude and direction for risks of albuminuria (OR, 1.81; 95% CI, 1.19 to 2.77), end-stage renal disease (OR, 1.58; 95% CI, 1.33 to 1.88), or low estimated glomerular filtration rate (OR, 1.79; 95% CI, 1.31 to 2.45). A reliance on published estimates and estimates provided on request rather than individual patient data and the possibility of reporting bias. Existing data indicate that low birth weight is associated with subsequent risk of CKD, although there is scope for additional well-designed population-based studies with accurate assessment of birth weight and kidney function and consideration of important confounders, including maternal and socioeconomic factors.
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                Author and article information

                Journal
                Int J Epidemiol
                Int J Epidemiol
                ije
                intjepid
                International Journal of Epidemiology
                Oxford University Press
                0300-5771
                1464-3685
                February 2013
                14 December 2012
                14 December 2012
                : 42
                : 1
                : 176-185
                Affiliations
                1Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, UK, 2Faculty of Medicine, University of Tsukuba, Tsukuba, Japan, 3Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden, 4International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh and 5International Maternal and Child Health, Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
                Author notes
                *Corresponding author. MRC International Nutrition Group, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. E-mail: Sophie.hawkesworth@ 123456lshtm.ac.uk
                Article
                dys215
                10.1093/ije/dys215
                3600625
                23243118
                ef9755a2-a478-4033-9902-e3c67c4306fc
                Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2012; all rights reserved.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 13 November 2012
                Page count
                Pages: 10
                Categories
                Developmental Epidemiology

                Public health
                arsenic,bangladesh,blood pressure,cadmium,kidney function
                Public health
                arsenic, bangladesh, blood pressure, cadmium, kidney function

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