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      Association of Arsenic with Adverse Pregnancy Outcomes/Infant Mortality: A Systematic Review and Meta-Analysis

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          Abstract

          Background

          Exposure to arsenic is one of the major global health problems, affecting > 300 million people worldwide, but arsenic’s effects on human reproduction are uncertain.

          Objectives

          We conducted a systematic review and meta-analysis to examine the association between arsenic and adverse pregnancy outcomes/infant mortality.

          Methods

          We searched PubMed and Ovid MEDLINE (from 1946 through July 2013) and EMBASE (from 1988 through July 2013) databases and the reference lists of reviews and relevant articles. Studies satisfying our a priori eligibility criteria were evaluated independently by two authors.

          Results

          Our systematic search yielded 888 articles; of these, 23 were included in the systematic review. Sixteen provided sufficient data for our quantitative analysis. Arsenic in groundwater (≥ 50 μg/L) was associated with increased risk of spontaneous abortion (6 studies: OR = 1.98; 95% CI: 1.27, 3.10), stillbirth (9 studies: OR = 1.77; 95% CI: 1.32, 2.36), moderate risk of neonatal mortality (5 studies: OR = 1.51; 95% CI: 1.28, 1.78), and infant mortality (7 studies: OR = 1.35; 95% CI: 1.12, 1.62). Exposure to environmental arsenic was associated with a significant reduction in birth weight (4 studies: β = –53.2 g; 95% CI: –94.9, –11.4). There was paucity of evidence for low-to-moderate arsenic dose.

          Conclusions

          Arsenic is associated with adverse pregnancy outcomes and infant mortality. The interpretation of the causal association is hampered by methodological challenges and limited number of studies on dose response. Exposure to arsenic continues to be a major global health issue, and we therefore advocate for high-quality prospective studies that include individual-level data to quantify the impact of arsenic on adverse pregnancy outcomes/infant mortality.

          Citation

          Quansah R, Armah FA, Essumang DK, Luginaah I, Clarke E, Marfoh K, Cobbina SJ, Nketiah-Amponsah E, Namujju PB, Obiri S, Dzodzomenyo M. 2015. Association of arsenic with adverse pregnancy outcomes/infant mortality: a systematic review and meta-analysis. Environ Health Perspect 123:412–421;  http://dx.doi.org/10.1289/ehp.1307894

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          Arsenic toxicity and potential mechanisms of action.

          Michael Hughes (2002)
          Exposure to the metalloid arsenic is a daily occurrence because of its environmental pervasiveness. Arsenic, which is found in several different chemical forms and oxidation states, causes acute and chronic adverse health effects, including cancer. The metabolism of arsenic has an important role in its toxicity. The metabolism involves reduction to a trivalent state and oxidative methylation to a pentavalent state. The trivalent arsenicals, including those methylated, have more potent toxic properties than the pentavalent arsenicals. The exact mechanism of the action of arsenic is not known, but several hypotheses have been proposed. At a biochemical level, inorganic arsenic in the pentavalent state may replace phosphate in several reactions. In the trivalent state, inorganic and organic (methylated) arsenic may react with critical thiols in proteins and inhibit their activity. Regarding cancer, potential mechanisms include genotoxicity, altered DNA methylation, oxidative stress, altered cell proliferation, co-carcinogenesis, and tumor promotion. A better understanding of the mechanism(s) of action of arsenic will make a more confident determination of the risks associated with exposure to this chemical.
          Article 0 comments Cited 254 times – based on 0 reviews     Review now
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            Is Open Access

            The Impact of Study Size on Meta-analyses: Examination of Underpowered Studies in Cochrane Reviews

            Rebecca Turner, Sheila M. Bird, Julian P. T. Higgins (2013)
            Background Most meta-analyses include data from one or more small studies that, individually, do not have power to detect an intervention effect. The relative influence of adequately powered and underpowered studies in published meta-analyses has not previously been explored. We examine the distribution of power available in studies within meta-analyses published in Cochrane reviews, and investigate the impact of underpowered studies on meta-analysis results. Methods and Findings For 14,886 meta-analyses of binary outcomes from 1,991 Cochrane reviews, we calculated power per study within each meta-analysis. We defined adequate power as ≥50% power to detect a 30% relative risk reduction. In a subset of 1,107 meta-analyses including 5 or more studies with at least two adequately powered and at least one underpowered, results were compared with and without underpowered studies. In 10,492 (70%) of 14,886 meta-analyses, all included studies were underpowered; only 2,588 (17%) included at least two adequately powered studies. 34% of the meta-analyses themselves were adequately powered. The median of summary relative risks was 0.75 across all meta-analyses (inter-quartile range 0.55 to 0.89). In the subset examined, odds ratios in underpowered studies were 15% lower (95% CI 11% to 18%, P<0.0001) than in adequately powered studies, in meta-analyses of controlled pharmacological trials; and 12% lower (95% CI 7% to 17%, P<0.0001) in meta-analyses of controlled non-pharmacological trials. The standard error of the intervention effect increased by a median of 11% (inter-quartile range −1% to 35%) when underpowered studies were omitted; and between-study heterogeneity tended to decrease. Conclusions When at least two adequately powered studies are available in meta-analyses reported by Cochrane reviews, underpowered studies often contribute little information, and could be left out if a rapid review of the evidence is required. However, underpowered studies made up the entirety of the evidence in most Cochrane reviews.
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              The epidemiology of adverse pregnancy outcomes: an overview.

              Michael S Kramer (2003)
              This paper provides an overview of the occurrence, etiology and temporal trends of adverse pregnancy outcomes. Disparities between developed and developing countries are highlighted for maternal mortality, infant mortality, stillbirth and low birth weight. The higher rate of low birth weight in developing countries is primarily due to intrauterine growth restriction rather than preterm birth. Much of the excess intrauterine growth restriction is caused by short maternal stature, low prepregnancy body mass index and low gestational weight gain (due to low energy intake). No important contribution has been established for micronutrient intake, nor have different fetal growth trajectories been demonstrated to reflect the timing of exposure to nutritional or other etiologic factors. Infant mortality has declined substantially over time both in developed and developing countries despite no decline (and even an increase) in low birth weight. Several developed countries have reported a temporal increase in fetal growth in infants born at term, a reduction in stillbirth rates and prevention of neural tube defects. More progress is required, however, in understanding the etiology and prevention of preterm birth.
              Article 0 comments Cited 142 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Environ Health Perspect
                Journal ID (iso-abbrev): Environ. Health Perspect
                Journal ID (publisher-id): EHP
                Title: Environmental Health Perspectives
                Publisher: NLM-Export
                ISSN (Print): 0091-6765
                ISSN (Electronic): 1552-9924
                Publication date (Electronic): 27 January 2015
                Publication date (Print): May 2015
                Volume: 123
                Issue: 5
                Pages: 412-421
                Affiliations
                [1 ]Centre for Environmental and Respiratory Health Research, Faculty of Medicine, University Of Oulu, Finland
                [2 ]Department of Biological, Environmental & Occupational Health Sciences, School of Public Health, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
                [3 ]Environment, Health and Hazards Lab, Department of Geography, Western University, London, Ontario, Canada
                [4 ]Environmental Health Group, Department of Chemistry, University of Cape Coast, Cape Coast, Ghana
                [5 ]Department of Geography, Western University Canada, London, Ontario, Canada
                [6 ]Ghana Health Service, Accra, Ghana
                [7 ]Public Health Unit (Biostatistics), Korle-bu Teaching Hospital, Accra, Ghana
                [8 ]School of the Environment, Jiangsu University, Jiangsu, China
                [9 ]Department of Economics, University of Ghana, Legon, Ghana
                [10 ]Department of Child, Adolescent and Adult Health, National Institute for Health and Welfare, Oulu, Finland
                [11 ]School of Health Sciences, University of Tampere, Tampere, Finland
                [12 ]Council for Scientific and Industrial Research, Accra, Ghana
                Author notes
                Address correspondence to R. Quansah, Centre for Environmental and Respiratory Health Research, P.O. Box 5000, FI-90014 University of Oulu, Finland. Telephone: 358 (0)406 724 292. E-mail: rquansah@ 123456ug.edu.gh
                Article
                Publisher ID: ehp.1307894
                DOI: 10.1289/ehp.1307894
                PMC ID: 4421764
                PubMed ID: 25626053
                SO-VID: 192067a8-7da1-49bf-b12f-d91f9984990c
                License:

                Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, “Reproduced with permission from Environmental Health Perspectives”); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.

                History
                Date received : 16 November 2013
                Date accepted : 23 January 2015
                Date: 27 January 2015
                Date: 01 May 2015
                Categories
                Subject: Review

                ScienceOpen disciplines: Public health
                Data availability:
                ScienceOpen disciplines: Public health

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