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      The Impact of Anemia on Child Mortality: An Updated Review

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          Abstract

          Iron deficiency anemia and child mortality are public health problems requiring urgent attention. However, the degree to which iron deficiency anemia contributes to child mortality is unknown. Here, we utilized an exhaustive article search and screening process to identify articles containing both anemia and mortality data for children aged 28 days to 12 years. We then estimated the reduction in risk of mortality associated with a 1-g/dL increase in hemoglobin (Hb). Our meta-analysis of nearly 12,000 children from six African countries revealed a combined odds ratio of 0.76 (0.62–0.93), indicating that for each 1-g/dL increase in Hb, the risk of death falls by 24%. The feasibility of a 1-g/dL increase in Hb has been demonstrated via simple iron supplementation strategies. Our finding suggests that ~1.8 million deaths in children aged 28 days to five years could be avoided each year by increasing Hb in these children by 1 g/dL.

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          Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial.

          Sunil Sazawal, Robert E Black, Mahdi Ramsan … (2006)
          Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa. However, there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful. We did a randomised, placebo-controlled trial, of children aged 1-35 months and living in Pemba, Zanzibar. We assigned children to daily oral supplementation with: iron (12.5 mg) and folic acid (50 mug; n=7950), iron, folic acid, and zinc (n=8120), or placebo (n=8006); children aged 1-11 months received half the dose. Our primary endpoints were all-cause mortality and admission to hospital. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59549825. The iron and folic acid-containing groups of the trial were stopped early on Aug 19, 2003, on the recommendation of the data and safety monitoring board. To this date, 24 076 children contributed a follow-up of 25,524 child-years. Those who received iron and folic acid with or without zinc were 12% (95% CI 2-23, p=0.02) more likely to die or need treatment in hospital for an adverse event and 11% (1-23%, p=0.03) more likely to be admitted to hospital; there were also 15% (-7 to 41, p=0.19) more deaths in these groups. Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death. In the presence of an active programme to detect and treat malaria and other infections, iron-deficient and anaemic children can benefit from supplementation. However, supplementation of those who are not iron deficient might be harmful. As such, current guidelines for universal supplementation with iron and folic acid should be revised.
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            Association of transmission intensity and age with clinical manifestations and case fatality of severe Plasmodium falciparum malaria.

            Chris Drakeley, Redempta Mbatia, Hugh Reyburn … (2005)
            There are concerns that malaria control measures such as use of insecticide-treated bed nets, by delaying acquisition of immunity, might result in an increase in the more severe manifestations of malaria. An understanding of the relationships among the level of exposure to Plasmodium falciparum, age, and severity of malaria can provide evidence of whether this is likely. To describe the clinical manifestations and case fatality of severe P falciparum malaria at varying altitudes resulting in varying levels of transmission. A total of 1984 patients admitted for severe malaria to 10 hospitals serving populations living at levels of transmission varying from very low (altitude >1200 m) to very high (altitude or =15 years: OR, 0.44; 95% CI, 0.27-0.73; P 1200 m: OR, 0.55; 95% CI, 0.26-1.15; P for trend = .03). The odds of cerebral malaria were significantly higher in low transmission intensity areas (altitude of residence 1200 m: OR, 3.76; 95% CI, 1.96-7.18; P for trend = .003) and with age 5 years and older (0-1 year: referent; 2-4 years: OR, 1.57; 95% CI, 0.82-2.99; 5 to or =15 years: OR, 6.24; 95% CI, 3.47-11.21; P<.001). The overall case-fatality rate of 7% (139 deaths) was similar at high and moderate levels of transmission but increased to 13% in low transmission areas (P = .03), an increase explained by the increase in the proportion of cases with cerebral malaria. Age and level of exposure independently influence the clinical presentation of severe malaria. Our study suggests that an increase in the proportion of cases with more fatal manifestations of severe malaria is likely to occur only after transmission has been reduced to low levels where the overall incidence is likely to be low.
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              An analysis of anemia and child mortality.

              Z Premji, F H Verhoeff, B Brabin (2001)
              The relationship of anemia as a risk factor for child mortality was analyzed by using cross-sectional, longitudinal and case-control studies, and randomized trials. Five methods of estimation were adopted: 1) the proportion of child deaths attributable to anemia; 2) the proportion of anemic children who die in hospital studies; 3) the population-attributable risk of child mortality due to anemia; 4) survival analyses of mortality in anemic children; and 5) cause-specific anemia-related child mortality. Most of the data available were hospital based. For children aged 0-5 y the percentage of deaths due to anemia was comparable for reports from highly malarious areas in Africa (Sierra Leone 11.2%, Zaire 12.2%, Kenya 14.3%). Ten values available for hemoglobin values <50 g/L showed a variation in case fatality from 2 to 29.3%. The data suggested little if any dose-response relating increasing hemoglobin level (whether by mean value or selected cut-off values) with decreasing mortality. Although mortality was increased in anemic children with hemoglobin <50 g/L, the evidence for increased risk with less severe anemia was inconclusive. The wide variation for mortality with hemoglobin <50 g/L is related to methodological variation and places severe limits on causal inference; in view of this, it is premature to generate projections on population-attributable risk. A preliminary survival analysis of an infant cohort from Malawi indicated that if the hemoglobin decreases by 10 g/L at age 6 mo, the risk of dying becomes 1.72 times higher. Evidence from a number of studies suggests that mortality due to malarial severe anemia is greater than that due to iron-deficiency anemia. Data are scarce on anemia and child mortality from non-malarious regions. Primary prevention of iron-deficiency anemia and malaria in young children could have substantive effects on reducing child mortality from severe anemia in children living in malarious areas.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nutrients
                Journal ID (iso-abbrev): Nutrients
                Journal ID (publisher-id): nutrients
                Title: Nutrients
                Publisher: MDPI
                ISSN (Electronic): 2072-6643
                Publication date (Electronic): 22 December 2014
                Publication date Collection: December 2014
                Volume: 6
                Issue: 12
                Pages: 5915-5932
                Affiliations
                [1 ]Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA; E-Mail: sps5032@ 123456psu.edu
                [2 ]Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; E-Mail: lchen78@ 123456jhu.edu
                [3 ]Program in Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; E-Mail: lcaulfi1@ 123456jhu.edu
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: lem118@ 123456psu.edu ; Tel.: +1-814-863-7132; Fax: +1-814-863-6103.
                Article
                Publisher ID: nutrients-06-05915
                DOI: 10.3390/nu6125915
                PMC ID: 4277007
                PubMed ID: 25533005
                SO-VID: fbd9c8a5-7be1-4ae2-8818-b0a79653f8c0
                Copyright © © 2014 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 01 August 2014
                Date revision received : 21 November 2014
                Date accepted : 02 December 2014
                Categories
                Subject: Review

                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: anemia,iron deficiency,child mortality
                Data availability:
                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: anemia, iron deficiency, child mortality

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