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      Severely malnourished children with a low weight-for-height have a higher mortality than those with a low mid-upper-arm-circumference: I. Empirical data demonstrates Simpson’s paradox

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          Abstract

          Background

          According to WHO childhood severe acute malnutrition (SAM) is diagnosed when the weight-for-height Z-score (WHZ) is <−3Z of the WHO 2006 standards, the mid-upper-arm circumference (MUAC) is < 115 mm, there is nutritional oedema or any combination of these parameters. Recently there has been a move to eliminate WHZ as a diagnostic criterion on the assertion that children meeting the WHZ criterion are healthy, that MUAC is universally a superior prognostic indicator of mortality and that adding WHZ to the assessment does not improve the prediction; these assertions have lead to a controversy concerning the role of WHZ in the diagnosis of SAM.

          Methods

          We examined the mortality experience of 76,887 6–60 month old severely malnourished children admitted for treatment to in-patient, out-patient or supplementary feeding facilities in 18 African countries, of whom 3588 died. They were divided into 7 different diagnostic categories for analysis of mortality rates by comparison of case fatality rates, relative risk of death and meta-analysis of the difference between children admitted using MUAC and WHZ criteria.

          Results

          The mortality rate was higher in those children fulfilling the WHO 2006 WHZ criterion than the MUAC criterion. This was the case for younger as well as older children and in all regions except for marasmic children in East Africa. Those fulfilling both criteria had a higher mortality. Nutritional oedema increased the risk of death. Having oedema and a low WHZ dramatically increased the mortality rate whereas addition of the MUAC criterion to either oedema-alone or oedema plus a low WHZ did not further increase the mortality rate. The data were subject to extreme confounding giving Simpson’s paradox, which reversed the apparent mortality rates when children fulfilling both WHZ and MUAC criteria were included in the estimation of the risk of death of those fulfilling either the WHZ or MUAC criteria alone.

          Conclusions

          Children with a low WHZ, but a MUAC above the SAM cut-off point are at high risk of death. Simpson’s paradox due to confounding from oedema and mathematical coupling may make previous statistical analyses which failed to distinguish the diagnostic groups an unreliable guide to policy. WHZ needs to be retained as an independent criterion for diagnosis of SAM and methods found to identify those children with a low WHZ, but not a low MUAC, in the community.

          Electronic supplementary material

          The online version of this article (10.1186/s12937-018-0384-4) contains supplementary material, which is available to authorized users.

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          Most cited references57

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          Maternal and child undernutrition and overweight in low-income and middle-income countries

          The Lancet, 382(9890), 427-451
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            Use and misuse of the receiver operating characteristic curve in risk prediction.

            The c statistic, or area under the receiver operating characteristic (ROC) curve, achieved popularity in diagnostic testing, in which the test characteristics of sensitivity and specificity are relevant to discriminating diseased versus nondiseased patients. The c statistic, however, may not be optimal in assessing models that predict future risk or stratify individuals into risk categories. In this setting, calibration is as important to the accurate assessment of risk. For example, a biomarker with an odds ratio of 3 may have little effect on the c statistic, yet an increased level could shift estimated 10-year cardiovascular risk for an individual patient from 8% to 24%, which would lead to different treatment recommendations under current Adult Treatment Panel III guidelines. Accepted risk factors such as lipids, hypertension, and smoking have only marginal impact on the c statistic individually yet lead to more accurate reclassification of large proportions of patients into higher-risk or lower-risk categories. Perfectly calibrated models for complex disease can, in fact, only achieve values for the c statistic well below the theoretical maximum of 1. Use of the c statistic for model selection could thus naively eliminate established risk factors from cardiovascular risk prediction scores. As novel risk factors are discovered, sole reliance on the c statistic to evaluate their utility as risk predictors thus seems ill-advised.
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              Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker.

              M. S. Pepe (2004)
              A marker strongly associated with outcome (or disease) is often assumed to be effective for classifying persons according to their current or future outcome. However, for this assumption to be true, the associated odds ratio must be of a magnitude rarely seen in epidemiologic studies. In this paper, an illustration of the relation between odds ratios and receiver operating characteristic curves shows, for example, that a marker with an odds ratio of as high as 3 is in fact a very poor classification tool. If a marker identifies 10% of controls as positive (false positives) and has an odds ratio of 3, then it will correctly identify only 25% of cases as positive (true positives). The authors illustrate that a single measure of association such as an odds ratio does not meaningfully describe a marker's ability to classify subjects. Appropriate statistical methods for assessing and reporting the classification power of a marker are described. In addition, the serious pitfalls of using more traditional methods based on parameters in logistic regression models are illustrated.
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                Author and article information

                Contributors
                Emmanuel.Grellety.Bosviel@ulb.ac.be
                mike@pollgorm.net
                Journal
                Nutr J
                Nutr J
                Nutrition Journal
                BioMed Central (London )
                1475-2891
                15 September 2018
                15 September 2018
                2018
                : 17
                : 79
                Affiliations
                [1 ]ISNI 0000 0001 2348 0746, GRID grid.4989.c, Research Center Health Policy and Systems - International Health, School of Public Health, , Université Libre de Bruxelles, ; Bruxelles, Belgium
                [2 ]ISNI 0000 0004 1936 7291, GRID grid.7107.1, Department of Medicine and Therapeutics, , University of Aberdeen, ; Aberdeen, Scotland
                Author information
                http://orcid.org/0000-0001-9736-414X
                Article
                384
                10.1186/s12937-018-0384-4
                6138885
                30217205
                b6c350ae-bb3b-4e45-8fea-28e93dfe8372
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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
                : 24 May 2017
                : 25 July 2018
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Nutrition & Dietetics
                nutrition,acute malnutrition,severe acute malnutrition,sam,mid-upper-arm circumference,muac,weight-for-height,whz,mortality,case fatality rate,wasting,oedema,kwashiorkor,diagnosis,simpson’s paradox,mathematical coupling,child,human,meta-analysis

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