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Biomedical Investigations for the Optimized Diagnosis and Monitoring of Severe Acute Malnutrition : The OptiDiag Study

Abstract : Current WHO diagnostic recommendations segregate non-edematous children with severe acute malnutrition (SAM) into one of three anthropometric phenotypes, those with: (1) low mid-upper arm circumference (MUAC) only; (2) low weight-for-height z-score (WHZ) only; or (3) both low MUAC and low WHZ—all of which are eligible for nutritional rehabilitation according to WHO guidelines.But, based on both ease of use and reports purporting higher mortality in SAM identified by MUAC, many agencies and some national governments use only MUAC as the sole diagnostic criterion for admission to therapeutic refeeding programs—disqualifying low WHZ only children from access to treatment. This diagnostic paradigm shift is premature because the links between anthropometric phenotype and functional severity have not yet been clearly delineated. In fact, recent secondary analyses of historic databases have shown that children with SAM that are excluded from treatment within the framework of a MUAC-only program (i.e., low WHZ only) have a similar risk of death as those who are included; moreover, children with both anthropometric deficits (i.e., low MUAC and low WHZ) have a higher risk of death.This dissertation aims to describe and compare the pathophysiology and functional severity associated with the anthropometric phenotypes of children with SAM today. Building on existing comparative work on vulnerability in SAM, it asks: how does the vulnerability profile of children with SAM who are excluded from treatment within the framework of a MUAC-only program (i.e., low WHZ only) compare to the profiles of those children who are included (i.e., low MUAC only and/or both low MUAC and low WHZ)?A multi-centric cohort study was conducted in uncomplicated, non-edematous children with SAM in Bangladesh, Burkina Faso and Liberia. Participants were recruited equally into each of the three anthropometric phenotypes. A wide range of clinical and biochemical indicators of health and nutritional status were collected at admission to, and at key time points throughout, therapeutic refeeding. We assessed emerging biomarkers of pathophysiology and viability in addition to traditional indicators of health status and nutritional deprivation. These included: serum leptin, a robust biochemical predictor of mortality in children with SAM; natural isotopic abundances of carbon and nitrogen (δ13C and δ15N) in hair, promising archives of metabolic status; bio-electric impedance, a portable, non-invasive technique for assessing body composition in the field-setting; and combined biochemical assessment of micronutrient deficiencies (vitamin A and iron) and inflammation (acute phase proteins).Analysis of these indicators demonstrated that all children with SAM (i.e., low WHZ and/or low MUAC) presents with clinical evidence of nutritional deprivation and micronutrient deficiencies, with significant heterogeneities on key criteria. Children with low WHZ only have biochemical and clinical deficits that are more severe than those in children with low MUAC only. These results also indicate that children with both anthropometric deficits have the highest risk of acute and post-discharge death and morbidity. On this basis, low WHZ must be retained as an independent diagnostic criterion, in line with WHO recommendations. Further research is urgently needed to develop innovative diagnostic solutions to identify low WHZ children in the community.
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Submitted on : Saturday, December 5, 2020 - 4:40:02 AM
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Trenton Dailey-Chwalibóg. Biomedical Investigations for the Optimized Diagnosis and Monitoring of Severe Acute Malnutrition : The OptiDiag Study. Santé publique et épidémiologie. Institut agronomique, vétérinaire et forestier de France; Universiteit Gent, 2020. English. ⟨NNT : 2020IAVF0005⟩. ⟨tel-03041552⟩

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