Severe acute malnutrition in childhood: Hormonal and metabolic status at presentation, response to treatment, and predictors of mortality

Sarah Bartz, Aaloke Mody, Christoph Hornik, James Bain, Michael Muehlbauer, Tonny Kiyimba, Elizabeth Kiboneka, Robert Stevens, John Bartlett, John V. St Peter, Christopher B. Newgard, Michael Freemark

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

Objective: Malnutrition is a major cause of childhood morbidity and mortality. To identify and target those at highest risk, there is a critical need to characterize biomarkers that predict complications prior to and during treatment. Methods: We used targeted and nontargeted metabolomic analysis to characterize changes in a broad array of hormones, cytokines, growth factors, and metabolites during treatment of severe childhood malnutrition. Children aged 6 months to 5 years were studied at presentation to Mulago Hospital and during inpatient therapy with milk-based formulas and outpatient supplementation with ready-to-use food.We assessed the relationship between baseline hormone and metabolite levels and subsequent mortality. Results: Seventy-seven patientswereenrolled in the study; a subsetwasfollowedupfrom inpatient treatment to the outpatient clinic. Inpatient and outpatient therapies increased weight/height z scores and induced striking changes in the levels of fatty acids, amino acids, acylcarnitines, inflammatory cytokines, and various hormones including leptin, insulin, GH, ghrelin, cortisol, IGF-I, glucagon- like peptide-1, and peptide YY.Atotal of 12.2% of the patients died during hospitalization; the major biochemical factor predicting mortality was a low level of leptin (P .0002), a marker of adipose tissue reserve and a critical modulator of immune function. Conclusions: We have used metabolomic analysis to provide a comprehensive hormonal and metabolic profile of severely malnourished children at presentation and during nutritional rehabilitation. Our findings suggest that fatty acid metabolism plays a central role in the adaptation to acute malnutritionandthatlowlevels of the adipose tissuehormoneleptin associate with,andmay predict, mortality prior to and during treatment.

Original languageEnglish
Pages (from-to)2128-2137
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number6
DOIs
StatePublished - Jun 2014

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