title: Severe acute malnutrition in childhood: hormonal and metabolic status at presentation, response to treatment, and predictors of mortality.
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 patients were enrolled in the study; a subset was followed up from 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. A total 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 malnutrition and that low levels of the adipose tissue hormone leptin associate with, and may predict, mortality prior to and during treatment.
authors.affiliation: Division of Pediatric Endocrinology and Diabetes (S.B., A.M., M.F.), the Pediatric Division of Quantitative Sciences and the Duke Clinical Research Institute (C.H.), the Sarah W. Stedman Nutrition and Metabolism Center (J.B., M.M., R.S., C.B.N., M.F.), and the Duke Global Health Institute (J.B., M.F.), Duke University Medical Center, Durham North Carolina 27705; the Mwanamugimu Nutrition Unit (T.K., E.K.), Mulago Hospital Complex, Kampala, Uganda; and Department of Global Research and Development (J.V.S.P.), Long Term Research, PepsiCo, Inc, Purchase, New York 10577.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bartz
authors.forename: Aaloke
authors.initials: A
authors.lastname: Mody
authors.forename: Christoph
authors.initials: C
authors.lastname: Hornik
authors.forename: James
authors.initials: J
authors.lastname: Bain
authors.forename: Michael
authors.initials: M
authors.lastname: Muehlbauer
authors.forename: Tonny
authors.initials: T
authors.lastname: Kiyimba
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kiboneka
authors.forename: Robert
authors.initials: R
authors.lastname: Stevens
authors.forename: John
authors.initials: J
authors.lastname: Bartlett
authors.forename: John V
authors.initials: JV
authors.lastname: St Peter
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.forename: Michael
authors.initials: M
authors.lastname: Freemark
mesh_terms: D000208:Acute Disease; D046688:Child Mortality; D015362:Child Nutrition Disorders / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D002675:Child, Preschool; D015331:Cohort Studies; D006304:Health Status; D006728:Hormones / Q000097:blood*; D006801:Humans; D007223:Infant; D044342:Malnutrition / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D044623:Nutrition Therapy; D011379:Prognosis; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014454:Uganda / Q000453:epidemiology
chemical_list: D006728:Hormones