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.

Figure 1.

Diagnosis and treatment of severe acute malnutrition in Mwanamugimu Nutrition Unit. AMA, against medical advice.

Figure 2.

Percentage change in metabolite levels from baseline. Values represent the means of 62 inpatients at baseline, 54 inpatients after 2 weeks of formula feeding, and 14 outpatients after 4–10 weeks of RUTF. Adiponectin refers to total adiponectin; similar trends were noted in HMW adiponectin. AA, amino acids; HGH, human GH.

Figure 3.

Baseline (pretreatment) leptin levels in children who survived or died during inpatient hospitalization. Horizontal bars represent mean ± SEM.