Location: Children's Nutrition Research CenterTitle: Metabolomic changes in serum of children with different clinical diagnoses of malnutrition
|DI GIOVANNI, VALERIA - University Of Amsterdam|
|BOURDON, CELINE - University Of Amsterdam|
|WANG, DOMINIC - University Of Amsterdam|
|SESHADRI, SWAPNA - University Of Amsterdam|
|SENGA, EDWARD - University Of Amsterdam|
|VERSLOOT, CHRISTIAN - University Of Amsterdam|
|VOSKUIJL, WIEGER - University Of Amsterdam|
|SEMBA, RICHARD - Johns Hopkins University School Of Medicine|
|TREHAN, INDI - National Institute On Aging (NIA, NIH)|
|MOADDEL, RUIN - National Institute On Aging (NIA, NIH)|
|ORDIZ, M - Washington University|
|ZHANG, LING - University Of Amsterdam|
|PARKINSON, JOHN - University Of Toronto|
|MANARY, MARK - Children'S Nutrition Research Center (CNRC)|
|BANDSMA, ROBERT - Hospital For Sick Children (SICKKIDS)|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/4/2016
Publication Date: 12/1/2016
Citation: Di Giovanni, V., Bourdon, C., Wang, D.X., Seshadri, S., Senga, E., Versloot, C.J., Voskuijl, W., Semba, R.D., Trehan, I., Moaddel, R., Ordiz, M.I., Zhang, L., Parkinson, J., Manary, M.J., Bandsma, R.H. 2016. Metabolomic changes in serum of children with different clinical diagnoses of malnutrition. Journal of Nutrition. 146(12):2436-2444.
Interpretive Summary: There are two clinical presentations of severe acute malnutrition (SAM): kwashiorkor and marasmus, and the mortality among children with SAM still remains high despite standard treatment protocols. We studied children from malawi to further evaluate differences between the two SAM types. It may be beneficial to further understand the metabolic changes that result in the observable characteristics that differentiate these two types of SAM.
Technical Abstract: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. We studied children aged 9-59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children.