TY - JOUR
T1 - Metabolomic changes in serum of children with different clinical diagnoses of malnutrition
AU - di Giovanni, Valeria
AU - Bourdon, Celine
AU - Wang, Dominic X.
AU - Seshadri, Swapna
AU - Senga, Edward
AU - Versloot, Christian J.
AU - Voskuijl, Wieger
AU - Semba, Richard D.
AU - Trehan, Indi
AU - Moaddel, Ruin
AU - Ordiz, M. Isabel
AU - Zhang, Ling
AU - Parkinson, John
AU - Manary, Mark J.
AU - Bandsma, Robert H.J.
N1 - Funding Information:
We thank Hilda Khengere, Alice Tsokonombwe, Agatha Gaussi, Patricia Banda, and Agnes Malamula for their hard work at Queen Elizabeth Central Hospital in Blantyre, Malawi, and Horris Chikwiri, Eleanor Chipofya, Rosemary Godwa, Lydia Kamenya, Jackson Makwinja, Jeanne Mbawa, Nester Mwase, and Vegas Riscado from the St. Louis Nutrition Project. Also, we thank Martin Post, Michael Leadley, and Denis Reynaud from the Analytical Facility for Bioactive Molecules at the Hospital for Sick Children. VDG, CB, RDS, IT, RM, MJM, and RHJB conceptualized and designed the study; VDG, CB, RDS, IT, MIO, MJM, and RHJB coordinated data collection and transfer; VDG, CB, DXW, and RHJB analyzed the data and drafted the final manuscript; ES assisted with the literature review and drafting of the manuscript; CJV, IT, MIO, and LZ assisted in analyzing and coordinating clinical samples; CJV and MIO created and managed the original database; SS, RM, and JP assisted in pathway analysis and contributed to the initial manuscript; WV coordinated and participated in patient recruitment and data collection; and RHJB had primary responsibility for the final content. All authors read and approved the final manuscript.
Publisher Copyright:
© American Society for Nutrition.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Background: 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. Objectives: 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. Methods: We studied children aged 9-59mo from Malawi whowere hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 withmarasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serumfrom 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. Results: 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 kynureninetryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAMhad profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improvedwith nutritional rehabilitation, butmost sphingomyelins and phosphatidylcholines did not. Conclusions: 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.
AB - Background: 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. Objectives: 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. Methods: We studied children aged 9-59mo from Malawi whowere hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 withmarasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serumfrom 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. Results: 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 kynureninetryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAMhad profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improvedwith nutritional rehabilitation, butmost sphingomyelins and phosphatidylcholines did not. Conclusions: 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.
KW - Children
KW - Kwashiorkor
KW - Marasmus
KW - Metabolites
KW - P180 kit
KW - Severe acute malnutrition
KW - Targeted metabolomics
UR - http://www.scopus.com/inward/record.url?scp=85007012181&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85007012181&partnerID=8YFLogxK
U2 - 10.3945/jn.116.239145
DO - 10.3945/jn.116.239145
M3 - Article
C2 - 27807038
AN - SCOPUS:85007012181
SN - 0022-3166
VL - 146
SP - 2436
EP - 2444
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 12
ER -