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Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation:
Suzanna Attia1, Christian J Versloot2, Wieger Voskuijl3,4
1Division of Gastroenterology, Hepatology, and Nutrition.
Insights
Diarrhea and inflammation significantly increase mortality risk in children with severe acute malnutrition (SAM). Intestinal pathogens were not linked to death, but inflammation and low short-chain fatty acids (SCFAs) were key factors.
Area of Science:
- Pediatric Gastroenterology
- Infectious Diseases
- Nutritional Science
Background:
- Diarrhea is common in children with severe acute malnutrition (SAM), but its causes and effects are not fully understood.
- Investigating the interplay of diarrhea, enteropathogens, and inflammation is crucial for understanding mortality in SAM.
Purpose of the Study:
- To examine the relationships between diarrhea, enteropathogens, systemic and intestinal inflammation, and mortality in children with complicated SAM.
- To identify key factors contributing to mortality in SAM.
Main Methods:
- Analyzed intestinal pathogens, cytokines, fecal calprotectin, and short-chain fatty acids (SCFAs) in 79 hospitalized children with SAM in Malawi.
- Utilized partial least squares (PLS) path modeling to assess the associations between variables, diarrhea, and death.
Main Results:
- Mortality was higher in younger children with diarrhea. Shigella, Giardia, and Campylobacter were common but not associated with death or diarrhea.
- Children who died had higher fecal calprotectin and lower levels of butyrate and propionate (SCFAs).
- Mortality was directly linked to high systemic inflammation, with diarrhea, high calprotectin, and low SCFAs indirectly contributing via systemic inflammation.
Conclusions:
- Diarrhea, intestinal inflammation, low SCFAs, and systemic inflammation are significantly associated with mortality in SAM, independent of enteropathogen presence.
- Findings enhance understanding of inflammatory processes in SAM, potentially guiding improved therapeutic strategies.
- Registered trial ISRCTN13916953.
Background:
Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear.
Objective:
We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their associations with mortality in children with SAM.
Design:
Intestinal pathogens (n = 15), cytokines (n = 29), fecal calprotectin, and the short-chain fatty acids (SCFAs) butyrate and propionate were determined in children aged 6-59 mo (n = 79) hospitalized in Malawi for complicated SAM. The relation between variables, diarrhea, and death was assessed with partial least squares (PLS) path modeling.
Results:
Fatal subjects (n = 14; 18%) were younger (mean ± SD age: 17 ± 11 compared with 25 ± 11 mo; P = 0.01) with higher prevalence of diarrhea (46% compared with 18%, P = 0.03). Intestinal pathogens Shigella (36%), Giardia (33%), and Campylobacter (30%) predominated, but their presence was not associated with death or diarrhea. Calprotectin was significantly higher in children who died [median (IQR): 1360 mg/kg feces (2443-535 mg/kg feces) compared with 698 mg/kg feces (1438-244 mg/kg feces), P = 0.03]. Butyrate [median (IQR): 31 ng/mL (112-22 ng/mL) compared with 2036 ng/mL (5800-149 ng/mL), P = 0.02] and propionate [median (IQR): 167 ng/mL (831-131 ng/mL) compared with 3174 ng/mL (5819-357 ng/mL), P = 0.04] were lower in those who died. Mortality was directly related to high systemic inflammation (path coefficient = 0.49), whereas diarrhea, high calprotectin, and low SCFA production related to death indirectly via their more direct association with systemic inflammation.
Conclusions:
Diarrhea, high intestinal inflammation, low concentrations of fecal SCFAs, and high systemic inflammation are significantly related to mortality in SAM. However, these relations were not mediated by the presence of intestinal pathogens. These findings offer an important understanding of inflammatory changes in SAM, which may lead to improved therapies. This trial was registered at www.controlled-trials.com as ISRCTN13916953.
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