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Intestinal disturbances associated with mortality of children with complicated severe malnutrition
Bijun Wen1,2, Amber Farooqui2, Celine Bourdon2,3
1Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada.
Insights
Intestinal disturbances are indirectly linked to mortality in children with complicated severe malnutrition (CSM). Understanding these gut issues can improve survival rates for critically ill children.
Area of Science:
- Pediatric critical care
- Gastroenterology
- Nutritional science
Background:
- Complicated severe malnutrition (CSM) in children carries a high mortality rate despite standard treatment.
- Limited evidence suggests intestinal dysfunction may impact prognosis in CSM.
- This study investigated the role of intestinal disturbances in CSM-related mortality.
Purpose of the Study:
- To evaluate the association between intestinal disturbances and mortality in hospitalized children with CSM.
- To identify specific markers of intestinal dysfunction in children with fatal outcomes from CSM.
Main Methods:
- A case-control study nested within a randomized controlled trial in Kenya and Malawi.
- Compared fecal metabolomics and enteropathy markers (MPO, calprotectin, I-FABP) between deceased children (cases) and discharged children (controls).
- Propensity score matching was used to control for age, HIV, and nutritional status.
Main Results:
- Fecal metabolomes of deceased children showed reduced amino acids, monosaccharides, and microbial products compared to controls.
- Short-chain fatty acid (SCFA) levels did not differ between groups.
- Enteropathy markers were not significantly different overall, but serum I-FABP was elevated in non-edematous cases, suggesting an indirect role of intestinal inflammation in mortality.
Conclusions:
- Intestinal disturbances are indirectly associated with acute mortality in children with CSM.
- Findings enhance understanding of the complex pathophysiological pathways contributing to CSM mortality.
- Further research into gut health interventions may improve outcomes for critically ill children.
Background:
Children admitted to hospital with complicated severe malnutrition (CSM) have high mortality despite compliance with standard WHO management guidelines. Limited data suggests a relationship between intestinal dysfunction and poor prognosis in CSM, but this has not been explicitly studied. This study aimed to evaluate the role of intestinal disturbances in CSM mortality.
Methods:
A case-control study nested within a randomized control trial was conducted among children hospitalized with CSM in Kenya and Malawi. Children who died (cases, n = 68) were compared with those who were discharged, propensity matched to the cases on age, HIV and nutritional status (controls, n = 68) on fecal metabolomics that targeted about 70 commonly measured metabolites, and enteropathy markers: fecal myeloperoxidase (MPO), fecal calprotectin, and circulating intestinal fatty acid binding protein (I-FABP).
Results:
The fecal metabolomes of cases show specific reductions in amino acids, monosaccharides, and microbial fermentation products, when compared to controls. SCFA levels did not differ between groups. The overall fecal metabolomics signature moderately differentiates cases from controls (AUC = 0.72). Enteropathy markers do not differ between groups overall, although serum I-FABP is elevated in cases in a sensitivity analysis among non-edematous children. Integrative analysis with systemic data suggests an indirect role of intestinal inflammation in the causal path of mortality.
Conclusions:
Intestinal disturbances appear to have an indirect association with acute mortality. Findings of the study improve our understanding of pathophysiological pathways underlying mortality of children with CSM.
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