Biomarkers of post-discharge mortality among children with complicated severe acute malnutrition

Area of Science:

• Pediatric Infectious Disease
• Nutritional Immunology
• Proteomics

Background:

• High mortality rates persist in children with Severe Acute Malnutrition (SAM) post-hospital discharge.
• The underlying biological mechanisms driving this post-discharge mortality remain poorly understood.
• Identifying these mechanisms is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate the biological profiles associated with mortality in children with SAM after hospital discharge.
• To identify potential biomarkers and biological pathways linked to increased risk of death.
• To understand the physiological state of clinically stable SAM children preceding mortality.

Main Methods:

• A nested case-control study was conducted among HIV-uninfected children (2-59 months) treated for complicated SAM in Kenyan hospitals.
• Plasma samples from children deemed clinically stable at discharge were analyzed using untargeted proteomics, cytokine assays, and leptin measurements.
• Cases (died within 60 days) were compared to controls (survived one year without readmission).

Main Results:

• Increased levels of calprotectin, von Willebrand factor, angiotensinogen, IL8, IL15, IP10, and TNFα were associated with mortality.
• Decreased levels of leptin, heparin cofactor 2, and serum paraoxonase were observed in children who died.
• Enriched biological processes among cases included acute phase response, cellular responses to lipopolysaccharide, neutrophil responses to bacteria, and endothelial responses.

Conclusions:

• Clinically stable children with SAM exhibit a sepsis-like inflammatory profile preceding death.
• This profile may indicate ongoing subclinical bacterial infection, bacterial product translocation, or immune dysregulation during nutritional recovery.
• These findings highlight potential targets for interventions to reduce post-discharge mortality in SAM.