Project Details

Enteric function: An opportunity to promote survival among children recovering from hospitalization

Kirkby Tickell, MBBS, MPH, PhD

Summary

BACKGROUND: Children being discharged from hospitals in low and middle income countries experience unacceptably high post-discharge mortality rates. Enteric dysfunction (ED) is characterized by malabsorption of nutrients and impaired enteric barrier function, and is likely to be a common condition among children recovering from acute illness. ED may be responsible for the increased morbidity and mortality experienced by children in the post-discharge period. GAP: This study will establish the role of ED in post-discharge childhood mortality, identifying risk factors for poor enteric function, and the clinical utility of blood and stool ED biomarker among acutely unwell children. HYPOTHESIS 1: Children with worse enteric function, as assessed by lactulose:rhamnose (LRR) test, at hospital discharge will have a higher incidence of growth failure than those with better enteric function. HYPOTHESIS 2: Biomarkers of systemic inflammation will link LRR to poor growth in the post-discharge period. METHODS: Children aged 2-23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent the lactulose rhamnose ratio (LRR) enteric permeability test and were compared to similarly aged children from the communities served by these hospitals. Associations between LRR of hospitalized children at discharge with post-discharge height-for-age (HAZ) and weight-for-age z-score (WAZ) trajectories were estimated. Linear regression was used to test if relationships between LRR and biomarkers of systemic inflammation (CRP, CD14, TNF, IL-6) and enterocyte damage (IFABP) were consistent across the hospitalized and community groups. RESULTS: 137 hospitalized children and 84 community participants were included. The hospitalized group had higher log LRR (0.43, 95%CI: 0.15, 0.71, p=0.003) than the community. Adjustment for weight-for-height z-score attenuated this association (0.31, 95%CI: 0.00, 0.62, p=0.049). LRR was not associated with changes in WAZ or HAZ in the post-discharge period. Effect estimates suggested LRR may have been associated with TNF (p=0.004), CD14 (p=0.078) and IL-6 (p=0.062) o community children, but there was no evidence of these association among hospitalized children. Interaction terms also suggested LRR had a different relationship with CRP (p=0.044), TNF (p=0.027), CD14 (p=0.078) and IL-6 (p=0.243) in the community and hospitalized groups. IMPACT: Enteropathy is more prevalent among children being discharged from hospital in comparison to community-based children. However, enteric permeability did not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children. This data supports ED as an interventional target for improving child health in the community, but suggests the findings of community cohorts may not be generalizable to children recovering from acute illness. Interventions aiming to reduce enteric permeability may not prove effective in reducing adverse child health outcomes in the early post-discharge period.