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Enteric Permeability, Systemic Inflammation, and Post-Discharge Growth Among a Cohort of Hospitalized Children in
Kirkby D Tickell1,2, Donna M Denno1,2,3, Ali Saleem2,4
1From the Department of Global Health, University of Washington, Seattle, Seattle, WA.
Insights
Increased gut permeability was common in hospitalized children but did not significantly impact their growth or systemic inflammation post-discharge. These findings suggest gut permeability is not a primary driver of poor outcomes in this population.
Area of Science:
- Pediatric Gastroenterology
- Infectious Diseases
- Global Health
Background:
- Gut permeability, assessed via lactulose-rhamnose ratio (LRR), is a key indicator of intestinal health.
- Children in low- and middle-income countries (LMICs) are vulnerable to conditions affecting gut health and growth.
- Understanding gut permeability's role in post-hospitalization recovery is crucial for improving child health outcomes in LMICs.
Purpose of the Study:
- To investigate the association between gut permeability and post-discharge growth in hospitalized children.
- To determine if gut permeability correlates with systemic inflammation markers after hospital discharge.
- To compare gut permeability and its associations in hospitalized versus community children in LMICs.
Main Methods:
- A comparative study involving hospitalized children (2-23 months) and age-matched community controls in Pakistan and Kenya.
- Lactulose-rhamnose ratio (LRR) testing was performed to assess gut permeability.
- Linear mixed-effects models and linear regression analyzed associations between LRR, growth parameters (LAZ, WAZ), and inflammatory markers (CRP, CD14, TNFα, IL-6).
Main Results:
- Hospitalized children exhibited significantly higher gut permeability (log-LRR) compared to community children.
- Increased gut permeability was not associated with changes in weight-for-age z score (WAZ) or length-for-age z score (LAZ) post-discharge.
- While gut permeability showed associations with certain inflammatory markers in community children, these links were not evident in hospitalized children.
Conclusions:
- Increased gut permeability is prevalent in children upon hospital discharge in LMICs.
- Gut permeability does not appear to be a significant predictor of systemic inflammation or impaired growth in these hospitalized children after discharge.
- Further research may be needed to identify other key factors influencing post-discharge recovery and growth in this vulnerable population.
Objectives:
To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries.
Methods:
Children aged 2-23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups.
Results:
One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15-0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00-0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα ( P = 0.017), CD14 ( P = 0.078), and IL-6 ( P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα ( P = 0.004) and approached significance with CD14 ( P = 0.078) and IL-6 ( P = 0.062) in community children, but there was no evidence of these associations among hospitalized children.
Conclusions:
Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children.
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