Dissertation

Understanding Pathways Underlying Inpatient Mortality of Children with Complicated Severe Malnutrition

Wen, Bijun

2022

Overview

Children admitted to hospitals with severe malnutrition are exceptionally vulnerable to death and account for a large proportion of early childhood mortality globally. In low- and middle- income countries, inpatient mortality rates of severely malnourished children remain high, despite implementation of the empirical management guidelines developed by the World Health Organization. Upon hospital admission, this group of children often present with a wide range of life-threatening illnesses and complications, making risk stratification and identification of underlying causes challenging. Severe malnutrition is also associated with concurrences of subclinical conditions, such as metabolic defects and enteric dysfunctions, that may not be clinically addressed but contribute to mortality. However, very few studies have investigated the pathophysiological pathways involved in the mortality of these children.Using medical records and biological samples among children hospitalized with severe malnutrition in African countries, Malawi and Kenya, the present research aimed to (1) identify clinical warning signs associated with inpatient mortality and evaluate their values in monitoring risks over the course of hospitalization, (2) define systemic pathways associated with mortality employing a multi-omic approach, and (3) evaluate the role of intestinal disturbances in mortality.It was found that monitoring the clinical warning signs: hypoglycemia, reduced consciousness, chest indrawing, not able to complete feeds, nutritional edema, diarrhea, and fever, can serve as a valuable tool for assessing children’s mortality risks during hospitalization. Compared to children who were discharged alive, children who died had distinct biomolecular profiles at admission, indicating that altered energy metabolism and systemic inflammation are associated with inpatient death. Furthermore, enteropathy was found to have a partial contributory role in the mortality of severely malnourished children.These findings alter our thinking around management of children hospitalized with severe malnutrition with important implications in providing novel evidence for guideline optimization to ultimately improve survival outcome of vulnerable children.

• Publisher: ProQuest Dissertations & Theses
• Subject: Biostatistics / Health sciences / Nutrition
• ISBN: 9798209904892