Advancing approaches to identify young children at risk for post-discharge mortality: Protocol for a prospective...

Childhood mortality rates following hospital discharge may outpace inpatient mortality rates in some sub-Saharan African settings. Broadly validated risk assessment tools and biomarkers to identify children at risk for post-discharge mortality (PDM) are lacking. Moreover, clinical diagnoses (eg, pneumonia, sepsis, etc.) that confer high risk of PDM share a common pathobiology that culminates in endothelial dysfunction. The objectives of this study are to (1) externally validate existing risk assessment tools for PDM at 60 days and (2) test the association between a marker of endothelial dysfunction (ie, the global arginine bioavailability ratio [GABR]) and 60-day PDM among young children.

This is a prospective, observational cohort study of neonates (aged 0-28 days, n=1000) and infants and children (aged 1-59 months, n=1000) consecutively discharged from two hospitals in Western Kenya (ie, Jaramogi Oginga Odinga Teaching and Referral Hospital [JOOTRH] and Siaya County Referral Hospital). Candidate variables for previously developed risk assessment tools identified through a systematic review and plasma samples will be collected on the day of hospital discharge. Caregivers of participants will receive telephone calls 30 days and 60 days following discharge to ascertain participants' vital status. Test characteristics and area under the receiver operating characteristic curves will be calculated for each risk tool to determine their discriminatory value. Risk predictiveness and calibration of each tool will also be determined. Mean and median levels of GABR will be compared between cases and matched controls, and conditional logistic regression will be used to test the association between GABR and PDM.

This protocol has received clearance from the Kenya Medical Research Institute Scientific Ethics Review Unit, the JOOTRH Ethics Research Committee, and the Emory University institutional review board. Our results will be disseminated through scientific presentations at national and international conferences and peer-reviewed publications.