Nucleated red blood cells as a biomarker for mortality in neonates following cardiac surgery

Abstract

Introduction: Nucleated red blood cells (NRBCs) are immature red cells that under normal conditions are not present in the peripheral circulation. Several studies have suggested an association between elevated NRBC and poor outcome in critically ill adults and neonates. We sought to determine if elevations in NRBC value following cardiac surgery and following clinical events during the hospital stay can be used as a biomarker to monitor for mortality risk in neonates post-cardiac surgery. Materials and methods: We constructed a retrospective study of 264 neonates who underwent cardiac surgery at Children’s Hospital, New Orleans between 2011 and 2020. Variables included mortality and NRBC value were recorded following cardiac surgery and following peri-operative clinical events. The study was approved by LSU Health IRB. Sensitivity, specificity, receiver operating characteristic (ROC) curves with area under the curve (AUC) and logistic regression analysis were performed. Results: Thirty-six patients (13.6%) died, of which 32 had an NRBC value ≥10/100 white blood cell (WBC) during hospitalisation. Multi-variable analysis found extracorporeal membrane oxygenation use (OR 10, 95% CI 2.9–33, p=<0.001), NRBC ≥10/100 WBC (OR 16.1, CI 4.1–62.5, p ≤ 0.001) and peak NRBC in the 14-day period post-cardiac surgery (continuous variable, OR 1.05, 95% CI 1.0–1.09, p = 0.03), to be independently associated with mortality. Using a cut-off NRBC value of 10/100 WBC, there was an 88.9% sensitivity and a 90.8% specificity, with ROC curve showing an AUC of 0.9 and 0.914 for peak NRBC value in 14 days post-surgery and entire hospitalisation, respectively. Conclusions: NRBC ≥10/100 WBC post-cardiac surgery is strongly associated with mortality. Additionally, NRBC trend appears to show promise as an accurate biomarker for mortality.

Nucleated red blood cells as a biomarker for mortality in infants and neonates requiring veno-arterial extracorporeal membrane oxygenation for cardiac disease

“…[1][2][3] NRBC value has been reported in many other settings, as a risk factor for mortality, including our recent publication showing NRBC to be an accurate biomarker for mortality following pediatric cardiac surgery. [11][12][13][14][15][16] However, its utility as a potential biomarker to trend when determining mortality risk on ECMO and post-decannulation in infants and neonates requiring VA ECMO has yet to be reported.…”

“…[7][8][9][10] Additionally, several studies have suggested an association between elevated NRBC and poor outcomes in critically ill adults and neonates. [11][12][13][14][15][16] While the presence of NRBCs in the peripheral blood has been studied in several clinical settings, it has yet to be studied in infants and neonates who require VA ECMO cannulation due to cardiac disease. We hypothesize that failure of NRBC value to decline while on ECMO and an increase in NRBC post-decannulation may be predicters of mortality.…”

“…7–10 Additionally, several studies have suggested an association between elevated NRBC and poor outcomes in critically ill adults and neonates. 11–16…”

Diagnostic Value and Prognostic Significance of Nucleated Red Blood Cells (NRBCs) in Selected Medical Conditions

“…Piggott et al suggested that a >50% increase in NRBC count after ECMO decannulation correlates with in-hospital mortality and that pre-ECMO NRBCs may be a useful biomarker of mortality dur-ng ECMO therapy and after decannulation [44]. Additionally, Piggott et al sought to determine whether an elevated NRBC count after cardiac surgery and subsequent hospitalization could be used as a marker to estimate the risk of neonatal mortality after such surgery [45]. Morton et al examined the correlation between NRBC counts and deaths among patients in intensive care units (ICU).…”