Volume, Conductivity and Scatter Properties of Leukocytes (VCS Technology) Is a Highly Sensitive and Specific Predictor of Blood Culture Proven Neonatal Sepsis

In spite of the availability of potent and specific antimicrobial therapy, neonatal septicemia remains as the major cause of mortality. As per WHO estimates, more than 1/3^rd of the estimated 4 million neonatal deaths around the world are caused by severe infections and a quarter, around 1 million, are due to neonatal sepsis/pneumonia alone. In India, in a community based study, septicemia and pneumonia accounted for 52% of neonatal deaths. In a hospital-based data from 17 institutions across the country, the national neonatal-perinatal database network reported 18.6% neonatal deaths to be due to sepsis. However, in extra-mural babies sepsis was the cause of death in 37.6%. The existing indices of sepsis screen include blood culture, which is the gold standard, complete blood count with peripheral blood smear for immature neutrophils, immature to total neutrophil (IT) ratio and C-reactive protein (CRP). The present study aims to evaluate the volume, conductivity and scatter properties of leukocytes (VCS technology) as an early predictor of neonatal sepsis. One hundred and thirty three consecutive neonates (0-28 days of life) admitted to neonatal intensive care unit for suspected sepsis were enrolled in the study together with 36 gestation-matched controls. The blood samples were run on the Beckman Coulter® LH750 and LH755 hematology analyzers to provide data on individual cell volume, high frequency conductivity and laser light scatter, generating a research population data (RPD) on every case. Simultaneous samples were also collected for blood culture and CRP. Peripheral blood smears were made on all cases. The table shows a comparison of Receiver Operating Characteristic (ROC) curves based on the analysis of variables comprising IT ratio, immature neutrophils, band cells+immature neutrophils, CRP, mean neutrophil volume (MNV), and MNV+CRP in neonates with blood culture proven sepsis in relation to negative controls. Using sepsis as a positive criterion, MNV shows the best ROC curve results in newborns with sensitivity of 95.5% and specificity of 82.1% at a cut-off value of >154.2 with AUC of 0.925. MNV is followed by CRP with sensitivity of 78.9% and specificity of 96.3% at a cut-off value of >7 with AUC of 0.891. When MNV and CRP are combined, both the sensitivity and the specificity are enhanced, the former reaching 100.0% and the latter 85.7% at a cut-off value of 154.8 with AUC of 0.968. Immature neutrophils alone have sensitivity of 27.3%, specificity of 89.3% at a cut-off of >2 with AUC 0.55. This had a lower performance than the immature neutrophils +band cells combined at sensitivity of 22.73% but specificity of 96.4% at a cut-off of >12 with AUC 0.597. IT ratio had much better performance compared to both immature neutrophils and immature neutrophils+band cells combined since it showed sensitivity of 66.7%, specificity of 67.9% at a cut-off of >0.09 with AUC 0.634. In comparison to MNV+CRP, the IT ratio+CRP (Rochester criteria) showed significantly lower performance with sensitivity of 84.2%, specificity of 92.9% at a cut-off of >7.04 with AUC 0.908. These results confirm previous preliminary reports by Raimondi et al wherein MNV+CRP showed a sensitivity of 95%, specificity of 97% at a cut-off value of >148 with AUC 0.957. The combination of MNV+CRP with a sensitivity of 100% and specificity of 85.7% may dramatically improve the early detection of neonatal sepsis, a clinical situation with a high mortality rate. It would be important to see how these parameters decrease after successful therapy. Further studies could evaluate IL-6 estimation in place of CRP to see if MNV+IL-6 could further enhance the predictive value. Also, prospective protocols on a larger number of cases and/or randomized co-operative studies could be designed to prove the clinical efficacy of the present findings so as to incorporate them in daily clinical practice.

No relevant conflicts of interest to declare.

Dayanand:Beckman Coulter: Employment. Simon-Lopez:Beckman Coulter: Employment.