Comparative Assessment of Cytokines and Other Inflammatory Markers for the Early Diagnosis of Neonatal Sepsis–A Case Control Study

Abstract

ObjectiveCytokines (IL-6, IL-8 and TNF-α), sCD163, and C-reactive protein were serially measured in an attempt to identify a set of tests which can reliably confirm or refute the diagnosis of neonatal sepsis at an early stage.MethodsOne hundred neonates suspected to have sepsis on clinical grounds and who met the inclusion criteria were enrolled for the study. Based on the positive or negative blood culture reports they were classified as infected (n = 50) and non-infected (n = 50) neonates respectively. Fifty healthy neonates without any signs of sepsis were also included in the study as control group. The initial blood sample was taken on day 0 (at the time of sepsis evaluation) and two further samples were taken on days 1 and 2 for monitoring the clinical progress and response to treatment. In the control group the cord blood and 48 hours venous sample was collected. Plasma CRP (ng/ml), IL-6 (pg/ml), IL-8 (pg/ml), TNF-α (ng/ml) and sCD163 (ng/ml) were determined by double antibody method Enzyme Linked Immunosorbent Assay in all the three blood samples.ResultsThe cut of levels for CRP at >19,689 ng/ml had a sensitivity of 68%, specificity of 92%, for IL-6 at >95.32 pg/ml had a sensitivity of 54%, specificity of 96%, for IL-8 at >70.86 pg/ml had a sensitivity of 78%, specificity of 70%, for sCD163 at >896.78 ng/ml had a sensitivity of 100%, specificity of 88% for the diagnosis of infection before antibiotics. TNF-α levels of >12.6 ng/ml showed 100% sensitivity and 72% specificity for the diagnosis of inflammation.ConclusionThe most powerful predictor to differentiate between the non-infected and infected neonates before antibiotics was sCD163. The most powerful indicator for evaluation of prognosis is IL-6. sCD163 can be used alone to screen for sepsis in neonates before the results of blood culture are received.

Raised IL-6 and C-reactive protein in neonatal sepsis in Eastern India

“…6,8,14,15 A study by Smulian et al, reported that IL-6 level showed a highly significant value even in umbilical cord blood in septic neonates. 16 Another study done by Buck et al, also showed similar sensitivity in culture positive and clinical sepsis neonates.…”

“…8 The blood culture is the gold standard for the diagnosis although it is time consuming and it may be negative due to inadequate sample collection or administration of antibiotics intrapartum or intermittent. 5 However, in this study we have taken only the neonates who were blood culture positive to study the cytokine IL-6 and the most commonly used acute phase reactant CRP or hs-CRP or ESR.…”

“…4,10,11 Fewer studies showed that CRP has high specificity and is a better indicator of severe bacterial infection in neonates which may be assumed by our results. 8 CRP is the most extensively studied and commonly available laboratory test used for the prognosis and diagnosis of neonatal sepsis. 1 A study by Hofer et al, dictated that serial CRP measurement along with other markers such as interleukins advances the diagnostic accuracy of neonatal sepsis.…”

CD64 index on neutrophils can diagnose sepsis and predict 30-day survival in subjects after ventilator-associated pneumonia

“…CD64 receptor on neutrophils is a Fcγ receptor 1 for immunoglobulines G (IgG) and has been found to be one of the most useful markers for diagnosis of infection or sepsis beside common CRP and PCT [17][18][19][20][21]. CD64 expression in patients with sepsis is normally induced within two to four hours.…”

Relationship between Early-Onset Neonatal Sepsis and Red Blood Cell Distribution Width (RDW)

“…Term and near-term neonates were diagnosed with suspected clinical sepsis based on a Töllner score of ≥10 or a Töllner score of 5-10 but with the presence of one or more of the following factors associated with an increased risk of infection: maternal fever (≥38°C), prolonged rupture of membranes >18 h and clinical chorioamnionitis [9,19,20]. Inclusion criteria were positive clinical signs of sepsis and/or a history of factors associated with a raised risk of infection.…”