Immunologic Parameters in Cord Blood Indicating Early-Onset Sepsis

Lehrnbecher, Thomas; Schrod, Lothar; Rutsch, P.; Roos, Thomas; Martius, J.; Stockhausen, H. B. von

doi:10.1159/000244366

Cited by 39 publications

(31 citation statements)

References 20 publications

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“…Several recent studies have explored the utility of measurement of two or more analytes for diagnosis of neonatal infection (11)(12)(13)17). For example, we have shown that CRP Ͼ 6 mg/liter and soluble ICAM-1 Ͼ 300 ng/ml in combination in plasma samples collected under endotoxin-free conditions (12,13) were independent predictors of infection and gave both a high sensitivity for clinical infection (95%) and an NPV of 97% (12).…”

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confidence: 94%

“…Biomarkers are identified through a four-step process of discovery by appropriate multiplex biochemical analysis followed by replication ideally in independent cohorts, validation of diagnostic sensitivity and specificity, and translation into a clinical diagnostic test (9). Numerous candidate biomarkers have been identified in neonatal sepsis: elevated plasma or serum levels of inter-leukin 6 (IL-6) 1 (11,13), tumor necrosis factor ␣ (TNF␣) (11,13), neutrophil elastase (NE) (14), C-reactive protein (CRP) (12,15), soluble CD14 (16,17), granulocyte colony-stimulating factor (G-CSF) (18), soluble intercellular adhesion molecule-1 (ICAM-1) (12), and soluble L-selectin (19) have shown association with infection in neonates. The value of physiological measurements in this context has also been examined recently (20).…”

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confidence: 99%

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Identification of Diagnostic Biomarkers for Infection in Premature Neonates

Kennedy

Halliday

Velkinburgh

et al. 2008

Molecular & Cellular Proteomics

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Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P-and E-selectins, interleukin 2 soluble receptor ␣, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.

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confidence: 94%

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confidence: 99%

Identification of Diagnostic Biomarkers for Infection in Premature Neonates

Kennedy

Halliday

Velkinburgh

et al. 2008

Molecular & Cellular Proteomics

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“…EOBI is usually defined as occurring up to 72 h after birth (2) and is associated with a high morbidity and mortality risk (1). The nonspecific clinical signs as well as the currently established biochemical and hematologic parameters have their diagnostic limitations (3,4) [reviewed in (5,6)]. …”

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confidence: 99%

Evaluation of IL-8-Concentrations in Plasma and Lysed EDTA-Blood in Healthy Neonates and Those with Suspected Early Onset Bacterial Infection

et al. 2004

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Plasma IL-8 is a diagnostic parameter of early-onset bacterial infection (EOBI) in neonates but has a short half-life. The detergent-lysed whole-blood (DLWB) IL-8 consists of both extracellular and cell-bound IL-8. The objective of this study was to investigate kinetics of plasma and DLWB IL-8 in healthy newborns and those with suspected EOBI and to test the hypothesis that determination of DLWB IL-8 results in higher sensitivity for EOBI detection. Sixty-one neonates with clinical and serologic signs of EOBI composed the study group; 188 neonates with risk factors but without EOBI served as control subjects. IL-8 concentrations were determined in plasma and DLWB. In the control group, DLWB IL-8 concentrations were 280-fold higher (9599 pg/mL; SD 4433) up to 24 h post partum than corresponding plasma levels (34.2 pg/mL; SD 18.1). The sensitivity of DLWB versus plasma IL-8 for EOBI was 0.97 versus 0.71 after 6 h and 0.70 versus 0.32 after 24 h. Corresponding values for specificity were 0.95 versus 0.90 after 6 h and 0.92 versus 0.99 after 24 h. After 24 h, the negative predictive value for DLWB versus plasma IL-8 was 0.80 versus 0.66. DLWB IL-8 showed a higher sensitivity for EOBI within 6 h after first clinical suspicion than plasma IL-8. It also remained elevated longer. Our results suggest that DLWB IL-8 results in a higher sensitivity for EOBI. Abbreviations CRP, C-reactive protein DLWB, detergent-lysed whole blood EOBI, early-onset bacterial infection I/T ratio, immature to total neutrophil ratio NPV, negative predictive value PPV, positive predictive value ROC, receiver operator characteristics Neonates are susceptible to infections (1). The differential diagnosis of early-onset bacterial infection (EOBI) therefore must always be present for the neonatologist, regardless of how minor, unexpected, or discrete the clinical symptoms. EOBI is usually defined as occurring up to 72 h after birth (2) and is associated with a high morbidity and mortality risk (1). The nonspecific clinical signs as well as the currently established biochemical and hematologic parameters have their diagnostic limitations (3,4) [reviewed in (5,6)].Plasma IL-8 is an appreciated, highly predictive, and easily accessible chemokine to detect EOBI (7). IL-8 secretion is not limited to infections (8 -10), yet it occurs within 1-3 h of endotoxin challenge (11). As with most cytokines, its plasma half-life is short (Ͻ4 h) (12,13). Circulating IL-8, which can be detected in plasma or serum via immunoassay, is immediately bound to two distinct high-affinity IL-8 receptors that are abundantly present on neutrophils before internalization and degradation (14,15). Therefore, plasma IL-8 reflects only a small portion of the total IL-8 blood pool, because the majority is cell associated (16 -18).Cell association is enhanced by chemokine binding, non-IL-8 -specific receptors. These have been identified on various cell types (19), including the Duffy antigen-related chemokine receptors (16), presented on erythrocytes. Duffy antigenrelated chemokine-li...

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“…Most recent attention has focused on the measurement of cytokines including interleukin-6 (IL-6) [5][6][7], tumour necrosis factor (TNF) [5][6][7] and granulocyte colony-stimulating factor (G-CSF) [9]. However, studies have also evaluated neutrophil elastase [4], C-reactive protein (CRP) [3,5], soluble CD14 [8] and soluble intercellular adhesion molecule-1 (sICAM-1) [5].…”

Section: Introductionmentioning

confidence: 99%

A Low Serum sICAM-1 Level May Assist in the Exclusion of Neonatal Infection

Edgar

Gabriel²,

Craig³

et al. 2002

Neonatology

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Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) in 46 samples from 46 infants undergoing intensive care were studied. Residual serum remaining after routine electrolyte analysis was utilised. sICAM-1 levels were determined by ELISA. Blind retrospective chart review was employed to determine whether infants were infected. Serum levels were significantly elevated in infants with proven and probable infection, compared with non-infected infants (p < 0.001). sICAM-1 levels in serum were comparable to levels previously established in plasma samples. The results suggest that serum sICAM-1 measurement is a simple and robust test that differentiates infected from non-infected infants and that a low level of serum sICAM-1 may particularly assist in the exclusion of infection.

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Immunologic Parameters in Cord Blood Indicating Early-Onset Sepsis

Cited by 39 publications

References 20 publications

Identification of Diagnostic Biomarkers for Infection in Premature Neonates

Identification of Diagnostic Biomarkers for Infection in Premature Neonates

Evaluation of IL-8-Concentrations in Plasma and Lysed EDTA-Blood in Healthy Neonates and Those with Suspected Early Onset Bacterial Infection

A Low Serum sICAM-1 Level May Assist in the Exclusion of Neonatal Infection

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