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This study aims to evaluate the diagnostic utilities of four leukocyte surface antigens-two lymphocyte antigens (CD25 and CD45RO) and two neutrophil antigens (CD11b and CD64)-for identification of late-onset nosocomial bacterial infection in preterm, very low birthweight infants, and to define the optimal cutoff value for each marker so that it may act as a reference with which future studies can be compared. Very low birthweight infants in whom infection was suspected when they were >72 h of age were eligible for the study. A full sepsis screen was performed in each episode. IL-6, C-reactive protein, and leukocyte surface antigens (CD25, CD45RO, CD11b, and CD64) were measured at 0 (at the time of sepsis evaluation), 24, and 48 h by standard biochemical methods and quantitative flow cytometric analysis. The diagnostic utilities including sensitivity, specificity, and positive and negative predictive values of each marker and combination of markers for predicting late-onset neonatal infection were determined. One hundred twenty-seven episodes of suspected clinical sepsis were investigated in 80 infants. Thirty-seven episodes were proven infection. The calculated optimal cutoff values for CD25, CD45RO, CD11b, and CD64 were 3,100, 2,900, 10,450, and 4,000 phycoerythrin-molecules bound per cell, respectively. An interim analysis of data after 68 episodes suggested that CD25 and CD45RO were poor predictors of neonatal infection with sensitivity or specificity

The normal range of serum cortisol concentrations and the appropriate levels of circulating cortisol in different clinical situations in preterm infants are not well defined. This study aimed to evaluate the impact of perinatal factors on circulating cortisol levels in preterm infants and to create a quantitative model that could estimate the "adjusted cortisol percentile." Serial serum cortisol concentrations were measured in 209 infants ≤ 32 wk gestation on d 1, 4, 7, 14, and 21 of life. Seven perinatal factors or conditions that could affect circulating cortisol level were identified. Serum cortisol levels were higher on d 4 (p = 0.007) and d 7 (p = 0.007) but lower on d 21 (p = 0.001) compared with d 1. Serum cortisol was also higher in infants on nasal continuous positive airway pressure (p = 0.003); requiring a second vasopressor (p0.001); with intraventricular hemorrhage (≥ grade 3; p0.001); with histologic chorioamnionitis (p = 0.007); with severe lung disease (p = 0.046); and with decreasing GA (p0.001). A mathematical equation was proposed based on factors derived in this preliminary study for estimating the adjusted cortisol percentile. Frontline neonatologists could now access the equation on our Web site (http://www.sta.cuhk.edu.hk/pswong/ACortP.html) to calculate the adjusted cortisol percentile, which could potentially improve the interpretation of circulating cortisol in different clinical situations.

Very low birth weight (VLBW) infants with suspected late-onset infection requiring sepsis screening were enrolled in a prospective study to evaluate the diagnostic utilities of a comprehensive panel of key chemokines and cytokines, both individually and in combination, to identify diagnostic markers for early recognition of bacterial sepsis and necrotizing enterocolitis (NEC). Plasma chemokines interleukin (IL)-8, interferon-gamma-inducible protein 10 (IP-10), monokine induced by interferon-gamma (MIG), monocyte chemoattractant protein 1 (MCP-1), growth-related oncogene-alpha (GRO-alpha), and regulated upon activation of normal T cell expressed and secreted (RANTES) and cytokines IL-1beta, IL-6, IL-10, IL-12p70, and tumor necrosis factor alpha (TNF-alpha) were measured at the onset of sepsis (0 h) and 24 h later. Of 155 suspected infection episodes, 44 were classified as infected. Concentrations of all studied inflammatory mediators (except IL-1beta and RANTES) were significantly higher in the infected than in the noninfected group at 0 h, but the levels decreased precipitously by 24 h. IP-10 with a plasma cutoff concentrationor = 1250 pg/mL could identify all septicemic and NEC cases and had the highest overall sensitivity (93%) and specificity (89%) at 0 h. We conclude that preterm infants have the ability to induce a robust chemokine and cytokine response during sepsis, and IP-10 is a sensitive early marker of infection.

This prospective study aimed to evaluate the diagnostic utilities of neutrophil CD64 expression for the identification of early-onset clinical infection and pneumonia in term infants and to define the optimal cutoff value so that it may act as a reference with which future studies can be compared. Term newborns in whom infection was suspected when they were

Atopic disease is characterized by an imbalance in cytokines secreted from Th1 and Th2 lymphocytes. The association between atopy and serum levels of atopy-related chemokines in umbilical cord blood (UCB) has not been evaluated. This study formulates the reference ranges of thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), eotaxin (EOX), monocyte chemotactic protein 1 (MCP-1), and interferon-gamma-inducible protein 10 (IP-10) in UCB of term neonates and investigates the relation between these chemokines and the development of atopy during infancy. The concentrations of total IgE and chemokines in UCB serum were measured by microparticle immunoassay and sandwich enzyme immunoassay, respectively. A total of 124 singleton healthy newborns were investigated. Fifty-three (43%) infants had family history of allergic diseases, and 26 (21%) had increased serum total IgE concentrations. The median (interquartile range) serum TARC, MDC, EOX, MCP-1, and IP-10 concentrations, in pg/mL, were 425 (300-639), 786 (561-1050), 36 (28-45), 156 (116-205), and 38 (29-49), respectively. Multiparity was associated with increased serum MDC (p = 0.017). Serum chemokine concentrations were not associated with total IgE levels or family history of allergies. The median (interquartile range) serum MDC concentrations in newborns who developed wheezing during infancy and those without wheezing were 1259 pg/mL (945-1523) and 782 pg/mL (551-992), respectively (p = 0.010). This study provides reference ranges of Th-specific chemokines in UCB serum of singleton term neonates. Increased serum MDC concentrations at birth are associated with the occurrence of wheezing during infancy.

The association between lung injury and thrombocytopenia was investigated by comparing the megakaryocyte and platelet counts, and platelet activation using P-selectin as a marker, between the prepulmonary (right atrial) and postpulmonary (left atrial) blood in adult and neonatal (preterm and term) rats with and without hyperoxic lung injury. In the healthy controls, the postpulmonary blood had lower megakaryocyte count (prepulmonary versus postpulmonary: Preterm: 8.7[0.6] versus 3.9[0.3] per ml, p < 0.001; Term: 8.7[1.1] versus 2.6[0.4] per ml, p < 0.001; Adult: median [interquartile ranges]: 2.5[1.0, 5.0] versus 1.0[0, 3.0] per ml, p < 0.001), higher platelet count (prepulmonary versus postpulmonary: Preterm: 491.2[11.1] x 10(9)/L versus 595.1[10.2] x 10(9)/L, p < 0.001; Term: 472.5[19.9] x 10(9)/L versus 579.3[26.2] x 10(9)/L, p < 0.001; Adult: 513.9[31.5] x 10(9)/L versus 664.7[28.8] x 10(9)/L, p < 0.001), but similar P-selectin expression. In contrast, the lung-damaged animals did not show any such differences in either megakaryocyte or platelet count, but P-selectin expression was greater in the postpulmonary blood (prepulmonary versus postpulmonary: Preterm: 38.7[3.9] versus 56.4[4.9]% platelets, p = 0.02; Term: 40.9[2.0] versus 54.0[4.2]% platelets, p = 0.002; Adults: 30.0[3.6] versus 49.1[4.7]% platelets, p = 0.003). Peripheral platelet and intra-pulmonary megakaryocyte counts in the lung-damaged rats were significantly lower than those in their respective controls. Intra-pulmonary thrombi or platelet aggregation were detected in the lung-damaged rats but not in the controls. These findings showed that hyperoxic lung damage reduced circulating platelets through (1) failure of the lungs to retain and fragment megakaryocytes to release platelets, and (2) platelet activation leading to platelet aggregation, thrombi formation and platelet consumption. The magnitude of platelet reduction was physiologically significant, as demonstrated by higher counts of megakaryocyte colony forming units in the bone marrow culture of the animals in the hyperoxia group when compared with the controls.