OBJECTIVES: Preterm neonates are at increased risk of sepsis compared with those born at term. We investigated immune status at birth and early neonatal life in very preterm neonates and its association with short-term outcomes. METHODS: Prospective observational study conducted at a university hospital recruiting 113 preterm neonates (23-32 weeks) and 78 controls. Monocyte major histocompatibility complex (MHC) class II expression, serum, and ex vivo lipopolysaccharide stimulated levels of six cytokines (tumor necrosis factor α, interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-12p70) were measured in umbilical cord blood and over the first 7 days. The presence of neonatal sepsis and histologic chorioamnionitis was recorded. RESULTS: Prematurity (preterm labor and preterm premature rupture of membranes cohorts), neonatal sepsis, and histologic chorioamnionitis were associated with significant reduction in monocyte MHC class II expression. Neonates who had evidence of subsequent protracted sepsis had low levels of MHC class II expression at birth. Serial monocyte MHC class II expression revealed a fall by day 2, in all preterm neonates, with the degree being influenced by both prematurity and sepsis, and incomplete recovery by day 7, suggesting immunoparalysis in preterm premature rupture of membranes and preterm labor cohorts. Whole blood lipopolysaccharide stimulation assay showed significantly lower tumor necrosis factor α, values in preterm neonates who subsequently developed sepsis indicating a degree of immunoparalysis. CONCLUSIONS: Our data support the concept that fetal exposure to inflammation before preterm delivery leads to subsequent endotoxin hyporesponsiveness (immunoparalysis), which increases the risk of subsequent sepsis and associated organ dysfunction.
OBJECTIVES: Preterm neonates are at increased risk of sepsis compared with those born at term. We investigated immune status at birth and early neonatal life in very preterm neonates and its association with short-term outcomes. METHODS: Prospective observational study conducted at a university hospital recruiting 113 preterm neonates (23-32 weeks) and 78 controls. Monocyte major histocompatibility complex (MHC) class II expression, serum, and ex vivo lipopolysaccharide stimulated levels of six cytokines (tumor necrosis factor α, interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-12p70) were measured in umbilical cord blood and over the first 7 days. The presence of neonatal sepsis and histologic chorioamnionitis was recorded. RESULTS: Prematurity (preterm labor and preterm premature rupture of membranes cohorts), neonatal sepsis, and histologic chorioamnionitis were associated with significant reduction in monocyte MHC class II expression. Neonates who had evidence of subsequent protracted sepsis had low levels of MHC class II expression at birth. Serial monocyte MHC class II expression revealed a fall by day 2, in all preterm neonates, with the degree being influenced by both prematurity and sepsis, and incomplete recovery by day 7, suggesting immunoparalysis in preterm premature rupture of membranes and preterm labor cohorts. Whole blood lipopolysaccharide stimulation assay showed significantly lower tumor necrosis factor α, values in preterm neonates who subsequently developed sepsis indicating a degree of immunoparalysis. CONCLUSIONS: Our data support the concept that fetal exposure to inflammation before preterm delivery leads to subsequent endotoxin hyporesponsiveness (immunoparalysis), which increases the risk of subsequent sepsis and associated organ dysfunction.
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