Abstract
ObjectiveTo determine if miRNA (miR) expression in umbilical cord blood and umbilical cord tissue differs between neonates with early onset sepsis (EOS) versus neonates without true infection.MethodsRetrospective case-control study design of human patients with EOS (n = 8), presumed sepsis (N = 12) and non-infected control patients (N = 21). Differential expression of >300 miRs was examined using the MIHS-3001ZE-miScript miRNA PCR Array Human miFinder 384HC. Expression levels of miRs were normalized using the global Ct mean of expressed miR and compared between groups. Data analysis was performed using GeneGlobe data analysis software. Ratios of over and under-expressed miRs were calculated and compared between groups using receiver operating characteristic (ROC) curves.ResultsBoth umbilical cord plasma and umbilical cord tissue revealed several miRs with differential expression with little overlap between the two specimen types. The most overexpressed miR in plasma of EOS patients was miR-211-5p and the most overexpressed in EOS cord tissue was miR-223-5p. ROC curves comparing the ratios of over and under-expressed miRs for EOS patients and controls resulted in an area under the curve of 0.787 for cord plasma (miR-211-5p/miR-142-3p) and 0.988 for umbilical cord tissue (miR-223-5p/miR-22-3p), indicating good discrimination.ConclusionsmiRs show differential expression in EOS versus non-infected controls and presumed sepsis. A ratio of over and under-expressed miRs can provide a potentially sensitive and specific diagnostic test for EOS.
Highlights
While acute chorioamnionitis is a relatively common condition affecting 1–4% of all births in the United States [1], infection of the neonate is less common affecting only 0.77–1 per 1000 livebirths [2, 3]
A major gap in addressing early onset sepsis (EOS) is the lack of reliability in identifying those infants who are infected amongst the many infants born with a history of clinical chorioamnionitis
Many premature neonates are treated with broad-spectrum antibiotics [6] which can lead to serious adverse consequences including disrupted gastrointestinal colonization, necrotizing enterocolitis, invasive fungal infections, and development of antimicrobial resistance [7]
Summary
While acute chorioamnionitis is a relatively common condition affecting 1–4% of all births in the United States [1], infection of the neonate is less common affecting only 0.77–1 per 1000 livebirths [2, 3]. Many premature neonates are treated with broad-spectrum antibiotics [6] which can lead to serious adverse consequences including disrupted gastrointestinal colonization, necrotizing enterocolitis, invasive fungal infections, and development of antimicrobial resistance [7]. To address this gap, a more reliable method for diagnosis of EOS is needed which utilizes either neonatal blood or tissue and identifies evidence of the fetal/neonatal inflammatory response to infection. Previous work has illustrated acute phase reactants [5] and even bacterial 16SrRNA DNA [8] can be found in the cord blood of patients with EOS; other blood and tissue markers such as miRNAs (miRs) have only recently been explored in EOS [9,10,11,12]
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