This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Neonatal sepsis is a major cause for mortality and morbidity. Diagnosis of sepsis is hampered by 48-72 hr delay in reporting and lack of sensitivity of blood cultures. Antepartum antibiotics and small volumes of blood available for culture further complicate diagnosis. Evaluation of inflammatory biomarkers (e.g. CRP, cytokines and chemokines) is a promising strategy. Correlation of inflammatory biomarker patterns with clinical data may lead us to a rapid and a sensitive method for diagnosis of sepsis and monitor recovery. Hypothesis: The profile of inflammatory mediators measured in neonates will be altered prior to, with the onset and with recovery from sepsis. Methods: This study is an observational cohort study. Infants who weigh =1,500 grams at birth and =32 weeks estimated gestational age admitted to the NICU at TCH are eligible. Infants will be enrolled in the first 10 days of life, after informed consent. Our estimated sample size is 200 infants (600 in total from other centers). Research data that will be collected are blood samples and clinical and laboratory data. An extra drop of blood during routine clinical monitoring of these infants will be used to measure inflammatory biomarker profile by Rules Based Medicine (RBM). No blood draws will be done solely for research purposes. After recruitment of the sample size, 100 infected and 100 non-infected matched controls will be identified. Samples surrounding the infection episode will be analyzed by RBM (7 samples/infant), for a total of 1400 samples. Anticipated results and significance: Clinical and other laboratory data will be correlated to blood inflammatory marker profiles. Analyses of temporal changes in the analyte profile and clinical data in infected and uninfected infants will identify a composite set of markers for rapid identification and monitor recovery from neonatal sepsis. Early diagnosis and therapy of neonatal sepsis will improve neonatal outcomes. Correctly identifying sepsis will avoid excessive antibiotic use and the emergence of antibiotic resistance. I. HYPOTHESES The profile of inflammatory mediators measured in neonates will be altered a) With the onset of sepsis. b) With recovery from sepsis c) Prior to the onset of infection. II.
SPECIFIC AIMS 1. To measure inflammatory biomarkers of infection in serial blood samples obtained from 200 eligible infants (=1,500 g at birth and =32 weeks gestational age), 100 with culture proven sepsis and 100 without. 2.Obtain daily clinical and other laboratory data from enrolled infants. 3.Correlate the inflammatory biomarker profile with clinical and other laboratory data to compile baseline values. 4.Compare baseline values between culture-proven infection and those without.
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