BIOMARKER PROFILES FOR EARLY DIAGNOSIS OF SEPSIS IN NEONATES

用于新生儿脓毒症早期诊断的生物标志物谱

• 批准号: 8166749
• 负责人: MOHAN VENKATESH
• 金额: $ 0.05万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166749
• 关键词: Antibiotic Resistance; Antibiotics; Biological Markers; Birth; Blood; Blood Volume; Blood specimen; Clinical; Clinical Data; Cohort Studies; Computer Retrieval of Information on Scientific Projects Database; Data; Diagnosis; Drops; Early Diagnosis; Enrollment; Evaluation; Funding; Gestational Age; Grant; Infant; Infection; Inflammation Mediators; Inflammatory; Informed Consent; Institution; Laboratories; Lead; Life; Measures; Medicine; Methods; Monitor; Morbidity - disease rate; Neonatal; Outcome; Pattern; Recovery; Reporting; Research; Research Personnel; Resources; Sample Size; Sampling; Sepsis; Source; United States National Institutes of Health; base; chemokine; clinically significant; cytokine; improved; infant monitoring; inflammatory marker; mortality; neonatal sepsis; neonate

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景：新生儿败血症是导致死亡和发病的主要原因。败血症的诊断受到48-72小时报告延迟和缺乏血培养敏感性的阻碍。产前抗生素和少量血液可用于培养进一步复杂化诊断。炎症生物标志物（如CRP，细胞因子和趋化因子）的评价是一个有前途的策略。炎症生物标志物模式与临床数据的相关性可能会导致我们快速和敏感的方法来诊断脓毒症和监测恢复。 假设：在新生儿中测量的炎症介质的概况将在脓毒症发生前、发生时和从脓毒症中恢复时改变。 方法：本研究是一项观察性队列研究。出生时体重≥ 1，500 g且估计胎龄≥ 32周的婴儿可在TCH入住NICU。婴儿将在知情同意后在出生后的前10天内入组。我们估计的样本量为200名婴儿（其他中心共600名）。将收集的研究数据包括血液样本以及临床和实验室数据。在这些婴儿的常规临床监测期间，将使用额外的一滴血通过基于规则的医学（RBM）测量炎症生物标志物特征。不会仅出于研究目的进行抽血。招募样本量后，将确定100例感染和100例未感染的匹配对照。将通过RBM分析感染事件周围的样本（7份样本/婴儿），共计1400份样本。 预期结果和意义：临床和其他实验室数据将与血液炎症标志物特征相关。对感染和未感染婴儿的分析物谱和临床数据的时间变化进行分析，将确定一组复合标志物，用于快速识别和监测新生儿败血症的恢复。新生儿败血症的早期诊断和治疗有助于改善新生儿预后。正确识别败血症将避免过度使用抗生素和抗生素耐药性的出现。 I. 假设 在新生儿中测量的炎症介质的概况将改变 a）、 出现败血症。 B） 从败血症中恢复过来 c）、 在感染开始之前。 二. 具体目标 1.测量200名合格婴儿（出生时≥ 1，500 g，胎龄≥ 32周）的系列血液样本中感染的炎症生物标志物，其中100名经培养证实为败血症，100名无败血症。 2.获取入选婴儿的每日临床和其他实验室数据。 3.将炎症生物标志物特征与临床和其他实验室数据相关联，以编制基线值。 4.比较培养证实感染和未感染的基线值。