Adult Biomarkers in Neonatal Brain Injury and Development

新生儿脑损伤和发育中的成人生物标志物

• 批准号: 10006591
• 负责人: ALLEN D EVERETT
• 金额: $ 53.05万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10006591
• 关键词: Acute; Adoption; Adult; Atlases; Baltimore; Benchmarking; Biological Assay; Biological Markers; Birth; Blood; Blood - brain barrier anatomy; Blood specimen; Brain; Brain Injuries; Brain-Derived Neurotrophic Factor; Cessation of life; Child; Childhood; Clinical; Data; Detection; Development; Diagnostic; Effectiveness; Enrollment; Enzyme-Linked Immunosorbent Assay; Evaluation; Future; Gestational Age; Glial Fibrillary Acidic Protein; Goals; Hypoxic Brain Damage; IL8 gene; Image; Immunoassay; Infant; Injury; Interleukin-1; Interleukin-6; Intervention Trial; Investigation; Investigational Therapies; Life; Literature; Longitudinal cohort; Low Birth Weight Infant; Magnetic Resonance Imaging; Measures; Medicine; Morbidity - disease rate; Neonatal; Neonatal Brain Injury; Neurodevelopmental Deficit; Neurodevelopmental Disability; Neurologic; Outcome; Pathway interactions; Pediatric Hospitals; Pregnancy; Premature Infant; Proteins; Research Design; Risk; Sampling; Severities; Testing; Therapeutic; Therapeutic Trials; Training; Treatment Efficacy; Triage; Validation; Vascular Endothelial Growth Factors; Very Low Birth Weight Infant; Vulnerable Populations; adverse outcome; age related; base; biomarker panel; brain cell; cell injury; cell type; cohort; cost; disability; early detection biomarkers; exhaustion; experience; hypoxia neonatorum; improved; improved outcome; inflammatory marker; innovation; intraventricular hemorrhage; mortality risk; natural hypothermia; neonatal hypoxic-ischemic brain injury; neonate; novel; novel diagnostics; novel therapeutics; premature; preterm newborn; prognostic; protein biomarkers; response; severe injury; standard care

Project Summary Circulating brain injury biomarkers have been studied extensively in adults, yet we have no clinically available biomarkers to acutely identify brain specific injury common in neonates, such as intraventricular hemorrhage (IVH) and neonatal hypoxic-ischemic encephalopathy (HIE), to follow therapeutic efficacy or evaluate new therapies in neonates at risk. Hurdles to adoption of brain injury biomarkers in the NICU have been the lack of normative data in the growing infant, effect of prematurity, relatively large sample volumes needed and no large studies with external validation. The overall goal of this proposal is to develop a multimarker circulating brain injury biomarker panel for neonatal IVH and HIE using well studied adult biomarkers, to provide a benchmark of therapeutic efficacy for current standard treatments and future investigational treatments, and to provide early prognostic information. The central hypothesis of this proposal is that circulating brain specific protein levels measured serially over days 0-7 of life in premature neonates and neonates with HIE will provide early injury detection, predict infants at risk for death or moderate-severe neurologic disability, predict therapeutic efficacy for therapeutic hypothermia, and serve as a basis for triaging neonates to appropriate new investigational therapies to decrease morbidity and improve outcomes. To examine our hypothesis we will utilize a novel multiplex panel of 4 brain specific proteins (BDNF, S100B, NSE and GFAP) and 4 brain injury related proteins (IL-1, IL-6, IL-8, VEGF) studied extensively in adults as biomarkers of brain injury, in training (Johns Hopkins Medicine, Baltimore, JHM) and external test (All Children’s Hospital JHM, St. Petersburg, FL) cohorts in the following Specific Aims: 1) Determine if circulating levels of brain injury biomarkers are dependent on gestational age using an existing cohort of longitudinal blood samples from premature and full term infants (N=400, 23-40 weeks gestation) admitted to the NICU without clinical brain injury to determine the effect of gestational age on baseline levels. 2) Determine in HIE if circulating brain injury biomarker levels during and after therapeutic hypothermia predict adverse outcomes including A) MRI abnormalities at 7-10 days and B) death or neurologic disability at 24 months. 3) Determine in IVH if circulating brain injury biomarker levels during the first 7 days of life in VLBW premature neonates are A) diagnostic for IVH, B) predict PVWMI brain injury at 6 weeks and C) neurologic disability at 24 months. Both of these aims will use concurrent IVH and HIE enrollment at JHM (training set) and ACH JHM (test set) for external validation. By focusing on a panel of blood brain barrier dependent and independent biomarker proteins studied exhaustively in adults, in a innovative and highly sensitive multiplex Pharma grade format, using large training and test cohorts we will confirm generalizability and efficacy in neonatal brain injury.

项目总结

项目成果

Blood biomarkers for neonatal hypoxic-ischemic encephalopathy in the presence and absence of sentinel events.

• DOI: 10.1038/s41372-020-00850-5
• 发表时间: 2021-06
• 期刊: Journal of perinatology : official journal of the California Perinatal Association
• 作者: Broni EK;Eke AC;Vaidya D;Tao X;Northington FJ;Everett AD;Graham EM
• 通讯作者: Graham EM

Interaction of hydrocortisone and illness severity on head growth in cohort of ELBW infants.

氢化可的松与疾病严重程度对 ELBW 婴儿头部生长的相互作用。

• DOI: 10.1038/s41390-023-02689-w
• 发表时间: 2023
• 期刊: Pediatric research
• 影响因子: 3.6
• 作者: Chen,Haiwen;Aziz,KhyzerB;Spahic,Harisa;Miller,Sarah;Guryildirim,Melike;Sellers,Austin;Brooks,Sandra;Kilborn,Alison;Everett,AllenD;Northington,FrancesJ;Stafstrom,CarlE;Chavez-Valdez,Raul
• 通讯作者: Chavez-Valdez,Raul

Perinatal blood biomarkers for the identification of brain injury in very low birth weight growth-restricted infants.

• DOI: 10.1038/s41372-021-01112-8
• 发表时间: 2021-09
• 期刊: Journal of perinatology : official journal of the California Perinatal Association
• 作者: Yue SL;Eke AC;Vaidya D;Northington FJ;Everett AD;Graham EM
• 通讯作者: Graham EM

Post-operative acute kidney injury is associated with a biomarker of acute brain injury after paediatric cardiac surgery.

术后急性肾损伤与小儿心脏手术后急性脑损伤的生物标志物相关。

• DOI: 10.1017/s1047951120000451
• 发表时间: 2020
• 期刊: Cardiology in the young
• 影响因子: 1
• 作者: Parsons,Michael;Greenberg,Jason;Parikh,Chirag;Brown,Jeremiah;Parker,Devin;Zhu,Jie;Vricella,Luca;Everett,AllenD
• 通讯作者: Everett,AllenD

Correction to: Clonidine for sedation in infants during therapeutic hypothermia with neonatal encephalopathy: pilot study.

更正：可乐定在新生儿脑病低温治疗期间用于婴儿镇静：初步研究。

• DOI: 10.1038/s41372-021-01245-w
• 发表时间: 2022
• 期刊: Journal of perinatology : official journal of the California Perinatal Association
• 作者: Gauda,EstelleB;Chavez-Valdez,Raul;Northington,FrancesJ;Lee,CarltonKK;Rudek,MichelleA;Guglieri-Lopez,Beatriz;Ivaturi,Vijay
• 通讯作者: Ivaturi,Vijay