# Adult Biomarkers in Neonatal Brain Injury and Development

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $530,508

## Abstract

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...

## Key facts

- **NIH application ID:** 10006591
- **Project number:** 5R01HD086058-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ALLEN D EVERETT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $530,508
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006591

## Citation

> US National Institutes of Health, RePORTER application 10006591, Adult Biomarkers in Neonatal Brain Injury and Development (5R01HD086058-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10006591. Licensed CC0.

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