Plasma biomarkers of evolving encephalopathy and brain injury in neonates with hypoxic ischemic encephalopathy (HIE)

Ruoying Li, Department of Neurology, Children's National Hospital, Washington, DC.
Jennifer K. Lee, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Rathinaswamy B. Govindan, Department of Pediatrics, The George Washington University School of Medicine; Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC.
Ernest M. Graham, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Allen D. Everett, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Jamie Perin, Department of Pediatrics, Center for Child and Community Health Research, Johns Hopkins University School of Medicine, Baltimore, MD.
Gilbert Vezina, Division of Diagnostic Imaging and Radiology, Children's National Hospital, Washington, DC; Department of Pediatrics, The George Washington University School of Medicine.
Aylin Tekes, Department of Radiology, Division of Pediatric Radiology and Pediatric Neuroradiology, Johns Hopkins University School of Medicine, Baltimore, MD.
May W. Chen, Division of Neonatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Frances Northington, Division of Neonatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Charlamaine Parkinson, Division of Neonatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Alexandra O'Kane, Department of Neurology, Children's National Hospital, Washington, DC.
Meaghan McGowan, Department of Neurology, Children's National Hospital, Washington, DC.
Colleen Krein, Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC.
Tareq Al-Shargabi, Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC.
Taeun Chang, Department of Neurology, Children's National Hospital, Washington, DC; Department of Pediatrics, The George Washington University School of Medicine.
An N. Massaro, Department of Pediatrics, The George Washington University School of Medicine; Division of Neonatology, Children's National Hospital, Washington, DC. Electronic address: an.massaro@fda.hhs.gov.

Document Type

Journal Article

Publication Date

8-6-2022

Journal

The Journal of pediatrics

DOI

10.1016/j.jpeds.2022.07.046

Keywords

MRI; NIRS; Tau; cerebral autoregulation; hypothermia; neonatal hypoxia-ischemia

Abstract

OBJECTIVE: To evaluate the relationship between a panel of candidate plasma biomarkers and (1) death or severe brain injury on magnetic resonance imaging (MRI) and (2) dysfunctional cerebral pressure autoregulation as a measure of evolving encephalopathy. STUDY DESIGN: Neonates with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) at two level IV NICUs were enrolled into this observational study. Patients were treated with therapeutic hypothermia (TH) and monitored with continuous blood pressure monitoring and near infrared spectroscopy (NIRS). Cerebral pressure autoregulation was measured by the hemoglobin volume phase index (HVP); higher HVP indicates poorer autoregulation. Serial blood samples were collected during TH and assayed for Tau, glial fibrillary acidic protein, and neurogranin. MRIs were assessed using National Institutes of Child Health and Human Development (NICHD) scores. The relationships between the candidate biomarkers and (1) death or severe brain injury on MRI (defined as an NICHD score of ≥ 2B) and (2) autoregulation were evaluated using bivariate and adjusted logistic regression models. RESULTS: Sixty-two patients were included. Elevated Tau levels on days 2-3 of TH were associated with death or severe injury on MRI (aOR 1.06, 95% CI 1.03-1.09; aOR 1.04, 95% CI 1.01-1.06, respectively). Higher Tau was also associated with poorer autoregulation (higher HVP) on the same day (p = 0.022). CONCLUSIONS: Elevated plasma levels of Tau are associated with death or severe brain injury by MRI and dysfunctional cerebral autoregulation in neonates with HIE. Larger scale validation of Tau as a biomarker of brain injury in neonates with HIE is warranted.

Department

Pediatrics

Link to Full Text

Share

COinS