Plasma biomarkers of evolving encephalopathy and brain injury in neonates with hypoxic ischemic encephalopathy (HIE)
The Journal of pediatrics
MRI; NIRS; Tau; cerebral autoregulation; hypothermia; neonatal hypoxia-ischemia
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.
Li, Ruoying; Lee, Jennifer K.; Govindan, Rathinaswamy B.; Graham, Ernest M.; Everett, Allen D.; Perin, Jamie; Vezina, Gilbert; Tekes, Aylin; Chen, May W.; Northington, Frances; Parkinson, Charlamaine; O'Kane, Alexandra; McGowan, Meaghan; Krein, Colleen; Al-Shargabi, Tareq; Chang, Taeun; and Massaro, An N., "Plasma biomarkers of evolving encephalopathy and brain injury in neonates with hypoxic ischemic encephalopathy (HIE)" (2022). GW Authored Works. Paper 1513.