RESUMO
OBJECTIVE: The objective of the study was 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 2 level IV neonatal intensive care units were enrolled into this observational study. Patients were treated with therapeutic hypothermia (TH) and monitored with continuous blood pressure monitoring and near-infrared spectroscopy. Cerebral pressure autoregulation was measured by the hemoglobin volume phase (HVP) index; a higher HVP index 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 scores. The relationships between the candidate biomarkers and (1) death or severe brain injury on MRI (defined as a National Institutes of Child Health and Human Development 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 index) on the same day (P = .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.
Assuntos
Lesões Encefálicas , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Recém-Nascido , Criança , Humanos , Hipóxia-Isquemia Encefálica/patologia , Imageamento por Ressonância Magnética/métodos , BiomarcadoresRESUMO
OBJECTIVE: To evaluate whether infants with hypoxic-ischemic encephalopathy and evidence of autonomic dysfunction have aberrant physiological responses to care events that could contribute to evolving brain injury. STUDY DESIGN: Continuous tracings of heart rate (HR), blood pressure (BP), cerebral near infrared spectroscopy, and video electroencephalogram data were recorded from newborn infants with hypoxic-ischemic encephalopathy who were treated with hypothermia. Videos between 16 and 24 hours of age identified 99 distinct care events, including stimulating events (diaper changes, painful procedures), and vagal stimuli (endotracheal tube manipulations, pupil examinations). Pre-event HR variability was used to stratify patients into groups with impaired versus intact autonomic nervous system (ANS) function. Postevent physiological responses were compared between groups with the nearest mean classification approach. RESULTS: Infants with intact ANS had increases in HR/BP after stimulating events, whereas those with impaired ANS showed no change or decreased HR/BP. With vagal stimuli, the HR decreased in infants with intact ANS but changed minimally in those with impaired ANS. A pupil examination in infants with an intact ANS led to a stable or increased BP, whereas the BP decreased in the group with an impaired ANS. Near infrared spectroscopy measures of cerebral blood flow/blood volume increased after diaper changes in infants with an impaired ANS, but were stable or decreased in those with an intact ANS. CONCLUSION: HR variability metrics identified infants with impaired ANS function at risk for maladaptive responses to care events. These data support the potential use of HR variability as a real-time, continuous physiological biomarker to guide neuroprotective care in high-risk newborns.