Serial plasma biomarkers of brain injury in infants with neonatal encephalopathy treated with therapeutic hypothermia.

BACKGROUND: Neonatal encephalopathy (NE) is a major cause of long-term neurodevelopmental disability in neonates. We evaluated the ability of serially measured biomarkers of brain injury to predict adverse neurological outcomes in this population. METHODS: Circulating brain injury biomarkers including BDNF, IL-6, IL-8, IL-10, VEGF, Tau, GFAP, and NRGN were measured at 0, 12, 24, 48, 72, and 96 h of cooling from 103 infants with NE undergoing TH. The biomarkers' individual and combinative ability to predict death or severe brain injury and adverse neurodevelopmental outcomes beyond 1 year of age was assessed. RESULTS: Early measurements of inflammatory cytokines IL-6, 8, and 10 within 24 HOL (AUC = 0.826) and late measurements of Tau from 72 to 96 HOL (AUC = 0.883, OR 4.37) were accurate in predicting severe brain injury seen on MRI. Late measurements of Tau were predictive of adverse neurodevelopmental outcomes (AUC = 0.81, OR 2.59). CONCLUSIONS: Tau was consistently a predictive marker for brain injury in neonates with NE. However, in the first 24 HOL, IL-6, 8, and 10 in combination were most predictive of death or severe brain injury. The results of this study support the use of a serial biomarker panel to assess brain injury over the time course of disease in NE. IMPACT: While recent studies have evaluated candidate brain injury biomarkers, no biomarker is in current clinical use. This study supports the use of a serial biomarker panel for ongoing assessment of brain injury neonates with NE. In combination, IL6, IL8, and IL10 in the first 24 h of cooling were more predictive of brain injury by MRI than each cytokine alone. Individually, Tau was overall most consistently predictive of adverse neurological outcomes, particularly when measured at or after rewarming.

Early Versus Late Brain Magnetic Resonance Imaging after Neonatal Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia.

OBJECTIVE: To evaluate the agreement in brain injury findings between early and late magnetic resonance imaging (MRI) in newborn infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia and to compare the ability of early vs late MRI to predict early neurodevelopmental outcomes. STUDY DESIGN: This was a prospective longitudinal study of 49 patients with hypoxic-ischemic encephalopathy who underwent therapeutic hypothermia and had MRI performed at both <7 and ≥7 days of age. MRIs were reviewed by an experienced neuroradiologist and assigned brain injury severity scores according to established systems. Scores for early and late MRIs were assessed for agreement using the kappa statistic. The ability of early and late MRI scores to predict death or developmental delay at 15-30 months of age was assessed by logistic regression analyses. RESULTS: Agreement between the early and late MRI was substantial to near perfect (k > 0.75, P < .001) across MRI scoring systems. In cases of discrepant scoring, early MRI was more likely to identify severe injury when compared with late MRI. Early MRI scores were more consistently predictive of adverse outcomes compared with late MRI. CONCLUSIONS: The results of this study suggest that a single MRI performed in the first week after birth is adequate to assess brain injury and offer prognostic information in this high-risk population.