Brain State of the Newborn as a Biomarker for Brain Injury in Infants with Hypoxic-Ischemic Encephalopathy

Objective To evaluate the use of a fully automated trend measure of cortical activity, Brain State of the Newborn (BSN), in early stratification of infants for add-on neuroprotective therapies during therapeutic hypothermia (TH). Study design Our retrospective cohort study included 167 infants with moderate-to-severe hypoxic-ischemic encephalopathy who underwent TH and continuous electroencephalography monitoring. The BSN trends were computed using fully automated pipelines, and we used a priori-defined thresholds at 6, 12, 24, and 36 hours after birth to assess prediction of an adverse postrewarming magnetic resonance imaging finding, defined as moderate-to-severe cortical or deep gray matter injury and/or severe white matter injury. Adverse outcome at 2 years of age was defined as death, cerebral palsy, or cognitive/motor scores <85 on the Bayley Scales of Infant Development-III. Results BSN-based prediction of an adverse outcome on MRI at 12-24 hours after birth showed high sensitivity (81%-87%) and specificity (73%-81%), and the corresponding area under the curve (AUC) ranged from 83% at 6 hours to 93% at 24 hours, stabilizing at 91% by 36 hours. In contrast, the prediction of adverse outcome at 2 years of age at 12-24 hours showed a moderate sensitivity (73%-77%) and specificity (70%-78%, AUC: 70%), whereas mortality prediction achieved high sensitivity (94%-99%) and specificity (69%-75%, AUC: 96%). Conclusions BSN offers a fully automated and unbiased measure of recovery in spontaneous cortical activity, holding promise as a bedside biomarker in identifying infants who could benefit from early add-on neuroprotective therapies.