ObjectiveTo investigate the clinical, electrographic, and neuroimaging characteristics in neonates with perinatal hypoxic-ischemic encephalopathy (HIE) who undergo reorientation of care (ROC) using standardized scoring systems. Study designA nested observational substudy within a prospective HIE cohort was conducted. Group 1 comprised infants whose parents received the medical recommendation for ROC, while Group 2 continued to receive standard care. Encephalopathy scores were monitored daily. Amplitude-integrated and continuous-video-integrated electroencephalogram (EEG) during therapeutic hypothermia were analyzed. Standardized scoring systems for cranial ultrasonography and post-rewarming brain MRI were deployed. ResultsThe study included 165 infants, with 35 in Group 1 and 130 in Group 2. By day 3, all infants in Group 1 were encephalopathic with higher Thompson scores (median 13 [IQR 10-19] vs. 0 [IQR 0-3], p<0.001). Electrographic background normalization within 48 hours occurred in 3% of Group 1 compared with 46% of Group 2 (p<0.001). Sleep-wake cycling was not observed in Group 1 and emerged in 63% of Group 2 within the first 72 hours (p<0.001). The number of anti-seizure medications received was higher in Group 1 (median 3 [IQR, 2-4] vs. 0 [IQR, 0-1], respectively; p< 0.001). Group 1 had higher cranial ultrasound injury scores (median 4 [IQR 2-7] vs. 1 [IQR 0-1], p<0.001) within 48 hours and post-rewarming brain MRI injury scores (median 33 [range 20-51] vs. 4 [range 0-28], p<0.001). ConclusionNeonates with perinatal HIE who underwent ROC presented with and maintained significantly more pronounced clinical manifestations, electrographic findings, and near-total brain injury as scored objectively on all modalities.