Heart Rate Variability as a Predictor of Region-Specific Brain Injury in Neonates with Perinatal Asphyxia: A Prospective Study in a Middle-Income Country

Background and Objectives: Neonates with moderate-to-severe hypoxic–ischemic encephalopathy (HIE) in low- and middle-income countries (LMICs) remain at high risk of neurological sequelae despite access to therapeutic hypothermia (TH). Real-time accessible biomarkers are required to improve risk stratification and guide neuroprotective care in these settings. This study evaluated the predictive capacity of heart rate variability (HRV) metrics for brain injury detected using magnetic resonance imaging (MRI) in neonates with HIE who underwent TH at an LMIC. Materials and Methods: We conducted a prospective observational study of 87 neonates treated with TH in a tertiary neonatal intensive care unit in Colombia. HRV was recorded during the first 24 h of TH, during rewarming, and 24 h after rewarming. Brain MRI was performed within the first week of life and scored using the Rutherford system. Associations between HRV metrics and global and regional brain injuries were analyzed using receiver operating characteristic (ROC) curves and multivariable logistic regression models. Results: Low-frequency (LF) and high-frequency (HF) powers were significantly lower in neonates with MRI abnormalities. LF power during rewarming demonstrated the highest predictive accuracy (AUC = 0.90), followed by HF power during the first 24 h (AUC = 0.80). Region-specific analyses showed that LF power reduction was significantly associated with white matter and basal ganglia injury. Conclusions: HRV, particularly LF power during rewarming, is a promising and accessible biomarker for regional brain injury in neonates with perinatal asphyxia treated with TH.