To evaluate clinical characteristics, therapeutic hypothermia timing, neurological complications, and early outcomes in neonates with HIE, focusing on challenges for outborn and preterm infants in tertiary care.

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal neurological morbidity and long-term disability globally. Timely therapeutic hypothermia (TH) is critical but challenging for outborn and preterm infants, exacerbating care disparities. Real-world data on neurological outcomes are vital to optimize clinical pathways across diverse healthcare systems, including U.S. and global settings.

We audited 39 neonates with HIE admitted to a tertiary neonatal unit in England from January 2023 to June 2025. Electronic records provided demographics, perinatal risk factors, Sarnat staging, TH timing, and complications (e.g., alanine aminotransferase >40 U/L, creatinine >100 µmol/L, PCO2 <4 kPa, prolonged coagulation, glucose <2 mmol/L on ≥2 measurements). Outcomes included seizures, MRI findings, hearing impairment, and survival. The audit was ethically registered.

Of 39 neonates (median gestation 38 weeks, IQR 35–39; birth weight 3040 g, IQR 2365–3405), 15% were ≤34 weeks, 59% outborn, 54% male. Most (74%) had emergency cesarean; 56% had perinatal risk factors. Encephalopathy was mild (21%), moderate (62%), or severe (10%). Nine (29%) did not receive TH; four initially mild cases progressed or had seizures beyond the TH window, including five ≤35 weeks. Four had delayed TH. Passive cooling occurred in 52% of outborn infants. Seizures affected 53%, treated primarily with phenobarbital. Among survivors, 26% had MRI-documented brain injury, 15% post-TH seizures, 3% hearing impairment. Overall, 95% survived; median stay was 9 days (IQR 7–13).

Despite robust survival, delays in detecting evolving encephalopathy and inefficient outborn transfers compromise neurological outcomes, especially for preterms lacking evidence-based neuroprotection. These findings, applicable across global and U.S. healthcare systems, urgently demand preterm TH trials and standardized transfer protocols to eliminate disparities, providing benchmarks for innovations in neonatal neurocritical care.