Oxygen Saturation Targeting in the Neonatal Intensive Care Unit

Oxygen (O₂) is vital for cellular development, function, proliferation, and repair, underscoring its critical role in organogenesis. Both hypoxia (reduced tissue O₂) and hyperoxia (excess tissue O₂), when prolonged, can trigger inflammation and oxidative stress, contributing to acute and long-term cardiopulmonary and neurodevelopmental morbidity. In sick neonates, immature defense mechanisms and coexisting morbidities demand nuanced and sometimes opposing strategies for O₂ saturation targets and therapeutic titration. Most current neonatal O₂ targeting guidelines are based on animal models or small clinical studies, resulting in recommendations with limited evidence. This narrative review aims to provide an updated overview of the physiological roles of O₂ in development, its delivery and consumption, approaches to O₂ saturation monitoring, and therapeutic targeting in neonates under both normal and pathological conditions. We also highlight key knowledge gaps and propose directions for future research on neonatal O₂ saturation targeting.