Reconsidering Oxygen at Birth for Preterm Infants

At birth, newborns must transition from the low-oxygen environment of the womb to postnatal normoxemia. Most preterm newborns require supplemental oxygen to support this process. Yet, active debate remains about the optimal starting fraction of inspired oxygen (Fio2) for preterm delivery room resuscitation. Historically, high oxygen concentrations (Fio2 of 1.0) were used routinely, guided by the belief that maximizing oxygen delivery was essential to support cardiorespiratory compromise. Over time, recognition of oxygen toxicity and associations between high Fio2 and increased mortality in more mature newborns prompted a shift toward lower oxygen strategies for preterm newborns. In 2015, international guidelines for preterm infants recommended initiating respiratory support with lower Fio2 (0.21-0.3), based largely on concerns that unnecessary oxygen exposure may cause harm without clear benefit for mortality, major morbidities, or neurodevelopment. However, the recent NETMOTION collaborative individual participant data network meta-analysis, pooling 12 randomized trials including 1055 preterm newborns, challenged the start low paradigm, finding that higher initial Fio2 (≥0.9) was associated with reduced mortality compared with lower (≤0.3) or intermediate (0.5-0.65) concentrations. These emerging data underscore that the optimal starting Fio2 for preterm newborns remains undefined—a question with direct implications for millions of premature newborns worldwide each year.