The fetus develops in a low oxygen environment, and the arterial partial pressure of oxygen (PaO
2) physiologically rises directly after birth [
38]. This abrupt change in oxygen content of blood and tissue may induce physiological maturation of metabolic processes after birth [
39]. However, an excess supply of oxygen resulting in hyperoxia might have detrimental effects on infants born prematurely. Oxygen supplementation is one of the most common therapeutic interventions in resuscitation of newborns [
40]. However, its historically generous use in the delivery room has been abandoned in the last years due to new evidence from clinical studies [
41]. In the ground breaking Resair 2 study by Saugstad et al., the authors showed that resuscitation of term babies after asphyxia could efficiently be performed with room air instead of 100 % oxygen [
42].
In preterm infants, current guidelines advocate the use of a mixture of air and oxygen according to the infants’ oxygen saturation (SpO
2). These are based on the observation that an increase in oxygenation after birth is a gradual process [
43]. A recent meta-analysis of studies comparing different initial fractions of oxygen (FiO
2) in delivery room stabilization and resuscitation of preterm infants ≤32 weeks showed a trend towards a lower mortality when the initial FiO
2 was 0.21–0.30 [
44]. Two studies found a significant increase of markers of oxidative stress in preterm infants resuscitated with 90–100 % oxygen compared to 21 or 30 % [
45,
46]. These findings indicate a possible mechanism how supplemental oxygen contributes to lung injury of preterm infants in the context of prenatal abnormalities, variables like positive pressure ventilation during transition and perinatal resuscitation and postnatal insults [
47].
Therefore, current guidelines recommend using an initial FiO
2 of 0.21–0.30 and to subsequently titrate FiO
2 according to the infant’s SpO
2 measured by pulse oximetry in order to avoid hyperoxia [
48‐
50]. SpO
2 measurement in preterm infants within the first minutes of life is feasible [
51], and it is supposed to replace color as the traditional parameter for oxygenation [
49]. However, aiming at variable SpO
2 target values within the first 10 min of life is difficult, and large deviations from SpO
2 targets during resuscitation of preterm infants have been observed in clinical studies [
52], suggesting that manual FiO
2 control in the delivery room is inadequate. A possible solution is the use of automated closed loop FiO
2 control, which has been proven to efficiently keep infants within a predefined SpO
2 target in the NICU, using various modes of ventilation, and using different algorithms (as reviewed in [
53]). Although automated FiO
2 control has not yet been tested in the delivery room setting in clinical trials [
54], we could show in a lamb model of preterm respiratory distress syndrome that closed-loop FiO
2 control is feasible during the transition after birth and during surfactant replacement therapy [
55]. Moreover, automated FiO
2 control during transition in the first 15 min of life resulted in less hyperoxia in our model [
55]. Automated FiO
2 control might therefore become a key element in balancing oxygen supplementation and in avoiding complications associated with early oxygen over- or underexposure.