High versus low initial oxygen to improve the breathing effort of preterm infants at birth

Although most preterm infants breathe at birth, their respiratory drive is weak
and often insufficient to aerate their lungs and establish gas exchange. Extra
oxygen is often needed to correct hypoxia, but could then lead to hyperoxia.
The optimal concentration of oxygen to start stabilisation after birth is still
not clear, as both hypoxia and hyperoxia can attribute to organ injury. To
reduce the risk of hyperoxia, currently an initial low oxygen concentration is
recommended during stabilisation, accepting the risk of a period of hypoxia.
However, hypoxia inhibits respiratory drive in preterm infants. Starting with a
higher level of oxygen could lead to a shorter duration of hypoxia and thus
stimulate breathing effort of preterm infants, but increase the risk for
hyperoxia. Improving the respiratory drive decreases the need for additional
ventilation or intubation and mechanical ventilation.

The objective of this study is to compare the direct effect of the
administration of an initial FiO2 of 1.0 versus 0.3 on respiratory effort
during stabilisation of preterm infants in the first 5 minutes after birth.
After evaluation of the initial settings, FiO2 will be titrated based on the
oxygen saturation target range.

A multi-center randomized controlled trial.

Based on randomization, stabilisation after birth will be started with a FiO2
of either 1.0 or 0.3, after which FiO2 will be titrated based on the oxygen
saturation target range. In both groups, other interventions needed for
stabilisation and thereafter will be given conform standard care.

Most preterm infants breathe insufficiently at birth and develop respiratory
distress syndrome. Previous studies demonstrated that achieving adequate
oxygenation directly after birth is difficult and additional oxygen
supplementation is required in most cases. The only difference between groups
in the proposed study is the initial FiO2 during stabilisation after birth.
After the initial setting, FiO2 will be titrated up in the low FiO2-group and
titrated down in the high FiO2-group following target ranges for oxygen
saturation.
In preterm infants at birth both hypoxia and hyperoxia needs to be avoided as
they are both associated to increased risk for organ injury. Currently the
starting FiO2 is low (0.3), increasing the risk for hypoxia in the first
minutes, insufficient respiratory drive and an increased risk for additional
ventilation or intubation and mechanical ventilation. When starting with a high
FiO2 (1.0), the risk for hypoxia will decrease, but could increase the risk for
hyperoxia. However, in both groups, the goal is to obtain normoxia in the
newborn as soon as possible after birth. To minimize risks for hypoxia and
hyperoxia in both groups FiO2 will be titrated based on oxygen saturations
guided by target ranges defined in this protocol.