Routine Or Selective Application of a Face Mask for Preterm Infants at Birth: the ROSA Trial
Routine Or Selective Application of a Face Mask for Preterm Infants at Birth: the ROSA Trial
International guidelines recommend giving positive pressure ventilation (PPV) by face mask to
 newborns who do not breathe or have a slow heart rate at birth. Preterm infants are at high
 risk of developing respiratory distress syndrome (RDS) and many are treated with continuous
 positive airway pressure (CPAP) in the neonatal intensive care unit (NICU). Though the
 majority of preterm infants breathe spontaneously at birth, many clinicians routinely apply a
 face mask to preterm infants shortly after birth in the delivery room (DR) to give them CPAP.
 However, applying a face mask may inhibit spontaneous breathing in newborns. In this study,
 premature babies will be randomly assigned to have a face mask routinely applied for CPAP
 shortly after birth; or to have a face mask selectively applied only for PPV if they are not
 breathing or have a slow heart beat in the first 5 minutes of life, or for CPAP if they have
 signs of respiratory distress after 5 minutes. The investigators will determine whether fewer
 participants who have the mask selectively applied receive PPV in the DR.
Newly born babies have fluid-filled lungs that they must quickly aerate after birth. Compared
 to infants born at term, preterm babies have greater difficulty in establishing and
 maintaining aeration of their lungs; this leaves them at increased risk of developing
 respiratory distress syndrome (RDS). Infants who develop RDS are treated with nasal
 continuous positive airway pressure (CPAP), and may progress to treatment with surfactant and
 mechanical ventilation, in the Neonatal Intensive Care Unit (NICU).

 The Neonatal Task Force of the International Liaison Committee on Resuscitation (ILCOR) makes
 recommendations on the treatment of infants at birth. ILCOR recommends assessing the
 breathing and heart rate (HR) of all newborns, and:

 1. Giving positive pressure ventilation (PPV) to babies who have a HR < 100bpm, gasping or
 apnoea

 2. Considering giving CPAP to babies who have laboured breathing or persistent cyanosis

 Most preterm infants breathe spontaneously at birth. Despite this, the majority of preterm
 infants have a facemask applied for respiratory support immediately after birth, usually
 before the HR has been determined. Clinicians presumably do this to give early support to
 infants they believe are at high risk of developing RDS in an attempt to prevent or lessen
 the severity of the disease.

 There is little evidence that giving preterm infants prophylactic nasal CPAP may be superior
 to supportive care with oxygen. A study that compared nasopharyngeal CPAP to supportive care
 with oxygen performed before antenatal steroids were routinely given found no difference in
 the rate of development of RDS with the application of CPAP. Two more recent studies did not
 show that early application of nasal CPAP reduced the rate of intubation or treatment with
 surfactant. In these studies CPAP was given by nasal prongs and was started at 15 - 30
 minutes of life, not immediately with a facemask. There is no evidence that facemask CPAP
 immediately after birth prevents or reduces the severity of RDS.

 Application of a face mask has been demonstrated to inhibit spontaneous breathing in many
 term infants. Cold gas flow, such as that provided by a T-piece, can inhibit spontaneous
 breathing in term infants. Application of a face mask for breathing support appears to
 inhibit breathing in a greater proportion of preterm infants. Considerable force is applied
 to the head when face mask PPV is given to a mannequin in the supine position.

 Routinely applying a face mask for respiratory support may be unnecessary in many premature
 babies. It may inhibit their spontaneous breathing and result in them receiving facemask PPV
 more frequently in the DR. It may also affect how well they breathe in the first day of life
 and increase the rate of treatment with nasal CPAP in the NICU.

 METHODS

 RANDOMISATION AND GROUP ASSIGNMENT Participants will be randomly assigned to "SELECTIVE" or
 "ROUTINE" groups in a 1:1 ratio. The group assignment schedule will be generated in blocks of
 4 using a random number table, and will be stratified by gestational age (23 - 27, 28 -
 31+6). It will be kept on a concealed from investigators and treating clinicians. Group
 assignment will be written on cards and placed in sequentially numbered, sealed, opaque
 envelopes. Infants of multiple gestations will be randomised as individuals.

 The envelopes will be contained in 2 boxes for GA strata and kept in the NICU. The next
 envelope in the sequence will be taken from the appropriate box and brought to the DR, where
 it will be opened just before delivery.

 MASKING It is not possible to mask caregivers to group assignment.

 INTERVENTIONS

 ALL INFANTS Infants in both groups will have their umbilical cord clamped at or after 1
 minute of age; they will not have a mask applied for respiratory support during this time.
 Infants will then be transferred to resuscitaire, placed supine under radiant heat and have a
 hat applied. All infants will be placed in polyethylene bag. A pulse oximeter will be placed
 on the right wrist.

 A T-piece device (Neopuff, Fisher & Paykel Healthcare, Auckland NZ; or Dräger Resuscitaire
 (Drager healthcare, Lübeck, Germany) and round face mask (Fisher & Paykel Healthcare,
 Auckland NZ) of appropriate size for the baby will be used to give respiratory support to
 infants in both groups. The T-piece will have gas flow set at 8 - 10 L/min, with settings
 PEEP 6cmH2O, and PIP 25cmH2O. There will be an air/oxygen blender in the circuit and the FiO2
 will be initially set at 30%. The FiO2 will not be adjusted before 5 minutes of age.

 SELECTIVE GROUP Infants assigned to the "SELECTIVE" group will be placed supine to breathe
 spontaneously. If SpO2 < 70% at 5 minutes and their respiratory effort is good, they will be
 given give free flow oxygen (i.e. the mask will be placed in front of, but not directly in
 contact with, the infant's face). The FiO2 may be increased at 1 minute intervals thereafter,
 aiming for SpO2 ≥ 90% at 10 minutes of life.

 Infants in the "SELECTIVE" group will have mask PPV if they are apnoeic or have HR < 100bpm
 at any time in the DR. Clinicians may consider applying facemask to give CPAP if the infants
 breathing is laboured (i.e. there are signs of respiratory distress - grunting,
 intercostal/subcostal/sternal recessions) after 5 minutes of age.

 ROUTINE GROUP Infants assigned to the "ROUTINE" group will be placed supine on the
 resuscitaire and have facemask CPAP applied as soon as possible after they arrive. If SpO2 <
 70% at 5 minutes, the FiO2 may be increased at 1 minute intervals, aiming for SpO2 ≥ 90% at
 10 minutes of life.

 Infants in the "ROUTINE" group will have facemask PPV if they are apnoeic or have HR < 100bpm
 at any time in the DR. Mask respiratory support may be withdrawn as and when desired by
 clinical staff.

 RESUCE TREATMENT All other treatments - i.e. endotracheal intubation for PPV, chest
 compressions, adrenaline, volume - w ill be given at the discretion of the treating
 clinicians and in accordance with ILCOR recommendations.

 SAMPLE SIZE ESTIMATION To show a reduction in the proportion of babies receiving PPV with
 routine application from 60% to 40% with selective application with 80% power and α of 0.05,
 the investigators need to recruit 200 infants.
Inclusion Criteria:

 -  Born before 32 weeks gestational age by best obstetric estimate

 Exclusion Criteria:

 -  Infants with major congenital anomalies