The purpose of this study is to evaluate the effect of LISA used in the delivery room (DR) in decreasing the intubation rates in preterm infants at 22-25 weeks gestational age (GA), during first 72 hours compared to the standard approach of stabilization on nasal CPAP in the DR and administering surfactant in the NICU.

Infants in both groups will be resuscitated per NRP algorithm. Infants who maintain a stable HR and respiratory effort on CPAP will qualify for the intervention. Infants in Group 1 (Intervention arm) will receive LISA in DR. CPAP will be titrated between 5-8 cm H20 after LISA. Infants in Group 2 (Control arm) will be transferred to NICU on CPAP. The CPAP level will be increased stepwise every 30 minutes to 7 cm H2O if FiO2 ≥0.3. Infants requiring CPAP 7 at FiO2 ≥0.3 will receive LISA. CPAP will be titrated between 5-8 cm H20 after LISA.

Infants in both arms requiring CPAP 7 and FiO2 >0.8 at 20 MOL in the delivery room will be intubated in DR. Any infant with a heart rate not responding with appropriate PPV will be intubated in the DR. CXR will be obtain on admission and umbilical lines will be placed. Infants in both arm who require FiO2 ≥0.6 for ≥1 hour, apnea requiring stimulation 3 times within one hour or ≥6 over 6 hour period, any apnea requiring PPV, or CO2 >0.65 in two consecutive blood gases drawn over two hours will be considered as reasons for intubation after LISA.

Primary outcome is the need for MV within 72 hours of life, secondary outcome includes need for MV during first week of life and during hospital stay, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), need for treatment of patent ductus arteriosus (PDA), composite death or BPD and mortality. This is a feasibility trial with the intention to enroll 30 infants in each arm of the study over three years.

This is a single center, unblinded, randomized control, feasibility trial to evaluate the use of LISA in the DR for extremely preterm infants born 22-25 weeks GA who were successfully resuscitated without being intubated. The study team will approach a mother who is at risk of delivering an infant between 22-25 week GA for consent to be included in the study. Infants will be resuscitated according to NRP algorithm. Infants who are successfully resuscitated without requiring intubation and mechanical ventilation (HR >100, regular spontaneous respiratory effort, able to maintain oxygenation per NRP target saturation goal) are eligible for enrollment. Randomization will be achieved by opening an opaque envelope.

• Intervention arm (DR-LISA): Infants with a stable heart rate and spontaneous respiratory effort on CPAP are eligible for surfactant therapy. A LISA catheter will be prepared for use prior to the birth of the infant. Surfactant will be drawn into a syringe soon after the initial stabilization. A trained physician will perform LISA. The infant will be maintained on CPAP by prongs during the procedure. PPV will be provided if needed after the procedure. The infant will be monitored in the DR for stable HR, respiration and SpO2 prior to being moved to a transporter. Infants requiring FiO2 >0.8 on CPAP 8 cm H2O to maintain SpO2 88-94% by 20 minutes of life will be intubated prior to transport. After admission to NICU, CPAP level will be titrated between 5-8 cm H20 based on FiO2 threshold ≥0.3
• Control arm: Infants will be resuscitated per NRP guidelines. Infant with stable HR and respiratory effort will be changed to binasal prongs and transported to NICU on CPAP. CPAP level be titrated between 5- 7 cm H2O in the DR. Infants requiring FiO2 >0.8 to maintain SpO2 88-94% by 20 minutes of life will be intubated in DR. After admission to NICU, CPAP will be escalated every 30 minutes up to a maximum level of 7 cm H2O at which point infant would qualify for LISA if the FiO2 requirement is ≥0.3. CPAP level will be titrated between 5-8 cm H20 based on FiO2 threshold ≥0.3. Infants in both groups who require FiO2 ≥0.6 for ≥1 hour, apnea requiring stimulation 3 times within one hour or ≥6 over 6 hour period, any apnea requiring PPV, or CO2 >0.65 in two consecutive blood gases drawn over two hours will be considered as reasons for intubation after LISA.

Repeat doses of surfactant will be administered every 12 hours for FiO2 ≥0.4 up to a maximum of three doses.

Inclusion Criteria:

• Infants born 22 -25 weeks GA
• Resuscitated without requiring intubation and maintaining HR >100, and spontaneous respiratory effort on CPAP 5-7 cm H2O)

Exclusion Criteria:

• Major congenital anomalies
• Infants receiving only comfort care
• Mothers with impaired decision making capacity