OBJECTIVE: Although earlier studies have suggested that early continuous airway positive pressure (CPAP) may be beneficial in reducing ventilator dependence and subsequent chronic lung disease in the extremely low birth weight (ELBW) infant, the time of initiation of CPAP has varied, and there are no prospective studies of infants who have received CPAP or positive end-expiratory pressure (PEEP) from initial resuscitation in the delivery room (DR). Current practice for the ELBW infant includes early intubation and the administration of prophylactic surfactant, often in the DR. The feasibility of initiating CPAP in the DR and continuing this therapy without intubation for surfactant has never been determined prospectively in a population of ELBW infants. This study was designed to determine the feasibility of randomizing ELBW infants of <28 weeks' gestation to CPAP/PEEP or no CPAP/PEEP during resuscitation immediately after delivery, avoiding routine DR intubation for surfactant administration, initiating CPAP on neonatal intensive care unit (NICU) admission, and assessing compliance with subsequent intubation criteria. METHODS: Infants who were of <28 weeks' gestation, who were born in 5 National Institute of Child Health and Human Development Neonatal Research Network NICUs from July 2002 to January 2003, and for whom a decision had been made to provide full treatment after birth were randomized to receive either CPAP/PEEP or not using a neonatal T-piece resuscitator (NeoPuff). Infants would not be intubated for the sole purpose of surfactant administration in the DR. After admission to the NICU, all nonintubated infants were placed on CPAP and were to be intubated for surfactant administration only after meeting specific criteria: a fraction of inspired oxygen of >0.3 with an oxygen saturation by pulse oximeter of <90% and/or an arterial oxygen pressure of <45 mm Hg, an arterial partial pressure of carbon dioxide of >55 mm Hg, or apnea requiring bag and mask ventilation. RESULTS: A total of 104 infants were enrolled over a 6-month period: 55 CPAP and 49 control infants. No infant was intubated in the DR for the exclusive purpose of surfactant administration. Forty-seven infants were intubated for resuscitation in the DR: 27 of 55 CPAP infants and 20 of 49 control infants. Only 4 of the 43 infants who had a birth weight of <700 g and 3 of the 37 infants of <25 weeks' gestation were resuscitated successfully without positive pressure ventilation, and no difference was observed between the treatment groups. All infants of 23 weeks' gestation required intubation in the DR, irrespective of treatment group, whereas only 3 (14%) of 21 infants of 27 weeks' required such intubation. For infants who were not intubated in the DR, 36 infants (16 CPAP infants and 20 control infants) were subsequently intubated in the NICU by day 7, in accordance with the protocol. Overall, 80% of studied infants required intubation within the first 7 days of life. The care provided for 52 (95%) of 55 CPAP infants and 43 (88%) of the 49 control infants was in compliance with the study protocol, with an overall compliance of 91%. CONCLUSIONS: This study demonstrated that infants could be randomized successfully to a DR intervention of CPAP/PEEP compared with no CPAP/PEEP, with intubation provided only for resuscitation indications, and subsequent intubation for prespecified criteria. Forty-five percent (47 of 104) of infants <28 weeks' gestation required intubation for resuscitation in the DR. CPAP/PEEP in the DR did not affect the need for intubation at birth or during the subsequent week. Overall, 20% of infants did not need intubation by 7 days of life. This experience should be helpful in facilitating the design of subsequent prospective studies of ventilatory support in ELBW infants.