Previous randomized prospective trials of term infants but including preterm infants of greater than 1000 grams have demonstrated that infants resuscitated with room air as compared to 100% oxygen had a shorter time to first breath and cry, higher 5 minute Apgar scores and reduced mortality. In addition these observations were found to apply to the subset of preterm infants in these trials. We have now completed two small randomized clinical trials that have prospectively evaluated the use of lower versus higher oxygen concentrations for the VLBW infant and utilizing a targeted strategy to achieve an acceptable SpO2 at a given postnatal age. Purpose: To conduct a prospective randomized multi-center clinical trial to evaluate the potential benefit of neonatal resuscitation using a targeted oxygen strategy initiated with a low oxygen concentration of 30% (LOWOX) compared to with the use of a 60% (HIOX) for the extremely low gestational age newborn (ELGAN). (Both Fio2 values are to be further discussed during planning period). Hypothesis: We hypothesize that during resuscitation of ELGAN the use of a targeted oxygen saturation initiated with LOWOX compared with HIOX will result in an increase in survival without Bronchopulmonary Dysplasia (BPD) and/or ROP, and an increase in survival without neurodevelopmental impairment (NDI) at 18-22 corrected months. Methods: A prospective randomized, blinded comparison of a targeted oxygen strategy with the use of 30% oxygen in ELGAN compared with 60% Oxygen. All infants will be monitored using pulse oximeters and oxygen blenders. Both groups will have a targeted strategy so that they will reach the desired SpO2 at 10 minutes of life. Resuscitation will begin with either 30% or 60% oxygen, and the oxygen concentration will be increased in the Low group for either continued bradycardia, or SpO2 values of less than 70% at 4 minutes, or less than 80% at 7 minutes, and Na SpO2 of 85% at 10 minutes. The proposed strategy for the HIOX group will be to continue the initial FiO2 for the first 10 minutes. After 10 minutes the HIOX group will be maintained within an SpO2 range of 90 to 95% for 2(4) hours, and the LOWOX group will be maintained between 85% - 90% for 2(4) hours. Planning: We will use the planning period to establish a steering committee, which will work with the future trial centers to: 1) Establish a final study design that will yield generalizable results which can be used in the greatest number of delivery rooms possible, and determine the actual initial FiO2 for the 2 groups. 2) Provide concise definitions for the trial, including neurodevelopmental, respiratory, and biochemical outcomes, and 3) Design case report forms and a manual of operations such that when the centers are recruited for the pending trial the greatest majority of their time will be spent recruiting subjects. 4) Develop St Center functions, data handling and analyses, and auditing.
t Narrative The proposed trial will evaluate the use of two different oxygen concentrations to assist very premature infants immediately following their delivery. Current recommendations allow the use of the lowest concentration (21% oxygen or """"""""room air"""""""") and the highest concentration (100% oxygen). Because there is concern that the use of 100% oxygen concentrations may be harmful and that room air may be ineffective, this trial will look at two intermediate concentrations and determine the oxygen level that produces the healthiest babies.
