Surfactant Positive Airway Pressure and Pulse Oximetry Trial

Study subjects were infants of 24 0/7ths to 27 6/7th weeks at birth for which a decision has
been made to provide full resuscitation as required. Infants 27 weeks or less gestation
(completed weeks by best obstetric estimate) were enrolled because more than 80% of such
infants in the Network are intubated, usually early in their neonatal course. The feasibility
trial demonstrated that the five NICHD centers involved could reduce intubation in the
delivery room to less than 50% of such infants if they are not intubated for surfactant. We
excluded infants of 23 weeks or less in view of their extremely high mortality and morbidity,
and their almost universal need for delivery room intubation for resuscitation. Secondary
studies included: neuroimaging/MRI, growth, and breathing outcomes.

Strata: There were two randomization strata, infants of 24 0/7ths to 25 6/7ths weeks, and
infants of 26 0/7ths-27 6/7ths weeks by best obstetrical estimate.

Randomization:

Randomization was stratified by gestational age group, occurred prior to delivery for
consented deliveries, and was performed by utilizing specially prepared double-sealed
envelopes. Deliveries were randomized as a unit, thus multiples, twins, triplets, etc. were
randomized to the same arm of the trial.

Informed Consent:

Parents were approached prior to delivery for informed consent, and their infants enrolled at
delivery.

Study Intervention: Mode of Ventilatory Support The intervention began after birth when the
infant was given to the resuscitation team. The conduct of the resuscitation followed usual
guidelines, and once stabilized, all Control infants in both strata received
prophylactic/early surfactant (within one hour of age), whereas all Treatment infants were
placed on CPAP/PEEP following stabilization, and were intubated only for resuscitation
indications.

Pulse Oximeter Allocation:

Infants were randomized to receive either a high- or low-saturation of peripheral oxygen
(SpO2) as monitored by a study oximeter immediately following NICU admission, with a maximum
allowable delay of two hours following admission.

The SUPPORT Trial recruitment was temporarily paused on November 23, 2005 based on concern
regarding pulse oximeter readings > 95% and due to concern regarding separation of the two
arms of the oximetry portion of the study. Further analyses were performed which showed that
infants on room air accounted for a significant portion of pulse oximetry saturations above
95%. Separation of the two groups was reanalyzed based on time spent in room air and the
duration of time spent at individual SpO2 values, which both showed group differences. The
trial was restarted on February 6, 2006.

Follow-up: Subjects will be seen for a follow-up visit at 18-22 months corrected age to look
at neurodevelopment.

Extended follow-up: Subjects enrolled in the Neuroimaging/MRI secondary study will also be
seen for a follow-up visit at 6-7 years to look at later school-age development. Subjects
attending the 6-7 year follow-up visit will be invited to participate in this secondary study
which will analyze the relationship of salivary cortisol and dehydroepiandrosterone (DHEA)
to: (a) blood pressure and adiposity; (b) prenatal and postnatal growth; and (c) DNA
methylation patterns.

Inclusion Criteria:

- Infants with a minimal gestational age of 24 weeks 0 days to 27 completed weeks (up to
27 6/7ths) by best obstetrical estimate

- Infants who will receive full resuscitation as necessary, i.e., no parental request or
physician decision to forego resuscitation

- Infants whose parents/legal guardians have provided consent for enrollment, or

- Infants without known major congenital malformations

Exclusion Criteria:

- Any infant transported to the center after delivery

- Infants whose parents/legal guardians refuse consent

- Infants born during a time when the research apparatus/study personnel are not
available

- Infants < 24 weeks 0 days or > 28 weeks 0 days, completed weeks of gestation