Hydrocortisone for BPD

Bronchopulmonary dysplasia (BPD) remains a leading morbidity of the extremely preterm infant,
and prolonged mechanical ventilation is associated with increased risk for BPD. Dexamethasone
has been used previously to facilitate extubation and decrease the incidence of BPD; however,
due to adverse effects on neurodevelopmental outcomes, the use of this drug has decreased.
One cohort study suggests that hydrocortisone (HC) may facilitate extubation. HC has thus far
not been associated with adverse neurodevelopmental outcomes in either cohort studies or
randomized controlled trials. A recent meta-analysis of postnatal corticosteroid therapy
begun after the first week of life suggested that "late therapy may reduce neonatal mortality
without significantly increasing the risk of adverse long-term neurodevelopmental outcomes,"
although the methodological quality of some of the follow-up was acknowledged to be limited.

This is a randomized controlled trial to study the efficacy and safety of a 10-day tapering
course of hydrocortisone treatment for infants <30 weeks estimated gestational age at birth
who remain intubated at 14 - 28 days postnatal age. Based on previous Network data these
criteria define a population with a risk of death or BPD at 36 weeks postmenstrual age of
approximately 65 - 75%. The primary outcome for this study will incorporate both (1) survival
without moderate to severe BPD by Network physiologic definition and (2) survival without
moderate or severe NDI at 18 - 22 months corrected age. Therefore, the results of this study
will be reported only when follow-up data are available unless (1) the trial is stopped early
by the DSMC because of strong evidence of benefit or harm, or (2) at the time all subjects
have completed treatment the DCC finds a substantial survival benefit favoring hydrocortisone
(p<0.001). Individual study assignment will remain masked until the follow-up is completed.
Secondary outcomes will include short term measures such as respiratory morbidities and
growth at 36 weeks postmenstrual age and long term measures including growth and other
outcomes at 22 - 26 months corrected age.

Secondary studies include:

1)Effect of Hydrocortisone on the Cardiac mass of Premature Intubated Infants - will
determine left ventricular mass index at 36 weeks postmenstrual age (or prior to
discharge/transfer if after 34 weeks) in infants enrolled in the hydrocortisone for BPD RCT,
and compare HC-treated infants to placebo-treated infants. It will similarly assess and
compare the incidence of pulmonary hypertension in these patients.

Extended follow-up: Subjects will be seen for a follow-up visit at 5-6 years corrected age to
assess functional developmental and respiratory outcomes at early school age. In a subset of
four Neonatal Research Network Clinical Centers, impulse oscillometry (IOS), which is the
optimal direct measure of lung capacity and function, will be performed to validate the
6-minute walk test and International Study of Asthma and Allergies in Childhood (ISAAC)
questionnaire as functional measures of pulmonary status.

Inclusion Criteria:

- infants <30 weeks estimated gestational age

- inborn at an NRN site or were admitted to an NRN site before 72 hours postnatal age

- have received at least 7days of mechanical ventilation;

- are receiving mechanical ventilation through an endotracheal tube .

Exclusion Criteria:

- Major congenital anomalies

- Decision to limit support

- Indomethacin or ibuprofen treatment within 48 hours of study drug

- Previous corticosteroid treatment for BPD

- Received hydrocortisone for 14 or more cumulative days

- Received hydrocortisone within 7 days of study entry