Bronchopulmonary dysplasia (BPD) affects up to half of extremely preterm infants, and is associated
with significant adverse respiratory, developmental, educational, and health economic outcomes. The NICHD
Neonatal Research Network (NRN) Hydrocortisone for BPD Trial has enrolled 652 of a planned total of 800
preterm infants at high risk for BPD in a placebo controlled trial of hydrocortisone (HC). The proposed
“Hydrocortisone for BPD Respiratory and Developmental (HYBRiD) Outcomes Study” builds on this ongoing
clinical trial to characterize the functional respiratory and developmental outcomes of this established
trial population at 5 years corrected age, or early school age. Functional assessments, which cannot be
performed before early school age, provide parents and schools with a realistic picture of a child's strengths
and challenges in every day scenarios, so that appropriate services can be provided to prevent school failure.
This proposed trial follow-up takes advantage of (1) a large, well-described, trial population of children
who had severe neonatal lung disease and are being followed until 2 years corrected age; (2) the support of
the NRN infrastructure, (3) the NRN's superb track records in school age trial follow-up and collaboration with
NHLBI, and (4) the long-standing successful relationship between the NRN Data Coordinating Center (DCC) at
RTI and the Clinical Coordinating Center (CCC) and NRN investigators. The CCC and DCC both have
extensive expertise and experience in the conduct and follow-up of large neonatal clinical trials.
The HYBRiD Outcomes Study will use novel functional assessments of early school age developmental
and respiratory outcomes to assess the impact of both HC exposure and severity of lung disease. The primary
outcome of functional impairment is defined as any one of four outcomes that can be measured directly in the
child: cognitive delay, motor impairment, academic delay, or poor functional exercise capacity as measured by
the 6-minute walk test (6MWT). The HYBRiD Outcome Study specific aims are, within the NRN HC for BPD
Trial at 5 years corrected age, to evaluate: (1) the impact of HC exposure on rates of functional impairment;
and (2) the relationship between severity of BPD (based on the categorical NIH consensus definition of BPD)
and functional impairment. The HYBRiD Outcome Study's functional respiratory outcomes, which are novel in
this population, will be validated with impulse oscillometry in the participants at a subset of centers.
Supported unanimously by the NRN, this study will address several critical knowledge gaps about the
early school age outcomes of children with neonatal respiratory failure, based on both the severity of BPD and
exposure to HC, as well as the relationships between respiratory and developmental outcomes. These results
will have immediate impact on counseling of parents in the neonatal intensive care unit and management of
neonates in the unit and after discharge. In addition, these data will be essential for the development of future
intervention studies aimed to improve the long-term outcomes of preterm infants with respiratory failure.