ABSTRACT
Premature birth is the leading cause of neonatal intensive care unit admissions and exerts a high burden of
disease and health care cost, approaching $13.4 billion annually in the United States. Advances in neonatal
medicine such as antenatal steroids and surfactant have improved survival, particularly in infants born extremely
premature (before 30 weeks’ gestational age). Consequently, bronchopulmonary dysplasia (BPD) is increasing
in prevalence. This often results in lifelong cardiopulmonary sequelae that overlap with chronic diseases such
as asthma, chronic obstructive pulmonary disease, and pulmonary hypertension, increasing the risk of premature
death. Unfortunately, the impact of extreme prematurity or postnatal steroid treatment on cardiopulmonary
structure and function has not been rigorously evaluated during early school age (6-8 years), when early
identification could prevent long-term adverse outcomes. Thus, significant changes can occur and remain
undetected during this critical age of rapid lung growth and alveolarization, a time during which intervention could
be the most advantageous. To address this unmet need, we will capitalize on two outstanding resources already
in place at Cincinnati Children’s: 1) cutting-edge proton and hyperpolarized-gas magnetic resonance imaging
(MRI) that can precisely characterize phenotypes of BPD in the Cincinnati BPD Center and 2) a well-
characterized population-based cohort of preterm infants from the NIH-funded Cincinnati Infant
Neurodevelopment Early Prediction Study (CINEPS) that will reach school age during this funding period. We
will recruit the CINEPS subgroup of extremely preterm infants (140 with BPD; 68 without BPD) and a new cohort
of 50 term-born controls and study them longitudinally at 6 and 8 years of age with proton and hyperpolarized
gas MRI, spirometry, plethysmography, diffusion capacity, and a parent questionnaire. The primary goal of this
proposal is to define changes in cardiopulmonary structure and function in extremely preterm infants
during early school age. We will further evaluate the effects of postnatal steroids therapy on lung structure
and function compared to untreated infants matched using propensity score weighting. This novel proposal
represents the first application of hyperpolarized gas MRI in a cohort of extremely preterm children. Further, this
proposal represents the most detailed evaluation of the trajectory of extreme prematurity on cardiopulmonary
structure and function through early school age. This high-impact research will define the progression of lung,
heart, and pulmonary vascular disease as well as response to postnatal therapies and provide a unique
opportunity for early identification of patients who will develop chronic changes related to extremely preterm birth
and BPD.