Trajectories of Regional Cardiopulmonary Structure and Function in A Longitudinal Cohort of Extremely Preterm Infants

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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.