Premature infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension often die. BPD is the most common morbidity of prematurity, and affects over 20,000 infants per year in the US. Nearly 1/5 of premature infants with BPD develop pulmonary hypertension, and almost 40% of those die. Neonatologists have increasingly turned to sildenafil, a potent pulmonary vasodilator, as a first line treatment for pulmonary hypertension in premature infants with BPD. Sildenafil is FDA-approved for treatment of pulmonary hypertension in adults, but neonatologists lack an adequate evidence base for its use in premature infants. However, diagnosing and monitoring pulmonary hypertension in this population is a major barrier for research. We will review screening echocardiograms from premature infants with BPD from The University of North Carolina at Chapel Hill and Duke University Medical Center, both sites of the NICHD Neonatal Research Network and the Pediatric Trials Network. The echocardiograms will be transferred to the Pediatric Echocardiography Reference Laboratory at the Duke Clinical Research Institute where a consensus panel of masked pediatric cardiologists will independently assess the echocardiograms. The long-term goal is to advance public health by optimizing treatment of pulmonary hypertension in premature infants. The short-term goals are to 1) Use echocardiography to define pulmonary hypertension in premature infants with BPD; 2) Correlate echocardiograms with clinical outcomes of premature infants with BPD; and 3) SA3: Validate echocardiographic response to sildenafil in premature infants with BPD. The proposal will be led by Dr. Laughon, a neonatologist with strong training in epidemiology and clinical pharmacology. Dr. Laughon has led multicenter clinical pharmacology trials in premature infants. The team assembled is uniquely qualified, and strengths include extensive clinical research experience; internationally recognized thought leadership in neonatal and pediatric cardiology quantitative methods; and a successful history of productive on time and on budget NIH projects. The research environment including the Translational and Clinical Sciences Institute at UNC and the DCRI at Duke provide a productive, collegial, and collaborative atmosphere in which to pursue the above research and training goals. At the conclusion of this proposal, the research team will have: 1) quantified the reliability echocardiograms in premature infants; 2) related echocardiograms to clinically important outcomes-i.e. mortality; and 3) determined the risk difference in outcomes of infants exposed and not exposed to sildenafil. These data are critically important for designing a full scale clinical trial of sildenafil in premature infants.
This proposal will determine the utility of echocardiogram for diagnosing and monitoring pulmonary hypertension in premature infants with bronchopulmonary dysplasia. This information is critical for the development of a full scale clinical trial of sildeafil in premature infants including: 1) inclusion/exclusion criteria; 2) endpoint development; and 3) risk difference (effect size) of sildenafil in this population.
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