Echocardiogram to Diagnose Pulmonary Hypertension in Premature Infants

 描述（由申请人提供）：患有支气管肺发育不良（BPD）和肺动脉高压的早产儿经常死亡。BPD是早产最常见的发病率，在美国每年影响超过20，000名婴儿。近1/5的BPD早产儿发生肺动脉高压，其中近40%死亡。新生儿医生越来越多地转向西地那非，一种有效的肺血管扩张剂，作为一线治疗肺动脉高压的早产儿BPD。西地那非是FDA批准用于治疗成人肺动脉高压，但儿科医生缺乏足够的证据基础，其用于早产儿。然而，诊断和监测这一人群的肺动脉高压是研究的主要障碍。我们将回顾来自查佩尔山的北卡罗来纳州大学和杜克大学医学中心（NICHD新生儿研究网络和儿科试验网络的两个站点）的BPD早产儿的筛查超声心动图。超声心动图将被转移至杜克临床研究所的儿科超声心动图参考实验室，由设盲的儿科心脏病专家组成的共识小组将独立评估超声心动图。长期目标是通过优化早产儿肺动脉高压的治疗来促进公共卫生。短期目标是：1）使用超声心动图来确定患有BPD的早产儿的肺动脉高压; 2）将超声心动图与患有BPD的早产儿的临床结局相关联; 3）SA 3：评估患有BPD的早产儿对西地那非的超声心动图反应。该提案将由Laughon博士领导，Laughon博士是一位在流行病学和临床药理学方面受过良好培训的药物学家。Laughon博士领导了早产儿的多中心临床药理学试验。组建的团队具有独特的资格，优势包括丰富的临床研究经验;国际公认的新生儿和儿科心脏病学定量方法的思想领导力;以及按时和按预算生产NIH项目的成功历史。研究环境，包括转化和临床科学研究所在斯坦福大学和DCRI在杜克提供了一个富有成效的，合议和协作的氛围，在追求上述研究和培训目标。在本提案结束时，研究小组将：1）量化早产儿超声心动图的可靠性; 2）将超声心动图与临床重要结局（即死亡率）相关; 3）确定暴露于和未暴露于西地那非的婴儿结局的风险差异。这些数据对于设计西地那非在早产儿中的全面临床试验至关重要。

 DESCRIPTION (provided by applicant): 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.