Early Prediction of Spontaneous Patent Ductus Arteriosus (PDA) Closure and PDA-Associated Outcomes

项目摘要/摘要 动脉导管未闭(PDA)在早产儿中非常常见，它与死亡和有害的长期畸形有关。 足月结局包括慢性肺部疾病和神经发育迟缓。尽管如此，药理学和/或 介入治疗关闭PDA可能使一些婴儿受益，所有早产儿普遍接受常规治疗 患有PDA的婴儿可能不会改善重要的预后。如果不治疗，大多数掌上电脑会自发关闭44- 经后几周年龄(PMA)。因此，pda的治疗方法越来越有争议，而且差异很大。 机构和个人提供者之间的关系。相关且仍未得到解答的临床问题不是是否要 用PDA治疗所有早产儿，但要治疗谁，什么时候治疗。治疗可能弊大于利， 由于所有形式的故意关闭PDA都有潜在的不良影响，特别是对早产的婴儿， PDA自发性闭合。不幸的是，临床医生目前无法在出生后的第一个月预测哪些婴儿 持续性PDA的风险最高，临床风险因素、回声测量和 血清生物标志物可能是预测PDA相关损害的最佳指标。美国儿科学会的掌上电脑 临床指导报告承认，早期识别PDA高危婴儿是一项关键研究 通知未来PDA的目标-治疗效果-试验。此应用程序的目标是使用 未经治疗的PDA婴儿预测自发性导管关闭时间的前瞻性队列 出生后第一个月和出生后第一个月出现的临床危险因素、回声测量和生物标志物 与长期损伤相关。临床、血清和尿液生物标记物(BNP、NTpBNP、NGAL、H-FABP)和 对出生后4周内连续收集的超声心动图参数进行检查。 此外，心肌变形成像(MDI)和组织多普勒成像(TDI)，创新 超声心动图方法，将有助于定量评价心肌功能。所有具体目标都将 收集和检查出生后第一个月内患有PDA的早产儿的数据。目标1将估计 使用超声心动图预测动脉导管自发性关闭的概率和预测导管关闭的时间， 生物标记物和临床预测指标。目标2将明确哪些超声心动图预测指标和生物标记物 与妊娠36周的死亡率和呼吸系统疾病的严重程度有关。目标3将确定哪些 超声心动图预测指标和生物标记物与22至26个月的神经发育有关。所有型号都将是 在单独的婴儿队列中进行了验证。该项目将极大地促进临床结果和 减少早产儿不必要和有害的过度治疗对PDA的管理 自发的PDA关闭，并将允许开发注重结果的试验，以检查 对于最有可能受益的“高危”婴儿，关闭动脉导管未闭的有效性。

Project Summary/Abstract Patent ductus arteriosus (PDA), very common in preterm infants, is associated with mortality and harmful long- term outcomes including chronic lung disease and neurodevelopmental delay. Although, pharmacologic and/or interventional treatments to close PDA likely benefit some infants, widespread routine treatment of all preterm infants with PDA may not improve important outcomes. Left untreated, most PDAs close spontaneously by 44- weeks postmenstrual age (PMA). Thus, PDA treatment is increasingly controversial and varies markedly between institutions and individual providers. The relevant and still unanswered clinical question is not whether to treat all preterm infants with PDA, but whom to treat and when. Treatment detriments may outweigh benefits, since all forms of deliberate PDA closure have potential adverse effects, especially in infants destined for early, spontaneous PDA closure. Unfortunately, clinicians cannot currently predict in the first month which infants are at highest risk for persistent PDA, and which combination of clinical risk factors, echo measurements, and serum biomarkers may best predict PDA-associated harm. The American Academy of Pediatrics in their PDA Clinical Guidance Report acknowledged early identification of infants at high-risk from PDA as a key research goal for informing future PDA-treatment effectiveness-trials. The objective in this application is to use a prospective cohort of untreated infants with PDA to predict spontaneous ductal closure timing and to identify clinical risk factors, echo measurements, and biomarkers that are present in the first postnatal month and associated with long-term impairment. Clinical, serum and urine biomarkers (BNP, NTpBNP, NGAL, H-FABP), and echocardiographic variables sequentially collected during each of the first 4 postnatal weeks will be examined. In addition myocardial deformation imaging (MDI) and tissue Doppler imaging (TDI), innovative echocardiographic methods, will facilitate the quantitative evaluation of myocardial performance. All Specific Aims will collect and examine data from preterm infants with PDA within the first postnatal month. Aim 1 will estimate the probability of spontaneous PDA closure and predict the timing of ductal closure using echocardiographic, biomarker, and clinical predictors. Aim 2 will specify which echocardiographic predictors and biomarkers are associated with mortality and severity of respiratory illness at 36-weeks PMA. Aim 3 will identify which echocardiographic predictors and biomarkers are associated with 22- to 26-month neurodevelopment. All models will be validated in a separate cohort of infants. This project will significantly contribute to clinical outcomes and management of PDA by reducing unnecessary and harmful overtreatment of infants with a high probability of early spontaneous PDA closure, and will permit the development of outcomes-focused trials to examine the effectiveness of PDA closure in those “high-risk” infants most likely to receive benefit.