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

自发性动脉导管未闭 (PDA) 闭合及 PDA 相关结果的早期预测

• 批准号: 10311538
• 负责人: Carl Backes
• 金额: $ 56.04万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10311538
• 关键词: Academy; Adverse effects; Age; Age-Months; American; Arteries; Biological Markers; Birth; Blood Circulation; Blood Vessels; Blood flow; Brain; Brain Injuries; Catheters; Chronic lung disease; Clinical; Clinical Treatment; Collection; Congestive Heart Failure; Data; Development; Duct (organ) structure; Early Intervention; Early identification; Echocardiography; Effectiveness; Enrollment; Frequencies; Future; Goals; Growth; Growth and Development function; Heart; Human; Image; Impairment; Individual; Infant; Infant Health; Institution; Intervention; Investigation; LCN2 gene; Left; Ligation; Link; Lung; Measurement; Measures; Methods; Mission; Modeling; Myocardial; Myocardial Ischemia; Natural History; Nature; Neurodevelopmental Impairment; Non-Steroidal Anti-Inflammatory Agents; Operative Surgical Procedures; Outcome; Patent Ductus Arteriosus; Patients; Pediatrics; Performance; Pharmaceutical Preparations; Pharmacology; Pregnancy; Premature Birth; Premature Infant; Probability; Process; Prospective Studies; Prospective cohort; Provider; Public Health; Pulmonary Hypertension; Quantitative Evaluations; Reporting; Research; Respiratory Disease; Retrospective Studies; Risk Factors; Sample Size; Serum; Severities; Severity of illness; Specific qualifier value; Testing; Tissues; Treatment Effectiveness; United States National Institutes of Health; Urine; Vulnerable Populations; base; clinical decision-making; clinical practice; clinical predictors; clinical risk; cohort; demographics; effectiveness trial; fetal; fetal blood; high risk; high risk infant; improved; in utero; innovation; mortality; mortality risk; neonatal care; neurodevelopment; novel; outcome prediction; overtreatment; postnatal; predictive marker; prospective; randomized trial; respiratory; routine provider; standard of care; targeted treatment; tool; treatment strategy; unnecessary treatment

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.

项目总结/文摘