Salivary miRNAs as Prognostic Markers of Pulmonary Hypertension Associated with Bronchopulmonary Dysplasia in Extremely Low Gestational Age Infants

唾液 miRNA 作为极低胎龄婴儿支气管肺发育不良相关肺动脉高压的预后标志物

• 批准号: 10739639
• 负责人: Roopa Siddaiah
• 金额: $ 17.36万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739639
• 关键词: 1 year old; Admission activity; Age; Alveolar; Biological Markers; Biometry; Bronchopulmonary Dysplasia; Cell Proliferation; Cells; Cessation of life; Childhood; Clinical; Clinical Research; Clinical Trials; Complex; Complication; Correlation Studies; Data; Development; Development Plans; Diagnosis; Disease; Early identification; Echocardiography; Etiology; Extremely low gestational age newborn; Feasibility Studies; Foundations; Future; Gene Expression; Genes; Genetic; Genetic Risk; Goals; Growth Factor Gene; Home; Hypoxia; Incidence; Infant; Insulin; Intervention; Intubation; Journals; Learning; Life; Logistic Regressions; Lung; Master of Science; Medical; Mentors; MicroRNAs; Modeling; Molecular; Morbidity - disease rate; Neonatal Intensive Care Units; Outcome; Oxygen; Pathologic; Pathway Analysis; Pathway interactions; Pediatrics; Peer Review; Physicians; Population; Pre-Eclampsia; Predictive Value; Pregnancy; Premature Infant; Prevalence; Prognostic Marker; Prospective Studies; Publishing; Pulmonary Hypertension; Recording of previous events; Regression Analysis; Regulation; Research Project Grants; Risk; Saliva; Salivary; Sampling; Scientist; Small for Gestational Age Infant; Statistical Data Interpretation; Stratification; Subgroup; Testing; Trachea; Tracheostomy procedure; Training; Transforming Growth Factor beta; Translational Research; Untranslated RNA; Vascular Endothelial Growth Factors; Ventilator; Very Low Birth Weight Infant; Vulnerable Populations; Work; angiogenesis; aspirate; biological adaptation to stress; biomarker identification; biomarker panel; career; career development; classification trees; design; differential expression; experience; extreme prematurity; genomic data; high risk; hospital readmission; improved; improved outcome; in silico; interest; intraamniotic infection; longitudinal analysis; lung development; meetings; migration; molecular marker; mortality; multidisciplinary; multiple omics; neonatal care; neonate; predictive marker; pulmonary vascular disorder; recruit; regression trees; respiratory; risk prediction; risk stratification; routine screening; saliva sample; screening; tool; transcriptome sequencing; treatment response; vascular bed

PROJECT SUMMARY/ABSTRACT With recent advances in neonatal care, there is improved survival of extremely premature babies with very low birth weight, although the complications of bronchopulmonary dysplasia (BPD) remain. One of the most severe of these complications is pulmonary hypertension (BPD-PH). The true incidence of BPD-PH in preterm babies is unknown, but prevalence is estimated to range from 17-40%. BPD and BPD-PH are typically diagnosed at 36 weeks postmenstrual age (PMA). BPD-PH leads to more days in the neonatal ICU, increased days of ventilator and oxygen requirement, and the need for tracheostomy and home ventilator support. Furthermore, these infants continue to have high mortality and morbidity with increased hospital readmissions in their first 2 years of life. Some clinical parameters and qualitative markers help predict development of BPD-PH at 36 weeks PMA, such as infants born small for gestational age, maternal history of preeclampsia, chorioamnionitis, and early periods of ventilator support at 7 and 28 days of life. However, we lack quantitative markers to predict development or long-term outcomes such as death, re-hospitalization, or response to therapies. A non-invasive quantitative predictor would help stratify these infants early on and be appropriate for these frequently intubated and medically fragile infants. In our preliminary study among infants with BPD-PH, we non-invasively obtained tracheal aspirate and identified a specific panel of microRNAs (small noncoding RNAs) associated with hypoxic stress response and angiogenic pathways. We have further conducted preliminary studies correlating tracheal aspirate samples with that of saliva from extreme preterm infants. In this proposed K23 project, the Candidate (with advice from an outstanding multidisciplinary team of mentors) will study salivary samples of extreme preterm infants for early identification of target miRNAs that could predict development of BPD-PH and its long-term outcomes. This will be a prospective study of infants born <28 weeks of gestation; saliva samples will be collected at 7 and 28 days of age and analyzed for markers that could predict BPD-PH at 36 weeks of gestation. The Candidate will evaluate miRNA expression in infants with BPD-PH over the first year of life and identify markers that predict diagnosis and outcomes, based on their echocardiogram findings and oxygen requirements. By the end of this K23, the Candidate will have learned how to design and carry out future miRNA studies and analyze their results. She also will have completed selected relevant courses as part of her Master’s Degree in Clinical Research and received guidance on career development. Data will be disseminated at meetings and published in peer-reviewed journals. In summary, this project will provide a strong platform for future R01-type applications and help continue the Candidate’s positive career trajectory and ultimate goal to become an independent physician-scientist and nationally recognized expert in BPD-PH in premature infants.

项目总结/摘要 随着新生儿护理的最新进展，极早产儿的存活率有所提高， 非常低的出生体重，尽管支气管肺发育不良（BPD）的并发症仍然存在。一个最 这些并发症中严重的是肺动脉高压（BPD-PH）。早产儿BPD-PH的真实发病率 婴儿情况不详，但据估计，患病率在17- 40%之间。BPD和BPD-PH通常被诊断为 月经后36周（PMA）。BPD-PH导致新生儿ICU天数增加， 呼吸机和氧气需求，以及气管切开术和家庭呼吸机支持的需要。此外，委员会认为， 这些婴儿的死亡率和发病率仍然很高， 多年的生活。一些临床参数和定性标志物有助于预测36周时BPD-PH的发展 PMA，如出生时小于胎龄的婴儿，母亲先兆子痫史，绒毛膜炎， 在出生后7天和28天早期给予呼吸机支持。然而，我们缺乏定量指标来预测 发展或长期结局，如死亡、再次住院或对治疗的反应。一种非侵入性 定量预测有助于早期对这些婴儿进行分层，并适用于这些经常插管的婴儿。 和医学上脆弱的婴儿在我们对BPD-PH婴儿的初步研究中，我们非侵入性地获得了 气管吸出物，并确定了与缺氧相关的一组特定的microRNA（小的非编码RNA）。 应激反应和血管生成途径。我们进一步进行了初步研究， 从极早产儿的唾液中吸出样本。 在这个拟议的K23项目中，候选人（在一个杰出的多学科团队的建议下， 导师）将研究极端早产儿的唾液样本，以早期鉴定 可以预测BPD-PH的发展及其长期结果。这将是一项针对婴儿的前瞻性研究 出生时妊娠<28周;将在7天和28日龄时收集唾液样本并分析标记物 可以预测妊娠36周时的BPD-PH。候选人将评估婴儿中的miRNA表达 与BPD-PH在生命的第一年，并确定预测诊断和结果的标志物，根据他们的 超声心动图检查结果和氧气需求。在本K23课程结束时，候选人将学会如何 设计和进行未来的miRNA研究并分析其结果。她还将完成选定的 相关课程作为她临床研究硕士学位的一部分，并接受了职业指导 发展数据将在会议上传播，并在同行评审的期刊上发表。总之，这 项目将为未来的R 01型应用程序提供一个强大的平台，并有助于继续候选人的积极 职业轨迹和最终目标是成为一个独立的医生，科学家和国家认可的 早产儿BPD-PH专家。