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.

项目概要/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 尽管支气管肺发育不良（BPD）的并发症仍然存在，但出生体重极低。 这些并发症中最严重的是肺动脉高压 (BPD-PH)。早产儿 BPD-PH 的真实发生率。 婴儿的情况未知，但 BPD 的患病率估计为 17-40%，BPD-PH 通常被诊断出来。 月经后 36 周 (PMA) 导致新生儿 ICU 住院天数增加，住院天数增加。 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， 这些婴儿的死亡率和发病率仍然很高，并且在出生后的头 2 个月内再次入院的人数增加 一些临床参数和定性标记有助于预测 36 周时 BPD-PH 的发展。 PMA，例如出生小于胎龄的婴儿、先兆子痫、绒毛膜羊膜炎的母亲病史，以及 出生后 7 天和 28 天的早期呼吸机支持 然而，我们缺乏定量标记来预测。 发展或长期结果，如死亡、再住院或对治疗的反应。 定量预测器将有助于尽早对这些婴儿进行分层，并适合那些经常插管的婴儿 在我们对患有 BPD-PH 的婴儿的初步研究中，我们通过非侵入性方法获得了这些婴儿的信息。 气管抽吸物并鉴定出与缺氧相关的一组特定的 microRNA（小非编码 RNA） 我们进一步进行了气管相关的初步研究。 抽取极端早产儿的唾液样本。 在这个拟议的 K23 项目中，候选人（在来自杰出多学科团队的建议下） 导师）将研究极端早产儿的唾液样本，以早期识别目标 miRNA 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。 妊娠<28周出生；将在7天和28天时收集唾液样本并进行标记物分析 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。 在生命的第一年患有 BPD-PH，并根据其预测诊断和结果的标记物 超声心动图检查结果和氧气需求 在本 K23 结束时，考生将了解如何进行。 她还将完成选定的研究，以设计和开展未来的 miRNA 研究并分析其结果。 作为临床研究硕士学位的一部分，她学习了相关课程，并获得了职业指导 数据将在会议上传播并在同行评审期刊上发表。 项目将为未来的 R01 型应用提供强大的平台，并帮助继续候选人的积极态度 成为一名独立的医师科学家并获得全国认可的职业轨迹和最终目标 早产儿 BPD-PH 专家。