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
基本信息
- 批准号:10739639
- 负责人:
- 金额:$ 17.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:1 year oldAdmission activityAgeAlveolarBiological MarkersBiometryBronchopulmonary DysplasiaCell ProliferationCellsCessation of lifeChildhoodClinicalClinical ResearchClinical TrialsComplexComplicationCorrelation StudiesDataDevelopmentDevelopment PlansDiagnosisDiseaseEarly identificationEchocardiographyEtiologyExtremely low gestational age newbornFeasibility StudiesFoundationsFutureGene ExpressionGenesGeneticGenetic RiskGoalsGrowth Factor GeneHomeHypoxiaIncidenceInfantInsulinInterventionIntubationJournalsLearningLifeLogistic RegressionsLungMaster of ScienceMedicalMentorsMicroRNAsModelingMolecularMorbidity - disease rateNeonatal Intensive Care UnitsOutcomeOxygenPathologicPathway AnalysisPathway interactionsPediatricsPeer ReviewPhysiciansPopulationPre-EclampsiaPredictive ValuePregnancyPremature InfantPrevalencePrognostic MarkerProspective StudiesPublishingPulmonary HypertensionRecording of previous eventsRegression AnalysisRegulationResearch Project GrantsRiskSalivaSalivarySamplingScientistSmall for Gestational Age InfantStatistical Data InterpretationStratificationSubgroupTestingTracheaTracheostomy procedureTrainingTransforming Growth Factor betaTranslational ResearchUntranslated RNAVascular Endothelial Growth FactorsVentilatorVery Low Birth Weight InfantVulnerable PopulationsWorkangiogenesisaspiratebiological adaptation to stressbiomarker identificationbiomarker panelcareercareer developmentclassification treesdesigndifferential expressionexperienceextreme prematuritygenomic datahigh riskhospital readmissionimprovedimproved outcomein silicointerestintraamniotic infectionlongitudinal analysislung developmentmeetingsmigrationmolecular markermortalitymultidisciplinarymultiple omicsneonatal careneonatepredictive markerpulmonary vascular disorderrecruitregression treesrespiratoryrisk predictionrisk stratificationroutine screeningsaliva samplescreeningtooltranscriptome sequencingtreatment responsevascular bed
项目摘要
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/文摘
项目成果
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