Cervicovaginal Biomarkers of Cervical Shortening and Cerclage Efficacy

宫颈缩短和环扎术功效的宫颈阴道生物标志物

• 批准号: 9104181
• 负责人: Luisa A Wetta
• 金额: $ 7.28万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-03 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9104181
• 关键词: Amniotic Fluid; Applications Grants; Biological Markers; Birth; Cervical; Cervical Cerclage; Cervix Uteri; Characteristics; Collagen; Diagnosis; Discipline of obstetrics; Epidemiologic Studies; Functional disorder; Future; Health; High Risk Woman; Infant; Infant Mortality; Infection; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Intervention; Intervention Trial; Knowledge; Lead; Length; Liquid substance; Measurement; Measures; Mediator of activation protein; Monitor; Morbidity - disease rate; Neonatal Mortality; Pathologic Processes; Pathway interactions; Patients; Phenotype; Play; Population; Pregnancy; Pregnancy Outcome; Premature Birth; Public Health; Race; Recording of previous events; Recurrence; Research; Research Personnel; Risk; Risk Factors; Serum; Survivors; Syndrome; Time; Ultrasonography; Woman; Women' s Group; cervicovaginal; clinical practice; cohort; cytokine; effective intervention; high risk; inflammatory marker; interest; potential biomarker; predicting response; randomized trial; response; routine care

 DESCRIPTION (provided by applicant): Preterm birth is the most important problem in obstetrics, because it occurs commonly and is associated with neonatal mortality as well as morbidity in survivors. Despite extensive research, little progress has been made in decreasing the rate of preterm birth, largely due to our general lack of understanding of the underlying pathophysiology. Epidemiological studies have identified numerous risk factors for preterm birth, especially a history of a prior spontaneous preterm birth and mid-trimester cervical shortening. Cervical shortening less than 25 mm (10th percentile) diagnosed by transvaginal ultrasonography in the mid-trimester is one of the most powerful markers of recurrent preterm birth in women with a history of a spontaneous preterm birth, and cervical cerclage has become a widely utilized effective intervention in these women. Nevertheless, not all women who undergo an ultrasound-indicated cerclage will subsequently deliver a term infant. There remains an incomplete understanding of the pathophysiologic mechanisms and pathways underlying the initiation of preterm birth, especially in regard to the pathway that includes asymptomatic cervical shortening. The contribution of inflammation to the spontaneous preterm birth syndrome is well- established, but less is known about the association between inflammation and cervical shortening. While prior studies have focused on a systemic inflammatory response, recent interest has shifted towards defining a potential set of biomarkers that could define characteristics of a more localized response. In this grant application, we propose to measure concentrations of inflammatory mediators and markers of collagen remodeling in a well-characterized cohort of high-risk women who have had a prior spontaneous preterm birth between 17 0/7 and 33 6/7 weeks' gestation. We will evaluate: 1.) whether cervicovaginal fluid analyte concentrations differ in women who develop cervical shortening (<25mm) compared to those women who maintain a cervical length (=25mm). 2.) In high-risk women who develop mid-trimester cervical shortening (<25mm), to evaluate: a) Whether cervicovaginal fluid analyte concentrations measured at the time that cervical shortening is recognized can identify women in whom cerclage confers the greatest benefit, or alternatively harm. b) Whether the change in cervicovaginal fluid analyte concentrations between the baseline measurement and the measurement at the diagnosis of cervical shortening can predict response to cerclage and subsequent pregnancy outcome. Realizing these aims will not only lead to a better understanding of the spontaneous preterm birth syndrome, but will also help clinicians define more individualized and effective strategies for managing women with cervical shortening who are at high risk for recurrent preterm birth. This information will also assist investigators in identifying which women are at the highest risk for recurrent preterm birth and who may be good candidates for future intervention trials of alternate therapies.

 描述（适用提供）：早产是产科中最重要的问题，因为它通常发生，并且与新生儿死亡率以及生存中的发病率有关。尽管进行了广泛的研究，但在降低早产率的降低率很少，这很大程度上是由于我们普遍缺乏对潜在的病理生理学的了解。流行病学研究已经确定了早产的许多危险因素，尤其是先前的赞助早产和孕期宫颈缩短的病史。宫颈缩短少于25毫米（第10个百分位数）在孕妇中期通过经阴道超声检查诊断为诊断出具有赞助早产史的女性，是重复早产的最强大的重复早产标记之一，并且宫颈cerclage已成为这些女性的有效干预。然而，并非所有经历超声指示的固定的妇女都会对早产倡议的病理生理机制和途径保持不完全理解，尤其是关于包括不对称宫颈缩短的途径。炎症对赞助商自发早产综合征的贡献是良好的，但对感染与宫颈缩短之间的关联知之甚少。虽然先前的研究集中在系统性炎症反应上，但最近有趣的转变朝着定义一组潜在的生物标志物，这些标志物可以定义更局部响应的特征。在此赠款应用中，我们建议在良好的高危妇女中衡量炎症介质的浓度和胶原蛋白重塑的标志物，而高危女性的同类群体则在17 0/7至33 6/7周之间具有先前的赞助早产。我们将评估：1。）是否有不同的宫颈流体分析物浓度不同。2。）在孕妇中期宫颈缩短（<25mm）的高风险女性中，以评估：a）a）宫颈缩短是否可以识别出cerclage赋予最大益处或其他伤害的女性。 b）基线测量和诊断宫颈缩短时的测量之间的宫颈液分析物浓度的变化是否可以预测对cerclage和随后的妊娠结局的反应。意识到这些目标不仅会更好地了解赞助商样早产综合症，而且还将帮助临床医生定义更有和有效的策略，以管理具有重复早产的高风险的宫颈缩短妇女。该信息还将帮助调查人员确定哪些妇女是重复出生的最高风险，哪些妇女可能是对替代疗法的未来干预试验的好候选者。