Fully Quantitative Cervical Elastography for Prediction of Preterm Birth in Nulliparous Patients

全定量宫颈弹性成像预测未产妇早产

• 批准号: 10657884
• 负责人: Molly Stout
• 金额: $ 72.51万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-14 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657884
• 关键词: 37 weeks gestation; Address; American; Area Under Curve; Birth; Black race; Cervical; Cervical stiffness; Cervix Uteri; Characteristics; Clinical; Data; Diagnostic tests; Discipline of obstetrics; Enrollment; Equipment; Family; Fetus; Gestational Age; Gynecology; Health; Health Care Costs; Hispanic; Image; Imaging Device; Infant; Investments; Length; Longitudinal cohort; Measurement; Measures; Methodology; Methods; Modeling; Neonatal Mortality; Not Hispanic or Latino; Nulliparity; Outcome; Patients; Pattern; Perinatology; Populations at Risk; Predictive Value; Pregnancy; Premature Birth; Prevention; Prevention Measures; Prevention strategy; Process; Prospective cohort; Receiver Operating Characteristics; Recording of previous events; Research; Risk; Risk Factors; Science; Standardization; Survivors; System; Techniques; Term Birth; Testing; Time; Tissues; Transvaginal Ultrasound; Treatment Cost; Uncertainty; United States; Woman; black patient; cervical remodeling; clinical predictors; clinical translation; clinically actionable; cohort; college; data standards; disorder risk; early pregnancy; elastography; ethnic disparity; ethnic diversity; health disparity; imaging modality; improved; individualized prevention; intervention effect; mortality risk; multidisciplinary; neonatal morbidity; novel; parous; participant enrollment; predictive modeling; pregnant; pressure; prevent; prospective; racial disparity; racial diversity; recruit; risk prediction model; risk stratification; serial imaging; ultrasound

ABSTRACT An estimated 13 million preterm births (PTBs) occur annually worldwide and PTB is the single most significant contributing factor to neonatal morbidity and mortality. The inability to correctly identify patients at risk for PTB limits efficient research progress by preventing assembly of cohorts actually at risk for the disease and leaves major research investments with heterogenous cohorts, modest or conflicting effects of interventions tested, and unclear clinical translation. Current PTB prediction is applied according to two primary risk factors: 1) prior PTB and 2) short cervical length on ultrasound. These two risk criteria are particularly problematic in nulliparous patients because they have no obstetric history to guide risk stratification, and cervical length has poor predictive ability. In fact, in a 2021 American College of Obstetrics and Gynecology practice bulletin on PTB prevention, the authors concluded that “whether and how to screen nulliparous women is a matter of uncertainty and debate.” Cervical tissue elastography is a promising technique to measure cervical remodeling. However, current systems are unable to quantify the pressure applied to the cervix, making the measurement non-quantitative and thereby preventing standardization between examiners, longitudinal within-patient comparisons, and between-patient comparisons. We have overcome this key limitation with a novel, precise, operator-independent, ultrasound- based imaging modality—fully quantitative cervical elastography system (Q-CES). Our preliminary data shows that 1) cervical stiffness, detectable by Q-CES in early pregnancy, is significantly associated with spontaneous PTB, and 2) Q-CES may have stronger predictive utility for spontaneous PTB than cervical length. The aims of this proposal will test the overall hypothesis that Q-CES values of cervical stiffness can more accurately predict spontaneous PTB than cervical length using a multicenter, diverse prospective cohort. In Aim 1 we will, for the first time, quantify normative Q-CES values of cervical stiffness in nulliparous patients who deliver at term versus preterm. In Aim 2 we will use Q-CES to develop a multiparametric risk prediction model for spontaneous PTB compared to existing models based on cervical length. We have an established, multidisciplinary team already performing Q-CES at all three centers in this proposal, with equipment in place and ready to be leveraged for this project. We will enroll 35% Black and Hispanic patients to ensure that our results can explore the persistent racial and ethnic disparities in PTB risk. Completion of these aims will allow us to, for the first time, numerically quantify cervical tissue stiffness longitudinally in pregnancy and to detect softening patterns predictive of spontaneous PTB. This will be directly clinically actionable and address a fundamental roadblock in PTB science by improving the ability to assemble rational research cohorts for more meaningful testing of known and as-yet-undeveloped PTB prevention strategies.

摘要 据估计，全世界每年有1300万早产儿(PTB)，其中PTB是最重要的 导致新生儿发病率和死亡率的因素。无法正确识别有肺结核风险的患者 通过防止实际处于疾病风险的队列的集合和叶子来限制有效的研究进展 具有不同队列的主要研究投资，测试的干预措施的适度或相互冲突的影响，以及 临床翻译不清楚。目前的肺结核预测是根据两个主要危险因素进行的：1)既往肺结核 (2)超声检查宫颈长度较短。这两个风险标准在临产时尤其成问题。 患者，因为他们没有产科病史来指导危险分层，而宫颈长度对预测很差 才能。事实上，在2021年美国妇产科学院关于结核病预防的实践公告中， 作者总结道：“是否以及如何筛查未分娩的妇女是一个充满不确定性和争议性的问题。” 宫颈组织弹性成像是一种很有前途的测量宫颈重塑的技术。然而，目前的系统 无法量化施加在宫颈上的压力，使得测量无法量化，从而 防止检查人员之间的标准化、患者内部的纵向比较和患者之间的标准化 比较。我们用一种新颖的、精确的、独立于操作员的超声波克服了这一关键限制- 基于成像模式-全定量颈椎弹性成像系统(Q-CES)。我们的初步数据 结果表明：1)妊娠早期可通过Q-CES检测到的宫颈僵硬与 Q-CES对自发性肺结核的预测作用强于宫颈长度。 这项提议的目的将检验颈椎僵硬的Q-CES值可以更多地 使用多中心、不同的前瞻性队列，准确预测自发性肺结核而不是宫颈长度。在AIM 1我们将首次量化未分娩患者宫颈僵硬的标准Q-CES值。 足月分娩与早产相比。在目标2中，我们将使用Q-CES来开发一个多参数风险预测模型 用于自发性肺结核与现有基于宫颈长度的模型进行比较。 我们有一个成熟的、多学科的团队，已经在本提案中的所有三个中心进行Q-CES， 设备已就位，并准备好用于该项目。我们将招收35%的黑人和西班牙裔患者 以确保我们的结果能够探索肺结核风险中持续存在的种族和民族差异。完成这些工作 AIMS将使我们第一次能够对怀孕期间宫颈组织的纵向硬度进行数值量化 并检测预测自发性肺结核的软化模式。这将直接在临床上可操作，并 通过提高组建合理研究队列的能力，解决结核病科学中的一个基本障碍 对已知和尚未制定的结核病预防战略进行更有意义的测试。