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

摘要 据估计，全世界每年发生1300万早产（PTB），PTB是最重要的一种。 是导致新生儿发病率和死亡率的主要因素。无法正确识别有PTB风险的患者 限制了有效的研究进展，因为它阻止了实际上有疾病风险的人群的聚集， 对异质性队列的重大研究投资，测试的干预措施的适度或冲突效果，以及 临床翻译不清楚根据两个主要风险因素应用当前PTB预测：1）既往PTB （2）超声显示宫颈长度较短。这两个风险标准在未经产的 患者，因为他们没有产科史，以指导危险分层，宫颈长度有不良的预测 能力事实上，在2021年美国妇产科学院关于PTB预防的实践公告中， 作者的结论是，“是否以及如何筛查未生育妇女是一个不确定和有争议的问题。” 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 不能量化施加到子宫颈的压力，使得测量是非定量的，从而 防止检查者之间、患者内纵向比较和患者间的标准化 比较。我们已经克服了这个关键的限制，一个新的，精确的，独立于操作员的，超声- 全定量宫颈弹性成像系统（Q-CES）。我们的初步数据 表明：1）在妊娠早期通过Q-CES检测到的颈部僵硬与以下因素显著相关： 自发性PTB，和2）Q-CES可能比宫颈长度对自发性PTB具有更强的预测效用。 本提案的目的是检验颈椎僵硬度的Q-CES值可以更好地 使用多中心、多样化的前瞻性队列，与宫颈长度相比，更准确地预测自发性PTB。在Aim中 1我们将首次量化未生育患者颈椎僵硬度的标准Q-CES值， 足月分娩和早产分娩。在目标2中，我们将使用Q-CES开发一个多参数风险预测模型 与基于宫颈长度的现有模型相比， 我们有一个成熟的多学科团队已经在本提案中的所有三个中心执行Q-CES， 准备好了设备可以用于这个项目我们将招募35%的黑人和西班牙裔患者， 以确保我们的研究结果能够探索PTB风险中持续存在的种族和民族差异。完成这些 aims将使我们能够第一次对怀孕期间颈部组织的纵向硬度进行数值量化 并检测预测自发性PTB的软化模式。这将是直接临床可操作的， 通过提高集合理性研究群体的能力，解决PTB科学中的一个根本性障碍 对已知和尚未开发的PTB预防策略进行更有意义的测试。

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.