Mechanisms for pelvic organ prolapse after obstetrical levator muscle injury

产科提肌损伤后盆腔器官脱垂的机制

基本信息

批准号：
8994287
负责人：
VICTORIA Lynn HANDA
金额：
$ 34.36万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-01-12 至 2017-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8994287
关键词：
3-Dimensional Address Adult Aging Area Biological Birth Bladder Bladder Dysfunction Case-Control Studies Cesarean section Childbirth Chronic Cohort Studies Complex Complication Data Development Epidemiologic Studies Evaluation Event Female Functional disorder Goals Health High Prevalence Image Injury Intestines Lead Life Measures Mission Muscle Muscle Weakness Muscle function National Institute of Child Health and Human Development Operative Surgical Procedures Organ Pathway interactions Pelvic Examination Pelvic Floor Disorders Pelvis Prevention Prevention strategy Public Health Reconstructive Surgical Procedures Reproductive Process Research Residual state Risk Risk Factors Risk Marker Role Structure Three-Dimensional Imaging Time Ultrasonography Uterine Prolapse Uterus Vagina Vaginal Prolapses Vaginal delivery procedure Woman burden of illness cohort cost levator ani muscle lifetime risk muscle strength muscular structure operation pelvic organ prolapse tool

项目摘要

DESCRIPTION (provided by applicant): Female pelvic organ prolapse (POP) is a disabling, chronic condition in which the uterus and vaginal walls protrude through the vagina, causing discomfort as well as bladder and bowel dysfunction. A woman's lifetime risk of POP surgery is 19%. Prevention strategies have not been identified because the biological mechanisms underlying POP are uncertain. Other than aging, the only known risk factor for POP is vaginal childbirth. Specifically, prior research by this team demonstrated that vaginal delivery is associated with a 5-fold increase in the odds of POP. However, the mechanisms for this association remain unknown. Studies proposed in this application will investigate whether obstetrical levator ani muscle injury (LAMI) contributes to POP through alterations in the structure and/or the function of the levator muscles. LAMI, which occurs after 20% of vaginal births, can be detected with 3-dimensional ultrasound imaging. The central hypothesis of this proposal is that LAMI leads to POP through two discrete mechanisms: chronic widening of the levator hiatus (change in structure) and weakness of the levator muscle complex (change in function). The specific aims of this proposal are: (1) to compare levator ani muscle structure and function between women with and without LAMI, as identified on 3D ultrasound; (2) to determine the relative contributions of LAMI, levator ani muscle structure and function to POP. To accomplish these aims, 460 vaginally parous women from this team's established longitudinal cohort study (R01HD056275) will be evaluated 5-15 years from delivery. Evaluation will include quantitative assessment of pelvic organ support, 3D imaging of the levator muscle complex, and objective measures of levator strength. 3D ultrasound is an exciting tool that provides dynamic, real time views of the levator muscle and will enable us to detect LAMI and to distinguish structural and functional differences between those with and without LAMI. Thus, the proposed studies will consider not only the role of LAMI in the development of POP, but also the long term sequelae of LAMI (such as chronic changes to the levator hiatus). LAMI has emerged as an important obstetrical complication that is currently not preventable, except by elective cesarean birth. This research will be significant because POP prevention will not be possible until the pathophysiology is elucidated and markers for POP risk are identified. The studies proposed in this application are expected to provide markers that will identify women at greatest risk for POP and will serve as a platform for developing effective prevention strategies. Given the high prevalence of POP, prevention is critical to reduce the public health burden.

描述（由申请人提供）：女性盆腔器官脱垂（POP）是一种致残性慢性疾病，子宫和阴道壁突出阴道，引起不适以及膀胱和肠道功能障碍。女性终生接受 POP 手术的风险为 19%。由于 POP 的生物学机制尚不确定，预防策略尚未确定。除了衰老之外，唯一已知的 POP 危险因素是阴道分娩。具体来说，该团队之前的研究表明，阴道分娩与 POP 的几率增加 5 倍相关。然而，这种关联的机制仍然未知。本申请中提出的研究将调查产科提肛肌损伤 (LAMI) 是否通过提肛肌结构和/或功能的改变导致 POP。 LAMI 发生在 20% 的阴道分娩后，可以通过 3 维超声成像来检测。该提议的中心假设是，LAMI 通过两种不同的机制导致 POP：提肌裂孔的慢性扩大（结构变化）和提肌复合体无力（功能变化）。该提案的具体目标是：(1) 比较 3D 超声确定的患有和不患有 LAMI 的女性之间的提肛肌结构和功能； (2)确定LAMI、提肛肌结构和功能对POP的相对贡献。为了实现这些目标，该团队已建立的纵向队列研究 (R01HD056275) 中的 460 名阴道分娩妇女将在分娩后 5-15 年进行评估。评估将包括盆腔器官支撑的定量评估、提肌群的 3D 成像以及提肌力量的客观测量。 3D 超声是一种令人兴奋的工具，它提供提上睑肌的动态、实时视图，使我们能够检测 LAMI 并区分患有和不患有 LAMI 的人之间的结构和功能差异。因此，拟议的研究不仅会考虑 LAMI 在 POP 发展中的作用，还会考虑 LAMI 的长期后遗症（例如提肌裂孔的慢性变化）。 LAMI 已成为一种重要的产科并发症，目前除选择性剖腹产外无法预防。这项研究意义重大，因为在阐明病理生理学并确定 POP 风险标记之前，不可能预防 POP。本申请中提出的研究预计将提供识别 POP 风险最大的女性的标记，并将作为制定有效预防策略的平台。鉴于 POP 的高发病率，预防对于减轻公共卫生负担至关重要。