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

• 批准号: 9204314
• 负责人: VICTORIA Lynn HANDA
• 金额: $ 33.96万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-12 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9204314
• 关键词: 3-Dimensional; 3D ultrasound; Address; Adult; Aging; Area; Barbering; Biological; Birth; Bladder; Bladder Dysfunction; Case-Control Studies; Cesarean section; Childbirth; Chronic; Clinical; Complex; Complication; Data; Development; Discipline of obstetrics; Evaluation; Event; Female; Functional disorder; Goals; High Prevalence; Injury; Intestines; Lead; Life; Longitudinal cohort study; 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; epidemiology study; imaging study; levator ani muscle; lifetime risk; muscle strength; muscular structure; operation; pelvic organ prolapse; public health relevance; tool

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，其中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。女性一生中接受POP手术的风险为19%。由于持久性有机污染物的生物机制尚不确定，因此尚未确定预防战略。除了衰老，唯一已知的POP风险因素是阴道分娩。具体来说，该研究小组先前的研究表明，阴道分娩与POP的几率增加5倍有关。然而，这种联系的机制仍然未知。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，可以通过三维超声成像检测到。该建议的中心假设是LAMI通过两个独立的机制导致POP：提肛肌裂孔的慢性增宽（结构变化）和提肛肌复合体的无力（功能变化）。该建议的具体目的是：（1）通过三维超声检查，比较有无LAMI的女性肛提肌的结构和功能;（2）确定LAMI、提肛肌结构和功能对POP的相对贡献。将对来自该团队已建立的纵向队列研究（R 01 HD 056275）的460名阴道分娩妇女在分娩后5-15年进行评价。评估将包括定量评估盆腔器官的支持，三维成像的提肌复合体，和客观措施的提肌力量。三维超声是一种令人兴奋的工具，它提供了动态的、真实的时间视图，使我们能够检测LAMI，并区分有无LAMI的患者之间的结构和功能差异。因此，拟议的研究不仅要考虑LAMI在POP发展中的作用，还要考虑LAMI的长期后遗症（如提肌裂孔的慢性变化）。LAMI已成为一种重要的产科并发症，目前无法预防，除非通过选择性剖宫产。这项研究将具有重要意义，因为只有在阐明其病理生理学和确定持久性有机污染物风险的标志物之后，才有可能预防持久性有机污染物。本申请中提议的研究预计将提供标志物，以确定最有可能感染持久性有机污染物的妇女，并将作为制定有效预防战略的平台。鉴于持久性有机污染物的高流行率，预防对于减轻公共卫生负担至关重要。