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.

Public Health Relevance

Vaginal childbirth substantially increases the risk of uterine and vaginal prolapse, conditions that cause chronic discomfort, contribute to bowel and bladder dysfunction, and necessitate reconstructive surgery for 19% of adult women. The research proposed in this application will distinguish how obstetrical injury to the pelvic muscles leads to uterine and vaginal prolapse. This research is intended to identify strategies that protect women from long term consequences of vaginal delivery and is therefore relevant to one of the core missions of the NICHD: to insure that women do not suffer harmful effects from reproductive processes.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD082070-03
Application #
9204314
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Tingen, Candace M
Project Start
2015-01-12
Project End
2017-12-31
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
3
Fiscal Year
2017
Total Cost
$305,609
Indirect Cost
$114,817
Name
Johns Hopkins University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Handa, Victoria L; Blomquist, Joan L; Roem, Jennifer et al. (2018) Longitudinal study of quantitative changes in pelvic organ support among parous women. Am J Obstet Gynecol 218:320.e1-320.e7
Handa, Victoria L; Blomquist, Joan L; Roem, Jennifer et al. (2018) Levator Morphology and Strength After Obstetric Avulsion of the Levator Ani Muscle. Female Pelvic Med Reconstr Surg :
Blomquist, Joan L; Muñoz, Alvaro; Carroll, Megan et al. (2018) Association of Delivery Mode With Pelvic Floor Disorders After Childbirth. JAMA 320:2438-2447
Hallock, Jennifer L; Handa, Victoria L (2016) The Epidemiology of Pelvic Floor Disorders and Childbirth: An Update. Obstet Gynecol Clin North Am 43:1-13
Memon, Hafsa U; Blomquist, Joan L; Dietz, Hans P et al. (2015) Comparison of levator ani muscle avulsion injury after forceps-assisted and vacuum-assisted vaginal childbirth. Obstet Gynecol 125:1080-7