Objective
To update a previously published systematic review and perform a meta-analysis on the risk factors for primary pelvic organ prolapse and prolapse recurrence.
Data Sources
PubMed and Embase were systematically searched. We searched from July 1, 2014 until July 5, 2021. The previous search was from inception until August 4, 2014.
Study Eligibility Criteria
Randomized controlled trials and cross-sectional and cohort studies conducted in the Western developed countries that reported on multivariable analysis of risk factors for primary prolapse or prolapse recurrence were included. The definition of prolapse was based on anatomic references, and prolapse recurrence was defined as anatomic recurrence after native tissue repair. Studies on prolapse recurrence with a median follow-up of ≥1 year after surgery were included.
Methods
Quality assessment was performed with the Newcastle-Ottawa Scale. Data from the previous review and this review were combined into forest plots, and meta-analyses were performed where possible. If the data could not be pooled, “confirmed risk factors” were identified if ≥2 studies reported a significant association in multivariable analysis.
Results
After screening, 14 additional studies were selected—8 on the risk factors for primary prolapse and 6 on prolapse recurrence. Combined with the results from the previous review, 27 studies met the inclusion criteria, representing the data of 47,429 women. Not all studies could be pooled because of heterogeneity. Meta-analyses showed that birthweight (n=3, odds ratio, 1.04; 95% confidence interval, 1.02–1.06), age (n=3, odds ratio, 1.34; 95% confidence interval, 1.23–1.47), body mass index (n=2, odds ratio, 1.75; 95% confidence interval, 1.17–2.62), and levator defect (n=2, odds ratio, 3.99; 95% confidence interval, 2.57–6.18) are statistically significant risk factors, and cesarean delivery (n=2, pooled odds ratio, 0.08; 95% confidence interval, 0.03–0.20) and smoking (n=3, odds ratio, 0.59; 95% confidence interval, 0.46–0.75) are protective factors for primary prolapse. Parity, vaginal delivery, and levator hiatal area are identified as “confirmed risk factors.” For prolapse recurrence, preoperative prolapse stage (n=5, odds ratio, 2.68; 95% confidence interval, 1.93–3.73) and age (n=2, odds ratio, 3.48; 95% confidence interval, 1.99–6.08) are statistically significant risk factors.
Conclusion
Vaginal delivery, parity, birthweight, age, body mass index, levator defect, and levator hiatal area are risk factors, and cesarean delivery and smoking are protective factors for primary prolapse. Preoperative prolapse stage and younger age are risk factors for prolapse recurrence after native tissue surgery.
Why was this study conducted?
This study aimed to perform an update of a systematic review and perform a meta-analysis on the risk factors for primary pelvic organ prolapse (POP) and POP recurrence after native tissue surgery.
Key findings
The risk factors for primary POP are vaginal delivery, parity, birthweight, older age, body mass index, levator defect, and a larger levator hiatal area. Cesarean delivery and smoking are protective factors against primary POP. The risk factors for POP recurrence are younger age and preoperative prolapse stage 3 or 4.
What does this add to what is known?
This systematic review and meta-analysis provides a comprehensive overview on all types of risk factors and illustrates the results in forest plots.
Introduction
Pelvic organ prolapse (POP) is a common medical condition worldwide impairing many women in their daily life. Although POP is not a life-threatening disease, it has a significant impact on the quality of life. Studies show that women have a lifetime risk of 12.6% to undergo surgical correction for POP by the age of 80 years. This number indicates not only the burden of POP on society and healthcare systems but also its financial impact on healthcare. With increasing life-expectancy in general, it is estimated that the number of care- seeking women and surgeries will increase tremendously in the coming 20–40 years. These high rates for POP surgery demand a focus on preventive strategies.
The key to finding the right prevention strategies is knowledge about etiology and risk factors. With an eye on the emerging preventive medicine, several studies investigating the risk factors for POP development and POP recurrence after surgery have been carried out. This knowledge about risk factors not only contributes to developing prevention strategies but also helps in the counseling of patients preoperatively and managing expectations. The systematic review by Vergeldt et al identified parity, vaginal delivery, age, and body mass index (BMI) as confirmed risk factors for the development of POP and preoperative stage 3 and 4 as confirmed risk factors for POP recurrence after native tissue repair (on the basis of definition in ≥2 studies with significant association in multivariable analysis). In the years after this publication, multiple studies have been published on this subject. Among others, the meta-analysis of Cattani et al identified forceps delivery and first vaginal birth as risk factors for anatomic and symptomatic primary POP. For POP recurrence, the meta-analysis of Friedman et al showed that levator defect, preoperative prolapse stage 3 or 4, family history of prolapse, and levator hiatal area are significant risk factors for POP recurrence. In this paper, we will update the review of Vergeldt et al and perform a meta-analysis not only on the risk factors for primary POP but also on POP recurrence for women in the Western developed countries.
Methods
This systematic review and meta-analysis was conducted in accordance with a prospectively registered protocol (International Prospective Register of Systematic Reviews [PROSPERO]; PROSPERO number CRD42021230813, March 26, 2021), the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. ,
Information sources and search strategy
A database search was performed by the primary reviewer (S.F.S.) and a librarian in PubMed and Embase using the search terms “pelvic organ prolapse” AND “recurrence” and “pelvic organ prolapse” AND “risk factors.” The search for the previous publication ended on August 4, 2014. Therefore, we searched from July 1, 2014 until July 5, 2021. The same search terms were used. No language restrictions were used. For the complete search, see appendix A .
Study selection and eligibility criteria
We used the same evaluation strategy as in the previous review. All the articles were evaluated by title and/or abstract by 2 independent reviewers (S.F.S. and M.C.). In case of disagreement, a third reviewer (K.B.K.) solved conflicts by consensus. Clinical studies reporting on the etiology or risk factors for primary POP or POP recurrence were included. A manual reference check of the included abstracts was performed. The included articles after abstract selection were screened on full text with a standardized in- and exclusion form. The authors were contacted to retrieve the article in case the full text was not available. Randomized controlled trials, cross-sectional and cohort studies conducted in the Western developed countries that reported on multivariable analysis with sufficient data (including odds, risk, or hazard ratio [HR] with 95% confidence intervals) of risk factors for POP or POP recurrence were included.
The definition of POP or POP recurrence had to be based on anatomic references or POP-Quantification (POP-Q) ≥ stage 2. For POP recurrence, only studies that reported on recurrence after native tissue repair with a median follow-up of at least 1 year were included. In case studies used the same population in multiple publications, only the most recent publication was included.
Data extraction
Data extraction was conducted by 2 reviewers (S.F.S. and M.C.) using a predefined data extraction form with data on study design, sample size, study population, definition of outcome, investigated risk factors, and results of the multivariable analysis. The corresponding authors were contacted in case additional information was needed on the study results. To provide a comprehensive overview, the results of the previous review were used again in this paper. The template data collection forms and data extracted from included studies are available on request.
Assessment of risk of bias
A quality assessment was performed by 2 independent reviewers (S.F.S. and M.C.) on the final included articles using the Newcastle-Ottawa Scale (NOS) for cross-sectional and cohort studies comprising of the following: participant selection, comparability of study groups, and assessment of outcome or exposure.
Data synthesis
In case a risk factor was studied in at least 2 studies using the same type of outcome and adjusted for at least the following confounders: parity, delivery mode, age, and BMI for primary POP and preoperative POP-Q stage for POP recurrence, we pooled the adjusted results with a random-effects meta-analysis using the inverse variance method on the log-transformed ratios and corresponding standard errors and presented the 95% confidence intervals of the back-transformed ratios. If necessary and possible, data conversion was applied (eg, conversion of per 1 year to per 10 years). In the case of a similar outcome but on the basis of different sets of adjustment variables, the results were only pooled in case of sufficiently low between-study heterogeneity (I 2 <50%). Variation across studies (heterogeneity) was estimated with a restricted maximum likelihood estimator for τ 2 . If studies could be pooled, an extra line in the forest plot below the studies was added to present the pooled result of the meta-analysis in bold. If the effects of a risk factor were presented in different measures, eg, odds ratio (OR) and HR, these were not pooled but were presented graphically in forest plots separated by effect measure. In addition to the risk factors identified by meta-analyses, we identified “confirmed risk factors” also. A confirmed risk factor was defined as a statistically significant association on the basis of multivariable data analysis that was reported in at least 2 studies that could not be pooled because of heterogenic outcome definitions or effect measures, without other studies reporting contradicting results. This definition was based on the definition used in the previous publication. No subgroup or sensitivity analyses were performed because of the small number of studies per potential risk factor and the large heterogeneity in risk factors. Publication bias was not evaluated, as the meta-analyses were based on 5 studies each at the most. All analyses were performed with the statistical software R version 3.6.3, packages meta version 2.4-0, and forest plot version 1.10.1. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to interpret the certainty in the body of the evidence. , As publication biases were not evaluated because of the small number of available studies per risk factor, the certainty of evidence was not downgraded for this domain.
Results
Study selection
A total of 5284 articles were retrieved by our search update. After the removal of duplicates, 3381 articles were screened by title and/or abstract. The full texts of 112 articles were evaluated using the in- and exclusion form. No extra articles were included after cross checking reference lists. After final selection, an additional 14 articles met our inclusion criteria, of which 8 articles were on the risk factors for primary POP and 6 articles were on the risk factors for POP recurrence. One article was excluded in the previous review and now included because of exclusion of an older study with the same population. Three articles that were included in the previous review were now partly or totally , excluded, because they used the same study population in a more recent publication or the country of investigation was not a Western developed one. Three studies appeared to meet the inclusion criteria but were excluded, because no separate analysis was performed for anatomic POP recurrence. In total (with the included articles of the previous publication), we included 16 articles on primary POP and 11 articles on POP recurrence. Figure 1 shows the flow diagram of the selection process. Because of high heterogeneity or differences in definitions and effect measures, not all studies could be pooled. Forest plots were made to visualize the results and to be able to recognize trends; see Figures 2–8 . The results of the studies that could not be included in the forest plots are listed in the tables; see appendix B .
Study characteristics
Studies on primary pelvic organ prolapse
The characteristics of the studies concerning the risk factors for primary POP are summarized in Table 1 . In total, data on 43,333 women were analyzed in 8 prospective cohort studies and 8 cross-sectional studies. POP was defined as POP-Q stage 2 or higher in 7 studies, POP beyond the hymen in 5 studies, degree 2 or 3 in the Baden-Walker classification in 1 study, the most descended point of the vaginal wall to the introitus or outside of the vagina (according to the Women’s Health Initiative classification system) in 1 study, the most dependent point of the vaginal wall or the cervix to or beyond the hymen and the most descended point of the vaginal wall −0.5 cm above the hymenal remnants in 1 study. See appendix table B.1 for the obstetrical risk factors for primary POP and appendix table B.2 for the nonobstetrical risk factors for primary POP.
| Reference | Study type | N/n | Inclusion criteria | Investigated risk factors | Adjustment variables |
|---|---|---|---|---|---|
| Progetto Menopausa Italia Study Group, 2000 Italy | Cross-sectional study | 21,449 /410 | Nonhysterectomized women around menopause attending an outpatient menopause clinic for general counseling about menopause | Age, BMI, smoking, education, delivery mode, parity, birthweight, age at menarche, age at menopause | Age, BMI, education, parity |
| Nygaard et al, 2004 United States | Cross-sectional study | 270/173 | Nonhysterectomized women enrolled in the WHI Hormone Replacement Therapy clinical randomized trial | Age, BMI, delivery mode, waist circumference, smoking, physical activity, education, occupation, birthweight, age at first and last delivery, hormone replacement therapy, family history, pulmonary disease, previous hernia surgery | BMI, waist circumference, education, parity, delivery mode, birthweight, at first and last delivery |
| Swift et al, 2005 United States | Cross-sectional study | 1004/218 | Women older than 18 y of age presenting for routine gynecologic healthcare | Age, BMI, smoking, ethnicity, occupation, income, parity, delivery mode, birthweight, gravidity, menopausal status, hormone replacement therapy, hysterectomy status, chronic illness, and constipation | Age, BMI, smoking, ethnicity, occupation, income, parity, delivery mode, birthweight, gravidity, hormone replacement therapy, hysterectomy status, and constipation |
| Slieker-Ten Hove et al, 2009 The Netherlands | Cross-sectional study | 649/227 | A general population of women aged 45–85 y | Age, BMI, smoking, physical activity, education, parity, menopausal status, family history, UI, prolapse during pregnancy | Smoking, physical activity, education, parity, menopausal status, family history, UI, prolapse during pregnancy |
| Whitcomb et al, 2009 United States | Cross-sectional study | 1137/762 | Women between 40 and 69 y of age who since age 18 y had been members of the Kaiser Permanente Medical Care Program of Northern California | Age, BMI, ethnicity, education, parity, and diabetes | Age, BMI, ethnicity, education, parity, and diabetes |
| Kudish et al, 2011 United States | Prospective cohort study | 12,650 /2266 | Nonhysterectomized, postmenopausal women enrolled in the WHI Estrogen plus Progestin Clinical Trial | Age, BMI, waist circumference, smoking, physical activity, ethnicity, parity, hormone replacement therapy, UI, pulmonary disease, and constipation | Age, BMI, waist circumference, smoking, physical activity, ethnicity, parity, hormone replacement therapy, UI, pulmonary disease, and constipation |
| Dietz et al, 2012 Australia | Cross-sectional study | 605/NA a | Women without previous incontinence or prolapse surgery with symptoms of pelvic floor dysfunction with data of 4-dimensional ultrasound | Levator defect, hiatal area on Valsalva | Levator defect, hiatal area on Valsalva |
| Handa et al, 2012 United States | Prospective cohort study | 449/64 | Women 5–10 years after first vaginal or cesarean delivery | Forceps delivery, vacuum delivery, episiotomy, spontaneous laceration | Maternal age>35 y at first delivery, multiparity, operative delivery |
| Glazener et al, 2013 United Kingdom/ New Zealand | Prospective cohort study | 762 / 182 | Women who delivered over a 12-mo period in 3 maternity units | Age at first delivery, BMI, parity, delivery mode | Age at first delivery, BMI, parity, delivery mode |
| VollØyhaug et al, 2015 Norway | Cross-sectional study | 608/280 | Women 16–24 y after first delivery who delivered between 1990 and 1997 through forceps, vacuum, cesarean delivery, or normal vaginal delivery | Delivery mode | Age, BMI, parity, delivery mode, and birthweight |
| VollØyhaug et al, 2016 Norway | Cross-sectional study | 608/275 | Women 16–24 y after first delivery who delivered between 1990 and 1997. | Age, BMI, parity, birthweight, hysterectomy status, levator defect, and levator hiatal area | Age, BMI, parity, birthweight, hysterectomy status, levator defect, and levator hiatal area |
| Blomquist et al, 2018 United States | Prospective cohort study | 1492/153 | Women 5–10 years after first vaginal or cesarean delivery | Age at first delivery, BMI, ethnicity, parity, delivery mode, genital hiatus | Age at first delivery, BMI, ethnicity, parity, delivery mode, genital hiatus |
| Handa et al, 2019 United States | Prospective cohort study | 453/116 | Women 5–10 years after first delivery with at least 1 vaginal delivery | Levator defect | Age, ethnicity, birthweight, forceps, prolonged second stage of labor |
| Lovejoy et al, 2019 United States | Prospective cohort study | 705/ 143 | Women 5–10 y after first delivery | Breastfeeding | BMI, ethnicity, education, parity, and imbalances between exposure groups |
| Urbankova et al, 2019 Czech republic | Prospective cohort study | 987/562 | Healthy women in their first pregnancy, singleton, and delivered vaginally at or beyond 37 wk | Age, fetal weight, length of first and second stage of labor, analgesia type | Age and duration first stage of labor |
| Nygaard et al, 2021 United States | Prospective cohort study | 562/53 | Women who were 18 y, English- or Spanish- speaking, nulliparous with a singleton gestation, 28 weeks’ gestation, planning vaginal delivery, not planning to move to a location precluding follow-up, and living within 60 miles of the research facility | Age, BMI, education, MVPA postpartum, high-risk delivery factor, breastfeeding, pelvic support in third trimester, Chronic cough at 5–10 wk postpartum | Age, BMI, ethnicity, education, high risk delivery factor, pelvic support in third trimester, breastfeeding |
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