Laura Scheufele, PT, DPT, WCS
November 9, 2016
Aim: Assess the strength, consistency and potential for bias in pooled associations from prior studies of the relationship between joint hypermobility (JHM) and pelvic organ prolapse (POP).
Study Design: Systematic review.
Materials and Methods:
Inclusion Criteria: Case-control and cross-sectional designs, with either population based samples and other sampling methods. Ethical approval not required.
Search of Pubmed, EMBASE, and CINAHL electronic databases through July 1, 2015. Keywords of joint hypermobility OR joint laxity OR connective tissue OR Ehlers-Danlos OR heritable disorder of connective tissue (HDCT) OR Marfan AND prolapse OR pelvic organ prolapse OR genitourinary prolapse OR urogenital prolapse NOT mitral.
Hand search of ICS and IUGA conference proceeding and lateral search techniques.
Two reviewers confirmed eligibility, and uncertainties resolved by consensus or discussion with third reviewer.
Data extracted: type of study design, patient characteristics, number of participants, country of origin, assessment tools for JHM and POP and statistical analyses used, outcomes relating to JHM or POP and estimation of association between JHM and POP.
Unadjusted and adjusted effect estimates recorded if odds ratio (OR) with 95% confidence intervals (CI). Unadjusted effect estimates recalculated when possible.
Used a five-question instrument provided by the Grading of Recommendations Assessment (GRADE) Working Group used to assess potential bias. Two authors independently assessed trial quality using these forms.
Meta-analysis performed using random-effects model and the metan command, and metaregression conducted using metareg command for Stata 12.0.
Heterogeneity of exposure effects analyzed using chi-square test.
Study selection: Of 269 articles screened, 18 eligible studies for the systematic review and of those 14 could be used for meta-analysis. Nine case controlled studies, six cross-sectional design and three were cohort studies. See Figure 1.
Median sample size was 136 (range 46-5648), mean age of cases when stated ranged from 32.5 to 70.1 and for controls 35.4 to 69.8.
POP assessment tools: Pelvic Organ Prolapse Questionnaire (POP-Q) n=9, Baden-Walker halfway scoring system n=3 and 2 with non-validated tools.
JHM assessed primarily with the Beighton criteria n=11, the Carter-Wilkinson score n=3, (a precursor to the Beighton criteria) self-assessing Hakim questionnaire n=3, and 3 based on non-validated assessment tools of JHM.
See Table 1 for a detailed listing of the included articles ad the characteristics in the systematic review.
Meta-analysis of 14 eligible studies resulted in an overall pooled OR of 2.37 (95% CI 1.54-3.64, I2=77% (high degree of heterogeneity) . See Figure 2 for Forest Plot.
The solid vertical line indicates point of no effect.
4 studies who mean touches the vertical line or is to the left , therefore do not support an association of joint hypermobility and POP.
I-squared value of 77% indicates a high degree of heterogeneity of the studies. This high rate is not desirable.
The high heterogeneity was explored using a meta regression of mean sample age, study date ad risk of bias as predictors. Overall meta-regression model performance was poor, with no evidence of association in effect size and year of publication (p=0.53), mean age of sample (p=0.30) or study risk of bias (p=0.49). There was no evidence of publication bias with visual inspection of funnel plot (See Figure 3) or formal regression.
Table 2 demonstrates results from bias GRADE assessment, demonstrating all studies at high risk for bias for at least one criterion.
Knuuti et al. confirmed an inherent abnormality in collagen metabolism in certain individuals affected by both JHM and POP and that women with clinical joint hypermobility had more recurrent prolapse.
Four studies reported a negative association between POP and JHM.
Hafizi et al. found no significant difference in mean Beighton scores between POP group and control groups.
Knoepp et al. concluded hypermobility did not increase relative odds for any pelvic floor disorder considered.
McIntosh et al. showed no association between JHM and POP in logistic regression models within an EDS population of continent vs. incontinent women, however the study was limited by self selection in the symptomatic group.
Main findings: Findings confirm an association between clinically significant POP and JHM. A strong pooled association with a clinically highly relevant effect size noted .
Conclusion: Evidence from eligible studies support that JHM is an indicator for POP.
Suggest JHM scoring could be used with other known risk factors to target at risk women for primary prevention. As JHM usually manifests early in childhood young adulthood, this could possibly be an early indicator of increased risk of POP during mid life.
Longitudinal studies needed to demonstrate prognostic significance of JHM on prolapse development and to determine impact on treatment outcome.
Thorough and systematic search without language restriction. As the studies were from many countries, data from wide range of populations with different social and ethnic characteristics.
Aims of selected studies differed widely. Often other primary parameters being assessed and the POP and/or JHM treated as secondary findings.
Findings are limited by the high heterogeneity between the studies that was not fully explained by methodological differences.
Primary studies are at high risk for both Berkson bias and spectrum bias.
Causal conclusions limited by study designs and inability in most studies to control for potential cofounding factors such as BMI, menopausal status and estrogen use. Some medical information obtained from questionnaires that could lead to underreporting of POP possibly because of stigma.
Summary of Beighton score: http://www.physio-pedia.com/Beighton_score