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.
Data Collection:
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.
Statistical Analysis:
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.
Results:
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.
Ÿ The solid
vertical line indicates point of no effect.
Ÿ 4 studies who
mean touches the vertical line or is to the left , therefore do not
support an association of joint
hypermobility and POP.
Ÿ 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.
Ÿ Hafizi et al. found no significant
difference in mean Beighton scores between POP group and control groups.
Ÿ Knoepp et al. concluded hypermobility
did not increase relative odds for any pelvic floor disorder considered.
Ÿ 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.
Discussion:
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.
Strengths:
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.
Weaknesses:
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.
Additional Reading:
Summary of Beighton score:
http://www.physio-pedia.com/Beighton_score
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