Cervical Stitch (Cerclage) For Preventing Pregnancy Loss: Individual Patient Data Meta-Analysis

DOI: 10.1111/j.1471-0528.2007.01515.
Systematic review
www.blackwellpublishing.com/bjog
Cervical stitch (cerclage) for preventing pregnancy

loss: individual patient data meta-analysis
AL Jorgensen,a Z Alfirevic,b C Tudur Smith,a PR Williamsona; on behalf of the cerclage IPD
Meta-analysis Group
a Centre for Medical Statistics and Health Evaluation, University of Liverpool, Liverpool, UK b Department of Obstetrics and Gynaecology,
University of Liverpool, Liverpool Womens Hospital, Liverpool, UK
Correspondence: Mrs AL Jorgensen, Centre for Medical Statistics and Health Evaluation, University of Liverpool, Shelleys Cottage,
Brownlow Street, Liverpool L69 3GS, UK. Email [email protected]
Accepted 6 August 2007. Published OnlineEarly 28 September 2007.
Background Several observational studies have claimed high
Main results The meta-analysis included seven trials and 2091
success rates for cerclage in women with cervical insufficiency. A

recent Cochrane review found no conclusive evidence of benefit,
although significant heterogeneity was present for some of the
important clinical outcomes.
randomised women. In singleton pregnancies, the reduction in

pregnancy loss or death before discharge from hospital following
cerclage failed to reach statistical significance (OR 0.81; 95% CI
0.601.10). Cerclage was found to have a detrimental effect on the
outcome of pregnancy loss or death before discharge from hospital
in multiple gestations (OR 5.88; 95% CI 1.1430.19), although
only a small number of multiple pregnancies were included in the
analysis. Neither indication for cerclage nor obstetric history was
found to have a statistically significant impact on the effect
of cerclage.
Objectives We undertook an individual patient data (IPD) meta-
analysis to examine effect of cerclage on neonatal and maternal

outcomes. In an attempt to explain the heterogeneity, we
investigated whether obstetric factors including multiple gestation
are associated with effectiveness.
Search strategy Search methods described in the original
Cochrane review were adopted and updated to December 2005.

Selection criteria This IPD systematic review and meta-analysis
was of randomised trials comparing cervical cerclage during

pregnancy with expectant management or no cerclage in women
with confirmed or suspected as having cervical insufficiency.
Analysis Multilevel logistic regression models stratified by trial
with random treatment effects were fitted to investigate the impact
of obstetric factors and multiple gestation on treatment effect.
Primary outcome measures were pregnancy loss or death before
discharge from hospital and absence of neonatal morbidity.
Conclusions Cerclage may reduce the risk of pregnancy loss or
neonatal death before discharge from hospital in singleton

pregnancies thought to be at risk of preterm birth, but further
large trials are needed to elucidate the risk-benefit ratio precisely.
Cerclage in multiple pregnancies should be avoided. The efficacy of
cerclage was not influenced by either indication for cerclage or
mothers obstetric history.
Keywords Cervical cerclage, cervical stitch, individual patient
data meta-analysis, neonatal death, neonatal morbidity, neonatal

mortality, preterm delivery, pregnancy loss, randomised
clinical trials.
Please cite this paper as: Jorgensen A, Alfirevic Z, Tudur Smith C, Williamson P; on behalf of the cerclage IPD Meta-analysis Group. Cervical stitch (cerclage) for
preventing pregnancy loss: individual patient data meta-analysis. BJOG 2007;114:14601476.
Introduction
Cervical cerclage is a surgical procedure involving suturing
the neck of the womb (cervix) with a purse type stitch to keep
the cervix closed during pregnancy. This has been used widely
in the management of pregnancies considered at high risk of
preterm birth.
Several observational studies in the past 50 years have
claimed high rates of successful pregnancy outcome in
1460
women with poor obstetric history attributed to cervical

insufficiency in whom cerclage was used. A recent Cochrane
review of randomised trials analysing outcomes including miscarriage, perinatal loss, maternal infection, maternal
morbidity, antepartum haemorrhage and preterm birth
found no conclusive evidence of such benefit.1 However,
significant statistical heterogeneity was present for some of
the important clinical outcomes. This heterogeneity was
attributed to the inconsistency in clinical definitions
2007 The Authors Journal compilation RCOG 2007 BJOG An International Journal of Obstetrics and Gynaecology
Cervical cerclage for preventing pregnancy loss
employed in the trials (e.g. varying cutoff points for defining

preterm birth) and in the different patient populations studied, however, neither meta-regression nor subgroup analyses
was undertaken.
Practically, methods of undertaking meta-analyses involve
collecting either aggregate data or data on each woman individually. The advantages of the latter approach, known as an
individual patient data (IPD) meta-analysis and described as
the yardstick,2 include the potential to ensure a more consistent definition of outcomes across trials, as well as a more
powerful analysis of whether treatment is more or less effective in particular subgroups.3 Although previous subgroup
analyses4 suggested that cerclage would be of benefit to the
subgroup of women with three or more second trimester
miscarriages or preterm births, the number of women contributing to each obstetric history subgroup, and hence the
power to detect treatment effect within each, was small.
An IPD meta-analysis investigating the effects of cervical
cerclage has previously been published.5 This analysis included
only women found to have short cervix on ultrasound and did
not investigate the effect of cerclage on neonatal morbidity.
The data were analysed as although obtained from a single
large trial recruiting from the same population, and an
assumption of homogeneity of treatment effect between trials
was made. Our work includes methods of random-effects
meta-regression and multilevel logistic regression models to
detect and allow for heterogeneity of effect. Widening our
inclusion criteria to include trials that recruited based on
obstetric history and using the aforementioned analysis techniques enabled us to not only examine the effect of cervical
cerclage in the general population of women at risk of preterm birth but also to investigate the impact that previous
obstetric history or cervical length may have on this effect.
Methods
We undertook an IPD meta-analysis to examine the effect
of cerclage on our prespecified neonatal and maternal
outcomes.6
Searching
The search methods described in the original Cochrane
review1 were adopted and updated to December 2005.
Selection and study characteristics

The types of studies considered for inclusion in the analysis
were randomised trials comparing cervical cerclage during
pregnancy (Shirodkar technique, McDonald technique, transabdominal and transvaginal methods), with expectant
management or no cerclage in women with confirmed or
suspected as having cervical insufficiency. Quasi-randomised
studies in which allocation was transparent (e.g. use of alternative allocation or medical record numbers) were excluded.
Data abstraction and validity assessment

Two reviewers independently assessed inclusion eligibility of
trials with any difference of opinion being resolved through
discussion. The methodological quality of each trial was
assessed in terms of method of generating randomisation
sequence, method of allocation concealment and potential
impact of losses to follow up. For each eligible trial, we requested
data on trial methods, treatment allocation, patient characteristics and outcome data. The data provided were cross-checked
against any published report of the trial, and where possible, the
chronological randomisation sequence was reviewed, as was the
balance of prognostic factors at baseline. Any queries were followed up with a nominated individual.
The primary outcomes were pregnancy loss or death before
discharge from hospital and absence of neonatal morbidity,
and secondary outcomes were preterm delivery (PTD) and
maternal morbidity. The impact of obstetric history and cervical length on the effect of cervical cerclage was also assessed.
We asked trialists to provide all outcome data collected and
not just those reported in publications to avoid bias due to
within-study selective reporting.7
Standardising pregnancy loss or death before

discharge from hospital outcome across trials
The primary outcome was pregnancy loss or neonatal death
before discharge from hospital. This outcome includes all miscarriages, stillbirths and neonatal deaths before discharge, and
the IPD available for each trial were standardised as summarised in Table 1. The use of a composite outcome appeared
justifiable here on the grounds that all events lead to the loss
of a baby, the prevention of which is the ultimate goal of using
cervical cerclage. The composite outcome was defined in accordance with ICH E9 guidelines since analysing the outcomes
separately would not be addressing the primary question of
interest.14 It was not possible to analyse the outcome pregnancy
loss or neonatal death at any time since most trials4,8,9,11,13
followed up to hospital discharge only. For trials where length
of follow up was unclear,10 we assumed that follow up was to
hospital discharge only. Furthermore, it was confirmed that
although follow up continued after hospital discharge, all
deaths in the trial of Rust et al.12 occurred before discharge.
In the trials of To et al.,13 Berghella et al.,9 MRC,4 Rust
et al.,12 Rush et al.11 and Althuisius et al.8 only viable pregnancies were included. This could not be directly confirmed
for the trial of Ezechi et al.,10 and so an assumption had to be
made that this was indeed the case.
Standardising neonatal morbidity outcome

across trials
Differing neonatal morbidity outcomes were recorded in the
trials, and so an alternative outcome of baby healthy when
discharged from hospital was chosen, representing the absence
1461
1462
Spontaneous
labour
Neonatal
morbidity
Neonatal
mortality
Berghella et al.9
Ezechi et al.10
MRC4
Intrauterine fetal
Neonatal deaths
Stillbirths only
Liveborn, viable;
deaths (IUFs)
were recorded. This
were recorded.
liveborn, dead
and neonatal
included miscarriages,
Apparent
and stillbirth/
deaths were
stillbirths
from published
abortion were
recorded. No
and deaths after
paper that
recorded. We
incidences of IUFs.
birth. We classified
total perinatal
classified
Neonatal mortality
as: miscarriages:
deaths equal
as: miscarriages:
therefore included
neonatal deaths at
to total
stillbirth/abortion
any neonatal deaths
,24 weeks 1 no NICU; stillbirths. We
at ,24 weeks;
stillbirths: neonatal
classified
stillbirths:
deaths at 24 weeks
as: miscarriages:
stillbirth/abortion
1 no NICU; neonatal
stillbirth at ,24
at 24 weeks;
deaths: neonatal
weeks; stillbirths: neonatal deaths:
death 1 NICU
stillbirth at 24
liveborn, dead
weeks; neonatal
deaths: none
IVH, RDS, NEC
Not available
Not recorded
Necrotising
enterocolitis,
and sepsis were
recorded. Trialists
RDS, IVH and
confirmed that if all
neonatal sepsis
these marked
were recorded.
negative, can
Trialists confirmed
assume baby was
not necessarily
healthy at discharge
case that baby
was healthy at
discharge if all
these pathologies
reported negative.
Hence, trial excluded
from analysis of
this outcome
Unclear if
Spontaneous
Not recorded
Data on indication
recorded
labour status
for delivery were
or not
was recorded
collected. All women
directly in trial
marked specifically as
spontaneous labour
were counted as having
spontaneous labour
Althuisius et al.8
Table 1. Standardising outcome measures across trials
Not recorded
Spontaneous
labour status
was recorded
directly in trial
(continued)
Type of labour
was recorded directly.
All women marked
as spontaneous
counted as having
spontaneous labour
IVH, positive
blood cultures,
retinopathy of
prematurity and BPD
were recorded.
Trialists confirmed
that if all these marked
negative, can assume
baby was healthy
at discharge
Perinatal morbidity
was recorded in
terms of
seriousness of
complications.
Baby counted as
healthy
at discharge if it
did not suffer
from any serious
complications of
prematurity
Any serious
complications of
prematurity
were recorded, and
so if none
was recorded,
can assume
baby was healthy
at discharge
To et al.13
Stillbirths and whether
baby was alive
at follow up recorded.
We classified as:
miscarriages: stillbirth
at ,24 weeks;
stillbirths: stillbirth at
24 weeks; neonatal
death: not a stillbirth
and not alive at
follow up
Rust et al.12
Miscarriages, stillbirths
Perinatal deaths
and neonatal deaths
were recorded.
all were recorded
Not possible
specifically with same
to classify into
classification as for this subcategories of
meta-analysis
miscarriages,
stillbirths and
neonatal deaths
but this composite
outcome was
sufficient for
our primary
outcome
Rush et al.11
Jorgensen et al.
Unclear if
recorded or not
Indication for delivery

and method of
delivery were
recorded; however,
no distinction was
made between
elective and
emergency
caesarean section.
Therefore,
trial excluded from
analysis of this
outcome
Method of
delivery was
recorded but
type of labour
not so trial
excluded from
analysis of this
outcome
Need for
induction
and/or need
for planned
caesarean
Temperature of
mother recorded.
If .38, we
classified as pyrexia.
Data does not match
published report
(one more in each
treatment group).
Analysis is based
on IPD data held
Not recorded
Rush et al.11
Not recorded
Rust et al.12
Whether mother
had fever or not was
recorded directly
To et al.13
Recorded only
Directly recorded
Not recorded
in cerclage group
as adverse event
from intervention.
As not recorded
in control group
also data excluded
from analysis
Recorded only
Recorded directly.
Recorded directly
Recorded directly
in cerclage group
The data does
not match published
as adverse event
from intervention.
report (one less in
cerclage group in
As not recorded
in control group
data than in published
also data excluded
report). Analysis is
from analysis
based on IPD held
Method of delivery
Indication for
Spontaneous labour Spontaneous labour,
delivery and method
was recorded but
induced labour,
and method of
type of labour not so of delivery were
emergency
delivery were
recorded; however,
trial excluded from
caesarean and
recorded. Women
no distinction was
analysis of this
elective caesarean
classed as not
made between elective
outcome
having spontaneous were recorded.
and emergency
Women having
labour or having
caesarean section.
either induced
spontaneous labour
Therefore, trial
labour, emergency
followed by
excluded from
caesarean or elective
emergency or
analysis of this
caesarean classified as
elective caesarean
outcome
yes for this analysis
classified as yes
for this analysis
Whether woman
had temperature
of .38 recorded
directly
MRC4
BPD, broncho pulmanary dysplasia; IVH, intraventricular haemorrhage; NEC, nectrotising enterocolitis; NICU, neonatal intensive care unit; RDS, respiratory distress syndrome.
Unclear if
recorded
or not
Recorded directly
Recorded
directly
Unclear if
recorded
or not
Unclear if
recorded
or not
PPROM
Not recorded
Ezechi et al.10
Not recorded
Not recorded
Berghella et al.9
Chorioamnionitis Recorded
directly
Pyrexia
Althuisius et al.8
Table 1. (Continued)
1463
Jorgensen et al.
of any detectable neonatal morbidity at discharge. Table 1

summarises the data recorded on this outcome in each trial,
and how these were classified for the purposes of this analysis.
The lead author for the trials of To et al.,13 Berghella et al.,9
Rust et al.12 and Rush et al.11 confirmed that if a baby had
suffered from any morbidity at all then this would have been
recorded. For the trial of Althuisius et al.,8 only neonatal diagnoses specifically requested were recorded if present. It does
not automatically follow that a baby with none of these specific
diagnoses was necessarily healthy at discharge; therefore, the
data from this trial were excluded. Neonatal morbidity data
were not collected in the trial of MRC,4 and confirmation
either way has not been obtained for the trial of Ezechi
et al.,10 hence these two trials have also been excluded.
As the outcome of interest was baby healthy when discharged from hospital, for the trials where it was certain or
there was a possibility that follow up continued after
discharge (Rust et al.),12 we made the assumption that any
neonatal morbidity recorded first occurred prior to discharge
from hospital.
The analysis was two-fold: first, a composite outcome was
analysed, the event of interest being defined as not suffering
from any of the following: miscarriage, stillbirth, neonatal
death before discharge from hospital or some pathology
recorded. As well as making sense clinically, this approach
ensured our analysis included all women randomised, thus
the balance achieved from randomisation was preserved. Second, an analysis was undertaken where all miscarriages, stillbirths and neonatal deaths prior to discharge were omitted.
Hence, in this second analysis, only babies still alive at discharge were included and so enabled conclusions to be drawn
relating to neonatal morbidity conditional on survival.
Standardisation of maternal morbidity and

other outcomes across trials
The maternal morbidity outcomes of pyrexia and chorioamnionitis were analysed. Preterm prelabour rupture of
membranes (PPROM), spontaneous labour and need for
induction or a planned caesarean were also examined. Table 1
summarises the data recorded on these outcomes.
Treatmentcovariate interactions
As mentioned above, one of the aims of our study was to investigate whether a womans obstetric history influenced the effect
of cervical cerclage. For this purpose, women were categorised
into one of the following mutually exclusive categories:
1 No previous PTD or second-trimester loss (STL) and no
previous cervical surgery.
2 One previous PTD or STL and no previous cervical surgery.
3 Two previous PTDs or STLs and no previous cervical surgery.
4 Three or more previous PTDs or STLs and no previous
cervical surgery.
5 Previous cervical surgery.
1464
These categories were chosen to reflect the subgroup analyses undertaken in the MRC trial4 since this trial had found
a significant treatment effect (P < 0.05) on the outcome of
PTD before 33 weeks of gestation in a subgroup of women
with no previous cervical surgery but with three or more
previous PTDs or STLs.
It was possible to undertake this categorisation in five4,8,1113
out of the seven included trials. For the trial of Ezechi et al.,10
cervical surgery history was not recorded and the numbers of
previous PTDs or STLs were not recorded separately in the
database available from the trial of Berghella et al.9 Hence,
these two trials were excluded from the analyses of interaction
between obstetric history and cerclage.
We were also interested in investigating whether a womans
cervical length influenced the effect of cerclage, and this was
possible again for five8,9,1113 of the seven included trials.
Statistical analysis
A study protocol6 and detailed statistical analysis plan (available on request from first author) were prepared in advance.
All analyses were conducted according to the analysis plan,
and the intention-to-treat principle was applied as far as
possible.
Clinical heterogeneity was assessed by reviewing differences
across trials in characteristics of randomised women. Statistical heterogeneity was assessed using forest plots, the I2 statistic and chi-square test as set out in the analysis plan. The I2
statistic estimates the proportion of total variability in effect
estimates that can be explained by heterogeneity. Pooled odds
ratios were calculated using Petos method.15 Since the trials
could be partitioned into two distinct groups with respect to
what the main indication was for intervention of cerclage
(either short cervix on ultrasound or obstetric history),
meta-regression incorporating a trial-level covariate representing main indication was also undertaken to investigate
whether this accounted for any observed heterogeneity.
To examine the impact that a womans obstetric history
and cervical length may have on the effect of cerclage, in
addition to accounting for some of the observed heterogeneity, regression models were built stratified by trial. These were
two-level logistic regression models16 as explained in greater
detail in the analysis plan, and the models were fitted using
version 2.02 of the MLwiN software package for multilevel
modelling. In summary, the models included a fixed-effects
indicator variable for each trial to account for any trialspecific characteristics. An indicator variable was also included
to represent treatment group; however, this was a randomeffects variable since it is assumed that treatment effect will be
similar, although not identical, across trials. Fixed-effect indicator variables to represent both treatmentobstetric history
and treatmentcervical length interaction effects were also
introduced to the models to examine the impact of these
two obstetric factors on treatment effect. To assess the effect
of a variable on outcome, models both with and without that

variable were compared using the likelihood ratio test.
Where IPD were not available, the reason was assessed for
the potential of bias. Results using aggregate data from these
trials were then compared with results using aggregate data
from trials where IPD had been supplied. The analysis plan
was reviewed in light of the availability of IPD but prior to any
comparative analyses.
Multiple pregnancies
Twin or triplet pregnancies have been excluded from the main
analyses because: (a) the prognosis for PTD and associated
health problems is considered to be different among twins/
triplets and (b) outcomes for such babies are not deemed to
be independent of one another. However, to investigate the
impact of multiple gestation on treatment effect for neonatal
outcomes, data on all babies (from singleton, twin and triplet
pregnancies) were used to fit three-level logistic regression
models. These models included treatment effect assumed to
be random at both the trial and the mothers level, a binary
covariate representing multiple gestation and also a treatmentmultiple gestation interaction term. Similar models
but these times limited to two levels with treatment assumed
random only at the trial level were also fitted to assess the
impact of multiple gestation on maternal outcomes. For each
outcome, a Wald test to assess the statistical significance of
including the interaction term was undertaken to assess
whether the effect of cerclage on outcome is indeed different
in multiple pregnancies.
Data for multiple gestation were available for 66 mothers
and 138 babies (Berghella et al.9: 4 twin pregnancies, MRC4:
28 twin pregnancies, Rust et al.12: 28 twin pregnancies and
6 triplet pregnancies).
Women entered into the trials more than once

It was apparent that women were entered more than once into
two trials (Rust et al.12: three women entered twice, MRC4:
exact number entered more than once unknown), and there
was a possibility that some women in the trial of Rush et al.11
were also entered more than once. No woman was entered
more than once into the trials of To et al.,13 Berghella et al.9
and Althuisius et al.,8 and we have not obtained confirmation
either way regarding the trial of Ezechi et al.10 Since it was not
always clear which women were entered more than once, we
have assumed that all pregnancies are independent regardless
of the fact that in some instances the same woman contributed with more than one pregnancy.
Results
some debate between reviewers regarding the eligibility of the

trial of Kassanos et al.17 However, since women randomised
to the no cerclage group in this trial were initially followed
up weekly with vaginal ultrasonograms with the possibility of
cerclage if a short cervix was found, it was decided that these
control women were not comparable with those in other
included trials, and the trial was excluded on this basis.
In total, nine trials were identified as being eligible for
inclusion, all published. Table 2 describes these trials and
summarises the results of assessing their methodological quality. For the trials where randomisation procedure was explicitly clarified,4,8,9,1113,19 the methods described were robust,
although for the majority of these trials we did not have
sufficient information to check that the methods had been
applied correctly. On inspecting key baseline characteristics
(Table 3), however, these appeared well balanced between the
two treatment groups for all trials. Due to the nature of the
intervention, it was not possible to blind patients or clinicians
to treatment for any of the trials.
Although the cerclage intervention varied with seven trials
using a McDonald type suture,812,18,19 one trial using a
Shirodkar type13 and one trial using a combination of more
than one type of suture4 undertaking a meta-analysis was
deemed appropriate. For two of the eligible trials, the authors
subsequently confirmed that IPD were no longer available,
and hence these trials have been excluded from our IPD
analyses (Lazar et al.,19 Dor et al.18).
Of the seven trials for which IPD were available, the main
indication for cerclage was the detection of short cervix on
ultrasound in four trials (Althuisius et al.,8 Berghella et al.,9
Rust et al.12 and To et al.13) and obstetric history in the
remaining three trials (Ezechi et al.,10 MRC4 and Rush
et al.11) For ease of interpretation, the forest plots have been
ordered such that the four trials where main indication was
ultrasound appear at the top, with the remaining three trials
appearing at the bottom.
Details of the eight excluded trials can be seen in the Quorum
diagram, Figure 1. A further three trials have been identified as continuing and therefore have not been included in
this analysis (Shennan A., pers. comm.; CIRCLE trial;26 Owen,
www.clinicaltrials.gov/;27 Silver, www.enh.org/).28
Baseline characteristics
A summary of baseline characteristics for the two treatment
groups in each trial can be seen in Table 3. Generally, most
characteristics were well balanced between the two intervention groups within trials, and any small imbalances observed,
as well as those between trials, were given consideration when
accounting for any observed statistical heterogeneity.
Description of studies
Replicating published results from IPD
The search identified 17 potential trials, and overall agreement between reviewers on eligibility was good. There was
The IPD analysis replicated the published data by Althuisius

et al.,8 Berghella et al.,9 MRC4 and To et al.13 For the trial of
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1466
Randomisation
procedure/allocation
concealment
Results of checking
randomisation
procedure
Not stated
Balanced blocks
generated by
randomisation
service. Allocation
by telephone or post
Ezechi et al.10
MRC4
Not possibledate
of randomisation/
randomisation
number not
provided
Not possible
to check
No
No
No
Not stated
No
No
Singleton pregnancies;
considered at high
risk of PTD because
cervical length
,25 mm before 27
weeks of gestation
Either at high
risk of PTD based
on previous obstetric
history and identified
during ultrasound
screening between 14
and 23 weeks 6 days
of gestation as having
funnelling or a short
cervix; or at low risk
but found incidentally
to have short cervix
One 1 previous PTD
Inclusion criteria
UK, France,
Obstetrician
Hungary, Norway,
uncertain whether
or not to use cervical
Italy, Belgium,
Zimbabwe, South
cerclage because of
Africa, Iceland,
previous: two or more
Ireland, Netherlands
second-trimester
and Canada
miscarriages/PTDs,
cervical surgery,
termination of
pregnancy or firsttrimester miscarriage;
or current cervical/
uterine abnormality; or
twin pregnancies
Nigeria
USA
The Netherlands
Blinding? Follow up after Location

hospital
of study
discharge?
Althuisius et al.8 Balanced blocks

Not possibledate
No
stratified for different
of randomisation/
inclusion criteria and
randomisation
two participating
number not
hospitals. Allocation
provided
by telephone
Berghella et al.9 Computer-generated
First block
No
balanced blocks.
imbalanced. Authors
Allocation by
confirmed an
sequentially
overlooked error
numbered opaque,
sealed envelopes
Study
Table 2. Characteristics of included studies
Preterm birth
,35 weeks
PTD ,34 weeks

of gestation;
neonatal survival;
neonatal morbidity
Primary
outcomes
(continued)
Suture vs
Length of
controlled
pregnancy; vital
management.
status of baby
More than one
following delivery
type of suture
was used
McDonalds type Gestational

suture vs no
age at
intervention
delivery; PTD
McDonald type
suture with
bedrest vs
bedrest alone
McDonald type
suture with
bedrest vs
bedrest alone
Intervention
Jorgensen et al.
Computer-generated
random allocation.
Allocation in
opaque, sealed
envelopes opened
by clinician
Computer-generated
random allocation.
Allocation in
opaque envelopes
opened at patients
bedside
Balanced blocks
stratified by centre.
Allocation by
telephone
Not stated
Randomisation
procedure not
stated. Allocation
by way of sealed
envelopes
Rust et al.12
To et al.13
Dor et al.18
Lazar et al.19
Randomisation
procedure/allocation
concealment
Rush et al.11
Study
Not possible
to check
Not possible
to check
Not possible
randomisation
number not
provided
Not possibledate
of randomisation/
randomisation
number not
provided
Not possibledate
of randomisation/
randomisation
number not
provided
Results of checking
randomisation
procedure
No
No
No
No
No
Not specified
Not specified
No
Yes in some
cases
Not stated
France
Israel
UK, Brazil,
South Africa,
Slovenia, Greece
and Chile
USA
South Africa
Blinding? Follow up after Location

hospital
of study
discharge?
Two, three
or four previous
pregnancies ended
spontaneously
before 37 weeks
as well as one or more
previous
pregnancy ended
spontaneously
between 14 and 36
weeks of gestation
Demonstrable
dilation of internal
os and either
prolapse of
membranes of
.25% total
cervical length or
distal cervical length
of ,2.5 cm between
16 and 24 weeks
of gestation
Singleton pregnancies;
cervical length of
15 mm or less
at between
22 weeks and
24 weeks 6 days
Conception after
induction of ovulation;
twin pregnancies
Score based
on obstetric history,
previous cervical surgery
history and other
cervical factors is within
a prespecified range
Inclusion criteria
McDonald type
suture vs no
suture
McDonald type
suture vs no
suture
Shirodkar suture
vs expectant
management
McDonald type
suture vs no
intervention
McDonald type
suture vs no
suture
Intervention
Obstetric
management;
duration of
pregnancy
Duration of
pregnancy
Delivery before
33 weeks
Gestational
age at delivery,
neonatal
morbidity
Gestational age
at delivery;
delivery before
37 weeks
Primary
outcomes
1467
1468
Fetal fibronectin:
yes
Bacterial vaginosis:
yes
Chlamydia: yes
Bishop score
.4: yes
Mean age at
randomisation
(SD)
Mean gestational
age at cerclage
procedure (SD)
Mean cervical
length (SD)
Mean BMI (SD)
Mean gestational
age at entry (SD)
Primigravida: yes
Previous
cerclage: yes
Previous cervical
surgery: yes
Funnelling: yes
Ethnic origin:
Non-Caucasian:
yes
Smoker: yes
Treatment
allocated
Compliant with
treatment
allocated: yes
Bedrest: yes
9 (56%)
10 (53%)
7 (23%)
12 (40%)
0 (0%)
Not stated
Not stated
Not stated Not stated

19.61 (2.40) 19.03 (2.2)
Not stated
Not stated
Not stated
Not stated
Not stated
N/A
Not stated
Not stated
19.90 (2.87) 19.56 (4.29) 15.69 (9.20) 16.67 (8.01)
N/A
0 (0%)
Not stated
Not stated
Not stated
N/A
Not stated
Not stated
14.63 (4.83)
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
227 (36%)
(21 missing)
134 (21%)
(1 missing)
193 (30%)
586 (92%)
635 (50%)
Cerclage
20.95 (2.93)
Not stated
12 (31%)
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
42 (52%)
No cerclage
27.69 (5.07)
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
39 (48%)
Cerclage
N/A
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
98 (100%)
0 (0%)
0 (0%)
3 (3%)
97 (99%)
98 (51%)
No cerclage
103 (50%)
No cerclage
1 (1%)
Not stated
20 (19%)
25 (26%)
(7 missing)
31 (30%)
Not stated
31 (30%)
25 (24%)
Not stated
20.67 (2.12)
N/A
28.03 (6.10) 28.88 (6.79)
1 (1%)
Not stated
19 (18%)
24 (25%)
(7 missing)
29 (28%)
Not stated
35 (34%)
16 (15%)
Not stated
104 (100%) 103 (100%)
104 (100%) 103 (100%)
104 (50%)
Cerclage
Rust et al.12
16.47 (3.71) 18.42 (2.92) 16.11 (7.72) 17.59 (6.24)
20.00.(1.41)
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
96 (100%)
0 (0%)
0 (0%)
9 (9%)
95 (99%)
96 (49%)
Cerclage
Rush et al.11
9.60 (3.46)
23.85
(0.71)
29.85
(6.06)
7 (6%)
(1 missing)
13 (10%)
(2 missing)
Not stated
Not stated
10 (8%)
121 (95%)
68 (54%)
7 (6%)
2 (2%)
0 (0%)
122 (96%)
127 (50%)
Cerclage
9.33 (3.57)
N/A
29.30 (5.90)
12 (10%)
(2 missing)
Not stated
Not stated
8 (6%)
17 (13%)
117 (93%)
78 (62%)
9 (7%)
2 (2%)
0 (0%)
124 (98%)
126 (50%)
No cerclage
To et al.13
Not stated
0 (0%)
0 (0%)
14 (13%)
13 (13%)
32 (25%)
(continued)
33 (26%)
Not stated
Not stated Not stated
Not stated
Not stated 26.45 (5.49) 25.96 (5.60)
14.89 (5.10) 17.56 (3.59) 14.87 (5.14) 20.67 (2.12) 21.15 (2.25) 23.52 (0.69) 23.49 (0.73)
Not stated
N/A
27.72 (4.98)
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
168 (27%)
(24 missing)
116 (19%)
(2 missing)
179 (28%)
581 (92%)
629 (50%)
No cerclage
MRC4
30.53 (4.57) 34.50 (4.93) 27.81 (6.4) 29.93 (6.85) 24.56 (4.81) 25.79 (4.81)
Not stated
Not stated
Not stated
Not stated
8 (28%)
Not stated
23 (79%)
2 (7%)
Not stated
29 (100%)
28 (93%)
29 (51%)
No cerclage
Ezechi et al.10
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
Not stated
9 (32%)
Not stated
25 (89%)
3 (11%)
Not stated
28 (100%)
27 (87%)
28 (49%)
Cerclage
Berghella et al.9
Not stated
10 (24%)
4 (25%)
0 (0%)
2 (11%)
6 (32%)
11 (69%)
8 (50%)
10 (53%)
9 (47%)
Not stated
2 (13%)
3 (16%)
Not stated
2 (13%)
4 (21%)
16 (100%)
14 (88%)
19 (100%)
19 (100%)
16 (46%)
No cerclage
19 (54%)
Cerclage
Althuisius et al.8
Table 3. Comparing baseline characteristics across trials
Jorgensen et al.
76 (61%)
69 (54%)
Not stated
32 (33%)
40 (42%)
258 (41%)
(2 missing)
277 (44%)
(1 missing)
42 (100%)
39 (100%)
16 (55%)
Not stated
Not stated
19 (68%)
Not stated
61 (48%)
(2 missing)
54 (43%)
42 (41%)
61 (62%)
47 (49%)
Not stated
Not stated
20 (69%)
5 (31%)
4 (21%)
20 (71%)
40(38%)
Not stated
Not stated
19 (18%)
79 (81%)
78 (81%)
260 (41%)
(2 missing)
193 (31%)
(2 missing)
285 (45%)
(1 missing)
201 (32%)
(1 missing)
Not stated
Not stated
13 (45%)
Not stated
15 (54%)
33 (32%)
49 (39%)
57 (45%)
34 (33%)
37 (38%)
44 (46%)
Not stated
Not stated
Not stated
Not stated
Not stated
3 (19%)
8 (42%)
Previous delivery
at greater than 37
weeks: yes
Previous STL: yes
Not stated
Not stated
40 (38%)
No cerclage
No cerclage
No cerclage
Cerclage
No cerclage
Cerclage
No cerclage
No cerclage
Cerclage
Cerclage
Cerclage
Potentially eligible studies identified by

searches (duplicates removed) n = 17
Cerclage
Studies excluded since

comparison of cerclage
technique only (n =1)
(Caspi et al.22)
Studies retrieved (n =16)

comparison of cerclage vs
pessary (n = 1)
(Foster et al.23)
Studies retrieved (n = 15)

women already included in
another of the included trials
(n = 2) (Szeverenyi et al,24
Althuisius et al.20)

women not randomised
(n = 1) ) (Varma T.R., pers.
comm.)

control group
subsequently received
elective cerclage (n = 2) )
(Kassanos et al.17, Beigi
and Zarrinkoub25)

comparison of inpatient vs
outpatient cerclage (n =1)
(Blair et al.21)
Studies included in the review (n = 9)
Figure 1. Quorum diagram.
BMI, body mass index.
Previous early
spontaneous
loss: yes
Previous PTD: yes
No cerclage
Cerclage
Althuisius et al.8
Berghella et al.9
Ezechi et al.10
MRC4
Rush et al.11
Rust et al.12
To et al.13
Ezechi et al.,10 the numbers randomised to the cerclage and

no cerclage groups have been reported in the paper as 38 and
43, respectively, whereas in the IPD, the corresponding numbers in each group are 39 and 42 and the data have been
analysed as such. The IPD obtained for the trial of Rush
et al.11 were handwritten in pencil and, due to its age, sometimes difficult to read. It was, therefore, not possible to replicate published results for some of the variables. Data on
1469
Jorgensen et al.
Figure 2. Forest plot comparing cerclage with no cerclage for outcome of pregnancy loss of death before discharge from hospital.
such variables have been excluded from the analyses, with the
exception of maternal pyrexia and PPROM for which there
were very small discrepancies (Table 1). We did not attempt
to replicate the results for the trial of Rust et al.12 since the
most recent paper published included only a subset of the
women available for IPD.
Pregnancy loss or death before discharge

from hospital
Singleton pregnancies only
The trial-specific odds ratios, together with the pooled odds
ratio and corresponding 95% CI are displayed in Figure 2.
These figures suggest little heterogeneity in treatment effect
across trials. The result of the meta-regression, introducing
a covariate representing main indication for cerclage (obstetric history versus short cervical length) was not statistically
significant (P = 061).
Introducing interaction terms between treatment and
obstetric history in a two-level logistic regression model did
not have a significant effect. The same applies for a treatment
cervical length interaction term (Table 4).
Multiple gestations
Including a treatmentmultiple gestation interaction effect in
a three-level logistic regression model including data on all
babies gave a significant result (Table 4), suggesting that cerclage has a detrimental effect on the outcome for such babies.
Calculating risk scores (data not shown) for babies grouped
into four categories depending on both singleton/multiple
pregnancy status and cerclage/no cerclage status demonstrated that using cerclage in singleton pregnancies decreased
the risk of pregnancy loss or death before discharge from
1470
hospital but that using cerclage in multiple pregnancies

increased the risk substantially.
Absence of neonatal morbidity

ratios and corresponding 95% CI for the two analyses are
displayed in Figure 3. It should be noted, however, that three
trials, representing 66% of randomised women, were excluded from the analysis of this outcome. These figures suggested no heterogeneity in treatment effect across trials.
Introducing a covariate representing indication for cerclage
in a meta-regression did not have a statistically significant
effect (P value including all babies: 064; P value excluding
babies not alive at discharge: 044).
When fitting two-level logistic regression models, introducing a treatmentobstetric history term did not have a statistically significant effect (Table 4). The same applied for
a treatmentcervical length interaction (Table 4).
Multiple gestations
Including a treatmentmultiple gestation interaction effect in
a three-level logistic regression model gave a significant result
(Table 4) for the analysis including all babies and this suggests
that cerclage has a detrimental effect on this outcome for
such babies.
Calculating risk scores (data not shown) for babies grouped
into four categories depending on both singleton/multiple
pregnancy status and cerclage/no cerclage status demonstrated that using cerclage in singleton pregnancies increased
the likelihood of a baby being healthy at discharge but that
using cerclage in multiple pregnancies decreased the likelihood
Table 4. Results from undertaking logistic regressions

Outcome
Pregnancy loss
or death before
discharge from hospital
Baby healthy
at discharge from
hospital (all babies)
Baby healthy
at discharge from
hospital
(babies alive at discharge only)
Spontaneous labour
Pyrexia
Chorioamnionitis
PPROM
Need for induction/caesarean section
Treatmentobstetric
history interaction*
Treatmentcervical
length interaction**
Treatmentmultiple gestation interaction
P value
P value
OR (95% CI)
P value
0.92
0.78
588 (1143019)***
0.03***
0.69
0.71
012 (002089)***
0.04***
0.69
0.37
0.54 (0.070.48)***
0.56***
0.83
0.56
0.6
0.44
0.68
0.19
0.8
0.96
0.32
0.08
108 (022544)****
Insufficient data available
365 (0472817)****
157 (034728)****
0.74 (016342)****
0.92****
0.21****
0.56****
0.70****
*The P values here are those obtained from undertaking a likelihood ratio test comparing a logistic regression model including treatmentobstetric
history interaction terms to a model without the interaction terms.
**The P values here are those obtained from undertaking a likelihood ratio test comparing a logistic regression model including treatmentcervical
length interaction term to a model without the interaction term.
***The odds ratios here are those obtained from fitting a multilevel logistic regression model with trial as the first level, woman as the second
level and baby as the third level. The model includes indicator variables to represent both treatment group (random effect) and multiple gestation
status (fixed effect) and also a treatmentmultiple gestation interaction variable. The P values are those obtained from undertaking a likelihood
ratio test to compare a model with the interaction variable to one without.
****The odds ratios here are those obtained from fitting a multilevel logistic regression model with trial as the first level and woman as the
second level. The model includes indicator variables to represent both treatment group (random effect) and multiple gestation status (fixed effect)
and also a treatmentmultiple gestation interaction variable. The P values are those obtained from undertaking a likelihood ratio test to compare
a model with the interaction variable to one without.
substantially. However, the test for an interaction was nonsignificant (Table 4) when excluding babies not alive at discharge from the analysis.
Maternal morbidity
ratio and corresponding 95% CI for each outcome are displayed in Figure 4. These figures suggested that there was significant heterogeneity in treatment effect for the outcomes of
chorioamnionitis and PPROM. On inspecting the forest plots
for these outcomes, treatment effect in the trial of Althuisius
et al.8 is noticeably different to the other trials; however, there
is no immediately apparent reason for this difference.
In a meta-regression model, indication for cerclage did not
have a statistically significant effect for any of the outcomes
(P value 0.36 or greater for all outcomes).
Finally, introducing treatmentobstetric history terms to
a logistic regression model did not have a significant effect
on any of the outcomes (Table 4), with similar nonsignificant
results for a treatmentcervical length interaction (Table 4).
Multiple gestations
The results from including a treatmentmultiple gestation
interaction term in a two-level logistic regression model are
summarised in Table 4. There was insufficient data on multiple pregnancies for which the outcome of pyrexia had been
measured to undertake the test for this outcome.
Preterm birth
We were interested in investigating the effect of cervical
cerclage on the timing of preterm births. For cutoffs
between 16 and 37 weeks of gestation, pooled odds ratios
were calculated. An increased confidence level of 99% was
used to calculate the intervals for these multiple pooled
odds ratios (Figure 5). The effect estimates favoured no
cerclage for the earlier cutoff points and cerclage for the
later cutoffs, although the results do not reach statistical
significance.
Statistical significance of the impact of obstetric history and
cervical length on treatment effect for the outcome of preterm
births before all these cutoffs was also assessed by way of
logistic regression models. Neither of these two factors was
1471
Jorgensen et al.
Figure 3. Forest plots comparing cerclage with no cerclage for outcome of (A) baby healthy when discharged from hospital (all babies); (B) baby healthy
when discharged from hospital (excluding babies not alive at discharge).
found to be statistically significant at the 1% level for any of

the gestational age cutoffs investigated.
There was not enough data on women in multiple pregnancies delivering before each gestational age cutoff to investigate the effect of multiple gestation on treatment effect for
this outcome (results not shown).
Comment on studies for which IPD were

not obtained
Two studies were eligible for inclusion in this meta-analysis for
which the authors confirmed that IPD were no longer available
(Dor et al.18 and Lazar et al.19). The trial of Dor et al.18 included
women with twin pregnancies only and so these women would
not have formed part of our main analysis even if IPD had been
available. For the trial of Lazar et al.,19 the aggregate results for
the outcomes of induced labour or caesarean section, preterm delivery before 32 weeks of gestation, preterm delivery
before 36 weeks of gestation and preterm delivery before 37
weeks of gestation were all obtainable from the published
paper and therefore for these four outcomes a comparison
was made between pooled results both excluding and including
the aggregate results from this trial. The results were found to
be almost identical (results not shown).
1472
Discussion
There continues to be considerable controversy about the value
of cervical cerclage in the management of women considered to
be at high risk of PTD. Our IPD review included trials where
main indication for cerclage was based on obstetric history, as
well as trials where the main indication was short cervical
length detected by ultrasound. The availability of IPD enabled
us to standardise outcome definitions across trials, which led to
an increase in the number of women contributing to each
outcome, and hence more precise effect estimates.
Although the overall results suggest that, in singleton pregnancies, cervical cerclage may reduce the risk of pregnancy
loss or death before discharge from hospital (OR 0.81), this
result did not reach statistical significance at the 5% level. The
true effect on the outcome of pregnancy loss or death before
discharge from hospital could range from a reduction in odds
of up to 40% in favour of cervical cerclage to an increase in
10% against the intervention. We believe that this trend
towards treatment benefit warrants further study. The confidence intervals for the absence of neonatal morbidity were
much wider since only three trials collected sufficient information on this outcome.
Figure 4. Forest plots comparing cerclage with no cerclage for outcomes of maternal morbidity.
In terms of maternal morbidity, a statistically significant

increased risk of maternal pyrexia was observed in the cerclage group. It was decided following publication of the protocol,6 but prior to analysis, that onset of labour was also of
interest since we wished to test the hypothesis that cervical
cerclage could damage the cervix and prevent spontaneous
labour or indeed cause morbidity that would force induction
or caesarean section. There was no significant evidence that
the likelihood of induction or caesarean section was higher in
the cerclage group. The data were quite limited because there
have been some difficulties in classifying women in terms of
this outcome for many of the trials (Table 1).
It is important to note that, although the trials included in

the review contributed data from over 2000 women in total,
the outcomes and covariates of interest were not recorded for
all women.
A previously published meta-analysis5 suggested that the
intervention of cervical cerclage in women with twin pregnancies increased the risk of preterm birth before 35 weeks of
gestation, although the number of women for which data was
available was small. Our analysis suggested that cerclage has
a detrimental effect on the outcome of pregnancy loss or
death before discharge from hospital and our composite
outcome of a baby being healthy at discharge, for multiple
1473
Jorgensen et al.
Figure 4. Continued from previous page.
gestations. These results must be interpreted with caution

due to the relatively small number of women with a multiple
gestation for which data were available.
The focus in studies to date has been on investigating
whether cervical cerclage has the ability to prevent preterm
birth. However, increasing gestational age at delivery does not
necessarily mean an improvement in the babys outcome. For
example, a baby delivered at 35 weeks of gestation may not
necessarily fare better than a baby delivered a few weeks earlier
if spontaneous delivery was artificially delayed. Care should
always be taken to ensure that the gestational age of preterm
birth is not mistaken as a surrogate outcome for pregnancy
loss or death before discharge from hospital/neonatal morbidity. It is for this reason that we chose pregnancy loss or
death before discharge from hospital and neonatal morbidity
as our primary focus. However, the timing of PTD is important in its own right for the purpose of investigating other
hypotheses of interest relating to the use of cervical cerclage.
These hypotheses are as follows:
1 That cervical cerclage delays delivery only for a short period
of time.
2 That cervical cerclage is only effective in improving neonatal outcome where the risk of preterm birth is during
a specific time interval.
1474
We undertook an exploratory analysis to investigate

whether the effect of cerclage varied according to gestational
age. On inspecting the point estimates for effect, there was
a suggestion of a change from favouring no cerclage to
favouring cerclage at around the 21-week cutoff point,
although the results did not reach statistical significance.
Due to the small number of events occurring at earlier gestations, the confidence intervals are very wide. The analysis
was limited further by the fact that some women were not
recruited until they had reached a gestational age greater than
some of the earlier cutoff points, which meant that they had
to be excluded from the analysis of those cutoffs. Excluding
such women meant that the balance achieved from randomisation was potentially disrupted. For these reasons, our
results must be treated with caution.
There is also a possibility that the stage of pregnancy at
which the cervical cerclage is administered may play a part in
how effective it will be. Indeed, the intervention may sometimes occur too late during the pregnancy to have any effect.
Gestational age of the cerclage procedure was recorded for
women in four trials.8,1113 We used these data to investigate
whether there was any association between gestational age
of the procedure and the outcome of pregnancy loss or
neonatal death before discharge from hospital by fitting
of using cervical cerclage to improve neonatal outcome.

Women should be advised of the increased risk of maternal
pyrexia and treated accordingly. Cerclage in multiple pregnancies should be avoided.
Implications for research

There is an urgent need for further large trials to elucidate the
risk-benefit ratio in singleton pregnancies with precision and
to identify groups most likely to benefit.
Conflicts of interest
Figure 5. Odds ratios of preterm delivery comparing cerclage with no

cerclage.
a two-level logistic regression. No significant association was

found (P = 0.26).
Neither obstetric history nor cervical length was found to
have a significant impact on the effect of cerclage on PTD.
Our five obstetric history categories were purposefully chosen
to reflect the subgroup analyses undertaken in the MRC
trial4 since this trial had found a significant treatment effect
(P < 0.05) on the outcome of PTD before 33 weeks of gestation in a subgroup of women with no previous cervical surgery but three or more previous PTDs or STLs. This result was
not confirmed in our analysis.
Similar analyses looking at the impact of obstetric history
and cervical length on cerclage effect were also undertaken for
the outcomes of pregnancy loss or death before discharge
from hospital, neonatal morbidity and maternal morbidity,
but no significant results were found.
We also found no evidence that the effect of cerclage in
trials where the main indication was short cervical length on
ultrasound was different from the effect in trials where indication was based on obstetric history alone.
Although it was apparent that some women were entered
into the trials of Rust et al.,12 Rush et al.11 and MRC4 more
than once, it was not always possible to identify them. For the
purpose of this review, it is therefore assumed that pregnancy
outcomes for the same woman are independent, although this
may have introduced a small amount of over-precision into
the results.
Z.A. and P.R.W. were authors of a paper that is included in

the IPD meta-analysis.13 Z.A. was an author of the non-IPD
systematic review on this topic.1 The authors declare that they
do not have any other competing interests.
Contribution to authorship
A.L.J. organised, cleaned and checked the individual patient
data sets, contacted the authors with queries, wrote the statistical analysis plan, performed data validation checks and
statistical analyses and co-wrote the review.
Z.A. assessed eligibility and methodological quality of
trials, liaised with individual trialists, provided clinical guidance and provided comments on the manuscript.
C.T.S. prepared the protocol, assessed eligibility and
methodological quality of the trials and provided comments
on the manuscript.
P.R.W. conceived the idea for undertaking the IPD metaanalysis, supervised A.L.J. on all aspects of the review, provided advice on the statistical analysis plan and the statistical
analyses and provided comments on the manuscript.
Cerclage IPD meta-analysis group members

A.L. Jorgensen (Liverpool); Z. Alfirvec (Liverpool); C. Tudur
Smith (Liverpool); P.R. Williamson (Liverpool); S.M.
Althulsivus (William Harvey Hospital, Kent); V. Berghella
(Thomas Jefferson University, Philadelphia; O.C. Ezechi
(Nigerian Institute of Medical Research); MRC/RCOG working party; R.W. Rush (previously from University of Cape
Town); O.A. Rust (Lehigh Valley Hospital and Health Network, Pennsylvania); M.S.T. (Fetal Medicine Foundation); K.
Nicolaides (Fetal Medicine Foundation).
Acknowledgements
Implications for practice
Although the results for the outcome of pregnancy loss or
death before discharge from hospital in singleton pregnancies
appears promising, further research is required before any
conclusive advice can be provided with regard to the benefits
The authors would like to thank the Fetal Medicine Foundation, a registered UK charity, for providing some financial
support for the project and also the cerclage IPD meta-analysis
group for kindly providing the data, responding to the various queries raised and providing valuable feedback on the
1475
Jorgensen et al.
draft paper. They would also like to thank Adrian Grant

(MRC/RCOG working party) who provided helpful comments on an earlier draft. j
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Cervical Stitch (Cerclage) For Preventing Pregnancy Loss: Individual Patient Data Meta-Analysis

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Cervical Stitch (Cerclage) For Preventing Pregnancy Loss: Individual Patient Data Meta-Analysis

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DOI: 10.1111/j.1471-0528.2007.01515.

Cervical stitch (cerclage) for preventing pregnancy

Accepted 6 August 2007. Published OnlineEarly 28 September 2007.

Background Several observational studies have claimed high

Main results The meta-analysis included seven trials and 2091

success rates for cerclage in women with cervical insufficiency. A

randomised women. In singleton pregnancies, the reduction in

Objectives We undertook an individual patient data (IPD) meta-

analysis to examine effect of cerclage on neonatal and maternal

Cochrane review were adopted and updated to December 2005.

was of randomised trials comparing cervical cerclage during

Conclusions Cerclage may reduce the risk of pregnancy loss or

neonatal death before discharge from hospital in singleton

data meta-analysis, neonatal death, neonatal morbidity, neonatal

women with poor obstetric history attributed to cervical

Cervical cerclage for preventing pregnancy loss

employed in the trials (e.g. varying cutoff points for defining

Selection and study characteristics

Data abstraction and validity assessment

Standardising pregnancy loss or death before

Standardising neonatal morbidity outcome

Table 1. Standardising outcome measures across trials

Indication for delivery

Cervical cerclage for preventing pregnancy loss

of any detectable neonatal morbidity at discharge. Table 1

Standardisation of maternal morbidity and

Cervical cerclage for preventing pregnancy loss

of a variable on outcome, models both with and without that

Women entered into the trials more than once

some debate between reviewers regarding the eligibility of the

Replicating published results from IPD

The IPD analysis replicated the published data by Althuisius

Blinding? Follow up after Location

Althuisius et al.8 Balanced blocks

Table 2. Characteristics of included studies

PTD ,34 weeks

McDonalds type Gestational

Blinding? Follow up after Location

Cervical cerclage for preventing pregnancy loss

Not stated Not stated

19.90 (2.87) 19.56 (4.29) 15.69 (9.20) 16.67 (8.01)

28.03 (6.10) 28.88 (6.79)

104 (100%) 103 (100%)

104 (100%) 103 (100%)

16.47 (3.71) 18.42 (2.92) 16.11 (7.72) 17.59 (6.24)

Table 3. Comparing baseline characteristics across trials

Potentially eligible studies identified by

Studies excluded since

Studies excluded since

Studies retrieved (n = 15)

Studies excluded since

Studies excluded since

Studies retrieved (n = 12)

Studies excluded since

Studies retrieved (n = 10)

Studies excluded since

Studies included in the review (n = 9)

Figure 1. Quorum diagram.