Does induction of labour increase the risk of

caesarean section? A systematic review and

meta-analysis of trials in women with intact
membranes
S Wood,
a,b
S Cooper,
a
S Ross
a,b
a
Departments of Obstetrics and Gynaecology, University of Calgary, Calgary, AB, Canada
b
Community Health Sciences, University of
Calgary, Calgary, AB, Canada
Correspondence: Dr S Wood, Department of Obstetrics and Gynaecology, University of Calgary, 4th Floor, North Tower, Foothills Medical
Centre, 1441 29th Street NW, Calgary, AB, T2N 4J8, Canada. Email Stephen.wood@albertahealthservices.ca
Accepted 8 February 2013. Published Online 3 July 2013.
Background Recent literature on the effect of induction of labour
(compared with expectant management) has provided conicting
results. Reviews of observational studies generally report an
increase in the rate of caesarean section, whereas reviews of
post-dates and term prelabour rupture of membrane (PROM
trials suggest either no difference or a reduction in risk.
Objective To evaluate with a systematic review and meta-analysis
of randomised controlled trials (RCTs) whether or not the
induction of labour increases the risk of caesarean section in
women with intact membranes.
Search strategy Literature search using electronic databases:
MEDLINE, EMBASE, and the Cochrane Database of Clinical
Trials.
Selection criteria RCTs comparing a policy of induction of labour
with expectant management in women with intact membranes.
Data collection and analysis A total of 37 trials were identied
and reviewed. Quantitative analyses with xed- and
random-effects models were performed with REVMAN 5.1.
Main results Of the 37 RCTs, 27 were trials of uncomplicated
pregnancies at 3742 weeks of gestation. The remaining ten
evaluated induction versus expectant management in pregnancies
with suspected macrosomia (two), diabetes in pregnancy (one),
oligohydramnios (one), twins (two), intrauterine growth
restriction (IUGR) (two), mild pregnancy-induced hypertension
(PIH) (one), and women with a high-risk score for caesarean
section (one). Meta-analysis of 31 trials determined that a policy
of induction was associated with a reduction in the risk of
caesarean section compared with expectant management (OR
0.83, 95% CI 0.760.92).
Authors Conclusions Induction of labour in women with intact
membranes reduces the risk of caesarean section. Review of the
trials suggests that this effect may arise from non-treatment
effects, and that additional trials are needed.
Keywords Caesarean section, clinical trials, induction of labour,
meta-analysis.
Please cite this Paper as: Wood S, Cooper S, Ross S. Does induction of labour increase the risk of caesarean section? A systematic review and meta-analysis
of trials in women with intact membranes. BJOG 2014;121:674685.
Introduction
Rising caesarean delivery rates in North America and Eur-
ope continue to be a major concern for health policy
experts, administrators, and medical professional associa-
tions.
1,2
A number of factors have been implicated, such as
the decline in rates of trial of labour after caesarean section,
and increasing rates of obesity, late maternal age, and
induced labour.
1,3,4
Reducing the frequency of induction is
often cited as an approach to reversing the trend in caesar-
ean section rates.
5
The association between induction of
labour and caesarean delivery is largely based on the nd-
ings of observational studies.
611
One clear limitation of
the observational literature is that induction is often indi-
cated by complications of pregnancy, which may indepen-
dently increase the risk of caesarean section. Additionally,
some authors have found that using survival analysis and
comparing the outcomes of women induced with those
who deliver at later gestational ages eliminates the effect of
induction
12
; however, this has not been a consistent nd-
674 2013 RCOG
DOI: 10.1111/1471-0528.12328
www.bjog.org
Systematic review
ing.
13
Therefore, a clearer picture may emerge from clinical
trials where women with a specic pregnancy complication
are randomised to a policy of induction of labour versus
further expectant management. In the setting of prelabour
rupture of membranes (PROM) at term, large clinical tri-
als, as well as meta-analysis, have clearly established that a
policy of induction does not increase the risk of caesarean
section.
14
Additionally, with induction for PROM, the risk
of caesarean section appears to be low,
15
perhaps indicating
the relative state of cervical maturation, or that the labour
process has already begun.
16
A 2006 Cochrane review of
trials of induction for post-term pregnancy concluded that
there was no difference in the risk of caesarean section
between induction and expectant management.
17
Caughey
and colleagues.
18
reviewed both observational studies and
clinical trials of elective induction. They found the obser-
vational studies consistently documented a lower rate of
caesarean section in women having spontaneous versus
induced labour. In contrast, meta-analysis of eight clinical
trials, six of which were post-dates trials, concluded that
caesarean section was reduced by induction. Of note, the
authors excluded all non-English articles.
Our goal was to evaluate whether induction of labour,
compared with a policy of expectant management, in
women with intact membranes increased the rate of caesar-
ean section. To that end, we undertook a systematic review
and meta-analysis.
Methods
We systematically searched Ovid MEDLINE (19502012,
week 23, 2010) and EMBASE (19802012, week 23). The
MEDLINE search for labour induction included the Medi-
cal Subject Headings (MeSH) term labour, induced and
the keywords induced labour, induction of labour, and
labour induced. EMBASE followed a similar strategy with
the MeSH term labour induction and keywords labour
induced, induction of labour, and induced labour. All
results were then limited to clinical trial. A review of the
Cochrane Database of Clinical Trials was also performed.
All citations were then independently reviewed by two of
the authors, S.W. and S.C. Titles and abstracts were
reviewed and full texts were obtained for all articles that
the reviewers felt were relevant, or also if they were uncer-
tain of their relevance. The references of these studies were
also searched for additional articles. Studies were included
if a policy of induction of labour, for indications other
than preterm rupture of membranes (PROM), was com-
pared with expectant management and outcome data on
route of delivery were provided. All three of the authors
independently assessed studies for potential selection, per-
formance, and attrition bias, as recommended for assessing
the quality of clinical trials in meta-analysis.
19
The compli-
ance with allocated treatment, as well as the degree of
crossover, were also assessed.
All studies were graded as high or low quality based on
three key quality indicators: adequate randomisation and
allocation concealment; limited losses to follow-up (<20%);
and intention-to-treat analysis.
18
Studies that were decient
in any of these areas were graded as low quality. Studies
were not included in the quantitative summary analysis,
unless intention-to-treat analysis was presented or could be
calculated from the available data. Quantitative analyses
with xed- and random-effects models were performed
with REVMAN 5.1 (The Nordic Center, The Cochrane Colla-
boration, Copenhagen). Statistical assessment for heteroge-
neity was performed and considered statistically signicant
if P < 0.05. A subgroup analysis limited to high-quality tri-
als was planned a priori.
Results
The literature search identied 2794 citations. A review of
the abstracts determined that there were 1368 unique cita-
tions. Details of the study selection are outlined in
Figure 1. Review of the abstracts identied 42 possible tri-
als for which the full articles were reviewed by all of the
authors. Three of the publications were not in English: one
was in German,
20
one was in French,
21
and one was in
Spanish
22
. These were reviewed with the assistance of two
obstetrician-gynaecologists and an Internal Medicine-OB
specialist at the authors institution. Five of the trials were
determined to be cervical ripening trials and were excluded.
A citation search identied two additional papers. One of
these, an abstract,
23
did not clearly report the frequency of
caesarean section in the two study groups, and was there-
fore excluded. The other was a conference abstract that did
supply sufcient data to be included.
24
Another article was
included as the trial protocol had been identied in our lit-
erature search,
25
and the publication of the nal results was
later identied.
26
Therefore, a total of 38 trials were
included in the review. Further review identied that one
of the trials was a duplicate publication of a previously
published German article
20,27
; therefore, only the English
version was included in the review. One trial, which rando-
mised women with twins to early term delivery versus stan-
dard care included women who planned to have a
caesarean section. The primary author of the article was
contacted and the details of the outcomes of the planned
vaginal delivery groups were kindly provided.
Of the remaining 37 studies, 27 were induction trials of
uncomplicated pregnancies at 3742 weeks of gesta-
tion.
21,22,2751
The remaining ten studies evaluated induc-
tion versus expectant management in pregnancies with
suspected macrosomia,
24,52
diabetes in pregnancy,
53
oligo-
hydramnios,
54
twins,
26,55
intrauterine growth restriction
2013 RCOG 675
Induction of labour and caesarean section
(IUGR),
56,57
mild pregnancy-induced hypertension (PIH),
58
and women with a high-risk score for caesarean section.
59
The characteristics of the 37 trials are outlined in
Table 1(and are further detailed in Table S1). The methods
of induction were not identical in all studies. The early
investigations generally used articial rupture of mem-
branes with oxytocin to achieve induction. Later studies
used combinations of cervical ripening with prostaglandins
or mechanical means, and subsequent oxytocin. Two stud-
ies used only prostaglandins for induction. In six trials,
women were only included if they had an unfavourable
cervix, and in ve trials only women with a favourable cer-
vix were enrolled. The remaining trials did not use cervical
status as an inclusion criterion. The reported overall caesar-
ean section rates varied between studies, with a range of 1
47%. Compliance with treatment in the induction groups
was not uniformly high, with reported rates of <70% in six
of the trials. In almost all of the studies induction of labour
became necessary in many of the expectantly managed
patients. The reported rates varied from 4 to a high of
50%. Most trials reported that the time to delivery
increased in the expectantly managed versus the induced
groups, but this was not reported in a sufciently uniform
manner to allow a quantitative summary. Typically, trials
reported latency to delivery of about 1 week in the expec-
tant management group. One trial reported no difference
in average gestational age at delivery between those induced
and those managed expectantly.
30
A review of trial quality rated 19 trials as high quality
and 17 trials as low quality (Tables 1 and S2). One trial
could not be graded as sufcient information was not
available from the abstract, and the authors did not
respond to requests for additional information.
24
The most
common reason for a low-quality score was unclear or
inadequate randomisation and allocation concealment. Of
the low-quality studies, six could not be included in the
meta-analysis either because of large post-randomisation
exclusions (>20%) or because of insufcient data to per-
form an intention-to-treat analysis. Only three trials docu-
mented a statistically signicant difference in caesarean
section rates between a policy of induction and expectant
management. Two of these trials reported a reduction in
Citation Search 4
Records identified through
database searching
(n = 2794)
Additional records identified
through other sources
(n = 0)
Records after duplicates removed
(n = 1368)
Records screened
(n = 1368)
Records excluded
not RCT (n = 292)
cervical ripening RCT
(n = 321)
Induction method RCT
(n = 346)
Term PROM RCT n = (71)
Active management of
labour RCT (n = 27)
other RCT (n=259)
non human RCT (n = 10)
Full-text articles assessed
for eligibility
(n = 42)
Full-text articles excluded,
post dates cervical
ripening trials
(n = 5)
Duplicate publication
(n = 1)
Studies selected for
review of trial quality
(n = 37)
Studies included in
quantitative synthesis
(meta-analysis)
(n = 31)
Citation Search n = 2
Eligible for inclusion n = 1
Figure 1. Flow diagram of studies included in the meta-analysis.
676 2013 RCOG
Wood et al.
T
a
b
l
e
1
.
S
t
u
d
y
c
h
a
r
a
c
t
e
r
i
s
t
i
c
s
o
f
r
a
n
d
o
m
i
s
e
d
c
o
n
t
r
o
l
l
e
d
t
r
i
a
l
s
o
f
i
n
d
u
c
t
i
o
n
i
n
s
u
b
j
e
c
t
s
w
i
t
h
i
n
t
a
c
t
m
e
m
b
r
a
n
e
s
S
t
u
d
y
n
S
t
u
d
y
p
o
p
u
l
a
t
i
o
n
M
e
t
h
o
d
o
f
i
n
d
u
c
t
i
o
n
C
a
e
s
a
r
e
a
n
s
e
c
t
i
o
n
r
a
t
e
:
i
n
d
u
c
t
i
o
n
g
r
o
u
p
%
(
n
)
C
a
e
s
a
r
e
a
n
s
e
c
t
i
o
n
r
a
t
e
:
e
x
p
e
c
t
a
n
t
g
r
o
u
p
%
(
n
)
Q
u
a
l
i
t
y
I
n
c
l
u
d
e
d
i
n
m
e
t
a
-
a
n
a
l
y
s
i
s
H
e
n
r
y
3
9
1
1
2
P
r
e
g
n
a
n
c
y
>
4
0
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
A
R
M
/
o
x
y
t
o
c
i
n
0
(
0
)
1
.
8
(
1
)
L
o
w
Y
e
s
C
o
l
e
a
n
d
c
o
l
l
e
a
g
u
e
s
3
3
2
3
7
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
3
9

4
0
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
A
R
M
/
o
x
y
t
o
c
i
n
4
.
5
(
5
)
7
.
7
(
9
)
L
o
w
Y
e
s
M
a
r
t
i
n
a
n
d
c
o
l
l
e
a
g
u
e
s
4
3
2
3
0
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
3
9
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
A
R
M
/
o
x
y
t
o
c
i
n
4
.
3
(
4
)
1
.
1
(
1
)
L
o
w
N
o
T
y
l
l
e
s
k
a
r
a
n
d
c
o
l
l
e
a
g
u
e
s
5
0
8
4
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
0
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
a
n
d
f
a
v
o
u
r
a
b
l
e
c
e
r
v
i
x
A
R
M
/
o
x
y
t
o
c
i
n
2
.
3
(
1
)
2
.
4
(
1
)
L
o
w
N
o
B
r
e
a
r
t
a
n
d
c
o
l
l
e
a
g
u
e
s
2
1
7
1
6
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
3
7

3
9
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
A
R
M
/
o
x
y
t
o
c
i
n
4
.
0
(
1
9
)
6
.
8
(
1
6
)
H
i
g
h
Y
e
s
K
a
t
z
a
n
d
c
o
l
l
e
a
g
u
e
s
4
2
1
5
6
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:

4
2
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
a
n
d
u
n
f
a
v
o
u
r
a
b
l
e
c
e
r
v
i
x
A
R
M
/
o
x
y
t
o
c
i
n
2
0
.
5
(
1
6
)
9
(
7
)
L
o
w
Y
e
s
S
a
n
d
e
a
n
d
c
o
l
l
e
a
g
u
e
s
4
9
1
6
6
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
0

4
1
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
a
n
d
f
a
v
o
u
r
a
b
l
e
c
e
r
v
i
x
A
R
M
/
o
x
y
t
o
c
i
n
U
n
a
b
l
e
t
o
c
a
l
c
u
l
a
t
e
U
n
a
b
l
e
t
o
c
a
l
c
u
l
a
t
e
L
o
w
N
o
C
a
r
d
o
z
o
a
n
d
c
o
l
l
e
a
g
u
e
s
3
1
4
0
2
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
1
3
/
7
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
P
G
E
3
m
g
v
a
g
i
n
a
l
l
y

A
R
M
/
o
x
y
t
o
c
i
n
1
4
.
3
(
2
8
)
1
1
.
6
(
2
4
)
L
o
w
N
o
A
u
g
e
n
s
e
n
a
n
d
c
o
l
l
e
a
g
u
e
s
2
9
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
2
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
O
x
y
t
o
c
i
n
6
.
5
(
1
4
)
1
0
.
3
(
2
0
)
H
i
g
h
Y
e
s
D
y
s
o
n
a
n
d
c
o
l
l
e
a
g
u
e
s
3
4
3
0
2
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:

4
1
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
a
n
d
u
n
f
a
v
o
u
r
a
b
l
e
c
e
r
v
i
x
P
G
E
3
m
g
v
a
g
i
n
a
l
l
y
o
r
0
.
5
m
g
i
n
t
r
a
c
e
r
v
i
c
a
l
l
y
/
o
x
y
t
o
c
i
n
1
4
.
5
(
2
2
)
2
7
.
3
(
4
1
)
H
i
g
h
Y
e
s
W
i
t
t
e
r
a
n
d
W
e
i
t
z
5
1
2
0
0
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
2
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
O
x
y
t
o
c
i
n
2
9
.
2
(
3
0
)
2
7
.
8
(
2
7
)
H
i
g
h
Y
e
s
B
e
r
g
s
j
o
a
n
d
c
o
l
l
e
a
g
u
e
s
3
0
1
8
8
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:

4
2
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
O
x
y
t
o
c
i
n
2
8
.
7
(
2
7
)
4
1
.
4
(
3
9
)
L
o
w
Y
e
s
E
g
a
r
t
e
r
a
n
d
c
o
l
l
e
a
g
u
e
s
2
7
3
4
5
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
2
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
a
n
d
f
a
v
o
u
r
a
b
l
e
c
e
r
v
i
x
P
G
E
3
m
g
v
a
g
i
n
a
l
l
y
1
.
1
(
2
)
1
.
8
(
3
)
L
o
w
Y
e
s
M
a
r
t
i
n
a
n
d
c
o
l
l
e
a
g
u
e
s
4
4
2
2
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:

4
1
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
a
n
d
u
n
f
a
v
o
u
r
a
b
l
e
c
e
r
v
i
x
L
a
m
i
n
a
r
i
a
/
A
R
M
/
o
x
y
t
o
c
i
n
1
6
.
7
(
2
)
1
0
(
1
)
H
i
g
h
Y
e
s
H
e
d
e
n
a
n
d
c
o
l
l
e
a
g
u
e
s
3
7
2
3
8
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
2
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
a
n
d
c
e
r
v
i
c
a
l
d
i
l
a
t
a
t
i
o
n
<
4
c
m
A
R
M
/
o
x
y
t
o
c
i
n
9
.
2
(
1
0
)
7
.
0
(
9
)
L
o
w
Y
e
s
H
a
n
n
a
h
a
n
d
c
o
l
l
e
a
g
u
e
s
3
6
3
4
0
7
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
1

4
4
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
a
n
d
c
e
r
v
i
x
<
3
c
m
d
i
l
a
t
e
d
A
R
M
/
o
x
y
t
o
c
i
n
P
G
E
2
0
.
5
m
g
i
n
t
r
a
c
e
r
v
i
c
a
l
l
y
2
1
.
1
%
(
3
6
0
)
2
4
.
5
%
(
4
1
8
)
H
i
g
h
y
e
s
H
e
r
a
b
u
t
y
a
a
n
d
c
o
l
l
e
a
g
u
e
s
4
0
1
0
8
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
2
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
a
n
d
u
n
f
a
v
o
u
r
a
b
l
e
c
e
r
v
i
x
P
G
E
2
0
.
5
m
g
i
n
t
r
a
c
e
r
v
i
c
a
l
l
y
/
o
x
y
t
o
c
i
n
4
7
.
4
(
2
7
)
4
7
.
1
(
2
4
)
L
o
w
Y
e
s
K
j
o
s
a
n
d
c
o
l
l
e
a
g
u
e
s
5
3
2
0
0
I
n
s
u
l
i
n
-
r
e
q
u
i
r
i
n
g
d
i
a
b
e
t
e
s
,
i
n
c
l
u
d
i
n
g
G
D
M
,
3
8
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
P
G
E
3
m
g
/
o
x
y
t
o
c
i
n
2
5
(
2
5
)
3
1
(
3
1
)
L
o
w
Y
e
s
M
c
N
e
l
l
i
s
a
n
d
c
o
l
l
e
a
g
u
e
s
4
5
4
4
0
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
1

4
3
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
a
n
d
u
n
f
a
v
o
u
r
a
b
l
e
c
e
r
v
i
x
P
G
E
0
.
5
m
g
i
n
t
r
a
c
e
r
v
i
c
a
l
l
y
/
o
x
y
t
o
c
i
n
2
0
.
8
(
5
5
)
1
8
.
3
(
3
2
)
H
i
g
h
Y
e
s
O
h
e
l
a
n
d
c
o
l
l
e
a
g
u
e
s
4
7
2
0
0
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
0
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n

4
d
a
y
s
P
G
E
3
m
g
i
n
t
r
a
v
a
g
i
n
a
l
l
y
U
n
a
b
l
e
t
o
c
a
l
c
u
l
a
t
e
5
.
8
(
6
)
L
o
w
N
o
2013 RCOG 677
Induction of labour and caesarean section
T
a
b
l
e
1
.
(
C
o
n
t
i
n
u
e
d
)
S
t
u
d
y
n
S
t
u
d
y
p
o
p
u
l
a
t
i
o
n
M
e
t
h
o
d
o
f
i
n
d
u
c
t
i
o
n
C
a
e
s
a
r
e
a
n
s
e
c
t
i
o
n
r
a
t
e
:
i
n
d
u
c
t
i
o
n
g
r
o
u
p
%
(
n
)
C
a
e
s
a
r
e
a
n
s
e
c
t
i
o
n
r
a
t
e
:
e
x
p
e
c
t
a
n
t
g
r
o
u
p
%
(
n
)
Q
u
a
l
i
t
y
I
n
c
l
u
d
e
d
i
n
m
e
t
a
-
a
n
a
l
y
s
i
s
G
o
n
e
n
a
n
d
c
o
l
l
e
a
g
u
e
s
5
2
2
8
4
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
3
8
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
a
n
d
E
F
W
4
0
0
0

4
5
0
0
g
P
G
E
/
o
x
y
t
o
c
i
n
1
9
.
4
(
2
6
)
2
1
.
6
(
3
0
)
L
o
w
Y
e
s
R
o
a
c
h
a
n
d
R
o
g
e
r
s
4
8
2
0
1
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
2
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
P
G
E
3
m
g
i
n
t
r
a
v
a
g
i
n
a
l
l
y
1
6
.
7
(
1
6
)
1
7
.
1
(
1
8
)
H
i
g
h
Y
e
s
A
m
a
n
o
a
n
d
c
o
l
l
e
a
g
u
e
s
2
8
1
9
4
U
n
c
o
m
p
l
i
c
a
t
e
d
n
u
l
l
i
p
a
r
a
:
3
9
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
L
a
m
i
n
a
r
i
a
/
o
r
a
l
P
G
E
/
I
V
P
G
F
2
a
/
o
x
y
t
o
c
i
n
6
.
3
(
4
)
5
.
6
(
4
)
L
o
w
N
o
S
u
z
u
k
i
a
n
d
c
o
l
l
e
a
g
u
e
s
5
5
3
6
T
w
i
n
p
r
e
g
n
a
n
c
y
:
3
7
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
,
w
i
t
h
c
e
p
h
a
l
i
c
-

r
s
t
t
w
i
n
P
G
E
0
.
5
m
g
o
r
a
l
l
y
/
o
x
y
t
o
c
i
n
1
7
.
6
(
3
)
3
1
.
6
(
6
)
L
o
w
Y
e
s
J
a
m
e
s
a
n
d
c
o
l
l
e
a
g
u
e
s
4
1
7
4
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
1
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
I
n
t
r
a
c
e
r
v
i
c
a
l
F
o
l
e
y
c
a
t
h
e
t
e
r
/
o
x
y
t
o
c
i
n
5
.
4
(
2
)
1
0
.
8
(
4
)
H
i
g
h
Y
e
s
C
h
a
n
r
a
c
h
a
k
u
l
a
n
d
H
e
r
a
b
u
t
y
a
3
2
2
5
0
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
1
3
/
7
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
,
w
i
t
h
f
a
v
o
u
r
a
b
l
e
c
e
r
v
i
x
A
R
M
/
o
x
y
t
o
c
i
n
2
6
.
6
(
3
3
)
2
1
.
6
(
2
7
)
L
o
w
Y
e
s
E
k
a
n
d
c
o
l
l
e
a
g
u
e
s
5
4
5
4
O
l
i
g
o
h
y
d
r
a
m
n
i
o
s
(
A
F
I
<
5
c
m
)
a
t
4
1
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
I
n
t
r
a
c
e
r
v
i
c
a
l
F
o
l
e
y
c
a
t
h
e
t
e
r
/
o
x
y
t
o
c
i
n
3
.
5
(
1
)
1
5
.
4
(
4
)
H
i
g
h
Y
e
s
G
e
l
i
s
e
n
a
n
d
c
o
l
l
e
a
g
u
e
s
3
5
6
0
0
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
1
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
,
w
i
t
h
u
n
f
a
v
o
u
r
a
b
l
e
c
e
r
v
i
x
I
n
t
r
a
c
e
r
v
i
c
a
l
F
o
l
e
y
c
a
t
h
e
t
e
r
/
m
i
s
o
p
r
o
s
t
o
l
5
0
l
g
v
a
g
i
n
a
l
l
y
/
o
x
y
t
o
c
i
n
1
9
.
3
(
5
8
)
2
2
(
6
6
)
H
i
g
h
Y
e
s
N
i
e
l
s
e
n
a
n
d
c
o
l
l
e
a
g
u
e
s
4
6
2
1
6
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:

3
9
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
,
w
i
t
h
f
a
v
o
u
r
a
b
l
e
c
e
r
v
i
x
A
R
M
/
o
x
y
t
o
c
i
n
6
.
9
(
8
)
7
.
2
(
8
)
H
i
g
h
Y
e
s
V
a
n
d
e
n
H
o
v
e
a
n
d
c
o
l
l
e
a
g
u
e
s
5
7
3
3
S
u
s
p
e
c
t
e
d
I
U
G
R

3
7
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
P
G
E
/
A
R
M
/
o
x
y
t
o
c
i
n
1
8
.
8
(
3
)
2
3
.
5
(
4
)
H
i
g
h
Y
e
s
H
e
i
m
s
t
a
d
a
n
d
c
o
l
l
e
a
g
u
e
s
3
8
5
0
8
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
4
1
2
/
7
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
P
G
E
0
.
5
m
g
o
r
m
i
s
o
p
r
o
s
t
o
l
5
0
l
g
/
A
R
M
/
o
x
y
t
o
c
i
n
1
1
.
0
(
2
8
)
1
3
.
0
(
3
3
)
H
i
g
h
Y
e
s
N
i
c
h
o
l
s
o
n
a
n
d
c
o
l
l
e
a
g
u
e
s
5
9
2
7
0
3
7
4
/
7
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
a
n
d
h
i
g
h
r
i
s
k
f
o
r
c
a
e
s
a
r
e
a
n
s
e
c
t
i
o
n
P
G
E
(
d
i
n
o
p
r
o
s
t
o
n
e
o
r
m
i
s
o
p
r
o
s
t
o
l
/
A
R
M
/
o
x
y
t
o
c
i
n
)
1
0
.
3
(
1
4
)
1
4
.
9
(
2
0
)
H
i
g
h
Y
e
s
K
o
o
p
m
a
n
s
a
n
d
c
o
l
l
e
a
g
u
e
s
5
8
7
5
6
M
i
l
d
P
I
H
a
t
3
6

4
1
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
I
n
t
r
a
c
e
r
v
i
c
a
l
o
r
i
n
t
r
a
v
a
g
i
n
a
l
P
G
E
/
i
n
t
r
a
c
e
r
v
i
c
a
l
F
o
l
e
y
c
a
t
h
e
t
e
r
/
o
x
y
t
o
c
i
n
1
4
.
3
(
5
4
)
1
9
.
0
(
7
2
)
H
i
g
h
Y
e
s
B
o
e
r
s
a
n
d
c
o
l
l
e
a
g
u
e
s
5
6
6
5
0
S
u
s
p
e
c
t
e
d
I
U
G
R
a
t
3
6

4
1
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
I
n
t
r
a
v
a
g
i
n
a
l
o
r
i
n
t
r
a
c
e
r
v
i
c
a
l
P
G
E
/
i
n
t
r
a
c
e
r
v
i
c
a
l
F
o
l
e
y
c
a
t
h
e
t
e
r
/
o
x
y
t
o
c
i
n
1
4
.
0
(
4
5
)
1
3
.
7
(
4
5
)
H
i
g
h
Y
e
s
B
e
n
i
t
o
-
R
e
y
e
s
a
n
d
c
o
l
l
e
a
g
u
e
s
2
2
2
0
0
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
>
4
2
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
,
w
i
t
h
u
n
f
a
v
o
u
r
a
b
l
e
c
e
r
v
i
x
P
G
E
2
/
A
R
M
/
o
x
y
t
o
c
i
n
1
2
.
7
(
1
3
)
1
8
.
4
(
1
8
)
H
i
g
h
Y
e
s
B
o
u
l
v
a
i
n
a
n
d
c
o
l
l
e
a
g
u
e
s
2
4
8
1
7
U
n
c
o
m
p
l
i
c
a
t
e
d
p
r
e
g
n
a
n
c
y
:
3
7

3
8
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
,
E
F
W
>
9
5
%
.
D
a
t
a
n
o
t
a
v
a
i
l
a
b
l
e
2
8
.
0
(
1
1
4
)
3
1
.
7
(
1
3
0
)
Y
e
s
D
o
d
d
a
n
d
c
o
l
l
e
a
g
u
e
s
2
6
1
4
9
T
w
i
n
p
r
e
g
n
a
n
c
y
:

3
7
w
e
e
k
s
o
f
g
e
s
t
a
t
i
o
n
N
o
d
e
t
a
i
l
s
p
r
o
v
i
d
e
d
3
1
(
2
2
)
2
6
.
9
(
2
1
)
H
i
g
h
Y
e
s
678 2013 RCOG
Wood et al.
the rate of caesarean section with induction,
34,36
and one
reported an increase in risk.
42
The remaining trials reported
non-signicant differences in the rate of caesarean section,
with most point estimates favouring a reduction in risk
with induction. A quantitative summary analysis combined
the results of 31 trials, with 6248 women randomised to
induction and 5918 women randomised to expectant man-
agement (Figure 2). The trials were ordered by year in
order to display any potential chronological effect, and
were subdivided by post-dates trials (41 weeks of gesta-
tion) and induction for other indications. In this analysis, a
policy of induction was associated with a reduction in the
risk of caesarean section compared with expectant manage-
ment (xed-effects model, OR 0.83, 95% CI 0.760.92,
P = 0.0002). There was no signicant statistical heterogene-
ity: v = 27.11, df = 30, P = 0.62, and I
2
= 0%. The same
results were obtained with a random-effects model
(OR 0.83, 95% CI 0.760.92). Visual inspection of the fun-
nel plot did not suggest any signicant publication bias.
The reduced risk of caesarean section was seen in both the
subgroups of the post-dates trials (OR 0.85, 95% CI 0.76
0.95) and in the trials of induction for other indications
(OR 0.81, 95% CI 0.690.95). Subgroup analysis of only
the 19 high-quality trials revealed a similar result (xed-ef-
fects model, OR 0.82 95% CI 0.730.91; random-effects
model, OR 0.82, 95% CI 0.730.91; Figure 3).
Details on the indication for caesarean section were
reported in 16 of the trials; however, in the majority the
number of outcomes was too few for any meaningful com-
parisons. Of the seven trials with sufcient numbers, three
reported an increase in the number of caesarean sections for
fetal distress in the expectant group, but this difference was
statistically signicant in only one study.
36,40,56
One trial
reported a non-signicant increase in the risk of abdominal
delivery for dystocia with expectant management.
59
The
remaining trials did not report any differences in indica-
tions for caesarean section between those randomised to
induction or those randomised to expectant management.
Meta-analysis of the risk of caesarean section for fetal
distress with induction versus expectant management did
not document a statistically signicant difference (Fig-
ure 4). A meta-analysis was also performed for the out-
comes of postpartum haemorrhage and operative vaginal
delivery (Figure 4): neither was increased with induction of
labour. Neonatal outcomes were also examined. A compos-
ite neonatal morbidity score was described in seven trials,
but only one reported a statistically signicant difference
between the study groups,
24
which, in that study, favoured
the induction arm. Unfortunately, the morbidity scores
were not sufciently similar to allow for a pooled analysis.
Some assessment of cord pH was reported in 13 trials. One
trial reported an increase in the rate of cord pH < 7.05
with expectant management 6% (19) versus 3% (9),
P = 0.043.
58
The other trials reported non-signicant dif-
ferences in mean pH or in the rate of low cord pH. As a
result of variable reporting between the trials, meta-analysis
was not feasible. Meta-analysis was performed for the fol-
lowing neonatal outcomes: an Apgar score at 5 min-
utes < 7; admission to the neonatal intensive care unit
(NICU); and perinatal death, excluding anomaly (Fig-
ure 4). No statistically signicant differences between
induction and expectant management were observed. Peri-
natal death was reduced with induction of labour, but the
result was not statistically signicant P = 0.05.
Discussion
Main ndings
Our meta-analysis of clinical trials of induction versus
expectant management in women with intact membranes
found that the induction of labour is associated with a
moderate but statistically signicant reduction in the risk
of caesarean section. This effect was evident in the sub-
groups of post-date trials, trials of induction for other indi-
cations, and in the analysis restricted to high-quality
studies. Differences in other maternal and neonatal out-
comes were not evident, but a non-statistically signicant
reduction in perinatal death was observed in the induction
group.
Strengths and limitations
Our reviews main strength is that it included all relevant
randomised clinical trials that we identied, and so added
to previous reviews by including reports in all languages as
well as those published since 2007. As our results are based
solely on randomised clinical trials, selection bias and con-
founding should be limited. This is in contrast to observa-
tional studies where selection bias and confounding can be
problematic. Admittedly, recent well-designed retrospective
studies in electively induced women, have also demon-
strated a reduction in caesarean section with induction,
compared with expectant management.
60,61
Our results were based on an intention-to-treat analysis.
Although this is a valid standard, it could also have affected
our ndings. In most of the trials there was less than per-
fect compliance with induction in the treatment groups,
and there were high rates of induction in the expectant
groups. These factors would tend to bias the results
towards the null, and therefore could have obscured a true
difference in the risk of caesarean section with induction.
A limitation of our review is that we did not include a
formal systematic review of cost effectiveness. Two of the
trials we reviewed, the Canadian Post Term Pregnancy
Trial and Hypertension and Pre-eclampsia Intervention
Trial at Term (HYPITAT), have published secondary eco-
nomic analyses.
62,63
Both of these analyses found that the
2013 RCOG 679
Induction of labour and caesarean section
increase in costs associated with induction of labour were
more than offset by a reduction in the frequency of fetal
testing. These results may not apply to term elective induc-
tions, but may be similar for induction for indications such
as small for gestational age (SGA), multiple pregnancy, and
maternal diabetes.
Interpretation
Some caution should be sounded before unreservedly
accepting the conclusion that induction of labour reduces
the risk of caesarean section. In our meta-analysis, this
result, especially in the post-date trials, is heavily inuenced
by the largest study in our review, the Canadian Post Dates
Figure 2. Forest plot for the outcome caesarean section in the selected trials, comparing a policy of induction of labour with that of expectant
management.
680 2013 RCOG
Wood et al.
Figure 3. Forest plot for the outcome caesarean section in high-quality trials only, comparing a policy of induction of labour with expectant
management.
No. of Summary
Studies Events Total Events Total Odds Ratio (95% CI)
Maternal outcomes
Post partum hemmorhage 5 87 1569 107 1331 0.78 [0.58, 1.05]
Operative vaginal delivery 20 871 4535 761 4281 1.09 [0.98, 1.22]
Cesarean section for fetal distress 16 236 3765 293 3744 0.87 [0.62, 1.23]
Neonatal outcomes
0.93 [0.63, 1.37] 4137 52 4113 48 18 APGAR <7 (5 min)
0.88 [0.75, 1.03] 3958 379 4041 337 15 NICU admission
0.37 [0.14, 1.00] 5860 10 6194 1 30 Perinatal death*
*excluding anomaly
Induction Expectant management
Odds ratio (95% CI)
Figure 4. Summary odds ratios and 95% condence intervals for selected secondary maternal and neonatal outcomes.
2013 RCOG 681
Induction of labour and caesarean section
Trial,
36
where cervical ripening with intracervical prosta-
glandin E was only planned for women in the immediate
induction group. Similar treatment was discouraged for
inductions in women who were expectantly managed. Even-
tually 32% of the expectant group were induced, but only
9% received prostaglandins for ripening, compared with
51% of the immediate induction group. In a recent Cochra-
ne review, cervical ripening with intracervical prostaglandins
was reported to reduce the risk of caesarean section com-
pared with oxytocin alone.
64
Therefore, this co-intervention
in the induction group may have biased their results. Addi-
tionally, a disproportionate number of women in the expec-
tant group had induction for suspected fetal compromise.
65
A similar trend was noted in our meta-analysis. Although
many of these were likely to be false-positive results, the
higher gestational ages in women who were expectantly
managed may have increased the anxiety of doctors, and led
to a greater number of caesarean sections. Similar labelling
has been documented as a factor in increasing the rate of
caesarean sections in women with gestational diabetes and
suspected macrosomia.
66,67
Such concern about poor out-
comes may affect delivery decisions for expectantly managed
women with PIH, SGA, oligohydramnios, and multiple
pregnancy. It may be that the results of our review reect
doctors discomfort with delayed delivery in high-risk
women that, once they are in labour, manifests as more fre-
quent caesarean sections: an example of research conrming
the biases of the health care community.
68
It is difcult to reconcile the results of this meta-analysis
with the consistent nding that lack of cervical maturation
prior to induction is strongly associated with subsequent cae-
sarean section.
69,70
Clinicians have generally pursued a policy
of expectant management, not only to allow spontaneous
labour, but also to provide time for cervical ripening should
induction become necessary later. Therefore, a policy of
delay would be expected to produce an improvement in cer-
vical state and related reduction in the risk of caesarean sec-
tion. A few possible explanations can be postulated to resolve
this paradox. First, although ripening would have eventually
occurred in many of expectantly managed women, the actual
delay to delivery was too short: most of the included trials
documented only modest differences between treatment
groups in gestational age at delivery. A second explanation is
that cervical state is a characteristic of the patient that is not
modiable by expectant management. Support for this sup-
position comes from Smith and colleaguess.
71
fascinating
cohort study, which found that greater cervical length at
mid-gestation in primiparous women was associated with an
increased risk of caesarean section at term, and that this was
largely because of poor progress in labour. Ultimately, either
one of these possibilities could explain both why the trials
that included only women with unripe cervixes had similar
ndings as those restricted to women with mature cervixes,
and the result of a subgroup analysis of Koopman and col-
leaguess.
58
trial, which found no differences in the risk of
caesarean section stratied by Bishop score.
Conclusion
Some readers may feel that the results of the trials and this
meta-analysis are sufcient to justify a policy of elective
induction. Before concluding this, it should also be care-
fully considered that only one of the trials was designed to
evaluate the impact of induction on the risk of caesarean
section.
59
Ideally, we feel that a trial primarily evaluating
the risk of caesarean section would have a number of fea-
tures that were not prominent in the trials where it was a
secondary outcome. First, cervical state should not be
known by the recruiting clinicians, or even by the women
themselves. This would reduce the signicant risk of
pre-randomisation exclusions of women with the most
adverse cervical ndings. Secondly, the latency to delivery
in the expectant group should be sufcient both for a
meaningful improvement in cervical state and for a signi-
cant number of women to go into labour spontaneously.
This can only be achieved if the treatment group is induced
when fetal maturation is assured (at 38 weeks of gestation?)
and the women are of sufciently low risk to anticipate a
delay in induction until at least 41 weeks of gestation. Fur-
thermore, there needs to be a strong commitment at study
sites to perform what might be perceived as elective
inductions in a timely fashion to reduce crossover. Finally,
an economic evaluation conducted alongside the trial will
be important. Until such rigorous trials are performed we
think it is premature to conclude that induction does not
affect the risk of caesarean section.
Ultimately, induction of labour is one of the common
treatments available to clinicians. It could also be argued
that, based on our results, it is one of the only interven-
tions that has been shown in a clinical trial to reduce the
risk of caesarean section.
72
Therefore, it may be that some
women at high risk of caesarean section, such as women of
late maternal age or women who are obese, could benet
from an elective induction. Ideally, this will be the subject
of further clinical trials.
Disclosure of interests
The authors have no interests to disclose.
Contribution to authorship
All authors contributed to the design of the study. SW and
SC reviewed all of the abstracts. All of the authors critically
appraised the selected articles. SW performed the statistical
analysis, and all the authors contributed to the interpreta-
tion of the results. SW drafted the article, which was
reviewed by SC and RS.
682 2013 RCOG
Wood et al.
Details of ethics approval
The study was approved by the local ethics review board
(ref. no. E23622).
Funding
The authors are members of the Partnership for Research
and Education in Mothers and Infants, which has been
funded by Ross Products, a division of Abbott.
Acknowledgements
The authors wish to acknowledge the nancial support of
their research group by Ross Products, a division of Ab-
bott. The authors also wish to thank Dr Magali Robert, Dr
Vreni Kuret, and Dr Eliana Castillo for their assistance with
reviewing the French, German, and Spanish articles. The
authors would also like to thank Ms Selphee Tang for assis-
tance with the gures.
Supporting Information
Additional Supporting Information may be found in the
online version of this article:
Table S1. Study characteristics of randomised controlled
trials of induction in subjects with intact membranes.
Table S2. Quality assessment of randomised controlled
trials of induction in subjects with intact membranes.
&
References
1 Guihard P, Blondel B. Trends in risk factors for caesarean sections in
France between 1981 and 1995: lessons for reducing the rates in
the future. BJOG 2001;108:4855.
2 Queenan JT. How to stop the relentless rise in cesarean deliveries.
Obstet Gynecol 2011;118:199200.
3 Rayburn WF, Zhang J. Rising rates of labor induction: present
concerns and future strategies. Obstet Gynecol 2002;100:1647.
4 Zhang J, Troendle J, Reddy UM, Laughon SK, Branch DW, Burkman
R, et al. Contemporary cesarean delivery practice in the United
States. Am J Obstet Gynecol 2010;203:326.
5 Singh R, Nath TA. Is the caesarean section rate a performance
indicator of an obstetric unit? J Matern Fetal Neonatal Med
2011;24:2047.
6 Boulvain M, Marcoux S, Bureau M, Fortier M, Fraser W. Risks of
induction of labour in uncomplicated term pregnancies. Paediatr
Perinat Epidemiol 2001;15:1318.
7 Dublin S, Lydon-Rochelle M, Kaplan RC, Watts DH, Critchlow CW.
Maternal and neonatal outcomes after induction of labor without
an identied indication. Am J Obstet Gynecol 2000;183:98694.
8 Heffner LJ, Elkin E, Fretts RC. Impact of labor induction, gestational
age, and maternal age on cesarean delivery rates. Obstet Gynecol
2003;102:28793.
9 Maslow AS, Sweeny AL. Elective induction of labor as a risk factor
for cesarean delivery among low-risk women at term. Obstet
Gynecol 2000;1:91722.
10 Vahratian A, Zhang J, Troendle JF, Sciscione AC, Hoffman MK.
Labor progression and risk of cesarean delivery in electively induced
nulliparas. Obstet Gynecol 2005;105:698704.
11 Yeast JD, Jones A, Poskin M. Induction of labor and the relationship
to cesarean delivery: A review of 7001 consecutive inductions. Am J
Obstet Gynecol 1999;1:62833.
12 Caughey AB, Nicholson JM, Cheng YW, Lyell DJ, Washington AE,
Caughey AB, et al. Induction of labor and cesarean delivery by
gestational age. Am J Obstet Gynecol 2006;195:7005.
13 Glantz JC, Glantz JC. Term labor induction compared with
expectant management. Obstet Gynecol 2010;115:706.
14 Dare MR, Middleton P, Crowther CA, Flenady VJ, Varatharaju B.
Planned early birth versus expectant management (waiting) for
prelabour rupture of membranes at term (37 weeks or more).
Cochrane Database of Syst Rev 2006;(1):CD005302.
15 Hannah ME, Ohlsson A, Farine D, Hewson SA, Hodnett ED, Myhr
TL, et al. Induction of labor compared with expectant management
for prelabor rupture of the membranes at term. TERMPROM study
group. N Engl J Med 1996;334:100510.
16 Challis JRG, Sloboda DM, Alfaidy N, Lye SJ, Gibb W, Patel FA, et al.
Prostaglandins and mechanisms of preterm birth. Reproduction
2002;124:117.
17 Gulmezoglu AM, Crowther CA, Middleton P. Induction of labour for
improving birth outcomes for women at or beyond term. Cochrane
Database of Syst Rev 2006;(4):CD004945.
18 Caughey AB, Sundaram V, Kaimal AJ, Gienger A, Cheng YW,
McDonald KM, et al. Systematic review: elective induction of labor
versus expectant management of pregnancy. Ann Intern Med
2009;151:25263.
19 Juni P, Altman DG, Egger M. Systematic reviews in health care:
assessing the quality of controlled clinical trials. BMJ 2001;323:426.
20 Husslein P, Egarter C, Sevelda P. Induction of labour with
prostaglandin E2 vvaginal tablets - A revival of elective induction?
Results of prospective randomised trial Geburtshilfe Frauenheilkd
1986;46:837.
21 Breart G, Goujard J, Maillard F, Chavigny C, Rumeau-Rouquette C,
Sureau C. Comparison of 2 obstetrical attitudes vis-a-vis inducing
labor at term. Randomized study. J Gynecol Obstet Biol Reprod
1982;11:10712.
22 Benito R V, Hurtado MR, Rodriguez RF, Reyes SD, Alvarez Leon EE,
Garcia Hernandez JA. Elective termination versus expectant
management in prolonged pregnancy: a prospective study of 200
pregnant women. Progresos de Obstetricia Y Ginecologia
2010;53:44653.
23 Suikkari AM, Jalkanen M, Heiskala H, Koskela O. Prolonged
pregnancy: induction or observation. Acta Obstet Gynecol Scand
Suppl 1983;116:58.
24 Boulvain M, Senat M-V, Rozenberg P, Irion O. Induction of labor or
expectant management for large-for-dates fetuses: a randomized
controlled trial. Am J Obstet Gynecol 2012;206(S1):2.
25 Dodd JM, Crowther CA, Haslam RR, Robinson JS. Timing of birth for
women with a twin pregnancy at term: a randomised controlled
trial. BMC pregnancy childbirth 2010;10:68.
26 Dodd JM, Crowther CA, Haslam RR, Robinson JS. Elective birth at
37 weeks of gestation versus standard care for women with an
uncomplicated twin pregnancy at term: the twins timing of birth
randomised trial. BJOG 2012;119:96473.
27 Egarter C, Koer E, Fitz R, Husslein P. Is induction of labor indicated
in prolonged pregnancy? Results of a prospective randomised trial
Gynecol Obstet Invest 1989;27:69.
28 Amano K, Saito K, Shoda T, Tani A, Yoshihara H, Nishijima M.
Elective induction of labor at 39 weeks of gestation: a prospective
randomized trial. J Obstet Gynaecol Res 1999;25:337.
29 Augensen K, Bergsjo P, Eikeland T, Askvik K, Carlsen J. Randomised
comparison of early versus late induction of labour in post-term
pregnancy. Br Med (Clin Res Ed) 1987;294:11925.
2013 RCOG 683
Induction of labour and caesarean section
30 Bergsjo P, Gui-dan H, Su-qin Y, Zhi-zeng G, Bakketeig LS.
Comparison of induced versus non-induced labor in post-term
pregnancy. A randomized prospective study. Acta Obstet Gynecol
Scand 1989;68:6837.
31 Cardozo L, Fysh J, Pearce JM. Prolonged pregnancy: the
management debate. BMJ 1986;293:105963.
32 Chanrachakul B, Herabutya Y. Postterm with favorable cervix: is
induction necessary? Eur J Obstet Gynecol Reprod Biol
2003;106:1547.
33 Cole RA, Howie PW, Macnaughton MC. Elective induction of
labour. A randomised prospective trial. Lancet 1975;1:76770.
34 Dyson DC, Miller PD, Armstrong MA. Management of prolonged
pregnancy: induction of labor versus antepartum fetal testing. Am J
Obstet Gynecol 1987;156:92834.
35 Gelisen O, Caliskan E, Dilbaz S, Ozdas E, Dilbaz B, Ozdas E, et al.
Induction of labor with three different techniques at 41 weeks of
gestation or spontaneous follow-up until 42 weeks in women with
denitely unfavorable cervical scores. Eur J Obstet Gynecol Reprod
Biol 2005;120:1649.
36 Hannah ME, Hannah WJ, Hellmann J, Hewson S, Milner R, Willan A.
Induction of labor as compared with serial antenatal monitoring in
post-term pregnancy. A randomized controlled trial. The Canadian
multicenter post-term pregnancy trial group. N Engl J Med
1992;326:158792.
37 Heden L, Ingemarsson I, Ahlstrom H, Solum T. Induction of labor
versus conservative management in prolonged pregnancy: controlled
study. International Journal of Feto-Maternal Medicine 1991;4:2316.
38 Heimstad R, Skogvoll E, Mattsson L-A, Johansen OJ, Eik-Nes SH,
Salvesen KA. Induction of labor or serial antenatal fetal monitoring
in postterm pregnancy: a randomized controlled trial. Obstet
Gynecol 2007;109:60917.
39 Henry GR. A controlled trial of surgical induction of labour and
amnioscopy in the management of prolonged pregnancy. J Obstet
Gynaecol Br Commonw 1969;76:7958.
40 Herabutya Y, Prasertsawat PO, Tongyai T, Isarangura Na Ayudthya
N. Prolonged pregnancy: the management dilemma. Int J Gynaecol
Obstet 1992;37:2538.
41 James C, George SS, Gaunekar N, Seshadri L. Management of
prolonged pregnancy: a randomized trial of induction of labour and
antepartum foetal monitoring. Natl Med J India 2001;14:2703.
42 Katz Z, Yemini M, Lancet M, Mogilner BM, Ben-Hur H, Caspi B.
Non-aggressive management of post-date pregnancies. Eur J Obstet
Gynecol Reprod Biol 1983;15:719.
43 Martin DH, Thompson W, Pinkerton JH, Watson JD. A randomized
controlled trial of selective planned delivery. Br J Obstet Gynaecol
1978;85:10913.
44 Martin JNJr, Sessums JK, Howard P, Martin RW, Morrison JC.
Alternative approaches to the management of gravidas with
prolonged-postterm-postdate pregnancies. J Miss State Med Assoc
1989;30:10511.
45 McNellis D, Medearis AL, Fowler S, Romero R, Sibai BM, Caritis SN,
et al. A clinical trial of induction of labor versus expectant
management in postterm pregnancy: the national institute of child
health and human development network of maternal-fetal medicine
units. Am J Obstet Gynecol 1994;170:71623.
46 Nielsen PE, Howard BC, Hill CC, Larson PL, Holland RH, Smith PN.
Comparison of elective induction of labor with favorable Bishop
scores versus expectant management: a randomized clinical trial. J
Matern Fetal Neonatal Med 2005;18:5964.
47 Ohel G, Rahav D, Rothbart H, Ruach M. Randomised trial of
outpatient induction of labor with vaginal PGE2 at 40-41 weeks of
gestation versus expectant management. Arch Gynecol Obstet
1996;258:10912.
48 Roach VJ, Rogers MS. Pregnancy outcome beyond 41 weeks
gestation. Int J Gynaecol Obstet 1997;59:1924.
49 Sande HA, Tuveng J, Fonstelien T. A prospective randomized study
of induction of labor. Int J Gynecol Obstet 1983;21:3336.
50 Tylleskar J, Finnstrom O, Leijon I. Spontaneous labor and elective
induction - a prospective randomized study. I. Effects on mother
and fetus. Acta Obstet Gynecol Scand 1979;58:5138.
51 Witter FR, Weitz CM. A randomized trial of induction at 42 weeks
gestation versus expectant management for postdates pregnancies.
Am J Perinatol 1987;4:20611.
52 Gonen O, Rosen DJD, Doln Z, Tepper R, Markov S, Fejgin MD.
Induction of labor versus expectant management in macrosomia: a
randomized study. Obstet Gynecol 1997;89:9137.
53 Kjos SL, Henry OA, Montoro M, Buchanan TA, Mestman JH.
Insulin-requiring diabetes in pregnancy: a randomized trial of active
induction of labor and expectant management. Am J Obstet
Gynecol 1993;169:6115.
54 Ek S, Andersson A, Johansson A, Kublicas M. Oligohydramnios in
uncomplicated pregnancies beyond 40 completed weeks. A
prospective, randomised, pilot study on maternal and neonatal
outcomes. Fetal Diagn Ther 2005;20:1825.
55 Suzuki S, Otsubo Y, Sawa R, Yoneyama Y, Araki T. Clinical trial of
induction of labor versus expectant management in twin pregnancy.
Gynecol Obstet Invest 2000;49:247.
56 Boers KE, Vijgen SM, Bijlenga D, van der Post JA, Bekedam DJ,
Kwee A, et al. Induction versus expectant monitoring for
intrauterine growth restriction at term: randomised equivalence trial
(DIGITAT). BMJ 2010;341:c7087.
57 van den Hove MM, Willekes C, Roumen FJ, Scherjon SA. Intrauterine
growth restriction at term: induction or spontaneous labour? Dis-
proportionate intrauterine growth intervention trial at term (DIGITAT): a
pilot study Eur J Obstet Gynecol Reprod Biol 2006;125:548.
58 Koopmans CM, Bijlenga D, Groen H, Vijgen SM, Aarnoudse JG,
Bekedam DJ, et al. Induction of labour versus expectant monitoring
for gestational hypertension or mild pre-eclampsia after 36 weeks
gestation (HYPITAT): a multicentre, open-label randomised
controlled trial. Lancet 2009;374:97988.
59 Nicholson JM, Parry S, Caughey AB, Rosen S, Keen A, Macones GA.
The impact of the active management of risk in pregnancy at term
on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol
2008;198:5115.
60 Cheng YW, Kaimal AJ, Snowden JM, Nicholson JM, Caughey AB.
Induction of labor compared to expectant management in low-risk
women and associated perinatal outcomes. Am J Obstet Gynecol
2012;207:5028.
61 Stock SJ, Ferguson E, Duffy A, Ford I, Chalmers J, Norman JE.
Outcomes of elective induction of labour compared with expectant
management: population based study. BMJ 2012;344:e2838.
62 Goeree R, Hannah M, Hewson S. Cost-effectiveness of induction of
labour versus serial antenatal monitoring in the Canadian
multicentre postterm pregnancy trial. CMAJ 1995;152:144550.
63 Vijgen SM, Koopmans CM, Opmeer BC, Groen H, Bijlenga D,
Aarnoudse JG, et al. An economic analysis of induction of labour
and expectant monitoring in women with gestational hypertension
or pre-eclampsia at term (HYPITAT trial). BJOG 2010;117:157785.
64 Alrevic Z, Kelly AJ, Dowswell T. Intravenous oxytocin alone for
cervical ripening and induction of labour. Cochrane Database of Syst
Rev 2009;(4):CD003246.
65 Menticoglou SM, Hall PF. Routine induction of labour at 41 weeks
gestation: nonsensus consensus. BJOG 2002;109:48591.
66 Melamed N, Yogev Y, Meizner I, Mashiach R, Ben-Haroush A.
Sonographic prediction of fetal macrosomia: the consequences of
false diagnosis. J Ultrasound Med 2010;29:22530.
684 2013 RCOG
Wood et al.
67 Naylor CD, Sermer M, Chen E, Sykora K. Cesarean delivery in
relation to birth weight and gestational glucose tolerance:
pathophysiology or practice style? Toronto trihospital gestational
diabetes investigators JAMA 1996;275:116570.
68 Ioannidis JPA. Why most published research ndings are false. PLOS
Med 2005;2:0696701.
69 Bishop EH. Pelvic scoring for elective induction. Obstet Gynecol
1964;24:2668.
70 Laughon SK, Zhang J, Troendle J, Sun L, Reddy UM. Using a simplied
Bishop score to predict vaginal delivery. Obstet Gynecol 2011;117:80511.
71 Smith GC, Celik E, To M, Khouri O, Nicolaides KH, Fetal Medicine
Foundation Second Trimester Screening Group. Cervical length at
mid-pregnancy and the risk of primary cesarean delivery. N Engl J
Med 2008;358:134653.
72 Chaillet N, Dumont A. Evidence-based strategies for reducing
cesarean section rates: a meta-analysis. Birth 2007;34:5364.
Mini commentary on Does induction of labour increase the risk of
caesarean section? A systematic review and meta-analysis of trials
in women with intact membranes
S Downe
Research in Childbirth and Health Group, University of Central Lancashire, Preston, UK
There is global interest in reducing cae-
sarean section rates. As Wood and col-
leagues note, studies of induction of
labour have variously reported both
increased and decreased caesarean rates.
The authors have undertaken a careful
and thorough meta-analysis, and have
shown consistent results in favour of
labour induction; however, they are jus-
tiably cautious about the policy impli-
cations of their ndings, on the basis
that the results may arise from
non-treatment effects. They propose
more better-designed studies. Very
importantly, they note the need for
future research to include cost-effective-
ness analyses, and an assessment of
womens views and experiences.
Apart from these factors, future stud-
ies should also assess unanticipated
long-term outcomes for mother and
baby. For example, there is growing evi-
dence that so-called late prematurity
(3738 weeks of gestation) may be
linked to a range of adverse outcomes for
infants in the longer term (Boyle et al.
BMJ 2012;344:e896). This is important,
given the known margin of error in dat-
ing of any particular pregnancy. Factors
that may independently affect labour
management decisions (and, conse-
quently, policy implementation deci-
sions) should also be taken into account.
For example, a study of associations
between induction of labour and rates of
caesarean section in the USA found that
the results varied with sociodemograph-
ics (parity, age, race, and education),
maternal behaviours (number of prena-
tal visits), and, intriguingly, service
design factors, such as hospital teaching
status and ownership (Wilson et al. J
Nurs Scholarship 2010;42:130138).
Wood et al. comment that induction
of labour seems to be the only technique
that has successfully reduced caesarean
section in the context of a randomised
controlled trial (RCT). This is not, in
fact, the case. The current Cochrane
review of continuous labour support
(Hodnett et al. Cochrane Database Syst
Rev 2012: art. no.: CD000012. DOI 10.
1002/14651858.CD000012.pub4) shows a
reduction in caesarean section rate that
is very similar to that found by Wood
et al. (OR 0.78, 95% CI 0.670.91).
RCTs of place of birth, and, particularly,
home birth, are notoriously hard to set
up. In the next-best approach, the popu-
lation-based birthplace study found very
signicant reductions in caesarean sec-
tion for planned birth centres or home
births, when compared with hospital
births [ranging from an adjusted OR of
0.31 (95% CI 0.230.41) for a planned
homebirth to 0.39 (95% CI 0.290.53)
for a planned birth in a birth centres],
with no increase in adverse outcomes,
except among neonates born at home to
primiparous women. These data suggest
that the mechanism that underlies high
and rising caesarean section rates is likely
to include local childbirth philosophies
and management approaches, as much
as maternal and fetal physiology.
In conclusion, in addition to the fac-
tors suggested by Wood et al., future
studies of the impact of induction of
labour on caesarean section rates should
take into account the contextual factors
and longer-term outcome measures
identied above. Indeed, it may be pre-
mature to undertake such studies at all,
until there is a more precise understand-
ing of the mechanisms that underpin
high and rising caesarean section rates,
and the consequent identication of fac-
tors that could plausibly be addressed by
additional interventions such as contin-
uous labour support, place of birth, and
labour induction.
Disclosure of interests
I am a co-author on the current Coch-
rane review of alternative versus con-
ventional institutional settings for
birth, and of a structured review of the
outcomes of free-standing, midwife-led
birth centres. I was the founding Chair
of the Royal College of Midwives Cam-
paign for Normal Birth. I have no
nancial interests in any of the issues
discussed in the commentary above.&
2013 RCOG 685
Induction of labour and caesarean section