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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.
&
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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