REVIEW ARTICLE
Induction of labor versus expectant management for post-datepregnancy: Is there sufficient evidence for a change in clinical practice?
ULLA-BRITT WENNERHOLM1, HENRIK HAGBERG1, BENGT BRORSSON2 &
CHRISTINA BERGH1
1Department of Obstetrics and Gynecology, the Institute of Clinical Sciences, Sahlgrenska University Hospital, Goteborg,
Sweden, and 2Department of Public Health and Caring Sciences, Akademiska sjukhuset, Uppsala, Sweden
AbstractObjectives. To compare perinatal and maternal outcomes between elective induction of labor versus expectant managementof pregnancies at 41 weeks and beyond. Design. Systematic review and meta-analysis. Methods. We searched PubMed,CINAHL, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effectiveness (DARE)and PsycINFO (1980 to November, 2007). Inclusion criteria were systematic reviews and randomized controlled trialscomparing elective induction of labor versus expectant management of pregnancies at 41 weeks and beyond. Three or morereviewers independently read and evaluated all selected studies. Data were extracted and analyzed using Review ManagerSoftware. Main outcome measures. Perinatal mortality. Results. Thirteen trials fulfilled the inclusion criteria for the meta-analysis. Elective induction of labor was not associated with lower risk of perinatal mortality compared to expectantmanagement (relative risks (RR): 0.33; 95% confidence intervals (CI): 0.10�1.09). Elective induction was associated with asignificantly lower rate of meconium aspiration syndrome (RR: 0.43; 95% CI: 0.23�0.79). More women randomized toexpectant management were delivered by cesarean section (RR: 0.87; 95% CI: 0.80�0.96). Conclusions. The meta-analysisillustrated a problem with rare outcomes such as perinatal mortality. No individual study with adequate sample size has beenpublished, nor would a meta-analysis based on the current literature be sufficient. The optimal management of pregnanciesat 41 weeks and beyond is thus unknown.
Key words: Post-term pregnancy, full-term pregnancy, induced labor, expectant management, perinatal death, meta-analyses
Introduction
Term pregnancy is defined as a pregnancy lasting
between 37 completed weeks and 41 weeks �6 days.
Pregnancies that reach or continue beyond 294 days
(42 gestational weeks) are described as post-term.
Five to ten percent of all pregnancies have been
considered post-term depending on diagnostic cri-
teria, dating policy and population investigated, but
the occurrence is declining in North America,
Australia and Europe, with the lowest recently
reported rate in Austria (0.4%) and the highest in
Denmark (8.1%) (1�3). This huge variation in post-
term pregnancy rate is also dependent on different
intervention strategies.
Post-term pregnancy conveys an increased risk of
perinatal mortality that is small in absolute terms
(4), but quite substantial (3- to 4-fold) if expressed
in relative numbers per fetus exposed in ongoing
pregnancies, rather than per delivery at each gesta-
tional week (4,5). The risk is particularly enhanced
for primiparas and in pregnancies complicated by
intrauterine growth restriction (4,6). There is also
an increased risk of low Apgar scores at 5 min (7),
encephalopathy (8) and admission to intensive care
(9) in post-term pregnancies, whereas no such
association has been observed for cerebral palsy
(10). At as early as 41 completed weeks an
increased risk of adverse neonatal outcomes has
Correspondence: Ulla-Britt Wennerholm, Department of Obstetrics and Gynecology, the Institute of Clinical Sciences, Sahlgrenska University Hospital, SE
416 85 Goteborg, Sweden. E-mail: [email protected]
Acta Obstetricia et Gynecologica. 2009; 88: 6�17
(Received 1 July 2008; accepted 26 September 2008)
ISSN 0001-6349 print/ISSN 1600-0412 online # 2009 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
DOI: 10.1080/00016340802555948
Acta Obstetricia et Gynecologica. 2009; 88: 6�17
(Received 1 July 2008; accepted 26 September 2008)
ISSN 0001-6349 print/ISSN 1600-0412 online # 2009 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
DOI: 10.1080/00016340802555948
been observed (5,6,11). The management of post-
term uncomplicated pregnancies is controversial.
Two major approaches have been employed: elec-
tive induction of labor at 41�42 weeks, and
expectant management with intermittent fetal mon-
itoring (e.g. cardiotocography, biophysical profile)
and selective induction of labor. These two man-
agements have been compared in randomized
controlled trials (RCT), and summarized and
evaluated in meta-analyses (Table I). According to
the most recent meta-analysis (12), significantly
lower perinatal mortality was found in the elective
induction arm, which has shifted practice in Europe
and North America (13) favoring elective induction
at 41�42 gestational weeks. However, most of the
RCTs included a limited number of women and
none of the RCTs was powered for evaluation of
perinatal mortality. Some of the studies were made
during the 1970s before the introduction of ultra-
sound dating, and some also included women who
were neither post-term nor close to post-term. The
studies utilized highly variable modes of fetal
surveillance in the expectant arm. Since the Co-
chrane review, another large, well-designed and
meticulously performed RCT (14) has been pub-
lished.
The aim of this study was to evaluate elective
induction of labor versus expectant management,
strictly including pregnancies of 41 weeks or beyond,
and including additional RCTs published after the
latest meta-analysis.
Material and methods
Search strategy/sources
We searched the PubMed, CINAHL, Cochrane
Database of Systematic Reviews, DARE and
PsycInfo databases for RCT and systematic reviews
published from 1980 to 19 November, 2007, using
the following words: (Meta-Analysis[ptyp] or Ran-
domised Controlled Trial[ptyp] or Controlled Clin-
ical Trial[ptyp]) and (induced labor or induction or
‘expectant management’) and (full-term pregnanc*
or full term pregnanc* or fullterm pregnanc* or
post-date deliver* or post date deliver* or postdate
deliver* or post-term pregnanc* or post term preg-
nanc*or postterm pregnanc* or prolonged preg-
nancy) and (perinatal death or fetal death or
intrauterine death or infant mortality or encephalo-
pathy or hypoxic-ischemic encephalopathy or cere-
bral palsy or meconium aspiration or Apgar or
attitudes or experiences or outcome).
The reference lists of identified studies were
searched manually.
Selection and validity assessment
RCTs and systematic reviews with induction of labor
at 41 weeks of gestation or more versus expectant
management were included. Studies published be-
fore 1980, when ultrasound dating was introduced,
were excluded, since this procedure changed the
precision in dating. We also excluded abstracts and
studies published in languages other than English,
assuming that the highest quality studies are pub-
lished as full articles and in English. We selected
trials assessing at least one of the following out-
comes: perinatal death, intrauterine fetal death, early
neonatal death, asphyxia, Apgar score B7 at 5 min,
meconium aspiration, admission to neonatal inten-
sive care unit, birthweight, cesarean section, assisted
vaginal delivery, perineal injury, postpartum hemor-
rhage and maternal satisfaction with the used
method.
Table I. Results from systematic reviews/meta-analyses comparing planned induction of labor at 41 weeks or later with expectant
management.
Myers et al. (AHRQ) (22).
Systematic review: 17
RCTs
Sanchez-Ramos et al. (23).
Meta-analysis: 16 RCTs;
OR; 95% CI
Gulmezoglu et al.* (12).
Meta-analysis: 19 RCTs;
RR; 95% CI
Wennerholm et al. (43).**
Meta-analysis: 13 RCTs;
RR; 95% CI
Perinatal death Favors labor induction 0.41; 0.14�1.18 0.30; 0.09�0.99 0.33; 0.10�1.09
Meconium aspiration
syndrome
No preference 0.46; 0.18�1.21 0.39; 0.21�0.75 0.43; 0.23�0.79
Cesarean delivery No preference 0.88; 0.78�0.99 41 weeks: 0.92; 0.76�1.12***;
42 weeks: 0.97; 0.72�1.31***
0.87; 0.80�0.96
*Seven studies (36�42) included in Gulmezoglu et al. (12) were excluded in Wennerholm et al. (43). Reasons for exclusions: interventions
before 41 weeks (36�38); published 1969 (39); published as abstracts (40,41); non-English language publication (42).
**One study (14) included in Wennerholm et al. (43) was not included in Gulmezoglu et al. (12).
***Pooled data for 41 and 42 weeks not available.
Induction of labor for post-date pregnancy 7
Validity of trials fulfilling inclusion criteria was
assessed using the JAMA validity score, the Swedish
Council on Technology Assessment in Health
Care (SBU) and the CONSORT checklist (15�18).
Criteria included external validity (eligibility, con-
secutive patients, patient number and reason for
non-participation, exclusion criteria clearly stated)
and internal validity (randomization procedure,
comparability of groups, blinding, compliance,
losses to follow-up, evaluation of outcome and side
effects, intention to treat) and precision (study
power). Quality rating was given for each study
according to SBU criteria, i.e. high, fair and poor.
Each reviewer independently assessed the validity of
included articles. Each article was assessed by at
least three reviewers. Two reviewers (UBW, CB)
extracted data. Disagreements were solved by dis-
cussion.
Potentially relevant titles identified after literature search (n= 69)
Titles excluded (n= 48) Inappropriate clinical question (trial of cervical ripening and not induction of labour, trial of two forms of induction of labour etc) (n=38) Data on pregnancies < 41 weeks (n=7) Non-English literature (n=1) Only published as abstracts (n=2)
Titles potentially appropriate (n=21) Titles excluded (n= 4) Alternate allocation trial (n=3) Quasi-randomised (n=1)
Articles with useful information (n=17) Randomised controlled trials included in meta-analysis (n=13, 14 articles) Systematic reviews (n=3)
Figure 1. Study selection process.
Figure 2. Labour induction versus expectant management at �41 weeks: Outcome: perinatal death.
8 U.-B. Wennerholm et al.
Analysis strategy
Statistical analyses were conducted using the Review
Manager Software (Rev Man 2003). We analyzed
categorical data using relative risks (RR) and 95%
confidence intervals (CI). For continuous outcomes,
we used weighted mean differences (WMD). We
assessed statistical heterogeneity between trials using
both the chi-squared test and the I2 statistic (19).
Where there was no statistical heterogeneity (p�0.1,
I2B25%), we pooled data using a fixed model.
Publication biases were checked using a funnel plot
(20). Subgroup analyses were performed for gesta-
tional age 41�0 and beyond and 42�0 and beyond,
respectively. Since management of induction differed
between the intervention and control group in the
largest study, the Canadian Multicenter Post-term
Pregnancy Trial (21), sensitivity analysis was carried
out excluding this trial. Ethical approval was not
required.
Results
Seventeen relevant publications were identified
(12,14,21�35). Three of these were systematic re-
views (12,22,23) and 14 were reports from RCTs
(14,21,24�35) (Tables I and II; Figure 1). Results
from one trial was reported in two publications
(14,29). Thus, results from 13 trials were used in
the meta-analyses. Excluded publications and rea-
sons for exclusion are given in Figure 1. In parti-
cular, articles included in the Cochrane review but
excluded in the present meta-analysis are specified in
Table I (36�42).
Descriptive data for each trial are presented in
Table II. Included trials were published between
1987 and 2007. The number of subjects in each trial
varied between 22 (32) and 3,418 (21).
Results are presented in Figures 2�12. A compar-
ison with previously performed meta-analyses is
presented in Table I.
Effects on perinatal mortality
There was no statistically significant difference in
perinatal deaths between the induction of labor and
expectant management groups (RR: 0.33, 95% CI:
0.10�1.09) (11 studies) (Figure 2). There was one
perinatal death in the induction of labor group and
eight in the expectant management group. There
were three perinatal deaths due to congenital
anomalies, one in the induction of labor and two in
the expectant management group. Of the eight
perinatal deaths observed in the expectant manage-
ment group, three were intrauterine fetal deaths
(Figure 3) and five occurred in the first seven days
of life (Figure 4). The perinatal death in the
induction of labor group occurred in the first seven
days of life.
Effects on other perinatal outcomes
Induction of labor was associated with fewer infants
with meconium aspiration syndrome compared with
expectant management (RR: 0.43; 95% CI: 0.23�0.79) (seven studies; Figure 5). There were no
significant differences in newborns with birth as-
phyxia (two studies; Figure 6), low Apgar scores (B7
at 5 min) (nine studies; Figure 7) or in intensive
care unit admissions (eight studies; Figure 8) be-
tween induction of labor or expectant management
groups. Newborns in the induction of labor group
had lower mean birthweight (WMD: �44.41; 95%
CI: �79.37 to �9.45) (eight studies; Figure 9).
Effects on cesarean delivery and assisted vaginal delivery
All 13 trials reported on cesarean deliveries. Women
in the induction of labor group were less likely to
have undergone a cesarean section than women in
the expectant management group (RR: 0.87; 95%
CI: 0.80�0.96) (Figure 10). Seven trials reported on
assisted vaginal delivery. There was no statistical
difference in the risk of assisted vaginal delivery
(Figure 11). When performing a sensitivity analysis
after excluding the Canadian Multicenter Post-term
Pregnancy Trial (21), no significant difference was
found for cesarean delivery rates between the two
groups (RR: 0.88; CI: 0.77�1.01).
Maternal complications and potential benefits
A few studies reported on maternal complications
such as postpartum hemorrhage, perineal trauma
and endometritis. No significant differences were
found for any of these maternal complications. Most
studies did not report individual data, making it
impossible to perform a meta-analysis on maternal
complications. Only one trial measured maternal
satisfaction. Maternal satisfaction was statistically
significantly higher in the induction of labor group
(Figure 12).
Subgroup analysis
In the 41-week group, induction of labor signifi-
cantly reduced the risk of meconium aspiration
syndrome (RR: 0.35; CI: 0.16�0.75) (five trials;
Figure 5). Women in the 41-week group whose labor
was induced were less likely to have undergone a
Induction of labor for post-date pregnancy 9
Table II. Characteristics of included randomized controlled trials and quality rating.
Trial, year Country No. of women
Definition of
post-date (d) Methods of induction Monitoring of control group
Quality
rating
Augensen, 1987 (24) Norway 409 290 Oxytocin infusion and amniotomy NST twice weekly Poor
Bergsjo, 1989 (25) China 188 294 Membrane stripping, oxytocin infusion
and amniotomy
Fetal kick counts, atropine test,
ultrasound and urinary estriol
Poor
Chanrachakul, 2003 (26) Thailand 249 290 Amniotomy and oxytocin infusion NST and AFI once weekly, twice
weekly after 43 weeks
Poor
Dyson, 1987 (27) USA 302 287 PGE2 gel intravaginally (3 mg) or PGE2
gel (0.5 mg) intracervically; and oxytocin
infusion with amniotomy
NST twice weekly, AFI weekly
between 41 and 42 weeks and twice
weekly after 42 weeks
Poor
Gelisen, 2005 (28) Turkey 600 287 Misoprostol 50 mg intravaginally every 6
h�3 and amniotomy and oxytocin infusion
or oxytocin infusion or Foley catheter with
balloon above the internal cervical os filled
with 50 ml saline and oxytocin infusion
NST and AFI twice weekly and BPP
once 3�5 days after randomization
Poor
Hannah, 1992 (21) Canada 3407 287 PGE2 gel (0.5 mg) intracervically, every 6
h�3 and/or oxytocin infusion/amniotomy
or both
Fetal kick counts daily, NST three
times weekly and AFI two to three
times weekly
Fair
Heimstad, 2007a,b (14,29) Norway 508 289 Misoprostol 50 ug intravaginally every 6 h or
PGE2 gel (0.5 mg) intracervically every 12 h
during 2 days or amniotomy and oxytocin
infusion
AFI, and NST every third day Fair
Herabutya, 1992 (30) Thailand 108 294 PGE2 gel (0.5 mg) intracervically every 6 h
and maximum three times, and amniotomy/
oxytocin or both
NST once weekly and twice weekly
after 43 weeks
Poor
James, 2001 (31) India 74 287 Extra-amniotically placed Foley catheter
with balloon filled with 20 ml saline if
Bishop score B5; if �5 membrane
stripping, after 12 h amniotomy, and
oxytocin infusion
Fetal kick counts daily and BPP on
alternate days
Poor
Martin, 1989 (32) USA 22 287 Laminaria tents and oxytocin infusion NST and AFI weekly Poor
NICHHD, 1994 (33) USA 440 287 PGE2 (0.5 mg) or placebo gel intracervically,
amniotomy and oxytocin infusion
NST and AFI twice weekly Fair
Roach, 1997 (34) Hong Kong 201 294 PGE2 pessaries (3 mg) vaginally every 6 h NST twice weekly and AFI once
weekly
Poor
Witter, 1987 (35) USA 200 294 Oxytocin and amniotomy Urinary estriol twice a week and
three times a week after 43 weeks
Poor
NST, non-stress test; AFI, amniotic fluid index; PGE2, prostaglandin E2; BPP, biophysical profile.
10
U.-B
.W
ennerh
olmet
al.
cesarean section than women with expectant
management (RR: 0.87; CI: 0.79�0.96) (nine trials;
Figure 10). Newborns in the 42-week induction
of labor group had lower mean birthweight (WMD
�101.58; 95% CI: �179.01 to �24.15) (three
studies; Figure 9). The gestational age subgroup
analysis did not show any other significant differ-
ences.
Figure 3. Labour induction versus expectant management at �41weeks. Outcome Intrauterine fetal death.
Figure 4. Labour induction versus expectant management at �41weeks. Outcome Early neonatal death (B7 days).
Induction of labor for post-date pregnancy 11
Discussion
The main finding in this meta-analysis is that there is
no significant difference in perinatal mortality be-
tween induction of labor at 41 weeks’ gestation or
later as compared to expectant management. These
results differ from the recent review by Gulmezoglu
et al. published in the Cochrane Collaboration (12),
where significantly lower perinatal mortality for
elective induction in pregnancies beyond 37 weeks
was found, however close to unity (RR: 0.30; 95%
CI: 0.09�0.99). Our results differ from that review
because of different selection criteria for the in-
cluded trials. We regarded it as more appropriate to
include only studies of 41 weeks or beyond, i.e. a
point in time where perinatal problems are known to
increase (5,6,11), since this is where discussion
about induction is focused today. We also excluded
two studies (40,41) published only as abstracts, one
study not published in English (42) and one study
published in 1969 (39) (Table I). These exclusions
fulfilled our exclusion criteria determined in advance
for this systematic review.
In our meta-analysis, no individual study reached
a level of high quality concerning validity and
precision, and only three trials (14,21,33) reached
a level of fair quality. Most studies were assessed as
being of poor quality, in spite of a randomized
design. This meta-analysis demonstrates the pro-
blems that arise when the primary outcome is a rare
event. A total of nine perinatal deaths occurred
among 6,617 newborns. Some studies included
perinatal deaths where the child had a severe
congenital malformation, while other studies ex-
cluded these newborns. It is clear that an additional
few perinatal deaths in either group may reverse the
risk. It can be noted that observations from a large
registry study from Sweden (4) indicated an in-
creased risk for stillbirth with gestational age for
primiparous but not for multiparous women. No
Figure 5. Labour induction versus expectant management at �41weeks: Outcome Meconium aspiration.
Figure 6. Labour induction versus expectant management at �41weeks: Outcome Asphyxia.
12 U.-B. Wennerholm et al.
subgroup analysis for parity was performed in the
studies included in this systematic review depending
on the limited number of perinatal deaths.
In this meta-analysis, we also found that induction
of labor compared with expectant management was
associated with a significantly lower risk of meco-
nium aspiration syndrome. However, meconium
aspiration syndrome is a poor indicator of neonatal
stress, and most newborns with meconium aspira-
tion syndrome recover and remain healthy.
The finding that the cesarean delivery rate was
significantly lower in the induction group might be
unexpected. In the largest trial in this meta-analysis,
the Canadian Multicenter Post-term Pregnancy
Trial (21), a significantly lower cesarean delivery
rate was also seen in the induction group, probably
Figure 7. Labour induction versus expectant management at �41weeks: Outcome Apgar score B7 at 5 min.
Figure 8. Labour induction versus expectant management at �41weeks: Outcome Admission to neonatal intensive care unit.
Induction of labor for post-date pregnancy 13
owing to different types of management of pregnan-
cies in the two groups, as discussed by the authors.
No prostaglandin was used in the expectant manage-
ment group. When we did a sensitivity analysis from
which the Canadian trial was excluded, a significant
difference in cesarean delivery rates between the two
groups was no longer detected.
Only one recent study investigated maternal
satisfaction (29). Women preferred induction of
labor to serial antenatal monitoring beyond 41 weeks
(74 vs 38% of the women said they would prefer the
same management in a subsequent pregnancy).
The main strength of this study was the restriction
to trials that only included pregnancies of 41 weeks
or more, which is a time point where neonatal
problems are known to arise. The weaknesses of
our conclusions are closely linked with the weak-
nesses of the individual trials, e.g. the poor quality of
Figure 9. Labour induction versus expectant management at �41weeks: Outcome: Birth weight.
Figure 10. Labour induction versus expectant management at �41weeks: Outcome: Caesarean section.
14 U.-B. Wennerholm et al.
most of the studies included, owing to shortcomings
in external and internal validity and small sample
sizes.
In conclusion, the present meta-analysis did not
demonstrate that there is a significant difference in
perinatal mortality when comparing a strategy of
elective induction with one of expectant manage-
ment. A change in attitudes encouraging more
induction may therefore be questionable from a
scientific point of view when the aim is to offer
women treatment according to the best available
evidence. Since no particular management has been
found to be superior from a medical point of view, a
strategy involving either induction or active expecta-
tion could be regarded as relevant and with possibi-
lities for individualization. The number of women
reaching 41 weeks is quite substantial. A change in
policy encouraging induction of labor would require
a huge increase in resources in the delivery wards.
Before advocating such a change in management,
the possibility of performing an adequately powered
randomized trial should be discussed.
Acknowledgements
We thank Anders Flisberg, Lars Ladfors, Therese
Svanberg, Margareta Wennergren and Anna Wess-
berg for their contributions. The study was funded
by grants from Sahlgrenska University Hospital.
Declaration of interest: The authors report no
conflicts of interest. The authors alone are respon-
sible for the content and writing of the paper.
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