DOI: 10.1111/j.1471-0528.2008.02065.

x
www.blackwellpublishing.com/bjog
Systematic review

Indications for induction of labour:

a best-evidence review
E Mozurkewich,a J Chilimigras,a E Koepke,a K Keeton,a VJ Kingb
a Division
of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
b Department of Family Medicine, Oregon Health and Science University, Portland, OR, USA
Correspondence: Dr E Mozurkewich, F4835, PO Box 0264, Mott Hospital, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0264, USA.
Email mozurk@umich.edu

Accepted 2 November 2008. Published Online 4 February 2009.

Background Rates of labour induction are increasing. we included the best evidence available from smaller randomised
trials and observational studies.
Objectives To review the evidence supporting indications for
induction. Main results We included 34 full text articles. For each indication,
we assigned levels of evidence and grades of recommendation
Search strategy We listed indications for labour induction and
based upon the GRADE system. Recommendations for induction
then reviewed the evidence. We searched MEDLINE and the
of labour for post-term gestation, PROM at term, and premature
Cochrane Library between 1980 and April 2008 using several terms
rupture of membranes near term with pulmonary maturity are
and combinations, including induction of labour, premature
supported by the evidence. Induction for IUGR before term
rupture of membranes, post-term pregnancy, preterm prelabour
reduces intrauterine fetal death, but increases caesarean deliveries
rupture of membranes (PROM), multiple gestation, suspected
and neonatal deaths. Evidence is insufficient to support induction
macrosomia, diabetes, gestational diabetes mellitus, cardiac disease,
for women with insulin-requiring diabetes, twin gestation, fetal
fetal anomalies, systemic lupus erythematosis, oligohydramnios,
macrosomia, oligohydramnios, cholestasis of pregnancy, maternal
alloimmunization, rhesus disease, intrahepatic cholestasis of
cardiac disease and fetal gastroschisis.
pregnancy (IHCP), and intrauterine growth restriction (IUGR). We
performed a review of the literature supporting each indication. Authors’ conclusions Research is needed to determine risks and
benefits of induction for many commonly advocated clinical
Selection criteria We identified 1387 abstracts and reviewed 418
indications.
full text articles. We preferentially included high-quality systematic
reviews or large randomised trials. Where no such studies existed, Keywords Best evidence, indications, induction.

Please cite this paper as: Mozurkewich E, Chilimigras J, Koepke E, Keeton K, King V. Indications for induction of labour: a best-evidence review. BJOG 2009;
116:626–636.

abour rupture of membranes (PROM) at term and fetal mac-

Introduction
rosomia. The goal of this review was to evaluate the evidence
Since the 1980s, rates of induction of labour have steadily supporting each indication for induction of labour.
increased. Induction currently occurs for almost 24% of
infants born between 37 and 41 weeks of gestation in the
Methods
USA.1 Rates of induction have also increased for preterm
gestations.1 In a large United States survey involving 1573 We compiled a list of indications for induction. We compre-
women with singleton gestations, 41% of respondents re- hensively searched the English language literature using
ported undergoing attempted medical induction of labour.2 MEDLINE and the following databases: Cochrane Database
Induction may be advocated to reduce fetal or neonatal of Systematic Reviews, ACP Journal Club, Database of
morbidity and mortality as with post-term pregnancy, oligo- Abstracts of Reviews of Effects, Cochrane Controlled Trials
hydramnios, suspected intrauterine growth restriction Register, Cochrane Methodology Register, NHS National
(IUGR) and fetal gastroschisis, to minimise maternal morbid- Institute for Health Research Health Technology Assessment
ity, as with maternal cardiac disease and pre-eclampsia/ database, and the NHS Economic Evaluation Database. The
eclampsia, or to benefit both mother and fetus as with prel- search covered the period from January 1980 to April 2008.

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 Induction indications: best evidence review

We used combinations of the following search terms: ‘induc- ischaemic encephalopathy, meconium aspiration syndrome,
tion of labor’, ‘indications’, ‘preterm premature rupture of or sepsis.
membranes’, ‘premature rupture of membranes’, ‘post-term Individual study quality ratings were assigned to each
pregnancy’, ‘fetal macrosomia’, ‘gestational diabetes’ or ‘dia- included study and systematic review by two independent
betes’, ‘oligohydramnios’, ‘antepartum testing’, ‘nonstress reviewers (E.M. and J.C.) according to the quality rating
test’ or ‘biophysical profile’, ‘intrauterine growth restriction/ system of the Scottish Intercollegiate Guidelines Network.4
retardation (IUGR)’, ‘small for gestational age’, ‘pregnancy- Differences in quality score assignments were resolved by
induced hypertension’ or ‘preeclampsia’, ‘multiple or twin consensus. When our review found that induction of labour
gestation’, ‘cardiac disease’ or ‘heart disease’, ‘gastroschisis’, resulted in statistical improvement in one of the outcomes of
‘fetal malformations’, ‘heart defects’ or ‘congenital anoma- interest, we calculated the number needed to treat (NNT) or
lies’, ‘alloimmunization’ or ‘Rh disease’. We included studies harm (NNH). This is the number of women who would need
that explored indications for induction of labour compared to undergo induction of labour to result in one fewer or
with expectant management or immediate delivery by caesar- additional case of the designated outcome.5 For each putative
ean section. We excluded trials comparing different methods indication for induction, the overall strength of scientific evi-
of induction of labour or evaluating elective induction of dence supporting this practice was assigned. In evaluating the
labour. Titles and abstracts were reviewed for possible exclu- strength of the evidence for each indication for induction, we
sion by two reviewers (E.M. and J.C.). If both reviewers adhered to the GRADE system6–8 that classifies the overall
excluded a citation, we eliminated that publication from fur- quality of evidence as high, moderate, low, and very low.
ther review. If at least one reviewer included the citation or if Recommendations resulting from this evidence base are clas-
there was insufficient information to make a determination sified as strong or weak based upon the strength of evidence
from the title and abstract, we obtained the full article for and the balance of benefits and harms of a treatment.8
review. Most of the abstracts were excluded because they were To assign a grade of recommendation for each indication,
not on topic, compared different methods of induction, or we assigned one of four categories: ‘net benefits’, in which
were commentaries, letters, or opinions. We also cross- labour induction clearly does more good than harm, ‘trade-
checked the reference lists of all related systematic reviews offs’, in which there are important trade-offs between the
for possible additional studies. benefits and harms, ‘uncertain trade-offs’ in which it is not
All full text articles were independently reviewed by two clear whether labour induction does more good or harm,
authors (E.M. and J.C.) for suitability for inclusion. We fol- and ‘net harm’ in which induction clearly does more harm
lowed the inclusion process outlined by the British Medical than good.8 We classified a recommendation as ‘strong’ if
Journal Clinical Evidence3 for performance of a ‘best evi- the quality of evidence was high and the evidence showed net
dence’ systematic review in the following manner: for each benefit for induction of labour. We classified a recommen-
indication for induction, we included systematic reviews dation as ‘weak’ if the level of the evidence was high but
identified by our search, together with randomised controlled there were important trade-offs between benefits and
trials (RCTs) published after the date of the systematic harms, or if the trade-offs were uncertain or the evidence
reviews’ search dates. We also sought any additional appro- showed no net benefit for induction. We also classified the
priate RCTs that had not been included in the systematic recommendation as ‘weak’ if the level of evidence was mod-
reviews. For indications for which no systematic reviews erate, low or very low. If no evidence existed regarding
existed, we included the best available evidence, including labour induction in a particular clinical circumstance, we
RCTs, non-randomised controlled clinical trials, cohort made no recommendation.
studies, case–control studies, and case series in a hierarchical
manner. For some indications, published studies compared
Results
expectant management with expedited delivery either by induc-
tion or caesarean section. In these cases, we included studies We reviewed 1387 abstracts from electronic database and
comparing expedited delivery to expectant management. bibliographic searches. We retrieved 418 full text articles that
To be included in this review, studies had to report on one were reviewed by the two reviewers. Based on the review
or more of the following outcomes of interest: mode of deliv- strategy and inclusion criteria outlined above, 34 studies were
ery, maternal morbidity, and fetal or neonatal morbidity and included in this review. Included studies are listed in Table 1.
mortality. Maternal morbidity was defined as chorioamnio- The flow of the citations, abstracts and full text articles
nitis, endometritis, transfusion, severe perineal trauma or through the review process is outlined in Figure 1. No studies
prolonged hospitalisation. Neonatal morbidity was defined evaluating induction of labour compared with expectant
as neonatal intensive care unit (NICU) admission, 5-minute management for women with maternal systemic lupus eryth-
Apgar score <7, respiratory distress syndrome (RDS), shoul- ematosis, red cell alloimmunisation, or non-reassuring or
der dystocia, birth injury, meningitis, pneumonia, hypoxic– suspicious antepartum fetal testing were identified. The

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 Mozurkewich et al.

Table 1. Included studies

Author Year Indication Type of study Quality

Sanchez-Ramos et al.9 2003 Post-term pregnancy Meta-analysis High

Gulmezoglu et al.10 2006 Post-term pregnancy Meta-analysis High
Heimstad et al.11 2007 Post-term pregnancy RCT High
Heimstad et al.12 2007 Post-term pregnancy RCT High
Mozurkewich and Wolf13 1997 PROM Meta-analysis High
Lin et al.14 2005 PROM Meta-analysis High
Dare et al.15 2006 PROM Meta-analysis High
da Graca Krupa et al.16 2005 PROM RCT High
Levy et al.17 2007 PROM RCT High
Hartling et al.18 2006 PPROM Meta-analysis High
Sanchez-Ramos et al.19 2002 Macrosomia Meta-analysis High
Irion and Boulvain20 2006 Macrosomia Meta-analysis High
Dodd and Crowther21 2006 Twins Meta-analysis High
Ek et al.22 2005 Oligohydramnios RCT Moderate
Boulvain et al.23 2006 Diabetes Meta-analysis High
Rioseco et al.24 1994 Cholestasis Case–control Moderate
Roncaglia et al.25 2002 Cholestasis Case series Moderate
Oron et al.26 2004 Cardiac disease Cohort Moderate
Rush et al.27 1983 Cardiac disease Case series Low
Sau et al.28 1993 Cardiac disease Case series Low
Odendaal et al.29 1990 Pre-eclampsia RCT Moderate
Sibai et al.30 1994 Pre-eclampsia RCT High
Alexander et al.31 1999 Pre-eclampsia Case series Moderate
Blackwell et al.32 2001 Pre-eclampsia Case series Moderate
Coppage and Polzin33 2002 Pre-eclampsia Case series Moderate
Mashiloane and Moodley34 2002 Pre-eclampsia Case series Moderate
Nassar et al.35 1998 Pre-eclampsia Case series Moderate
Hall et al.36 2001 Pre-eclampsia Case series Moderate
Magann et al.37 1994 Pre-eclampsia Case series Moderate
Tukur et al.38 2007 Eclampsia RCT Low
GRIT Study Group39 2003 IUGR RCT High
Thornton et al.40 2004 IUGR RCT High
van den Hove et al.41 2006 IUGR RCT High
Logghe et al.42 2005 Gastroschisis RCT High

evidence concerning induction of labour in all other circum- authored by Gulmezoglu10 included 12 trials with 5939 sub-
stances of interest is summarised below. jects, conducted between 1969 and 2005, comparing induc-
tion of labour with serial antenatal monitoring at or beyond
Post-term pregnancy 41 completed weeks of gestation (287 days). Of these, there
Our search strategy identified two systematic reviews that were 10 trials in which women were randomised at 41 weeks
combined studies in which women were randomly assigned of gestation and two trials in which women were randomised
to induction of labour by a variety of methods including at 42 weeks of gestation. The combined analysis of data from
membrane stripping, amniotomy, prostaglandin E2 (PGE2) these 12 trials found one fetal or neonatal death in 2986
gel, misoprostol, laminaria, Foley catheter and extra-amniotic pregnancies allocated to induction of labour versus 9 fetal
saline infusion or to expectant management.9,10 Expectant or neonatal deaths among 2953 pregnancies allocated to
management was usually defined as antenatal testing (bio- expectant management (relative risk 0.30, 95% CI: 0.09–
chemical tests or fetal heart rate monitoring and amniotic 0.99, NNT = 369).10 The authors combined six studies includ-
fluid assessment) sometimes followed by induction of labour ing 1713 participants (four involving randomisation at 41
at 42, 43 or 44 weeks. Both systematic reviews support routine weeks and two involving randomisation at 42 weeks) that
induction of labour after 41 or 42 completed weeks of gest- reported the incidence of meconium aspiration syndrome
ation, but differ in their main findings. For the primary in the newborn. Induction of labour was associated with fewer
outcome of perinatal death, the Cochrane systematic review cases of meconium aspiration syndrome than expectant

628 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology
 Induction indications: best evidence review

[22.0%], NNT = 51). In particular, induction of labour was

associated with fewer caesarean deliveries for non-reassuring
1387
abstracts fetal heart rate tracings (143 of 2295 [6.2%] versus 183 of
reviewed 2301 [8.0%], NNT = 58). Although Gulmezoglu found no
difference in caesarean deliveries and Sanchez-Ramos re-
ported a reduction, neither review found that induction of
labour increased caesarean deliveries, even in the subgroup of
969 women with unfavourable cervices.
excluded We identified one RCT published after the systematic
reviews’ search dates. This study, performed in Norway
between 2002 and 2004, randomly assigned 508 women with
singleton gestations at 41 weeks of gestation (289 days) to
labour induction using combinations of amniotomy, oxyto-
418 cin, PGE2 or misoprostol or to serial fetal surveillance until
full text the onset of spontaneous labour, abnormal antenatal assess-
reviewed ment or 300 days of gestation.11 This study found no differ-
ences in fetal or neonatal morbidity or in mode of delivery
between groups. The authors conducted phone interviews of
study participants 6 months after delivery12 and found that
384 74% of participants preferred induction at 41 weeks over
excluded serial antenatal monitoring. Seventy-four percent of women
randomised to induction said they would prefer the same
management in future pregnancies compared with 38% of
women randomly assigned to serial antenatal monitoring.12

34 Summary
included Induction of labour for gestations at or beyond 41 weeks (287
studies days) may reduce perinatal mortality and meconium aspira-
tion syndrome and does not result in more caesarean deliv-
eries than serial antenatal monitoring, even among women
Figure 1. Flow diagram. whose cervix is not favourable for induction. Quality of evi-
dence: High, grade of recommendation for induction of
management (12 of 860 [1.4%] versus 31 of 853 [3.6%]), labour beyond 41 completed weeks: strong.
although this comparison was statistically significant only in
the 41-week subgroup (relative risk 0.29, 95% CI: 0.12–0.68, PROM at term
NNT = 41). The authors found no difference in caesarean Our search identified three systematic reviews of studies eval-
deliveries in 10 trials randomising women at 41 completed uating management of PROM at term.13–15 The systematic
weeks of gestation (559 of 2883 [19.4%] versus 630 of 2872 reviews by Mozurkewich and Wolf13 and by Dare et al.15 com-
[21.9%]) and five trials randomising women at 42 completed pared expedited induction of labour (via oxytocin, PGE2 or
weeks of gestation (110 of 407 [27.3%] versus 111 of 403 caulophyllum) with conservative management. Expedited
[27.5%]). induction was defined as commencing between 2 and 12
The Sanchez-Ramos9 review included 16 studies with 6588 hours after rupture of membranes.13,15 Conservative or expec-
subjects who were randomised to undergo either induction of tant management was usually defined as observation from 24
labour or expectant management at or beyond 41 completed hours to 4 days after rupture of membranes followed by in-
weeks’ of gestation. These studies were published between duction if spontaneous labour did not result.13,15 Mozurkewich
1969 and 2002, and 12 of these studies were also included and Wolf included 23 trials with 7493 participants, while Dare
in the Cochrane review. There were fewer perinatal deaths et al. included 12 trials with 6814 participants. Of these, seven
among pregnancies allocated to induction of labour (3 of studies were included in both reviews. Neither systematic
3159 versus 10 of 3067) although this difference did not reach review found any difference in rates of caesarean delivery or
statistical significance (OR 0.41, 95% CI: 0.14–1.18). Sanchez- neonatal infections.
Ramos also found that a policy of routine induction of labour While Mozurkewich and Wolf analysed outcomes sepa-
resulted in fewer caesarean deliveries than serial antenatal rately by method of labour induction, Dare et al. computed
monitoring (661 of 3292 [20.1%] versus 709 of 3216 outcomes of induction of labour by any method compared

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 Mozurkewich et al.

Table 2. Summary: quality of evidence and grades of recommendation8

Indication Quality of Benefits/harm Grade of

evidence recommendation

Post-term pregnancy High Net benefits Strong

PROM High Net benefits Strong
PPROM Moderate Uncertain trade-offs Weak
Macrosomia Moderate Net harm Weak (against induction)
Twin gestation Low Uncertain trade-offs Weak
Oligohydramnios Low Uncertain trade-offs Weak
Diabetes Moderate Uncertain trade-offs Weak
Cholestasis Very low Uncertain trade-offs Weak
Cardiac disease Very low Uncertain trade-offs Weak
Mild pre-eclampsia No evidence — No recommendation
Severe pre-eclampsia (preterm) induction versus expectant Moderate Uncertain trade-offs Weak (against induction)
Severe pre-eclampsia (preterm) induction versus caesarean section Very low Uncertain trade-offs Weak
Eclampsia (induction versus caesarean section) Low Uncertain trade-offs Weak
IUGR/SGA (preterm) High Trade-offs Weak
IUGR/SGA (term) Low Uncertain trade-offs Weak
Gastroschisis Low Uncertain trade-offs Weak

SGA, small for gestational age.

with expectant management. In this ‘all methods’ analysis, expectant management. Misoprostol also significantly in-
Dare et al.15 found that a policy of expedited labour induc- creased uterine tachysystole, but not hyperstimulation syn-
tions reduced admissions to the NICU from about 17.0 to drome, compared with expectant management or placebo.
12.6% (six studies, 5679 participants, relative risk 0.73, 95% No differences in mode of delivery, caesarean delivery for fetal
CI: 0.58–0.91, NNT = 23). Both systematic reviews found distress, chorioamnionitis, neonatal sepsis or NICU admissions
reduced incidence of chorioamnionitis and endometritis with were found.
expedited induction of labour compared with expectant man- Our search identified two small RCTs comparing induction
agement. For the effect of induction of labour by any method with misoprostol with expectant management that were pub-
on chorioamnionitis, Dare et al. combined 10 studies includ- lished after the systematic reviews’ search dates.16,17 The pri-
ing 6611 women. Induction of labour reduced chorioamnio- mary outcome for the da Graca Krupa16 study, which
nitis from 9.9 to 6.8% (relative risk 0.74, 95% CI: 0.56–0.97, randomised 150 participants to vaginal misoprostol or pla-
NNT = 33). For the outcome of expedited induction of labour cebo, was time to delivery. The authors demonstrated a sig-
by any method on endometritis, Dare et al. combined four nificantly shorter time from recruitment to delivery with
studies including 445 subjects. This comparison found that misoprostol compared with expectant management. Vaginal
induction of labour reduced postpartum endometritis from misoprostol use resulted in significantly fewer caesarean
8.3 to 2.3% (relative risk 0.30, 95% CI: 0.10–0.95, NNT = 17). deliveries than expectant management (20 versus 30.7%),
Dare et al. reported increased maternal satisfaction with in- but also resulted in more uterine contractile abnormalities.
duction of labour compared with expectant management, No other significant differences were observed. With the
although this finding was based on a single large trial.43 The exception of the finding on mode of delivery, the results were
findings of these two reviews were heavily influenced by the in agreement with the published meta-analysis by Lin et al.14
results of the large multicentre TermPROM study by Hannah The other recent trial of misoprostol for PROM at term rand-
et al.43 omised 130 women with PROM and unfavourable cervices to
The systematic review by Lin et al.14 addressed a different oral misoprostol or placebo, followed by oxytocin if the
clinical question: the role of induction of labour with miso- woman was not in labour by 12 hours after rupture of mem-
prostol for prelabour premature rupture of membranes at branes.17 Oral misoprostol resulted in a significantly shorter
term. The authors combined six small trials including a total time to delivery and reduced need for oxytocin; there was no
of 451 participants comparing induction of labour with miso- difference in other outcomes of interest.
prostol with expectant management or placebo. In this analysis,
use of misoprostol significantly increased the likelihood of vag- Summary
inal delivery at less than 12 hours, but not less than 24 hours, Expedited induction of labour after PROM reduces cho-
compared with women who were allocated to placebo or rioamnionitis, endometritis, and admissions to a neonatal

630 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology
 Induction indications: best evidence review

intensive care unit. Quality of evidence: high, grade of rec- gested that the risk for caesarean delivery may be increased
ommendation for induction of labour: strong. when induction of labour is undertaken for presumed macro-
somia (149 of 898 [16.6%] versus 214 of 2540 [8.4%], NNH =
Preterm prelabour rupture of membranes 12), a finding not confirmed in the small RCTs.19 Larger
Our search identified one systematic review comparing inten- randomised studies are underway to further elucidate this
tional delivery by immediate induction of labour with expec- question.
tant management in women with preterm prelabour rupture
of membranes (PPROM) between 30 and 36 weeks of gesta- Summary
tion.18 This systematic review combined four small RCTs with 1 Induction of labour does not improve outcomes in the
a total of 389 participants.44–47 Two of the included studies setting of suspected fetal macrosomia. Quality of evidence:
required demonstration of fetal lung maturity for entry.44,45 moderate, grade of recommendation against induction of
Antibiotics and steroids were not given in any of the included labour: weak.
trials, so expectant care in these trials may not have been 2 Induction of labour may increase caesarean deliveries.
comparable with expectant care as it is currently practiced. Level of evidence: low, grade of recommendation against
In their analysis, the authors found that immediate induc- induction of labour: weak.
tion significantly reduced chorioamnionitis (9 of 190 versus
41 of 199, risk difference –0.16, 95% CI –0.23 to –0.10, NNT = Twin pregnancy
6).18 In addition, maternal length of stay was significantly We identified one systematic review addressing the question
shortened by immediate induction of labour (from 4.5 to of whether fetal morbidity and mortality of twin gestations
2.5 days, weighted mean difference –1.39, 95% CI: –2.03, are reduced by induction. This Cochrane review included
–0.75). There was no difference in any neonatal outcome of a single RCT allocating 36 twin pregnancies to induction
interest including perinatal death, confirmed early-onset neo- at 37 weeks of gestation or expectant management.49 The
natal sepsis, RDS, intraventricular haemorrhage, necrotising reviewers found this study severely underpowered to detect
enterocolitis or neonatal length of stay. improvements in perinatal morbidity or mortality with
In summary, no definitive study establishing the optimal induction. The review found no differences in birthweight,
timing of delivery after PPROM has been carried out. The route of delivery, or maternal or neonatal outcome. The
gestational age at which induction of labour should be carried authors conclude that there is currently insufficient data to
out in the absence of demonstrated pulmonary maturity has support elective delivery of otherwise uncomplicated twin
not been established. A multicentre RCT is continuing to pregnancies after 37 weeks of gestation.21 Definitive recom-
further elucidate timing of delivery and risks and benefits mendations for timing of delivery for twin gestations should
of induction.48 await completion of large, adequately powered RCTs now
underway.21
Summary
In women with PPROM, induction of labour reduces the Summary
incidence of chorioamnionitis. Subjects in available trials The only RCT of induction of labour for twin gestations at 37
may not be representative of current patients with PPROM, weeks is not appropriately powered to determine the benefits
as they did not receive glucocorticoids or antibiotics. The and harms of induction. Quality of evidence for induction of
optimal gestational age for induction of labour is not estab- labour: low, grade of recommendation: weak.
lished. Quality of evidence: moderate, grade of recommenda-
tion for labour induction: weak. Oligohydramnios
We identified one randomised pilot study of induction of
labour for isolated oligohydramnios.22 In this study, the
Suspected macrosomia investigators randomised 54 women with oligohydramnios
Our search identified two systematic reviews addressing and pregnancies at 41 weeks of gestation (288 days) to induc-
induction for suspected macrosomia.19,20 The review by Irion tion of labour or expectant management until 42 weeks.
and Boulvain20 included only two small RCTs involving 313 Women with suspected IUGR, abnormal fetal cardiotoco-
women. The review by Sanchez-Ramos et al.19 included these graphy or abnormal umbilical artery Doppler studies were
two RCTs as well as nine observational studies including 3751 excluded. The investigators found no difference in any of their
subjects in total. Observational and RCTs were analysed sep- outcomes of interest including birthweight, mode of deliv-
arately. Despite these methodological differences, the Irion ery, umbilical blood pH, Apgar scores or admission to
and Sanchez-Ramos analyses agreed in their main result, find- neonatal intensive care. However, this study was under-
ing no difference in caesarean deliveries or shoulder dystocia. powered to detect any potential benefits of induction for
Sanchez-Ramos’ analysis of non-randomised studies sug- oligohydramnios and did not study induction for isolated

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 Mozurkewich et al.

oligohydramnios at other gestational ages. There is currently authors found rates of intrauterine fetal demise in this series
insufficient evidence to recommend routine induction of of actively managed women to be significantly lower than
labour for oligohydramnios. historic controls in the published literature (0 of 218 versus
14 of 888, NNT = 63). Based on these data, the authors
Summary recommend induction of labour.
Induction of labour for oligohydramnios at term is advocated
by expert opinion to reduce perinatal morbidity and mortal- Summary
ity, but the only RCT available is not appropriately powered One cohort study of women with IHCP suggests that induc-
to test this potential benefit. Quality of evidence: low, grade of tion of labour may reduce intrauterine fetal death compared
recommendation: weak. with expectantly managed historic controls, but this finding
should be confirmed by properly conducted prospective
Diabetes mellitus requiring insulin cohort studies and RCTs. Quality of evidence: very low, grade
We identified one systematic review,23 which included one of recommendation: weak.
RCT that assigned 200 women with insulin-requiring gesta-
tional diabetes mellitus or pre-existing type II diabetes to Maternal cardiac disease
either induction at 38 weeks of gestation or expectant care.50 We identified one cohort study and two case series concerning
This study found no difference in the rate of caesarean deliv- induction of labour for severe maternal cardiac disease.26–28
ery between these approaches but found that fetal macroso- The two case series studies were carried out in developing
mia, defined as birthweight >4000 g was significantly reduced world settings27,28 and lacked control groups. Although they
by induction of labour (relative risk 0.56, 95% CI: 0.32–0.98, aimed to demonstrate safety of the induction methods
NNT = 8). The birthweight of 23% of the babies born to employed (PGE2 or oxytocin), these studies included very
expectantly managed women was at or above the 90th per- small numbers of subjects (37 and 21 respectively) and no
centile compared with 10% of the babies born to induced major conclusions regarding potential beneficial or harmful
women. There were more cases of shoulder dystocia in the effects can be drawn. The third study26 was a prospective
expectantly managed group, but this difference was not sta- cohort study comparing 47 women with cardiac disease
tistically significant. There were no differences in other fetal who underwent induction of labour with 74 women with
or maternal morbidities. Further research is needed to con- cardiac disease who were managed expectantly. The induction
firm this finding and evaluate fetal, neonatal, and maternal and control groups were not well matched. The women who
morbidity. were induced had more severe cardiac disease than those in
the expectant management group. There were significantly
Summary more caesarean deliveries performed in the expectant man-
Induction of labour in women with diabetes in pregnancy agement group than in the labour induction group, but this
reduces fetal macrosomia. Quality of evidence: moderate, difference may have been accounted for by the increased
grade of recommendation: weak. number of women with prior caesarean sections in the expec-
tant management group. No other differences in maternal or
Intrahepatic cholestasis of pregnancy neonatal outcome were found.
We identified one case–control study24 and one case series25
addressing the question of whether perinatal outcomes in Summary
IHCP are improved by induction. In a small case–control No harmful or beneficial effects have been demonstrated for
study, Rioseco et al.24 compared perinatal outcomes (mortal- induction of labour for maternal cardiac disease. Quality of
ity, abnormal fetal heart rate tracings, Apgar score <7 at 1 and evidence: very low, grade of recommendation: weak.
5 minutes, and small for gestational age) among 320 cases
who were actively managed with antenatal testing and induc- Hypertension/pre-eclampsia/eclampsia
tion of labour at 38 weeks with 320 control women who Our search did not identify any studies comparing induction
delivered at the same institution and who did not have intra- of labour with expectant management for mild pre-eclampsia
hepatic cholestasis of pregnancy (IHCP). Because no differ- or pregnancy-induced hypertension, although one multi-
ence in outcomes was demonstrated between the case and centre RCT of induction of labour versus conservative
control groups, the authors concluded that induction of management for mild pre-eclampsia or pregnancy-induced
labour was beneficial. Roncaglia et al., followed 206 women hypertension at term is continuing.51 We identified two RCTs
with cholestasis of pregnancy.25 In this case series, 56 women comparing induction of labour (or expedited delivery) with
had spontaneous or indicated preterm delivery. Of the expectant management (or delayed delivery) in the setting of
remainder, 146 of 150 women underwent induction of labour severe pre-eclampsia remote from term.29,30 The Odendaal
at 37 weeks of gestation or at the time of diagnosis. The study randomly assigned 38 women with severe pre-eclampsia

632 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology
 Induction indications: best evidence review

between 28 and 34 weeks to immediate induction of labour or 2 Expectant management for severe pre-eclampsia remote
caesarean section or to expectant management until 34 weeks from term increases birthweight and reduces neonatal mor-
of gestation. In women assigned to expectant care, delivery bidity. Quality of evidence: moderate, grade of recommen-
before 34 weeks was carried out for worsening pre-eclampsia, dation: weak.
development of haemolysis, elevated liver enzymes and low 3 Induction of labour versus caesarean delivery with severe
platelet count (HELLP) syndrome, or signs of fetal compro- pre-eclampsia remote from term: induction of labour is
mise.29 Pregnancies assigned to expectant care were pro- associated with high rates of intrapartum caesarean section
longed by about 7 days on average, and significantly fewer but no increased harm when compared with elective cae-
neonates born to mothers assigned to expectant care required sarean section. Quality of evidence: very low, Grade of
assisted ventilation (2 of 18 versus 7 of 20) or had one or more recommendation: weak.
neonatal complications (6 of 18 versus 15 of 20).29 4 Induction of labour versus caesarean delivery for eclamp-
The Sibai study included 95 women with severe pre- sia: induction of labour may shorten maternal length of
eclampsia between 28 and 32 weeks of gestation who were stay and reduce maternal complications. Quality of evi-
randomly assigned to expedited delivery, whether by induc- dence: low, grade of recommendation: weak.
tion or caesarean section, or expectant care.30 This study
found that expectant management prolonged pregnancy by Suspected IUGR
an average of 15.4 days, increased birthweight, and reduced Our search identified two RCTs of early delivery for IUGR.
neonatal morbidity as measured by NICU admissions and The Growth Restriction Intervention Trial is a multicentre
days of NICU care required. A comparison of delivery by induc- RCT that allocated 548 women with 588 fetuses between 24
tion of labour versus caesarean section was not performed. Of and 36 weeks with suspected fetal compromise (abnormal
note, pregnancies with any sign of fetal compromise, multifetal umbilical artery Doppler studies) to immediate delivery
gestations, underlying medical disease, or with HELLP syn- (whether by induction of labour or caesarean section) or
drome or low platelets (<100 000) were excluded from study. expectant management until the obstetrician was no longer
In addition, our search identified seven case series compar- uncertain about the need for delivery.39 Expectant manage-
ing induction of labour with caesarean section for severe pre- ment resulted in a 4-day average prolongation of pregnancy
eclampsia remote from term.31–37 These studies in aggregate compared with immediate induction in this study. There were
address the question of failed inductions at various gestational more stillbirths in the delayed intervention group, but these
ages and the question of whether a trial of labour is harmful to were balanced by an increase in neonatal deaths in the early
the fetus compared with elective caesarean section. Most intervention group. Overall, there was no difference in
authors found that induction of labour led to caesarean deliv- perinatal mortality, but immediate induction increased the
ery in a majority of instances in which it was attempted at number of labours resulting in caesarean delivery. Two-year
gestational ages less than 30–34 weeks.31,32,35–37 Most of these follow-up studies of infant development were conducted on
series found no evidence of maternal, fetal or neonatal harms 98% of surviving randomised participants. There was no
when induction of labour was carried out,31–33,36 and two overall difference in severe disability between the groups.
authors found exposure to labour to be beneficial in reducing However, in the subgroup of pregnancies randomised before
neonatal pulmonary morbidity.33,36 By contrast, in a small 31 weeks of gestation, there were more children with severe
series from a developing world setting, elective caesarean sec- disability in the immediate delivery group compared with the
tion appeared to be associated with reduced fetal or neonatal delayed delivery group (14 of 107 [13%] versus 5 of 83
mortality.34 [5%]).40
We found one small pilot study that randomised 50 nul- The Disproportionate Intrauterine Growth Intervention
liparous patients with eclampsia and unfavourable cervical Trial at Term study was a small pilot RCT comparing labour
status to caesarean section or induction of labour with miso- induction with expectant management for suspected fetal
prostol.38 This study, carried out in a developing world set- growth restriction at term.41 This study randomised 33
ting, found decreased maternal length of stay and ‘maternal women with suspected IUGR (fetal abdominal circumference
complications’ with induction of labour compared with cae- at <10th percentile) to immediate induction or expectant
sarean section, but was underpowered to detect differences in management. The study was not appropriately powered to
most neonatal outcomes. assess differences in mode of delivery or perinatal morbidity
or mortality. Expectant management resulted in pregnancy
Summary prolongation by 14.9 days on average. No advantage of labour
1 Induction of labour for mild pre-eclampsia at term: induction was documented other than reduced need for ante-
No studies comparing benefits and harms exist. Quality natal surveillance. The investigators are currently undertaking
of evidence: no evidence, grade of recommendation: no a large multicentre RCT to determine whether induction of
recommendation. labour may reduce perinatal mortality.52

ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology 633
 Mozurkewich et al.

Summary Induction of labour for premature rupture of membranes

1 In preterm pregnancies with suspected IUGR, induction at term reduces chorioamnionitis, endometritis, and NICU
of labour does not reduce perinatal deaths or overall admissions without increasing caesarean deliveries. However,
long-term disability. Caesarean delivery is less likely with no difference in neonatal infectious morbidity has been dem-
expectant management. Quality of evidence: high, grade of onstrated. Limited evidence suggests that induction of labour
recommendation: weak. may reduce chorioamnionitis without worsening neonatal
2 The currently available RCT of induction of labour for morbidity in the setting of preterm PPROM at 30–36 weeks
suspected IUGR at term lacked statistical power to demon- of gestation, particularly if fetal pulmonary maturity has been
strate any benefit or harm for induction of labour. Quality established.
of evidence: low, grade of recommendation: weak. We also found high-quality evidence suggesting that rates
of intrauterine fetal demise may be reduced by induction of
Gastroschisis labour in the setting of IUGR before term, but these intra-
We identified one RCT of elective preterm delivery of the fetus uterine deaths may be offset by neonatal deaths such that
with gastroschisis. This study included 42 women with pre- overall perinatal mortality is not reduced.
natally diagnosed gastroschisis who were randomly assigned to Evidence supporting induction of labour for insulin-
induction of labour at 36 weeks of gestation or expectant requiring diabetes mellitus, oligohydramnios, and twin ges-
management until spontaneous onset of labour.42 The primary tations is inconclusive, because existing RCTs lack sufficient
outcomes of the study were time to full enteral feeding and statistical power to evaluate important maternal and neonatal
length of neonatal hospital stay. Both induced and spontane- outcomes. There is currently not enough high-quality evi-
ous labours were associated with high rates of caesarean deliv- dence to recommend routine induction of labour in these
ery (39%), primarily for fetal distress. There were trends settings. Likewise, no beneficial effects of induction for sus-
towards a shorter time to full enteral feeds (30.5 versus 37.5 pected macrosomia have been found.
days) and towards shorter neonatal hospital stay (47.5 days The literature supports expectant management (delayed
versus 53 days) in the induction group, although these differ- induction) in carefully selected mothers with severe pre-
ences were not statistically significant. This study did not have eclampsia as this may result in improved neonatal out-
statistical power to detect differences in intrauterine or neo- comes. Induction of labour for severe pre-eclampsia remote
natal deaths. Thus, this study did not demonstrate a definitive from term may be associated with high rates of caesarean
benefit for elective induction at 36 weeks of gestation. delivery.
Our review may have been limited by restricting our
Summary search to the English-language literature and by publication
There is no demonstrated benefit or harm for induction of bias. We found that further research is necessary to identify
labour at 36 weeks of gestation for fetal gastroschisis, but the potential risks and benefits of induction of labour in the
only available trial was underpowered to detect most out- setting of insulin-requiring diabetes mellitus, oligohy-
comes. Quality of evidence: low, grade of recommendation: dramnios, twin gestation, gastroschisis, maternal cardiac
weak. For all indications, the quality of evidence and grades of disease, and IUGR at term. Further research to determine
recommendation are summarized in Table 2. optimal timing of delivery in the setting of PPROM is also
needed.
Discussion
Conclusion
Our best evidence review of the literature suggests that induc-
tion of labour in the clinical settings of post-term pregnancy Women facing a decision about induction should have the
may reduce meconium aspiration syndrome and perinatal best available evidence to help them make an informed choice
deaths. However, the absolute risk of perinatal death with about the risks and benefits of the procedure. Clinicians
expectant management is quite small. Although induction of should use the best available evidence to support decision-
labour at 41 weeks of gestation has been criticised because a very making and need to acknowledge when insufficient evidence
large number of labour inductions are required to prevent one is available to definitively guide care. A number of common
perinatal death,53 our number needed to treat estimate for indications for induction of labour do not have a strong evi-
induction (NNT = 369) compares favourably with intrapartum dence base from which to guide practice. Researchers and
prophylaxis for group B streptococcus (GBS)-positive women funding agencies should prioritise studies that can help to
(NNT = 1191) and universal screening for GBS (NNT = 5704), definitively guide care in these situations.
interventions routinely recommended in the USA, Canada, and
Australia.54 Caesarean deliveries are not increased by a policy of Disclosure of interests
induction of labour at or beyond 41 weeks of gestation. None.

634 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology
 Induction indications: best evidence review

Contribution to authorship 14 Lin MG, Nuthalapaty FS, Carver AR, Case AS, Ramsey PS. Misoprostol
E.M., J.C. and E.K. performed the literature searches required for this for labour induction in women with term premature rupture of mem-
branes: a meta-analysis. Obstet Gynecol 2005;106:593–601.
review. E.M. and J.C. reviewed all abstracts and full text articles,
15 Dare MR, Middleton P, Crowther CA, Flenady VJ, Varatharaju B.
performed all assessments of study quality, and wrote and edited
Planned early birth versus expectant management (waiting) for prela-
the manuscript. K.K. and V.J.K. participated in the formulation of bour rupture of membranes at term (37 weeks or more). Cochrane
the methods of this review and assisted in the writing and editing of Database Syst Rev 2006:CD005302.
the manuscript and the assignment of evidence grades. 16 da Graca Krupa F, Cecatti JG, de Castro Surita FG, Milanez HMBP,
Parpinelli MA. Misoprostol versus expectant management in prema-
ture rupture of membranes at term. BJOG 2005;112:1284–90.
Details of ethics approval 17 Levy R, Vaisbuch E, Furman B, Brown D, Volach V, Hagay ZJ. Induction
This is a best evidence review of previously published data and as of labour with oral misoprostol for premature rupture of membranes at
such does not require ethics approval. term in women with unfavourable cervix: a randomized, double-blind,
placebo-controlled trial. J Perinat Med 2007;35:126–9.
18 Hartling L, Chari R, Friesen C, Vandermeer B, Lacaze-Masmonteil T.
Funding A systematic review of intentional delivery in women with preterm
This project was financially supported by Childbirth Connection prelabor rupture of membranes. J Matern Fetal Neonatal Med 2006;
through a grant from the New Hampshire Charitable Foundation. j 19:177–87.
19 Sanchez-Ramos L, Bernstein S, Kaunitz AM. Expectant management
versus labour induction for suspected fetal macrosomia: a systematic
review. Obstet Gynecol 2002;100:997–1002.
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636 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology