Methods of term labour induction for women with a previous caesarean section

  • Review
  • Intervention

Authors


Abstract

Background

Induction of labour is a common obstetric intervention, with between 20% and 30% of births reported to occur following induction of labour. Women with a prior caesarean delivery have an increased risk of uterine rupture, particularly when labour is induced. For women who have had a previous caesarean birth and who require induction of labour in a subsequent pregnancy, it is unclear which method of cervical ripening and labour induction is preferable.

Objectives

To assess the benefits and harms associated with different methods used to induce labour in women who have had a previous caesarean birth and require induction of labour in a subsequent pregnancy.

Search methods

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2012) and reference lists of retrieved studies.

Selection criteria

All randomised controlled trials comparing any method of third trimester cervical ripening or labour induction, with placebo/no treatment or other methods in women with prior caesarean section requiring labour induction in a subsequent pregnancy were included.

Methods of cervical ripening or labour induction could include: prostaglandin medication (including oral or vaginal prostaglandin E2 (PGE2) and misoprostol); mifepristone; mechanical methods (including Foley catheters and double balloon catheters); oxytocin, or placebo.

Data collection and analysis

The two review authors independently assessed studies for inclusion and trial quality. Any disagreement was resolved by discussion. Both review authors independently extracted data and data were checked for accuracy.

Main results

Two studies (involving a total of 80 women) were included. However, the two included studies used different methods and thus, meta-analysis was not appropriate. The two included studies compared 2.5 mg vaginal PGE2 inserts versus oxytocin (Taylor and colleagues) and misoprostol versus oxytocin (Wing and colleagues). Risk of bias in the included studies was judged 'low' and 'unclear' respectively.

Vaginal PGE2 inserts versus oxytocin - Taylor and colleagues included 42 women, equally distributed over both groups. Baseline characteristics, and reasons for labour induction were comparable between the groups. There were no significant differences in any of the outcome measures reported (caesarean section, instrumental vaginal deliveries, epidural analgesia, Apgar score, perinatal death). One uterine rupture occurred in the prostaglandin group, after the use of prostaglandins and oxytocin, while no ruptures occurred in the oxytocin group (one study, 42 women; risk ratio (RR) 3.00, 95% confidence interval (CI) 0.13 to 69.70).

Misoprostol versus oxytocin - the study conducted by Wing and colleagues was stopped prematurely due to safety concerns after the inclusion of 38 women. Seventeen women had been included in the misoprostol group, and 21 women in the oxytocin group. There were no significant difference in the only outcome measure reported by the authors, uterine rupture, which occurred twice in the misoprostol group, and did not occur in the oxytocin group (one study; 38 women; RR 6.11, 95% CI 0.31 to 119.33).

Authors' conclusions

There is insufficient information available from randomised controlled trials on which to base clinical decisions regarding the optimal method of induction of labour in women with a prior caesarean birth.

Résumé scientifique

Méthodes de déclenchement du travail à terme pour les femmes ayant précédemment accouché par césarienne

Contexte

Le déclenchement du travail est une intervention obstétrique courante, entre 20 % et 30 % des naissances rapportées ayant lieu suite au déclenchement du travail. Les femmes ayant déjà accouché par césarienne présentent un risque accru de rupture utérine, surtout quand le travail est déclenché. Pour les femmes ayant déjà accouché par césarienne et qui nécessiteront le déclenchement du travail lors d'une grossesse ultérieure, on ignore quelle méthode de maturation cervicale et de déclenchement du travail est préférable.

Objectifs

Évaluer les bénéfices et les risques associés aux différentes méthodes utilisées pour déclencher le travail chez les femmes ayant déjà accouché par césarienne et qui nécessiteront le déclenchement du travail lors d'une grossesse ultérieure.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre des essais cliniques du groupe Cochrane sur la grossesse et la naissance (31.07.12) et dans les références bibliographiques des études trouvées.

Critères de sélection

Tous les essais contrôlés randomisés comparant une méthode de maturation cervicale ou de déclenchement du travail au troisième trimestre, à un placebo/l'absence de traitement ou d'autres méthodes chez les femmes ayant déjà accouché par césarienne et qui nécessiteront le déclenchement du travail lors d'une grossesse ultérieure, ont été inclus.

Les méthodes de maturation cervicale ou de déclenchement du travail peuvent notamment comprendre : un traitement par des prostaglandines (incluant les prostaglandines E2 orales ou vaginales (PGE2) et le misoprostol oral ou vaginal) ; la mifépristone ; des méthodes mécaniques (incluant des cathéters de Foley et des cathéters à doubles ballonnets) ; l'ocytocine ou un placebo.

Recueil et analyse des données

Les deux auteurs de la revue ont évalué de manière indépendante les études à inclure, ainsi que la qualité méthodologique des essais. Les désaccords ont été résolus par la discussion. Les deux auteurs ont extrait les données et vérifié leur exactitude de façon indépendante.

Résultats principaux

Deux études (totalisant 80 femmes) ont été incluses. Cependant, les deux études incluses ont utilisé des méthodes différentes et la méta-analyse n'était donc pas appropriée. Les deux études incluses ont comparé des inserts de PGE2 vaginale de 2,5 mg à l'ocytocine (Taylor et collaborateurs) et le misoprostol à l'ocytocine (Wing et collaborateurs). Le risque de biais dans les études incluses a été jugé comme étant 'faible' ou 'incertain', respectivement.

Inserts de PGE2 vaginale comparée à l'ocytocine - Taylor et collaborateurs ont inclus 42 femmes, également réparties entre les deux groupes. Les caractéristiques initiales, et les raisons du déclenchement du travail étaient comparables entre les groupes. Il n'y avait aucune différence significative quel que soit le résultat mesuré considéré (césarienne, accouchements par voie basse avec assistance instrumentale, analgésie péridurale, score d'Apgar et mortalité périnatale). Une rupture utérine s'est produite dans le groupe sous prostaglandines, suite à l'utilisation des prostaglandines et de l'ocytocine, tandis que dans le groupe sous ocytocine aucune rupture n'a été signalée (une étude, 42 femmes ; risque relatif (RR) 3,00, intervalle de confiance (IC) à 95 % 0,13 à 69,70).

Misoprostol comparé à l'ocytocine - l'étude conduite par Wing et collaborateurs a été arrêtée prématurément en raison de problèmes de sécurité après l'inclusion de 38 femmes. Dix-sept femmes avaient été incluses dans le groupe sous misoprostol, et 21 femmes dans le groupe sous ocytocine. Il n'y avait aucune différence significative dans l'unique résultat mesuré rapporté par les auteurs, la rupture utérine, qui s'est produite chez deux femmes dans le groupe sous misoprostol, et ne s'est pas produite dans le groupe sous ocytocine (une étude ; 38 femmes ; RR 6,11, IC à 95 % 0,31 à 119,33).

Conclusions des auteurs

Il n'y a pas suffisamment de données disponibles dans les essais contrôlés randomisés sur lesquelles baser des décisions cliniques concernant la meilleure méthode de déclenchement du travail chez les femmes ayant déjà accouché par césarienne.

Plain language summary

Induction methods for women who have had a prior caesarean birth

Worldwide, caesarean birth is common, with percentages ranging from 25% to 50% of reported births. Current clinical practice guidelines support vaginal birth and trial of labour among women who have had a previous caesarean birth. Women with a prior caesarean birth have an increased risk of uterine scar rupture, particularly when labour is induced. This is a serious complication, often leading to negative outcomes for mother and child, such as hysterectomy, genitourinary tract injury, and postpartum blood transfusions for the mother, and neurological impairment or even death for the child. Labour induction is a common obstetric procedure that is carried out when the risk of continuing pregnancy outweighs the benefits. Methods include: prostaglandin medication (including oral or vaginal prostaglandins E2 (PGE2) or misoprostol); mifepristone; mechanical methods (including Foley catheters and double balloon catheters); and oxytocin. The goal of this review was to assess the harms and benefits of different methods of induction of labour in women with a prior caesarean birth, should induction of labour be required in their present pregnancy.

Two randomised controlled studies (involving 80 women in their third trimester) met our inclusion criteria. The studies used different methods of inducing labour, vaginal PGE2 inserts versus oxytocin, and misoprostol versus oxytocin.. Comparing PGE2 to oxytocins, no differences were found in the risk of caesarean section, nor other primary or secondary outcomes, of which only instrumental vaginal deliveries, epidural analgesia, Apgar score, perinatal death were reported. One uterine rupture was reported in the PGE2 group. The second study compared misoprostol to oxytocin. This study was stopped prematurely after the inclusion of 38 women because of the occurrence of two uterine ruptures in the misoprostol group. This study did not report on other outcomes than uterine rupture. Risk of bias in the included studies was judged as low or unclear. They were underpowered to detect clinically relevant differences in the outcomes measured.

Based on our review of literature, we conclude that too little information is available from randomised controlled trials to advise on the best methods of labour induction in women with a prior caesarean birth.

Résumé simplifié

Méthodes de déclenchement pour les femmes ayant déjà accouché par césarienne

Partout dans le monde, la césarienne est courante, ses pourcentages variant de 25 % à 50 % des naissances rapportées. Les directives actuelles pour la pratique clinique soutiennent l'accouchement par voie basse et la tentative de travail chez les femmes ayant déjà accouché par césarienne. Les femmes ayant déjà accouché par césarienne présentent un risque accru de rupture de la cicatrice utérine, surtout quand le travail est déclenché. Il s'agit d'une complication grave, conduisant souvent à des résultats négatifs pour la mère et l'enfant, tels que l'hystérectomie, des lésions de l'appareil génito-urinaire, et des transfusions sanguines post-partum pour la mère, ainsi qu'un déficit neurologique, voire le décès pour l'enfant. Le déclenchement du travail est une procédure obstétrique courante pratiquée lorsque les risques de poursuivre la grossesse l'emportent sur les avantages. Les méthodes comprennent : un traitement par des prostaglandines (incluant les prostaglandines E2 orales ou vaginales (PGE2) ou le misoprostol oral ou vaginal) ; la mifépristone ; des méthodes mécaniques (incluant des cathéters de Foley et des cathéters à doubles ballonnets) ; et l'ocytocine. L'objectif de cette revue était d’évaluer les risques et les bénéfices des différentes méthodes de déclenchement du travail chez les femmes ayant déjà accouché par césarienne, dans le cas où le déclenchement du travail serait nécessaire pour leur grossesse en cours.

Deux essais contrôlés randomisés (totalisant 80 femmes dans leur troisième trimestre) ont répondu à nos critères d'inclusion. Les études ont utilisé différentes méthodes de déclenchement du travail, des inserts de PGE2 vaginale comparée à l'ocytocine, et le misoprostol comparé à l'ocytocine. Dans les comparaisons de PGE2 à l'ocytocine, aucune différence n'a été détectée au niveau du risque de césarienne, ni des autres critères de jugement principaux ou secondaires, parmi lesquels seuls les accouchements par voie basse avec assistance instrumentale, l'analgésie péridurale, le score d'Apgar et la mortalité périnatale ont été rapportés. Une rupture utérine a été rapportée dans le groupe sous PGE2. La seconde étude a comparé le misoprostol à l'ocytocine. Cette étude a été arrêtée prématurément après l'inclusion de 38 femmes en raison de la survenue de deux ruptures utérines dans le groupe sous misoprostol. Cette étude n'a pas rendu compte des critères de jugement autres que la rupture utérine. Le risque de biais dans les études incluses a été jugé comme étant faible ou incertain. Elles n'étaient pas assez puissantes pour détecter des différences cliniquement pertinentes dans les critères mesurés.

D’après notre revue de la littérature, nous avons conclu que les données disponibles dans les essais contrôlés randomisés sont trop insuffisantes pour conseiller les meilleures méthodes de déclenchement du travail chez les femmes ayant déjà accouché par césarienne.

Notes de traduction

Traduit par: French Cochrane Centre 22nd March, 2013
Traduction financée par: Instituts de Recherche en Sant� du Canada, Minist�re de la Sant� et des Services Sociaux du Qu�bec, Fonds de recherche du Qu�bec-Sant� et Institut National d'Excellence en Sant� et en Services Sociaux pour la France: Minist�re en charge de la Sant�

Background

Description of the condition

Worldwide, caesarean birth is common. In Australia in 2007, almost 31% of women gave birth by caesarean section (Laws 2009), with similar figures reported from the United States (Martin 2009). While the overall rate of caesarean section is lower in the United Kingdom, accounting for approximately 25% of all births (NHS 2009), rates of almost 50% have been reported in some private hospitals in Argentina, Brazil and Chile (Belizan 1999). Women who have had a prior caesarean birth are at increased risk of complications during a subsequent labour, including risk of uterine rupture, presenting unique circumstances related to the mode of birth in a subsequent pregnancy. The particular benefits and harms associated with both elective repeat caesarean section and vaginal birth after caesarean section are discussed in the Cochrane review 'Planned elective repeat caesarean section versus planned vaginal birth for women with a previous caesarean section' (Dodd 2004). Current clinical practice guidelines support vaginal birth and trial of labour among women who have had a prior caesarean birth (ACOG 2006; RCOG 2008).

Induction of labour is a common obstetric intervention, with between 20% and 30% of births reported to occur following induction of labour (Laws 2009; Martin 2009; Peristat 2008). For women who have had a previous caesarean birth and who require induction of labour in a subsequent pregnancy, it is unclear whether labour should be induced, or if birth should occur by repeat elective caesarean section. This question is considered in more detail in the Cochrane review 'Elective repeat caesarean section versus induction of labour for women with a previous caesarean birth' (Dodd 2006).

An uncommon, but potentially life-threatening complication for both the woman and her infant associated with vaginal birth, is that of uterine scar rupture (where the previous caesarean scar breaks down). Uterine scar rupture is associated with a significant risk of maternal morbidity, such as hysterectomy, genitourinary tract injury, postpartum blood transfusions, and maternal death (Chuahan 2003; Zwart 2008). Increased infant morbidity and perinatal death have been reported (Chuahan 2003). Uterine rupture is reported to occur more commonly after induction of labour, compared with spontaneous labour in women who have had a previous caesarean birth.

The focus of this current systematic review is to address the method of induction of labour, should it be required, in women who have had a previous caesarean section. The review will draw on the methodology of the Cochrane generic protocol related to methods of induction of labour (Hofmeyr 2009).

Description of the intervention

Induction of labour is carried out when the risks of continuing the pregnancy outweigh the benefits. Common indications for labour induction include post-term pregnancy, prelabour rupture of membranes, intrauterine growth restriction of the fetus, maternal hypertensive disorders, and other maternal conditions. Many different methods are available for labour induction, including pharmacological methods (mainly prostaglandin analogues and oxytocin), and mechanical methods, such as Foley catheters.

Prospective and retrospective cohort studies have shown an increased risk of uterine rupture in women who have had a prior caesarean birth following induction of labour, especially when prostaglandin preparations are used for cervical ripening (Landon 2004; Lydon-Rochelle 2001; Smith 2004). The risk of uterine rupture following mechanical dilation for ripening of the cervix is reported to be lower than with prostaglandins (Bujold 2004; Landon 2004; Ravasia 2000), approximating the risk after spontaneous onset of labour.

The observed increase in risk of uterine rupture following prostaglandin administration may reflect changes that are induced in the connective tissue of the uterine scar, thereby, weakening it. Equally, it could be reflective of the woman’s cervix being ‘unfavourable’ for labour (Bujold 2004; Kayani 2005), which in turn has been recognised to be associated with adverse maternal and infant outcomes following the trial of labour (Landon 2005).

The use of oxytocin to induce labour in women who have had a prior caesarean birth is also associated with an increased risk of uterine rupture (36/10,000 women without the use of oxytocin compared with 87/10,000 women following oxytocin use) (Landon 2005).

Clinical practice guidelines vary worldwide in relation to induction of labour for women who have had a previous caesarean section. The Society of Obstetricians and Gynaecologists of Canada clinical practice guidelines state that prostaglandins E2 (PGE2) should only be used in exceptional circumstances, and after appropriate counselling on the risk of uterine rupture, recommending that a Foley catheter be used in these women (SOGC 2005). The UK National Institute for Clinical Excellence (NICE) guidelines do not make any explicit recommendations, but do not discourage the use of prostaglandin (RCOG 2008). In contrast, practice guidelines issued by the American College of Obstetricians and Gynaecologists state that the use of prostaglandins for cervical ripening or induction of labour in most women who have had a previous caesarean section should be discouraged (ACOG 2006).

Why it is important to do this review

Cohort studies suggest that for women who have had a previous caesarean birth and require induction of labour in a subsequent pregnancy, there are potential benefits and harms associated with the induction of labour. These benefits and harms may vary considerably with the method used to induce labour.

Objectives

To assess the benefits and harms associated with different methods used to induce labour in women who have had a previous caesarean birth and require induction of labour in a subsequent pregnancy.

Methods

Criteria for considering studies for this review

Types of studies

All randomised controlled trials (with reported data for women and infants) comparing any method of term cervical ripening or labour induction, with placebo/no treatment or other methods, not including the comparison of induction of labour versus expectant management. Quasi-randomised controlled trials, and those presented only as an abstract were eligible for inclusion. Cluster-randomised and cross-over trials are not relevant to this intervention and were not eligible for inclusion.

Types of participants

Pregnant women with a live fetus, who have had a previous caesarean section, requiring induction of labour in the third trimester of pregnancy.

Types of interventions

All methods of cervical ripening or labour induction including: prostaglandin medication (including oral or vaginal PGE2 and misoprostol); mifepristone; mechanical methods (including Foley catheters and double balloon catheters); oxytocin, or placebo compared with placebo or any other method were included.

Types of outcome measures

Clinically relevant outcomes for trials of methods of cervical ripening/labour induction have been prespecified and published in the Cochrane generic protocol relating to induction of labour (Hofmeyr 2009).

Primary outcomes

(1) Vaginal delivery not achieved within 24 hours (or period specified by trial authors).
(2) Uterine hyperstimulation with fetal heart rate (FHR) changes.
(3) Caesarean section.
(4) Serious neonatal morbidity or perinatal death (e.g. seizures, birth asphyxia defined by trialists, neonatal encephalopathy, disability in childhood).
(5) Serious maternal morbidity or death (e.g. uterine rupture, admission to intensive care unit, septicaemia).

Secondary outcomes
Measures of effectiveness

(6) Cervix unfavourable/unchanged after 12 to 24 hours.
(7) Oxytocin augmentation.

Complications

(8) Uterine hyperstimulation without FHR changes.
(9) Uterine rupture.
(10) Epidural analgesia.
(11) Instrumental vaginal delivery.
(12) Meconium-stained liquor.
(13) Apgar score less than seven at five minutes.
(14) Neonatal intensive care unit admission.
(15) Neonatal encephalopathy.
(16) Perinatal death.
(17) Disability in childhood.
(18) Neonatal infection.
(19) Neonatal antibiotics.
(20) Maternal side-effects (all).
(21) Maternal nausea.
(22) Maternal vomiting.
(23) Maternal diarrhoea.
(24) Other maternal side-effects.
(25) Postpartum haemorrhage.
(26) Chorioamnionitis.
(27) Endometritis.
(28) Maternal antibiotics.
(29) Serious maternal complications (e.g. intensive care unit admission, septicaemia but excluding uterine rupture).
(30) Maternal death.

Measures of satisfaction

(31) Woman not satisfied.
(32) Caregiver not satisfied.

’Uterine rupture’ includes all clinically significant ruptures of unscarred or scarred uteri. Trivial scar dehiscence noted incidentally at the time of surgery were excluded.

In the reviews, we use the term ’uterine hyperstimulation without FHR changes’ to include uterine tachysystole (more than five contractions per 10 minutes for at least 20 minutes) and uterine hypersystole/hypertonus (a contraction lasting at least two minutes) and ’uterine hyperstimulation with FHR changes’ to denote uterine hyperstimulation syndrome (tachysystole or hypersystole with FHR changes such as persistent decelerations, tachycardia or decreased short-term variability).

Outcomes are included in the analysis if data are available according to treatment allocation and reasonable measures were taken to minimise observer bias. While all the above outcomes were sought, only outcomes with available data appear in the analysis tables. Data not pre-stated were extracted and reported as not pre-specified.

Search methods for identification of studies

Electronic searches

We contacted the Trials Search Co-ordinator to search the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 July 2012). 

The Cochrane Pregnancy and Childbirth Group’s Trials Register is maintained by the Trials Search Co-ordinator and contains trials identified from:

  1. monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);

  2. weekly searches of MEDLINE;

  3. weekly search of EMBASE;

  4. handsearches of 30 journals and the proceedings of major conferences;

  5. weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.

Details of the search strategies for CENTRAL, MEDLINE and EMBASE, the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service can be found in the ‘Specialized Register’ section within the editorial information about the Cochrane Pregnancy and Childbirth Group.

Trials identified through the searching activities described above are each assigned to a review topic (or topics). The Trials Search Co-ordinator searches the register for each review using the topic list rather than keywords. 

Searching other resources

We searched the reference lists of retrieved studies.

We did not apply any language restrictions.

Data collection and analysis

Selection of studies

Two review authors (Marta Jozwiak (MJ) and Jodie Dodd (JD)) independently assessed for inclusion all the potential studies we identified as a result of the search strategy. We resolved any disagreement through discussion.

Data extraction and management

We designed a form to extract data. For eligible studies, two review authors (MJ and JD) extracted the data using the agreed form. We resolved discrepancies through discussion. We entered data into Review Manager software (RevMan 2011) and checked them for accuracy.

When information regarding any of the above was unclear, we attempted to contact authors of the original reports to provide further details.

Assessment of risk of bias in included studies

Two review authors (MJ and JD) independently assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We resolved any disagreement by discussion.

(1) Sequence generation (checking for possible selection bias)

We described for each included study the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.

We assessed the method as:

  • low risk of bias (any truly random process, e.g. random number table; computer random number generator);

  • high risk of bias (any non-random process, e.g. odd or even date of birth; hospital or clinic record number);

  • unclear risk of bias.   

(2) Allocation concealment (checking for possible selection bias)

We described for each included study the method used to conceal allocation to interventions prior to assignment and assessed whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment.

We assessed the methods as:

  • low risk of bias (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);

  • high risk of bias (open random allocation; unsealed or non-opaque envelopes, alternation; date of birth);

  • unclear risk of bias.

(3) Blinding (checking for possible performance bias)

We described for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We considered that studies were at low risk of bias if they were blinded, or if we judged that the lack of blinding could not have affected the results. We assessed blinding separately for different outcomes or classes of outcomes.

We assessed the methods as:

  • low, high or unclear risk of bias for outcome assessors.

Due to the nature of the intervention it was not feasible to blind the patient and/or caregiver to the intervention.

(4) Incomplete outcome data (checking for possible attrition bias through withdrawals, dropouts, protocol deviations

We described for each included study, and for each outcome or class of outcomes, the completeness of data including attrition and exclusions from the analysis. We stated whether attrition and exclusions were reported, the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. Where sufficient information was reported, or could be supplied by the trial authors, we re-included missing data in the analyses which we undertook. We assessed methods as:

  • low risk of bias (20% or fewer participants excluded; or missing data is balanced across groups and judged unlikely to influence the outcome, or missing data have been imputed using appropriate methods);

  • high risk of bias (more than 20% participants excluded; when data is missing, and this is judged to potentially alter the findings of the study);

  • unclear risk of bias.

(5) Selective reporting bias

We described for each included study how we investigated the possibility of selective outcome reporting bias and what we found.

We assessed the methods as:

  • low risk of bias (where it is clear that all of the study’s pre-specified outcomes and all expected outcomes of interest to the review have been reported);

  • high risk of bias (where not all the study’s pre-specified outcomes have been reported; one or more reported primary outcomes were not pre-specified; outcomes of interest are reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported);

  • unclear risk of bias.

(6) Other sources of bias

We described for each included study any important concerns we have about other possible sources of bias.

We assessed whether each study was free of other problems that could put it at risk of bias:

  • low risk of other bias;

  • high risk of other bias;

  • unclear whether there is risk of other bias.

(7) Overall risk of bias

We made explicit judgements about whether studies were at high risk of bias, according to the criteria given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). With reference to (1) to (6) above, we planned to assess the likely magnitude and direction of the bias and whether we consider it is likely to impact on the findings. We planned to explore the impact of the level of bias through undertaking sensitivity analyses - see Sensitivity analysis

Measures of treatment effect

Dichotomous data

For dichotomous data, we present results as summary risk ratio with 95% confidence intervals. 

Continuous data

For continuous data, we planned to use the mean difference if outcomes were measured in the same way between trials. We planned to use the standardised mean difference to combine trials that measured the same outcome, but used different methods.  

Dealing with missing data

For included studies, we noted levels of attrition. We planned to explore the impact of including studies with high levels of missing data in the overall assessment of treatment effect by using sensitivity analysis.

For all outcomes, we carried out analyses, as far as possible, on an intention-to-treat basis, i.e. we attempted to include all participants randomised to each group in the analyses, and all participants were analysed in the group to which they were allocated, regardless of whether or not they received the allocated intervention. The denominator for each outcome in each trial is the number randomised minus any participants whose outcomes are known to be missing.

Assessment of heterogeneity

In future updates of this review, we plan to assess statistical heterogeneity in each meta-analysis using the T², I² and Chi² statistics. We will regard heterogeneity as substantial if the I² is greater than 30% and either the T² is greater than zero, or there is a low P value (less than 0.10) in the Chi² test for heterogeneity. 

Assessment of reporting biases

In future updates of this review, if there are 10 or more studies in the meta-analysis, we plan to investigate reporting biases (such as publication bias) using funnel plots. We plan to assess funnel plot asymmetry visually, and use formal tests for funnel plot asymmetry. For continuous outcomes, we will use the test proposed by (Egger 1997), and for dichotomous outcomes, we will use the test proposed by (Harbord 2006). If asymmetry is detected in any of these tests or is suggested by a visual assessment, we will perform exploratory analyses to investigate it.

Data synthesis

The two included studies used considerably different methods and thus meta-analysis was not appropriate. In future updates, we will carry out statistical analysis using the Review Manager software (RevMan 2011). We will use fixed-effect meta-analysis for combining data where it is reasonable to assume that studies are estimating the same underlying treatment effect: i.e. where trials are examining the same intervention, and the trials’ populations and methods are judged sufficiently similar. If there is clinical heterogeneity sufficient to expect that the underlying treatment effects differ between trials, or if substantial statistical heterogeneity is detected, we will use random-effects meta-analysis to produce an overall summary if an average treatment effect across trials is considered clinically meaningful. The random-effects summary will be treated as the average range of possible treatment effects and we will discuss the clinical implications of treatment effects differing between trials. If the average treatment effect is not clinically meaningful, we will not combine trials.

If we use random-effects analyses, the results will be presented as the average treatment effect with its 95% confidence interval, and the estimates of T² and I².

Subgroup analysis and investigation of heterogeneity

We did not carry out any planned subgroup analysis due to insufficient data. However, In future updates, if we identify substantial heterogeneity, we will investigate it using subgroup analyses and sensitivity analyses. We will consider whether an overall summary is meaningful, and if it is, use random-effects analysis to produce it.

We will carry out the following subgroup analyses:

  1. previous vaginal birth (yes versus no);

  2. number of previous caesarean births (one versus two versus three or more);

  3. indication for previous caesarean birth(s) (failure to progress versus fetal distress versus other);

  4. indication for labour induction (hypertensive disorders versus post-term pregnancy versus intrauterine growth restriction versus maternal disease versus other indication);

  5. favourability of the cervix (favourable versus unfavourable);

  6. status of membranes (ruptures versus unruptured);

  7. gestational age (37 to 40 weeks versus 40 to 41 weeks versus more than 41 weeks).

The subgroup analysis will be restricted to the primary outcomes.

We will assess subgroup differences by interaction tests available within RevMan (RevMan 2011). We will report the results of subgroup analyses quoting the χ2 statistic and P value, and the interaction test I² value.

Sensitivity analysis

Sensitivity analyses were not required. Criteria for sensitivity analysis in future updates include all aspects of quality assessment as mentioned above, including selection, performance and attrition bias. We will perform sensitivity analysis taking into account quasi-randomised controlled trials and studies that were reported as an abstract only (not confirmed in subsequent publication). Sensitivity analysis will be restricted to the primary outcomes.

Results

Description of studies

Results of the search

The search of the Cochrane Pregnancy and Childbirth Group's Trials Register retrieved 15 reports. These 15 papers reported on 10 different studies. Two studies were included (Taylor 1993; Wing 1998) and eight studies were excluded (Arraztoa 1994; Ben-Aroya 2001; Hamdan 2009; Lelaidier 1994; Morales 1986; Rayburn 1999; Sciscione 2001; Spallicci 2007).

Included studies

Two studies (involving 80 women) were included (Taylor 1993; Wing 1998).

In the Taylor 1993 study, women were randomly assigned to induction of labour using 2.5 mg vaginal prostaglandin E2 (PGE2) inserts followed by amniotomy after three hours and oxytocin infusion if labour had not been established six hours after prostaglandin administration, or to amniotomy and oxytocin infusion. Forty-two women were recruited, equally distributed across both treatment groups. Participants were women at or beyond term, whose only previous birth was by lower segment transverse caesarean section, and who required induction of labour either because of prolonged pregnancy or pre-eclampsia.

In contrast, the Wing 1998 study compared vaginal misoprostol with amniotomy and oxytocin. Women requiring induction of labour with a singleton pregnancy in cephalic presentation with one prior caesarean section were eligible for inclusion. Women were randomly assigned to either 25 mcg vaginal misoprostol every six hours (maximum of four doses), or to an oxytocin infusion using a standardised protocol. Recruitment to the trial ceased prematurely after 38 women had been randomised, due to safety concerns.

Excluded studies

Eight studies were excluded (Arraztoa 1994; Ben-Aroya 2001; Hamdan 2009; Lelaidier 1994; Morales 1986; Rayburn 1999; Sciscione 2001; Spallicci 2007).

The studies by Arraztoa, Morales and Rayburn compared a pharmacological method of induction of labour with ongoing expectant management of the pregnancy (Arraztoa 1994; Morales 1986; Rayburn 1999). The Ben-Aroya 2001 study did not involve a randomised comparison, while Hamdan 2009 compared weekly membrane sweeping with weekly vaginal examination, in women who did not require induction of labour.

The Lelaidier 1994 study compared mifepristone with placebo as a pre-induction agent, followed by vaginal prostaglandin induction in all women after an observation period of four days. Spallicci 2007 compared hyaluronidase with placebo in women with a prior caesarean birth at term, who did not require induction of labour. Sciscione 2001 compared transcervical Foley catheter with misoprostol to induce labour in women with a prior caesarean birth. However, the trial inclusion criteria were modified to exclude women with a prior caesarean birth, following the occurrence of a uterine rupture in the misoprostol group.

For more details, see Characteristics of excluded studies.

Risk of bias in included studies

In the Taylor 1993 study, allocation concealment was considered adequate. While blinding is not described, this is unlikely to be feasible due to the nature of the intervention. Data of all randomised women are included in the report, and the expected outcomes are reported. The overall risk of bias of this study was judged to be low (see Characteristics of included studies).

In the Wing 1998 study, details of the method of generating the randomisation sequence, allocation concealment, and blinding were not provided. Furthermore, the manuscript describes only the cases of uterine rupture, with no other clinical outcomes reported. The overall risk of bias was therefore considered unclear (see Characteristics of included studies).

Effects of interventions

The data from the two included studies were not combined because the studies used different methods and thus, meta-analysis was not considered appropriate.

Prostaglandin E2 (PGE2) inserts versus oxytocin

A single study involving 42 women compared vaginal PGE2 with oxytocin for induction of labour (Taylor 1993). There were no statistically significant differences identified between the two treatment groups for the primary outcomes: caesarean section (one study; 42 women; risk ratio (RR) 0.67, 95% confidence interval (CI) 0.22 to 2.03, Analysis 1.1), serious neonatal morbidity or perinatal death (one study; 42 women; RR 3.00, 95% CI 0.13 to 69.70, Analysis 1.2), or serious maternal morbidity or death (one study; 42 women; RR 3.00, 95% CI 0.13 to 69.70, Analysis 1.3). One woman was identified to have a uterine rupture following prostaglandin administration (one study; 42 women; RR 3.00, 95% CI 0.13 to 69.70, Analysis 1.4). There were no statistically significant differences identified in the secondary maternal or infant outcomes, including use of epidural analgesia (one study; 42 women; RR 1.42, 95% CI 0.93 to 2.17, Analysis 1.5), instrumental vaginal birth (one study; 42 women; RR 1.25, 95% CI 0.39 to 4.02, Analysis 1.6), or infant Apgar score of less than seven at five minutes of age (one study, 42 women; RR not estimable, Analysis 1.7).

Misoprostol verus oxytocin

One study comparing misoprostol and oxytocin was included (Wing 1998). However, this trial was stopped following recruitment and randomisation of 38 women (17 women misoprostol group; 21 women oxytocin group. The only outcome reported was uterine rupture, which occurred in two women in the misoprostol group (one study; 38 women; RR 6.11, 95% CI 0.31 to 119.33, Analysis 2.1).

Discussion

Summary of main results

Two small randomised trials were included in the review, one of which was terminated prematurely due to safety concerns of uterine rupture. The available evidence from randomised controlled trials relating to methods of induction of labour for women with a prior caesarean section is inadequate, the available studies are underpowered to detect clinically relevant differences in the primary and secondary outcome measures.

Overall completeness and applicability of evidence

There is insufficient information available from randomised trials to inform the optimal method of induction of labour in women with a prior caesarean birth.

Agreements and disagreements with other studies or reviews

While there is limited information available from randomised trials, lower quality evidence is available from observational studies.

In a large retrospective population based study, Lydon-Rochelle and colleagues evaluated the risk of uterine rupture among women with a prior caesarean birth, comparing the risks following the spontaneous onset of labour, as well as following induction of labour (using both prostaglandin and other methods to induce labour). Where labour occurred spontaneously, the risk of uterine rupture was reported to be 5.2 per 1000 women (56 of 10,789 women), increasing to 7.7 per 1000 women (15 of 1960 women) where labour was induced with “non-prostaglandin” methods, and further increasing to 24.5 per 1000 women (nine of 366 women) where labour was induced with prostaglandin preparations (Lydon-Rochelle 2001). When expressed as a risk ratio (RR) comparing the chance of uterine rupture among women who had a repeat elective caesarean section, spontaneous labour increased the chance of rupture by three-fold (RR 3.3, 95% confidence interval (CI) 1.8 to 6.0), induction with non-prostaglandin methods by almost five-fold (RR 4.9, 95% CI 2.4 to 9.7), and induction with prostaglandin preparations by over 15.5-fold (RR 15.6, 95% CI 8.1 to 30.0). Specific information was not presented for different prostaglandin preparations (for example, PGE2, or misoprostol).

The US based NICHD group conducted a prospective evaluation of women with a prior caesarean birth (Landon 2004). In this study, induction of labour following the use of prostaglandin medication was associated with a non-significant increase in risk of uterine rupture when compared with mechanical methods of induction, for example, the Foley catheter (risk of uterine rupture 140 per 10,000 inductions following PGE2 compared with 89 per 10,000 inductions following mechanical dilation of the cervix with a Foley catheter) (Landon 2004). In contrast, Scottish data from more than 36,000 women with a prior caesarean birth, of whom 4600 women had labour induced with prostaglandins, demonstrated an increased risk of uterine rupture and subsequent perinatal death following prostaglandin induction (risk of uterine rupture 4.5 per 10,000 non-induced labours versus 11 per 10,000 labours induced with prostaglandins in women with a prior caesarean) (Smith 2004). Raviasia et al conducted a retrospective cohort study reviewing all births between 1992 and 1998 in a Canadian hospital (Ravasia 2000). In this series, of the 172 women who underwent induction with prostaglandins, five suffered a uterine rupture (2.9%), compared with one of 129 in women who were induced with a Foley catheter (0.78%), and two of 274 women who did not require cervical ripening (0.73%), In a similar study evaluating mechanical cervical dilation in women with a prior caesarean section, Bujold and colleagues demonstrated a similar risk of uterine rupture between Foley catheter induction and spontaneous onset of labour (1.78% versus 1.2%) (Bujold 2004).

The risk associated with uterine scar rupture following the use of misoprostol is less well documented. Misoprostol is an oral prostaglandin E1 analogue, licensed for use in the treatment of gastric ulcer disease. There is increasing recognition of its use as a prostaglandin agent to induce labour following oral, vaginal and buccal administration (Alfirevic 2006; Hofmeyr 2010; Muzonzini 2004). However, its use to induce labour in women with a previous caesarean has been questioned, with several case reports indicating an increased risk of uterine rupture (Bennett 1997; Choy-Hee 2001; Cunha 1999; Phillips 1996; Plaut 1999).   

While there are documented potential risks associated with induction of labour among women with a previous caesarean section, induction of labour is considered by many to be preferable to a repeat elective caesarean section. In an Australian survey of practice relating to care of women with a prior caesarean section in a subsequent birth, two-thirds of obstetrician respondents indicated that induction of labour was preferable to a repeat elective caesarean (Dodd 2003). While manufacturers of both oxytocin and PGE2 specifically list previous caesarean as a contraindication to use in their product information brochures, almost two-thirds of Australian obstetricians (Dodd 2003) and 25% of Canadian obstetricians (Brill 2003) use vaginal PGE2 in this setting. Additionally, 80% of Australian obstetricians use oxytocin in women with a previous caesarean birth (Dodd 2003). These figures are similar to those reported in England, where 76% of obstetricians would consider use of prostaglandin analogues, and 86% of consultants would use oxytocin to induce labour in women with a previous caesarean birth (Gupta 2011).

Authors' conclusions

Implications for practice

There is insufficient information available from randomised controlled trials on which to base clinical decisions regarding the optimal method of induction of labour in women with a prior caesarean birth.

Implications for research

Appropriately designed and conducted randomised trials are required to evaluate methods of induction of labour for women who have had a prior caesarean birth, including evaluation of mechanical methods of induction, with adequate reporting of clinically relevant maternal and infant outcomes. As these are not likely to be undertaken due to results from previous reports, and if undertaken are likely to be underpowered to evaluate the risk of infrequent but serious adverse outcomes, we suggest adequately powered prospective cohort studies.

Acknowledgements

As part of the pre-publication editorial process, this review has been commented on by four peers (an editor and three referees who are external to the editorial team), a member of the Pregnancy and Childbirth Group's international panel of consumers and the Group's Statistical Adviser.

Data and analyses

Download statistical data

Comparison 1. Prostaglandin E2 versus oxytocin
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Caesarean section142Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.22, 2.03]
2 Serious neonatal morbidity/perinatal death142Risk Ratio (M-H, Fixed, 95% CI)3.0 [0.13, 69.70]
3 Serious maternal morbidity or death142Risk Ratio (M-H, Fixed, 95% CI)3.0 [0.13, 69.70]
4 Uterine rupture142Risk Ratio (M-H, Fixed, 95% CI)3.0 [0.13, 69.70]
5 Epidural analgesia142Risk Ratio (M-H, Fixed, 95% CI)1.42 [0.93, 2.17]
6 Instrumental vaginal delivery142Risk Ratio (M-H, Fixed, 95% CI)1.25 [0.39, 4.02]
7 Apgar score < 7 at 5 minutes142Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 1.1.

Comparison 1 Prostaglandin E2 versus oxytocin, Outcome 1 Caesarean section.

Analysis 1.2.

Comparison 1 Prostaglandin E2 versus oxytocin, Outcome 2 Serious neonatal morbidity/perinatal death.

Analysis 1.3.

Comparison 1 Prostaglandin E2 versus oxytocin, Outcome 3 Serious maternal morbidity or death.

Analysis 1.4.

Comparison 1 Prostaglandin E2 versus oxytocin, Outcome 4 Uterine rupture.

Analysis 1.5.

Comparison 1 Prostaglandin E2 versus oxytocin, Outcome 5 Epidural analgesia.

Analysis 1.6.

Comparison 1 Prostaglandin E2 versus oxytocin, Outcome 6 Instrumental vaginal delivery.

Analysis 1.7.

Comparison 1 Prostaglandin E2 versus oxytocin, Outcome 7 Apgar score < 7 at 5 minutes.

Comparison 2. Misoprostol versus oxytocin
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Uterine rupture138Risk Ratio (M-H, Fixed, 95% CI)6.11 [0.31, 119.33]
Analysis 2.1.

Comparison 2 Misoprostol versus oxytocin, Outcome 1 Uterine rupture.

Appendices

Appendix 1. Technical terms

Uterine rupture: where the previous caesarean scar breaks down.

Induction of labour: where labour is stimulated artificially.

Hysterectomy: surgical removal of the uterus/womb.

Genitourinary tract injury: injury at the time of surgery to other organs, commonly the bladder.

Prostaglandin: a hormone given to soften the cervix in preparation for labour.

Oxytocin: a hormone given through a drip into a vein to stimulate the uterus to contract.

Contributions of authors

Marta Jozwiak and Jodie Dodd both assessed the studies yielded by the search for inclusion and assessed the methodological quality of studies. Marta Jozwiak performed data extraction and entered the data, Jodie Dodd checked the data for any inconsistencies.

Marta Jozwiak and Jodie Dodd drafted the review.

Declarations of interest

Jodie Dodd: none known.

Marta Jozwiak is involved in a randomised controlled trial on induction of labour with Foley catheter compared with induction of labour with prostaglandins. Any decisions relating to the assessment of the trial for inclusion in this review, assessing trial quality, or data extraction will be carried out by two individuals not directly involved with the trial (i.e. Jodie Dodd and a third party).

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • The University of Adelaide, Discipline of Obstetrics and Gynaecology, Australia.

  • The Australian National Health and Medical Research Council Practitioner Fellowship, Australia.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Taylor 1993

MethodsProspective randomised trial, sealed numbered envelopes, no sample size calculation.
ParticipantsWomen requiring labour induction due to prolonged pregnancy or pre-eclampsia, 1 previous pregnancy delivered by lower segment caesarean section, singleton in cephalic presentation, GA ≥ 37 weeks, BS < 9, no cephalopelvic disproportion anticipated.
InterventionsAmniotomy and IV oxytocin (n = 21) versus 2.5 mg PGE2 pessary, followed by amniotomy 3 hours later + oxytocin (if necessary) 6 hours later (n = 21).
OutcomesInduction to delivery time, analgesia, mode of delivery, uterine rupture.
Notes

Only half of the women included had an unfavourable cervix (BS < 6).

1 uterine rupture in PGE 2 group (after oxytocin) reported in abstract Sellers 1988.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk'predetermined code envelope.'
Allocation concealment (selection bias)Low riskSealed envelopes.
Incomplete outcome data (attrition bias)
All outcomes
Low riskData of all women included were reported, no ITT analysis done.
Selective reporting (reporting bias)Unclear riskPublished report includes expected outcomes, but no outcome measures were prespecified in the methods section.
Other biasLow riskThe baseline characteristics were comparable between the groups.
Blinding of participants and personnel (performance bias)
All outcomes
High riskNot feasible.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskBlinding was not described in the report.

Wing 1998

  1. a

    BS: Bishop Score
    GA: gestational age
    ITT: intention-to-treat
    IV: intravenous
    PGE2: prostaglandin E2
    RCT: randomised controlled trial

MethodsPrematurely terminated RCT, due to safety concerns.
ParticipantsWomen with a singleton pregnancy in cephalic presentation with one prior caesarean section were eligible for inclusion.
Interventions25 mcg misoprostol every 6 hours (maximum of 4 doses) (n = 17) versus IV oxytocin (n = 21).
OutcomesNot described in detail, included uterine tachysystole, hypertonus, hyperstimulation syndrome, uterine dehiscence (defined at laparotomy or digital examination), uterine rupture (that required emergency laparotomy).
Notes2 uterine ruptures occurred in the misoprostol group and the trial was ended prematurely due to safety concerns.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskMethod of sequence generation not described.
Allocation concealment (selection bias)Unclear riskMethod not described in the report.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe expected outcomes are not described; the report only describes the cases of uterine rupture in detail.
Selective reporting (reporting bias)Unclear riskThis report only describes the cases of uterine rupture in detail.
Other biasUnclear riskThe study was terminated prematurely due to safety concerns.
Blinding of participants and personnel (performance bias)
All outcomes
High riskBlinding was not feasible due to the nature of the interventions.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskBlinding was not described in the report.

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Arraztoa 1994Compares, in women with a prior caesarean birth in labour, a pharmacologic approach (oxytocin + epidural) to expectant management (spontaneous evolution). Does not compare methods of induction for women in whom labour is induced.
Ben-Aroya 2001Is not a randomised controlled trial, but rather a cohort study.
Hamdan 2009Compares weekly membrane sweeping to weekly vaginal examination, does not compare 2 different methods of cervical ripening or induction.
Lelaidier 1994Mifepristone was used as a pre-induction agent, only after the women were randomised.
Morales 1986Compares induction of labour with oxytocin to expectant management in women with premature rupture of membranes, not especially women with a prior caesarean birth.
Rayburn 1999Compares weekly administration of cervical PGE2 gel to expectant management in women with a prior caesarean birth, not 2 different methods of cervical ripening or induction.
Sciscione 2001Initially all women were included, subsequently women with a prior caesarean were excluded.
Spallicci 2007Women did not require induction of labour.

Ancillary