Oral prostaglandin E2 for induction of labour

Linda French

doi:10.1002/14651858.CD003098

. 2001 Apr 23;2001(2):CD003098. doi: 10.1002/14651858.CD003098

Oral prostaglandin E2 for induction of labour

Linda French ^1,^✉

Editor: Cochrane Pregnancy and Childbirth Group

PMCID: PMC8407181 PMID: 11406075

Abstract

Background

This is one of a series of reviews of methods of cervical ripening and labour induction using standardized methodology.

Objectives

To determine the effects of oral prostaglandin E2 for third trimester induction of labour.

Search methods

The Cochrane Pregnancy and Childbirth Group's Trials Register (January 2007) and bibliographies of relevant papers. We updated this search on 8 June 2012 and added the results to the awaiting classification section of the review.

Selection criteria

Clinical trials comparing oral prostaglandin E2 used for third trimester cervical ripening or labour induction with placebo or no treatment or other methods listed above it on a predefined list of labour induction methods.

Data collection and analysis

A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two‐stage method of data extraction.

Main results

There were 19 studies included in the review. Of these 15 included a comparison using either oral or intravenous oxytocin with or without amniotomy. The quality of studies reviewed was not high. Only seven studies had clearly described allocation concealment. Only two studies stated that providers or participants, or both, were blinded to treatment group.

For the outcome of vaginal delivery not achieved within 24 hours, in the composite comparison of oral PGE2 versus all oxytocin treatments (oral and intravenous, with and without amniotomy), there was a trend favoring oxytocin treatments (relative risk (RR) 1.97, 95% confidence interval (CI) 0.86 to 4.48).

For the outcome of cesarean section, in the comparison of PGE2 versus no treatment or placebo, PGE2 was favored (RR 0.54, 95% CI 0.29 to 0.98). Otherwise, there were no significant differences between groups for this outcome.

Oral prostaglandin was associated with vomiting across all comparison groups.

Authors' conclusions

Oral prostaglandin consistently resulted in more frequent gastrointestinal side‐effects, in particular vomiting, compared with the other treatments included in this review. There were no clear advantages to oral prostaglandin over other methods of induction of labour.

[Note: The six citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]

Plain language summary

Oral prostaglandin E2 for induction of labour

Oral prostaglandin E2 is no more effective than other methods of induction but has more adverse effects.

Induction of labour is sometimes considered beneficial in some clinical circumstances, e.g., when the baby is not growing properly, when there is pre‐eclampsia or when gestation goes beyond the normal length of pregnancy. There are many varying methods used to try to stimulate labour including administration of drugs, mechanical methods such as sweeping of the membranes, and more natural methods like nipple stimulation and having sex. Care needs to be taken to balance the stimulation of labour without over‐stimulating and causing the baby difficulties. Prostaglandin E2 (PGE2) is a hormone given either by mouth or by insertion through the vagina to prepare and stimulate the cervix and bring on labour. This review looked at oral PGE2 compared with no intervention, and compared with several other methods of induction. The review identified 19 studies involving 2688 women, looking at eight differing comparisons. The review found that none of the trials assessed the effectiveness of oral PGE2 in inducing labour, but overall the trials found that PGE2 caused more frequent gastrointestinal adverse effects, particularly vomiting. There were no clear advantages to oral PGE2 over other methods used to bring on labour, except that women may prefer a method that does not require an intravenous infusion. Over stimulation of the baby may possibly be a possible problem with PGE2, but the increased incidence of gastrointestinal side‐effects do not favor its use.

Background

Prostaglandins are hormones with a number of functions, and are normally produced at various sites in the body. They are derived from a fatty acid, arachidonic acid, which is generally available when needed. The role of endogenous prostaglandins in cervical ripening and initiation of labour was discovered in the 1960s.

Synthetically produced prostaglandins E2 (PGE2) and F2alpha (PGF2a) have been available for oral administration in several developed countries since the early 1970s. By 1977 five small trials had been published regarding use of PGE2 for cervical ripening. These were reviewed (Chalmers 1989) with the conclusion that the data failed to demonstrate suitability for this purpose. Vaginal administration has become the preferred route for the purpose of cervical ripening. PGE2 has also been studied as an agent for the induction of labour. The use of PGE2 as an agent for cervical ripening and labour induction is the subject of this review.

The gastrointestinal side‐effects of oral prostaglandins are important, and apparently more pronounced for PGF2a (Yeung 1977).

This review is one of a series of reviews of methods of labour induction using a standardized protocol. A review of the synthetic prostaglandin misoprostol is reviewed separately, seeAlfirevic 2006. For more detailed information on the rationale for this methodological approach, please refer to the currently published protocol (Hofmeyr 2000). For other currently published Cochrane Reviews on methods of induction of labour, seeAlfirevic 2006; Alfirevic 2009; Boulvain 2005; Boulvain 2008; Bricker 2000; Hapangama 2009; Hofmeyr 2010; Howarth 2001; Hutton 2001; Jozwiak 2012; Kavanagh 2001; Kavanagh 2005; Kavanagh 2006a; Kavanagh 2006b; Kelly 2001a; Kelly 2001b; Kelly 2009; Kelly 2011; Luckas 2000; Muzonzini 2004; Smith 2003; Smith 2004; Thomas 2001

Objectives

To determine, from the best available evidence, the effectiveness and safety of oral prostaglandin E2 for third trimester induction of labour.

Methods

Criteria for considering studies for this review

Types of studies

Clinical trials comparing oral prostaglandin E2 for labour induction with placebo/no treatment or other methods of labour induction. This review includes only induction methods listed with lower numbers on a predefined list of methods of labour induction (see 'Methods of the review'). Studies comparing a low or constant dosing of oral prostaglandin with a high or incremental dosing regimen are also included. Additionally, studies comparing oral prostaglandin with oral oxytocin, with and without amniotomy, are also included. We have included only studies that have some form of random allocation of participants to study groups, and that report at least one of the prestated outcomes. Oral administration of the prostaglandin analogue misoprostol is reviewed separately (Alfirevic 2006).

Types of participants

Pregnant women due for third trimester induction of labour, carrying a viable fetus.

Predefined subgroup analyses were (see list below): previous cesarean section or not; nulliparity or multiparity; membranes intact or ruptured, and cervix unfavorable, favorable or undefined. Only those outcomes with data will appear in the analysis tables.

Types of interventions

Oral prostaglandin compared with placebo/no treatment or any other method above it on a predefined list of methods of labour induction.

Types of outcome measures

Clinically relevant outcomes for trials of methods of cervical ripening/labour induction have been prespecified by two authors of labour induction reviews (Justus Hofmeyr and Zarko Alfirevic). Differences were settled by discussion.

Five primary outcomes were chosen as being most representative of the clinically important measures of effectiveness and complications. Subgroup analyses are limited to the primary outcomes:   (1) vaginal delivery not achieved within 24 hours;   (2) uterine hyperstimulation with fetal heart rate (FHR) changes;   (3) cesarean 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, septicemia).

Perinatal and maternal morbidity and mortality are composite outcomes. This is not an ideal solution because some components are clearly less severe than others. It is possible for one intervention to cause more deaths but less severe morbidity. However, in the context of labour induction at term this is unlikely. All these events will be rare, and a modest change in their incidence will be easier to detect if composite outcomes are presented. The incidence of individual components will be explored as secondary outcomes (see below).

Secondary outcomes relate to measures of effectiveness, complications and satisfaction.

Measures of effectiveness:

(6) cervix unfavorable/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) maternal side‐effects (all);   (19) maternal nausea;   (20) maternal vomiting;   (21) maternal diarrhoea;   (22) other maternal side‐effects;   (23) postpartum hemorrhage (as defined by the trial authors);   (24) serious maternal complications (e.g. intensive care unit admission, septicemia but excluding uterine rupture);   (25) maternal death.

Measures of satisfaction:

(26) woman not satisfied;   (27) caregiver not satisfied.

'Uterine rupture' will include all clinically significant ruptures of unscarred or scarred uteri. Trivial scar dehiscence noted incidentally at the time of surgery will be excluded.

Additional outcomes may appear in individual primary reviews, but will not contribute to the secondary reviews.

While all the above outcomes will be sought, only those with data will appear in the analysis tables.

The terminology of uterine hyperstimulation is problematic (Curtis 1987). In the reviews we have used the term 'uterine hyperstimulation without FHR changes' to include uterine tachysystole (more than 5 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 were included in the analysis: if reasonable measures were taken to minimise observer bias; and data were available for analysis according to original allocation.

Search methods for identification of studies

Electronic searches

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register by contacting the Trials Search Co‐ordinator (January 2007). We updated this search on 8 June 2012 and added the results to Studies awaiting classification.

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

monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);
weekly searches of MEDLINE;
weekly searches of EMBASE;
handsearches of 30 journals and the proceedings of major conferences;
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.

The first search was performed simultaneously for all reviews of methods of inducing labour, as outlined in the generic protocol for these reviews (Hofmeyr 2000).

Searching other resources

we searched the reference lists of trial reports and reviews.

We did not apply any language restrictions.

Data collection and analysis

A strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. Many methods have been studied, in many different categories of women undergoing labour induction. Most trials are intervention‐driven, comparing two or more methods in various categories of women. Clinicians and parents need the data arranged by category of woman, to be able to choose which method is best for a particular clinical scenario. To extract these data from several hundred trial reports in a single step would be very difficult. We have therefore developed a two‐stage method of data extraction. The initial data extraction will be done in a series of primary reviews arranged by methods of induction of labour, following a standardized methodology. The data will then be extracted from the primary reviews into a series of secondary reviews, arranged by category of woman.

To avoid duplication of data in the primary reviews, the labour induction methods have been listed in a specific order, from one to 25. Each primary review includes comparisons between one of the methods (from two to 25) with only those methods above it on the list. Thus, the review of intravenous oxytocin (4) will include only comparisons with intracervical prostaglandins (3), vaginal prostaglandins (2) or placebo (1). Methods identified in the future will be added to the end of the list. The current list is as follows:

placebo/no treatment;
vaginal prostaglandins (Kelly 2009);
intracervical prostaglandins (Boulvain 2008);
intravenous oxytocin (Alfirevic 2009);
amniotomy (Bricker 2000);
amniotomy plus intravenous oxytocin (Howarth 2001);
vaginal misoprostol (Hofmeyr 2010);
oral misoprostol (Alfirevic 2006);
mechanical methods including extra‐amniotic Foley catheter (Jozwiak 2012);
membrane sweeping (Boulvain 2005);
extra‐amniotic prostaglandins (Hutton 2001);
intravenous prostaglandins (Luckas 2000);
oral prostaglandins (this review);
mifepristone (Hapangama 2009);
oestrogens alone of with amniotomy (Thomas 2001);
corticosteroids (Kavanagh 2006a);
relaxin (Kelly 2001b);
hyaluronidase (Kavanagh 2006b);
castor oil, bath and/or enema (Kelly 2001a);
acupuncture (Smith 2004);
breast stimulation (Kavanagh 2005);
sexual intercourse (Kavanagh 2001);
homeopathic methods (Smith 2003);
nitric oxide (Kelly 2011);
buccal or sublingual misoprostol (Muzonzini 2004);
hypnosis;
other methods for induction of labour.

The primary reviews are analysed by the following subgroups:

previous cesarean section or not;
nulliparity or multiparity;
membranes intact or ruptured;
cervix favorable, unfavorable or undefined.

The secondary reviews will include all methods of labour induction for each of the categories of women for which subgroup analysis has been done in the primary reviews, and will include only five primary outcome measures. There will thus be six secondary reviews of methods of labour induction in the following groups of women:

nulliparous, intact membranes (unfavorable cervix, favorable cervix, cervix not defined);
nulliparous, ruptured membranes (unfavorable cervix, favorable cervix, cervix not defined);
multiparous, intact membranes (unfavorable cervix, favorable cervix, cervix not defined);
multiparous, ruptured membranes (unfavorable cervix, favorable cervix, cervix not defined);
previous cesarean section, intact membranes (unfavorable cervix, favorable cervix, cervix not defined);
previous cesarean section, ruptured membranes (unfavorable cervix, favorable cervix, cervix not defined).

Each time a primary review is updated with new data, those secondary reviews which include data which have changed, will also be updated.

The trials included in the primary reviews first published in 2001 were extracted from an initial set of trials covering all interventions used in induction of labour (see above for details of search strategy). The data extraction process was conducted centrally. This was co‐ordinated from the Clinical Effectiveness Support Unit (CESU) at the Royal College of Obstetricians and Gynaecologists, UK, in co‐operation with the Pregnancy and Childbirth Group of The Cochrane Collaboration. This process allowed the data extraction process to be standardized across all the reviews.

The trials were initially reviewed on eligibility criteria, using a standardized form and the basic selection criteria specified above. Following this, data were extracted to a standardized data extraction form which was piloted for consistency and completeness. The pilot process involved the researchers at the CESU and previous review authors in the area of induction of labour.

Information was extracted regarding the methodological quality of trials on a number of levels. This process was completed without consideration of trial results. Assessment of selection bias examined the process involved in the generation of the random sequence and the method of allocation concealment separately. These were then judged as adequate or inadequate using the criteria described in Table 1 for the purpose of the reviews.

1. Methodological quality of trials.

Methodological item	Adequate	Inadequate
Generation of random sequence.	Computer‐generated sequence, random‐number tables, lot drawing, coin tossing, shuffling cards, throwing dice.	Case number, date of birth, date of admission, alternation.
Concealment of allocation.	Central randomization, coded drug boxes, sequentially sealed opaque envelopes.	Open allocation sequence, any procedure based on inadequate generation.

Date	Event	Description
12 May 2008	Amended	Converted to new review format.
25 January 2007	New search has been performed	Search repeated. Four reports have been assessed and added to the list of excluded studies.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	3	195	Risk Ratio (M‐H, Fixed, 95% CI)	0.54 [0.29, 0.98]
7 Oxytocin augmentation	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	0.21 [0.10, 0.47]
8 Uterine hyperstimulation without fetal heart rate changes	2	150	Risk Ratio (M‐H, Fixed, 95% CI)	4.0 [0.46, 34.81]
11 Instrumental vaginal delivery	1	45	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [0.47, 3.33]
20 Vomiting	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 71.92]
21 Diarrhoea	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 71.92]
28 Maternal postpartum infections requiring antibiotics	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.34, 1.24]
29 Neonatal infections requiring antibiotics	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	0.45 [0.17, 1.21]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	0.64 [0.27, 1.51]
7 Oxytocin augmentation	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	0.21 [0.10, 0.47]
8 Uterine hyperstimulation without fetal heart rate changes	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 71.92]
20 Vomiting	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 71.92]
21 Diarrhoea	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 71.92]
28 Maternal postpartum infections requiring antibiotics	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.34, 1.24]
29 Neonatal infections requiring antibiotics	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	0.45 [0.17, 1.21]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.30, 2.32]
11 Instrumental vaginal delivery	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.42, 2.81]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	1	8	Risk Ratio (M‐H, Fixed, 95% CI)	0.29 [0.07, 1.20]
11 Instrumental vaginal delivery	1	8	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.03, 9.46]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	2	63	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.33, 1.47]
6 Cevrvix unfavorable/unchanged after12‐24 hours	1	33	Risk Ratio (M‐H, Fixed, 95% CI)	2.13 [0.21, 21.22]
11 Instrumental vaginal delivery	3	108	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.44, 1.54]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	1	30	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.36, 4.97]
11 Instrumental vaginal delivery	1	30	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.24, 4.18]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.24, 1.65]
11 Instrumental vaginal delivery	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [0.38, 4.12]
13 Apgar score < 7 at 5 minutes	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.07, 15.12]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vaginal delivery not achieved within 24 hours	3	494	Risk Ratio (M‐H, Fixed, 95% CI)	1.97 [0.86, 4.48]
2 Uterine hyperstimulation with fetal heart rate changes	4	642	Risk Ratio (M‐H, Fixed, 95% CI)	7.0 [0.37, 132.10]
3 Cesarean section	14	2204	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.83, 1.59]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vaginal delivery not achieved within 24 hours	1	201	Risk Ratio (M‐H, Fixed, 95% CI)	3.09 [0.13, 74.96]
2 Uterine hyperstimulation with fetal heart rate chnages	1	69	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Cesarean section	8	824	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.68, 1.68]
5 Serious maternal morbidity or death	1	35	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Uterine hyperstimulation without fetal heart rate changes	3	409	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 4.06]
10 Epidural analgesia	2	270	Risk Ratio (M‐H, Fixed, 95% CI)	0.87 [0.56, 1.35]
11 Instrumental vaginal delivery	6	624	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.48, 1.02]
12 Meconium‐stained liquor	1	69	Risk Ratio (M‐H, Fixed, 95% CI)	2.75 [0.30, 25.15]
13 Apgar score < 7 at 5 minutes	4	576	Risk Ratio (M‐H, Fixed, 95% CI)	0.50 [0.13, 1.97]
14 Neonatal intensive care unit admission	1	69	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.21, 2.50]
16 Perinatal death	1	35	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
20 Vomiting	3	305	Risk Ratio (M‐H, Fixed, 95% CI)	5.56 [2.15, 14.38]
21 Diarrhoea	2	236	Risk Ratio (M‐H, Fixed, 95% CI)	8.13 [1.03, 63.93]
22 Gastrointestinal effects	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.61, 41.22]
23 Postpartum haemorrhage	2	313	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.17, 1.12]
26 Women not satisfied	1	69	Risk Ratio (M‐H, Fixed, 95% CI)	0.25 [0.08, 0.82]
27 Caregiver not satisfied	1	69	Risk Ratio (M‐H, Fixed, 95% CI)	1.83 [0.61, 5.53]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	3	171	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.53, 2.09]
8 Uterine hyperstimulation without fetal heart rate changes	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 4.06]
11 Instrumental vaginal delivery	2	75	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.43, 1.68]
13 Apgar scrore < 7 at 5 minutes	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.06, 15.53]
22 Gastrointestinal effects	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.61, 41.22]
23 Postpartum haemorrhage	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.01, 2.01]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	1	244	Risk Ratio (M‐H, Fixed, 95% CI)	2.38 [0.77, 7.38]
8 Uterine hyperstimulation without fetal heart rate changes	1	244	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Instrumental vaginal delivery	1	244	Risk Ratio (M‐H, Fixed, 95% CI)	0.48 [0.23, 0.97]
13 Apgar score < 7 at 5 minutes	1	244	Risk Ratio (M‐H, Fixed, 95% CI)	0.48 [0.04, 5.18]
23 Postpartum haemorrhage	1	244	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.15, 1.21]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	2	126	Risk Ratio (M‐H, Fixed, 95% CI)	1.29 [0.53, 3.12]
8 Uterine hyperstimulation without fetal heart rate changes	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 4.06]
11 Instrumental vaginal delivery	1	30	Risk Ratio (M‐H, Fixed, 95% CI)	1.5 [0.29, 7.73]
13 Apgar scrore < 7 at 5 minutes	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.06, 15.53]
19 Postpartum haemorrhage	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.01, 2.01]
22 Gastrointestinal effects	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.61, 41.22]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	1	34	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.32, 4.98]
11 Instrumental vaginal delivery	1	34	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.30, 1.42]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Cesarean section	1	11	Risk Ratio (M‐H, Fixed, 95% CI)	0.6 [0.07, 4.83]
2 Instrumental vaginal delivery	1	11	Risk Ratio (M‐H, Fixed, 95% CI)	0.6 [0.07, 4.83]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	4	435	Risk Ratio (M‐H, Fixed, 95% CI)	2.11 [0.84, 5.31]
8 Uterine hyperstimulation without fetal heart rate changes	1	103	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
10 Epidural analgesia	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.51, 1.21]
11 Instrumental vaginal delivery	3	332	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.43, 1.55]
13 Apgar score < 7 at 5 minutes	2	145	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.12, 6.12]
20 Vomiting	2	229	Risk Ratio (M‐H, Fixed, 95% CI)	3.60 [0.41, 31.59]
21 Diarrhoea	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
23 Postpartum haemorrhage	2	290	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	1	103	Risk Ratio (M‐H, Fixed, 95% CI)	0.40 [0.04, 4.31]
8 Uterine hyperstimulation without fetal heart rate changes	1	103	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Instrumental vaginal delivery	1	103	Risk Ratio (M‐H, Fixed, 95% CI)	2.15 [0.61, 7.65]
13 Apgar score < 7 at 5 minutes	1	103	Risk Ratio (M‐H, Fixed, 95% CI)	2.43 [0.10, 58.31]
23 Postpartum haemorrhage	1	103	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	2	229	Risk Ratio (M‐H, Fixed, 95% CI)	6.33 [0.81, 49.52]
10 Epidural analgesia	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.51, 1.21]
11 Instrumental vaginal delivery	2	229	Risk Ratio (M‐H, Fixed, 95% CI)	0.51 [0.23, 1.14]
13 Apgar score < 7 at 5 minutes	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.30 [0.01, 7.07]
20 Vomiting	2	229	Risk Ratio (M‐H, Fixed, 95% CI)	3.60 [0.41, 31.59]
21 Diarrhoea	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
23 Postpartum haemorrhage	1	187	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vaginal delivery not achieved within 24 hours	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.34, 3.97]
2 Uterine hyperstimulation with fetal heart rate changes	2	473	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Cesarean section	4	822	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.56, 1.77]
4 Serious perinatal morbidity/perinatal death	1	280	Risk Ratio (M‐H, Fixed, 95% CI)	1.5 [0.25, 8.84]
7 Oxytocin augmentation	1	264	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.28, 1.41]
8 Uterine hyperstimulation without fetal heart rate changes	2	473	Risk Ratio (M‐H, Fixed, 95% CI)	2.32 [0.10, 56.20]
11 Instrumental vaginal delivery	4	822	Risk Ratio (M‐H, Fixed, 95% CI)	1.40 [0.91, 2.17]
13 Apgar score < 7 at 5 minutes	1	264	Risk Ratio (M‐H, Fixed, 95% CI)	1.97 [0.18, 21.46]
16 Perinatal death	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
19 Nausea	1	280	Risk Ratio (M‐H, Fixed, 95% CI)	23.0 [1.37, 386.56]
20 Vomiting	3	558	Risk Ratio (M‐H, Fixed, 95% CI)	6.15 [2.35, 16.08]
23 Postpartum haemorrhage	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.20, 6.76]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	1	264	Risk Ratio (M‐H, Fixed, 95% CI)	2.22 [0.70, 7.02]
7 Oxytocin augmentation	1	264	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.28, 1.41]
11 Instrumental vaginal delivery	1	264	Risk Ratio (M‐H, Fixed, 95% CI)	0.87 [0.45, 1.67]
13 Apgar score < 7 at 5 minutes	1	264	Risk Ratio (M‐H, Fixed, 95% CI)	1.97 [0.18, 21.46]

PERMALINK

Oral prostaglandin E2 for induction of labour

Linda French

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Background

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Measures of effectiveness:

Complications:

Measures of satisfaction:

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

1. Methodological quality of trials.

Results

Description of studies

Excluded studies

Included studies

Risk of bias in included studies

Randomization

Blinding

Intent to treat

Effects of interventions

Primary outcomes

Secondary outcomes

Gastrointestinal side‐effects

Oxytocin augmentation

Uterine hyperstimulation without FHR changes

Epidural analgesia

Instrumental vaginal delivery

Meconium stained liquor

Apgar score less than seven at five minutes

Neonatal intensive care unit admission

Postpartum hemorrhage

Women not satisfied

Caregiver not satisfied

Other outcomes

Maternal or neonatal infection requiring antibiotics

Discussion

Authors' conclusions

Implications for practice.

Implications for research.

What's new

History

Acknowledgements

Data and analyses

Comparison 10. Oral prostaglandin vs placebeo or no treatment: all women.

10.3. Analysis.

10.7. Analysis.

10.8. Analysis.

10.11. Analysis.

10.20. Analysis.

10.21. Analysis.

10.28. Analysis.

10.29. Analysis.

Comparison 11. Oral prostaglandin vs placebo or no treatment: all women, unfavorable cervix.

11.3. Analysis.

11.8. Analysis.

11.11. Analysis.

Comparison 12. Oral prostaglandin vs placebo or no treatment: all women, ruptured membranes, variable or undefined cervix.

12.3. Analysis.

12.7. Analysis.

12.8. Analysis.

12.20. Analysis.

12.21. Analysis.

12.28. Analysis.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.20, 3.54]
11 Instrumental vaginal delivery	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	3.38 [0.37, 31.16]
20 Vomiting	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	14.59 [0.85, 251.01]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vaginal delivery not achieved within 24 hours	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.86, 10.43]
2 Uterine hyperstimulation with fetal heart rate changes	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	7.0 [0.37, 132.10]
3 Cesarean section	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.07, 8.38]
6 Cervix unfavorable/unchanged after 12‐24 hours	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.32, 27.87]
7 Oxytocin augmentation	2	223	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.36, 1.90]
11 Instrumental vaginal delivery	2	223	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.35, 3.75]
12 Meconium‐stained liquor	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
13 Apgar score < 7 at 5 minutes	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	0.52 [0.02, 12.44]
20 Vomiting	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.31, 5.65]
21 Diarrhoea	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.25, 101.58]
23 Postpartum haemorrhage	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 5.34]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vaginal delivery not achieved within 24 hours	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.56, 7.12]
2 Uterine hyperstimulation with fetal heart rate changes	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 70.30]
20 Vomiting	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.33, 26.92]
21 Diarrhoea	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.25, 99.16]
23 Postpartum haemorrhage	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vaginal delivery not achieved within 24 hours	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	7.0 [0.38, 128.87]
2 Uterine hyperstimulation with fetal heart rate changes	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.25, 99.16]
20 Vomiting	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 5.17]
21 Diarrhoea	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
23 Postpartum haemorrhage	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 5.17]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3 Cesarean section	2	46	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.33, 2.99]
6 Cervix unfavorable/unchanged after 12‐24 hours	1	16	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 3.61]
11 Instrumental vaginal delivery	2	46	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.28, 1.92]

Methods	Allocation: list of random numbers.   Blinding: none described.   Study period: not stated.
Participants	Inclusion criteria: multiparous women requiring induction of labor with Bishop score > 3.   Setting: Maternity hospital, London, UK.   Number of participants: n = 42.
Interventions	Oral PGE2 solution 0.5 mg every 2 hours as needed with increases by 0.5 mg per dose 2 mg (n = 22) vs IV oxytocin (n = 20). All women had amniotomy at start of induction.
Outcomes	Time of induction to delivery.   Mode of delivery.   Apgar score of infant.   Umbilical artery pH.   Hypertonus.   Hypertonus with fetal bradycardia.   Gastrointestinal side‐effects.
Notes	The prostaglandin solution was acceptable to all women who received it.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear

Methods	Allocation: "random", not further described.   Blinding: none.   Study period: not stated.
Participants	Inclusion criteria: women with gestation of at least 36 weeks, indication for induction of labor, and Bishop score less than 6.   Setting: University hospital, Cape Town, South Africa.   Number of participants: n = 33.
Interventions	Oral PGE2 1 mg hourly up to 5 mg (n = 16) vs intravaginal PGE2, 1 x 4 or 6 mg dose (n = 17).
Outcomes	Bishop score after 12 hours.   Cesarean sections.   Instrumental vaginal deliveries.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear

Methods	Allocation: concealed.   Blinding: double‐blind.   Study period: not stated.
Participants	Inclusion criteria: women with 36‐41 weeks' gestation with low or moderate Bishop score.   Setting: University hospital, San Francisco, CA.   Number of participants: n = 50.
Interventions	Oral PGE2 1 mg every 3 hours for 3 doses (n = 25) vs placebo (n = 25).
Outcomes	Mean change in Bishop score.   Cesarean section.   Uterine hypertonus.
Notes	Oxytocin infusion was started 9‐11 hours after 3rd oral dose. If labor was not achieved, it was discontinued and spontaneous labor ensued 1‐18 days later.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Low risk	A ‐ Adequate

Methods	Allocation: "randomized", not further described.   Blinding: allocation stated to be concealed, otherwise no blinding described.   Study period: not stated.
Participants	Inclusion criteria: women with PROM at 38‐41 weeks' gestation and no uterine contractions 3 hours after rupture.   Setting: University hospital Center, Dallas, Texas.   Number of participants: n = 100.
Interventions	Oral PGE2 0.5 mg every 30‐60 minutes starting 3 hours after PROM for up to 6 hours (n = 50) vs no treatment until 12 hours after PROM (n = 50). For both groups IV oxytocin was begun at 12 hours after PROM if not in active labor.
Outcomes	Time from PROM to delivery.   Fetal bradycardia.   Mode of delivery.   Gastrointestinal side‐effects.
Notes	Subgroups were considered based on parity and Bishop score at 3 hours after PROM.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Low risk	A ‐ Adequate

Methods	Allocation: sealed envelopes.   Blinding: none described.   Study period: not stated.
Participants	Inclusion criteria: women admitted for induction of labor with favorable cervix, singleton pregnancy, and clear amniotic fluid on amniotomy   Setting: general hospital, Isle of Sheppey, UK.   Number of participants: n = 100 (50 primigravidae, and 50 multigravidae).
Interventions	Oral PGE2 0.5 mg initial dose increasing up to 2 mg if needed, total 5 mg maximum (n = 50) vs oral oxytocin starting at 100 IU and escalating at 1/2 hour intervals as needed up to 4400 IU total dose (n = 50). Both groups had amniotomy performed at the beginning of induction.
Outcomes	Time to onset of labor.   Induction to delivery interval.   Duration of labor.   Mode of delivery.   Uterine hyperactivity.   Gastrointestinal side‐effects.   Apgar < 7 at 1 minute.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Low risk	A ‐ Adequate