Dataset Information

Labour induction with prostaglandins: a systematic review and network meta-analysis.

ABSTRACT:

Objectives

To assess the effectiveness and safety of prostaglandins used for labour induction.

Design

Systematic review with Bayesian network meta-analysis

Data sources

The Cochrane Pregnancy and Childbirth Group's Database of Trials (which incorporates the results of a broad generic search for all pregnancy and postpartum trials). Sources included are CENTRAL, Medline, Embase, NHS Economic Evaluation Database, CINAHL, relevant journals, conference proceedings, and registries of ongoing trials.

Eligibility criteria for selecting studies

Randomised clinical trials of prostaglandin or prostaglandin analogues used for third trimester cervical ripening or labour induction versus placebo or no treatment, alternative prostaglandin dose or administration, or a different type of prostaglandin. We included studies recruiting women with a viable fetus, but had no other restrictions relating to indication for labour induction or language of publication. Outcomes assessed were serious neonatal morbidity (trialist defined) or perinatal death; serious maternal morbidity (trialist defined) or death; vaginal delivery not achieved within 24 hours, caesarean section, and uterine hyperstimulation with fetal heart rate changes.

Results

280 randomised clinical trials were included (48 068 women) in the review. Maternal and neonatal mortality and serious morbidity were rarely reported and are summarized narratively. Unresolved inconsistency was observed for the hyperstimulation outcome. Relative to placebo, the odds of failing to achieve a vaginal delivery were lowest for vaginal misoprostol (≥50 µg) (odds ratio 0.06 (95% credible interval 0.02 to 0.12)), with a 39% absolute probability of event (95% credible interval 1% to 94%). Compared with placebo, odds of caesarean section were lowest for titrated oral misoprostol solution (<50 µg) (odds ratio 0.65 (0.49 to 0.83)), with an absolute probability of event of 15% (3% to 40%).

Conclusions

Low dose(<50 µg) titrated oral misoprostol solution had the lowest probability of caesarean section, whereas vaginal misprostol (≥50 µg) had the highest probability of achieving a vaginal delivery within 24 hours. These findings have important implications for a series of current national and international guidelines for induction of labour and future research in this area.

Systematic review registration

PROSPERO 2013:CRD42013005116.

SUBMITTER: Alfirevic Z

PROVIDER: S-EPMC4353287 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:As the number of indications for labour induction continue to increase, the focus has shifted to performing these procedures in an outpatient setting. This study aims to systematically review published data from randomized controlled trials that compare outpatient with inpatient labour induction, to ascertain the role of outpatient labour induction for low-risk pregnancies. METHODS:We conducted a systematic review wherein we searched MEDLINE, EMBASE, Biosis Previews®, and International Pharmaceutical Abstracts from inception to January 2020 to identify randomized controlled trials that reported on maternal, fetal and resource-related outcomes following outpatient versus inpatient labour induction. Pooled incidences and mean differences were calculated using random-effects meta-analysis. Risk-of-bias was assessed using the Cochrane Risk of Bias tool. Subgroup analysis was conducted based on the method of induction. RESULTS:Of the 588 records identified, 12 publications, representing nine independent randomized controlled trials conducted in Australia, Europe and North America, were included. These reported on 2615 cases of labour induction (1320 outpatients versus 1295 inpatients). Overall, apart from a higher number of suspicious fetal heart rate tracings [RR?=?1.43 (1.10, 1.86)] and a shorter mean length of hospital stay [MD?=?282.48?min (160.23, 404.73) shorter] in the outpatient group, there were no differences in delivery method, adverse outcomes or resource-use between the two arms. On subgroup analysis, when comparing the use of balloon catheters in both arms, those induced as outpatients had fewer caesarean deliveries [RR?=?0.52 (0.30, 0.90)], a shorter admission-to-delivery interval [MD?=?370.86?min (19.19, 722.54) shorter], and a shorter induction to delivery interval [MD?=?330.42?min (120.13, 540.71) shorter]. CONCLUSION:Outpatient labour induction in resource-rich settings is at least as effective and safe, in carefully selected patient populations, when compared with inpatient labour induction. Whether outpatient labour induction results in lower rates of caesarean deliveries needs to be explored further. TRIAL REGISTRATION:This systematic review was prospectively registered in Prospero ( CRD42019118049 ).

Project description:Prostaglandins are thought to be important mediators in the initiation of human labour, however the evidence supporting this is not entirely clear. Determining how, and which, prostaglandins change during pregnancy and labour may provide insight into mechanisms governing labour initiation and the potential to predict timing of labour onset. The current study systematically searched the existing scientific literature to determine how biofluid levels of prostaglandins change throughout pregnancy before and during labour, and whether prostaglandins and/or their metabolites may be useful for prediction of labour. The databases EMBASE and MEDLINE were searched for English-language articles on prostaglandins measured in plasma, serum, amniotic fluid, or urine during pregnancy and/or spontaneous labour. Studies were assessed for quality and risk of bias and a qualitative summary of included studies was generated. Our review identified 83 studies published between 1968-2021 that met the inclusion criteria. As measured in amniotic fluid, levels of PGE2, along with PGF2α and its metabolite 13,14-dihydro-15-keto-PGF2α were reported higher in labour compared to non-labour. In blood, only 13,14-dihydro-15-keto-PGF2α was reported higher in labour. Additionally, PGF2α, PGF1α, and PGE2 were reported to increase in amniotic fluid as pregnancy progressed, though this pattern was not consistent in plasma. Overall, the evidence supporting changes in prostaglandin levels in these biofluids remains unclear. An important limitation is the lack of data on the complexity of the prostaglandin pathway outside of the PGE and PGF families. Future studies using new methodologies capable of co-assessing multiple prostaglandins and metabolites, in large, well-defined populations, will help provide more insight as to the identification of exactly which prostaglandins and/or metabolites consistently change with labour. Revisiting and revising our understanding of the prostaglandins may provide better targets for clinical monitoring of pregnancies. This study was supported by the Canadian Institutes of Health Research.

Project description:ObjectivesTo compare the clinical effectiveness and cost-effectiveness of labour induction methods.MethodsWe conducted a systematic review of randomised trials comparing interventions for third-trimester labour induction (search date: March 2014). Network meta-analysis was possible for six of nine prespecified key outcomes: vaginal delivery within 24 hours (VD24), caesarean section, uterine hyperstimulation, neonatal intensive care unit (NICU) admissions, instrumental delivery and infant Apgar scores. We developed a decision-tree model from a UK NHS perspective and calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit, and cost-effectiveness acceptability curves.Main resultsIn all, 611 studies comparing 31 active interventions were included. Intravenous oxytocin with amniotomy and vaginal misoprostol (≥50 μg) were most likely to achieve VD24. Titrated low-dose oral misoprostol achieved the lowest odds of caesarean section, but there was considerable uncertainty in ranking estimates. Vaginal (≥50 μg) and buccal/sublingual misoprostol were most likely to increase uterine hyperstimulation with high uncertainty in ranking estimates. Compared with placebo, extra-amniotic prostaglandin E2 reduced NICU admissions. There were insufficient data to conduct analyses for maternal and neonatal mortality and serious morbidity or maternal satisfaction. Conclusions were robust after exclusion of studies at high risk of bias. Due to poor reporting of VD24, the cost-effectiveness analysis compared a subset of 20 interventions. There was considerable uncertainty in estimates, but buccal/sublingual and titrated (low-dose) misoprostol showed the highest probability of being most cost-effective.ConclusionsFuture trials should be designed and powered to detect a method that is more cost-effective than low-dose titrated oral misoprostol.Tweetable abstractNew study ranks methods to induce labour in pregnant women on effectiveness and cost.

Project description:BackgroundThe proportion of women undergoing induction of labour (IOL) has risen in recent decades, with significant variation within countries and between hospitals. The aim of this study was to review research supporting indications for IOL and determine which indications are supported by evidence and where knowledge gaps exist.MethodsA systematic scoping review of quantitative studies of common indications for IOL. For each indication, we included systematic reviews/meta-analyses, randomised controlled trials (RCTs), cohort studies and case control studies that compared maternal and neonatal outcomes for different modes or timing of birth. Studies were identified via the databases PubMed, Maternity and Infant Care, CINAHL, EMBASE, and ClinicalTrials.gov from between April 2008 and November 2019, and also from reference lists of included studies. We identified 2554 abstracts and reviewed 300 full text articles. The quality of included studies was assessed using the RoB 2.0, the ROBINS-I and the ROBIN tool.Results68 studies were included which related to post-term pregnancy (15), hypertension/pre-eclampsia (15), diabetes (9), prelabour rupture of membranes (5), twin pregnancy (5), suspected fetal compromise (4), maternal elevated body mass index (BMI) (4), intrahepatic cholestasis of pregnancy (3), suspected macrosomia (3), fetal gastroschisis (2), maternal age (2), and maternal cardiac disease (1). Available evidence supports IOL for women with post-term pregnancy, although the evidence is weak regarding the timing (41 versus 42 weeks), and for women with hypertension/preeclampsia in terms of improved maternal outcomes. For women with preterm premature rupture of membranes (24-37 weeks), high-quality evidence supports expectant management rather than IOL/early birth. Evidence is weakly supportive for IOL in women with term rupture of membranes. For all other indications, there were conflicting findings and/or insufficient power to provide definitive evidence.ConclusionsWhile for some indications, IOL is clearly recommended, a number of common indications for IOL do not have strong supporting evidence. Overall, few RCTs have evaluated the various indications for IOL. For conditions where clinical equipoise regarding timing of birth may still exist, such as suspected macrosomia and elevated BMI, researchers and funding agencies should prioritise studies of sufficient power that can provide quality evidence to guide care in these situations.