Interventions for treating hyperemesis gravidarum: a Cochrane systematic review and meta-analysis.

INTRODUCTION: While nausea and vomiting in early pregnancy are very common, affecting approximately 80% of the pregnancies, hyperemesis gravidarum is a severe form affecting 0.3-1.0% of the pregnancies. Although hyperemesis gravidarum is rarely a source of mortality, it is a significant source of morbidity. It is one of the most common indications for hospitalization in pregnancy. Beyond the maternal and fetal consequences of malnutrition, the severity of hyperemesis symptoms causes a major psychosocial burden leading to depression, anxiety, and even pregnancy termination. The aim of this meta-analysis was to examine all randomized controlled trials of interventions specifically for hyperemesis gravidarum and evaluate them based on both subjective and objective measures of efficacy, maternal and fetal/neonatal safety, and economic costs. MATERIAL AND METHODS: Randomized controlled trials were identified by searching electronic databases. We included all randomized controlled trials for the treatment of hyperemesis gravidarum. The primary outcome was intervention efficacy as defined by severity, reduction, or cessation in nausea/vomiting; number of episodes of emesis; and days of hospital admission. Secondary outcomes included other measures of intervention efficacy, adverse maternal/fetal/neonatal outcomes, quality of life measures, and economic costs. RESULTS: Twenty-five trials (2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. Selected comparisons reported below: No primary outcome data were available when acupuncture was compared with placebo. There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (risk ratio (RR) 1.40, 95% CI 0.79-2.49 and RR 1.51, 95% CI 0.92-2.48, respectively). Midwife-led outpatient care was associated with fewer hours of hospital admission than routine inpatient admission (mean difference (MD) - 33.20, 95% CI -46.91 to -19.49) with no difference in pregnancy-unique quantification of emesis and nausea (PUQE) score, decision to terminate the pregnancy, miscarriage, small-for-gestational age infants, or time off work when compared with routine care. Women taking vitamin B6 had a slightly longer hospital stay compared with placebo (MD 0.80 days, 95% CI 0.08-1.52). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI -0.40-1.40) or side effects. A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI -0.15-3.55, and MD -0.10, 95% CI -1.63-1.43; one study, 83 women, respectively). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23-4.69, and RR 2.38, 95% CI 1.10-5.11, respectively). There were no clear differences between groups for other side effects. In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (risk ratio (RR) 0.70, 95% CI 0.56-0.87, RR 0.48, 95% CI 0.34-0.69, and RR 0.31, 95% CI 0.11-0.90, respectively). There were no clear differences between groups for other important outcomes including quality of life and other side effects. In a single trial with 30 women, those receiving ondansetron had no difference in duration of hospital admission compared to those receiving promethazine (mean difference (MD) 0.00, 95% CI -1.39-1.39), although there was increased sedation with promethazine (RR 0.06, 95% CI 0.00-0.94). Regarding corticosteroids, in a study with 110 participants there was no difference in days of hospital admission compared to placebo (MD -0.30, 95% CI -0.70-0.10), but there was a decreased readmission rate (RR 0.69, 95% CI 0.50-0.94; 4 studies, 269 women). For hydrocortisone compared with metoclopramide, no data were available for primary outcomes and there was no difference in the readmission rate (RR 0.08, 95% CI 0.00-1.28; one study, 40 women). In a study with 80 women, compared to promethazine, those receiving prednisolone had increased nausea at 48 h (RR 2.00, 95% CI 1.08-3.72), but not at 17 days (RR 0.81, 95% CI 0.58-1.15). There was no clear difference in the number of episodes of emesis or subjective improvement in nausea/vomiting. CONCLUSIONS: While there were a wide range of interventions studied, both pharmaceutical and otherwise, there were a limited number of placebo controlled trials. In comparing the efficacy of the commonly used antiemetics, metoclopramide, ondansetron, and promethazine, the results of this review do not support the clear superiority of one over the other in symptomatic relief. Other factors such as side effect profile medication safety and healthcare costs should also be considered when selecting an intervention.

Pharmacological and mechanical interventions for labour induction in outpatient settings.

BACKGROUND: Induction of labour is carried out for a variety of indications and using a range of methods. For women at low risk of pregnancy complications, some methods of induction of labour or cervical ripening may be suitable for use in outpatient settings. OBJECTIVES: To examine pharmacological and mechanical interventions to induce labour or ripen the cervix in outpatient settings in terms of effectiveness, maternal satisfaction, healthcare costs and, where information is available, safety. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2016) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials examining outpatient cervical ripening or induction of labour with pharmacological agents or mechanical methods. Cluster trials were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed evidence using the GRADE approach. MAIN RESULTS: This updated review included 34 studies of 11 different methods for labour induction with 5003 randomised women, where women received treatment at home or were sent home after initial treatment and monitoring in hospital.Studies examined vaginal and intracervical prostaglandin E2 (PGE2), vaginal and oral misoprostol, isosorbide mononitrate, mifepristone, oestrogens, amniotomy and acupuncture, compared with placebo, no treatment, or routine care. Trials generally recruited healthy women with a term pregnancy. The risk of bias was mostly low or unclear, however, in 16 trials blinding was unclear or not attempted. In general, limited data were available on the review's main and additional outcomes. Evidence was graded low to moderate quality. 1. Vaginal PGE2 versus expectant management or placebo (5 studies)Fewer women in the vaginal PGE2 group needed additional induction agents to induce labour, however, confidence intervals were wide (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.27 to 0.99; 150 women; 2 trials). There were no clear differences between groups in uterine hyperstimulation (with or without fetal heart rate (FHR) changes) (RR 3.76, 95% CI 0.64 to 22.24; 244 women; 4 studies; low-quality evidence), caesarean section (RR 0.80, 95% CI 0.49 to 1.31; 288 women; 4 studies; low-quality evidence), or admission to a neonatal intensive care unit (NICU) (RR 0.32, 95% CI 0.10 to 1.03; 230 infants; 3 studies; low-quality evidence).There was no information on vaginal birth within 24, 48 or 72 hours, length of hospital stay, use of emergency services or maternal or caregiver satisfaction. Serious maternal and neonatal morbidity or deaths were not reported. 2. Intracervical PGE2 versus expectant management or placebo (7 studies) There was no clear difference between women receiving intracervical PGE2 and no treatment or placebo in terms of need for additional induction agents (RR 0.98, 95% CI 0.74 to 1.32; 445 women; 3 studies), vaginal birth not achieved within 48 to 72 hours (RR 0.83, 95% CI 0.68 to 1.02; 43 women; 1 study; low-quality evidence), uterine hyperstimulation (with FHR changes) (RR 2.66, 95% CI 0.63 to 11.25; 488 women; 4 studies; low-quality evidence), caesarean section (RR 0.90, 95% CI 0.72 to 1.12; 674 women; 7 studies; moderate-quality evidence), or babies admitted to NICU (RR 1.61, 95% CI 0.43 to 6.05; 215 infants; 3 studies; low-quality evidence). There were no uterine ruptures in either the PGE2 group or placebo group.There was no information on vaginal birth not achieved within 24 hours, length of hospital stay, use of emergency services, mother or caregiver satisfaction, or serious morbidity or neonatal morbidity or perinatal death. 3. Vaginal misoprostol versus placebo (4 studies)One small study reported on the rate of perinatal death with no clear differences between groups; there were no deaths in the treatment group compared with one stillbirth (reason not reported) in the control group (RR 0.34, 95% CI 0.01 to 8.14; 77 infants; 1 study; low-quality evidence).There was no clear difference between groups in rates of uterine hyperstimulation with FHR changes (RR 1.97, 95% CI 0.43 to 9.00; 265 women; 3 studies; low-quality evidence), caesarean section (RR 0.94, 95% CI 0.61 to 1.46; 325 women; 4 studies; low-quality evidence), and babies admitted to NICU (RR 0.89, 95% CI 0.54 to 1.47; 325 infants; 4 studies; low-quality evidence).There was no information on vaginal birth not achieved within 24, 48 or 72 hours, additional induction agents required, length of hospital stay, use of emergency services, mother or caregiver satisfaction, serious maternal, and other neonatal, morbidity or death.No substantive differences were found for other comparisons. One small study found that women who received oral misoprostol were more likely to give birth within 24 hours (RR 0.65, 95% CI 0.48 to 0.86; 87 women; 1 study) and were less likely to require additional induction agents (RR 0.60, 95% CI 0.37 to 0.97; 127 women; 2 studies). Women who received mifepristone were also less likely to require additional induction agents (average RR 0.59, 95% CI 0.37 to 0.95; 311 women; 4 studies; I² = 74%); however, this result should be interpreted with caution due to high heterogeneity. One trial each of acupuncture and outpatient amniotomy were included, but few review outcomes were reported. AUTHORS' CONCLUSIONS: Induction of labour in outpatient settings appears feasible and important adverse events seem rare, however, in general there is insufficient evidence to detect differences. There was no strong evidence that agents used to induce labour in outpatient settings had an impact (positive or negative) on maternal or neonatal health. There was some evidence that compared to placebo or no treatment, induction agents administered on an outpatient basis reduced the need for further interventions to induce labour, and shortened the interval from intervention to birth.We do not have sufficient evidence to know which induction methods are preferred by women, the interventions that are most effective and safe to use in outpatient settings, or their cost effectiveness. Further studies where various women-friendly outpatient protocols are compared head-to-head are required. As part of such work, women should be consulted on what sort of management they would prefer.

Nitric oxide donors for cervical ripening and induction of labour.

BACKGROUND: Sometimes it is necessary to bring on labour artificially because of safety concerns for the mother or baby. This review is one of a series of reviews of methods of labour induction using a standardised protocol. OBJECTIVES: To determine the effects of NO donors (isosorbide mononitrate (ISMN), isosorbide dinitrate (ISDN), nitroglycerin and sodium nitroprusside) for third trimester cervical ripening or induction of labour, in comparison with placebo or no treatment or other treatments from a predefined hierarchy. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (15 August 2016) and the reference lists of trial reports. SELECTION CRITERIA: Clinical trials comparing NO donors for cervical ripening or labour induction with other methods listed above it on a predefined list of methods of labour induction. Interventions include NO donors (isosorbide mononitrate, isosorbide dinitrate, nitroglycerin and sodium nitroprusside) compared with other methods listed above it on a predefined list of methods of labour induction. DATA COLLECTION AND ANALYSIS: This review is part of a series of reviews focusing on methods of induction of labour, based on a generic protocol. Three review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. In this update, the quality of the evidence for the main comparison was assessed using the GRADE approach. MAIN RESULTS: We included 23 trials (including a total of 4777 women). Included studies compared NO donors with placebo, vaginal prostaglandin E2 (PGE2), intracervical PGE2, vaginal misoprostol and intracervical Foley catheter. The majority of the included studies were assessed as being at low risk of bias. Nitric oxide versus placebo There was no evidence of a difference for any of the primary outcomes analysed: vaginal delivery not achieved in 24 hours (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.83 to 1.15; one trial, 238 women; low-quality evidence), uterine hyperstimulation with fetal heart rate (FHR) changes (RR 0.09, 95% CI 0.01 to 1.62; two trials, 300 women; low-quality evidence), caesarean section (RR 0.99, 95% CI 0.88 to 1.11; nine trials, 2624 women; moderate-quality evidence) or serious neonatal morbidity/perinatal death (average RR 1.61, 95% CI 0.08 to 33.26; two trials, 1712 women; low-quality evidence). There were no instances of serious maternal morbidity or death (one study reported this outcome).There was a reduction in an unfavourable cervix at 12 to 24 hours in women treated with NO donors (average RR 0.78, 95% CI 0.67 to 0.90; four trials, 762 women), and this difference was observed in both subgroups of standard release and slow release formulation. Women who received NO donors were less likely to experience uterine hyperstimulation without FHR rate changes (RR 0.05, 95% CI 0.00 to 0.80; one trial, 200 women), and more likely to experience side effects, including nausea, headache and vomiting. Nitric oxide donors versus vaginal prostaglandins There was no evidence of any difference between groups for uterine hyperstimulation with FHR changes or caesarean section (RR 0.97, 95% CI 0.78 to 1.21; three trials, 571 women). Serious neonatal morbidity and serious maternal morbidity were not reported. There were fewer women in the NO donor group who did not achieve a vaginal delivery within 24 hours (RR 0.63, 95% CI 0.47 to 0.86; one trial, 400 primiparae women). Nitric oxide donors versus intracervical prostaglandins One study reported a reduction in the number of women who had not achieved a vaginal delivery within 24 hours with NO donors (RR 0.63, 95% CI 0.47 to 0.86; one trial, 400 women). This result should be interpreted with caution as the information was extracted from an abstract only and a full report of the study is awaited. No differences were observed between groups for uterine hyperstimulation with FHR changes (RR 0.33, 95% CI 0.01 to 7.74; one trial, 42 women) or serious neonatal morbidity/perinatal death (RR 0.33, 95% CI 0.01 to 7.74; one trial, 42 women). Fewer women in the NO donor group underwent a caesarean section in comparison to women who received intracervical prostaglandins (RR 0.63, 95% CI 0.44 to 0.90; two trials, 442 women). No study reported on the outcome serious maternal morbidity or death. Nitric oxide donors versus vaginal misoprostol There was a reduction in the rate of uterine hyperstimulation with FHR changes with NO donors (RR 0.07, 95% CI 0.01 to 0.37; three trials, 281 women). There were no differences in caesarean section rates (RR 1.00, 95% CI 0.82 to 1.21; 761 women; six trials) and no cases of serious neonatal morbidity/perinatal death were reported. One study found that women in the NO donor group were more likely to not deliver within 24 hours (RR 5.33, 95% CI 1.62 to 17.55; one trial, 150 women). Serious maternal morbidity or death was not reported.In terms of secondary outcomes, there was an increase in cervix unchanged/unfavourable with NO (RR 3.43, 95% CI 2.07 to 5.66; two trials, 151 women) and an increase in the need for oxytocin augmentation with NO induction (RR 2.67, 95% CI 1.31 to 5.45; 7 trials; 767 women), although there was evidence of significant heterogeneity which could not be fully explained. Uterine hyperstimulation without FHR was lower in the NO group, as was meconium-stained liquor, Apgar score less than seven at five minutes and analgesia requirements. Nitric oxide donors versus intracervical catheter There was no evidence on any difference between the effects of NO and the use of a Foley catheter for induction of labour for caesarean section (RR 1.00, 95% CI 0.39 to 2.59; one trial, 80 women). No other primary outcomes were reported. One study of 75 participants did not contribute any data to the review.For all comparisons, women who received NO donors were more likely to experience side effects such as headache, nausea or vomiting. AUTHORS' CONCLUSIONS: Available data suggests that NO donors can be a useful tool in the process of induction of labour causing the cervix to be more favourable in comparison to placebo. However, additional data are needed to assess the true impact of NO donors on all important labour process and delivery outcomes.

Interventions for treating hyperemesis gravidarum.

BACKGROUND: Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for hospitalization during pregnancy. While a previous Cochrane review examined interventions for nausea and vomiting in pregnancy, there has not yet been a review examining the interventions for the more severe condition of hyperemesis gravidarum. OBJECTIVES: To assess the effectiveness and safety, of all interventions for hyperemesis gravidarum in pregnancy up to 20 weeks' gestation. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (20 December 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomized controlled trials of any intervention for hyperemesis gravidarum. Quasi-randomized trials and trials using a cross-over design were not eligible for inclusion.We excluded trials on nausea and vomiting of pregnancy that were not specifically studying the more severe condition of hyperemesis gravidarum. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed the eligibility of trials, extracted data and evaluated the risk of bias. Data were checked for accuracy. MAIN RESULTS: Twenty-five trials (involving 2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. The comparisons covered a range of interventions including acupressure/acupuncture, outpatient care, intravenous fluids, and various pharmaceutical interventions. The methodological quality of included studies was mixed. For selected important comparisons and outcomes, we graded the quality of the evidence and created 'Summary of findings' tables. For most outcomes the evidence was graded as low or very low quality mainly due to the imprecision of effect estimates. Comparisons included in the 'Summary of findings' tables are described below, the remaining comparisons are described in detail in the main text.No primary outcome data were available when acupuncture was compared with placebo, There was no clear evidence of differences between groups for anxiodepressive symptoms (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.40; one study, 36 women, very low-quality evidence), spontaneous abortion (RR 0.48, 95% CI 0.05 to 5.03; one study, 57 women, low-quality evidence), preterm birth (RR 0.12, 95% CI 0.01 to 2.26; one study, 36 women, low-quality evidence), or perinatal death (RR 0.57, 95% CI 0.04 to 8.30; one study, 36 women, low-quality evidence).There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (RR 1.40, 95% CI 0.79 to 2.49 and RR 1.51, 95% CI 0.92 to 2.48, respectively; very low-quality evidence).In a study with 92 participants, women taking vitamin B6 had a slightly longer hospital stay compared with placebo (mean difference (MD) 0.80 days, 95% CI 0.08 to 1.52, moderate-quality evidence). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI -0.40 to 1.40, low-quality evidence) or side effects.A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI -0.15 to 3.55, and MD -0.10, 95% CI -1.63 to 1.43; one study, 83 women, respectively, very low-quality evidence). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23 to 4.69, and RR 2.38, 95% CI 1.10 to 5.11, respectively; moderate-quality evidence). There were no clear differences between groups for other side effects.In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (RR 0.70, 95% CI 0.56 to 0.87, RR 0.48, 95% CI 0.34 to 0.69, and RR 0.31, 95% CI 0.11 to 0.90, respectively, moderate-quality evidence). There were no clear differences between groups for other important outcomes including quality of life and other side effects.In a single trial with 30 women, those receiving ondansetron had no difference in duration of hospital admission compared to those receiving promethazine (MD 0.00, 95% CI -1.39 to 1.39, very low-quality evidence), although there was increased sedation with promethazine (RR 0.06, 95% CI 0.00 to 0.94, low-quality evidence) .Regarding corticosteroids, in a study with 110 participants there was no difference in days of hospital admission compared to placebo (MD -0.30, 95% CI -0.70 to 0.10; very low-quality evidence), but there was a decreased readmission rate (RR 0.69, 95% CI 0.50 to 0.94; four studies, 269 women). For other important outcomes including pregnancy complications, spontaneous abortion, stillbirth and congenital abnormalities, there was insufficient evidence to identify differences between groups (very low-quality evidence for all outcomes). In other single studies there were no clear differences between groups for preterm birth or side effects (very low-quality evidence).For hydrocortisone compared with metoclopramide, no data were available for primary outcomes and there was no difference in the readmission rate (RR 0.08, 95% CI 0.00 to 1.28;one study, 40 women).In a study with 80 women, compared to promethazine, those receiving prednisolone had increased nausea at 48 hours (RR 2.00, 95% CI 1.08 to 3.72; low-quality evidence), but not at 17 days (RR 0.81, 95% CI 0.58 to 1.15, very low-quality evidence). There was no clear difference in the number of episodes of emesis or subjective improvement in nausea/vomiting. There was insufficient evidence to identify differences between groups for stillbirth and neonatal death and preterm birth. AUTHORS' CONCLUSIONS: On the basis of this review, there is little high-quality and consistent evidence supporting any one intervention, which should be taken into account when making management decisions. There was also very limited reporting on the economic impact of hyperemesis gravidarum and the impact that interventions may have.The limitations in interpreting the results of the included studies highlights the importance of consistency in the definition of hyperemesis gravidarum, the use of validated outcome measures, and the need for larger placebo-controlled trials.

Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term.

BACKGROUND: Prostaglandins have been used for induction of labour since the 1960s. This is one of a series of reviews evaluating methods of induction of labour. This review focuses on prostaglandins given per vaginam, evaluating these in comparison with placebo (or expectant management) and with each other; prostaglandins (PGE2 and PGF2a); different formulations (gels, tablets, pessaries) and doses. OBJECTIVES: To determine the effects of vaginal prostaglandins E2 and F2a for third trimester cervical ripening or induction of labour in comparison with placebo/no treatment or other vaginal prostaglandins (except misoprostol). SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 March 2014) and bibliographies of relevant papers. SELECTION CRITERIA: Clinical trials comparing vaginal prostaglandins used for third trimester cervical ripening or labour induction with placebo/no treatment, with each other, or other methods listed above it on a predefined list of labour induction methods. DATA COLLECTION AND ANALYSIS: We assessed studies and extracted data independently. MAIN RESULTS: Seventy randomised controlled trials (RCTs) (11,487 women) are included. In this update seven new RCTs (778 women) have been added. Two of these new trials compare PGE2 with no treatment, four compare different PGE2 formulations (gels versus tablets, or sustained release pessaries) and one trial compares PGF2a with placebo. The majority of trials were at unclear risk of bias for most domains.Overall, vaginal prostaglandin E2 compared with placebo or no treatment probably reduces the likelihood of vaginal delivery not being achieved within 24 hours. The risk of uterine hyperstimulation with fetal heart rate changes is increased (4.8% versus 1.0%, risk ratio (RR) 3.16, 95% confidence interval (CI) 1.67 to 5.98, 15 trials, 1359 women). The caesarean section rate is probably reduced by about 10% (13.5% versus 14.8%, RR 0.91, 95% CI 0.81 to 1.02, 36 trials, 6599 women). The overall effect on improving maternal and fetal outcomes (across a variety of measures) is uncertain.PGE2 tablets, gels and pessaries (including sustained release preparations) appear to be as effective as each other, small differences are detected between some outcomes, but these maybe due to chance. AUTHORS' CONCLUSIONS: Prostaglandins PGE2 probably increase the chance of vaginal delivery in 24 hours, they increase uterine hyperstimulation with fetal heart changes but do not effect or may reduce caesarean section rates. They increase the likelihood of cervical change, with no increase in operative delivery rates. PGE2 tablets, gels and pessaries appear to be as effective as each other, any differences between formulations are marginal but may be important.

Outpatient versus inpatient induction of labour for improving birth outcomes.

BACKGROUND: More than 20% of women undergo induction of labour in some countries. The different methods used to induce labour have been the focus of previous reviews, but the setting in which induction takes place (hospital versus outpatient settings) may have implications for maternal satisfaction and costs. It is not known whether some methods of induction that are effective and safe in hospital are suitable in outpatient settings. OBJECTIVES: To assess the effects on outcomes for mothers and babies of induction of labour for women managed as outpatients versus inpatients. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013). SELECTION CRITERIA: Published and unpublished randomised and quasi-randomised trials in which inpatient and outpatient methods of cervical ripening or induction of labour have been compared. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial reports for inclusion. Two review authors carried out data extraction and assessment of risk of bias independently. MAIN RESULTS: We included four trials, with a combined total of 1439 women in the review; each trial examined a different method of induction and we were unable to pool the results from trials.1. Vaginal PGE2 (two studies including 1028 women). There were no differences between women managed as outpatients versus inpatients for most review outcomes. There was no evidence of a difference between the likelihood of women requiring instrumental delivery in either setting (risk ratio (RR) 1.29; 95% confidence interval (CI) 0.79 to 2.13). The overall length of hospital stay was similar in the two groups.2. Controlled release PGE2 10 mg (one study including 300 women). There was no evidence of differences between groups for most review outcomes, including success of induction. During the induction period itself, women in the outpatient group were more likely to report high levels of satisfaction with their care (satisfaction rated seven or more on a nine-point scale, RR 1.42; 95% CI 1.11 to 1.81), but satisfaction scores measured postnatally were similar in the two groups.3. Foley catheter (one study including 111 women). There was no evidence of differences between groups for caesarean section rates, total induction time and the numbers of babies admitted to neonatal intensive care. AUTHORS' CONCLUSIONS: The data available to evaluate the efficacy or potential hazards of outpatient induction are limited. It is, therefore, not yet possible to determine whether induction of labour is effective and safe in outpatient settings.

Castor oil, bath and/or enema for cervical priming and induction of labour.

BACKGROUND: Castor oil, a potent cathartic, is derived from the bean of the castor plant. Anecdotal reports, which date back to ancient Egypt have suggested the use of castor oil to stimulate labour. Castor oil has been widely used as a traditional method of initiating labour in midwifery practice. Its role in the initiation of labour is poorly understood and data examining its efficacy within a clinical trial are limited. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. OBJECTIVES: To determine the effects of castor oil or enemas for third trimester cervical ripening or induction of labour in comparison with other methods of cervical ripening or induction of labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013) and bibliographies of relevant papers. SELECTION CRITERIA: Clinical trials comparing castor oil, bath or enemas used for third trimester cervical ripening or labour induction with placebo/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: Three trials, involving 233 women, are included. There was no evidence of differences in caesarean section rates between the two interventions in the two trials reporting this outcome (risk ratio (RR) 2.04, 95% confidence interval (CI) 0.92 to 4.55). There were no data presented on neonatal or maternal mortality or morbidity.There was no evidence of a difference between castor oil and placebo/no treatment for the rate of instrumental delivery, meconium-stained liquor, or Apgar score less than seven at five minutes. The number of participants was too small to detect all but large differences in outcome. All women who ingested castor oil felt nauseous (RR 59.92, 95% CI 8.46 to 424.52). AUTHORS' CONCLUSIONS: The three trials included in the review contain small numbers of women. All three studies used single doses of castor oil. The results from these studies should be interpreted with caution due to the risk of bias introduced due to poor methodological quality. Further research is needed to attempt to quantify the efficacy of castor oil as an cervical priming and induction agent.

Mechanical methods for induction of labour.

BACKGROUND: Mechanical methods were the first methods developed to ripen the cervix and induce labour. During recent decades they have been substituted by pharmacological methods. Potential advantages of mechanical methods, compared with pharmacological methods, may include simplicity of preservation, lower cost and reduction of the side effects. OBJECTIVES: To determine the effects of mechanical methods for third trimester cervical ripening or induction of labour in comparison with placebo/no treatment, prostaglandins (vaginal and intracervical prostaglandin E2 (PGE2), misoprostol) and oxytocin. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2011) and bibliographies of relevant papers. We updated this search on 16 January 2012 and added the results to the awaiting classification section of the review. SELECTION CRITERIA: Clinical trials comparing mechanical methods used for third trimester cervical ripening or labour induction with methods listed above it on a predefined list of methods of labour. A comparison with amniotomy will be added, should this comparison be made in future trials.Different types of intervention have been considered as mechanical methods: (1) introduction of laminaria tents, or their synthetic equivalent (Dilapan), into the cervical canal; (2) the introduction of a catheter through the cervix into the extra-amniotic space, with or without traction; (3) use of a catheter to inject fluidsin the extra-amniotic spaceIn addition, we made other comparisons: (1) specific mechanical methods (balloon catheter and laminaria tents) compared with any prostaglandins or with oxytocin; (2) addition of prostaglandins or oxytocin to mechanical methods compared with prostaglandins alone. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors independently extracted data. MAIN RESULTS: For this update we have included a further 27 studies. The review includes 71 randomised controlled trials (total of 9722 women), ranging from 39 to 588 women per study. Most studies reported on caesarean section, all other outcomes are based on substantially fewer women. Four additional studies are ongoing.Mechanical methods versus no treatment: one study (48 woman) reported on women who did not achieve vaginal delivery within 24 hours (risk ratio (RR) 0.90; 95% confidence interval (CI) 0.64 to 1.26). The risk of caesarean section was similar between groups (six studies; 416 women, RR 1.00; 95% CI 0.76 to 1.30). There were no cases of severe neonatal and maternal morbidity.Mechanical methods versus vaginal PGE2 (17 studies;1894 woman): The proportion of women who did not achieve vaginal delivery within 24 hours was not significantly different (three studies; 586 women RR 1.72; 95% CI 0.90 to 3.27); however, for the subgroup of multiparous women the risk of not achieving delivery within 24 hours was higher (one study; 147 women RR 4.38, 95% CI 1.74 to 10.98), with no increase in caesarean sections (RR 1.19, 95% CI 0.62-2.29). Compared with intracervical PGE2 (14 studies;1784 women and misoprostol there was no significant difference in the proportion of women not achieving vaginal delivery within 24 hours.Mechanical methods reduced the risk of hyperstimulation with fetal heart rate changes when compared with vaginal prostaglandins: vaginal PGE2 (eight studies; 1203 women, RR 0.16; 95% CI 0.06 to 0.39) and misoprostol (3% versus 9%) (nine studies; 1615 women, RR 0.37; 95% CI 0.25 to 0.54). Risk of caesarean section between mechanical methods and prostaglandins was comparable. Serious neonatal and maternal morbidity were infrequently reported and did not differ between the groups.Mechanical methods compared with induction with oxytocin (reduced the risk of caesarean section (five studies; 398 women, RR 0.62; 95% CI 0.42 to 0.90). The likelihood of vaginal delivery within 24 hours was not reported. Hyperstimulation with fetal heart rate changes was reported in one study (200 participants), and did not differ. There were no reported cases of severe maternal or neonatal morbidity. AUTHORS' CONCLUSIONS: Induction of labour using mechanical methods results in similar caesarean section rates as prostaglandins, for a lower risk of hyperstimulation. Mechanical methods do not increase the overall number of women not delivered within 24 hours, however the proportion of multiparous women who did not achieve vaginal delivery within 24 hours was higher when compared with vaginal PGE2. Compared with oxytocin, mechanical methods reduce the risk of caesarean section.

Nitric oxide donors for cervical ripening and induction of labour.

BACKGROUND: Sometimes it is necessary to bring on labour artificially because of safety concerns for the mother or baby. This review is one of a series of reviews of methods of labour induction using a standardised protocol.Induction of labour occurs in approximately 20% of pregnancies in the UK. The ideal agent for induction of labour would induce cervical ripening without causing uterine contractions. Currently most commonly used cervical ripening or induction agents result in uterine activity or contractions, or both. Cervical ripening without uterine contractility could occur safely in an outpatient setting and it may be expected that this would result in greater maternal satisfaction and lower costs. OBJECTIVES: To determine the effects of nitric oxide (NO) donors for third trimester cervical ripening or induction of labour, in comparison with placebo or no treatment or other treatments from a predefined hierarchy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2010) and the reference lists of trial reports and reviews. SELECTION CRITERIA: Clinical trials comparing NO donors for cervical ripening or labour induction to other methods listed above it on a predefined list of methods of labour induction. The trials include some form of random allocation to either group; and report one or more of the prestated outcomes. NO donors (isosorbide mononitrate, nitroglycerin and sodium nitroprusside) are compared to other methods listed above it on a predefined list of methods of labour induction. DATA COLLECTION AND ANALYSIS: This review is part of a series of reviews focusing on methods of induction of labour. Three review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. MAIN RESULTS: We considered 19 trials; we included 10 (including a total of 1889 women) trials, excluded eight trials and one trial report is awaiting classification. Included studies compared NO donors to placebo, vaginal prostaglandin E2, intracervical PGE2 and vaginal misoprostol. All included studies were of a generally high standard with a low risk of bias.There are very limited data available to compare nitric oxide donors to any other induction agent. There is no evidence of any difference between any of the prespecified outcomes when comparing NO donors to other induction agents, with the exception of an increase in maternal side effects. AUTHORS' CONCLUSIONS: NO donors do not appear currently to be a useful tool in the process of induction of labour. More studies are required to examine how NO donors may work alongside established induction of labour protocols, especially those based in outpatient settings.

Different methods for the induction of labour in outpatient settings.

BACKGROUND: Induction of labour is carried out for a variety of indications and using a range of pharmacological, mechanical and other methods. For women at low risk, some methods of induction of labour may be suitable for use in outpatient settings. OBJECTIVES: To examine pharmacological and mechanical interventions to induce labour in outpatient settings in terms of feasibility, effectiveness, maternal satisfaction, healthcare costs and, where information is available, safety. The review complements existing reviews on labour induction examining effectiveness and safety. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2009) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials examining outpatient cervical ripening or induction of labour with pharmacological agents or mechanical methods. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed eligible papers for risk of bias. We checked all data after entry into review manager software. MAIN RESULTS: We included 28 studies with 2616 women examining different methods of induction of labour where women received treatment at home or were sent home after initial treatment and monitoring in hospital.Studies examined vaginal and intracervical PGE(2), vaginal and oral misoprostol, isosorbide mononitrate, mifepristone, oestrogens, and acupuncture. Overall, the results demonstrate that outpatient induction of labour is feasible and that important adverse events are rare. There was no strong evidence that agents used to induce labour in outpatient settings had an impact (positive or negative) on maternal or neonatal health. There was some evidence that, compared to placebo or no treatment, induction agents reduced the need for further interventions to induce labour, and shortened the interval from intervention to birth. We were unable to pool results on outcomes relating to progress in labour as studies tended to measure a very broad range of outcomes.There was no evidence that induction agents increased interventions in labour such as operative deliveries. Only two studies provided information on women's views about the induction process, and overall there was very little information on the costs to health service providers of different methods of labour induction in outpatient settings. AUTHORS' CONCLUSIONS: Induction of labour in outpatient settings appears feasible. We do not have sufficient evidence to know which induction methods are preferred by women, or the interventions that are most effective and safe to use in outpatient settings.

Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term.

BACKGROUND: Prostaglandins have been used for induction of labour since the 1960s. Initial work focused on prostaglandin F2a as prostaglandin E2 was considered unsuitable for a number of reasons. With the development of alternative routes of administration, comparisons were made between various formulations of vaginal prostaglandins. OBJECTIVES: To determine the effects of vaginal prostaglandins E2 and F2a for third trimester cervical ripening or induction of labour in comparison with placebo/no treatment or other vaginal prostaglandins (except misoprostol). SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2009) and bibliographies of relevant papers. SELECTION CRITERIA: Clinical trials comparing vaginal prostaglandins used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. DATA COLLECTION AND ANALYSIS: We assessed studies and extracted data independently. MAIN RESULTS: Sixty-three (10,441 women) have been included.Vaginal prostaglandin E2 compared with placebo or no treatment reduced the likelihood of vaginal delivery not being achieved within 24 hours (18.1% versus 98.9%, risk ratio (RR) 0.19, 95% confidence interval (CI) 0.14 to 0.25, two trials, 384 women). The risk of the cervix remaining unfavourable or unchanged was reduced (21.6% versus 40.3%, RR 0.46, 95% CI 0.35 to 0.62, five trials, 467 women); and the risk of oxytocin augmentation reduced (35.1% versus 43.8%, RR 0.83, 95% CI 0.73 to 0.94, 12 trials, 1321 women) when PGE2 was compared to placebo. There was no evidence of a difference between caesarean section rates, although the risk of uterine hyperstimulation with fetal heart rate changes was increased (4.4% versus 0.49%, RR 4.14, 95% CI 1.93 to 8.90, 14 trials, 1259 women).PGE2 tablet, gel and pessary appear to be as efficacious as each other and the use of sustained release PGE2 inserts appear to be associated with a reduction in instrumental vaginal delivery rates (9.9 % versus 19.5%, RR 0.51, 95% CI 0.35 to 0.76, NNT 10 (6.7 to 24.0), five trials, 661 women) when compared to vaginal PGE2 gel or tablet. AUTHORS' CONCLUSIONS: PGE2 increases successful vaginal delivery rates in 24 hours and cervical favourability with no increase in operative delivery rates. Sustained release vaginal PGE2 is superior to vaginal PGE2 gel with respect to some outcomes studied.Further research is needed to assess the best vehicle for delivering vaginal prostaglandins and this should, where possible, include some examination of the cost-analysis.

Intravenous oxytocin alone for cervical ripening and induction of labour.

BACKGROUND: Oxytocin is the commonest induction agent used worldwide. It has been used alone, in combination with amniotomy or following cervical ripening with other pharmacological or non-pharmacological methods. OBJECTIVES: To determine the effects of oxytocin alone for third trimester cervical ripening and induction of labour in comparison with other methods of induction of labour or placebo/no treatment. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2009) and bibliographies of relevant papers. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing intravenous oxytocin with placebo or no treatment, or with prostaglandins (vaginal or intracervical) for third trimester cervical ripening or labour induction. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and carried out data extraction. MAIN RESULTS: Sixty-one trials (12,819 women) are included.When oxytocin inductions were compared with expectant management, fewer women failed to deliver vaginally within 24 hours (8.4% versus 53.8%, risk ratio (RR) 0.16, 95% confidence interval (CI) 0.10 to 0.25). There was a significant increase in the number of women requiring epidural analgesia (RR 1.10, 95% CI 1.04 to 1.17). Fewer women were dissatisfied with oxytocin induction in the one trial reporting this outcome (5.9% versus 13.7%, RR 0.43, 95% CI 0.33 to 0.56).Compared with vaginal prostaglandins, oxytocin increased unsuccessful vaginal delivery within 24 hours in the two trials reporting this outcome (70% versus 21%, RR 3.33, 95% CI 1.61 to 6.89). There was a small increase in epidurals when oxytocin alone was used (RR 1.09, 95% CI 1.01 to 1.17).Most of the studies included women with ruptured membranes, and there was some evidence that vaginal prostaglandin increased infection in mothers (chorioamnionitis RR 0.66, 95% CI 0.47 to 0.92) and babies (use of antibiotics RR 0.68, 95% CI 0.53 to 0.87). These data should be interpreted cautiously as infection was not pre-specified in the original review protocol.When oxytocin was compared with intracervical prostaglandins, there was an increase in unsuccessful vaginal delivery within 24 hours (50.4% versus 34.6%, RR 1.47, 95% CI 1.10 to 1.96) and an increase in caesarean sections (19.1% versus 13.7%, RR 1.37, 95% CI 1.08 to 1.74) in the oxytocin group. AUTHORS' CONCLUSIONS: Comparison of oxytocin with either intravaginal or intracervical PGE2 reveals that the prostaglandin agents probably increase the chances of achieving vaginal birth within 24 hours. Oxytocin induction may increase the rate of interventions in labour.A suggestion that for women with prelabour rupture of membranes induction with vaginal prostaglandin may increase risk of infection for mother and baby warrants further study.

Outpatient versus inpatient induction of labour for improving birth outcomes.

BACKGROUND: More than 20% of women undergo induction of labour in some countries. The different methods used to induce labour have been the focus of previous reviews, but the setting in which induction takes place (hospital versus outpatient settings) may have implications for maternal satisfaction and costs. It is not known whether some methods of induction that are effective and safe in hospital are suitable in outpatient settings. OBJECTIVES: To assess the effects on outcomes for mothers and babies of induction of labour for women managed as outpatients versus inpatients. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2008). SELECTION CRITERIA: Published and unpublished randomised and quasi-randomised trials in which inpatient and outpatient methods of cervical ripening or induction of labour have been compared. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial reports for inclusion. Two review authors carried out data extraction and assessment of risk of bias independently. MAIN RESULTS: We included three trials, with a combined total of 612 women in the review; each examined a different method of induction and we were unable to pool the results from trials.1. Vaginal PGE2 (One study including 201 women). There were no differences between women managed as out- versus inpatients for most review outcomes. Women in the outpatient group were more likely to have instrumental deliveries (risk ratio (RR) 1.74; 95% confidence interval (CI) 1.03 to 2.93). The overall length of hospital stay was similar in the two groups.2. Controlled release PGE2 10mg (one study including 300 women). There was no evidence of differences between groups for most review outcomes, including success of induction. During the induction period itself, women in the outpatient group were more likely to report high levels of satisfaction with their care (satisfaction rated seven or more on a nine-point scale RR 1.42; 95% CI 1.11 to 1.81), but satisfaction scores measured postnatally were similar in the two groups.3. Foley catheter (one study including 111 women). There was no evidence of differences between groups for caesarean section rates, total induction time and the numbers of babies admitted to neonatal intensive care. AUTHORS' CONCLUSIONS: The data available to evaluate the efficacy or potential hazards of outpatient induction are limited. It is, therefore, not yet possible to determine whether induction of labour is effective and safe in outpatient settings.