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Efficacy and safety of double balloon catheter and dinoprostone for labor induction in multipara at term

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Efficacy and safety of double balloon catheter and dinoprostone for labor induction in multipara at term

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Efficacy and safety of double balloon catheter and dinoprostone for labor induction in multipara at term

Abstract

Purpose

The aim of this study was to comparatively assess the efficacy and safety of double balloon catheter (DBC) and dinoprostone as labor-inducing agents just for multipara at term.

Methods

A retrospective cohort study was conducted among multipara at term with a Bishop score < 6 who needed planned labor induction from January 1, 2020, to December 30, 2020 in Maternal and Child Health Hospital of Hubei province, Tongji Medical College, Huazhong University of Science and Technology. They were divided into DBC group and dinoprostone group, respectively. Baseline maternal data, maternal and neonatal outcomes were recorded for statistical analysis. Total vaginal delivery rate, rate of vaginal delivery within 24 h, rate of uterine hyperstimulation combined with abnormal fetal heart rate(FHR) were regarded as the primary outcome variables. The difference between groups was considered statistically significant when p value < 0.05.

Results

A total of 202 multiparas was included for analysis (95 women in DBC group vs 107 women in dinoprostone group). There were no significant differences in total vaginal delivery rate and rate of vaginal delivery within 24 h between groups. Uterine hyperstimulation combined with abnormal FHR occurred exclusively in dinoprostone group.

Conclusion

DBC and dinoprostone seem to be equally effective, while, DBC seems to be safer than dinoprostone.

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FormalPara What does this study add to the clinical work

This is the first time to compare the efficacy and safety of double balloon catheter and dinoprostone for labor induction just in multipara at term, providing more data for clinical practice guidelines.

Introduction

Induction of labor (IOL) is an obstetrical procedure that has been increasingly used in recent years. The proportion of people experiencing IOL increased by nearly 10% from 2007 to 2017, with IOL rate exceeding 25.5% (1 in 4) in 2017 [ 1]. With the implementation of two-child policy, the rate of labor induction at term has been increased to more than 30% in 2013 in China [ 2]. Following the publication of the ARRIVE trial [ 3] and the implementation of three-child policy, the IOL rate is expected to rise in the future in China.

For women with an unfavorable cervix (Bishop score < 6) [ 4, 5, 6], the additional step of cervical ripening is required during induction of labor. There are mechanical and pharmacologic methods of cervical ripening. Approved by the United States Food and Drug Administration (FDA) in 2013, the Cook Cervical Ripening Balloon (Cook Inc; Bloomington, IN) can lead to cervical ripening by either direct mechanical dilation of the cervix or stimulation of prostaglandin released from the amnion, chorion, and decidua [ 7, 8]. Dinoprostone is chemically identical to endogenous prostaglandin E2 (PGE2), which has been approved by the FDA for cervical ripening and has been widely used in several countries throughout the world. There have been many studies comparatively studying the effectiveness and safety of the two labor induction methods [ 9, 10, 11, 12, 13]. It is well known that the history of vaginal delivery itself is of vital importance for the success of induction, but the vast majority of studies have focused on primipara or have not fully distinguished between primipara and multipara. However, the optimal method for labor induction for multipara at term with an unfavorable cervix remains unknown.

In this retrospective cohort study conducted in our birth centre from January 1, 2020, to December 30, 2020, the efficacy and safety of DBC and dinoprostone as labor-inducing agents for multipara were comparatively analyzed.

Materials and methods

Ethical approval and patient consent

The study protocol was approved by the Ethics Committee of Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology [(2019) IEC (XM008)]. All included women signed written informed consent for therapeutic procedures and for the publication of those reports.

Selection of patients and study design

The flowchart of the experimental design is shown in Fig. 1. In this retrospective cohort study, a total of multiparas aged 18-50 years with gestational ages ≥ 37 weeks, history of previous vaginal delivery, singleton gestation, vertex presentation, intact membranes, normal preinduction fetal heart rate tracing, Bishop score < 6, fetal weight of less than 4500 g with a ultrasound or clinical estimated were included. The exclusion criteria were pregnant women aged less than 18 years or older than 50 years, primipara, previous cesarean section. During the observation period at our birth centre from January 1st, 2020 to December 30th, 2020, a total of 252 multiparas were enrolled in this study. Among them, 4 cases with missing data, 18 cases with Bishop scores ≥ 6, 6 cases with gestation age < 37 weeks by ultrasound, 17 cases with premature rupture of membranes, and 5 cases with prior cesarean section history were excluded, and the remaining 202 cases were included in our study. Based on the methods of IOD, the 202 cases were divided into two groups: DBC group ( n = 95) and dinoprostone group ( n  = 107).

The multiparas in DBC group were treated with DBC (Cervical Ripening Balloon; Cook OB/GYN, Spencer, IN, USA) for labor induction. The DBC involved 2 balloons (uterine and vaginal balloons). First, the uterine balloon (red piston, marked with "U") was inserted into uterine cavity by long oval forceps under direct visualization and 40 mL of normal saline solution was injected in. Then the vaginal balloon (green piston, marked with "V") was pulled out of the cervical orifice slightly, and 40 mL of normal saline solution was injected in. When they were correctly situated on either end of the cervix, the fluid amount in both balloons was alternatively increased by 20 mL each time until each balloon reached 80 mL. The external end of the device was taped to the patient's leg without tension after ensuring that the balloons were positioned correctly. When symptoms of sweating or flustering were unbearable, then 10-20 mL of normal saline was withdrawn from both balloons until the patient could tolerate the DBC. The DBC should be removed immediately upon the occurrence of any of the following events, including spontaneous labor, expulsion, spontaneous ruptured membranes, or unexplained vaginal bleeding. If those events do not happen, the DBC device will be removed after holding for 12 h [ 14].

The multiparas in dinoprostone group were induced with a slow-release vaginal insert containing 10 mg of dinoprostone (prostaglandins PGE2 Propess ®, Ferring SAS, Gentilly, France). The slow-release vaginal insert was stored in a freezer at a temperature between − 20 and − 10 °C. Dinoprostone should be removed in case of spontaneous exit, labor, being placed in the vagina for over 24 h.

After the removal or self-expulsion of the IOL agents, patients underwent a vaginal examination and then transferred to the delivery ward for spontaneous labor or augmentation by oxytocin infusion and/or artificial rupture of membranes with a 60-min interval if uterine contractions were not adequate. Epidural analgesia was provided under maternal request after uterine orifice dilation was more than or equal to 1 cm. Continuous monitoring of uterine activity and fetal heart rate was performed during active labor.

Observation indicators

Information including maternal age, maternal body mass index (BMI) before pregnancy and at time of IOL, gestational age at time of delivery, gravidity, parity, abortion history, vaginal delivery history, indication for IOL, initial Bishop score, labor and perinatal period were collected and recorded in a form specially designed for this trial. To compare the efficacy and safety of DBC and dinoprostone for labor induction, total vaginal delivery rate, rate of vaginal delivery within 24 h, rate of uterine hyperstimulation combined with abnormal fetal heart rate and rate of fetal distress were regarded as the primary outcome variables. Secondary outcome variables include indications for cesarean section, insertion to active labor, length of first stage of labor, length of second stage of labor, length of third stage of labor, length of total labor, oxytocin augmentation, artificial rupture of membrane, postpartum hemorrhage, meconium staining of amniotic fluid, precipitate labor, episiotomy, perineal laceration, intrapartum fever, neuraxial analgesia. Neonatal outcomes include newborn weight, neonatal asphyxia, neonatal intensive care unit (NICU) admission. Cesarean section on maternal request is defined as the cesarean section based solely on maternal request without any maternal or fetal medical indications. Insertion to active labor is defined as the time from placing the DBC or applying dinoprostone to the start of regular contractions. Uterine hyperstimulation is defined as contractions more than 5 in 10 min for more than 20 min or contractions lasting more than 2 min in duration [ 15]. Fetal distress is defined as the symptoms that endanger the health and life of the fetus in utero due to acute or chronic hypoxia. Precipitate labor is defined as labor not exceeding 3 h. Failed induction is defined as no active labor within 48 h of induced labor. Neonatal asphyxia is defined as having an Apgar score ≤ 7 at 1 min. Adverse neonatal outcome variables include neonatal asphyxia, neonatal intensive care unit admission.

Statistical methods

All analyses were conducted using the Statistical Package of Social Sciences software (SPSS Version 26.0 Inc., Chicago, IL, USA). Continuous variables were presented as means ± standard deviation and categorical variables were presented as frequency and percentage (%). Student's t test was performed to compare the variables in a Gaussian distribution. The chi-square test or Fisher's exact test were used to evaluate the categorical variables. The Mann-Whitney test was used to evaluate the difference in a non-Gaussian distribution between two groups. The difference was considered statistically significant when p  < 0.05.

Results

As shown in Table 1, baseline characteristics of multiparas with labor induction in DBC group and dinoprostone group were comparatively analyzed. There were no significant differences in maternal age, BMI at delivery, gravidity, parity, abortion history, vaginal delivery history, indication for IOL, initial Bishop score between the two groups ( p  > 0.05).

Overall, natural delivery rate, cesarean section rate and forceps delivery rate were 89.1% (180/202), 9.9% (20/202) and 1.0% (2/202), respectively. The total vaginal delivery rate was 93.7% in DBC group and 86.9% in dinoprostone group, with no significant difference between the two groups ( p > 0.05), as shown in Table 2. The vaginal delivery (including forceps) rates within 24 h, 36 h, 48 h, > 48 h were 75.8%, 88.4%, 92.6%, 93.7% in DBC group, and 71.0%, 82.2%, 83.2%, 86.9% in dinoprostone group, and there was no statistical differences between in the two groups ( p > 0.05), as shown in Table 2.

Further, the indications for cesarean section in DBC group included fetal distress ( n = 4), antepartum hemorrhage ( n = 1), maternal request cesarean section ( n = 1), and those in dinoprostone included fetal distress ( n = 11), failed induction ( n = 2), cesarean section on maternal request ( n  = 1).

The main maternal outcome variables of DBC group and in dinoprostone group were comparatively analyzed (Table 3). The rate of uterine hyperstimulation combined with abnormal FHR was higher in the dinoprostone group than in the DBC group (5.6% vs. 0%, p = 0.019), and the rates of meconium staining of amniotic fluid and intrapartum fever in the dinoprostone group were higher than in the DBC group (19.6% vs. 9.5%, p = 0.043 and 19.6% vs. 8.4%, p = 0.023). The rates of oxytocin augmentation and artificial rupture of membrane were higher in the DBC group than in the dinoprostone group (77.9% vs. 19.6%, p < 0.001 and 63.2% vs. 10.3%, p < 0.001). Moreover, there were no significant difference in the rates of precipitate delivery, fetal distress, neuraxial analgesia, postpartum hemorrhage, episiotomy, perineal laceration between the two groups ( p > 0.05). The median time of insertion to active labor in the DBC group was 992.3 m, which was longer than that in the dinoprostone group (753.2 m, p < 0.001), but there were no significant difference in the median time of first stage of labor, second stage of labor, third stage of labor and the total labor between the two groups ( p  > 0.05).

Table 4 shows the main outcomes of newborns. Neonatal outcomes were similar in both study groups. The average birth weight in the DBC group and the dinoprostone group was 3399.1 ± 383.7 g and 3480.8 ± 381.0 g ( p  = 0.131). There were two newborns having an Apgar ≤ 7 at 1 min in the dinoprostone group, but one newborn in the DBC group. There were two newborns staying in neonatal intensive care unit for each groups.

Discussion

Nowadays, double balloon catheter (DBC) and dinoprostone as two useful methods for induction of labor in pregnant women at term have been widely used in clinical practice [ 16, 17, 18]. In our trial, we compared the efficacy and safety of DBC and dinoprostone as labor-inducing agents just in multipara at term. Our findings indicate that DBC and Dinoprostone seem to be equally effective since there were no differences in rate of vaginal delivery within 24 h, total vaginal delivery rate and cesarean section rate under the two different methods. However, DBC seems to have a more higher safety than dinoprostone as it led to lower rates of uterine hyperstimulation combined with abnormal FHR, amniotic fluid fecal staining, renatal fever, and there was a downward trend of fetal distress in DBC group compared with dinoprostone group.

The rate of vaginal delivery within 24 h was recommended by members of guidelines development groups in WHO (World Health Organization) and NICE (National Institute for Health and Clinical Excellence) as the most clinically relevant indication to evaluate the effectiveness of labor induction methods. Moreover, vaginal delivery rate and cesarean section rate have also been used as important indicators to evaluate the effectiveness of labor induction methods. Several studies have compared the efficacy of balloon catheters and dinoprostone, and conflicting results were obtained. A Cochrane analysis [ 19] found that there may be little or n significant difference in the rate of vaginal delivery within 24 h ((RR 1.01, 95% CI 0.82-1.26) and rate of cesarean section (RR 1.00, 95% CI 0.92-1.09) when using balloon and vaginal PGE2 as labor-inducing agents, which is consistent with the results of another analysis [ 20]. Du et al. [ 21] reported that the overall vaginal delivery rate in women treated with double balloon catheter was similar with that of dinoprostone (71.6% vs. 62.8%; p > 0.05), but more women were vaginally delivered within 24 h in dinoprostone group (52.26% vs. 37.62%, p = 0.0079). Suffecool et al. [ 22] reported that more women were vaginally delivered within 24 h in double balloon catheter group (87.1% vs. 47.4%, p = 0.002) than in dinoprostone group. In our trial, there were no significant differences in rate of total vaginal delivery rate, rate of vaginal delivery within 24 h and rate of cesarean section between DBC group and dinoprostone group, although the time from start of induction to active labor was longer in DBC group than in dinoprostone group, and these results are similar to those reported in the recent meta-analysis mentioned above [ 19, 20].

For a method to induce labor, safety seems to be a more important index than efficacy. As an exogenous PGE2, dinoprostone can not only stimulate cervical remodeling, but also initiate uterine contractions via stimulating endogenous prostaglandin F2α production or sensitizing the myometrium to the effects of endogenous or exogenous oxytocin [ 18]. The most significant adverse event associated with dinoprostone is uterine hyperstimulation. Wing et al. [ 23] found that the rate of uterine hyperstimulation combined with FHR accounted for 4.0% in the dinoprostone group, while Rugarn et al. [ 24] reported this rate was 1.2%. DBC was used to induce labor by mechanically dilating the cervix and stimulating the release of prostaglandins from the amniotic membrane, chorionic membrane and decidua to ripen the cervix. In the Cochrane analysis [ 19], a balloon catheter probably reduces the rate of uterine hyperstimulation combined with FHR (RR 0.35, 95% CI 0.18-0.67), rate of serious neonatal morbidity or perinatal death (RR 0.48, 95% CI 0.25-0.93) and may slightly reduce the rate of aneonatal intensive care unit (NICU) admission (RR 0.82, 95% CI 0.65-1.04). A recent trial conducted by Grace et al. published in 2021 [ 15] reported that the rates of uterine hyperstimulation and fetal distress were lower in DBC group than vaginal prostaglandin group in the first 12 h. However, a multicentre randomized controlled trial in Australian [ 10] showed that there were no statistically significant differences in the primary outcome variables (18.6% vs. 25.8%; RR 0.77, 95% CI 0.51-1.02; p = 0.070) or in the rate of meconium stained liquor (12.6% vs. 11.2%, p = 0.647) between DBC group and dinoprostone group, but uterine hyperstimulation occurred exclusively in the dinoprostone group (3.0% versus 0%; p = 0.029). Considering that maternal factors and fetal intrauterine conditions would affect neonatal outcomes, Diguisto et al. [ 9] observed no difference in the rate of cesarean delivery due to nonreassuring fetal status for prolonged pregnancies between DBC group and dinoprostone group (5.8% vs. 5.3%, 95% CI 2.1-3.1%, p = 0.70). Jorge et al. [ 11] comparatively studied the safety of dinoprostone and DBC for labor induction in women at term with fetal growth restriction and no differences were observed between the two groups in terms of meconium, intrapartum fever, pH, Apgar scores or the rate of neonatal admissions. In our trial, there were totally14 cesarean section cases in dinoprostone group, including 11 cases due to fetal distress, 2 case due to failed induction, and 1 case on maternal request, accounting for 78.6% (11/14), 14.3%(2/14), 7.1%(1/14), respectively. Fetal distress caused by overstimulation of the uterus accounted for 54.5% (6/11), with the remaining 45.5% (5/11) caused by umbilical cord and placenta factors in the dinoprostone group. In contrast, there were 6 cases of cesarean section in the DBC group, 4 of which were due to fetal distress caused by umbilical cord factors, and none of the participants experienced uterine overstimulation. It was found that uterine hyperstimulation combined with abnormal FHR occurred exclusively in dinoprostone group, and DBC reduced the risk of amniotic fluid fecal staining. There was a downward trend of fetal distress in the DBC group as compared with the dinoprostone group, although the difference did not reach statistical significance (4.2% vs. 10.3%, p  = 0.101).

As for the risk of infection, a 2015 meta-analysis [ 25] showed that Foley catheters for induction of labor was not associated with an increased risk of infection since patients who underwent cervical ripening using a Foley catheter had similar rates of chorioamnionitis (RR 0.96, 95% CI 0.66-1.38), endometritis (RR 1.03, 95% CI 0.66-1.6),pooled maternal infection (RR 0.95, 95% CI 0.81-1.12), and neonatal infection (RR 0.9, 95% CI 0.58-1.39) compared with those using prostaglandins. However, our research found that the rate of prenatal fever in DBC group was lower than that in dinoprostone group. The reason may be that dinoprostone is a PGE2 analog as well as potent systemic mediator of inflammation and infection, which leads to pyrexia among people during labor.

To our knowledge, this study is the first retrospective cohort study comparing the efficacy and safety of double balloon catheter (DBC) and dinoprostone and as labor-inducing agents for multipara at term. However, there are some limitations in this study. First, this study is a retrospective and single center study, the selection of labor induction method may be subjective, and the results are not so objective as the multi-center prospective studies. Second, the sample size of this study is relatively small, the rate of maternal complications such as postpartum hemorrhage, birth canal injury and the rate of neonatal complications such as neonatal asphyxia and NICU admission were very low, so it is uncertain whether there is a difference in the rate of serious complications under the two labor induction methods.

Conclusion

Double balloon catheter and dinoprostone seem to be equally effective, but double balloon catheter seem to be more safe than dinoprostone for induction of labor for multipara at term.

Data availability

Access to the qualitative data will be given upon request to the corresponding author after taking any necessary precautions to safeguard participants' privacy and confidentiality.

References

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Acknowledgements

We would like to thank all the participants of the trial. We will like to thank the obstetricians and nurses for the diagnosis and treatment of these pregnant women.

Funding

This work was supported by the Foundation from Health and Family Planning Commission of Hubei Province (No: WJ2018h0133; No: WJ2019H297) and Innovative Research Team of Hubei Provincial Science and Technology Department (No: 2019CFA033). All of the foundations agreed to fund obstetric researchers for data analysis, English editing and other costs related to the dissemination of the study.

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Authors and Affiliations

Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, No. 745, Wuluo Road, Hongshan District, Wuhan, 430070, China

Lu Yuan, Jing Peng, Lijun Yang & Yun Zhao

Contributions

ZY conceived the study, analyzed the data, interpreted the results, and revised the manuscript. YLJ conceived the study, analyzed the data, interpreted the results. YL drafted the manuscript. PJ collected the data. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Lijun Yang or Yun Zhao.

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Conflict of interest

The authors have stated explicitly that there are no conflicts of interest regarding the publication of this article.

Ethics approval

The study protocol was approved by the Ethics Committee of Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology ([2019] IEC (XM008)).

Consent to participate

All included women signed written informed consent for therapeutic procedures and for the publication of those reports.

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Yuan, L., Peng, J., Yang, L. et al. Efficacy and safety of double balloon catheter and dinoprostone for labor induction in multipara at term. Arch Gynecol Obstet 309, 533-540 (2024). https://doi.org/10.1007/s00404-022-06891-9
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Keywords

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Efficacy and safety of double balloon catheter and dinoprostone for labor induction in multipara at term - Archives of Gynecology and Obstetrics

# data[].attributes.attachment_link.description
Purpose The aim of this study was to comparatively assess the efficacy and safety of double balloon catheter (DBC) and dinoprostone as labor-inducing agents just for multipara at term.

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Continuing Education Activity

Prostaglandin E2 is an FDA-approved medication used both for the evacuation of uterine contents and labor induction. It is in the prostaglandin class of drugs. This activity outlines the indications, action, and contraindications for prostaglandin E2 as it is used as an abortifacient or a labor inducer. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent to the interprofessional team members of patients in need of uterine evacuation or labor induction.

Objectives:

Outline the mechanism of action of prostaglandin E2.

Describe the adverse effects of prostaglandin E2.

Identify the indications for the different forms of prostaglandin E2.

Explain the importance of interprofessional team communication in the administration and monitoring of prostaglandin E2.

Access free multiple choice questions on this topic.
Indications

Prostaglandin E2 (PGE2), also known by the name dinoprostone, is a naturally occurring compound involved in promoting labor, though it is also present in the inflammatory pathway.[1] Prostaglandin E2 is FDA approved for cervical ripening for the induction of labor in patients for which there is a medical indication for induction. When used as a vaginal suppository, it is indicated as an abortifacient from gestational week 12 to 20 or for the evacuation of uterine contents for the management of missed abortion and intrauterine fetal death up to 28 weeks. Prostaglandin E2 is also useful for the management of gestational trophoblastic disease. Importantly, it is not a feticidal agent. Given its oxytocic properties, the administration of dinoprostone should only be at the proper dosages by experienced clinicians.[2]

Mechanism of Action

While the exact mechanism of action is unknown, prostaglandin E2 causes contractions in the myometrium via direct stimulation. It binds to G protein-coupled receptors (GPCRs) EP1-4 that lead to a variety of downstream events depending on the EP subtype and cell-type-specific expression patterns.[3] For example, EP receptors in the myometrium act via cell membrane calcium channels and intracellular cyclic 3'5'-adenosine monophosphate (cAMP). As some of the known receptors for prostaglandin E2 antagonize each other, researchers have hypothesized that the expression of these receptors determines the specific effects. The efficacy of prostaglandin E2 during pregnancy may link to the expression of these receptors. Prostaglandin E2 also promotes cervical dilation, effacement, and softening, similar to the natural progression of pregnancy, possibly due to increased collagenase secretion.[4]

The role of prostaglandin E2 in inflammation is complex; it has demonstrated pro-inflammatory activity in specific settings and plays an anti-inflammatory role in others.[5] These diverse functions appear to depend on the cell type and expression patterns of various receptors. It can promote the activation of inflammatory Th17 cells but suppress IL-2 and IL-12 production in other T cell subsets. Importantly, though in vitro experiments have demonstrated that prostaglandin E2 can inhibit T-cell production, in vivo studies have not yet shown similar results.[6]

Administration

PGE2 is administered vaginally as a suppository, gel, or insert.

The vaginal suppository is for the evacuation of uterine contents. One 20 mg suppository is inserted into the posterior fornix of the vagina every three hours until abortion occurs. If the abortion does not occur within twenty-four hours, or if there are severe side effects, the clinician should stop the drug.[7]

The endocervical gel and vaginal inserts are agents for cervical ripening induction. The cervical gel has a more rapid release than the vaginal insert but might be less convenient, as the procedure requires more vaginal examinations.[4] PGE2 is inserted into the posterior fornix and replaced every six hours until labor induction, as determined by regular, painful contractions.[8] However, drug administration should cease if there are no contractions within twenty-four hours or if there are severe adverse effects, including membrane rupture or uterine hyperstimulation.[9]

Adverse Effects

The most common side effects of prostaglandin E2 concern its impact on gastrointestinal smooth muscle. The suppository correlates with the most severe side effects, with two-thirds of patients experiencing vomiting, two-fifths experiencing diarrhea, and one-third experiencing nausea. Other adverse effects include temperature elevation in half of the patients, headache in one-tenth, and shivering and chills in one-tenth. Anti-emetics and anti-diarrheal medications may be necessary before and during the drug administration to counteract these side effects.[9]

The insert and gel have a less than one percent incidence of gastrointestinal symptoms. However, studies have shown that they have links to a higher chance of uterine hyperstimulation with and without fetal distress (greater than 2%) versus placebo (under1%). Additionally, they also have an increased chance of fetal distress without uterine hyperstimulation (over 2%) versus placebo (1%). There were also associated fetal heart rate changes, with and without distress. In all of these cases, removal of the product resulted in a return to normal, though one case did require treatment with tocolytics.[10]

Contraindications

Prostaglandin E2 is contraindicated in patients with a known hypersensitivity to prostaglandins. As an oxytocic agent, prostaglandin E2 should be avoided in scenarios in which vaginal delivery or the induction of labor is contraindicated and should be stopped before administering oxytocin.

Suppository

Clinicians should avoid the suppository should in patients with acute inflammatory pelvic disease, as well as patients with active cardiac, renal, pulmonary, or hepatic disease. Additionally, it requires caution in patients with a history of these diseases and patients with a history of cervical malignancy, asthma, hypo- or hypertension, anemia, jaundice, pulmonary disease, or epilepsy. The prostaglandin E2 suppository is not indicated for uterine evacuation for fetuses at the stage of viability.[11]

Gel/Insert

The gel or insert versions used for cervical ripening are contraindicated in patients with fetal distress where delivery is not imminent or who have vaginal bleeding during pregnancy, marked cephalopelvic disproportion, and/or multipara with six or more previous term pregnancies. Prostaglandin E2 should also be avoided when prolonged uterine contraction may pose a risk to uterine integrity or fetal safety, such as with prior cesarean section or major uterine surgery. Prostaglandin E2 for labor induction should also be avoided in patients with a history of asthma, glaucoma, or heart disease.[12]

Monitoring

Prostaglandin E2 administration should only take place in a specialized care setting under clinician supervision.

Suppository

Patients should be monitored for adverse effects, especially pyrexia, and the drug should be stopped if any severe adverse reactions occur. Abortion via prostaglandin E2 suppository may be incomplete, which may require further measures such as dilation and curettage.[11]

Gel/Insert

Uterine activity, fetal status, and progression of cervical dilation all require monitoring. In particular, the healthcare team should look for any signs of uterine hyperstimulation, sustained uterine contractions, and fetal distress. If these or any other adverse effects present, the insert should be removed and drug administration stopped. Prostaglandin E2 should also be discontinued before amniotomy and before the administration of oxytocin.[13]

Toxicity

Prostaglandin E2 overdose typically manifests as uterine hyperstimulation, and stopping the drug is the most effective treatment. Also, beta-adrenergic drugs, such as terbutaline, may be used in case of continued symptoms.[13]

Enhancing Healthcare Team Outcomes

Given prostaglandin E2's oxytocic properties and potential side effects, its administration and possible adverse effects require careful monitoring. The most effective way to do this requires an interprofessional team of clinicians, nurses, and pharmacists to keep track of the patient's progress. The team should be especially careful to remove prostaglandin E2 before administering other oxytocic drugs, especially when inducing labor.

The pharmacist should make sure that the clinicians are aware of the potential adverse effects of the drug and how to manage them, assist in preventing the above drug interactions, and verify all dosing. If side effects develop, both the nursing staff and pharmacy staff should report back to the clinical team. Neonatal nursing staff will be an invaluable asset during the entire labor and delivery process, regardless of what manner it occurs, assisting during the procedure and taking care of the neonate and mother subsequently.

Followup to prostaglandin E2 administration is typically by either the evacuation of uterine contents or labor. Because of this, patients require constant close observation and will often need further procedures soon after the drug's desired effect.

Communication among members of the healthcare team will help with understanding the progression of the drug's effects and the expected outcome, and the next steps to be taken.[14] [Level 3] Given the potential for adverse events with prostaglandin E2, its use requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level 5]

References

1.

2.

3.

4.

5.

Nakanishi M, Rosenberg DW. Multifaceted roles of PGE2 in inflammation and cancer. Semin Immunopathol. 2013 Mar;35(2):123-37. [ PMC free article: PMC3568185 ] [ PubMed: 22996682 ]

6.

7.

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9.

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11.

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13.

14.

O'Dwyer S, Raniolo C, Roper J, Gupta M. Improving induction of labour - a quality improvement project addressing Caesarean section rates and length of process in women undergoing induction of labour. BMJ Qual Improv Rep. 2015;4(1) [ PMC free article: PMC4693078 ] [ PubMed: 26734422 ]

Disclosure: Michael Xi declares no relevant financial relationships with ineligible companies.

Disclosure: Valerie Gerriets declares no relevant financial relationships with ineligible companies.

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Prostaglandin E2 is an FDA-approved medication used both for the evacuation of uterine contents and labor induction. It is in the prostaglandin class of drugs. This activity outlines the indications, action, and contraindications for prostaglandin E2 as it is used as an abortifacient or a labor inducer.

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Conventional versus modified application of COOK Cervical Ripening Balloon for induction of labor at term: a randomized controlled trial

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Conventional versus modified application of COOK Cervical Ripening Balloon for induction of labor at term: a randomized controlled trial

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A total of 227 pregnant women who met the criteria participated in this study, with 119 initially assigned in the control group and 108 in the study group. In the control group, 2 cases were excluded later; one case had spontaneous rupture of membranes, the other case had heavy vaginal bleeding shortly after placement of CCRB (this case was later diagnosed with placenta previa after emergent cesarean section). Therefore, data from the 117 cases in the control group and 108 cases in the study group were further analyzed and reported (Fig. 1).

Baseline clinical characteristics

The age, gravidity, height, body weight, BMI, gestational age, indications of IOL, initial Bishop scores, and neonatal birth weight were compared. There were no significant differences in basic clinical characteristics, indications of IOL, and neonatal birth weight between the two groups (Table 1).

Primary outcomes

We observed that the uterine balloons were discharged in 25.6% cases of the control group and 20.4% cases of the study group at 6 am of the next day. The improvement of the Bishop score, successful induction rate, spontaneous delivery rate, cesarean section rate, and the indications were compared between the two groups (Table 2).

The improved Bishop scores at 12 h after the placement of CCRB in the study group was significantly higher than that of the control group (3.06 ± 0.97 vs. 2.52 ± 0.79, p = 0.000), and the improvement was even larger when CCRB was discharged (4.37 ± 0.87 vs. 2.52 ± 0.79, p  = 0.000).

By analyzing the five scoring items of the Bishop score respectively, we found that in both groups, the dilation item was increased by more than 1 point, the most in the five items, followed by the cervical consistency item, while the effacement and position of cervix items increased less, and the station item score even decreased.

Similar improvements were observed in the study group when CCRB was discharged, except the total score and dilation item score improved more than those at 12 h and the improvement of the effacement score came to second place in the study group. The successful induction rate in the study group was significantly higher than that in the control group (100% vs 95.73%, p = 0.030). The spontaneous delivery rate in the study group was higher than that in the control group (87.04% vs 79.49%), but there was no significant difference ( p = 0.131). The indications of cesarean section in two groups were also analyzed. With 14 cases undergoing cesarean section in the study group, 9 for fetal distress, 4 for the abnormal stage of labor (2 for arrested active phase, 1 for arrested descent, and 1 for protracted second stage), and 1 for maternal loss of confidence due to long induction time. In the control group, 24 cases underwent cesarean section, with 10 for fetal distress, 6 for abnormal stage of labor (3 for arrested active phase, 2 for arrested descent, and 1 for protracted second stage), and 8 for losing confidence due to long induction time. The cases of cesarean section due to psychological factors in the control group were significantly higher than that in the study group (6.84% vs. 0.93%, p  = 0.024).

Delivery process

Eventually, 93 cases in the control group and 94 cases in the study group were spontaneous delivery. The process of delivery was compared between the two groups (Table 3).

The durations of first stage of labor and full labor in the study group were significantly shorter than those of the control group (for the first stage (6.17 ± 2.85) h vs. (7.27 ± 2.90) h, p = 0.010; for the full labor (7.07 ± 3.18) h vs. (8.09 ± 3.11) h, p  = 0.028).

Delivery rate within 24 h was significantly higher in the study group than that in the control group (79.79% vs. 55.91%, p  < 0.05).

There was no significant difference in the pain scores during placement of CCRB between the two groups (4.10 ± 1.33 vs. 3.94 ± 1.15, p = 0.379). However, the use of labor analgesia in the control group was significantly higher than that in the study group (35.48% vs. 22.34%; p  = 0.047).

Kaplan-Meier curves were used to compare cumulative successful vaginal delivery rates between the two groups. All cases achieved vaginal delivery within 48 h in the study group while there were still a few cases not achieving successful vaginal delivery after 72 h in the control group. The median time from placement of CCRB to vaginal delivery in the study group was significantly shorter than that of the control group (Log-Rank test, p < 0.001) (Fig. 3).

Remaining not delivery cases at the time from placement of CCRB to vaginal delivery (excluding cesarean delivery cases)

Cervical ripening effects with different initial Bishop scores

To find the ripening effects of the modified method on the cervix with different initial maturities, we stratified the cases of the two groups with initial Bishop scores (Table 4).

There were 187 cases achieving vaginal delivery in this study. For the 130 cases with initial Bishop scores ≤ 3 points, 66 cases of the control group and 64 cases of the study group achieved vaginal delivery. For the remaining 57 cases with initial Bishop scores of 4-6 points, 27 cases in the control group and 30 cases in the study group achieved vaginal delivery.

For patients with the initial Bishop scores ≤ 3 points, the Bishop score improved significantly in the study group compared with that in the control group both at 12 h of placement and when CCRB was discharged ( p = 0.000, p = 0.000). The durations of the first stage and full labor were significantly shorter than those in the control group ( p = 0.009, p  = 0.036).

For those with the initial Bishop scores of 4-6 points, the improvement of the Bishop score in the study group was significantly higher than that in the control group when CCRB was discharged ( p = 0.000). There was no significant difference in the improvement of the Bishop score at 12 h of placement, the first stage of labor, or the total stage of labor in the study group compared with the control group ( p  > 0.05).

Similarly, each assigned item of the Bishop score was analyzed. The dilatation score improved the most, the cervical consistency score improved the second, and the effacement and position score of the cervix improved the least, while the fetal presentation position score even decreased in both groups whether the initial Bishop scores were high or low at 12 h of placement. When CCRB was discharged, the improvement of the effacement score came to second place in the study group.

Delivery-related risks and outcomes

The occurrence of delivery-related risks and outcomes in the two groups were analyzed (Table 5). There were no significant differences in the incidence of placental abruption, intrauterine infection, postpartum hemorrhage, cervical laceration, perineal laceration, forceps delivery, episiotomy, umbilical cord prolapse, neonatal hypoxic or asphyxia, and neonatal death between the two groups ( p  > 0.05).

Effects of different timing of rupture of membranes on the delivery process

We then analyzed the effects of different timing of rupture of membranes on the delivery process (Table 6).

In the control group, the first stage of labor was (6.23 ± 1.60) h if amniotomy or spontaneous rupture of membranes occurred before regular contractions, and was (7.59 ± 3.13) h if membranes raptured after regular contractions; the difference in the lengths of first stage was significant ( p  = 0.009). There were no significant differences in either the length of full labor or the induction-delivery time, regardless of the timing of membranes rupture (before or after regular contractions).

In the study group, the induction-delivery time with membranes ruptured before regular contractions was significantly shorter than that with membranes ruptured after regular contractions ((20.38 ± 5.32) h vs. (25.00 ± 8.60) h, p  = 0.015). There were no significant differences in the length of either first stage or full labor, regardless of the timing of membranes rupture (before or after regular contractions).

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Conventional versus modified application of COOK Cervical Ripening Balloon for induction of labor at term: a randomized controlled trial - BMC Pregnancy and Childbirth

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Background This study aims to evaluate the efficacy and safety of the modified application of COOK Cervical Ripening Balloon (CCRB) for induction of labor (IOL) at term in primipara. Methods A total of 227 singleton full-term pregnancies with indications of IOL were enrolled and randomly divided into the control and study groups in our hospital from January 2021 to December 2021.

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A snapshot of women’s and clinicians’ perceptions of the double balloon catheter for induction of labor

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A snapshot of women’s and clinicians’ perceptions of the double balloon catheter for induction of labor

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INTRODUCTION

Induction of labor is rising globally and is growing steadily in the state of New South Wales, Australia. In 2011, 26.5% of labors were induced compared to 31.1% in 2016. The most common reasons for induction of labor were prolonged pregnancy, gestational diabetes and prelabor rupture of membranes.

There are numerous methods of induction of labor such as membrane sweeping, amniotomy, prostaglandins, balloon catheters and the double balloon catheter (DBC). Balloon catheters for cervical ripening are well established in the literature as being both effective and safe. While balloon catheters often take longer to ripen the cervix, they have a better safety profile: reduced hyperstimulation, tonic contractions and fetal heart rate changes.

There is minimal evidence on women's attitudes and experiences of double balloon catheter use and clinician's opinions of catheter effectiveness and ease of use. Numerous studies have explored the experiences of women who have had an induction of labour. In contrast, there is minimal research which has investigated women's and clinician's views of the double balloon catheter as an induction of labor process.

Interestingly, motivation for this study was the result of anecdotal reports from midwives about workload issues, namely the extended waiting periods of women being induced and the timing and delays of double balloon catheter insertion and removal. Midwives at the hospital are not accredited in the insertion of a double balloon catheter and often need to wait for an available doctor to perform the procedure.

The aim of this study was to explore the views regarding double balloon catheter insertion and effectiveness from women being induced with the catheter and the clinicians involved in the catheter insertion and care.

METHODS

This is a prospective descriptive survey of two de-identified, self-reported questionnaires, that was undertaken between September and November 2016, in a tertiary hospital in Sydney, NSW, Australia. Two de-identified, self-reported questionnaires were distributed (Supplementary file). One was administered to women (n=26) of term gestation with a singleton pregnancy that were admitted to the antenatal ward for an induction of labor (at post double balloon catheter removal) and the other was administered to midwives or doctors (n=42) involved in the double balloon catheter insertion and care of the women.

The double balloon catheter is a soft, thin tube that is inserted vaginally through the cervix, two balloons are inflated, one on the side of the internal os (orifice) providing pressure and overstretching the lower uterine segment and indirectly causing localized prostaglandin. The other balloon is inflated on the side of the external os, pressure is applied and dilation of cervix results from this pressure on both sides. Cervical ripening was performed with 0.3 mg/h slow release intravaginal dinoprostone over 12 hours for a Bishop's score <7. If the Bishop score was still <6, a Cook® cervical ripening balloon was routinely inserted into the cervix, the balloons filled as per the manufacturer's instructions and removed after another 12 hours. Induction of labor was by artificial rupture of the membranes prior to commencing an oxytocin infusion. The key indications for induction of the study setting included gestational diabetes, reduced fetal movements, prolonged pregnancy and prelabor rupture of membranes. Figure 1 provides an overview, step by step, of what occurs when a woman is admitted to the antenatal ward for induction of labor.

Figure 1

Data collection and analysis

We collected data relating to the views of women and clinicians regarding double balloon catheter insertion and effectiveness. The catheter was inserted either digitally or via visualization of the cervix using a speculum at the clinician's discretion. We did not collect data on individual practitioner insertion styles. Double balloon catheter placement time varied however; most occurred between 9 p.m. and 1 a.m. The variation was due to the heavy workload of the medical staff which delayed both medical review and insertion of vaginal prostaglandin in the morning, and midwives being not accredited to perform catheter insertion. Clinical data were collected on women's views on method and effectiveness of induction of labor, pain relief, artificial rupture of membranes, opinions on having the double balloon catheter in a future pregnancy as well as the option of the insertion as an outpatient. The effectiveness of the double balloon catheter was determined to be the successful artificial rupture of membranes after removal of the double balloon catheter. Clinical data were also collected from clinicians directly involved in both the insertion and care of the double balloon catheter. These data included the views of clinicians on ease of insertion, effectiveness, insertion and removal timing, and the option of the double balloon catheter as an outpatient measure. Demographic data were collected from the maternity database.

Survey data were analyzed using frequency tabulations. Oral and written information on the study was provided to all participants, who then provided voluntary oral consent to participate. The study had local ethical clearance from the Sydney Local Health District Ethics Review Committee (RPAH Zone).

RESULTS

The mean age of the women participants was 31 years, pre-pregnancy body mass index was 23 (kg/m ²), and the majority (≥58%) of women were born in a country other than Australia and New Zealand. Women with diabetes in pregnancy and women born in South Asia were more likely to be induced than other women. Women born in South-East Asia were more likely to go into spontaneous labor at 38(+0/7) to 39(+6/7) weeks' gestation and women born in Australia or New Zealand were more likely to progress beyond 40 completed weeks' gestation. Of the 42 clinicians who participated in the survey, 64% (n=27) were midwives, 29% doctors (n=12) and 7% student midwives (n=3) ( Table 1). Most midwives, doctors and midwifery students were familiar with the hospital's induction of labor policy, 93% (n=25), 92% (n=11), and 100% (n=3), respectively ( Table 2).

Table 1

Table 2

The majority (96%, n=22) of women having an induction of labor, had prostaglandin and 61% (n=14) had an artificial rupture of membranes performed successfully. On the issue of pain, 100% (n=23) reported that the insertion of the catheter was painful ( Table 3). Most of the women (87%, n=20) required pain relief post double balloon catheter insertion and 75% (n=15) stated that the pain relief was effective ( Table 3).

Doctors and midwives consistently believed that the double balloon catheter to be effective in ripening the cervix on most occasions, 83% (n=10) and 81.5% (n=22) respectively, compared to 33% of student midwives (n=1) ( Table 2). Sixty-one percent (n=14) of women said they would consent to double balloon catheter insertion in the future and this result was consistent with the 61% (n=14) who reported that an artificial rupture of membranes could be performed post catheter removal ( Table 3).

The double balloon catheter was perceived as appropriate in an outpatient setting by most clinicians, 59% of midwives (n=16), 67% (n=8) of doctors, and 67% (n=2) of student midwives ( Table 2). When the women were asked if they would be happy to be discharged home with double balloon catheter in situ, only 13% (n=3) agreed ( Table 3).

On the issue of the timing of double balloon catheter insertion and removal, 77% (n=21) of midwives felt timing of insertion and removal needed to be improved compared to 33% (n=4) of doctors ( Table 2). Only 43% of women (n=10) reported insertion and removal was performed at an appropriate time of day ( Table 3).

DISCUSSION

The double balloon catheter for induction of labor was well-accepted by the majority of the women and clinicians surveyed at a tertiary hospital in the state of New South Wales, Australia. Our study found that the catheter was a well-accepted method with the majority of the pregnant women reporting that they would consent to the procedure in a future pregnancy, if clinically indicated. This finding is consistent with the results of another study that found that women receiving the double balloon catheter, in combination with oral misoprostol, would recommend the method to others.

The majority of midwives and doctors agreed that on most occasions the double balloon catheter was effective as a cervical ripening device. This finding is consistent with current literature that the double catheter is more effective than prostaglandins.

Our study highlights an inconsistency between clinician's perceptions about timing of double balloon catheter insertion and removal. The majority of midwives agreed that this needed to be improved, while only a third of doctors felt the same way. Interestingly, motivation for this study was the result of anecdotal reports from midwives about workload issues, namely the extended waiting periods of women being induced and the timing and delays of double balloon catheter insertion and removal. Possible solutions to these delays include: a designated treatment room, scheduling systems for catheter insertions and organized staff training, especially for upgrading the skills of midwives.

This study found that women consistently regarded the double balloon catheter insertion as painful to varying degrees, with some describing the pain as unbearable. The pain experienced compared to other cervical ripening methods varies between studies. Wilkinson et al. reported that the double balloon catheter is often more painful than other cervical ripening methods. Interestingly, in the study of Jozwiak et al., women reported the highest levels of discomfort with prostaglandins, then the double balloon catheter, and the lowest discomfort with the single balloon catheter. Similarly, in the study of Pennell et al., women reported higher levels of pain with both the double balloon catheter and prostaglandins compared to the single balloon catheter. Although our study did not compare the catheter to other methods of induction of labor, our findings are consistent with the current literature.

The majority of women in our study reported that the pain relief offered to them post insertion was effective. This finding is similar to that of Kehl et al., where women were not bothered by the double balloon catheter once in situ. Insertion using digital technique is reported as slightly more acceptable compared to insertion with a speculum. Similarly, digital insertion technique is associated with significantly higher tolerance of single balloon catheter insertion. This is an area for further research.

When it comes to outpatient setting for cervical ripening with double balloon catheter, our findings are inconsistent with the literature, for the pregnant women but not the clinicians. In regard to the perceived acceptability, the majority of clinicians considered this to be appropriate whereas women did not. Double balloon catheter in the outpatient setting has been associated with improved relaxation, privacy and sleep, compared to women in the inpatient setting. Most importantly, double balloon catheter in the outpatient setting has been found to be as safe and effective as standard inpatient care. Furthermore, the outpatient setting allows women the benefit of the comfort of their own home without increasing their anxiety.

The evidence for outpatient double balloon catheter insertion indicates better acceptability by pregnant women, contrary to our findings. We propose several reasons for the contrasting views between clinicians and women. Firstly, double balloon catheter management in the outpatient setting may not have been clearly explained or discussed with the women we surveyed. Women may have been unaware that double balloon catheter in the outpatient setting depended on being identified as 'low-risk', with normal fetal heart rate patterns prior to discharge, follow-up at the hospital the next day, and clear guidance on when to call the hospital, i.e. rupture of membranes. Secondly, some women may have cultural perceptions that the hospital is safer than home. Finally, some of the women surveyed may have been induced for reasons deemed high-risk, as our selection criteria did not differentiate between high-risk and low-risk induction of labor.

Limitations

The study had some limitations. Firstly, the sample size was small which makes it difficult to draw any major conclusions. We did not differentiate between primiparous and multiparous women. This distinction may have highlighted a difference in views to note for future induction of labor planning. Lastly, it was difficult to track exactly how many women were administered a double balloon catheter in the study period due to a lack of clear documentation in the maternity database.

CONCLUSIONS

Our study found the double balloon catheter to be a well-accepted method of cervical ripening among women and clinicians, while revealing differing attitudes between women and clinicians regarding timing and outpatient cervical ripening. Considering the increasing rates of induction of labor, further research into the acceptability of double balloon catheter for cervical ripening is required. Our study contributes to the current literature but highlights the need for further investigation into outpatient options. Additionally, it highlights the need to undertake qualitative research to further explore women's views, experiences and perceptions on induction of labor, to ensure clinical practice is woman-centered and evidenced-based, and to guide policy and protocol.

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A snapshot of women's and clinicians' perceptions of the double balloon catheter for induction of labor

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Introduction: Induction of labor (IOL) is rising globally and is growing steadily in the state of New South Wales, Australia. There are numerous methods of induction of labor, including the double balloon catheter (DBC). There is minimal evidence on women's attitudes and experiences and...

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Double balloon catheters: A promising tool for induction of labor in multiparous women with unfavorable cervices

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Double balloon catheters: A promising tool for induction of labor in multiparous women with unfavorable cervices

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Abstract

Objective:

To compare the effectiveness and safety of oxytocin and a cervical ripening balloon in women with unfavorable cervices for inducing labor.

Material and Methods:

A total of eighty pregnant women between 37-41 gestational weeks having singleton pregnancies and intact membranes with unfavorable cervices were randomized into two groups, cervical ripening balloon (n=40) and oxytocin infusion (n=40). The primary outcomes were the labor time and the route of delivery. Secondary outcomes were the effect of parity on time of labor, and obstetric and perinatal outcomes.

Results:

The median time to delivery was 9.45 hours in cervical ripening balloon group and 13.2 hours in the oxytocin group in multiparous women. The differences were statistically significant (p<0.001). The median time until delivery was 11.48 hours in cervical ripening balloon group and 13.46 hours in the oxytocin group; the differences were statistically significant (p<0.001). Cesarean delivery ratios were similar in both groups (p=0.431).

Conclusion:

The results of the present study are promising for balloon use, especially in multiparous women. It is beneficial to support these data with wide ranging population-based studies.

Keywords: Double-balloon catheter, labor induction, unfavorable cervix

Introduction

The mechanisms of birth and the initiating factors of labor are still obscure. The main goal of obstetrics is the health of both the mother and the baby. The management of the labor process is an important part of obstetric practice. Although labor initiates spontaneously in a vast majority of pregnancies, induction of labor (IOL) may be needed in a wide variety of conditions including post-term pregnancies, preterm premature membrane rupture, preeclampsia, eclampsia, hemolysis, elevated liver enzyme levels, and low platelet levels-HELLP syndrome, fetal demise, maternal diabetes mellitus, fetal distress, maternal cholestasis, and chorioamnionitis. In such situations, an unfavorable uterine cervix is one of the major obstacles to successful IOL ( 1).

The uterine cervix retains its physical integrity by remaining firm during pregnancy until the beginning of labor. Just before labor, the cervix softens and becomes more distensible; this process is called cervical ripening. However, if induction is indicated before onset of spontaneous labor, cervical conditions come to the fore for a successful delivery. The Bishop scoring system is commonly used for evaluation of the cervix ( 2, 3). In general, when the Bishop score is less than six, the success rate of IOL is poor ( 3, 4, 5). Unfortunately, nearly 50% of women with an indication of IOL have an unfavorable cervix with a Bishop score of less than six ( 2).

Oxytocin is one of the commonly preferred pharmacologic methods used for inducing labor ( 6). However, systemic adverse effects including tachycardia, flushing, and uterine tachysystole are the disadvantages experienced during its infusion. The primary effect of oxytocin is on myometrial contractility and the secondary effect is on cervical ripening in interactions with steroid hormones, prostaglandins (PGs), and probably nitrite oxide (NO) ( 7, 8).

Alternatively, a cervical ripening balloon is used for IOL. Such balloons may be speculated to cause fewer systemic adverse effects because of their local and limited effect and because they are mechanical in nature ( 9). On the other hand, high cost and application difficulties are some of the disadvantages experienced when these devices are preferred for IOL. The proposed mechanism of the cervical ripening balloon during labor induction is apparently mechanical, but interestingly, cervical ripening is also achieved pharmacologically via the Ferguson reflex. This is a neuroendocrine reflex and has as its afferent limb the sensory nerves from the vagina and cervix (Franken Hauser nerves), the ascending somatosensory pathways in the spinal cord (the anterolateral columns) and an incompletely described projection through the brainstem and medial forebrain bundle that ultimately reaches the hypothalamic magnocellular nuclei. The efferent limb of the reflex is the blood-borne carriage from the paraventricular nucleus and supraoptic nucleus of oxytocin. Oxytocin secretion is a consequence of this neuroendocrine reflex induced by tactile stimulation of the reproductive tract ( 9).

Although both procedures are implemented in different ways, both oxytocin and cervical ripening balloons have similar mechanisms in terms of their molecular action ( 8, 9). Hypothetically, a cervical ripening balloon might have lesser adverse effects during IOL as compared with oxytocin because of having a closer physiologic mechanism to oxytocin secretion ( 10, 11). In this study, we aimed to compare the effectiveness and safety of oxytocin (Synpitan ®) and cervical ripening balloons (Cook ®) for IOL in unfavorable cervices.

Material and Methods

This prospective randomized study was conducted at a tertiary care hospital. Ethics committee approval was obtained (approval number 154-4958/2009). After giving informed consent, patients were assigned to one of the induction methods according to a computer-generated randomized list. A total of 80 pregnant women with singleton pregnancies between 37 and 41 gestational weeks and intact membranes with unfavorable cervices were randomized and assigned to either the cervical ripening balloon group (n=40) or the oxytocin infusion (n=40) group. A visual analogue scale (VAS) was used to determine pain perception in both groups. All participants rated the pain using the VAS during the labor process (in the VAS scale, pain is rated from zero to ten in which zero indicates no pain and ten the worst possible pain).

The presence of vaginal bleeding, pregnancies from in vitro fertilization, non-cephalic presentation, multi-fetal pregnancies, prior uterine or cesarean surgery, an estimated fetal weight over 4500 grams, and obstetric complications (hypertensive disorders, post-term pregnancies or fetal growth disorders) were the exclusion criteria for labor induction.

Oxytocin infusion

Administration started with ten units of oxytocin per 1000 mL 0.9% saline with a rate of 10 mU/min adjusted by infusion pump. The infusion rate was increased by 1 mU/min every 15 minutes, until three strong uterine contractions were achieved in a one-minute period (200-250 Montevideo units). The maximum dosage was set as 60 mU/minutes. All cases were monitored for fetal heart rate and uterine contractions until delivery.

Cervical ripening balloon insertion

All patients were placed in the lithotomy position. The balloon was inserted using ring forceps passing through the internal cervical ostium and into the extra-amniotic space. The uterine part of the balloon was inflated with 40 mL saline and pulled back to the level of the internal ostium and the vaginal part of the balloon was inflated with 20 mL saline. The position of the balloon was checked. Once the correct position was established, both balloons were inflated with up to 80 mL. All patients were monitored by means of fetal heart rate and uterine contractions until delivery.

The groups were compared with respect to the interval between the time of induction and delivery, the amnion membrane rupture time, pain perception during labor, the amount of hemorrhage after delivery, the route of delivery, and the first and fifth minute APGAR scores. The primary outcomes were the induction to delivery interval and the cesarean ratios. Secondary outcomes included the effect of parity on the time to the onset of labor, in addition to obstetric and perinatal outcomes.

Statistical analysis

After performing normalization tests on parametric data, Student's t-test was used for data with normal distribution. The Mann-Whitney U test was used for data with non-normal distribution. Non-parametric values were analyzed using the chi-square test. IBM statistics SPSS 20.0 software was used for statistical analysis. P values <0.005 were considered statistically significant.

Results

The study was conducted at a tertiary care hospital in the department of obstetrics and gynecology. A total of 80 pregnant women aged between 22 and 29 years were enrolled. The mean ages were 24.75±3.57 years in the oxytocin group and 25.13±3.84 years in the balloon group. The demographic parameters of both groups were similar ( Table 1 ). The cesarean ratio in the oxytocin group was 20% (eight out of 40 women) and in the balloon group it was 27.5% (11 out of 40 women). The cesarean ratios were similar between the groups (p=0.431) ( Table 1 ). The mean time until delivery was 13.46 hours in the oxytocin group and 11.48 hours in the cervical ripening balloon group; the differences were statistically significant (p<0.001). In the multiparous women, the median time until delivery was 13.2 hours in the oxytocin group and 9.45 hours in the cervical ripening balloon group; the differences were statistically significant (p<0.001) ( Table 2 , ​,3). 3 ). The estimated fetal weight and APGAR scores of the newborns were similar in both groups. The mean hemoglobin changes from the pre-partum to post-partum period were 1.7 g/dL; the hemoglobin changes were not statistically significant (p=0.884). Pain perception scores were higher in the oxytocin group and this change was statistically significant (p<0.001). Neonatal intensive care hospitalization was needed for 10% (four out of 40 babies) in the oxytocin group and 2.5% (one out of 40 babies) in the balloon group. The difference was not statistically significant (p=0.359). The mean time to amnion membrane rupture was 10.9 hours in the oxytocin group and 9.6 hours in the balloon group. This difference was statistically significant (p=0.019) ( Table 4 ).

Discussion

In this study, we compared the effects of oxytocin and cervical ripening balloons in term pregnancies with unfavorable cervices. The most commonly preferred induction agent is intravenous oxytocin infusion. Oxytocin is known as the hormone that starts uterine contractions. However, according to recent research, the effect of oxytocin for parturition is not limited to the initiation of uterine contractions, it is also effective in cervical ripening ( 8). The proposed mechanism of oxytocin for cervical ripening is the secretion of local NO and PGs (especially PG F2a) through oxytocin receptor action located at the amnion membrane and placental decidua (8). Similarly, cervical ripening balloons initiate secretion of oxytocin, NO and PGs (especially PG F2a) via the Ferguson reflex ( 9). At the molecular level, both induction methods may have similar mechanisms in IOL.

When comparing the two methods in respect to labor time, a shorter time interval from induction to delivery was observed in women induced with balloon catheters. In multiparous women induced with double-balloon catheters, the time interval to delivery was observed to be markedly shorter than in that experienced by the oxytocin group. A relatively high positioning of the fetal head in multiparous women may place insufficient pressure on the uterine cervix in the oxytocin group. The imitating effect of the fetal head provided by the balloon catheter may be the cause of this difference. In studies comparing cervical ripening balloons with dinoprostone (known as a good cervical ripening agent), the mean time interval from induction to delivery was found to be similar between groups ( 12, 13, 14, 15). Pressure on the uterine cervix may be the major factor providing similar cervical changes with dinoprostone. Interestingly, in our study, the time interval to delivery in primiparous women was similar between both groups. Engagement of the fetal head with the pelvis may the determining factor affecting cervical ripening and the time interval to delivery. Some studies have argued that cervical ripening balloons could impede fetal head engagement with the birth canal and risk cord prolapse ( 16, 17). Other recent studies found that cervical ripening balloons function like a pillow for the fetal head, owing to the ellipsoid and cylindrical nature of the balloon ( 18, 19). In accordance with this idea, caesarean ratios were detected as being similar in both groups.

In a review published in 2008, increased maternal and fetal infection rates were reported as the result of balloon catheter use in labor induction ( 20). On the other hand, more recent studies found no risk of increased infection due to balloon catheter use ( 21, 22). The results of the present study support these latter studies.

Perception of pain is one of the troublesome adverse effects of catheter insertion. Contrary to our expectations, pain perception in the balloon group was lower as compared with the oxytocin group. There can be several factors affecting this result; perhaps the lack of a need for traction with double- balloon catheter use or the physiologic secretion of oxytocin ensured tolerable pain during labor. However, as the balloon application is a newly preferred method for inducing labor, more frequent patient contact could be achieved as a result of the desire to manage possible problems that might hinder the induction process. This increased attention can cause bias in patients such that they felt more comfortable and safer as compared with those in the oxytocin group.

In the present study, our priority was to compare easily obtained, preserved, applied, and cost-effective methods for the IOL in unfavorable cervices. Dinoprostone could be a good alternative for the study design, as it involves simplicity in application, but its high cost and the difficulties involved in its preservation ruled out its use in this study. However, misoprostol is a good alternative for the study design because it provides cost effectiveness, ease of application, and preservation conditions. Unfortunately, misoprostol is not licensed for use in labor induction in our country. Another limitation of the study was our relative inexperience with the balloon in comparison with oxytocin for labor induction.

In summary, the argument regarding labor induction in unfavorable cervices is still continuing. The aim of the this study was to compare our routine labor induction procedure (oxytocin) with the new cervical ripening balloon catheters in women with unfavorable cervices. Similar cesarean ratios were observed in both groups. The balloon catheters provided a shorter time interval to delivery and lower pain perception during labor, especially in multiparous women. Post-partum hemorrhage, APGAR scores, and fetal and maternal outcomes were similar in both groups.

Oxytocin is still a safe, effective, easily applicable, easily preserved, and cost-effective method for labor induction. However, the results of our study are promising for balloon use, especially in multiparous women. The main problems with cervical ripening balloons are the involved cost and application difficulties. By manufacturing reusable catheters, the cost problem can be solved; application difficulties can be resolved by increasing application frequency. The latter situation is bound up with cost effectiveness. Once these disadvantages are resolved, cervical ripening balloons may become a good alternative to oxytocin for inducing labor, especially in multiparous women. It would be beneficial to support these data with large-scale population-based studies.

Footnotes

Ethics Committee Approval: Ankara University Faculty of Medicine Research Ethics Committee, decision no: 154-4958.

Informed Consent: N/A.

Peer-review: Externally peer-reviewed.

Contributed by

Author Contributions: Concept - F.S., F.T.; Design - F.S., F.T.; Supervision - F.T., A.G., F.S.; Materials - F.T., A.G.; Data Collection or Processing - F.T., A.G.; Analysis or Interpretation - F.T., F.S., A.G.; Writing - F.T., A.G.

Conflict of Interest: No conflict of interest is declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.

References

1. Calder AA. The management of the unripe cervix In: Keirse MJNC, ABM Anderson, J Bennebroek Gravenhorst, editors. Human Parturition. Leiden University Press, The Hague. 1979. [ Google Scholar]

9. Johnson MH. Essential Reproduction 6th edition. Blackwell Publishing. 2007;p:247-8. [ Google Scholar]

17. Hasegawa J, Sekizawa A, Ikeda T, Koresawa M, Ishiwata I, Kawabata M, et al. The use of balloons for uterine cervical ripening is associated with an increased risk of umbilical cord prolapse: population based questionnaire survey in Japan. BMC Pregnancy Childbirth. 2015;15:4. [[ PMC free article] [ PubMed] Google Scholar]

Articles from Journal of the Turkish German Gynecological Association are provided here courtesy of Turkish German Gynecological Association

# data[].attributes.attachment_link.title
Double balloon catheters: A promising tool for induction of labor in multiparous women with unfavorable cervices

# data[].attributes.attachment_link.description
To compare the effectiveness and safety of oxytocin and a cervical ripening balloon in women with unfavorable cervices for inducing labor.A total of eighty pregnant women between 37-41 gestational weeks having singleton pregnancies and intact membranes ...

# data[].attributes.headline
Socioeconomic inequalities and adverse pregnancy outcomes in the UK and Republic of Ireland: a systematic review and meta-analysis

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Socioeconomic inequalities and adverse pregnancy outcomes in the UK and Republic of Ireland: a systematic review and meta-analysis

# data[].attributes.attachment_link.readable_text
Original research

Katie Thomson, ¹ Malcolm Moffat, ¹ Oluwatomi Arisa, ¹ Amrita Jesurasa, ² Catherine Richmond, ¹ Adefisayo Odeniyi, ¹ Clare Bambra, 1, ³ Judith Rankin, 1, ³ Heather Brown, 1, ³ Julie Bishop, ⁴ Susan Wing, ⁴ Amy McNaughton, ⁴ and Nicola Heslehurst 1, ³

Abstract

Objective

There has been an unprecedented rise in infant mortality associated with deprivation in recent years in the United Kingdom (UK) and Republic of Ireland. A healthy pregnancy can have significant impacts on the life chances of children. The objective of this review was to understand the association between individual-level and household-level measures of socioeconomic status and adverse pregnancy outcomes.

Design

Systematic review and meta-analysis.

Data sources

Nine databases were searched (Medline, Embase, Scopus, ASSIA, CINAHL, PsycINFO, BNI, MIDRIS and Google Scholar) for articles published between 1999 and August 2019. Grey literature searches were also assessed.

Study selection criteria

Studies reporting associations between individual-level or household socioeconomic factors on pregnancy outcomes in the UK or Ireland.

Results

Among the 82 353 search results, 53 821 titles were identified and 35 unique studies met the eligibility criteria. Outcomes reported were neonatal, perinatal and maternal mortality, preterm birth, birth weight and mode of delivery. Pooled effect sizes were calculated using random-effects meta-analysis. There were significantly increased odds of women from lower levels of occupation/social classes compared with the highest level having stillbirth (OR 1.40, 95% CI 1.23 to 1.59, I ² 98.62%), neonatal mortality (OR 1.39, 95% CI 1.22 to 1.57, I ² 97.09%), perinatal mortality (OR 1.39, 95% CI 1.23 to 1.57, I ² 98.69%), preterm birth (OR 1.41, 95% CI 1.33 to 1.50, I ² 70.97%) and low birth weight (OR 1.40, 95% CI 1.19 to 1.61, I ² 99.85%). Limitations relate to available data, unmeasured confounders and the small number of studies for some outcomes.

Conclusions

This review identified consistent evidence that lower occupational status, especially manual occupations and unemployment, were significantly associated with increased risk of multiple adverse pregnancy outcomes. Strategies to improve pregnancy outcomes should incorporate approaches that address wider determinants of health to provide women and families with the best chances of having a healthy pregnancy and baby and to decrease pregnancy-related health inequalities in the general population.

PROSPERO registration number

PROSPERO CRD42019140893.

Keywords: epidemiology, maternal medicine, fetal medicine, public health

Search strategy broad and wide-ranging resulting in the inclusion of 17 130 631 mothers and babies in the analysis from 35 studies.

No restriction by pregnancy outcome; results therefore provide a comprehensive overview of the effects of socioeconomic status.

Results are limited to the UK and Ireland only.

Between countries and over time, the occupational classifications used have changed.

Occupational data dominates the evidence base; limited data were available for other measures of inequality (eg, housing, income and car ownership).

Introduction

There has been a sustained increase in infant mortality in England, disproportionately affecting the most deprived areas,1 2 and a reduction in life expectancy for the first time in 120 years, with similar trends in the rest of the UK.1 The evidence base that demonstrates the increase in children and families living in poverty, and the association with increasing mortality rates and reduction in life expectancy, is compelling. The recent Marmot review1 identified that 30% of children in England are living in poverty, and those in the most deprived 10% are almost twice as likely to die and more likely to have illness or long-term disability.

Central to understanding the relatively low performance of the UK and ROI compared with other HICs is documenting the scale of inequalities related to adverse pregnancy outcomes across the social gradient. Important individual factors to explore the ' causes of the causes'1 include employment, education, income and housing. While there have been a number of systematic reviews that examine the impact of deprivation,6 12 13 these are out of date and focus on area-based measures (such as the Index of Multiple Deprivation) as an inadequate proxy for individual measures of socioeconomic status (SES), which can be more difficult to collate. There is some evidence from a meta-analysis published in 201214 that individual-level social class is significantly associated with an increase in low birth weight (LBW) and infant mortality, and the authors concluded that future research should focus on the more proximal individual-level determinants of health. Using individual-level socioeconomic indicators provides a richer way of understanding the relative importance of particular SES factors and their direct and indirect impact on a range of adverse pregnancy outcomes. This is an essential first step to understand and then mitigate their effect on the most vulnerable groups in our communities. This systematic review and meta-analysis aimed to understand the association between individual-level and household-level measures of SES and adverse pregnancy outcomes in the UK and ROI. We hypothesised that there would be an association between low SES measures and increased risk of adverse pregnancy outcomes.

Methods

Protocol, search strategy and study selection

The systematic review was registered with PROSPERO (CRD42019140893) and conducted in line with MOOSE guidelines15 ( online supplemental appendix S1). Nine electronic databases were searched between 1 January 1999 and 7 August 2019 ( online supplemental appendix S2). The start date of 1999 was included as it coincided with the start of the English Health Inequalities Strategy.16 The databases were searched using key words and Medical Subject Headings (MeSH) developed by an information specialist at Newcastle University (CR).

Searching for epidemiological studies using databases alone systematically misses a proportion of relevant studies; therefore, in line with MOOSE guidelines, supplementary searches were carried out. Backwards and forwards citation chaining of included studies were undertaken and relevant systematic reviews were assessed. Finally, literature searches comprising key data sources for the UK and ROI ( online supplemental appendix S3) were run, and experts in key organisations in each of the countries were contacted.17

The inclusion criteria for the review were determined a priori in terms of Population, Exposure, Comparison, Outcome and Study design18:

Population: the unborn fetus, neonate (child under 28 days of age) or mother in the UK or ROI.

Exposure: any individual-level or household-level socioeconomic factor such as employment, education, income, housing, poverty/low wage, social isolation and car ownership. Aggregate area-level measures of SES (such as the Index of Multiple Deprivation) were excluded.

Comparison: studies with individual-level or household-level exposures that compare low to high SES.

Outcomes: pregnancy outcomes related to the fetus, neonate or mother. We did not exclude outcomes if they were relevant to the fetus, neonate or mother during pregnancy or within 28 days postnatal as we wanted to provide a comprehensive overview of the existing evidence base.

Study design: observational studies with cohort, case-control, longitudinal or cross-sectional designs.

The results from the database searches were imported into Endnote,19 and duplicates were removed. Screening the titles and abstracts was managed in Covidence.20 Title, abstract and full-text screening were completed independently in duplicate. Where multiple studies reported data from the same cohort, decisions on which study to include were based on sample size, time period and categories used to define determinants and outcomes. We included any studies that met the inclusion criteria and reported an association between the exposure and outcomes of interest, regardless of whether this was the primary aim of the study. Decisions on inclusion and exclusion of studies were recorded using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart.

Data extraction and quality appraisal

Data extractions were carried out using a standardised protocol independently by two reviewers for each included study (KT, OA and MM), and discrepancies were validated by a third reviewer (AO and NH). Data were extracted on the characteristics of the included studies and the results reported on associations between inequality exposure variables and pregnancy outcomes ( online supplemental appendix S4). Authors of primary studies were contacted if needed to request additional data or clarify reported results ( online supplemental appendix S5). The Newcastle-Ottawa scale was used to assess information bias, selection bias and confounding in case-control and cohort studies ( online supplemental appendix S6).21 Stars were awarded for high-quality aspects of study design. A maximum of eight stars was attainable for cohort studies (0-2 stars deemed as low quality, 3-5 moderate quality and 6-8 high quality) and nine stars for case-control studies (0-3 stars for low quality, 4-6 for moderate quality and 7-9 for high quality). Any discrepancies on screening, extraction and quality appraisal were resolved through discussion between the reviewers (KT, OA, MM and AO) and the project lead (NH).

The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology was used to address the quality of the evidence.22 Only those outcomes considered most important were evaluated using GRADE, and due to the available evidence, only inequalities in occupation/social class were considered. Quality of evidence for each pregnancy outcome was assessed based on study design (the baseline rating for observational studies is low), risk of bias, imprecision of estimates, inconsistency of results from different studies, indirectness of study results (ie, lack of applicability) and publication bias.23

Evidence synthesis and statistical analysis

A meta-analysis was used to calculate a pooled odds ratio (OR) and a 95% CI where there were at least two studies reporting the same outcome and comparable individual-level or household-level SES exposures. Meta-analysis was only possible for occupation-derived social class. Subgroups for this variable were included in the meta-analysis where possible to stratify analysis comparing intermediate-level or lowest-level of occupation/social class to highest level. Heterogeneity was explored through meta-regression for factors including duration of data collected, country, region, date and sample size, location, publication date and quality. I ² values of 25%, 50% and 75% were used to indicate low, moderate and high levels of heterogeneity.24 Publication bias was investigated using Egger's test and funnel plots. Sensitivity analysis was performed for each meta-analysis by excluding one dataset at a time to identify the effect of any individual dataset on the pooled effect size and between-study heterogeneity. All analyses were conducted in Stata V.16.25

Narrative synthesis methods described by Popay et al 26 were used to report outcomes with insufficient data to include in a meta-analysis and to integrate the narrative and meta-analysis data. Preliminary synthesis involved grouping all data into themes based on outcomes reported and type of SES measure. The associations between SES determinants and pregnancy outcomes reported by the studies, or calculated using data reported in the studies, were tabulated according to pregnancy outcome themes (eg, birth weight outcomes) and subgrouped by the level of SES determinant (eg, occupation). Where required, data were transformed to be comparable between studies (eg, using reported frequency data to recalculate ORs into more comparable SES categories). Authors were contacted when insufficient data were reported in the published studies to calculate ORs. Relationships between studies are reported by discussion of reciprocal and refutational patterns in the data, including the statistical significance and direction of effect. The narrative synthesis is supplemented by a discussion of the wider evidence base and the strengths and limitations of this review including the gaps in the existing literature.

Patient and public involvement

Patients or the public were not involved in any aspect of the study design, conduct or in the development of the research question or outcome measures.

Results

The database searches identified 53 821 records after duplicates had been removed. A further 9414 references and citations and 529 grey literature data sources were screened ( figure 1 ), of which 1439 were screened at full-text level (reasons for exclusion are detailed in online supplemental appendix S7). Forty-one studies met the inclusion criteria, six of these reported duplicate data ( online supplemental appendix S8). Thirty-five studies were included reporting unique data for 17 130 631 mothers and babies, 27 were conducted in the UK and 8 in the ROI ( table 1 ). The studies were published between the years 1999 and 2019 (with data reported from 1990 onwards), 10 were case control and 25 were cohort studies. The majority of studies reported national-level data, and these datasets are assumed to be nationally representative. All studies scored between three and eight on the Newcastle-Ottawa Scale ( online supplemental appendix S9). The studies were rated as either high quality (n=4 case-control, n=18 cohort) or moderate quality (n=6 case-control, n=7 cohort), with no low-quality studies. Most studies (n=23) reported outcomes associated with occupation-derived social class using different classifications ( online supplemental appendix S10), which were grouped into: (1) highest level (managerial/professional) occupations; (2) intermediate-level occupations; and (3) lowest level (routine/manual/partly skilled) occupations.27 Seventeen studies investigated associations with education, seven for employment and income/finances, four for housing and one for car ownership. Pregnancy outcomes reported were mortality (stillbirth, neonatal, perinatal and maternal), LBW, preterm birth (PTB), mode of delivery, maternal morbidity and congenital anomalies ( table 1 ).

Table 1

Author, publication year, country

Study design and period

Registry/data source

Description of population, sample size

Inequality exposure

Pregnancy outcome

Risk of bias

Cohort study 2009

National Perinatal Reporting System (NPRS) and the Hospital In-Patient Enquiry scheme (HIPE).

All nulliparous singleton births to women discharged from the 19 publicly funded hospital maternity units for whom an NPRS and HIPE record was available. n=29 870.

Occupation/
social class.

Mode of delivery.

6
High

Clemens and Dibben 2016, Scotland90

Cohort study 1994-2008

The Scottish Longitudinal Study (SLS) and the Scottish Morbidity Record (SMR).

Singleton births from the SLS, a 5% sample of the Scottish population that links census records and maternity hospital inpatient data from the SMR.
Sample size not reported.

Education.
Occupation/
social class.

Preterm birth.

5
Moderate

Collingwood Bakeo and Clarke 2006, England and Wales89

Cohort study 1990s

Office for National Statistics (ONS) Longitudinal Study.

Singleton, live births to mothers in the ONS Longitudinal Study, a 1% sample of the population of England and Wales for which linked census data are available. n=57 129 (no. of rooms/cars), n=49 212 (economic activity) and n=56 988 (no. of people in household).

Employment.
Housing.
Car ownership.

Low birth weight.

7
High

Cohort study 1996-2000

Births and deaths recorded by local registrars and forwarded to the ONS.

Births registered in England and Wales by local registrars. Parents' age obtained from the ONS and birth weight derived from birth notifications supplied to local registrars by the National Health Service.
n=306 067.

Income.1

Low birth weight.

7
High

Cohort study 2000-2002

Millennium Cohort Study (MCS).

Live singleton births whose parents were enrolled in the MCS. The MCS is a retrospective study designed to disproportionately include comparative samples of children born in advantaged, disadvantaged and ethnically diverse regions of England, Scotland, Northern Ireland and Wales. Eligible births were selected from a random sample of UK electoral wards using the register of children eligible for child benefit. Data were collated using interviews and linked in turn to hospital medical records.
n=18 239.

Education.
Occupation/
social class.

Mode of delivery.

5
Moderate

Fairley and Leyland 2006, Scotland79

Cohort study 1980-2000

Data linked to the registrar general's birth registration.

All live singleton hospital births in Scotland linked to registrar general's birth registrations.
n=283 032(1990-1994) and n=281 001(1995-2000).

Occupation/
social class.

Low birth weight.
Preterm birth.
Small for gestational age.

5
Moderate

Cohort study 1990-1991, 1999-2000.

Information Services, National Health Service National Services Scotland.

Routine maternity discharge data from live singleton births in Scottish hospitals from two time periods. n=105 247 (1990) and n=70 667 (1999-2000).

Occupation/
social class.

Mode of delivery.

7
High

Case-control study 2005-2014

UKOSS.

Cases were from any obstetrician-led maternity unit in the UK reporting cases of amniotic-fluid embolism (AFE) (or a severe maternal outcome caused by AFE). The controls were the two women who delivered immediately before the case in the same hospital.
Cases: n=120.
Controls: n=3834.

Occupation/
social class.

Amniotic-fluid embolism (AFE).
Severe maternal outcome caused by AFE.

7
High

Cohort study 2009-2011

Perinatal episode electronic record (PEER).

Births within the 19 maternity units in the West Midlands using the database derived from the regional NHSnet-based PEER hosted by the West Midlands Perinatal Institute. n=105 476.

Employment.

Stillbirth.

6
High

Martinson and Reichman 2016, UK83

Cohort study 2000-2002

MCS and The UK data archive.

Live singleton births whose parents were enrolled in the MCS. Data were collated from an interview conducted by a home visitor within 9 months of delivery. n=12 018.

Education.
Income.

Low birth weight.

4
Moderate

Cohort study 1991-1992

The Avon Longitudinal Study of Parents and Children (ALSPAC).

Women with a singleton, liveborn infant and a term pregnancy mode of delivery who were involved in ALSPAC, a longitudinal cohort study in Avon, England.
n=13 678.

Education.
Income.

Mode of delivery.
Preterm birth.
Intrauterine growth restriction.

7
High

Cohort study 1999-2001

Eastern Regional Health Authority (ERHA).3

All births in the ERHA (encompassing the Northern, the East Coast and the South Western Area health boards).
n=63 571.

Employment.
Occupation/
social class.

Low birth weight.

3
Moderate

Cohort study 2001-2003

Lifeways cohort.

Women involved in the Lifeways cohort who were Irish-born and recruited in either a predominantly rural region (University College Hospital Galway) or an urban area (Coombe Women's Hospital in Dublin). Baseline data for mothers were collected using a self-completed questionnaire. Pregnancy outcomes were derived from hospital records. n=1048.

Education.

Mid-low birth weight.
Macrosomia.

6
High

Case-control study 2009-2013

Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK (MBRRACE-UK) and UKOSS.

Cases were from women who died from direct or indirect causes during pregnancy or within 42 days of the end of pregnancy in the UK. Population controls were obtained from UKOSS.
Cases: n=383.
Controls: n=3310.

Employment.

Maternal mortality.

7
High

National Perinatal Reporting System (NPRS), 1990-1993 and 2002-2018, ROI4 29

Cohort study 1990-1993; 1999-2016

NPRS.

The NPRS collects information on birth records each year from 19 maternity units and all practising self-employed community midwives.
n=1 352 878.

Occupation/
social class.

Very low birth weight (VLBW).
Low birth weight.
Mid-low birth weight.
Macrosomia.
Stillbirth.
Neonatal death.
Perinatal death.

6
High

National Records of Scotland (NRS), 201930

Cohort study 2000 - 2018

NRS.

Births registered in Scotland by local registrars. Birth records derived from notifications supplied to local registrars by the National Health Service.
n=1 675 973.

Occupation/
social class.

Stillbirths.
Perinatal mortality.
Neonatal mortality.

6
High

Cohort study 2001-2003

Lifeways cohort.

Women involved in the Lifeways cohort who were Irish born and recruited in either a predominantly rural region or an urban area.
n=1124.

Education.5
Occupation/
social class.

Low birth weight.
Mid-low birth weight.
Preterm birth.5
Small for gestational age.

7
High

Cohort study 2001-2003

Lifeways cohort.

Women involved in the Lifeways cohort who were Irish-born and recruited in either a predominantly rural region or an urban area. n=924.

Education.
Housing.
Income.

Preterm birth.

7
High

ONS 1999-2017, England and Wales31

Cohort study 1999-2017

ONS.

Births registered in England and Wales by local registrars. Birth records derived from notifications supplied to local registrars by the National Health Service.
n=12 799 233.

Occupation/
social class.

VLBW.
Low birth weight.
Mid-low birth weight.
Macrosomia.
Stillbirths.
Perinatal mortality.
Neonatal mortality.

6
High

Cohort study 1990-1991

Avon Longitudinal Study of Parents and Children (ALSPAC).

Women with a singleton, liveborn infant and a term pregnancy mode of delivery who were involved in ALSPAC, a longitudinal cohort study in Avon, England.
n=8925 (maternal social class).
n=12 078 (home ownership).

Occupation/
social class.
Employment.
Housing.

Mode of delivery.

5
Moderate

Cohort study 2007-2010

The Born in Bradford (BiB) cohort.

Women with singleton live births who consented to take part in the BiB study (who attended the antenatal service in Bradford and were booked to give birth in Bradford). A baseline questionnaire was used together with data recorded in the electronic maternity system.
n=10 850.

Education.

Preterm birth.

5
Moderate

Cohort study 2007-2011

BiB and British Isles Network of Congenital Anomalies Register.

Women with singleton live births who consented to take part in the BiB study. Anomalies were classified into six groups: single anomalies, several anomalies within the same anomaly group, metabolic disorders, syndromal associations, chromo somal syndromes and more than one unrelated anomaly.
n=13 776.

Education.

Congenital anomalies.

6
High

Cohort study 2009

NPRS and HIPE scheme.

All women with singleton births (live and stillborn) discharged from 19 publicly funded hospitals for whom NPRS and HIPE data were available.
n=69 304.

Occupation/
social class.

Induction of labour.

6
High

Snelgrove and Murphy 2015, UK93

Cohort study 2000-2002

MCS and The UK data archive.

Live singleton births whose parents were enrolled in the MCS. Data were collated from an interview conducted by a home visitor within 9 months of delivery. n=17 285.

Education.
Employment.
Housing.
Income.
Occupation/
social class.

Preterm birth.

7
High

Cohort study 2007-2010

BiB.

Women with singleton live births who consented to take part in the BiB study. A baseline questionnaire was used together with data recorded in the electronic maternity system.
n=9680.

Education.7
Occupation/
social class.
Income/finances.

Preterm birth.7
Small for gestational age.

8
High

Cohort study 1993-1995

All Wales Perinatal Survey/ Child Health System Database/ ONS/ Cardiff Births Survey.

Data relating to stillbirths and infant deaths were identified using the All Wales Perinatal Survey. Survivors born to women resident in South Glamorgan (Wales) recorded prospectively by the Cardiff Births Survey were used as a comparison.
n=16 842.

Occupation/
social class.

Stillbirth.
Neonatal death.
Perinatal death.

4
Moderate

Cohort study 2009-2013

Coombe Women and Infants University Hospital Dublin.

All women who delivered a baby weighing ≥500 g at Coombe Women and Infants University Hospital Dublin.
n=38 528.

Occupation/
social class.

Preterm birth.
Spontaneous preterm birth.
Elective preterm birth.

6
High

Cohort study 2004-2016

University Hospital Southampton.

Women aged 18 years or older who had a live singleton birth at the University Hospital Southampton National Health Service Trust.
n=43 787.

Education.
Employment.

Small for gestational age.

8
High

Case-control study 1998-1999

Three maternity units (and attached neonatal intensive care units) in Southeast England.

Infants who were very preterm (VP)/VLBW (<1500 g or <32 weeks of gestation) and admitted to one of three neonatal intensive care units in southeast England. Of the 214 survivors, 112 were randomly approached and parents of 90 infants consented. Full-term infants (37-42 weeks' gestation) from the same maternity units were approached in order to match to the VP/VLBW sample characteristics.
Cases: n=90.
Controls: n=115.

Education.
Income.

VLBW.
Very preterm birth.

4
Moderate

Mortality

Six studies reported stillbirth, neonatal mortality, perinatal mortality and maternal mortality ( online supplemental appendix S11 tables a-d). Individual and household inequality measures reported were paternal, maternal and primary household occupation/social class.

Stillbirth was reported by five studies28-32 for 12 642 203 births ( online supplemental appendix S11, table a), and four29-32 could be pooled into the meta-analysis. Perinatal mortality was reported by three studies29 31 32 for 11 189 810 births ( online supplemental appendix S11, table b), and neonatal mortality was reported by three studies30-32 for 11 580 610 births ( online supplemental appendix S11, table c), and all could be pooled in meta-analysis. There were significantly increased odds for the pooled lowest/intermediate occupation compared with highest for all three outcomes (stillbirth: OR 1.40 95% CI 1.23 to 1.59 ( figure 2 ); perinatal mortality: OR 1.39 95% CI 1.23 to 1.57 ( figure 3 ); neonatal mortality: OR 1.39 95% CI 1.22 to 1.57 ( figure 4 )). All subgroup meta-analyses showed highest odds among the lowest level of occupation/social class compared with the highest level (stillbirth: OR 1.61 95% CI 1.37 to 1.88; perinatal mortality: OR 1.57 95% CI 1.41 to 1.74; neonatal mortality: OR 1.58, 95% CI 1.44 to 1.74; figures 2-4 ). Heterogeneity was high for all meta-analyses and was not explained by any of the factors included in meta-regression ( online supplemental appendix S12Aiii, Biii, Ciii). Sensitivity analysis demonstrated that the meta-analysis results were robust to the effect of any individual studies for all stillbirth analyses ( online supplemental appendix S12Aiv) and for perinatal and neonatal mortality overall pooled meta-analyses and lowest versus highest occupation subgroups ( online supplemental appendix S12Biv, Civ); however, the significance changed with the removal of the Office for National Statistics (ONS) 2002-2017 dataset in the intermediate subgroup for both outcomes. There was evidence of publication bias for stillbirth ( online supplemental appendix S12Aii) but not for perinatal or neonatal mortality ( online supplemental appendix S12Bii, Cii). One study28 not able to be pooled in the stillbirth meta-analysis reported increased odds of stillbirth among unemployed mothers (OR 1.24, 95% CI 1.00 to 1.54) and fathers (OR 2.26, 95% CI 1.69 to 3.02) compared with those who were employed ( online supplemental appendix S11, table a). Maternal mortality was reported by one study33 that showed a significantly increased odds among unemployed women compared with those in employment following adjustment for confounding factors (AOR 1.81, 95% CI 1.08 to 3.04, online supplemental appendix S11 table d). GRADE scores showed very low-quality evidence for stillbirth and low-quality of evidence for neonatal, perinatal and maternal mortality ( online supplemental appendix S13).

Preterm birth

Eight studies79 84 86 90-94 reported a combination of adjusted and unadjusted associations between PTB and occupation/social class, employment status, education, housing and income ( online supplemental appendix S11, tables n-q). Meta-analysis was possible for the association between occupation/social class and preterm birth, which was reported by two studies79 90 for 515 752 births ( online supplemental appendix S11, table n). The pooled meta-analysis for lowest/intermediate occupation compared with highest identified a significantly increased odds (OR 1.41, 95% CI 1.33 to 1.50; figure 8 ). The subgroup meta-analysis identified that the highest odds for PTB were in the lowest level occupation category (OR 1.51, 95% CI 1.42 to 1.60). Heterogeneity was moderate for the lowest level occupation subgroup analysis but substantial for the overall meta-analysis and the intermediate occupation subgroup ( figure 8 ), and these were not explained by the factors included in meta-regression ( online supplemental appendix S12Giii). Sensitivity analysis demonstrated that the meta-analysis results were robust to the effect of any individual studies ( online supplemental appendix S12Giv), and there was no evidence of publication bias ( online supplemental appendix S12Gii). The GRADE score for preterm birth showed very low-quality evidence ( online supplemental appendix S13).

Additional data reported for PTB included employment, education, housing and income or other finance measures. Two studies93 94 reported significantly increased odds of PTB (overall, spontaneous and elective) among unemployed women compared with employed ( online supplemental appendix S11, table n). Five studies84 90-93 reported an overall lack of association between education and PTB ( online supplemental appendix S11, table o). Two studies84 93 reported the association between income and PTB, and another86 reported the association between financial difficulties and PTB ( online supplemental appendix S11, table p). For income, there was a significantly increased odds among women in the lowest income group84 in one study but not in another.93 There were also significantly increased odds among women 'not managing financially' but not for 'being behind with bills'.86 A significantly increased risk of PTB was reported for babies born to women living in crowded homes compared with non-crowded homes,91 and there was conflicting evidence91 93 for rented housing ( online supplemental appendix S11, table q).

Mode of delivery

Five studies reported the associations between occupation/social class and caesarean delivery (emergency, elective or any, a combination of unadjusted and adjusted data),95-98 instrumental delivery (all adjusted for confounders)96 and induction (all unadjusted).99 Meta-analysis was possible for caesarean delivery. Any caesarean section (elective or emergency combined) was reported by three studies95 96 98 for 50 345 births, whereas emergency and elective caesarean were reported separately by four studies95-98 for >47 496 births (sample size not reported for one study,97 online supplemental appendix S11, table r), and all were included in the meta-analysis. The meta-analysis identified a significantly reduced odds of emergency caesarean (OR 0.85, 95% CI 0.77 to 0.94; figure 9 ), elective caesarean (OR 0.83, 95% CI 0.76 to 0.91; figure 10 ) and any caesarean (OR 0.80, 95% CI 0.74 to 0.86; figure 11 ) for the pooled lowest/intermediate occupation/social class compared with the highest level. The subgroup meta-analysis identified that the lowest occupation/social class had the lowest odds of all caesarean categories ( figures 9-11 ). There was moderate heterogeneity for any caesarean delivery, and this was significantly reduced in the subgroup analysis ( figure 11 ). Heterogeneity was moderate for elective caesarean, which was reduced by subgrouping ( figure 10 ) and further partly explained by the date of data collection ( online supplemental appendix S12Iiii). There was high heterogeneity for emergency caesarean pooled data, which was partly explained by subgrouping ( figure 9 ) and further explained to a very small degree by sample size but not by the other factors included in meta-regression ( online supplemental appendix 12Hii). Sensitivity analysis demonstrated that the meta-analysis results were robust to the effect of individual studies ( online supplemental appendix S12Hiv, Iiv, Jiv), and there was no evidence of publication bias for any category of caesarean section ( online supplemental appendix S12Hii, Iii, Jii). The GRADE score for caesarean section showed low-quality evidence ( online supplemental appendix S13).

Additional data for caesarean delivery identified a significantly decreased odds among women in the lowest income quintile84 ( online supplemental appendix S11, table s), living in council housing, housing association or privately rented accommodation ( online supplemental appendix S11, table t) and among women who bent or stood a lot and physically exerted themselves at work98 but an increased odds among women who mostly sat, undertook demanding tasks, worked during pregnancy and worked more than 50 hours ( online supplemental appendix S11, table v).98 There was an overall lack of association with maternal education84 96 ( online supplemental appendix S11, table u). There was limited data for instrumental delivery96 and induction99 ( online supplemental appendix S11, tables w-x) with some conflicting results depending on parity and previous mode of delivery.

Other outcomes reported

Six studies reported no significant associations between occupation and placental problems,100 maternal morbidity,101 102 myocardial infarction,103 antenatal stroke104 or amniotic fluid embolism105 ( online supplemental appendix S11, table y). One study reported associations between education level and congenital anomalies106 with significantly increased odds of congenital anomalies for educational attainment levels below a diploma, degree or higher degree qualification ( online supplemental appendix S11, table z). All data were unadjusted for confounding factors.

Discussion

Meta-analysis from this systematic review of 17 130 631 births in the UK and ROI identified that lower level occupation/social class is associated with a significantly increased risk of stillbirth, neonatal mortality, perinatal mortality, preterm birth and LBW by approximately 40%. Additional data narratively summarised suggest there is also an increased risk of stillbirth, maternal mortality and preterm birth among unemployed parents. Further individual level SES factors with some, although limited, evidence of increased risk of adverse pregnancy outcomes include lowest level of education (compared with women who have a degree), housing and income.

Overall, the data on individual and household measures of inequality suggest women (and families) experiencing lower SES face generally worse pregnancy outcomes compared with women who have a higher social status. Education, housing, income, taxation and social protection policies have undermined social mobility, leading to widening and persistent inequalities.1 Austerity has been associated with widening inequalities in a variety of health outcomes, including infant mortality rate.2 107 In response to economic hardship, women are less likely to adopt positive health-related behaviours due to the need to focus on coping in the short term rather than planning for the future.1 108 As such, poverty experienced by those in lower SES might also be a pathway leading to worse pregnancy outcomes alongside poorer nutrition, housing insecurity, financial stress2 and the wider social determinants of health. These associations may be mediated by health behaviours and other risk factors, whereby mothers facing economic hardship are, for example, more likely to smoke during pregnancy. Our analysis has demonstrated a relationship between low SES and PTB (which increases the risk of subsequent infant mortality), and this is also related to low maternal weight and smoking.82 Furthermore, deprivation is related to poor diet,109 low levels of physical activity,110 increased obesity,111 late access to (and low engagement with) antenatal care,112 increased drug113 and alcohol use,114 and exposure to domestic violence.115 Tackling the fundamental drivers of poor pregnancy outcomes is imperative as they are associated with lower educational attainment and disadvantage throughout the lifecourse,116 117 therefore, contributing to the intergenerational cycle of inequality. This has implications considering the post-COVID-19 economic recovery, and the need for governments to not follow austerity again and instead focus on policies that will not further exacerbate inequalities, particularly for women and children.

This review has many strengths as well as limitations. Our search strategy was broad and wide ranging, which included multiple databases supplemented by searching citations and reference lists and contacting experts in each of the four UK regions and the ROI. The grey literature sources resulted in several large datasets being included from national records in all nations of the UK and the ROI. Using national datasets, supplemented by additional academic publications, has resulted in large sample sizes for some outcome/SES combinations, particularly for occupation and for stillbirths, neonatal mortality, PTB and birth weight. We did not restrict by language, and all screening, data extraction and quality assessments were carried out in duplicate to minimise human error. We also did not restrict by pregnancy outcome; consequently, we have wide ranging outcomes highlighting the effects of SES on the health of the mother and baby during pregnancy and up to 28 days postnatal. However, we did have to exclude studies that reported perinatal mental health or breastfeeding outcomes due to the lack of clarity in reporting the time periods of measurement for these outcomes and therefore these require further exploration capturing a longer postnatal period than 28 days. Using a validated quality appraisal tool, all included studies were rated moderate to high quality. However, our findings refer to UK and ROI only, and therefore, further research should be undertaken to enable an understanding of how pregnancy outcomes relate to socioeconomic determinants across other HICs. Furthermore, rich data sources from the ONS and National Records of Scotland were used extensively in this review to document the association between occupation-derived social class and birth weight, stillbirth, neonatal and perinatal mortality. Over the 28 years for which we had data, the occupational classifications evolved in line with changing labour market conditions as did the reporting of birth registrations; therefore, the categories with which we analysed data are not directly comparable. Broad groupings of lowest, intermediate and higher level occupations were required to be able to pool data, which may not reflect any differences within these groups (eg, any differences between unemployed vs manual employment that would have been grouped as lowest level). Additionally, the use of national datasets such as ONS required the calculation of effect sizes using aggregate frequency data provided in the reports; therefore, we were unable to account for potential confounding variables. There was inconsistency in the reporting of adjusted data throughout, where occupation-derived social class included mostly adjusted data for SGA and instrumental delivery, some adjusted data for LBW, preterm and caesarean delivery, and a lack of adjusted data for other outcomes such as offspring mortality, VLBW and macrosomia. However, most education, income/finances and housing data were adjusted, although reported to a lesser extent overall. We had intended to explore adjustment for confounding variables in the meta-regression as an a priori factor; however, this was not possible due to the limited availability of adjusted data for occupation-derived social class used in the meta-analyses. There were some outcomes where both unadjusted and adjusted data were available (eg, LBW online supplemental appendix S11f). Comparing these, the effect sizes and significance were similar in the univariable and multivariable models that included multiple sociodemographic and behavioural factors. There are some additional limitations with the use of routine data sources such as issues of accuracy of data recorded in routine health records and the comparability and granularity of variables between datasets. However, routine datasets tend to be nationally representative and adequately powered to explore patterns in population health, in a timely manner. These strengths are especially important for research where outcomes are relatively rare, such as stillbirth and congenital anomalies, which would require extensive funding and time to collect prospectively. In addition, for research into health inequalities, the use of routine data are a timely method of identifying potentially vulnerable groups who require additional support. Alternative methods that incorporate lengthy data collection periods could be considered unethical when alternative existing data sources are available.

This review is subject to the usual limitations of observational research whereby we cannot claim that there is a causal relationship between individual and household measures of socioeconomic disadvantage and pregnancy outcomes. As such, the quality of evidence highlighted by GRADE was typically low or very low. Although outcomes were downgraded (eg, for inconsistency as heterogeneity was high for all meta-analyses), due to the use of national datasets showing large effects, upgrading also occurred. We have also only found a limited number of studies for some outcome/SES combinations, and therefore, it is possible that there is publication bias (that negative results are less likely to be published) and selective reporting within studies that may impact the assessment of risk of bias. To negate this, where possible, we calculated associations between inequality exposures and pregnancy outcomes when these had not been published (eg, if frequency data were reported in a paper but no association or by using frequency data published in nationally representative datasets such as ONS). In the meta-analysis, only stillbirth had significant evidence of publication bias. The positive associations with stillbirth may therefore be an artefact of significant associations being more likely to be published as only one reported association included in the meta-analysis was not significant. However, we should also consider the sample sizes that contributed to these significant associations, the largest being provided by the ONS (2002-17) and including >7.8 million women in the comparison of lowest versus highest occupation-derived social class and >6.5 million women in the intermediate versus highest comparison. There are some methodological deviations from the published protocol. First, we limited studies to the UK and ROI only, due to the volume of studies from European HICs that we retrieved in the search. Second, we anticipated only including a meta-analysis if there were three of more studies reporting associations between the same exposure and outcome. However, we made the decision to include meta-analysis of two studies in the final paper due to the limited amount of data available for some combinations of exposure and outcome. Most of these studies reported multiple effect sizes for subgroups of participants, which could contribute to the overall pooled estimate and be valuable to explore under-reported exposure and outcome combinations.

While there was substantial evidence for some SES measures, there were very limited data available for housing, income and car ownership, and a lack of data for other measures of individual or household inequality that may be important including other measures of poverty and social isolation. Furthermore, there was a lack of consistency in definitions used between studies, particularly for education, which made direct comparisons difficult, and it was not possible to pool these data in a meta-analysis. Future studies should explore these other axes of inequalities in addition to gain a broader insight into the relative importance and interplay of socioeconomic variables and pregnancy outcomes. Similarly, although we did identify a range of pregnancy outcomes, there was an absence of evidence available for other outcomes that require further exploration, such as miscarriage, postpartum haemorrhage, gestational diabetes, hypertensive disorders of pregnancy, measures of newborn health (eg, Apgar score), attachment and the need for high-risk healthcare services (eg, neonatal intensive care). This systematic review did not include pregnancy outcomes beyond 28 days postnatal, such as breast feeding, postnatal depression and infant mortality. These additional inequality measures and health outcomes warrant further research to supplement the existing evidence base and inform public health and maternity policy and practice, particularly in light of rising inequalities in infant mortality in the UK.2

This study looked specifically for socioeconomic inequalities in pregnancy outcomes in the UK and Ireland alone. These countries have broadly comparable inequalities, which are typically higher compared with other parts of Europe owing to a minimal welfare state.121 Cross-country analysis does, however, suggest there may be important differences in pregnancy outcomes2 10 11 and health more generally.122 Although evidence for occupation/social class differences was greatest in this review, there has in recent times been a move to reframe health inequalities away from individual 'labels' to instead focus on power relations and to interrogate the processes that produce them.123 As such, identifying inequalities during pregnancy is a step towards informing where services could adapt provision to effectively support populations that are socioeconomically disadvantaged. However, targeting interventions solely at the most disadvantaged groups will not reduce the steepness of the social gradient; for example, we identified that women in the intermediate-level occupations were also at increased risk of some adverse pregnancy outcomes. Proportionate universalism instead advocates a universal approach with a scale and intensity that is proportionate to the level of disadvantage.124 This requires engagement between health professionals and people from lower socioeconomic groups in shared decision making, which is too often characterised by less information giving, less directions and less socioemotional and partnership building.125 Our review demonstrated that lower SES women are less likely to have a caesarean section, which could be protective against the increased harm associated with an operative birth; however, this could highlight that women from deprived communities are less likely to request a caesarean, or more worryingly, be involved in discussions around birthing options. A greater consciousness of structural constraints, and a willingness by health professionals to systematically break them down, may empower marginalised, lower socioeconomic patients to be more involved in decisions around their care and help reduce inequalities in the long term.

This review has highlighted that systematic collection of routine data in pregnancy allows for associations between upstream socioeconomic factors and pregnancy outcomes to be established as evidenced in the included large national datasets for occupation-derived social class and various pregnancy outcomes. Thus, improvements to the quality and completeness of routinely collected national datasets in the antenatal and perinatal period could have a powerful impact on policy development.

Overall, the findings from this review highlight that pregnancy outcomes are also associated with factors that lie upstream of the health behaviours of women and the care they receive in pregnancy and labour. These findings support the need for 'whole system' approaches to explore and address socioeconomic inequalities and pregnancy outcomes. Key areas for action may include: improved surveillance; analysis of the policy landscape impacting pregnant women and their families, with consideration of the role of different sectors and settings (including the National Health Service); and timely and rigorous research and evaluation efforts to further develop understanding of population needs for pregnant women and their families and the ways to address these needs.

Conclusion

The findings from this review provide evidence that there is a worsening of health for both babies and pregnant women who experience higher levels of individual and household socioeconomic deprivation. The strongest current evidence base is for increased risk of mortality, LBW and PTB among lower level occupation-derived social classes. Strategies to improve pregnancy outcomes should consider this evidence base and incorporate approaches that address the wider determinants of health to provide women and their families with the best chance of having a healthy pregnancy and baby and to decrease pregnancy-related health inequalities in the general population.

Acknowledgments

The project is a collaboration between Public Health Wales and Fuse (UKCRC Centre for Translational Research Public Health). NH, HB, CB and JR are members of Fuse, the Centre for Translational Research in Public Health (www.fuse.ac.uk). Fuse is a Public Health Research Centre of Excellence funded by the five North East Universities of Durham, Newcastle, Northumbria, Sunderland and Teesside. We would like to thank our colleagues at Public Health Wales, Frank Dixon (National Records of Scotland) and Leslie Marr (The Scottish Health Council) for their help with regards sourcing grey literature. We would also like to thank authors of the studies who provided additional data including Aoife Brick (Economic and Social Research Institute) and Chris Dibben (University of Edinburgh).

Footnotes

Contributors: AM, AJ, JB, SW, CB, HB, NH and JR conceived the study idea and developed the proposal. CR developed the search strategy with contributions from KT, OA, NH, JR, CB, AJ and SW. CR, KT, OA and AO carried out the database searches and supplementary searches. KT, OA, MM, AO and NH completed the screening, data extraction and quality appraisals. MM ran the meta-analysis with support from NH and HB. KT and NH wrote the first draft of the manuscript. All authors edited drafts of this article and approved the final version. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. NH is the guarantor.

Funding: The review was commissioned by Public Health Wales. Three public health consultants from Public Health Wales are authors on the paper.

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from Public Health Wales for the submitted work; AJ, SW, JB and AM are all employees of Public Health Wales.

Patient consent for publication: Not required.

Provenance and peer review: Not commissioned; externally peer reviewed.

Data availability statement: All data relevant to the study are included in the article or uploaded as supplementary information.

Supplemental material: This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

References

8. O'Connell R, Owen C, Padley M, et al.. Which types of family are at risk of food poverty in the UK? A relative deprivation approach. Soc Policy Soc 2019;18:1-18. 10.1017/S1474746418000015 [[ CrossRef] Google Scholar]

17. Stroup DF, Berlin JA, Morton SC. Meta-analysis of observational studies in epidemiology a proposal for reporting. JAMA 2000;283:2008-12. [[ PubMed] Google Scholar]

20. Veritas Health Innovation . Covidence systematic review software, 2019. Available: www.covidence.org

26. Popay J, Roberts H, Sowden A. Guidance on the conduct of narrative synthesis in systematic reviews: a product from the ESRC methods programme. 92. Lancaster: Lancaster University, 2006. [ Google Scholar]

80. McAvoy H, Sturley J, Burke S. Unequal at birth: inequalities in the occurrence of low birthweight babies in Ireland. 96. Dublin/Belfast: Institute of Public Health in Ireland, 2006. [ Google Scholar]

85. Murrin C, Segonds-Pichon A, Fallon UB, et al.. Self-reported pre-pregnancy maternal body mass index and infant birth-weight. Ir Med J 2007;100:20-3. [[ PubMed] Google Scholar]

89. Collingwood Bakeo A, Clarke L. Risk factors for low birthweight based on birth registration and census information, England and Wales, 1981-2000. Health Stat Q 2006:15-21. [[ PubMed] Google Scholar]

124. Marmot M, Allen J, Goldblatt P. Fair society healthy lives (the Marmot review). 242. London: Institute of Health Equity, University College London, 2010. [ Google Scholar]

Articles from BMJ Open are provided here courtesy of BMJ Publishing Group

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Original research: Socioeconomic inequalities and adverse pregnancy outcomes in the UK and Republic of Ireland: a systematic review and meta-analysis

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There has been an unprecedented rise in infant mortality associated with deprivation in recent years in the United Kingdom (UK) and Republic of Ireland. A healthy pregnancy can have significant impacts on the life chances of children. The objective of ...

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Balloon Dilators for Labor Induction: a Historical Review

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Balloon Dilators for Labor Induction: a Historical Review

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Abstract

A number of recent articles attribute the origin of the use of cervical balloon dilation in the induction of labor to either Barnes in the 1860s or Embrey and Mollison in the 1960s. This review examines the historical record and reveals that, based on current practice attribution should rather be made to two contemporaries of Barnes: the Storer and Mattei. More importantly, Storer's warning about the rubber used in dilators was ignored, leading to decades of possibly unnecessary deaths following childbirth. To conduct this study key search terms for PubMed, Google Scholar and the website of the University of Ryerson were utilized as "Barnes", "Woodman", "balloon dilation", "balloon catheter", "foley", "colpeurynter", "cervix uteri" and "induction." Subsequent analysis was done on downloaded articles using BibDesk.

Keywords: balloon dilation, cervical dilation, foley catheter, hydrostatic dilator, induction of labor

Introduction

The use of balloons for dilation is widespread in contemporary medical practice, including in obstetrics and gynecology, dilatation and curettage, induction of labor, control of hemorrhaging, sonohysterography and hysterosalpingography, and fertility treatment. The scope of this analysis will be limited to the use of balloon dilators in induction of labor. The goal of this review is to point out inaccurate attribution of prior art, specifically the tendency of contemporary authors to attribute the origin of cervical balloon dilation in the induction of labor to either Barnes in the 1860s ( 1) or Embrey and Mollison in the 1960s ( 2). Had Barnes and others paid closer attention to Storer's earlier balloon dilator work ( 3), which raised the issue of rubber's biocompatibility risks, the infection and mortality rate during labor from the 1860s onward may have been reduced.

Survey of the Literature

In 1591 Alpinus described how air could be used to inflate distensible material in the urethra ( 4). Later, Bromfeild used liquid-based distention of animal intestine to remove stones in a girl's bladder ( 5). Animal-sourced balloon dilators were replaced with vulcanized rubber by the 1850s. The new material could be more easily cleaned prior to usage, although it carried similar risks of bursting and leaking.

In 1854 Gariel described balloon dilator designs for the cervix ( 6), but no medical interventions using these devices were published. It was reported in 1855 that Braun had used water-distended rubber balloons to dilate the cervix ( 7). Braun applied his colpeurynter during a labor that had already commenced but was complicated by the presenting of the baby's shoulder.

Mattei detailed use of a rehydrated sheep's bladder design to dilate the cervix during labor in patients in 1855 as an alternative to digital dilation. Mattei suggested that the ideal placement of the balloon was within the uterus and that traction should be applied to dilate the cervix. Like Braun, this method was applied to labor which had already commenced and the procedure lasted only a few minutes ( 8).

In 1859 a controversy began when Murray claimed to have used a rubber-based air-distended dilator to induce labor ( 6). It was immediately recognized that Murray's work was too closely tied to his supervisor, Keiller, to consider it Murray's own unique accomplishment ( 9). Storer, in response to Murray, made a claim ( 3) for the use of a balloon dilator for the induction of labor. Storer observed that vulcanized rubber was bulky and apt to break down after contact with bodily fluids ( 10), opting for the more hygienic gold-beater's skin, a material commonly used for condoms. Unlike Keiller and Murray, Storer used water to distend the balloon. Barnes ( 11) and Tarnier ( 12) improved on these earlier designs which were subsequently well received ( 1, 13), even though they broke down ( 14) or burst ( 15). Tarnier's device spawned both the Boissard and Voorhees designs ( 15, 16). By the early 20th century warnings were raised about the Voorhees design ( 17) and alternatives ( 18), and it was concluded that they were not optimal for induction of labor ( 18).

The decline of the invasive and infection-prone balloon corresponds to the ascension of pharmacological alternatives from ergot to oxytocin and prostaglandins. Embrey and Mollison's use of the foley catheter reintroduced the medical community to induction balloons ( 2). The foley is the most commonly used balloon dilator ( 19) but there are alternatives ( 20).

Analysis

While Barnes first published results seven years after Mattei, his name quickly became synonymous with the balloon dilator. Woodman criticized Tarnier for not citing Barnes' earlier work but did not cite any of Barnes' predecessors either ( 1). Likewise, Corner made no mention of Barnes' predecessors ( 13). The deferral to Barnes is possibly due to his standing within the medical community ( 13, 21). More recently, Embrey and Mollison, as well as Calder glossed over historical prior art ( 2, 22). Further issues regarding addressing of prior art are expanded upon below.

Oversights in the Historical Record

Many historical examinations of balloons for labor induction go no further than Embrey and Mollison, either limiting the scope to the foley instantiation ( 23) or mistakenly limiting any balloon-based cervical ripening to them ( 24). Bani-Irshaid et. al wrongly attribute use of the foley catheter to Krause in 1833 - one hundred years before its actual invention ( 25, 26). While Embrey and Mollison were the first to use one particular instantiation of a balloon catheter, the foley, they were not the first to use balloons.

The following are very clear-cut cases in which attribution is incorrect. Lurie and Rabinerson misstated Barnes' role in 1997 ( 27). Similarly Mozurkewich ( 28) and Guinn et al. attribute the balloon's origin to Barnes ( 29, 30). Pettker et al. also wrongly refer to Barnes as the first implementer ( 31). Williamson mistakenly advanced the introduction of Barnes' fiddle-shaped dilator to 1852 ( 32), eight years earlier than Barnes admits to in any of his own publications.

Other works overlook important contributions by some of the main players in the 1859 controversy related to Murray's original publication. Hibbard makes mention of both Barnes and Murray but neither Keiller nor Storer ( 33). Duchatel ignores the 1859 controversy but cites relevant and important work by Mattei ( 16).

Credit should be attributed to the design which bears the critical design and application features which are used today: a relatively hygienic material, distention with water, dilation of the cervix using pressure from above, and application to the induction of labor.

Mattei used dehydrated sheep's bladders because of convenience, not hygiene. Storer made it clear that vulcanized rubber was a poor choice for dilation due to its propensity for breaking down after contact with bodily fluids. In the long term, it appears that while the balloons were mechanically effective, they carried a hygienic risk, which led most practitioners to abandon them prior to Embrey and Mollison's reintroduction. Storer was correct in his concerns about vulcanized rubber but it is difficult to know if, had others used goldbeater's skin, the outcome would have been different prior to the introduction of latex.

The issue of water distention is an important one. Bromfeild described water-based urethral dilation in 1773 ( 5). Air-based techniques were later proposed by Gariel ( 34) and implemented by Keiller and Murray ( 9). Barnes, a strong fluid distention advocate, wrongly attributed Murray (and, by extension, Keiller) as the first to have used fluid to distend a cervical dilator balloon ( 35) as Murray specifically states that he used air to distend his air pessary in 1859. It was Storer rather who correctly applied fluid (i.e. liquid) rather that the more dangerous air alternative ( 10), just as today it is standard practice to use saline solution to distend the foley during induction.

Embrey and Mollison were not the first to place their balloon dilator in or against the interior os of the cervix, as is common practice today ( 36). Both Mattei and Storer advocated for the "from above downwards" ( 10) approach to dilating the cervix, as opposed to applying force from the vagina upwards or radially within the cervix itself.

Judging by today's standards, the water-distended balloon dilators of both Mattei and Storer appear to be the forebears of the contemporary foley dilator. Storer's approach, however, was perhaps more hygienic than Mattei's sheep's bladder or the vulcanized rubber used by Barnes and others.

Conclusion

This review examined the historical record related to the development of balloon dilators, specifically those used in dilation of the cervix to induce labor. While some attribute invention of the contemporary hydrostatic dilators such as the foley catheter to either Embrey or Mollison in the 1960s or to Barnes one century prior, credit should be partially given to Keiller and Murray for their approach which was nearly completely correct, except for their use of air. However, both Mattei and Storer applied liquid-based distention in a downwards manner prior to Barnes' first published results. Storer's results stand out for his hygienic concerns. Had Barnes and others paid closer attention to Storer's earlier work, subsequent infection and mortality rates may have been reduced.

Acknowledgments

The author would like to thank Donald Smith for proofreading the document. The author states that he has no financial conflict of interest or other interests that influence this manuscript.

References

28. Mozurkewich E. Commentary on Foley catheter insertion for preinduction cervical ripening was faster and more efficacious than prostaglandin E[ ₂ gel. Evidence-based Obstet Gynaecol. 2000;2(2):41. Google Scholar]

Articles from Journal of Medical Ethics and History of Medicine are provided here courtesy of Tehran University of Medical Sciences

# data[].attributes.attachment_link.title
Balloon Dilators for Labor Induction: a Historical Review

# data[].attributes.attachment_link.description
A number of recent articles attribute the origin of the use of cervical balloon dilation in the induction of labor to either Barnes in the 1860s or Embrey and Mollison in the 1960s. This review examines the historical record and reveals that, based on ...

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Which level of risk justifies routine induction of labor for healthy women?

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Which level of risk justifies routine induction of labor for healthy women?

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Abstract

Although induction of labor can be crucial for preventing morbidity and mortality, more and more women (and their offspring) are being exposed to the disadvantages of this intervention while the benefit is at best small or even uncertain. Characteristics such as an advanced maternal age, a non-native ethnicity, a high Body Mass Index, an artificially assisted conception, and even nulliparity are increasingly considered an indication for induction of labor. Because induction of labor has many disadvantages, a debate is urgently needed on which level of risk justifies routine induction of labor for healthy women, only based on characteristics that are associated with statistically significant small absolute risk differences, compared to others without these characteristics. This commentary contributes to this debate by arguing why induction of labour should not routinely be offered to all women where there is a small increase in absolute risk, and no any other medical risks or complications during pregnancy. To underpin our statement, national data from the Netherlands were used reporting stillbirth rates in groups of women based on their characteristics, for each gestational week from 37 weeks of gestation onwards.

Section snippets

Funding

This study was funded by Cooperative of Midwifery Practices Leiden and larger Leiden.

Council of Europe
Convention for the protection of human rights and dignity of the human being with regard to the application of biology and medicine: convention on human rights and biomedicine

The risk of stillbirth and infant death by each additional week of expectant management stratified by maternal age

Labor Induction versus Expectant Management in Low-Risk Nulliparous Women

Continuous support for women during childbirth

Women's experiences of induction of labour-findings from a Swedish regional study

World Health Organization. WHO Guidelines Approved by the Guidelines Review Committee. WHO recommendations: Induction...

There are more references available in the full text version of this article.

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Which level of risk justifies routine induction of labor for healthy women?

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Although induction of labor can be crucial for preventing morbidity and mortality, more and more women (and their offspring) are being exposed to the disadvantages of this intervention while the benefit is at best small or even uncertain.

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Caesarean Birth

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Methods of induction of labour: a network meta‐analysis

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Methods of induction of labour: a network meta‐analysis

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Cochrane Database Syst Rev. 2023; 2023(1): CD015234.

Monitoring Editor: Cochrane Pregnancy and Childbirth Group, Siwanon Rattanakanokchai, Ioannis D Gallos, Chumnan Kietpeerakool, Nuntasiri Eamudomkarn, Zarko Alfirevic, Olufemi T Oladapo, Doris Chou, Ben Willem J Mol, Wentao Li, Pisake Lumbiganon, Arri Coomarasamy, and Malcolm J Price

Objectives

This is a protocol for a Cochrane Review (intervention). The objectives are as follows:

To compare the effectiveness and safety profiles for the different methods of cervical ripening and labour induction at or beyond term labour using network meta‐analysis, and to provide rankings of the available treatments according to their effectiveness and safety profile.

Background

Please see Appendix 1 for a glossary of terms.

Description of the condition

Labour induction is the use of medical procedures or medications to induce labour by ripening the cervix or stimulating uterine contractions, or both. It is typically recommended when the risk of continued pregnancy is considered to outweigh the benefits ( Cunningham 2018). There are various maternal and fetal indications for induction of labour. Common indications from a maternal perspective are pre‐eclampsia with severe feature and pre‐labour rupture of membranes. Fetal indications are intrauterine growth restriction, risk of stillbirth in prolonged gestation, and other concerns regarding fetal well‐being ( Cunningham 2018; Leduc 2013). The incidence of labour induction has increased steadily during the last few decades. In high‐income countries, approximately one‐quarter of term labour (at or beyond 37 weeks of gestation) is preceded by labour induction, while in the UK large maternity hospitals report rates well over 30% ( Caughey 2009; Martin 2007). The rates of labour induction in low‐ and middle‐income countries, however, are generally lower than that of high‐income countries ( Guerra 2011; Vogel 2013).

Although induction of labour may lower the number of caesarean sections, stillbirths, and admissions to the neonatal unit, it may also be potentially associated with excessive uterine contractions (uterine hyperstimulation). Excessive uterine contractions may result in uterine rupture and uterine atony ( WHO 2018), as well as place the fetus at risk of fetal brain oxygenation deficiency resulting in neonatal seizures ( Jensen 2009). Furthermore, it is reported that induced labour may be more painful than spontaneous labour ( NICE 2021). The likelihood of complications is likely to differ between the different methods of induction of labour used and also depends on the characteristics of pregnant woman and fetus, including a history of caesarean section and preterm labour ( Berghella 2020).

There appear to be significant differences in the effectiveness and safety of cervical ripening and labour induction methods used in 1) women with a history of caesarean delivery and 2) women without a history of caesarean delivery. For women with a previous caesarean section who require delivery before the onset of spontaneous labour, the evidence remains unclear whether labour should be induced or a repeat elective caesarean section should be performed ( Dodd 2017). Most of the available evidence evaluating the benefits and harms of induced labour in women with a previous caesarean section has been drawn from non‐randomised studies. One systematic review of eight observational studies concluded that induction of labour is likely to increase the risk of uterine rupture/dehiscence and postpartum haemorrhage in women attempting labour after a previous caesarean section when compared to spontaneous labour ( Rossi 2015). Methods that are recommended to induce labour for women with a previous caesarean section from evidence‐based guidelines, such as National Institute for Health and Care Excellence (NICE), American College of Obstetricians and Gynecologists (ACOG), and Society of Obstetricians and Gynaecologists of Canada (SOGC), are varied ( ACOG 2006; Leduc 2013; RCOG 2008). There is a limited amount of evidence from randomised controlled trials on this question ( West 2017).

The indications for inducing labour differ depending on whether induction is for preterm labour (before 37⁺⁰ completed weeks of gestation) or at or beyond term labour (gestational age at or beyond 37⁺⁰ weeks). This is because these two groups differ in terms of the clinical characteristics of the mother or fetus, as well as the severity of adverse effects that may occur when each induction of labour method is used in each population ( NICE 2021). For women at first pregnancy with no contraindications, physicians might attempt to inhibit labour for preterm pregnancy in order to accelerate fetal lung maturation. In women who experienced preterm premature rupture of membranes (PPROM) prior to 37⁺⁰ weeks of gestation, waiting for labour to begin naturally with careful monitoring results in better outcomes for both mother and baby when compared to early planned birth ( Bond 2017). Our review thus focuses on induction of labour at or beyond term labour only.

Description of the intervention

Methods of induction of labour are designed to induce the onset of labour by softening and maturing the cervix or stimulating uterine contractions, or both ( Leduc 2013). The methods currently used to induce labour can be classified into five different categories ( Alfirevic 2016b; Cunningham 2018):

Each category has different mechanisms of action and a variety of effects. The choices of methods depend on maternal characteristics, national clinical guidelines, policies, clinical experiences, and the resources available in each healthcare setting ( Alfirevic 2016b).

Mechanical methods

Mechanical induction methods aim to ripen the cervix. This can be accomplished directly by cervical canal dilatation, indirectly through released prostaglandin or oxytocin secretions, or through use of both. The mechanical methods used for inducing labour include various types of catheters and Laminaria tents ( Cunningham 2018).

The conventional Foley urinary catheter, double‐balloon catheter, or extra‐amniotic saline infusion can be utilised to ripen the cervix. The catheter is inserted into the cervical canal to reach an extra‐amniotic space, and then inflated with 30 to 60 cm ³ of water to hold it in place. After that, the cervical canal then gradually dilates and releases prostaglandin or oxytocin secretions, which could induce the onset of labour ( Keirse 1983).

Laminaria tents are made from sterile seaweed or synthetic materials. This treatment dilates the cervical canal in the same way as Foley catheters. Laminaria tents are inserted into the cervical canal. They gradually enlarge and dilate the cervical canal after absorbing water. Indirectly, prostaglandin secretions are released, assisting in the promotion of labour onset ( Gelber 2006).

Surgical methods

Surgical methods are performed by a physician to create a tiny hole in the amniotic sac or detach the inferior pole of the membranes from the lower uterine segment. These procedures could promote the onset of labour by releasing prostaglandins and oxytocin from intrauterine tissues, which can increase uterine contractions and accelerate cervical maturation ( Tenore 2003).

Artificial (iatrogenic) rupture of the membranes, often known as amniotomy, is the intentional rupture of the amniotic sac performed by a physician during labour. With the use of a special tool, a physician punctures the amniotic sac through the vagina. Prostaglandin levels in the uterine cavity are expected to rise as a result of this operation, which is expected to shorten the uterine muscle and allow the uterus to contract more often and more strongly ( Wiqvist 1974). However, if this technique is employed alone for labour induction, the onset of labour is uncertain ( Cunningham 2018).

Membrane sweeping is a method in which a healthcare provider inserts one or two fingers into a woman's cervix and uses a circular motion to detach the membranes from a lower uterine segment. This approach could reduce the need for formal induction of labour methods (pharmacological methods or amniotomy) ( Finucane 2020). The aim of membrane sweeping is to soften and ripen the cervix by releasing prostaglandins from the intrauterine tissues and increase uterine activity by releasing oxytocin ( Keirse 1979).

Pharmacological methods

In recent decades pharmacological methods have been preferred over mechanical and surgical methods for inducing labour due to their effectiveness. There are various pharmacological methods available for inducing labour. These include prostaglandin E1, prostaglandin E2, oxytocin, and nitric oxide donor. The main pharmacological effects of these medications work by stimulating uterine contractions and maturing the cervix. Some of these medications can be administered via multiple routes, such as orally, vaginally, intravenously, or intracervically. The success of inducing labour and the chances of adverse outcomes may depend on the drug class and route of administration. Pharmacological methods should be used with caution for women with a history of caesarean section delivery since they might increase the chance of uterine rupture compared to women who delivered with spontaneous labour ( Rossi 2015).

Prostaglandin E1: misoprostol is a synthetic prostaglandin E1 (PGE1) analogue. This medication could be used to induce labour by maturing the cervix and stimulating uterine contraction. Misoprostol can be administered in multiple routes (oral, buccal, sublingual, vaginal). In a clinical setting, oral misoprostol can be administered as low‐dose (25 µg) or high‐dose (50 µg) regimens ( Leduc 2013). Each route of administration has a different mechanism and onset of action. Oral misoprostol is rapidly absorbed and has a rapid onset of action, whereas vaginal misoprostol is slowly absorbed but has a longer duration of action ( Abdel‐Aleem 2003; Zieman 1997). Sublingual and buccal misoprostol appear to have a quicker onset of action than oral and vaginal misoprostol because they avoid the first‐pass metabolism by the liver ( Tang 2002). Controlled‐release misoprostol vaginal pessary has been developed and evaluated in clinical trials over the last decade to minimise the number of applications and vaginal examinations required during labour induction.

Prostaglandin E2: dinoprostone is equivalent to prostaglandin E2 (PGE2) which is used to ripen the cervix and stimulate the myometrium of the gravid uterus to contract more intensely. Dinoprostone is available in various forms (gels, tablets, suppositories, or pessaries) and routes (oral, intravenous, vaginal, or intracervical) ( Leduc 2013). Oral and intravenous dinoprostone have been found to be associated with more gastrointestinal side effects than other routes and methods and are therefore not currently recommended for use ( French 2001; Luckas 2000). Vaginal dinoprostone and controlled‐release dinoprostone vaginal pessary are two forms that are recommended in current practice.

Prostaglandin F2 alpha: dinoprost is a synthetic prostaglandin F2 alpha (PGF2alpha) analogue. Prostaglandin F2 alpha acts via the PGF2 alpha receptor to stimulate myometrial contractility ( Liang 2008). Routes of administration include oral and intracervical. Nowadays, dinoprost is partly substituted by dinoprostone.

Oxytocin: oxytocin is a hormone made in a part of the brain that causes the uterus to contract ( Leduc 2013). A synthetic form of oxytocin is usually used to induce labour via the intravenous route when the cervix is favourable (Bishop score more than 6). There are two regimens for inducing labour: lower dose and higher dose. A lower‐dose regimen typically involves an initial dose of 0.5 to 2.0 milliunits (mU)/minute, followed by a maintenance dose of 1.0 to 2.0 mU/min every 15 to 60 minutes. A higher‐dose regimen involves an initial dose of 6.0 mU/min, followed by a maintenance dose of 2.0 to 6.0 mU/min every 15 to 40 minutes. A higher‐dose regimen likely leads to a shorter time to delivery but might increase the risk of adverse effects such as hyperstimulation ( Cunningham 2018).

Progesterone antagonists are also known as progesterone blockers: progesterone is a hormone that decreases uterine contractility. Mifepristone is one progesterone antagonist agent that can inhibit progesterone activities, thus increasing uterine contractions and sensitivity of the uterus to the actions of prostaglandins ( Hapangama 2009).

Nitric oxide: nitric oxide donors, including isosorbide mononitrate (ISMN), isosorbide dinitrate (ISDN), nitroglycerin and sodium nitroprusside, are considered to be potential mediators for cervical ripening while having no impact on uterine contraction. The relaxing of cervical smooth muscle is the main mechanism of this drug ( Buhimschi 1995).

Combined methods

Amniotomy plus intravenous oxytocin and mechanical methods plus pharmacological methods have been used widely for inducing labour in women with a favourable cervix (Bishop score more than 6). When compared to either oxytocin or amniotomy alone, combined methods have the potential to shorten the time of delivery. However, information regarding the safety of this approach is currently insufficient ( de Vaan 2019; Howarth 2001). Hence, it will be important to investigate the evidence on effectiveness, pain, and safety in the current review.

Alternative methods

Acupuncture, castor oil, herbal supplements, homeopathy, and sexual intercourse are considered to be alternative methods for inducing labour. The international and national evidence‐based guidelines state that there is still insufficient information regarding their efficacy and safety, and therefore do not recommend using them to induce labour ( NICE 2021; WHO 2011).

How the intervention might work

Methods of induction of labour aim to decrease time to delivery by ripening the cervix or stimulating uterine contractions, or both. There are numerous clinical components that must be examined prior to induction to assess the chances of success of induction and decrease the likelihood of complications including induction failure, leading to potentially avoidable caesarean section and adverse neonatal outcomes. Factors associated with the success rates of labour induction include gestational age, estimated fetal birthweight, presence of a favourable cervix, maternal age, maternal parity status, and body mass index (BMI) ( Cunningham 2018).

Why it is important to do this review

There is one non‐Cochrane Review assessing the effectiveness and safety of various methods of induction of labour using network meta‐analysis (NMA) ( Alfirevic 2016a; Alfirevic 2016b). That review included 611 trials (900 reports), and the effectiveness and safety of 31 active interventions for third‐trimester labour induction were assessed. The NMA findings suggested that the most effective interventions in achieving vaginal births were oxytocin with amniotomy and vaginal misoprostol. Insufficient data were available or there was too much uncertainty to determine which treatments were the safest. However, the recommendations of this review were not made in conjunction with the GRADE approach ( Neumann 2018; Puhan 2014).

As further trials evaluating the methods of induction of labour have been published in recent years, we propose to conduct a systematic review and NMA to update the evidence regarding the effectiveness and safety of the methods for induction labour for at or beyond term labour with or without previous caesarean section and provide the evidence summaries using the GRADE approach.

Objectives

To compare the effectiveness and safety profiles for the different methods of cervical ripening and labour induction at or beyond term labour using network meta‐analysis, and to provide rankings of the available treatments according to their effectiveness and safety profile.

Methods

Criteria for considering studies for this review

Types of studies

We will include individually randomised controlled trials (RCTs) and cluster‐RCTs. Studies published in abstract form only will be eligible for inclusion if sufficient information is provided. We will exclude cross‐over trials, quasi‐randomised trials (trials in which the investigator randomly allocates participants to intervention or control groups using an allocation method that falls short of genuine randomisation, including date of birth), non‐randomised trials/quasi‐experimental studies (studies in which the investigator assigns participants to intervention or control group without randomisation techniques), and observational studies.

Types of participants

All pregnant women, singleton or multiple, with a live fetus requiring cervical ripening and induction of labour at or beyond term labour (as defined by trialists). We will include induction of labour, either in outpatient or inpatient settings, in this review. We will not include studies involving premature or mixed‐term labour where the term and preterm labour data cannot be separated. We will include trials that recruited only women with previous caesarean section and trials that recruited only women without previous caesarean section. For trials that recruited a mix of women with or without previous caesarean section, we will include such trials if over 50% of women did not have previous caesarean section. We will analyse data and present the findings separately for trials that primarily focused on the effects of induction of labour among 1) women with previous caesarean section and 2) women without previous caesarean section and a mix of women with or without previous caesarean section.

Types of interventions

We will include all cervical ripening and induction of labour methods recommended in any of the five guidelines of international reach ( Appendix 2). We will use the following guidelines of international reach to define our interventions of direct interest: American College of Obstetricians and Gynecologists (ACOG) guidelines ( ACOG 2009; ACOG 2014), National Institute for Health and Care Excellence (NICE) guideline ( NICE 2021), Royal College of Obstetricians and Gynaecologists (RCOG), International Federation of Gynecology and Obstetrics (FIGO) ( Morris 2017), and World Health Organization (WHO) guidelines ( WHO 2011; WHO 2018).

This review will also include any other cervical ripening and labour induction methods where Cochrane Reviews have recommended further research to determine their true effects on important labour process and delivery outcomes ( Appendix 3). However, we will not include methods that are not currently used in clinical practice (such as extra‐amniotic prostaglandins, intravenous prostaglandin, and relaxin) or that are considered to be alternative methods (such as castor oil or enemas, hypnosis, acupuncture, and homeopathy) ( Alfirevic 2016b).

We anticipate that the methods recommended in these five guidelines and those proposed by Cochrane Reviews will be sufficient to identify all currently available methods that are relevant for current clinical practice. Eligible interventions that were identified from the five guidelines and those proposed by Cochrane Reviews are listed below and shown in Figure 1 .

Oral misoprostol (25 and 50 µg)

Sublingual and buccal misoprostol

Controlled‐release misoprostol vaginal pessary

Vaginal dinoprostone (tablet and gel)

Controlled‐release dinoprostone vaginal pessary

Balloon catheters (Foley urinary catheters, double‐balloon devices, and extra‐amniotic saline infusion)

Balloon catheters plus oxytocin

Balloon catheters plus misoprostol

Comparator interventions (placebo, no treatment, or expectant management)

We will not include membrane sweeping in this review because it is considered to be an adjunctive treatment used to avoid the use of formal induction of labour methods. A Cochrane Review evaluating the effects of membrane sweeping for labour induction was recently published ( Finucane 2020).

If practicable, we will include cervical ripening and induction of labour methods that emerge during the conduct of the review if they are included in revised editions of ACOG, NICE, RCOG, FIGO, or WHO guidelines.

Trials will be eligible if they administered cervical ripening and induction of labour methods mentioned in the list of eligible interventions at or beyond term labour and compared them with another method listed in the intervention list, placebo, no treatment, or expectant management (waiting for labour to start spontaneously without treatments for inducing labour). We will amalgamate placebo, no treatment, and expectant management into a single comparator node.

We will combine different dosages of misoprostol, dinoprostone, and oxytocin into the same node. We will not include studies comparing different dosages of the same interventions (such as 25 µg oral misoprostol versus 50 µg oral misoprostol).

We will include multi‐arm trials in this review. We assume that any participant who meets the inclusion criteria of the review is equally likely to be randomised to any eligible intervention.

Types of outcome measures

We plan to include studies that meet our eligibility criteria whether or not they report on our outcomes of interest. The outcomes of this review are based on the core outcome set for trials on induction of labour, Dos Santos 2018, and priority outcomes for decision‐making proposed by the WHO ( WHO 2018).

Primary outcomes

For woman

1. Vaginal delivery not achieved within 24 hours

2. Caesarean section due to non‐reassuring fetal status

3. Uterine hyperstimulation with changes in the heartbeat of the baby before birth

For infant

1. Perinatal death (defined as the sum of early neonatal death and stillbirth)

2. Severe neonatal morbidity as defined by trial authors

Main outcomes for summary of findings tables

We will present all five primary outcomes in the summary of findings tables.

Secondary outcomes

For woman

1. Vaginal delivery not achieved with the primary method

2. Maternal not satisfied with the care related to induction of labour (defined as the dissatisfaction of women related to induction of labour experience which is measured by any measurement before discharging the women from the postpartum ward)

3. Time from induction of labour to delivery (measured as hours)

4. Blood loss 500 mL or more within 24 hours of delivery

5. Blood loss 1000 mL or more within 24 hours of delivery

6. Mean volume of blood loss (mL)

7. Uterine scar dehiscence or rupture (defined as an incomplete uterine scar separation with intact serosa and a full‐thickness disruption of the uterine wall, respectively)

8. Maternal death (defined as death during and following childbirth within 42 days)

9. Admission to intensive care unit

10. Pain related to induction of labour

For infant

1. Use of mechanical ventilation

2. Admission to the neonatal intensive care unit

3. A 5‐minute Apgar score of less than 7

Search methods for identification of studies

Electronic searches

We will search the current version of the Cochrane Pregnancy and Childbirth's Trials Register in collaboration with their Information Specialist.

The Register is a database containing over 34,000 reports of controlled trials in the field of pregnancy and childbirth. It represents the contemporary results of over 30 years of searching. For full current search methods used to populate Pregnancy and Childbirth's Trials Register (including the detailed search strategies for CENTRAL and MEDLINE, the list of journal and conference proceedings searched, plus the list of journals reviewed via the current awareness service), please follow this link.

Briefly, Cochrane Pregnancy and Childbirth's Trials Register is maintained by their Information Specialist and contains trials identified from:

monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains Cochrane's centralised searches of Embase, MEDLINE/PubMed, CINAHL, ICTRP and ClinicalTrials.gov;

weekly searches of MEDLINE (Ovid);

regular scanning of 30 journals and the proceedings of major conferences; and

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

Search results are screened by two people, and the full texts of all relevant trial reports identified through the searching activities described above are reviewed. Based on the intervention described, each trial report is assigned a number that corresponds to a specific Pregnancy and Childbirth review topic (or topics), and is then added to the Register. The Information Specialist searches the Register for each review using this topic number rather than keywords. This results in a more specific search set that will be fully accounted for in the relevant review sections (Included, Excluded, Awaiting Classification, or Ongoing).

In addition, we plan to search ClinicalTrials.gov (clinicaltrials.gov/) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/) for unpublished, planned, and ongoing trial reports using the search methods detailed in Appendix 4 (note these terms are draft terms and there may be some edits made once run. The full search methods for these sources will be reported in the review).

Searching other resources

We will scan the reference lists for included and excluded studies of previous network meta‐analysis study Alfirevic 2016b for additional trials. We will search the reference lists of retrieved studies.

We will not apply any language or date restrictions.

Data collection and analysis

Selection of studies

We will use Mendeley software for merging reference lists ( Mendeley), after which at least two review authors will independently screen the titles and abstracts and full articles via Covidence software ( Covidence). If eligibility is unclear, we will contact the trial authors for additional information. Any disagreements will be resolved by discussion or by consulting a third review author if required. We will create a study flow diagram to illustrate the number of records that have been identified, included, excluded, or awaiting classification.

Screening eligible studies for trustworthiness

We plan to include in the analysis only studies that were judged as being sufficiently trustworthy. We will apply the Cochrane Pregnancy and Childbirth Trustworthiness Screening tool (CPC‐TST) to assess the trustworthiness of evidence for all studies that meet our eligibility criteria. This evaluation will be independently performed by two review authors. The trustworthiness criteria are as follows.

Research governance

Are there any retraction notices or expressions of concern listed on the Retraction Watch Database (retractiondatabase.org/) relating to this study?

Was the study prospectively registered (for those studies published after 2010)? If not, was there a plausible reason?

When requested, did the trial authors provide/share the protocol and/or ethics approval letter?

Did the trial authors engage in communication with the Cochrane Review authors within the agreed timelines?

Did the trial authors provide individual participant data (IPD) upon request? If not, was there a plausible reason?

Baseline characteristics

Is the study free from characteristics of the study participants that appear too similar, e.g. distribution of the mean (standard deviation) and median (interquartile range, or range) excessively narrow or excessively wide, as noted by Carlisle 2017?

Feasibility

Is the study free from characteristics that could be implausible (e.g. large numbers of women with a viable fetus undergoing cervical ripening and induction of labour at or beyond term labour recruited within one month)?

In cases with (close to) zero losses to follow‐up, is there a plausible explanation?

Results

Is the study free from results that could be implausible? (e.g. massive risk reduction for main outcomes with small sample size)?

Do the numbers randomised to each group suggest that adequate randomisation methods were used (e.g. is the study free from issues such as unexpectedly even numbers of women 'randomised' including a mismatch between the numbers and the methods, if the authors say 'no blocking was used' but still end up with equal numbers, or if the authors say they used 'blocks of 4' but the final numbers differ by 6)?

We will not include studies assessed as being potentially 'high risk' in the review. Where a study is classified as 'high risk' for one or more of the above criteria, we will attempt to contact the study authors to address any possible lack of information/concerns. If adequate information remains unavailable, the study will remain in 'awaiting classification', and the reasons and communications with the author (or lack thereof) described in detail.

The process is described in full in Figure 2 .

Abstracts

We will only include data from abstracts if, in addition to the trustworthiness assessment, the study authors have confirmed in writing that the data to be included in the review have come from the final analysis and will not change. If such information is not available/provided, the study will remain in 'awaiting classification' (as above).

Data extraction and management

We will use Microsoft Access to create an electronic data extraction form, which will be piloted first before being implemented ( Microsoft Access). At least two review authors will independently extract information from the eligible studies using the agreed‐upon form. The data, specifically for numerical data, short text fields such as author name and email address, data from drop‐down lists, and Yes/No data, will then be imported into Stata software version 17.0 to check for discrepancies between the two review authors, which will be done by one review author (SR) ( Stata). Any disagreements will be resolved by discussion or by consulting a third review author if required. If additional information is needed, we will contact the trial authors of the original reports. We plan to collect data from each included study on the following characteristics.

Report: first author (with contact information), corresponding author (with contact information), publication year, journal, type of publication (full text, abstract, trial registration, or unpublished data)

Methods: study design and treatment assignment mechanism

Study: study dates, country in which the study was conducted, criteria for enrolled participants, number of participants assessed for eligibility, number randomised, number that received treatment, and number analysed

Participants: maternal age and BMI

Intervention: intervention and comparison, route, dose, and duration

Outcomes: all prespecified outcomes

Binary outcomes: we will record the number of events and the total number of participants in each arm. When contrast‐based information is available, we will extract adjusted treatment effect and standard error or lower and upper confidence interval.

Continuous outcomes: we will extract the mean and standard deviation for each study arm. When contrast‐based information is available, we will extract adjusted treatment effect and standard error or lower and upper confidence interval.

Cluster‐RCTs: we will extract a cluster‐adjusted treatment effect (such as risk ratio or mean difference, or both) and standard error.

Note: funding for the trial; study authors' declarations of interest

We will extract data for the following potential effect modifiers.

Gestational age (term labour/post‐term labour/mixed)

Parity (nulliparous/multiparous/mixed)

Cervical conditions: as defined by trialists using Bishop score (unfavourable/favourable/mixed)

Dosage of intervention (low dose/high dose)

History of caesarean section (women with a history of caesarean delivery/women without a history of caesarean delivery/mixed)

Assessment of risk of bias in included studies

Two review authors will independently assess the risk of bias of each included study using the Cochrane risk of bias tool for randomised trials and for cluster‐randomised trials, RoB 1 ( Higgins 2017). After risk of bias assessment, review authors will record their judgements in an electronic data extraction form. Risk of bias judgements will then be imported into Stata software version 17.0 to check for discrepancies between the two review authors, which will be done by one review author (SR) ( Stata). Any disagreements will be resolved by discussion or by consulting a third review author if required.

(3.1) Blinding of participants and personnel (checking for possible performance bias)

We will describe for each included study the methods used, if any, to blind study participants and personnel from the knowledge of which intervention a participant received. We will consider studies to be at low risk of bias if they were blinded, or if we judge that the lack of blinding would be unlikely to affect results. We will assess blinding separately for different outcomes or classes of outcomes.

We will assess the methods as:

low, high, or unclear risk of bias for participants;

low, high, or unclear risk of bias for personnel.

(3.2) Blinding of outcome assessment (checking for possible detection bias)

We will describe for each included study the methods used, if any, to blind outcome assessors from the knowledge of which intervention a participant received. We will assess blinding separately for different outcomes or classes of outcomes.

We will assess methods used to blind outcome assessment as:

low, high, or unclear risk of bias.

(6) Other bias (checking for bias due to problems not covered by (1) to (5) above)

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

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

In cluster‐randomised trials, particular biases to consider include the following.

Measures of treatment effect

Relative treatment effects

Dichotomous data

For studies reporting zero events in one arm, we will add a correction factor of 0.5 into all cells of the study results to estimate the effect sizes. We will exclude studies with zero events in all arms from the statistical analysis.

We will express the treatment effects of outcomes as risk ratio (RR) and 95% confidence intervals (CIs). We will present network meta‐analysis estimates of all dichotomous outcomes in league tables, which will show summary RRs and CIs for all pair‐wise comparisons. We will also use forest plots to present the results from pair‐wise, indirect, and network (combining direct and indirect) analyses for the comparisons of induction of labour methods versus placebo, no treatment, or expectant management.

Continuous data

For maternal satisfaction, time from induction of labour to delivery, volume of blood loss, and pain related to induction of labour outcomes, we will use mean difference (MD) if outcomes are measured using the same unit of measurement across trials. If the trials measured the same outcome using different measurements, we will use the standardised mean difference (SMD).

We will express treatment effects of all continuous outcomes as MD or SMD and 95% CIs. We will interpret SMD results as follows ( Schünemann 2022):

SMD less than 0.40 = small effect;

SMD greater than 0.40 and less than 0.69 = medium effect;

SMD 0.70 or greater = large effect;

We will present network meta‐analysis estimates of treatment effects for all continuous outcomes in the league table, which will show the summary MD or SMD for all pair‐wise comparisons with CIs. We will also use forest plots to present the results from pair‐wise, indirect, and network (combining direct and indirect) analyses for the comparisons of induction of labour methods versus placebo, no treatment, or expectant management.

Relative treatment ranking

We will use the Surface Under the Cumulative Ranking curve (SUCRA), a Bayesian statistical method for estimating treatment ranking, to rank the effects of all interventions on all primary outcomes. SUCRA value indicates the cumulative probability of efficacy (or safety) for each intervention when compared to the other available interventions. SUCRA values range from 0.00 to 1.00, where a higher value indicates a more effective treatment ( Chaimani 2021; Hutton 2015). After conducting a network meta‐analysis, we will rank treatments with 10,000 iterations in order to increase the precision of ranking probabilities. To illustrate the distribution of ranking probabilities for each intervention and outcome, rankograms will be generated by using the sucra command in Stata software ( Chaimani 2015).

Unit of analysis issues

Cluster‐randomised trials

We plan to include cluster‐randomised trials in the analyses along with individually randomised trials. If cluster‐RCTs performed an analysis that did not account for design effects, we will extract the following information to adjust their sample sizes according to the methods in the Cochrane Handbook for Systematic Reviews of Interventions ( Higgins 2021):

For cluster‐RCTs that do not provide ICC, we will use external estimates obtained from similar studies. If we use ICCs from other sources, we will report this and conduct sensitivity analyses to investigate the effect of variation in the ICC.

We will consider combining the results from cluster‐randomised trials with those from individually randomised trials if there is little heterogeneity between the study designs, and an interaction between the effect of intervention and the choice of randomisation unit is considered to be unlikely. We will also acknowledge heterogeneity in the randomisation unit and perform a sensitivity analysis to investigate the effects of the randomisation unit.

Other unit of analysis issues

Trials with multiple intervention groups

We will include multiple intervention trials in the review, and will account for the correlations between the treatment effects in network meta‐analysis. We will treat multi‐arm trials as multiple independent two‐arm studies in standard pair‐wise meta‐analysis.

Trials with multiple pregnancies

We will include trials with multiple pregnancies in the review. For maternal outcomes, the denominator will be number of women in each arm. For outcomes relating to babies, we will account for the clustering of events using the methods outlined in the Pregnancy and Childbirth Group Methodological Guidelines and the Cochrane Handbook.

Dealing with missing data

For included studies, we will note levels of attrition. We will explore the impact of including studies with high levels of missing data in the overall assessment of treatment effect by using sensitivity analysis. For all outcomes, we will carry out analyses on an intention‐to‐treat basis as far as possible, that is we will attempt to include all participants randomised to each group in the analyses, and all participants will be analysed in the group to which they were allocated, regardless of whether or not they received the allocated intervention. The denominator for each outcome in each trial will be the number of pregnant women randomised minus any participants whose outcomes are known to be missing.

We will first try to contact the first or corresponding authors of each trial to obtain missing or incomplete data. For trials reporting their findings in graphs only, we will use Plot Digitizer software to extract data from graphs ( Plot Digitizer). We will estimate standard errors from the width of CIs if trials did not report standard errors. In cases of an included study reporting their treatment effects as median and range or interquartile range, we will estimate mean and standard deviation from those values using the methods proposed by Wan and colleagues ( Wan 2014).

Assessment of heterogeneity

Because of the significant differences in effectiveness, safety, and methods used for cervical ripening and labour induction among 1) women with a history of caesarean delivery and 2) women without a history of caesarean delivery and a mix of women with or without a history of caesarean delivery, we will analyse and report the findings separately for these two populations ( Berghella 2020; Cunningham 2018; Leduc 2013).

To assess the occurrence of clinical heterogeneity, we will use descriptive statistics to present the distributions of study and participant characteristics across all included studies. We will examine the presence of clinical heterogeneity by comparing this information between each pair‐wise comparison. We will consider the following characteristics: maternal age, BMI, gestational age, parity, and cervical conditions.

We will examine statistical heterogeneity in each pair‐wise meta‐analysis by visual inspection of the overlap of CIs in the forest plots. We will also quantify heterogeneity levels using the I ² statistic. We will interpret the I ² statistic according to the guidelines in the Cochrane Handbook ( Deeks 2021), as follows:

0% to 40% might not be important;

30% to 60% may represent moderate heterogeneity;

50% to 90% may represent substantial heterogeneity;

75% to 100% represents considerable heterogeneity.

For network meta‐analysis, we will assess statistical heterogeneity in the entire network by considering the magnitude of the between‐study variance parameter (Tau ²) derived from the network meta‐analysis models. We will compare the magnitude of the heterogeneity variance with empirical distribution for dichotomous outcomes, as proposed by Turner 2012.

Assessment of transitivity across treatment comparisons

We will assess the transitivity assumption by comparing the distribution of potential effect modifiers across the available direct comparisons in the network. In this context, we expect that the transitivity assumption will hold assuming that: 1) the common treatment used to compare different methods for cervical ripening and labour induction indirectly is similar when it appears in different trials (e.g. oral misoprostol is administered in a similar way in oral misoprostol versus vaginal dinoprostone trials and in oral misoprostol versus oxytocin plus amniotomy trials); 2) all direct comparisons in the network do not differ with respect to the distribution of effect modifiers (e.g. the effect modifiers of oral misoprostol versus vaginal dinoprostone trials and of oral misoprostol versus oxytocin plus amniotomy trials). We will consider the following potential effect modifiers.

We will evaluate the transitivity assumption by comparing the distribution of these three prespecified potential effect modifiers across the different pair‐wise comparisons. If all participants in the network meta‐analysis have similar prespecified effect modifiers, we will accept the transitivity assumption.

Assessment of statistical inconsistency

We will evaluate inconsistency in network meta‐analysis using local and global approaches to complement the evaluation of transitivity.

Local approaches for evaluation of inconsistency

We will apply the Loop‐specific approach to assess the presence of local inconsistency ( Bucher 1997). This method evaluates the consistency assumption in each closed network loop separately by estimating the absolute difference between direct and indirect comparisons (inconsistency factor: IF). P < 0.05 indicates evidence of inconsistency between direct and indirect estimates. Due to the low power of this test to detect inconsistency, we will interpret the findings cautiously and look for inconsistency by considering the range of values contained in CIs of the incoherence factors and statistical significance ( Chaimani 2021; Hutton 2015). We will assume a common heterogeneity estimate within each loop. We will use the ifplot command in Stata software version 17.0 to perform Loop‐specific testing ( Chaimani 2015).

Global approaches for evaluation of inconsistency

We will use the design‐by‐treatment interaction model to evaluate the assumption of global consistency in each network ( Higgins 2012). We will infer the presence of inconsistency if the P value from the design‐by‐treatment model is less than 0.05. Stata software version 17.0 with the mvmeta command will be used to fit the model ( White 2009).

Assessment of reporting biases

For the pair‐wise meta‐analysis of primary outcomes, we will create funnel plots to investigate reporting biases (such as publication bias) if 10 or more studies are included in the meta‐analysis. We will assess funnel plot asymmetry visually. If a visual assessment suggests asymmetry, we will perform sensitivity analysis to investigate small‐study effects by excluding studies with fewer than 400 participants. For network meta‐analysis of primary outcomes, we will examine small‐study effects by plotting comparison‐adjusted funnel plots, which we will assess visually. We will set placebo, no treatment, or expectant management as a common comparator. If appropriate, we will assess the potential for small‐study effects by excluding studies with fewer than 400 participants.

Data synthesis

For each outcome, we will consider whether an overall summary result is meaningful.

Methods for direct treatment comparisons

We will conduct standard pair‐wise meta‐analyses with a random‐effects model for all primary and secondary outcomes with at least two available trials ( DerSimonian 1986). If there is clinical heterogeneity or considerable statistical heterogeneity, we will synthesise the findings narratively and present the results using forest plots without calculating an overall estimate. We will use Review Manager 5 for all analyses ( Review Manager 2020).

Methods for indirect treatment comparisons

Before conducting a network meta‐analysis, we will initially evaluate feasibility by generating network plots. We will use the network map command in Stata software to create network plots for all outcomes ( White 2015). For each network plot that is suitable for conducting a network meta‐analysis, and where the distribution of effect‐modifying factors across all comparisons meets the transitivity assumption, we will perform a network meta‐analysis.

We will perform random‐effects network meta‐analyses within a frequentist framework by pooling study‐specific treatment effects. A meta‐regression model that includes covariates will be used to determine the relative effects and ranking of all available induction methods. Using this modelling approach, the correlations between effect sizes from multi‐arm studies are addressed. We will use Stata software version 17.0 with the mvmeta command to analyse all network meta‐analyses ( White 2015).

Subgroup analysis and investigation of heterogeneity

Assumptions when estimating heterogeneity

In standard pair‐wise meta‐analyses, we will estimate a different heterogeneity variance for each pair‐wise comparison. In network meta‐analysis, we will assume a common estimate for the heterogeneity variance across the different comparisons.

Subgroup analysis

If we identify substantial heterogeneity, we will examine it further through subgroup analyses.

If inconsistency is detected in the networks for the primary outcomes, we will perform subgroup analyses by evaluating relative effects and assessing model fit for the following factors for those outcomes.

Gestational age (term labour/post‐term labour/mixed)

Parity (nulliparous/multiparous/mixed)

Cervical conditions: as defined by trialists using Bishop score (unfavourable/favourable/mixed)

Dosage of pharmacological methods (low dose/high dose)

Setting of induction of labour (inpatient setting/outpatient setting)

Types of balloon catheters (Foley urinary catheters/double‐balloon devices/extra‐amniotic saline infusion)

We will first visually compare the network diagrams of each subgroup to determine subgroup differences. Following that, for each subgroup, we will do a pair‐wise and network meta‐analysis and evaluate their relative treatment effects and ranking. We will look for qualitative interactions between subgroups in which the direction of effect might be reversed, that is if an intervention was beneficial to one subgroup but harmful to another.

Sensitivity analysis

We will perform sensitivity analyses for all primary outcomes in which substantial heterogeneity is identified.

Risk of bias: we will remove trials that are judged to be at high risk or unclear risk for overall risk of bias. We will judge studies as at overall low risk of bias if they are judged to be at low risk of bias for all domains.

Randomisation unit: we will remove cluster‐randomised trials to examine the effect of the randomisation unit.

Mixed population studies: as mentioned previously, we will analyse data and present findings separately for trials that primarily focused on the effects of induction of labour in 1) women with previous caesarean section and 2) women without previous caesarean section and a mix of women with or without previous caesarean section. We will analyse the latter group by including studies that only recruited women without a previous caesarean section.

Abstract‐only data: we will remove trials presented only as abstracts from the analyses.

Split the comparator interventions node: we will split interventions in the comparator interventions node and treat them separately as three nodes (placebo, no treatment, and expectant management).

Summary of findings and assessment of the certainty of the evidence

We will create summary of findings tables presenting the evidence for all primary outcomes comparing all cervical ripening and induction of labour methods with the reference comparator of placebo, no treatment, or expectant management. Each table will present key features of the evidence relating to a single outcome, with one table for each of our five primary outcomes, in accordance with the GRADE approach.

We will use the GRADE approach to assess the certainty of effect estimates from network meta‐analysis ( Brignardello‐Petersen 2019; Puhan 2014). There are three steps for grading evidence using the GRADE approach.

We will assess the certainty of the direct evidence for each primary outcome based on five domains of the standard GRADE approach: 1) limitations in study design (risk of bias), 2) inconsistency of results, 3) indirectness of evidence, 4) imprecision, and 5) publication bias. We will display the certainty of the direct evidence for all comparisons and outcomes on the network diagram.

We will assess the certainty of indirect evidence if either the indirect evidence contributes more to the estimates than direct evidence, or the direct evidence shows a lack of certainty (moderate, low, very low certainty). To assess the certainty of indirect evidence, we will choose the most dominant first‐order loop (the loop that has one common comparator) and rate the certainty of each of the direct estimates from that loop. We will choose the lowest of the two ratings to represent the certainty of indirect evidence. Finally, we will examine the differences in study characteristics that may affect the treatment effect on the direct comparisons that form the basis of the indirect estimate.

To assess the certainty of network evidence, we will first select the rating of the most precise of the indirect and direct estimates, or the highest of these two ratings if both contribute similarly. This rating will then be adjusted based on 1) the coherence of effect estimates from direct and indirect estimates and 2) the precision of the network estimate.

At each of the above stages, at least two review authors will independently appraise the certainty ratings of direct, indirect, and network evidence. Any disagreements will be resolved by discussion or by consulting a third review author if required. We will rate the certainty of network evidence for each outcome as 'high', 'moderate', 'low', or 'very low', in accordance with the GRADE approach and explained below.

High certainty: we are very confident that the true effect lies close to that of the estimated effect.

Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimated effect, but there is a possibility that it is substantially different.

Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimated effect.

Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimated effect.

Acknowledgements

This project was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to Cochrane Pregnancy and Childbirth. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Evidence Synthesis Programme, the NIHR, National Health Service (NHS), or the Department of Health and Social Care.

The World Health Organization and Siwanon Rattanakanokchai, Chumnan Kietpeerakool, Nuntasiri Eamudomkarn, Zarko Alfirevic, Ben Willem J Mol, Wentao Li, Pisake Lumbiganon, Arri Coomarasamy, and Malcolm J Price retain copyright and all other rights in their respective contributions to the manuscript of this review as submitted for publication.

We would like to thank Lisa Winer for her help in copy editing the final draft.

Appendices

Appendix 1. Glossary of terms

Bishop score: the scoring system used by medical professionals to rate the readiness of the cervix for delivery. This tool is helpful in predicting the potential for successful induction of labour.

Intrauterine growth restriction: a condition in which an unborn baby is smaller than expected because it is not growing at a normal rate inside the womb.

Pre‐eclampsia: a maternal disorder that is related to high blood pressure and often a significant amount of protein in the urine. This condition generally occurs during the second half of pregnancy or soon after delivery.

Pre‐eclampsia with severe feature (formerly severe pre‐eclampsia): the subset of pregnant women with pre‐eclampsia who develop severe high blood pressure and/or signs or symptoms of organ dysfunction.

Pre‐labour rupture of membranes: leakage of amniotic fluid before onset of labour.

Prolonged gestations: a pregnancy that has extended to or beyond 42 weeks of gestation.

Stillbirth: delivery of a baby who dies after 28 weeks of pregnancy, but before or during delivery.

Umbilical cord prolapse: umbilical cord that slips down in front of the baby through the open cervix (entrance of the womb) after a rupture of fetal membranes.

Uterine atony: failure of the uterus to contract following delivery.

Uterine hyperstimulation: an abnormally rapid rate and intensity of uterine contraction during delivery.

Appendix 2. Recommended methods of induction of labour

Appendix 3. List of interventions recommended by Cochrane Reviews for further research to determine their true effects

No. Cochrane Review Suggested intervention Note

9

Smith CA. Homoeopathy for induction of labour.
Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD003399. DOI: 10.1002/14651858.CD003399.

Homeopathy

Considered as an alternative method

19

Alfirevic Z, Aflaifel N, Weeks A. Oral misoprostol for induction of labour. Cochrane Database of Systematic Reviews 2014, Issue 6. Art. No.: CD001338. DOI: 10.1002/14651858.CD001338.pub3.

Oral misoprostol
(25 μg or 50 μg)

‐

20

Budden A, Chen LJY, Henry A. High‐dose versus low‐dose oxytocin infusion regimens for induction of labour at term. Cochrane Database of Systematic Reviews 2014, Issue 10. Art. No.: CD009701.
DOI: 10.1002/14651858.CD009701.pub2.

Oxytocin

‐

21

Nishi D, Shirakawa MN, Ota E, Hanada N, Mori R.
Hypnosis for induction of labour. Cochrane Database of Systematic Reviews 2014, Issue 8. Art. No.: CD010852. DOI: 10.1002/14651858.CD010852.pub2.

Hypnotic

Considered as an alternative method

23

Boulvain M, Irion O, Dowswell T, Thornton JG. Induction of labour at or near term for suspected fetal macrosomia. Cochrane Database of Systematic Reviews 2016, Issue 5. Art. No.: CD000938. DOI: 10.1002/14651858.CD000938.pub2.

‐

‐

26

Vogel JP, Osoti AO, Kelly AJ, Livio S, Norman JE, Alfirevic Z. Pharmacological and mechanical interventions for labour induction in outpatient settings. Cochrane Database of Systematic Reviews 2017, Issue 9. Art. No.: CD007701.
DOI: 10.1002/14651858.CD007701.pub3.

‐

‐

28

de Vaan MDT, ten Eikelder MLG, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KWM, Mol BWJ, Boulvain M. Mechanical methods for induction of labour. Cochrane Database of Systematic Reviews 2019, Issue 10. Art. No.: CD001233.
DOI: 10.1002/14651858.CD001233.pub3.

Balloon with low‐dose misoprostol or
a combination of mechanical methods with low‐dose misoprostol

‐

Appendix 4. Search methods for WHO ICTRP and ClinicalTrials.gov

All search lines will be run separately
ClinicalTrials.gov
Advanced search

Interventional Studies | labor induction
ICTRP
Searched for 'all synonyms'

induc* AND labour

induc* AND labor

Contributions of authors

Olufemi T Oladapo (OTO), Ioannis D Gallos (IDG), Arri Coomarasamy (AC), Pisake Lumbiganon (PL), Malcolm J Price (MJP), and Siwanon Rattanakanokchai (SR) conceived the idea for this protocol.

SR, MJP, IDG, AC, PL, and Zarko Alfirevic (ZA) designed the review.

SR, MJP, IDG, AC, PL, and ZA provided a methodological perspective.

IDG, AC, PL, ZA, and Chumnan Kietpeerakool (CK) provided a clinical perspective.

SR, MJP, and IDG provided statistical advice and input.

SR and MJP drafted the protocol.

IDG, PL, AC, CK, ZA, OTO, Doris Chou (DC), Nuntasiri Eamudomkarn (NE), Ben Willem Mol (BWM), and Wentao Li (WL) reviewed the protocol and provided critical feedback.

MJP is the guarantor for this review.

Sources of support

Internal sources

University of Birmingham, UK

The authors of this protocol are employed by the institutions indicated by their respective affiliations except where otherwise stated.

Khon Kaen University, Thailand

The authors of this protocol are employed by the institutions indicated by their respective affiliations except where otherwise stated.

Cochrane Thailand, Thailand

Technical support

University of Liverpool, UK

The authors of this protocol are employed by the institutions indicated by their respective affiliations except where otherwise stated.

Monash University, Australia

The authors of this protocol are employed by the institutions indicated by their respective affiliations except where otherwise stated.

World Health Organization, Switzerland

The authors of this protocol are employed by the institutions indicated by their respective affiliations except where otherwise stated.

External sources

No sources of support provided

Declarations of interest

Siwanon Rattanakanokchai: has declared that they have no conflict of interest.

Ioannis D Gallos: reports being an Editor for Cochrane Pregnancy Childbirth, and reports no involvement in the editorial process for this protocol.

Chumnan Kietpeerakool: has declared that they have no conflict of interest.

Nuntasiri Eamudomkarn: has declared that they have no conflict of interest.

Zarko Alfirevic: reports being the Co‐ordinating Editor of Cochrane Pregnancy Childbirth, and reports no involvement in the editorial process for this protocol. ZA reports having previously published work in this area ( Alfirevic 2016a; Alfirevic 2016b).

Olufemi T Oladapo: reports being an Editor for Cochrane Pregnancy Childbirth, and reports no involvement in the editorial process for this protocol.

Doris Chou: has declared that they have no conflict of interest.

Ben Willem Mol: reports being an Editor for Cochrane Pregnancy Childbirth, and reports no involvement in the editorial process for this protocol. BWM also reports receiving consultancy fees from GUERBET LLC, Merck, and ObsEva and being involved in studies eligible for inclusion in this review (PROBAAT I and PROBAAT II).

Wentao Li: has declared that they have no conflict of interest.

Pisake Lumbiganon: has declared that they have no conflict of interest.

Arri Coomarasamy: has declared that they have no conflict of interest.

Malcolm J Price: has declared that they have no conflict of interest.

References

Additional references

Chaimani 2015

Chaimani A, Salanti G. Visualizing assumptions and results in network meta-analysis: the network graphs package. Stata Journal 2015;15(4):905-50. [Google Scholar]

Cunningham 2018

Cunningham F, Leveno KJ, Bloom SL, Dashe JS, Hoffman BL, Casey BM, et al, editor(s). Williams Obstetrics. 25th edition. New York: McGraw Hill, 2018. [Google Scholar]

Keirse 1979

Keirse MJNC. Endogenous prostaglandins in human parturition. In: Keirse MJNC, Anderson ABM, Bennebroek-Gravenhorstm J, editors(s). Human Parturition. Leiden: Leiden University Press, 1979:101. [Google Scholar]

RCOG 2008

National Collaborating Centre for Women's and Children's Health (UK). Induction of Labour. London: Royal College of Obstetricians and Gynaecologists, 2008. [www.ncbi.nlm.nih.gov/books/NBK53617/] [Google Scholar]

White 2009

White IR. Multivariate random-effects meta-analysis. Stata Journal 2009;9(1):40-56. [Google Scholar]

White 2015

White IR. Network meta-analysis. Stata Journal 2014;15(4):951-85. [Google Scholar]

Articles from The Cochrane Database of Systematic Reviews are provided here courtesy of Wiley

# data[].attributes.attachment_link.title
Methods of induction of labour: a network meta‐analysis

# data[].attributes.attachment_link.description
This is a protocol for a Cochrane Review (intervention). The objectives are as follows:To compare the effectiveness and safety profiles for the different methods of cervical ripening and labour induction at or beyond term labour using network meta‐analysis, ...

# data[].attributes.attachment_link.title
Induction of Labor - StatPearls - NCBI Bookshelf

# data[].attributes.attachment_link.description
Induction of labor (IOL) is a common obstetric intervention that stimulates the onset of labor using artificial methods[1]. Rates of labor induction have nearly doubled since 1990.[2] There is substantial variation in IOL rates worldwide, and this can be attributed to variability in the guidelines and lack of consensus on the clinical practice guidelines on IOL. Nowadays, in high-income countries, the proportion of neonates born following IOL is estimated to be approximately 25%. In contrast, the corresponding rates are generally lower in low- and middle-income countries (LMIC).[1] This article reviews indications, contraindications, complications, and methodologies for labor induction (IOL).

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Professional standards of practice and behaviour for nurses, midwives and nursing associates. All standards apply within your professional scope of practice.

Contents:

About us

The Nursing and Midwifery Council exists to protect the public. We do this by making sure that only those who meet our requirements are allowed to practise as a nurse or midwife in the UK, or a nursing associate in England. We take action if concerns are raised about whether a nurse, midwife or nursing associate is fit to practise.

It is against the law to claim to be, or to practise as, a nurse or midwife in the UK, or as a nursing associate in England, if you are not on the relevant part of our register.

It is also a criminal offence for anyone who, with intent to deceive, causes or permits someone else to falsely represent them as being on the register, or makes a false representation about them being on the NMC register.

Publication date: 29 January 2015
Effective from: 31 March 2015
Updated to reflect the regulation of nursing associates: 10 October 2018

A note on this version of the Code

All regulators review their Codes from time to time to make sure they continue to reflect public expectations. This new version of the Code is substantially similar to the 2015 version, but it has been updated to reflect our new responsibilities for the regulation of nursing associates. In joining the register, nursing associates will uphold the Code.

The current versions of our Code, standards and guidance can always be found on our website. Those on our register should make sure they are using the most up to date version of the Code.

For more information about the Code, please visit: www.nmc.org.uk/code.

Introduction

The Code contains the professional standards that registered nurses, midwives and nursing associates ¹ must uphold. Nurses, midwives and nursing associates must act in line with the Code, whether they are providing direct care to individuals, groups or communities or bringing their professional knowledge to bear on nursing ² and midwifery practice in other roles, such as leadership, education, or research. The values and principles set out in the Code can be applied in a range of different practice settings, but they are not negotiable or discretionary.

Our role is to set the standards in the Code, but these are not just our standards. They are the standards that patients and members of the public tell us they expect from health professionals. They are the standards shown every day by those on our register.

When joining our register, and then renewing their registration, nurses, midwives and nursing associates commit to upholding these standards. This commitment to professional standards is fundamental to being part of a profession. We can take action if those on our register fail to uphold the Code. In serious cases, this can include removing them from the register.

The Code sets out common standards of conduct and behaviour for those on our register. This provides a clear, consistent and positive message to patients, service users and colleagues about what they can expect of those who provide nursing or midwifery care.

The professions we regulate have different knowledge and skills, set out in three distinct standards of proficiency. They can work in diverse contexts and have different levels of autonomy and responsibility. However, all of the professions we regulate exercise professional judgement and are accountable for their work.

Nurses, midwives and nursing associates uphold the Code within the limits of their competence. This means, for example, that while a nurse and nursing associate will play different roles in an aspect of care, they will both uphold the standards in the Code within the contribution they make to overall care. The professional commitment to work within one's competence is a key underpinning principle of the Code (see section 13) which, given the significance of its impact on public protection, should be upheld at all times.

In addition, nurses, midwives and nursing associates are expected to work within the limits of their competence, which may extend beyond the standards they demonstrated in order to join the register.

The Code should be useful for everyone who cares about good nursing and midwifery.

Patients and service users, and those who care for them, can use it to provide feedback to nurses, midwives and nursing associates about the care they receive.

Those on our register can use it to promote safe and effective practice in their place of work.

Employer organisations should support their staff in upholding the standards in their professional Code as part of providing the quality and safety expected by service users and regulators.

Educators can use the Code to help students understand what it means to be a registered professional and how keeping to the Code helps to achieve that.

For the many committed and expert practitioners on our register, this Code should be seen as a way of reinforcing professionalism. Through revalidation, nurses, midwives and nursing associates provide evidence of their continued ability to practise safely and effectively. The Code is central to the revalidation process as a focus for professional reflection. This gives the Code significance in the professional life of those on our register, and raises its status and importance for employers.

The Code contains a series of statements that taken together signify what good practice by nurses, midwives and nursing associates looks like. It puts the interests of patients and service users first, is safe and effective, and promotes trust through professionalism.
1 Anyone practising as a registered nurse or midwife in the UK, or a nursing associate in England, has to be registered with us. The nursing associate role is being used only in England.
² We have used the phrase 'nursing' in this document to apply to the work of nurses and nursing associates. Nursing associates are a distinct profession with their own part of our register, but they are part of the nursing team.

Prioritise people

You put the interests of people using or needing nursing or midwifery services first. You make their care and safety your main concern and make sure that their dignity is preserved and their needs are recognised, assessed and responded to. You make sure that those receiving care are treated with respect, that their rights are upheld and that any discriminatory attitudes and behaviours towards those receiving care are challenged.

1 Treat people as individuals and uphold their dignity

To achieve this, you must:

1.1 treat people with kindness, respect and compassion

1.2 make sure you deliver the fundamentals of care effectively

1.3 avoid making assumptions and recognise diversity and individual choice

1.4 make sure that any treatment, assistance or care for which you are responsible is delivered without undue delay

1.5 respect and uphold people's human rights
The fundamentals of care include, but are not limited to, nutrition, hydration, bladder and bowel care, physical handling and making sure that those receiving care are kept in clean and hygienic conditions. It includes making sure that those receiving care have adequate access to nutrition and hydration, and making sure that you provide help to those who are not able to feed themselves or drink fluid unaided.
2 Listen to people and respond to their preferences and concerns

To achieve this, you must:

2.1 work in partnership with people to make sure you deliver care effectively

2.2 recognise and respect the contribution that people can make to their own health and wellbeing

2.3 encourage and empower people to share decisions about their treatment and care

2.4 respect the level to which people receiving care want to be involved in decisions about their own health, wellbeing and care

2.5 respect, support and document a person's right to accept or refuse care and treatment

2.6 recognise when people are anxious or in distress and respond compassionately and politely

3 Make sure that people's physical, social and psychological needs are assessed and responded to

To achieve this, you must:

3.1 pay special attention to promoting wellbeing, preventing ill health and meeting the changing health and care needs of people during all life stages

3.2 recognise and respond compassionately to the needs of those who are in the last few days and hours of life

3.3 act in partnership with those receiving care, helping them to access relevant health and social care, information and support when they need it

3.4 act as an advocate for the vulnerable, challenging poor practice and discriminatory attitudes and behaviour relating to their care

4 Act in the best interests of people at all times

To achieve this, you must:

4.1 balance the need to act in the best interests of people at all times with the requirement to respect a person's right to accept or refuse treatment

4.2 make sure that you get properly informed consent and document it before carrying out any action

4.3 keep to all relevant laws about mental capacity that apply in the country in which you are practising, and make sure that the rights and best interests of those who lack capacity are still at the centre of the decision-making process

4.4 tell colleagues, your manager and the person receiving care if you have a conscientious objection to a particular procedure and arrange for a suitably qualified colleague to take over responsibility for that person's care (see the note below)
You can only make a 'conscientious objection' in limited circumstances. For more information, please visit our website at www.nmc.org.uk/standards/code/conscientious-objection-by-nurses-and-midwives/
5 Respect people's right to privacy and confidentiality

As a nurse, midwife or nursing associate, you owe a duty of confidentiality to all those who are receiving care. This includes making sure that they are informed about their care and that information about them is shared appropriately.

To achieve this, you must:

5.1 respect a person's right to privacy in all aspects of their care

5.2 make sure that people are informed about how and why information is used and shared by those who will be providing care

5.3 respect that a person's right to privacy and confidentiality continues after they have died

5.4 share necessary information with other health and care professionals and agencies only when the interests of patient safety and public protection override the need for confidentiality

5.5 share with people, their families and their carers, as far as the law allows, the information they want or need to know about their health, care and ongoing treatment sensitively and in a way they can understand

Practise effectively

You assess need and deliver or advise on treatment, or give help (including preventative or rehabilitative care) without too much delay and to the best of your abilities, on the basis of the best evidence available and best practice. You communicate effectively, keeping clear and accurate records and sharing skills, knowledge and experience where appropriate. You reflect and act on any feedback you receive to improve your practice.

6 Always practise in line with the best available evidence

To achieve this, you must:

6.1 make sure that any information or advice given is evidence-based, including information relating to using any health and care products or services

6.2 maintain the knowledge and skills you need for safe and effective practice

7 Communicate clearly

To achieve this, you must:

7.1 use terms that people in your care, colleagues and the public can understand

7.2 take reasonable steps to meet people's language and communication needs, providing, wherever possible, assistance to those who need help to communicate their own or other people's needs

7.3 use a range of verbal and non-verbal communication methods, and consider cultural sensitivities, to better understand and respond to people's personal and health needs

7.4 check people's understanding from time to time to keep misunderstanding or mistakes to a minimum

7.5 be able to communicate clearly and effectively in English

8 Work cooperatively

To achieve this, you must:

8.1 respect the skills, expertise and contributions of your colleagues, referring matters to them when appropriate

8.2 maintain effective communication with colleagues

8.3 keep colleagues informed when you are sharing the care of individuals with other health and care professionals and staff

8.4 work with colleagues to evaluate the quality of your work and that of the team

8.5 work with colleagues to preserve the safety of those receiving care

8.6 share information to identify and reduce risk

8.7 be supportive of colleagues who are encountering health or performance problems. However, this support must never compromise or be at the expense of patient or public safety

9 Share your skills, knowledge and experience for the benefit of people receiving care and your colleagues

To achieve this, you must:

9.1 provide honest, accurate and constructive feedback to colleagues

9.2 gather and reflect on feedback from a variety of sources, using it to improve your practice and performance

9.3 deal with differences of professional opinion with colleagues by discussion and informed debate, respecting their views and opinions and behaving in a professional way at all times

9.4 support students' and colleagues' learning to help them develop their professional competence and confidence

10 Keep clear and accurate records relevant to your practice

This applies to the records that are relevant to your scope of practice. It includes but is not limited to patient records.

To achieve this, you must:

10.1 complete all records at the time or as soon as possible after an event, recording if the notes are written some time after the event

10.2 identify any risks or problems that have arisen and the steps taken to deal with them, so that colleagues who use the records have all the information they need

10.3 complete all records accurately and without any falsification, taking immediate and appropriate action if you become aware that someone has not kept to these requirements

10.4 attribute any entries you make in any paper or electronic records to yourself, making sure they are clearly written, dated and timed, and do not include unnecessary abbreviations, jargon or speculation

10.5 take all steps to make sure that all records are kept securely

10.6 collect, treat and store all data and research findings appropriately

11 Be accountable for your decisions to delegate tasks and duties to other people

To achieve this, you must:

11.1 only delegate tasks and duties that are within the other person's scope of competence, making sure that they fully understand your instructions

11.2 make sure that everyone you delegate tasks to is adequately supervised and supported so they can provide safe and compassionate care

11.3 confirm that the outcome of any task you have delegated to someone else meets the required standard

12 Have in place an indemnity arrangement which provides appropriate cover for any practice you take on as a nurse, midwife or nursing associate in the United Kingdom

To achieve this, you must:

12.1 make sure that you have an appropriate indemnity arrangement in place relevant to your scope of practice

For more information, please visit: www.nmc.org.uk/indemnity

Preserve safety

You make sure that patient and public safety is not affected. You work within the limits of your competence, exercising your professional 'duty of candour' and raising concerns immediately whenever you come across situations that put patients or public safety at risk. You take necessary action to deal with any concerns where appropriate.

13 Recognise and work within the limits of your competence

To achieve this, you must, as appropriate:

13.1 accurately identify, observe and assess signs of normal or worsening physical and mental health in the person receiving care

13.2 make a timely referral to another practitioner when any action, care or treatment is required

13.3 ask for help from a suitably qualified and experienced professional to carry out any action or procedure that is beyond the limits of your competence

13.4 take account of your own personal safety as well as the safety of people in your care

13.5 complete the necessary training before carrying out a new role

14 Be open and candid with all service users about all aspects of care and treatment, including when any mistakes or harm have taken place

To achieve this, you must:

14.1 act immediately to put right the situation if someone has suffered actual harm for any reason or an incident has happened which had the potential for harm

14.2 explain fully and promptly what has happened, including the likely effects, and apologise to the person affected and, where appropriate, their advocate, family or carers

14.3 document all these events formally and take further action (escalate) if appropriate so they can be dealt with quickly
The professional duty of candour is about openness and honesty when things go wrong. "Every healthcare professional must be open and honest with patients when something goes wrong with their treatment or care which causes, or has the potential to cause, harm or distress." Joint statement from the Chief Executives of statutory regulators of healthcare professionals.
15 Always offer help if an emergency arises in your practice setting or anywhere else

To achieve this, you must:

15.1 only act in an emergency within the limits of your knowledge and competence

15.2 arrange, wherever possible, for emergency care to be accessed and provided promptly

15.3 take account of your own safety, the safety of others and the availability of other options for providing care

16 Act without delay if you believe that there is a risk to patient safety or public protection

To achieve this, you must:

16.1 raise and, if necessary, escalate any concerns you may have about patient or public safety, or the level of care people are receiving in your workplace or any other health and care setting and use the channels available to you in line with our guidance and your local working practices

16.2 raise your concerns immediately if you are being asked to practise beyond your role, experience and training

16.3 tell someone in authority at the first reasonable opportunity if you experience problems that may prevent you working within the Code or other national standards, taking prompt action to tackle the causes of concern if you can

16.4 acknowledge and act on all concerns raised to you, investigating, escalating or dealing with those concerns where it is appropriate for you to do so

16.5 not obstruct, intimidate, victimise or in any way hinder a colleague, member of staff, person you care for or member of the public who wants to raise a concern

16.6 protect anyone you have management responsibility for from any harm, detriment, victimisation or unwarranted treatment after a concern is raised

For more information, please visit our website at www.nmc.org.uk/raisingconcerns.

17 Raise concerns immediately if you believe a person is vulnerable or at risk and needs extra support and protection

To achieve this, you must:

17.1 take all reasonable steps to protect people who are vulnerable or at risk from harm, neglect or abuse

17.2 share information if you believe someone may be at risk of harm, in line with the laws relating to the disclosure of information

17.3 have knowledge of and keep to the relevant laws and policies about protecting and caring for vulnerable people

18 Advise on, prescribe, supply, dispense or administer medicines within the limits of your training and competence, the law, our guidance and other relevant policies, guidance and regulations

To achieve this, you must:

18.1 prescribe, advise on, or provide medicines or treatment, including repeat prescriptions (only if you are suitably qualified) if you have enough knowledge of that person's health and are satisfied that the medicines or treatment serve that person's health needs

18.2 keep to appropriate guidelines when giving advice on using controlled drugs and recording the prescribing, supply, dispensing or administration of controlled drugs

18.3 make sure that the care or treatment you advise on, prescribe, supply, dispense or administer for each person is compatible with any other care or treatment they are receiving, including (where possible) over-the-counter medicines

18.4 take all steps to keep medicines stored securely

18.5 wherever possible, avoid prescribing for yourself or for anyone with whom you have a close personal relationship

Prescribing is not within the scope of practice of everyone on our register. Nursing associates don't prescribe, but they may supply, dispense and administer medicines. Nurses and midwives who have successfully completed a further qualification in prescribing and recorded it on our register are the only people on our register that can prescribe.

For more information, please visit: www.nmc.org.uk/standards

19 Be aware of, and reduce as far as possible, any potential for harm associated with your practice

To achieve this, you must:

19.1 take measures to reduce as far as possible, the likelihood of mistakes, near misses, harm and the effect of harm if it takes place

19.2 take account of current evidence, knowledge and developments in reducing mistakes and the effect of them and the impact of human factors and system failures (see the note below)

19.3 keep to and promote recommended practice in relation to controlling and preventing infection

19.4 take all reasonable personal precautions necessary to avoid any potential health risks to colleagues, people receiving care and the public
Human factors refer to environmental, organisational and job factors, and human and individual characteristics, which influence behaviour at work in a way which can affect health and safety - Health and Safety Executive. You can find more information at www.hse.gov.uk
Promote professionalism and trust
20 Uphold the reputation of your profession at all times
You uphold the reputation of your profession at all times. You should display a personal commitment to the standards of practice and behaviour set out in the Code. You should be a model of integrity and leadership for others to aspire to. This should lead to trust and confidence in the profession from patients, people receiving care, other health and care professionals and the public.

To achieve this, you must:

20.1 keep to and uphold the standards and values set out in the Code

20.2 act with honesty and integrity at all times, treating people fairly and without discrimination, bullying or harassment

20.3 be aware at all times of how your behaviour can affect and influence the behaviour of other people

20.4 keep to the laws of the country in which you are practising

20.5 treat people in a way that does not take advantage of their vulnerability or cause them upset or distress

20.6 stay objective and have clear professional boundaries at all times with people in your care (including those who have been in your care in the past), their families and carers

20.7 make sure you do not express your personal beliefs (including political, religious or moral beliefs) to people in an inappropriate way

20.8 act as a role model of professional behaviour for students and newly qualified nurses, midwives and nursing associates to aspire to

20.9 maintain the level of health you need to carry out your professional role

20.10 use all forms of spoken, written and digital communication (including social media and networking sites) responsibly, respecting the right to privacy of others at all times

For more guidance on using social media and networking sites, please visit: www.nmc.org.uk/standards

21 Uphold your position as a registered nurse, midwife or nursing associate

To achieve this, you must:

21.1 refuse all but the most trivial gifts, favours or hospitality as accepting them could be interpreted as an attempt to gain preferential treatment

21.2 never ask for or accept loans from anyone in your care or anyone close to them

21.3 act with honesty and integrity in any financial dealings you have with everyone you have a professional relationship with, including people in your care

21.4 make sure that any advertisements, publications or published material you produce or have produced for your professional services are accurate, responsible, ethical, do not mislead or exploit vulnerabilities and accurately reflect your relevant skills, experience and qualifications

21.5 never use your status as a registered professional to promote causes that are not related to health

21.6 cooperate with the media only when it is appropriate to do so, and then always protecting the confidentiality and dignity of people receiving treatment or care

22 Fulfil all registration requirements

To achieve this, you must:

22.1 meet any reasonable requests so we can oversee the registration process

22.2 keep to our prescribed hours of practice and carry out continuing professional development activities

22.3 keep your knowledge and skills up to date, taking part in appropriate and regular learning and professional development activities that aim to maintain and develop your competence and improve your performance

For more information, please visit: www.nmc.org.uk/standards

23 Cooperate with all investigations and audits

This includes investigations or audits either against you or relating to others, whether individuals or organisations. It also includes cooperating with requests to act as a witness in any hearing that forms part of an investigation, even after you have left the register.

To achieve this, you must:

23.1 cooperate with any audits of training records, registration records or other relevant audits that we may want to carry out to make sure you are still fit to practise

23.2 tell both us and any employers as soon as you can about any caution or charge against you, or if you have received a conditional discharge in relation to, or have been found guilty of, a criminal offence (other than a protected caution or conviction)

23.3 tell any employers you work for if you have had your practice restricted or had any other conditions imposed on you by us or any other relevant body.

23.4 tell us and your employers at the first reasonable opportunity if you are or have been disciplined by any regulatory or licensing organisation, including those who operate outside of the professional health and care environment
When telling your employers, this includes telling (i) any person, body or organisation you are employed by, or intend to be employed by, as a nurse, midwife or nursing associate; and (ii) any person, body or organisation with whom you have an arrangement to provide services as a nurse, midwife or nursing associate. For more information, please visit our website at www.nmc.org.uk
23.5 give your NMC Pin when any reasonable request for it is made

24 Respond to any complaints made against you professionally

To achieve this, you must:

24.1 never allow someone's complaint to affect the care that is provided to them

24.2 use all complaints as a form of feedback and an opportunity for reflection and learning to improve practice

25 Provide leadership to make sure people's wellbeing is protected and to improve their experiences of the health and care system

To achieve this, you must:

25.1 identify priorities, manage time, staff and resources effectively and deal with risk to make sure that the quality of care or service you deliver is maintained and improved, putting the needs of those receiving care or services first
Throughout their career, all our registrants will have opportunities to demonstrate leadership qualities, regardless of whether or not they occupy formal leadership positions.
25.2 support any staff you may be responsible for to follow the Code at all times. They must have the knowledge, skills and competence for safe practice; and understand how to raise any concerns linked to any circumstances where the Code has, or could be, broken

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Read the NMC Code, code of conduct for nurses and midwives, online

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Overview | Inducing labour | Guidance | NICE

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This guideline covers the circumstances for inducing labour, methods of induction, assessment, monitoring, pain relief and managing complications. It aims to improve advice and care for pregnant women who are thinking about or having induction of labour

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This guideline covers the routine antenatal care that women and their babies should receive. It aims to ensure that pregnant women are offered regular check‑ups, information and support. We have also published a guideline on postnatal care, which covers the topics of emotional attachment and baby feeding.

The guideline uses the terms 'woman' or 'mother' throughout. These should be taken to include people who do not identify as women but who are pregnant. Similarly, where the term 'parents' is used, this should be taken to include anyone who has main responsibility for caring for a baby.

The Royal College of Obstetricians and Gynaecologists has produced guidance on COVID-19 and antenatal care for all midwifery and obstetric services.

Recommendations

This guideline includes recommendations on:

Who is it for?

Healthcare professionals

Commissioners of antenatal care services

Women using antenatal services, their partners, their families, and the public

Guideline development process
How we develop NICE guidelines
This guideline was commissioned by NICE and developed in partnership with the Royal College of Obstetricians and Gynaecologists (RCOG).

This guideline updates and replaces NICE guideline CG62 (published March 2008).

Your responsibility

The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals and practitioners are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or the people using their service. It is not mandatory to apply the recommendations, and the guideline does not override the responsibility to make decisions appropriate to the circumstances of the individual, in consultation with them and their families and carers or guardian.

All problems (adverse events) related to a medicine or medical device used for treatment or in a procedure should be reported to the Medicines and Healthcare products Regulatory Agency using the Yellow Card Scheme.

Local commissioners and providers of healthcare have a responsibility to enable the guideline to be applied when individual professionals and people using services wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with complying with those duties.

Commissioners and providers have a responsibility to promote an environmentally sustainable health and care system and should assess and reduce the environmental impact of implementing NICE recommendations wherever possible.

# data[].attributes.attachment_link.description
This guideline covers the routine antenatal care that women and their babies should receive. It aims to ensure that pregnant women are offered regular check‑ups, information and support. We have also published a guideline on postnatal care, which covers the topics of emotional attachment and baby feeding.

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NICE Insertion of a Double Balloon Catheter 

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NICE Insertion of a Double Balloon Catheter 

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4 Efficacy

This section describes efficacy outcomes from the published literature that the committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedures overview.

4.1 A nested study (n=186) within a quasi‑randomised controlled trial (RCT) of 188 pregnant women, comparing a double balloon catheter (DBC) plus extra‑amniotic saline infusion (EASI; n=60) against a single balloon catheter (SBC) plus EASI (n=126), reported that 'ripening success' (defined as an increase in Bishop score of 2 points or more with or without cervical dilation of 3 cm or more) was similar between the DBC and SBC groups (96% versus 93% respectively; p=0.55).

4.2 An RCT of 330 nulliparous pregnant women with unfavourable cervices compared 3 methods (DBC [n=107] versus SBC [n=110] versus prostaglandin gel [dinoprostone, n=113]) for induction of labour at term. The induction‑to‑delivery interval was longer in the DBC group (median 24.5 hours, 95% confidence interval [CI] 23.7 to 30.6) than the SBC group (median 23.2 hours, 95% CI 20.8 to 25.8) or the prostaglandin gel group (23.8 hours, 95% CI 21.7 to 26.8; a single p value of 0.043 was cited). The quasi‑RCT of 188 women at term with singleton pregnancy, comparing DBC (n=100) against SBC plus EASI (n=88) for induction of labour, reported that time from device insertion to delivery was significantly longer in the DBC group compared with the SBC plus EASI group (20.5 hours versus 17.3 hours respectively; p=0.03). The nested study (n=186) in this RCT, comparing DBC plus EASI (n=60) against SBC plus EASI (n=126), reported balloon insertion to delivery interval was significantly shorter in the DBC plus EASI group compared with the SBC plus EASI group (14.2 hours versus 15.5 hours respectively; p=0.04).

4.3 The RCT of 330 nulliparous pregnant women with unfavourable cervices, comparing 3 methods (DBC [n=107] versus SBC [n=110] versus prostaglandin gel [n=113]), reported no difference in caesarean delivery rates between any of the groups (DBC 43% versus SBC 36% versus prostaglandin gel 37%; a single p value of 0.567 was cited). The nested study (n=186) within the quasi‑RCT of 188 women, comparing DBC plus EASI (n=60) against SBC plus EASI (n=126), reported that caesarean section delivery rate was significantly lower in the DBC group than the SBC group (8% versus 20% respectively; p=0.05).

4.4 An RCT of 210 pregnant women with unfavourable cervices, comparing DBC (n=105) against prostaglandin gel (n=103), reported that more women in the DBC group had a vaginal delivery within 24 hours than those in the prostaglandin gel group (69% versus 49% respectively; odds ratio 2.22; 95% CI, 1.26 to 3.91). An RCT of 326 pregnant women with an unfavourable cervix at term, comparing DBC plus oral misoprostol (n=162) against oral misoprostol alone (n=151), reported that the rate of spontaneous vaginal delivery within 48 hours did not differ significantly between the groups (80% [101/162] versus 85% [90/106] respectively; p=0.29).

4.5 The nested study (n=186) within the quasi‑RCT of 188 patients, comparing DBC plus EASI (n=60) against SBC plus EASI (n=126), reported that there was no significant difference in maternal satisfaction (assessed on a scale of 1-10, with higher scores indicating greater satisfaction; 7.7 in the DBC group versus 7.0 in the SBC group, p=0.42). An RCT of 122 women, comparing DBC plus oral misoprostol (n=59) against oral misoprostol alone (n=63), reported a significant positive birth experience (on the German language version of Salmon Item List score) in the DBC plus misoprostol group compared with the misoprostol alone group (87.7 versus 79.3 respectively; p=0.030).

4.6 In the RCT of 326 pregnant women, comparing DBC plus oral misoprostol (n=162) against oral misoprostol alone (n=151), Apgar scores of less than 7 (at 5 minutes) were reported more in the DBC plus oral misoprostol group than in the oral misoprostol alone group (8 versus 1 respectively; p=0.04). In the quasi‑RCT of 188 patients and the nested study (n=186), Apgar scores of less than 7 (at 5 minutes) were similar between the study groups.

4.7 The specialist advisers listed efficacy outcomes as the proportion of women having a vaginal birth or caesarean delivery; the interval from start of induction to delivery; and the change in Bishop's score to enable artificial rupture of membranes (a score of 8 or more indicates that the cervix is ripe).

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Insertion of a double balloon catheter for induction of labour in pregnant women without previous caesarean section

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Evidence-based recommendations on insertion of a double balloon catheter for induction of labour in pregnant women without previous caesarean section. The catheter aims to help induction by causing dilation of the cervix when the cervix is unfavourable for induction.

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Annual information about maternity and childbirth from NHS providers for 2021-22. Includes antenatal booking appointments and birth information in interactive charts and infographics. 

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Double- versus single-balloon catheters for labour induction and cervical ripening: a meta-analysis

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Double- versus single-balloon catheters for labour induction and cervical ripening: a meta-analysis

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Research article

Open access

Published:

Show authors

BMC Pregnancy and Childbirth 19, Article number: 358 (2019) Cite this article

15k Accesses

23 Citations

Metrics

Abstract

Background

The induction of labour is an increasingly common procedure in the obstetrics field. Various methods have been used to induce labour, among which balloon catheters play an important role. Whether the specifically designed double-balloon catheter is better than the single-balloon device in terms of efficacy, efficiency, safety and patient satisfaction remains controversial. Identifying even small differences between these two devices could be useful to guide clinical practices, to further explore their mechanisms, and to promote a better understanding of the optimal methods for inducing labour.

Methods

Using the population, intervention, comparison, outcomes and study designs (PICOS) principle, we searched the PubMed, EMBASE, OVID, SCI, CENTRAL, ClinicalTrial.gov, and CDSR databases to identify relevant randomised controlled trials (RCTs) from inception through February 14, 2018. The primary outcome was the caesarean delivery rate, and the secondary outcomes focused on efficacy, efficiency, safety, and patient satisfaction. The relative risks or mean differences, including their 95% confidence intervals, were calculated using fixed-effects or random-effects models. All statistical analyses were completed with RevMan version 5.3.

Results

From a total of 1326 articles, 7 RCTs involving 1159 women were included. There were no significant differences in primary outcomes (RR, 0.88 [0.65, 1.2]; p-value, 0.43) or secondary outcomes identified between single- and double-balloon catheters. However, heterogeneity existed for some aspects.

Conclusion

Both kinds of balloon catheter have similar levels of efficacy, efficiency, safety and patient satisfaction; however, the single-balloon method is considered to be more cost-effective.

Peer Review reports

Background

Labour induction refers to the process of artificially stimulating the uterus to begin labour [ 1], which is an increasingly common procedure. Cervical status, measured by the Bishop score [ 2], is a good predictor for the outcome of labour induction. If the cervix is unfavourable, no method is highly successful, and a ripening process is generally employed to obtain cervical effacement and dilatation prior to induction [ 3, 4, 5]. Methods used for cervical ripening can be broadly divided into mechanical devices and pharmacologic options [ 6, 7]. Compared with pharmacologic agents, mechanical methods, which were the first methods developed to ripen the cervix or induce labour [ 8], have similar levels of effectiveness but incur fewer episodes of adverse events (such as uterine tachysystole), have lower costs and are easier to preserve [ 6].

The balloon catheter, including both double- and single-balloon catheters, appears to be a widely accepted mechanical method and is recommended by the WHO for the induction process [ 9]. The original version of the Foley (single-balloon) catheter was initially described by Barnes in 1863 but was not described again until 1967, by Embrey and Mollison [ 10]. In 1991, Atad described the first double-balloon variation [ 11]. The Cook Cervical Ripening Balloon (CCRB), which uses an identical mechanism to that of the Atad catheter, was approved by the United States Food and Drug Administration (USFDA) in 2013 [ 12]. Only the double-balloon catheter (either Atad or Cook) is specifically designed and licensed for labour induction, while the Foley catheter is used beyond instructions.

Mechanical ripening devices apply pressure to the internal face of the cervix, directly overstretching the lower uterine segment and indirectly increasing the localised secretion of prostaglandin [ 13]. In addition to the local effect, mechanisms that involve neuroendocrine reflexes (such as the Ferguson reflex) may promote the onset of contractions [ 14]. Purportedly, the double-balloon (either Atad or Cook) option has an additional cervico-vaginal balloon, which applies greater pressure to both sides of the cervix and avoids the need for traction [ 11].

Given the increasing induction rate, the knowledge of even small differences between methods could be useful, not only to guide clinical practices but also to further explore the mechanism underlying the mechanical induction of labour and may promote a better understanding of the optimal methods for labour induction. However, studies examining the superiority of the double-balloon catheter reveal mixed results [ 15, 16, 17, 18, 19, 20, 21, 22, 23]. We conducted this meta-analysis and systematic review using the best available evidence to assess the efficacy, efficiency, safety and patient satisfaction of double-balloon catheters in comparison with those of single-balloon devices among women who underwent labour induction with unfavourable cervixes.

Methods

Search strategy

Together with a clinical librarian (R.O.), an electronic literature search was conducted with the PubMed, EMBASE, OVID, SCI (via WOS), CENTRAL (The Cochrane Central Register of Controlled Trials) and ClinicalTrial.gov databases from inception through ebruary 14, 2018. The searching strategy was based on the PICOS principle, utilising medical subject headings and Boolean logic-based free-text combinations of the following search items: "labour induction", "cervical ripening", "balloon", "Foley", "Cook" and "Atad". In addition, we used sensitivity-maximising search filters to identify randomised controlled trials [ 24]. With the abovementioned databases, several meta-analyses and systematic reviews were identified. Aiming to identify more pertinent meta-analyses or systematic reviews, an additional search was performed in the CDSR (Cochrane Database of Systematic Reviews) database. All of the reference lists from the relevant reviews were manually retrieved to locate further eligible trials. There were no language restrictions. Differences of opinion were resolved by team discussion.

Study selection and data collection

All related RCTs that directly compared the double-balloon catheter with the single-balloon catheter for the purposes of labour induction or cervical ripening were included in the analysis. There were no restrictions with regards to settings, demographics, obstetrics characteristics (e.g., race, maternal age, and gestational weeks) and outcome measures. We excluded the following types of studies: (1) studies of balloon catheters used for outpatient purposes; and (2) protocols, observational studies, and secondary analyses of previous studies and guidelines. Prior to the formal review process, we performed pretesting with the kappa statistic to calculate the level of agreement between the inclusion/exclusion decisions of different reviewers and adjusted our criterion until kappa ≧ 0.75.

To improve the precision of the collected data, two reviewers (X.Y.L., Y.W.), one who majored in obstetrics and one who did not, screened each record for eligibility and independently extracted and tabulated the following information from the text, tables, and graphs: lead author; publication year; country of origin; study design; participants and intervention characteristics; outcomes; and sponsor. Prior to determining the categories for the data collection forms, a pilot test was performed using representative samples of the studies to be reviewed. All of the collected data are available upon request.

Due to the uncertain benefits of blinded assessments and the large workload, we did not conceal the general contents of the studies during this process. Any disagreements were resolved through discussion, or if necessary, through consultation with a third reviewer (F.Z.) who specialises in evidence-based medicine. When information regarding any of the extracted data points listed above was unclear, an attempt was made to access further details by contacting the authors of the original reports.

Selection of outcomes

The primary and secondary outcomes were defined before trial retrieval was performed. The primary outcome was the caesarean delivery rate. The secondary outcomes included: (1) catheter placement (placement difficulty/failure, spontaneous expulsion); (2) intervals (insertion to delivery, insertion to expulsion/removal, expulsion to delivery); (3) Bishop score increment; (4) vaginal delivery (vaginal delivery within 24 h, normal vaginal delivery, assisted vaginal delivery); (5) analgesia usage; (6) maternal adverse events (death, infection, postpartum haemorrhage); (7) neonatal adverse events (death, low Apgar score, NICU admission); (8) length of hospitalisation; and (9) satisfaction ( pain during the process, maternal total satisfaction). While we attempted to collect all of the above datapoints from all of the analysed studies, only those that provided all of the data appear in the analysis tables.

Quality assessment

Two independent investigators (X.Y.L., Y.W.) openly (not blinded) assessed the methodological quality of the included RCTs based on Cochrane risk-of-bias tool. Quality was graded based on the following criteria [ 25]: (1) high quality: both randomisation and allocation concealment were assessed as having low risks of bias, and all other items were assessed as having low or unclear levels of risk; (2) low quality: either randomisation or allocation concealment was assessed as having a high risk of bias, regardless of the risk levels of other items; and (3) moderate quality: trials did not meet the criteria for high or low quality. Discrepancies were resolved by consensus.

Statistical analysis

All statistical analyses were performed with RevMan version 5.3, with the help of a statistician (X.N.Z.). The relative risks (RRs) and mean differences (MDs), with corresponding 95% confidence intervals (CIs), were used to describe the intervention effects for dichotomous and continuous variables, respectively. All potential data conversions utilised standard formulae recommended by the Cochrane Handbook [ 24].

Heterogeneity was identified by Cochrane's Q test and the I ²-statistic test, in which a Q test p-value < 0.1 and an I ² value ≥50% indicated significant heterogeneity. When both the p-value and the I ² value displayed no heterogeneity, we chose the fixed-effect model. Else, a random-effect model was used.

Subgroup analysis was pre-specified and performed on parity. A sensitivity analysis was conducted to identify studies involving data conversions that may have exerted a disproportionate influence on the pooled estimates. We assessed publication bias by examining funnel plots for the primary outcome only.

Results

Study characteristics

The literature search and screening process is shown in Fig. 1. Initially, 1326 potentially relevant records were identified. The titles and abstracts were reviewed, and 12 relevant trials were further screened. After thorough investigation, 7 RCTs, containing 1159 women and available data (577 and 582 in the double- and single-balloon groups, respectively), were determined to be eligible for inclusion [ 15, 16, 17, 18, 19, 20, 21]. The characteristics of the included trials are summarised in Table 1. Table 2 shows the risk of bias and the corresponding quality of each individual trial, which is illustrated in Fig. 2a and b. Basic demographic and obstetric variables are presented in Table 3. Except for postdates, which only two studies reported and which show slight heterogeneity, all other variables were comparable.

Literature search and screening process

a Risk of bias graph. b. Risk of bias summary

Of the 7 RCTs, 3 trials [ 15, 18, 21] focused on nulliparous women, while 2 trials [ 17, 20] conducted subgroup analysis by parity. These 5 trials, which included 781 women (595 nulliparous and 186 multiparous), were suitable for parity subgroup analysis.

Effects of interventions

All trials reported the rates of caesarean section. There were no significant differences in the rates of caesarean delivery (RR, 0.88 [0.65, 1.2]; p-value, 0.43) among trials, but heterogeneity existed (Q p-value, 0.04; I ², 55%) (Fig. 3a). A corresponding funnel plot is shown in Fig. 3b. During sensitivity analysis, heterogeneity disappeared only when Salim 2011 [ 20] was excluded (Q p-value, 0.11; I ², 45%), while the pooled effect was always robust (no significant differences). The secondary outcomes, shown in Table 4, did not differ obviously between the two types of catheter, except for the Bishop score increment (MD, 0.57 [0.28, 0.86]; p-value, 0.0001).

a Forest plot of cesarean delivery. b. Funnel plot of cesarean delivery

Subgroup analysis results by parity are shown in Tables 5 and Table 6. Only the Bishop score increment in nulliparous women exhibited a statistically significant difference; however, heterogeneity was demonstrated among studies (MD, 1.08 [0.38, 1.78]; Q p-value, 0.11; I ², 56%; p-value, 0.002), suggesting that the double-balloon catheter may have a greater ability to increase the Bishop score. Unless otherwise highlighted, studies were homogeneous, and sensitivity analysis displayed no meaningful changes.

Discussion

Summary of main results

Efficacy and efficiency

Balloon catheters were initially designed for cervical dilatation and ripening during labour induction. The best indicator of efficacy is the Bishop score increment. However, when correlated with baseline data, the Bishop score served only as a secondary outcome. No significant differences were observed for obstetric characteristics (including the Bishop score before catheter insertion) between women treated with the single-balloon catheter and those treated with the double-balloon catheter. Therefore, we could use the Bishop score after catheter removal (the second Bishop score) to roughly calculate this effect size, and it was not necessary to perform covariance analyses to adjust the baseline data. According to our analysis, the double-balloon catheter increases the Bishop score more significantly, especially for nulliparous women. However, this result was not observed for the multiparous subgroup. In support of this finding, one study [ 17] reported a Bishop score > 6 at balloon removal, and a similar trend in was observed for both general and subgroup subjects. Additionally, the ripening success rates (defined by the individual articles) appeared to be higher in the double-balloon groups, but without enough statistical power to determine significance [ 16, 19, 22, 23]. Atad et al. also reported similarly large average increments in the Bishop scores for both nulliparous and multiparous women for the double-balloon catheter, without a single-balloon catheter comparison group [ 11]. Later, the researchers reported that the Bishop score increment when employing the single-balloon catheter was lower than that achieved by the double-balloon catheter, with a higher failure rate [ 26].

Efficiency, best evaluated by the interval length and the 24 h delivery rate, is comparable regardless of parity. In the double-balloon catheter group, the interval from insertion to delivery appears to be longer, while the interval from expulsion to delivery appears to be shorter, though neither measure achieves significance. Ahmed, et al. [ 15] stated that women treated with a single-balloon catheter had a shorter insertion to amniotomy time ( p = 0.02) than women treated with a double-balloon catheter, while Pennell, et al. [ 18] found that the length of labour did not significantly differ ( p = 0.152) between the two groups; there is little consensus on the time from insertion to active labour, with Pennell, et al. [ 18] preferring the single-balloon catheter ( p = 0.014), while Rab, et al., [ 19] demonstrated no obvious differences. Ahmed and Mei-Dan [ 15, 22] suggested that the shorter interval between insertion and expulsion for the single-balloon catheter likely resulted in the observed shorter induction to delivery interval, although the second Bishop score was lower in this group.

The frequency of placement difficulty or failure and spontaneous expulsion are similar between the two groups. In addition, Salim, et al. [ 20] found that women who spontaneously expelled their catheter demonstrated favourable outcomes with regards to shorter times from induction to delivery (1.10 [1.06-1.15]; p = 0.001) and a significantly lower proportion of operative deliveries (2.15 [1.26-3.69]; p  = 0.003).

Safety

Both maternal and neonatal adverse events are of great concern. Although we hoped to consider mortality data, no study provided this information. Other measurements were also equivalent, including maternal infection, postpartum haemorrhage, low Apgar scores and NICU admissions. Some studies also [ 18, 20] reported placental abruptions, uterine hyperstimulation, cord prolapse, malpresentation, and Apgar < 4 at 1 min, with no significant differences between groups.

Satisfaction

Patient-reported outcomes (PROs), such as maternal satisfaction, represent what is most important to patients about a condition and its treatment [ 24]. However, few reports related to PROs were found. Here, we can report patient satisfaction based on two original reports [ 15, 19], both evaluated by the visual analogue scale (VAS) [ 27], with identical measurement times and protocols. The pooled results of these two studies suggests similar satisfaction levels for the two catheter types.

Comprehensive outcomes

Delivery modes, which are of particular clinical concern, represent a comprehensive measurement of the effectiveness and safety of labour induction protocols and can incorporate economic evidence. Caesarean section delivery is the most frequently used outcome pre-specified by trials. According to our analysis, no strong evidence exists to demonstrate which mechanical device is more effective, and heterogeneity exists among studies. Similarly, both normal and assisted vaginal delivery rates were comparable between groups, regardless of parity, as were the rates of analgesia usage during the ripening process and the lengths of hospitalisation.

Heterogeneity

Heterogeneity exists in many results, which may be the result of differences in study design or quality, participants, interventions, demographic feature or local policies. During our heterogeneity test, three studies [ 17, 19, 20] were potential candidates for being the sources of heterogeneity. Unlike other studies, Rab et al. [ 19] enrolled women who had experienced a stillbirth and had scarred uteri, which could be responsible increasing the general heterogeneity. Additional differences among these studies involved parity and balloon volumes (discussed below).

Applicability of evidence

Guide clinical Practice

Despite the fact that the double-balloon makes results in more favourable Bishop scores, it appears to result in prolonged intervals. No differences were observed for delivery mode, which is the most meaningful obstetrical outcome. As for the economical consideration, it is mainly related to hospitalization length, delivery mode and device itself. What is noteworthy is that the single balloon (Foley catheter) is approximately 30-40 times cheaper than the double-balloon catheter at different institutions, and the difference of price varies from countries to countries. As the producers offered that Foley catheters cost approximately $1.12, while Cook catheters cost approximately $39.33. As for our hospital in China, the single balloon catheter costs 20-30 RMB while the double one costs 600 RMB, and the price for placing balloon catheters is about 600 RMB in both situations. Considering the fact that caesarean section and hospitalization length were similar in the two groups, and when coupled with a substantial price differences in the devices, the single balloon catheter seems like to be more cost-effective for labour induction, particularly in low resource settings.

Exploring the mechanisms

Practically, in our hospital, we prefer to place a balloon catheter at night, avoiding expulsion due to daily activity. Thus far, no studies have focused on this issue as a potential mechanism for labour induction. Theoretically, the insertion of a foreign object could increase the risk of intrauterine infections; however, the limited data from our analysis and previous studies did not show any evidence that the cervical ripening balloon catheter contributes to increased infection occurrences [ 6, 18, 20, 22, 28, 29, 30, 31]. More studies are required to address the effects of the balloon-catheters on the rupturing of membranes and infection. In addition, physiologic differences in the mechanism through which balloon catheters induce labour according to parity also must be assessed.

Prior research demonstrated that a Bishop score > 5 was associated with a greater likelihood of vaginal delivery [ 32, 33]. Although a higher Bishop score was achieved in the double-balloon group in our analysis, there were no differences in the vaginal delivery rates between the two groups. This result interested us, and we hypothesise that there may exist a threshold for the Bishop score that, once achieved, no further effects will be generated; after this threshold is met, the level of hormone secretions takes precedence over cervical conditions. Similar what is observed in our practice, favourable outcomes are rarely observed with balloon usage alone, unless augmentations (e.g., prostaglandin or oxytocin) are utilised.

The larger volume, the application of pressure on two sides (harder expulsion), and the ability to abandon traction when using the double-balloon catheter may explain the observed outcomes. The larger volume balloon may increase the separation between the amniotic membranes and the uterine decidua, resulting in an increase in the local secretion of prostaglandins and enhancing the cervical ripening process. Though 60 ml and 80 ml Foley catheters are more effective than 30 ml catheters [ 34, 35, 36], 80 ml + 80 ml Atad or COOK balloons do not demonstrate superiority to smaller Foley catheters, which may be due to other factors (e.g., traction). We hypothesise that traction may have a greater effect on the induction of labour and that the one-sided application of pressure may interfere with the labour pattern less than two-sided pressure. In theory, traction may cause discomfort for patients. However, this finding has not been confirmed by our analysis. Instead, speculum application prior to catheter insertion, which followed the same procedure in both groups, appears to be the main source of discomfort [ 15].

Further studies are required to investigate the possible biological mechanisms on cervical ripening and the sources of discomfort, to provide practice guidelines and instrument improvement.

Identifying the optimal methods for various populations

Although there were no restrictions on settings, demographics or obstetrics characteristics, the participants from all of the included studies, except for Rab [ 19], were women with viable singletons and without scarred uteri, making the applicability of our evidence limited. Vaginal birth after caesarean delivery (VBAC) has received increasing attention [ 37], but identifying the optimal method for labour induction in this specific population remains controversial. Pharmacological methods are often rejected in VBAC women because of greater risks of complications. However, whether balloon catheters can and should be utilised in women with scarred uteri, which manufacturers do not recommend, requires further studies. In addition, twins and other multiple pregnancies are contraindications for the use of balloon catheters, despite the increased frequency of multiple pregnancies. Whether balloon catheters can be used in situations with multiple pregnancies also deserves further study.

Strengths and limitations

In the current meta-analysis, no demographic or obstetric characteristics were restricted, which increases the applicability of the evidence. We performed evaluations examining evidence of bias and applied quality grades strictly based on the original reports and the Cochrane handbook. The 7 included trials are all rigorous in design, enabling the appraisal and interpretation of their results. Additionally, because bias is more important for studies with subjective events and positive results than for studies with negative results and objective outcomes, such as our analysis, it was acceptable to assume that bias would not practically undermine the results of our analysis.

When extracting data, some outcomes with various forms required data conversions, which likely led to analytical bias. Although we conducted sensitivity analysis specifically to test this possibility, it cannot be clearly determined whether these conversions influenced our outcomes. In addition, the outcomes we chose for this analysis are widely used in practice to avoid potential inconsistencies, and appropriate subgroup analyses were performed to identify potential sources of heterogeneity; however, heterogeneity remained too comprehensive to analyse fully.

The sample size of the current analysis had adequate power for the evaluation of the primary outcome. For some secondary outcomes, fewer data points were available, which may result in insufficient power and higher risks of publication bias. To minimise this bias and to involve more relevant studies, we have done our best to search databases using a wide range of publication years, to consider potentially eligible reviews and to fully utilise trial registration databases, with sensitivity-maximising search filters. Unfortunately, we are still incapable of accessing conference abstracts or proceedings and grey literature. Thus, publication bias cannot be excluded completely, and caution should be taken.

The procedures performed during our analysis to reduce bias and assess risks can provide direction for further research, although not all of these are necessary.

Conclusions

Both kinds of balloon catheter perform similarly with regards to efficacy, efficiency, safety and patient satisfaction. The single-balloon device appears to be more economical and practical, particularly in low resource settings.

Availability of data and materials

All data generated or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

CCRB:

Cook Cervical Ripening Balloon

CDSR:

Cochrane Database of Systematic Reviews

CENTRAL:

Cochrane Central Register of Controlled Trials

CIs:

Confidence intervals

MDs:

Mean differences

PICOS:

Population, intervention, comparison, outcomes and study designs

PROs:

Patient-reported outcomes

RCTs:

Randomised controlled trials

RRs:

Relative risks

USFDA:

United States Food and Drug Administration

VAS:

Visual analogue scale

VBAC:

Vaginal birth after caesarean delivery

References

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Funding

The National Natural Science Foundation of China (No. 81771614 and No. 81771613).

The National Key Research and Development Program of China (No.2016YFC1000407).

The funders had no involvement in the study design, data collection and analysis, interpretation of data and preparation of the manuscript.

Author information

Author notes

Xiyao Liu and Yu Wang contributed equally to this work.

Authors and Affiliations

1. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China

Xiyao Liu, Xin Luo & Hongbo Qi

2. First Clinical Institute, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China

Yu Wang

3. School of Public Health and Management, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China

Fan Zhang, Xiaoni Zhong & Rong Ou

Contributions

HBQ, XL and XYL contributed to the protocol design. The literature search was conducted by XYL and YW, with the help of RO. Study screening and data extraction were independently performed by XYL and YW. FZ contributed to resolving disagreements during these processes. All statistical analyses were completed with the aid of XNZ. XYL and YW reviewed and prepared the manuscript. HBQ and XL are guarantors of this manuscript. All authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Xin Luo.

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Liu, X., Wang, Y., Zhang, F. et al. Double- versus single-balloon catheters for labour induction and cervical ripening: a meta-analysis. BMC Pregnancy Childbirth 19, 358 (2019). https://doi.org/10.1186/s12884-019-2491-4
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DOI: https://doi.org/10.1186/s12884-019-2491-4

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# data[].attributes.attachment_link.title
Double- versus single-balloon catheters for labour induction and cervical ripening: a meta-analysis - BMC Pregnancy and Childbirth

# data[].attributes.attachment_link.description
Background The induction of labour is an increasingly common procedure in the obstetrics field. Various methods have been used to induce labour, among which balloon catheters play an important role. Whether the specifically designed double-balloon catheter is better than the single-balloon device in terms of efficacy, efficiency, safety and patient satisfaction remains controversial.

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Patient satisfaction with the cervical ripening balloon as a method for induction of labour: a randomised controlled trial

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Patient satisfaction with the cervical ripening balloon as a method for induction of labour: a randomised controlled trial

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Sheri Ee-lin Lim, PhD, MRCOG, ¹ Toh Lick Tan, MBBS, MRCOG, 1, ² Grace Yang Huang Ng, MBChB, ¹ Shephali Tagore, MBBS, MRCOG, ³ Ei Ei Phyo Kyaw, BDS, BSc(Hons), ³ and George Seow Heong Yeo, FRCOG, FAMS ³

Abstract

INTRODUCTION

Evidence has shown that balloon catheters are as effective as prostaglandins (PGE) in achieving vaginal delivery within 24 hours of the start of induction of labour (IOL), with lower rates of uterine hyperstimulation, and similar Caesarean section and infection rates. International guidelines recommend mechanical methods as a method of IOL. We designed a prospective randomised controlled study to evaluate patient acceptance of the cervical ripening balloon (CRB) for IOL.

METHODS

Suitable women with a singleton term pregnancy without major fetal anomaly suitable for vaginal delivery were recruited and randomised to receive the CRB or PGE on the day of IOL. Characteristics of the women, labour and birth outcomes were obtained from case notes. Pain and satisfaction scores were obtained by interviewing the women at IOL and after delivery. The main outcome measures were participant characteristics, labour and birth outcomes, pain score, satisfaction scores, and whether the participant would recommend the mode of IOL.

RESULTS

There was no difference in the pain score between the two groups at the start of IOL, but thereafter, pain scores were lower in the CRB group compared to the PGE group (4.5 ± 2.3 vs. 5.6 ± 2.4, p = 0.044). Women were equally satisfied with both methods and equally likely to recommend their method for IOL.

CONCLUSION

Patient experience of IOL with CRB or PGE was equally satisfactory, although pain during induction was lower in the CRB group. We found that both methods of IOL are acceptable to women and should be made available to provide more options.

Keywords: acceptability, cervical ripening, Cook balloon, labour induction, mechanical ripening

INTRODUCTION

The frequency of induction of labour (IOL) has dramatically risen in the last decade. Approximately one in five deliveries in the United Kingdom and United States are induced, making it a very common intervention for pregnant women.( 1, 2) Prostaglandins (PGE) have long replaced traditional mechanical methods as the mainstay of cervical ripening to induce labour. The National Institute for Health and Care Excellence guidelines for IOL( 2) recommend the use of vaginal PGE as the preferred method of induction and state that mechanical methods, including balloon catheters and laminaria tents, should not be routinely used. However, since the publication of these guidelines more than a decade ago, mechanical methods have been recommended by the American Congress of Obstetricians and Gynecologists,( 1) World Health Organization( 3) and Canada( 4) IOL guidelines. This international resurgence comes after the Cochrane review on mechanical methods for IOL,( 5) which found that mechanical methods were as effective as PGE in achieving vaginal delivery within 24 hours of the start of the intervention, with lower risk of uterine hyperstimulation. Similar Caesarean section and infection rates were also found. Other advantages of mechanical methods are their stability at room temperature and relatively easy insertion.

However, little information is available about women's acceptance of balloon devices for IOL. In our department in a maternity teaching hospital in Singapore, IOL is carried out using PGE as the standard of care. We designed a randomised controlled study to evaluate the use of a cervical ripening balloon (CRB) compared to PGE to assess patient satisfaction with Prostin (Pfizer, New York City, NY, USA) and the Cook ® Cervical Ripening Balloon (Cook Medical, Bloomington, IN, USA) in the local Singapore population. Our choice of the double balloon catheter was based on the hypothesis that it would be as effective as PGE in achieving vaginal delivery. Patient acceptance of this alternative method would allow clinicians and patients to tailor individual care. We have also found in an unpublished study that trainees with no previous experience could rapidly achieve competency in insertion of the CRB when training is supplemented by lectures, simulation and supervision, which supports the implementation of the CRB as an alternative IOL method.

METHODS

This study was carried out from 2014 to 2015 at KK Women's and Children's Hospital, Singapore. Pregnant women aged 21-40 years old at term (37+0 weeks to 41+6 weeks) with a singleton pregnancy who were suitable for a vaginal delivery were invited to join the study. Pregnancies with major fetal anomaly or scarred uterus were excluded. Women were randomised to either the CRB or PGE arm. Identical envelopes were prepared, each containing a folded paper; 75 envelopes had the words 'Cervical Ripening Balloon' and another 75 had the word 'Prostin'. The envelopes were shuffled and sealed. They were then labelled sequentially with an allocation number from 1 to 150. Recruited participants were allocated to the next random allocation number in sequence. After recruitment, the women were checked to ensure that their cervical dilatation was less than 3 cm, membranes were still intact, presentation was cephalic and cardiotocography (CTG) was normal. Those who withdrew from the study were excluded. The detailed methodology has been described in a previous published study.( 6)

Identification of eligible pregnant women occurred in the antenatal outpatient clinic after the woman received antenatal counselling by her attending doctor, or in labour ward triage. A member of the research team explained the study and obtained consent if the woman was agreeable. It was stressed that the study was voluntary and did not affect her medical care and the woman was free to withdraw from the study without prejudice. Women who needed time to consider joining the study were followed up the next day or at the next antenatal visit. A patient information leaflet on IOL, with information on the study, members of the team and their contact details, was made available to the patient. The cost of CRB and PGE induction was comparable. On average, the CRB was slightly cheaper (CRB SGD 200 vs. PGE SGD 228), as 47% women receiving PGE required more than one dose given 6-8 hours apart, necessitating more blocks of time on labour ward as per our hospital's protocol for IOL.

On the day of IOL, the patient was reviewed by one of the study doctors to ensure patient eligibility. A presentation scan, vaginal examination for cervical dilatation and CTG were performed before IOL was initiated. Women who had placement of the CRB were examined abdominally and vaginally. The perineum and vagina were cleaned using antiseptic solution. The CRB was introduced into the endocervix by direct visualisation. The uterine and vaginal balloon reservoirs were gradually inflated at approximately one, two and three hours after insertion of the CRB until there was 80 mL in each balloon. CTG monitoring was carried out for more than 20 minutes before and after insertion of the CRB and inflation of the double balloon catheter. If the woman was not in labour after inflation of the balloons, she was transferred to the antenatal ward to ambulate, then sent to the labour ward for removal of the CRB 12 hours later, or when spontaneous expulsion of the catheter or rupture of the membranes occurred.

Women who were randomised to the PGE arm had placement of 3 mg of Prostin (dinoprostone vaginal tablets) intravaginally. The patient was asked to remain recumbent for 30 minutes. Fetal heart and uterine activity was monitored continuously for at least two hours before the patient was transferred to the antenatal ward to ambulate, provided that the CTG was satisfactory and the patient was not in labour. If there was inadequate response, a further dose of Prostin was given six hours later in the labour ward. Amniotomy and/or syntocinon infusion was given as necessary. If amniotomy was not possible after two doses of PGE or after the CRB was removed, the induction was deemed as a failed IOL. The patient would then leave the study and the attending doctor would take over her subsequent management. This usually included a further dose of PGE.

After delivery, a member of the study team interviewed the patients. Information collected included patients' views on pain felt during the induction process, overall satisfaction, comments and whether they would recommend their mode of induction to other women ( Fig. 1 ). No patients were lost to follow-up, as we were able to follow up on all recruited patients within a few days of delivery. Characteristics of labour and birth outcomes were obtained from medical case notes.

Normally distributed data was presented as mean ± standard deviation, and p-values were calculated using Student's t-test. For categorical data, p-values were calculated with Pearson's chi-square or Fisher's exact tests. A p-value of 0.05 was used as the cut-point for significance. This data was collected, collated and analysed using IBM SPSS Statistics version 19.0 (Armonk, NY, USA). The study was approved by the SingHealth Centralised Institutional Review Board (reference number 2013/553/D).

RESULTS

A total of 138 women were approached to join the study, but 40 women declined. Hence, a total of 98 women were enrolled. 14 women were excluded from analysis: seven went into spontaneous labour before their IOL, two were found to have non-cephalic fetal presentation, one had confirmed rupture of membranes prior to IOL, one was found to have a gestation less than 37+0 weeks, and three women presented for IOL when the research team was unavailable. One woman randomised to the CRB arm withdrew from the study after 8 hours 55 minutes due to discomfort from the balloon catheter. The remaining 83 cases were analysed and their characteristics are shown in Table I .

There was no significant difference between the characteristics of the women in the CRB and PGE arms in terms of maternal age (28.2 ± 5.3 years vs. 28.7 ± 5.0 years; p = 0.646), ethnicity (p = 0.222), proportion of primigravidae (61.3% vs. 44.2%; p = 0.174), weight (64.4 ± 15.0 kg vs. 63.9 ± 13.2 kg; p = 0.861), BMI (25.5 ± 5.0 kg/m ² vs. 25.0 ± 5.1 kg/m ²; p = 0.706), gestational age (39.4 ± 1.1 weeks vs. 39.2 ± 1.9 weeks; p = 0.357) and primary indication for IOL (p = 0.108).

Induction to vaginal delivery time and vaginal delivery rate were similar in both arms of the study ( Table II ).( 7) Compared to the PGE arm, participants undergoing CRB IOL achieved active labour in a shorter span of time and were more likely to require oxytocin infusion for augmentation, as uterine contractions at the time of artificial rupture of membranes were less frequent. One case of uterine hyperstimulation was found in the PGE arm, although this was not clinically significant. The patient progressed rapidly from 4 cm to full dilatation within 40 minutes, and achieved a normal vaginal delivery. The baby's Apgar scores were 9 at one minute and five minutes. No case of uterine rupture was observed. The birth outcomes of both arms of the study were also similar, with no case of stillbirth ( Table III ). There were two cases of neonatal intensive care unit admission in the PGE arm for continuous positive airway pressure therapy. Both were discharged from the neonatal intensive care unit within 24 hours.

The pain scores at the start of IOL were similar. However, the pain score in the CRB group was significantly lower than in the PGE group during the induction process (4.5 ± 2.3 vs. 5.6 ± 2.4; p = 0.044) ( Table IV ). Epidural rates were similar in the two groups. Nevertheless, both groups expressed good satisfaction scores (CRB 3.4 ± 1.5 vs. PGE 3.2 ± 1.4; p = 0.465), and the majority of the women said they would recommend their method of IOL (CRB 71.0% vs. PGE 69.2%; p = 1.000) ( Table IV ). As part of the pro forma, patients were asked to comment on their IOL experience post delivery. 22 free-text comments were recorded, with an equal number of comments from each arm. Comments from the PGE arm were related to speed, pain and effectiveness, in descending order. Four out of 11 comments from this arm were complaints that the induction process took too long. The majority (five out of 11) of comments from the CRB group were mainly related to discomfort (including the patient who withdrew from the study due to discomfort) regarding the catheter tube strapped to the leg or pressure from the balloon catheter. Two women would still recommend this method of IOL to other women, and the other two would not. The patient who withdrew from the study was not included in the analysis and her comments were not recorded. Other comments in the CRB group pertained to pain (n = 2), perceived effectiveness (n = 2, one of whom achieved a normal vaginal delivery) and speed of the process (n = 1).

The patient who withdrew from the study was from the CRB group. Our records showed that insertion of the CRB was successful at the first attempt by a trained medical officer, taking five minutes and requiring no assistance. The CRB was in situ for 10 hours 55 minutes before the patient complained that the discomfort she felt was 'too unbearable'. The CRB was removed and the patient proceeded to have a PGE IOL. She received three doses of PGE and reached 3 cm cervical dilatation before artificial rupture of membranes and augmentation was carried out. The patient reached full dilatation but requested for an emergency Caesarean section, as she felt that her labour was taking too long. She delivered a female baby weighing 3,215 g with an Apgar score of 9 at one minute and five minutes. She was discharged well from hospital a few days later.

DISCUSSION

To the best of our knowledge, this is the first randomised controlled trial comparing acceptance of the CRB to that of PGE as an IOL method. The CRB was felt to be a less painful method of IOL as compared to PGE. In our local population, it was equally accepted and considered satisfactory. This study will serve as a platform to carry out more studies using the CRB, especially in higher-risk pregnancies and the outpatient setting.

The 2012 Cochrane review assessing the effects of mechanical methods of IOL was a landmark review endorsing the efficacy of mechanical methods in achieving delivery within 24 hours of the start of the intervention, with fewer episodes of uterine hyperstimulation compared to PGE. The study specifically reviewed a subgroup managed with transcervical Foley balloons, showing that the device was effective in increasing the favourability of the cervix compared to a placebo.( 5) Randomised controlled trials comparing single to double balloon catheters for IOL showed that they were equally efficacious.( 7, 8) Double balloon catheters used in IOL have been found to result in fewer labour complications such as hyperstimulation and non-reassuring fetal heart patterns.( 8) Amid the emergence of new evidence on efficacy and safety in using mechanical methods for IOL, especially in higher-risk pregnancies including oligohydramnios( 9, 10) or scarred uteri,( 5, 11) as well as their use in the outpatient setting,( 12- 15) there is little data on women's acceptance of mechanical methods as an alternative for inducing labour.

Two publications have assessed women's acceptance of the balloon catheter for cervical ripening. Kehl et al explored the acceptability of a double balloon catheter used concomitantly with oral misoprostol.( 16) The double balloon catheter was accepted by the women and was found to have a positive impact on the birth experience. The trial found that women were not bothered by the placement of the device or the presence of the catheter. They reported that in a subsequent pregnancy, they would consider the methods they had tried and also recommend it to others. Cervical ripening with balloon catheters has been associated with significantly less pain than PGE, while single balloon catheters caused less pain than double balloon catheters (36% vs. 55%, pain score ≥ 4). An Australian randomised pilot controlled study by Wilkinson et al( 17) compared inpatients' with outpatients' balloon catheter for cervical ripening. They found that most women reported some discomfort with insertion and wearing the catheter, but were equally satisfied with their care in both cases, felt that their baby was safe and felt less isolated when they were at home during the cervical ripening process. To the best of our knowledge, our study is the first to evaluate women's acceptance of the double balloon catheter compared to vaginal PGE as a method of IOL.

In assessing patient satisfaction with the CRB as a method of IOL, it was essential to assess the efficacy of the two methods, CRB and PGE. The results of our study were in keeping with the available evidence that mechanical methods are as efficacious as pharmacological methods in terms of induction to vaginal delivery time as well as vaginal delivery rates. Comparisons of patient characteristics, labour and birth outcomes were undertaken to identify any confounding factors that might have affected the experience of the women, and the maternal and neonatal outcomes were similar. In light of the similar efficacy of the CRB and PGE, it is possible to separate patient satisfaction from the outcome of delivery.

The pain score at the start of IOL was assessed to evaluate the pain during the insertion of the CRB compared to that with PGE. Interestingly, there was no difference in the pain score although the CRB, due to the nature of the product, required more time to insert than PGE, on average, and necessitated the use of a speculum. As more than one dose of PGE was often required before amniotomy was performed, it was not possible to compare the pain felt at the second PGE insertion as a distinct intervention. Instead, pain felt during the induction process was compared between the groups as a whole, and the pain felt during the induction process was significantly less in the CRB group. The onset of uterine contractions for PGE vaginal suppository is within 10 minutes and lasts up to 2-3 hours. Women in the PGE group often required more than one dose (46.1%) to bring about adequate cervical ripening and were subject to regular painful contractions and an additional vaginal examination for reinsertion of PGE that is likely to have affected their pain score.

The CRB group had significantly fewer regular contractions at the time of amniotomy compared to the PGE group despite similar successful vaginal delivery outcomes within 24 hours, suggesting that the CRB is efficacious while incurring less pain. The CRB required augmentation more often even though it enabled the group to reach cervical dilatation > 4 cm faster than the PGE group. The CRB ripens the cervix through direct pressure on the cervix while concomitantly stimulating endogenous PGE release, which aids in cervical ripening. The increase in local PGE leads to a series of complex changes within the cervix, including an increase in collagen degradation, hyaluronic acid, leucocyte chemotaxis and interleukin-8 release. These changes, coupled with uterine contractions, culminate in cervical effacement and dilatation. The level of endogenous PGE released as a result of the CRB may not be sufficient to bring about adequate uterine contractions within the period of induction of labour, thus requiring more augmentation compared to the PGE group.

Free-text comments from our patients included discomfort due to the catheter, but that did not affect the overall satisfaction score. It was noted that one patient from the CRB arm withdrew from the study, stating discomfort from the catheter as a reason. Her satisfaction score was therefore not included in the study's results, as she did not complete the induction. This case was interesting, as the patient received both methods of induction. We can postulate that her overall satisfaction score for CRB as a method of IOL would be low, but it was equally likely that she would be displeased with both methods of induction, as her induction with PGE also took a longer time and required three doses of PGE. If she had been included in the statistics, it is unlikely to have significantly affected the study outcome. Of note, 3 mg PGE vaginal tablets are used as the standard method of IOL in our hospital (controlled-release dinoprostone vaginal pessary is not available). A patient who does not wish to continue using PGE has no recourse to withdraw, as PGE is not easily removed. Furthermore, the lack of an alternative IOL method means patients are likely to deliver by Caesarean section if they decline PGE. This further reinforces the need to evaluate a safe alternative method of IOL that is acceptable to patients.

A limitation of the study was the small sample size. Nevertheless, the sample size was similar to that of other studies that examined women's acceptance of the double balloon catheter as a method of IOL. Kehl's 2013 study( 16) included an analysis of 79 questionnaires of women who were randomly assigned to a group that used oral misoprostol and a double balloon catheter, or to a control group that used oral misoprostol as a method for inducing labour. They similarly found that the double balloon catheter was accepted by the women and had a positive impact on the birth. Our pilot study contributes to the little information that is available about women's satisfaction with the CRB as a method of IOL. Completion of this pilot study also provided baseline information and prompted a subsequent larger prospective study of the CRB versus PGE, offering women in our hospital a choice of either method of IOL, which was previously not provided. The latter study was in progress at the time of publication and evaluated adverse events as well as patient satisfaction. Another limitation was that this pilot study was carried out in a single institution. Expansion of the study to other institutions with larger numbers would provide a better representation of women's satisfaction with the CRB as a method of IOL in Singapore.

Another limitation involves patient satisfaction, which is defined as a person's critical evaluation of an experience that is influenced by one's expectations, perceptions, attitudes and personal values. It is a valuable outcome measure for quality of care.( 18) Patient satisfaction is determined by the differences between what is expected and what actually happens. Although the study was randomised, the patient's personal background relating to the use of either method may influence the consideration of whether a method was efficacious or satisfactory. This is especially true for PGE: for instance, a patient may have a bad impression of PGE if her relative previously underwent IOL using PGE and had a bad experience. On the other hand, she may change her mind and evaluate PGE induction positively if her own delivery outcome is good. Similarly, the perception that CRB is a new method of IOL and not standard care may negatively influence another patient's perception of the induction process. In these scenarios, the patient's experience of IOL may be affected unless she is able to compare the two methods in her own obstetric history.

However, we attempted to minimise any bias towards either method of IOL. Patients were only recruited and uniformly counselled by a member of the study team. In addition, randomisation of patients to either group reduced the impact of any preconceptions as to which method was superior. Future studies may take into account previous induction methods that a patient has been exposed to and her acceptance of that IOL method.

In conclusion, this study explored the key clinical outcomes of efficacy and safety of the CRB as a method of IOL as well as the assessment of patient satisfaction in both groups, affirming previous positive findings in published data. The CRB was found to be equally acceptable when compared with PGE as a method of IOL among patients in a Singapore tertiary hospital setting.

ACKNOWLEDGEMENT

We are grateful for the CRBs provided by Cook Medical for the study.

REFERENCES

2. National Collaborating Centre for Women's and Children's Health (UK) Induction of Labour. NICE Clinical Guidelines No. 70. London: RCOG Press; 2008. [[ PubMed] Google Scholar]

4. Induction of Labour. The Society of Obstetricians and Gynaecologists of Canada (SOGC) Clinical Practice Guideline No. 296, September 2013 [ Google Scholar]

5. Jozwiak M, Bloemenkamp KW, Kelly AJ, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2012:CD001233. [[ PubMed] Google Scholar]

6. Tan TL, Ng GY, Lim SE, et al. Cervical ripening balloon as an alternative for induction of labour: a randomized controlled trial. BJMP. 2015;8:a806. [[ PMC free article] [ PubMed] Google Scholar]

11. Jozwiak M, Dodd JM. Methods of term labour induction for women with a previous caesarean section. Cochrane Database Syst Rev. 2013:CD009792. [[ PubMed] Google Scholar]

12. Dowswell T, Kelly AJ, Livio S, Norman JE, Alfirevic Z. Different methods for the induction of labour in outpatient settings. Cochrane Database Syst Rev. 2010:CD007701. [[ PMC free article] [ PubMed] Google Scholar]

15. Henry A, Madan A, Reid R, et al. Outpatient Foley catheter versus inpatient prostaglandin E2 gel for induction of labour: a randomised trial. BMC Pregnancy Childbirth. 2013;13:25. [[ PMC free article] [ PubMed] Google Scholar]

17. Wilkinson C, Adelson P, Turnbull D. A comparison of inpatient with outpatient balloon catheter cervical ripening: a pilot randomized controlled trial. BMC Pregnancy Childbirth. 2015;15:126. [[ PMC free article] [ PubMed] Google Scholar]

Articles from Singapore Medical Journal are provided here courtesy of Wolters Kluwer -- Medknow Publications

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Patient satisfaction with the cervical ripening balloon as a method for induction of labour: a randomised controlled trial

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Evidence has shown that balloon catheters are as effective as prostaglandins (PGE) in achieving vaginal delivery within 24 hours of the start of induction of labour (IOL), with lower rates of uterine hyperstimulation, and similar Caesarean section and ...

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Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials

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Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials

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Balloon labour induction and the price of elegance

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Balloon labour induction and the price of elegance

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Research Methods for Nurses and Midwives 

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Research Methods for Nurses and Midwives 

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Intrapartum interventions and outcomes for women and children following induction of labour at term in uncomplicated pregnancies: a 16-year population-based linked data study

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Intrapartum interventions and outcomes for women and children following induction of labour at term in uncomplicated pregnancies: a 16-year population-based linked data study

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Double-balloon catheter for induction of labour: Rates of caesarean birth and outcomes when used beyond 12 and 24 h

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Double-balloon catheter for induction of labour: Rates of caesarean birth and outcomes when used beyond 12 and 24 h

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