Learning Objectives:After participating in this continuing professional development activity, the provider should be better able to:

1. Identify indications for and contraindications to induction of labor.

2. Describe methods used for induction of labor, including medications and procedures.

3. Explain best practices for induction of labor in patients with special circumstances.

4. Define failed induction of labor.

Induction of labor is defined as the process of stimulating uterine contractions before the onset of labor with the goal of achieving a vaginal delivery.1 In 2020, over 31% of gravid patients in the United States underwent induction of labor, and this number has steadily increased over the past 10 years.2 Induction of labor is generally recommended when the benefits of delivery outweigh the risks of remaining pregnant.1 Given the growing number of patients undergoing induction of labor on a yearly basis, our aim is to review best practices for this process. We identify indications for and contraindications to induction of labor, summarize applicable medical and procedural methods, and consider special circumstances for patients undergoing induction, including those with a history of cesarean delivery, current intrauterine fetal demise (IUFD), or personal history of trauma. Lastly, we outline definitions of failed induction of labor with indications to consider an alternative timing or approach to delivery.

Indications

Induction of labor is indicated for many different maternal and fetal conditions, and may also be planned without underlying medical comorbidities for psychosocial indications, risk of precipitous delivery, or as an elective process. In each of these clinical scenarios, it is essential to weigh the maternal and neonatal risk of delivery with the risks of continuing pregnancy.

A prerequisite to scheduling an induction of labor is to confirm the patient's estimated due date (EDD). Last menstrual period (LMP) should be documented, and calculated EDD should ideally be concordant with dating by ultrasound. Ultrasound measurement in the first trimester is the most reliable method to establish an accurate gestational age and EDD, and should be used independently if LMP is unknown. If LMP and first-trimester ultrasound are unavailable, dating should be estimated by second or third-trimester ultrasound as available, but should be considered suboptimal, and taken into account when considering induction. Pregnancies resulting from in vitro fertilization should utilize the date of transfer and age of embryo to determine EDD.3

Recommendations for planned timing of induction of labor depend upon the indication for induction. Induction of labor should not be elected before 39⁰/₇ weeks of estimated gestational age (EGA) unless medically indicated.4

Common indications for induction and suggested timing based on weeks of gestation are summarized in Table 1, adapted from the American College of Obstetricians & Gynecologists Committee Opinion on Medically Indicated Late-preterm and Early-Term Deliveries.5 Preterm is defined as a pregnancy at less than 34⁰/₇ weeks of EGA. Late preterm is defined as 34⁰/₇ to 36⁶/₇ weeks of EGA, whereas early term is defined as 37⁰/₇ to 38⁶/₇ weeks of EGA. If induction of labor is medically indicated before 37⁰/₇ weeks of EGA, administration of antenatal corticosteroids for fetal lung maturity should be considered.5 Additional defined time frames when induction may also be indicated are full-term (39⁰/₇-40⁶/₇ weeks of EGA), late-term (41⁰/₇-41⁶/₇ weeks of EGA), and post-term pregnancies (³42⁰/₇ weeks).6 Induction of labor in a late-term pregnancy should be considered, whereas induction in post-term pregnancies is highly recommended due to a known increase in perinatal morbidity with continued gestation beyond 42⁰/₇ weeks of EGA.7

Table 1. Common Indications for Induction of Labor*

Further recommendations to consider induction of labor in patients at or beyond 39⁰/₇ weeks of EGA are actively evolving. In 2018, the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management) sought to delineate maternal and perinatal outcomes after induction of labor at 39 weeks in low-risk nulliparous women. This large multicenter study looked primarily at rates of perinatal death or severe neonatal complications in low-risk nulliparous women at 39 weeks 0 days to 39 weeks 4 days who underwent induction of labor versus expectant management. The main secondary outcome was the rate of cesarean delivery in each arm. This study demonstrated that induction of labor in low-risk nulliparous women did not result in a significantly lower frequency of adverse perinatal outcomes but did result in significantly lower rates of cesarean deliveries.8 Secondary analyses from this trial are anticipated, and further studies to evaluate the maternal and perinatal outcomes of induction of labor in expanded populations. Induction of labor in patients at or beyond 39⁰/₇ weeks of EGA can also be considered for psychosocial indications and in patients with a history of precipitous delivery with patient counseling and shared decision-making.

Contraindications

Any condition which would preclude a vaginal delivery would also be considered a contraindication to induction of labor. Examples can be considered in terms of maternal, fetal, and placental complications precluding vaginal birth, and are outlined in Table 2. This is not a comprehensive list, but includes more commonly encountered diagnoses.1,9

Table 2. Contraindications to Induction of Labor

Methods for Induction of Labor

Primary steps to begin an induction of labor depend upon the cervical examination. Providers can use the Bishop score (Table 3) to determine whether a cervix is favorable or unfavorable, with an unfavorable cervix being defined as a score of 6 or less.10

Table 3. Bishop Scoring System

Cervical Ripening

If the cervical examination is deemed unfavorable, cervical ripening should be initiated. Cervical ripening is a process of softening and thinning the cervix, which can improve the effectiveness of oxytocin administered later in the induction process.11 Cervical ripening can be accomplished by procedural approaches including membrane sweeping or stripping and mechanical dilation and by administration of prostaglandins.

Membrane Sweeping

Membrane sweeping or stripping is a process by which the amnion is separated from the lower uterine segment by sweeping the finger in a 360-degree fashion during a cervical digital examination. This procedure results in the release of endogenous prostaglandins and phospholipase A from the cervix and lower uterine segment, and can increase the likelihood of spontaneous labor within 48 hours. Further studies to determine the optimal timing and frequency of membrane sweeping are indicated.12

Mechanical Cervical Ripening

Proposed mechanisms of mechanical ripening include endogenous prostaglandin production through induction of a stretch force on myometrial cells and amnion that overlie the internal cervical os. Common methods of mechanical induction include use of a cervical Foley balloon catheter or osmotic dilators.13

Both single and double Foley balloon catheters are available for use in the induction of labor process. Double-balloon catheters incorporate a component that applies direct pressure to the external os. In a systematic review, the more costly double-balloon catheters were reported to result in higher pain scores, and did not demonstrate superior efficacy compared with single-balloon catheters.14 As such, use of single-balloon (Foley) catheters is recommended at this time. Balloon catheters are placed transcervically followed by inflation of the balloon tip with saline, generally between 30 and 60 mL, and traction is applied to the free end of the catheter.1,13 Data have demonstrated that balloon volumes greater than 30 mL can reduce time from induction to delivery.15 When the cervix has reached 3 to 4 cm dilated, the balloon is often expelled, typically achieving a favorable Bishop score.

Osmotic dilators, more commonly used for first and second-trimester pregnancy termination, achieve cervical dilation through the absorption of water and an associated expansion in diameter.1,13 Osmotic dilators may be associated with an increased risk of peripartum infections felt to be related to a longer duration of labor compared with alternative methods.16 Use of a balloon catheter may be a more optimal approach for induction of labor at later gestational ages if mechanical dilation is considered.

Pharmacologic Cervical Ripening

Misoprostol is a prostaglandin-E1 analogue used commonly as a pharmacologic induction agent. When used for induction of labor, misoprostol is most commonly administered orally or vaginally at doses of 25 to 50 [mu]g initially, followed by 25 [mu]g every 3 to 6 hours as per provider preference.1,9,17 Contraindications to misoprostol include more than 3 contractions in 10 minutes and previous uterine scar.1 Vaginal administration of misoprostol may result in a shorter interval to vaginal delivery as compared with the oral route.18 More recently, the Induction with MisoPRostol: Oral mucosa versus Vaginal Epithelium (IMPROVE) study compared the efficacy and safety of buccal versus vaginal administration of misoprostol. In this triple-blinded, placebo-controlled study, vaginal administration of misoprostol resulted in shorter time to vaginal delivery and a lower number of cesarean deliveries for nonreassuring fetal status compared with the buccal administration group.19 Although vaginal administration may have more favorable results, the need for repetitive vaginal examinations for placement by trained staff may limit its routine use.

An alternative cervical ripening agent is dinoprostone, an analogue of prostaglandin-E2. Dinoprostone is available as a vaginal gel or vaginal insert.1 In comparison with vaginal misoprostol, vaginal dinoprostone is associated with lower rates of uterine tachysystole, and the vaginal insert is readily removed if needed for nonreassuring fetal status. However, despite higher rates of uterine tachysystole with misoprostol, a parallel increase in adverse neonatal outcomes has not been reported.17 Further, when compared with dinoprostone, vaginal misoprostol is significantly less expensive and results in a shorter interval to vaginal delivery,17 and therefore may be a preferable agent for cervical ripening.

Outpatient Cervical Ripening

Prostaglandin analogues are not widely used for cervical ripening in the outpatient setting at this time due to perceived risks of uterine hyperstimulation and limited data regarding safety of administration without fetal surveillance.1,9 Cervical ripening with a Foley balloon, however, has been documented to be safe for use in the outpatient setting. A 2020 meta-analysis of available randomized controlled trials comparing inpatient versus outpatient Foley catheter induction demonstrated outpatient insertion was associated with a lower cesarean delivery rate and shorter hospital stay.20 Initiation of the induction process with cervical Foley insertion in the outpatient setting is an acceptable approach for select patients.

Nipple Stimulation

Nipple stimulation is an inexpensive method for labor induction, which offers women control during their induction course.1,21 This method has only been studied in low-risk pregnancies, and protocols vary with use of breast pumps for stimulation versus manual nipple stimulation. The goal of any approach is to cause regular uterine contractions. A 2005 Cochrane review evaluated breast stimulation for induction compared with no intervention, and noted an increased likelihood of entering labor in the stimulation group, which only reached statistical significance in patients with a favorable cervix. There was notably a significant reduction in postpartum hemorrhage in the nipple stimulation groups.21 Further study is needed to better delineate protocols for nipple stimulation, and safety and efficacy across patient populations.

Amniotomy

Amniotomy, also known as artificial rupture of membranes, can be performed during the cervical examination, typically after cervical ripening, to augment the induction process.1,9,22 This procedure performed before the onset of active labor is termed early amniotomy, whereas when performed during active labor is termed late amniotomy. A 2020 meta-analysis by De Vivo et al22 demonstrated that early amniotomy after cervical ripening may shorten the interval from induction start to delivery and was not associated with increased risk of cesarean delivery when compared with patients who underwent late amniotomy or spontaneous rupture of membranes. Amniotomy is not associated with increased pain, but may result in an increased risk of infection, abnormal fetal heart rate tracing, bleeding, and cord prolapse.23 As with all procedures, patients should be informed on the potential risks and benefits of amniotomy after cervical ripening as a part of the induction process.

Oxytocin

Oxytocin has been used since the early 1900s in the field of obstetrics when it was first identified to aid in postpartum hemorrhage and then used as a method to induce labor.24 Oxytocin is typically used either concurrently with mechanical ripening or after cervical ripening during induction. Protocols for oxytocin are generally categorized into low-dose and high-dose regimens. Low-dose regimens start at a dose of 0.5 to 2 mU/min and increase by 1 to 2 mU/min every 15 to 40 minutes. High-dose protocols start at a dose of 6 mU/min and increase by 3 to 6 mU/min every 15 to 40 minutes.1 High-dose regimens have been associated with an increased risk of uterine tachysystole, but associated adverse perinatal outcomes have not been demonstrated consistently across studies.25 Until further data are available on the safety profile of high-dose regimens, low-dose regimens should be considered. Hospital-specific protocols should be used for provider guidance on oxytocin administration for induction and augmentation of labor.

Combined Mechanical and Pharmacologic Approaches

Several studies have evaluated the efficacy and safety of combining mechanical and pharmacologic approaches to induction with results favoring a combined approach. Levine et al26 randomized patients to induction of labor initiated with vaginal misoprostol versus Foley catheter alone versus cervical Foley with concurrent administration of vaginal misoprostol versus cervical Foley with concurrent administration of oxytocin. Both combination methods achieved a faster time to delivery, and when adjusted for parity and censored for cesarean delivery, the cervical Foley-misoprostol combination was superior to both single-agent methods studied.26 Gomez et al27 compared vaginal and buccal administration of misoprostol combined with cervical Foley catheter placement for induction. Vaginal administration of misoprostol was notably superior to buccal administration in this study with a faster time to delivery and greater percentage of vaginal delivery within 24 hours. There were no significant differences in cesarean delivery rates or maternal or neonatal outcomes studied.27 Based on these reported outcomes, a combined mechanical and pharmacologic approach to induction should be considered when clinically feasible.

Special Considerations

Patients With Prior Cesarean Delivery

Patients who have a history of 1 or 2 cesarean deliveries remain candidates for induction of labor apart from those with a history of classical cesarean delivery, or cesarean delivery with extension into the active segment due to the increased risk of uterine rupture.28 Multiple studies have documented an increased risk of uterine rupture in patients with prior cesarean undergoing induction of labor compared with spontaneous labor, with a less than 2% risk in the former, and less than 1% risk in the latter. Despite the slightly higher risk of uterine rupture, benefits of vaginal delivery and avoidance of additional cesarean deliveries may favor induction. Recommendations for methods of induction in patients with a prior cesarean delivery are centered upon risks of uterine rupture. Prostaglandin analogues for cervical ripening have consistently demonstrated the highest risk of uterine rupture among available options,28,29 and are therefore not recommended in this patient population.1 The use of Foley catheters for induction in patients with prior cesarean deliveries is considered a safe alternative for ripening, as available studies have not demonstrated an increased risk of uterine rupture with Foley catheter induction.29 The use of oxytocin for induction and augmentation of labor in patients with a prior uterine scar has been studied with mixed results. When an increased risk of uterine rupture was documented, this risk remained small (~1.1%), and as such use of oxytocin may be considered with close monitoring in this patient population.28,29

Induction in Second- or Third-Trimester Intrauterine Fetal Demise

In the event of second- or third-trimester IUFD, options for management may include dilation and evacuation (depending on gestational age and provider experience), hysterotomy, or induction of labor. Mode of delivery is a shared decision between the patient and the provider, and involves a thorough discussion of all potential risks and benefits. If induction of labor is elected at less than 28 weeks of EGA, misoprostol in higher dosing regimens (400-600 [mu]g every 4-6 hours) is a recommended approach. As an additional adjunct, mifepristone administered 24 to 48 hours in advance of misoprostol initiation has been shown to reduce time to delivery when compared with misoprostol alone. In the event of a prior cesarean delivery involving the lower uterine segment, misoprostol induction may be considered in the second trimester. Optimal dosing regimens for this population have yet to be determined, but lower doses (200 [mu]g) may be considered. For women with or without a prior uterine scar, high-dose oxytocin regimens are an appropriate alternative if prostaglandins are not available.30 Beyond 28 weeks of EGA, the regimens described earlier for induction for a viable pregnancy are generally used for induction for IUFD.1

Trauma-Informed Care in Induction of Labor

In the care of all patients, it is important to acknowledge an individual's lived experiences, and past or ongoing traumatic events that impact their life narrative. Trauma can take many forms-intimate partner violence, sexual assault, separation from family, and racism-and has also been described related to prior difficult birth experiences. To build trust and create a safe environment for patients, all members of the care team should employ a trauma-informed approach to care.31 When considering an approach to induction of labor, a patient's history and preferences must be taken into account. Use of vaginally administered medications or placement of a cervical Foley may result in retraumatization for some patients, and can readily be avoided by opting for alternative regimens such as oral misoprostol. Shared decision-making in the process of induction of labor, as with all components of the birth process, is paramount to enabling a safe, secure experience for patients and their providers.

Failed Induction of Labor

The length of labor may be increased in patients undergoing induction of labor compared with those in spontaneous labor.9,32 Inductions declared as failed without adequate attempt at achieving a vaginal birth can lead to an increased incidence of primary cesarean deliveries. A failed induction may be declared in the latent phase of labor (<6-cm dilation) if a patient has not reached the goal of regular contractions and cervical change either after rupture of membranes and oxytocin administration for 12 to 18 hours, or with intact membranes and oxytocin administration for at least 24 hours.32 Maternal and fetal status should be closely monitored throughout with appropriate intervention to optimize perinatal outcomes as indicated.

Summary

Induction of labor is a safe and effective process to achieve vaginal birth when the benefits of delivery outweigh the risks of remaining pregnant. The incidence of induction of labor is steadily increasing with an anticipated continued rise pending further studies reporting on the risks and benefits of delivery after 39 weeks of EGA in broader populations. Providers who offer induction of labor should consider best practices for timing, methods for cervical ripening, and optimal regimens to promote regular contractions and cervical change. Special considerations should be recognized for patients with a prior uterine scar, and those undergoing induction for IUFD. All parts of the induction process should be followed with a trauma-informed lens, and shared decision-making between the patient and the provider. Understanding that inductions of labor may result in a longer interval to delivery compared with spontaneous labor and allowing adequate time for progression through the latent phase of labor with close maternal and fetal monitoring will optimize chances for a successful vaginal birth.

Practice Pearls

* Induction of labor is recommended when the benefits of delivery outweigh the risks of remaining pregnant.

* Indications for inductions of labor include maternal, fetal, or social/elective.

* Before proceeding with scheduling an induction of labor, it is imperative to have an accurate estimated due date.

* Methods to induce labor include cervical ripening with mechanical methods or prostaglandins, membrane sweeping, nipple stimulation, amniotomy, and oxytocin administration.

* The combination of mechanical cervical ripening with Foley balloon and prostaglandin or oxytocin administration has been demonstrated to have shorter time to delivery and a higher percentage of deliveries within 24 hours compared with single-method induction of labor.

* Patients with less than 2 prior cesarean deliveries, apart from those with a prior scar involving the active uterine segment, are candidates for induction of labor; prostaglandin analogues should be avoided in these patients due to increased risk of uterine rupture.

* A failed induction of labor should not be declared in the latent phase of labor on oxytocin until at least 12 to 18 hours after rupture of membranes, or at least 24 hours with intact membranes.

References