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Induction of Labor


Key Abbreviations

American College of Obstetricians and Gynecologists ACOG
Confidence interval CI
Electronic fetal monitoring EFM
Hazard ratio HR
Hemolysis/elevated liver enzymes/low platelets HELLP
Induction of labor IOL
Intrauterine growth restriction IUGR
National Institute of Child Health and Human Development NICHD
Neonatal intensive care unit NICU
Odds ratio OR
Premature rupture of membranes PROM
Prostaglandin PG
Prostaglandin E 1 (misoprostol) PGE1
Prostaglandin E 2 (dinoprostone) PGE2
Randomized clinical trial RCT
Relative risk RR
Society for Maternal-Fetal Medicine SMFM

Induction of Labor: Definition/Epidemiology

Induction of labor occurs by stimulating uterine contractions before the spontaneous onset of labor. Induction of labor is one of the most commonly performed obstetric procedures in the United States, with more than 23% of singleton births having undergone induction in 2012. Fig. 12.1 , from the National Center for Health Statistics, illustrates induction of labor rates over time from 1990 to 2012.

Fig. 12.1, Induction of Labor by Gestational Age: United States, 1990–2012.

Indications/Contraindications

The indications for induction of labor are not absolute, and induction should be undertaken only when the benefits of delivery to either mother or fetus outweigh the risks of pregnancy continuation. Clinical factors that should be taken into account when an induction is being considered are maternal and fetal condition, gestational age, and cervical examination status. However, induction of labor for medical indications should not be delayed based on cervical exam status. Many accepted medical and obstetric indications for labor induction exist ( Box 12.1 ). Contraindications include those that preclude vaginal delivery.

Box 12.1
Accepted Indications for Labor Induction

Maternal Medical Conditions

  • Hypertensive disorders (gestational hypertension, preeclampsia with or without severe features)

  • Chronic hypertension

  • Diabetes (pregestational or gestational)

  • Renal disease

  • Cholestasis

  • Hypercoagulable disorder (history of venous thromboembolism, acquired or inherited thrombophilia, sickle cell disease)

  • Systemic lupus erythematosus

Fetal Conditions

  • Fetal growth restriction

  • Alloimmunization

  • Oligohydramnios

  • Nonreassuring fetal testing

  • Multiple gestation

Elective

  • Prolonged pregnancy

  • Premature rupture of membranes

  • Chorioamnionitis

  • Abruptio placentae

Indications and contraindications for induction should be reviewed along with the alternatives. Risks and benefits of induction should be discussed with the patient (see later). Confirmation of gestational age is critical. Fetal weight should be estimated, clinical pelvimetry should be performed, and fetal presentation should be confirmed; in addition, a cervical examination should be performed and documented and labor induction should be performed at a location where personnel are available who are familiar with the process and its potential complications. Uterine activity and electronic fetal monitoring (EFM) are recommended for any gravida receiving uterotonic medications ( Box 12.2 ). Evaluation of fetal lung maturity status is controversial and in general not recommended. During the 2011 workshop entitled “Timing of Indicated Late-Preterm and Early-Term Birth” —sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and Society for Maternal-Fetal Medicine—the role of fetal lung maturity was reviewed. The consensus was that amniocentesis and assessment of fetal lung maturity should not alter delivery management if significant maternal or fetal risk warrants delivery. Conversely, since documented fetal lung maturity does not demonstrate that there will be lower nonrespiratory morbidity, fetal lung maturity alone should not be a reason to proceed with delivery if it could otherwise be safely delayed.

Box 12.2
Evaluation Before Induction of Labor

Maternal

  • Confirm indication for induction

  • Review contraindications to labor and/or vaginal delivery

  • Perform clinical pelvimetry to assess the shape and adequacy of the bony pelvis

  • Assess the cervical condition (assign Bishop score)

  • Review risks, benefits, and alternatives of induction of labor with the patient

Fetal/Neonatal

  • Confirm gestational age

  • Estimate fetal weight, either by clinical or ultrasound examination

  • Determine fetal presentation and lie

  • Confirm fetal well-being

Hypertensive Disorders

In women with mild gestational hypertension or preeclampsia without severe features, investigators in the Netherlands performed a large multi-center trial in which 756 patients with singleton gestations at 36 to 41 6/7 weeks of gestation were randomized to receive induction ( n = 377) or expectant monitoring ( n = 379). The primary outcome was a composite of adverse maternal outcomes and included eclampsia, HELLP (hemolysis/elevated liver enzymes/low platelets) syndrome, pulmonary edema, thromboembolic disease, placental abruption, progression to severe disease, and postpartum hemorrhage. Induction of labor was associated with a significant reduction in adverse maternal outcomes compared with expectant management, 31% versus 44% (RR 0.71, 95% CI 0.59 to 0.86, P = .0001). There was no difference in the frequency of neonatal complications or cesarean delivery. Based on these findings, The American College of Obstetricians and Gynecologists (ACOG) Hypertension Task Force recommended, to improve maternal outcomes, delivery at or beyond 37 0/7 weeks for mild gestational hypertension or preeclampsia without severe features rather than expectant management.

Prolonged Pregnancy

In a joint committee opinion, the ACOG and the Society for Maternal-Fetal Medicine (SMFM) discourage the use of the label term pregnancy and instead replaced it with the labels early term, full term, late term, and postterm . Postterm pregnancy (≥42 weeks of gestation) is associated with increased risks for the fetus and mother (see Chapter 29 ). According to a large epidemiologic study by Hilder and colleagues, the perinatal mortality rate—which combines stillbirths (fetal death after 20 weeks of gestation) and early neonatal deaths (death of a liveborn infant within the first 28 days of life)—at greater than 42 weeks of gestation is approximately twice that at term (4 to 7 deaths vs. 2 to 3 deaths per 1000 deliveries) and increases more than sixfold at 43 weeks of gestation and beyond.

Two large prospective population-based cohort evaluations of singleton pregnancies, with dating based on ultrasound, have been performed. Nakling and Backe found the incidence of postterm pregnancies (≥42 weeks) to be 7.6%, with 0.3% of pregnancies progressing to 301 days (43 weeks of gestation) if inductions were not permitted prior to 43 weeks. This investigation found a significantly increased rate of perinatal mortality after 41 weeks of gestation. Heimstad and colleagues also found an increased rate of intrauterine fetal demise at 42 weeks of gestation (1.55%) compared with that at 39 weeks (0.43%) and 38 weeks (0.25%), P = .03 for statistical trend. These studies have supported the older epidemiologic data that reported an increase in perinatal morbidity beyond 42 weeks. For these reasons, common practice has been to recommend delivery by 42 0/7 weeks.

Postterm pregnancy is also associated with increased maternal risks for pregnancies after 41 weeks, including an increase in labor dystocia, risk of cesarean, risk of hemorrhage, and an increase in severe perineal injury. Factors that may contribute to the increased rate of perinatal deaths, intolerance of labor, and risk of cesarean are uteroplacental insufficiency, meconium aspiration, fetal growth disturbances (both intrauterine growth restriction [IUGR] and macrosomia), and intrauterine infection.

Overall, comparisons of induction of labor versus expectant management in observational studies have found no difference in cesarean delivery among women who are induced or a decreased risk of same in such women. This is also true for women with an unfavorable cervix. Hannah et al. conducted a large multicenter trial comparing induction of labor at 41 weeks versus antenatal surveillance two to three times a week in uncomplicated singleton gestations dilated to 3 cm or less. Among 3407 women, 360 of 1701 (21.2%) underwent cesarean in the induction group compared with 418 of 1706 (24.5%) in the monitoring group ( P = .03) with no difference in perinatal mortality and neonatal morbidity. A meta-analysis revealed that women at less than 42 0/7 weeks of gestation who underwent induction of labor had a lower cesarean delivery rate than those who received expectant management. In this meta-analysis, 11 randomized controlled trials (RCTs) and 25 observational studies were included and expectant management of pregnancy was associated with higher odds of cesarean delivery than was induction of labor (OR, 1.22; 95% CI,1.07 to 1.39). Also, in a 2012 Cochrane meta-analysis of 22 RCTs including 9383 women that compared induction of labor in term/posterm pregnancies versus expectant management, induction was associated with decreased perinatal death (RR, 0.31; 95% CI, 0.12 to 0.88), cesarean delivery (RR, 0.89; 95% CI, 0.81 to 0.97), and meconium aspiration syndrome (RR, 0.50; 95% CI, 0.34 to 0.73). Based on all of this information, labor induction between 41 0/7 weeks and 42 0/7 weeks should be considered for women who remain undelivered by this gestational age. Induction after 42 0/7 weeks and no later than 42 6/7 weeks is recommended to reduce the risk of perinatal morbidity and mortality.

Non–medically Indicated (Elective) Induction

Non–medically indicated induction of labor refers to the initiation of labor in an individual with a term pregnancy who is free of medical or obstetric indications. Although previously not recommended, non–medically indicated induction of labor at or after 39 weeks may be appropriate and acceptable based on newer data. Conversely, non–medically indicated induction of labor prior to 39 weeks of gestation remains contraindicated.

The results of studies demonstrating an increased frequency of respiratory morbidity of infants induced prior to 39 weeks of gestation supports avoiding non–medically indicated inductions prior to that gestational age. A large study by Tita and colleagues of 19 centers in the Maternal Fetal Medicine Units Network evaluated patients undergoing elective cesarean delivery without any clear medical indication at less than 39 weeks versus at or after 39 weeks. The primary outcome was a composite adverse neonatal outcome including death, treated hypoglycemia, respiratory complications, sepsis, and admission to a neonatal intensive care unit (NICU). Birth at 37 or 38 weeks was associated with an increased risk of the primary adverse neonatal outcome ( Fig. 12.2 ). A recent secondary analysis of elective early-term births in a large observational study demonstrated that there were worse neonatal outcomes even with confirmation of pulmonary maturity.

Fig. 12.2, Weeks of Gestation at Delivery.

“Impending” macrosomia, a favorable cervix, an increased risk for preeclampsia (such as having a prior history of preeclampsia), or concerns about intrauterine growth restriction (e.g., a fetus with an estimated weight at the 19th percentile) are not accepted medical indications for induction prior to 39 weeks. Additionally, preterm or early-term induction is not medically indicated for maternal anxiety or discomfort related to normal pregnancy, previous pregnancy with labor abnormalities such as rapid labor or shoulder dystocia, or simply because the mother lives far from the hospital.

Previously, concerns have been raised that induction of labor increases the rate of cesarean delivery as well as health care costs. However, these conclusions were based on a faulty comparison of women who are induced with those in spontaneous labor. In fact, most observational studies that compare induction of labor with expectant management—which is the actual clinical alternative to labor induction—have found either no difference or a decreased risk of cesarean delivery among women who are induced. In addition, several RCTs have been undertaken. In a systematic review by Caughey and colleagues, nine RCTs were evaluated in which women undergoing expectant management were compared with those electively induced. This meta-analysis revealed an increased risk of cesarean delivery in the expectant management group compared with the induction group (RR, 1.22; 95% CI, 1.07 to 1.39). Similarly, a Cochrane review examined 19 trials that included 7984 women and found that women induced at 37 to 40 completed weeks were less likely to have a cesarean delivery than those in the expectant management group (RR, 0.58; 95% CI, 0.34 to 0.99). In an observational study, Caughey and colleagues also examined the risk of cesarean delivery for each week of gestational age ranging from 38 to 41 weeks. In their retrospective study, which again compared induction with expectant management, cesarean delivery was decreased in the induction groups. With regard to perinatal outcomes, it appears that fewer electively induced infants have meconium passage and therefore likely have a reduced incidence of meconium aspiration syndrome. Macrosomia may also be reduced, as noted in an ecologic study performed by Zhang and colleagues. This study revealed that the increased induction rate between 1992 and 2003 (14% to 27%) was significantly associated with reduced mean fetal birthweight ( r = −0.54; 95% CI, −0.71 to −0.29) and rate of macrosomia ( r = −0.55; 95% CI, −0.74 to −0.32).

The most recent study demonstrating the potential benefit of non–medically indicated induction of labor was the ARRIVE study, performed by the Maternal Fetal Medicine Unit Network by Grobman and colleagues. In this study 6106 nulliparous women at 41 hospitals with no medical indication for delivery were randomized to either planned induction of labor at 39 0/7 to 39 4/7 weeks or expectant management. The primary outcome was a composite of adverse perinatal events. The proportion of neonates with the primary perinatal outcome was lower in the induction group than in the expectant-management group (4.3% vs. 5.4%, RR, 0.80; 95% CI, 0.64 to 1.00; P = .049). The rate of cesarean delivery was also decreased in the induction of labor group (18.6% vs. 22.2%, RR, 0.84; 95% CI, 0.76 to 0.93) along with the rate of preeclampsia/gestational hypertension (9.1% vs. 14.1%; RR, 0.94; 95% CI, 0.56 to 0.74). There were no differences in the magnitudes of association of induction with either the primary perinatal outcome or cesarean delivery regardless of cervical status, body mass index (BMI), maternal age, or race/ethnicity. The number needed to treat to prevent one cesarean was 28, to prevent one baby requiring neonatal respiratory support was 83, and to prevent one woman with hypertensive disorder was 20. This large randomized trial suggests that offering induction of labor to nulliparous women after 39 0/7 weeks is acceptable and may, in fact, be associated with decreased maternal and perinatal risks.

Prediction of Labor Induction Success/Failure

The cervical examination status, often referred to as the Bishop score, was developed by Bishop in 1964 as a prelabor scoring system to assess the likelihood of going into spontaneous labor; it was not originally intended to be used to evaluate patient for the success of induction. The Bishop score is the system most commonly used in clinical practice in the United States to evaluate the cervix prior to induction. It tabulates a score based on the station of the presenting part and four characteristics of the cervix: (1) dilation, (2) effacement, (3) consistency, and (4) position ( Table 12.1 ). The modified Bishop score, which gives double the amount of points for cervical dilation, was developed by Lange et al. in 1982 and incorporates only three components of the original Bishop score (station, cervical dilation, and cervical length) ( Table 12.2 ). The modified Bishop score has since been used in numerous trials on induction of labor.

TABLE 12.1
Traditional Bishop Score System
SCORE
Parameter 0 1 2 3
Dilation (cm) Closed 1–2 3–4 ≥6
Effacement (%) 0–30 40–50 60–70 ≥80
Length (cm) ≥3 2–3 1–2 <1
Station −3 −2 −1, 0 +1, +2
Consistency Firm Medium Soft —
Position Posterior Midposition Anterior —

TABLE 12.2
Modified Bishop Score System
SCORE
Parameter 0 1 2 3
Station (cm) −3 −2 −1, 0 +1, +2
Effacement (%) 0–30 40–50 60–70 ≥80
Length (cm) ≥3 2–3 1–2 <1
SCORE
0 2 4 6
Dilation (cm) 0 1–2 3–4 >4

Studies have evaluated cutoffs to determine favorability of the cervix prior to induction of labor. As an example, a study conducted from 1997 to 1999 of 4635 spontaneous and 2647 induced labors in nulliparous women at term reported that the cesarean delivery rates were almost doubled for women with induced labors with Bishop scores below 5 compared with those with Bishop scores of 5 or higher (32% vs. 18%). In general a Bishop score of 6 or below is considered unfavorable, and cervical ripening should be considered prior to starting an induction of labor since these women are at higher risk for a cesarean. A Bishop score of 8 or above means that the probability of a vaginal delivery after an induction is equivalent to spontaneous labor and that the value of cervical ripening is less clear. It should be noted, however, that although an unfavorable cervix implies an increased chance of a cesarean after labor induction, it does not signify that the risk is raised specifically because of the labor induction. As noted earlier, an unfavorable cervix (for example at term) has been demonstrated in randomized trials to serve as a more general marker of the risk of cesarean delivery regardless of whether labor induction or expectant management is undertaken.

Numerous observational studies have evaluated risk factors for cesarean among women undergoing an induction of labor. The most common demographic and clinical factors identified are maternal age, higher BMI, greater gestational age, height, race, parity, neonatal birthweight, and unfavorable cervical examination. These are, however, risk factors for cesarean among women who present in spontaneous labor as well, thereby limiting the ability to truly predict risk of cesarean specifically for induced women.

To date there have been two studies that specifically evaluated the utility of combining known clinical factors in an effort to predict the success of labor induction. In one retrospective study of 785 nulliparous women undergoing a term induction of labor, Tolcher et al. identified older maternal age, shorter maternal height, greater BMI, greater weight gain, older gestational age, hypertension, diabetes, and initial cervical dilation of less than 3 cm to be risk factors for cesarean. They created a nomogram with an area under the curve of 0.709 (95% CI, 0.67 to 0.75), which has not yet been validated. Levine et al. also evaluated risk factors for cesarean after induction; however, they limited their analysis to term women with singleton pregnancies and an unfavorable cervical exam (Bishop score ≤6 and cervical dilation ≤2 cm). They also excluded any woman with ruptured membranes. They found that the following five factors were predictors of cesarean delivery: shorter maternal height, increasing BMI, nulliparity, gestational age greater than 40 weeks, and modified Bishop score. They derived a predictive model and nomogram ( Fig. 12.3 ) that went through both internal and external validation. They created a calculator that can be found online at http://www.uphs.upenn.edu/labor-induction-calculator/ . It should be noted that this calculator provides information as to the risk of cesarean with induction but does not convey who will have a lower chance of cesarean with expectant management.

Fig. 12.3, Nomogram.

Other attempts to use biomarker and sonographic assessments to predict the success of induction have had limited success. Elevated fetal fibronectin (fFN) concentration in cervicovaginal secretions has been thought to represent a disruption or inflammation of the chorionic-decidual interface and could plausibly be associated with successful induction. Nevertheless, studies that have evaluated fFN have demonstrated its limited ability to add substantively to the capacity of other clinical markers to predict induction success. For example, although Crane et al. found that fFN was associated with successful induction, it was not determined to be superior to Bishop score. Cervical length by ultrasound assessment at the time of induction has also had mixed results, with no studies demonstrating definitive improvement in prediction accuracy over cervical examination and Bishop score alone. The lack of clinical utility over Bishop score alone was confirmed in a recent large meta-analysis of 31 prospective studies that included 5029 women.

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