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Induction of labor with oxytocin

Induction of labor with oxytocin
Author:
William Grobman, MD
Section Editor:
Charles J Lockwood, MD, MHCM
Deputy Editor:
Vanessa A Barss, MD, FACOG
Literature review current through: Jun 2022. | This topic last updated: Jul 11, 2022.

INTRODUCTION — Induction of labor refers to techniques for stimulating uterine contractions to accomplish delivery prior to the spontaneous onset of such contractions. Clinicians recommend induction to patients when they believe allowing the pregnancy to continue is at least as risky for the mother and/or fetus/newborn as delivery.

Use of oxytocin for induction in patients with an unscarred uterus will be discussed here. Methods of cervical ripening and induction in patients with a scarred uterus (eg, a previous cesarean birth or other extensive transmyometrial surgery) are reviewed separately.

(See "Induction of labor: Techniques for preinduction cervical ripening".)

(See "Cervical ripening and induction of labor in women with a prior cesarean birth".)

PREVALENCE — The frequency of labor induction in the United States was 31.4 percent in 2020, more than tripling since 1990 when it was 9.5 percent [1]. World Health Organization data, which included 373 health-care facilities in 24 countries, showed that approximately 10 percent of births involved labor induction [2]. However, these data were from 2010; robust recent global data are not available.

INDICATIONS AND CONTRAINDICATIONS

Medical and obstetric indications — Delivery before the onset of spontaneous labor is indicated when the maternal/fetal risks associated with continuing the pregnancy are thought to be at least as great as the maternal/fetal/newborn risks associated with delivery [3]. The risk of continuing the pregnancy is influenced primarily by the severity of the maternal/fetal condition and the risk of delivery is influenced primarily by the gestational age (ie, newborn risks from early birth). The relative risk rarely can be determined with precision. When delivery before the onset of spontaneous labor is desired, induction of labor and cesarean birth are the only available options. Induction is generally preferred when there are no contraindications to labor and vaginal birth, given the increased maternal risks associated with cesarean birth. (See 'Contraindications' below and "Cesarean birth: Postoperative issues".)

Examples of some common conditions where induction is often medically/obstetrically indicated include, but are not limited to, the following [3]:

Postterm pregnancy (see "Postterm pregnancy")

Prelabor rupture of membranes (see "Preterm prelabor rupture of membranes: Clinical manifestations and diagnosis" and "Prelabor rupture of membranes at term: Management")

Hypertensive disorders – Preeclampsia; eclampsia; HELLP syndrome (hemolysis, elevated liver enzymes, low platelets); gestational hypertension; chronic hypertension (see "Preeclampsia: Management and prognosis" and "Eclampsia" and "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)" and "Gestational hypertension" and "Chronic hypertension in pregnancy: Preconception, pregnancy, and postpartum issues and management")

Diabetes (see "Pregestational (preexisting) diabetes mellitus: Obstetric issues and management" and "Gestational diabetes mellitus: Obstetric issues and management")

Fetal growth restriction (see "Fetal growth restriction: Evaluation and management", section on 'Timing of delivery')

Twins (see "Twin pregnancy: Labor and delivery")

Chorioamnionitis (see "Intraamniotic infection (clinical chorioamnionitis)")

Placental abruption (see "Acute placental abruption: Management and long-term prognosis")

Oligohydramnios (see "Oligohydramnios: Etiology, diagnosis, and management")

Intrahepatic cholestasis of pregnancy (see "Intrahepatic cholestasis of pregnancy")

Alloimmunization with fetal anemia (see "RhD alloimmunization in pregnancy: Management" and "Management of non-RhD red blood cell alloantibodies during pregnancy")

Fetal demise (see "Stillbirth: Maternal care")

Some other maternal disease states and fetal anomalies also warrant labor induction. These are discussed in UpToDate topics that review management of specific maternal and fetal disorders.

Contraindications — In each of the following settings, there is general consensus that the maternal/fetal risks associated with labor and vaginal birth, and therefore induction, are greater than the risks associated with cesarean birth; therefore, induction of labor is contraindicated.

Prior classical or other high-risk cesarean incision (see "Choosing the route of delivery after cesarean birth", section on 'Prior transfundal uterine incision')

Prior uterine rupture (see "Choosing the route of delivery after cesarean birth", section on 'Prior uterine rupture or dehiscence')

Prior extensive complete transmural uterine incision (see "Uterine fibroids (leiomyomas): Issues in pregnancy", section on 'Patients with prior myomectomy')

Active genital herpes simplex infection (see "Genital herpes simplex virus infection and pregnancy", section on 'Route of delivery')

Placenta previa or vasa previa (see "Placenta previa: Management" and "Velamentous umbilical cord insertion and vasa previa")

Umbilical cord prolapse or persistent funic presentation (see "Umbilical cord prolapse")

Transverse fetal lie (see "Transverse fetal lie")

Invasive cervical cancer (see "Cervical cancer in pregnancy", section on 'Considerations about delivery')

Category III fetal heart rate tracing (see "Intrapartum category I, II, and III fetal heart rate tracings: Management", section on 'Category III pattern')

"Elective" induction — An induction traditionally has been considered "elective" when there is no medical indication that suggests that the benefits of delivery clearly outweigh the risks. Although in the past an induction of labor in low-risk patients at 39 weeks was called "elective," some have advocated a terminology change given data (discussed below) that suggest outcomes are at least as good as, if not in some cases better than, expectant management [4].

Elective induction at ≥39 weeks

Overview — Based on randomized trials and observational studies in which patients undergoing induction at ≥39 weeks were compared with those undergoing expectant management, it appears that labor induction among low-risk patients at ≥39 weeks who have well-dated pregnancies is a reasonable option. Potential advantages include [5-13]:

Reduction in cesarean birth

Reduction in other adverse neonatal and maternal outcomes (eg, preeclampsia)

Reduction in macrosomia (and its consequences)

Reduction in stillbirth

Ability to control the time of birth when this could be important (eg, patients with a history of rapid labor or who live far from the hospital and thus risk of out-of-hospital birth)

Evidence

In the multicenter ARRIVE trial, which evaluated the perinatal and maternal consequences of planned induction of labor at 39+0 to 39+4 weeks of gestation versus expectant management in over 6100 low-risk nulliparous patients across the United States, induction resulted in [9]:

Reduced risk of cesarean birth (18.6 versus 22.2 percent, relative risk [RR] 0.84, 95% CI 0.76-0.93).

Reduced risk of hypertensive disorders of pregnancy (9.1 versus 14.1 percent, RR 0.64, 95% CI 0.56-0.74).

Reduced risk of neonatal respiratory support (3.0 versus 4.2 percent, RR 0.71, 95% CI 0.55-0.93).

A statistically similar frequency of the composite outcome of perinatal death or severe neonatal complications (4.3 versus 5.4 percent, RR 0.80, 95% CI 0.64-1.00).

Planned secondary analyses of data from the ARRIVE trial found that, compared with patients assigned to expectant management, patients induced at 39 weeks had [11-13]:

Fewer antepartum visits, tests, and treatments

Longer duration on the labor and delivery unit (by approximately six to seven hours)

Shorter postpartum maternal and neonatal hospital durations

Similar total costs

The lowest rate of cesarean birth: 17.3 percent at 39 weeks, 22 percent at 40 weeks, and 37.5 percent at 41 to 42 weeks of gestation

The lowest rate of a composite adverse perinatal outcome: 5.1 percent at 39 weeks, 5.9 percent at 40 weeks, and 8.2 percent at 41 to 42 weeks of gestation. The composite outcome included death, respiratory support, five-minute Apgar score 3 or less, hypoxic ischemic encephalopathy, seizure, sepsis, meconium aspiration syndrome, birth trauma, intracranial or subgaleal hemorrhage, or hypotension requiring vasopressor support.

Data from observational studies support the concept that elective induction of labor among nulliparous patients at 39 weeks in typical clinical settings has an effectiveness similar to the efficacy demonstrated in the ARRIVE study. For example, in a 2019 meta-analysis of six cohort studies in which the pregnancy outcomes of >66,000 patients undergoing elective labor induction at 39 weeks were compared with those of >584,000 patients undergoing expectant management beyond that gestational age, elective induction was associated with a significantly lower risk of cesarean birth, maternal peripartum infection, and adverse perinatal outcomes (respiratory morbidity, intensive care unit admission, perinatal mortality) [10].

Long-term outcome data regarding the outcomes of children born after elective induction versus expectant management are limited. In one study, third-grade math and reading scores were similar among those born after induction at 39 weeks of gestation and those born after expectant management beyond that gestational age in a United States population [14]. However, because inductions were for both elective and medical indications, these results may be biased toward the null (ie, making outcomes of expectant management appear more favorable).

In a cohort study from Australia that focused specifically on elective birth at 39 weeks, developmental outcomes at four to six years of age were similar to those born after that gestational age, regardless of whether the elective delivery occurred after labor induction or scheduled cesarean [15]. In another Australian study, the results of a literacy and numeracy test at eight years of age also were similar regardless of whether elective induction was undertaken at 39 weeks or the patient was managed expectantly [16].

Recommendations of selected groups

The American College of Obstetricians and Gynecologists (ACOG) has concluded that offering elective induction of labor to low-risk nulliparous patients at ≥39+0 weeks of gestation is a reasonable option that patients and their obstetric providers should discuss, with consideration of available resources [17]. These recommendations apply to well-dated pregnancies. ACOG recommends against elective induction of suboptimally dated pregnancies [18]. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight", section on 'Suboptimally dated pregnancies'.)

In addition, ACOG has stated that maternal anxiety or discomfort related to normal pregnancy, the distance between the patient’s residence and the hospital, or a previous pregnancy with shoulder dystocia are not appropriate indications for early-term induction (37+0 to 38+6 weeks) [19], although they may be appropriate reasons for induction at ≥39+0 weeks.

The Society for Maternal-Fetal Medicine also concluded that it is reasonable to offer elective induction to low-risk nulliparous patients who are ≥39+0 weeks of gestation and recommended that providers who choose this approach ensure that patients meet the eligibility criteria of the ARRIVE trial [20].

Elective induction before 39 weeks — Elective induction before 39+0 weeks of gestation should be avoided [19,21]. The morbidity of birth before 37+0 weeks (ie, preterm birth) is well-established; early-term birth (37+0 to 38+6 weeks) is also associated with greater neonatal morbidity and health care utilization during the entire first year of life compared with birth at 39+0 to 40+6 weeks [22-28].

To emphasize the importance of avoiding elective induction before 39+0 weeks, the National Quality Forum, the Joint Commission, and the Leapfrog Group made elective delivery prior to 39+0 weeks a maternal performance measure ("the 39 week rule") and collect data from hospitals on elective deliveries performed at 37+0 to 38+6 weeks of gestation [29].

PREINDUCTION ASSESSMENT AND PATIENT PREPARATION

Checklist — A thorough evaluation of maternal and fetal status is important before undertaking labor induction to make sure the indication is appropriate and to confirm the absence of contraindications to labor or vaginal birth:

Review the data used to estimate gestational age and date of delivery, given that gestational age is a factor that is considered in timing of induction.

Determine fetal presentation.

Estimate fetal weight, given the risks associated with a small or large for gestational age birth weight.

Perform a cervical examination to decide whether a cervical ripening agent is indicated.

Review the fetal heart rate pattern to confirm that the use of ripening agents or oxytocin is not contraindicated.

Patient preparation and laboratory tests — Patient preparation and laboratory tests are generally the same as in patients in spontaneous labor (which includes a review for risk factors for problems that may develop during labor and birth [eg, past history of shoulder dystocia, postpartum hemorrhage]). In addition to standard preparation,

The indications for and alternatives to induction, planned drugs and procedures including side effects and complications, and the possibility of cesarean birth should be discussed. (See "Labor and delivery: Management of the normal first stage".)

A ripening process is generally employed prior to administering oxytocin in patients with an unfavorable cervix to shorten the duration of labor. Procedures to promote cervical ripening, especially administration of prostaglandins, may initiate labor and obviate the need for oxytocin [30]. (See "Induction of labor: Techniques for preinduction cervical ripening", section on 'Prostaglandins'.)

ASSESSING THE CHANCE OF A SUCCESSFUL INDUCTION

Clinical assessment — The likelihood that induction will result in vaginal birth depends on both cervical and noncervical factors.

A favorable cervix is associated with a shorter duration of induction and higher likelihood of vaginal birth whereas the converse is true when the cervix is unfavorable [31,32]. However, it should be noted that an unfavorable cervix does not mean that avoiding labor induction and managing the patient expectantly will result in a higher chance of vaginal birth; patients with unfavorable cervixes are still at increased risk for cesarean birth with expectant management, and the ARRIVE trial demonstrated that the cesarean birth rate was lower with induction regardless of cervical status.

Noncervical factors associated with a higher chance of successful induction (as well as with higher chance of vaginal birth after spontaneous labor) include [33-36]:

Multiparity

Ruptured membranes

Lower body mass index (BMI)

Taller height

Lower estimated fetal weight

Absence of comorbidities associated with placental insufficiency (eg, preeclampsia)

In preterm gestations, a study of labor induction using data from the National Institute of Child Health and Human Development Consortium on Safe Labor found that multiparity was the best predictor of vaginal birth (multiparity versus nulliparity: odds ratio [OR] 6.8, 95% CI 6.4-7.2, n = 6555 patients) [37]. Higher gestational age also was associated with vaginal birth: Patients <34 weeks of gestation were less likely to give birth vaginally than those ≥34 weeks of gestation; nevertheless, 57 percent of patients induced at 24 to 28 weeks, 54 percent of those induced at 28 to 31 weeks, and 67 percent of those induced at 31 to 34 weeks had a vaginal birth.

Bishop score — The Bishop score is the cervical assessment system most commonly used in clinical practice in the United States [38]. Despite its limitations, it appears to be as, or more, predictive of successful induction than fetal fibronectin [33] or sonographic measurement of cervical length [39]. Cervical scoring systems other than the Bishop score exist but are rarely used for predicting labor outcome (eg, Fields system; Burnett, Caldor, and Friedman modifications of the Bishop system [40]).

The Bishop score is based on the station of the presenting part and four cervical characteristics: dilation, effacement, consistency, and position (table 1). Cervical dilation is considered to be the most important of the five scoring elements [33].

There is no universally accepted threshold for a favorable or unfavorable score. Higher Bishop scores are associated with a higher chance of vaginal birth [38,41-43], while lower Bishop scores have been associated with a higher chance of cesarean birth [34]. Using the Bishop scoring system, most obstetricians consider a score ≥6 as favorable and a score ≤3 as unfavorable; scores of 4 or 5 are in a gray zone. If the cervix is favorable, oxytocin is administered without cervical ripening. If the cervix is unfavorable, cervical ripening is recommended. (See "Induction of labor: Techniques for preinduction cervical ripening".)

Of note, a simplified Bishop scoring system appears to be as predictive as the original system. In a cohort of over 5400 nulliparas undergoing labor induction at term, only dilation, station, and effacement, which represent three of the original five characteristics comprising the Bishop score, were significantly associated with vaginal birth [44]. For predicting successful labor induction (defined as achieving vaginal birth), a simplified Bishop score using these three components had similar or better positive predictive value (87.7 versus 87.0 percent), negative predictive value (31.3 versus 29.8 percent), positive likelihood ratio (2.3 versus 2.2), and correct classification rate (51.0 versus 47.3 percent) compared with the conventional Bishop score.

Nonprognostic factors

The time of day when induction is started does not appear to be an important independent factor in success [45].

Early administration of neuraxial analgesia does not appear to lower the chance of vaginal birth [46]. (See "Adverse effects of neuraxial analgesia and anesthesia for obstetrics", section on 'Effects on the progress and outcome of labor'.)

Several investigators have attempted to derive models to predict the chance that induction will result in cesarean birth [47-50]. One group developed an internet-based calculator to estimate this risk for patients at term with an unfavorable cervix [47]. A different group developed a seven-variable calculator, which is also available online [48]. A third group developed calculators for nulliparas with term and preterm pregnancies, which are available online and as a mobile app [49]. The area under the curve (AUC) in an external validation cohort of the first two models was 0.75 [48] and 0.77 [47] in a systematic review, and these were among the three models with the best discriminative capacity [51]. (Note: A perfect test has an AUC equal to 1.0 whereas a test that performs no better than chance would have an AUC of 0.5.)

The usefulness of these calculators in clinical practice remains uncertain. The overall predictive value of the best models is modestly better than a coin toss. Also, they were developed to evaluate the chance that a cesarean might occur if an induction were undertaken and not to indicate which patients would have a higher chance of vaginal birth if they were expectantly managed rather than induced. Similarly, they may not provide information as to which patients would have lower morbidity by avoiding labor altogether. Thus, before routine introduction into clinical practice, the benefit of their use needs to be proven.

INDUCTION PROCEDURE

Uterine and fetal heart rate monitoring — When oxytocin is administered, uterine activity and fetal heart rate (FHR) should be continuously monitored so that the dose can be adjusted based on labor progress, uterine activity, and the FHR pattern.

Oxytocin administration — Synthetic oxytocin administration is the most common and proven method of labor induction [52,53]. In a 2016 network meta-analysis of labor induction methods, use of intravenous (IV) oxytocin plus amniotomy and use of vaginal misoprostol were the two approaches most likely to achieve vaginal birth within 24 hours [54].

Pharmacology/pharmakokinetics — Exogenous oxytocin administration produces periodic uterine contractions first demonstrable at approximately 20 weeks of gestation. Myometrial responsiveness increases with advancing gestational age until 34 weeks, at which time it levels off until spontaneous labor begins, when it increases rapidly [55]. Increases in myometrial sensitivity are due primarily to increases in myometrial oxytocin receptor binding sites [56]. Receptor activation triggers signaling events that stimulate contractions, primarily by elevating intracellular calcium levels [57].

Oxytocin cannot be administered orally because the polypeptide is degraded into small, inactive forms by gastrointestinal enzymes. Thus, it is administered intravenously; via this route, its plasma half-life has been estimated to be three to six minutes [58]. Low-dose oxytocin protocols are based on studies showing approximately 40 minutes are required for any particular dose of oxytocin to reach a steady-state concentration and maximal uterine contractile response [59]. (See 'Dose titration' below.)

Progress during spontaneous labor is not related to increasing oxytocin concentration, uterine contractions are not associated with changes in plasma oxytocin concentration, and hypocontractile labor does not appear to be the result of a deficit of oxytocin [60]. However, variations in genes related to the oxytocin receptor appear to be associated with the amount of oxytocin required during induction and the duration of labor [61].

Timing — Timing of initiation of oxytocin administration is only an issue in patients who have received prostaglandins for cervical ripening. In such patients, oxytocin can be initiated, if indicated:

6 to 12 hours after the final dose of dinoprostone gel

30 minutes after removal of dinoprostone insert

4 hours after the final misoprostol dose

In patients who had cervical ripening with a balloon catheter, oxytocin can be initiated while the catheter is in place or after it has been removed. Oxytocin can also be initiated concurrently with amniotomy. (See 'Amniotomy' below and "Induction of labor: Techniques for preinduction cervical ripening", section on 'Procedure'.)

Infusion pump — Oxytocin is administered intravenously by an infusion pump to allow continuous, precise control of the dose administered. We suggest hospitals implement a standardized protocol to minimize errors in oxytocin administration [62-64]. (See "Reducing adverse obstetric outcomes through safety sciences", section on 'Oxytocin administration'.)

A common regimen is to make a solution of 60 units oxytocin in 1000 mL crystalloid (60 milliunits in one mL) to allow the infusion pump setting (mL/hour) to match the dose administered (milliunits/minute) (eg, a pump infusion rate of 1 mL/hour equals 1 milliunit/minute).

Dose — Oxytocin dosing regimens vary among and within countries [65], differing in initial dose (0.5 to 6 milliunits/minute), time period between dose increments (10 to 60 minutes), and maximum dose (16 to 64 milliunits/minute) [62]. The regimens are categorized as either high or low dose.  

High- versus low-dose regimens — Examples of high- and low-dose oxytocin infusion regimens for induction or augmentation of labor are described in the table (table 2). Either approach is acceptable as the regimen that achieves optimal maternal and perinatal outcomes has not been identified.

Available evidence is insufficient to allow a clear conclusion as to whether using a high- versus a low-dose regimen alters the cesarean birth rate or substantively alters other maternal or neonatal outcomes, although the data do suggest that the length of labor and some outcomes, such as risk of chorioamnionitis, may be lower with higher-dose regimens:

In a meta-analysis of nine randomized trials (2391 participants) comparing high- versus low-dose oxytocin regimens for induction of labor, using a high-dose regimen appeared to reduce the induction-to-delivery interval (mean difference in the overall group: -0.90 hours, 95% CI -2.28 to + 0.49; mean difference on sensitivity analysis limited to high quality trials: -1.94 hours, 95% CI -0.99 to -2.89), but there was no clear effect on risk for cesarean birth (RR 0.96, 95% CI 0.81-1.14) [66]. Although high-dose regimens resulted in a higher rate of tachysystole, maternal and perinatal complication rates were similar for both regimens.

In a subsequent large randomized double-blind trial comparing high- (initial and incremental rates of 6 milliunits/min) with standard-dose (initial and incremental rates of 2 milliunits/min) oxytocin augmentation in 1002 nulliparous patients, the cesarean birth rate was approximately 14 percent for both groups (relative risk [RR] 1.01; 95% CI 0.75-1.37), but the high-dose group had a shorter mean labor duration (9.1 versus 10.5 hours; mean difference -1.4 hours, 95% CI -2.2 to -0.6) and lower incidence of chorioamnionitis (10.4 versus 15.6 percent; RR 0.67, 95% CI 0.48-0.92), with a trend toward less umbilical artery acidemia (RR 0.55, 95% CI 0.29-1.01) [67].

Dose titration

Goal – For both high- and low-dose oxytocin regimens, the dose is typically increased until labor progress is normal or uterine activity reaches at least 200 to 250 Montevideo units (ie, the peak strength of contractions in mmHg measured by an internal monitor multiplied by their frequency per 10 minutes).

The dose should be adjusted as needed to achieve a pattern to avert tachysystole. The occurrence of adverse effects, such as sustained FHR abnormalities and tachysystole, should lead to a dose reduction until they resolve.

Maximum dose – Although there is no evidence-based optimal upper limit for the oxytocin dose, most regimens limit the infusion dose to no more than 40 milliunits/minute during labor with a live fetus in the third trimester. There is no maximum cumulative dose limit for oxytocin known to be associated with improved outcomes.

Should oxytocin be discontinued in the active phase? — In patients who achieve a desirable labor pattern and progress, there is no consensus about whether the oxytocin dose should be discontinued or continued. In a 2022 meta-analysis of randomized trials of continued versus discontinued oxytocin in the active phase of induced labor at ≥36 weeks of gestation, the risk of cesarean with discontinuation was statistically similar to that with continuation in the subgroup of patients who actually reached the active phase and thus received the intervention (RR 0.82, 95 % CI 0.60-1.10) [68]. Furthermore, there were no between-subgroup differences in the indication for the cesarean births that were performed. Of note, the trials were marred by many sources of bias and differences in the cervical dilation (4, 5, or 6 cm) defining the onset of the active phase of labor.

Based on available data, either discontinuation or continuation is reasonable, as long as labor is progressing and the fetal heart rate pattern is reassuring. If discontinued, oxytocin can be restarted if labor progress slows. If continued, continuous fetal heart rate monitoring is essential to identify potential tachysystole with fetal heart rate changes requiring discontinuation or dose reduction.

Other approaches to dosing

"Oxytocin rest" or break – We recommend not routinely stopping oxytocin and then restarting the infusion after a period of time for the purpose of improving labor progress. Oxytocin-induced desensitization of the oxytocin receptor has been demonstrated in vitro, but the clinical value of this finding in patients who receive prolonged oxytocin stimulation has not been demonstrated [69-71]. Although it has been hypothesized that stopping oxytocin if labor is not progressing and then restarting the drug several hours later will improve myometrial contractility, no randomized trials have shown clear evidence of benefit of this approach.

Pulsatile dosing – Some investigators have described pulsatile administration of IV oxytocin at 6- to 10-minute intervals as it theoretically could better simulate normal labor than continuous oxytocin administration [72,73]. However, pulsatile administration does not improve outcomes such as reducing the frequency of cesarean birth. Furthermore, the time from the start of the infusion to delivery may be longer than with continuous oxytocin administration. Pulsatile oxytocin administration requires special equipment and is rarely used in contemporary obstetric practice.

Side effects

Tachysystole – (See 'Tachysystole' below.)

HyponatremiaOxytocin has a similar structure to vasopressin (antidiuretic hormone) and can cross-react with the renal vasopressin receptor. If higher doses (eg, 50 milliunits/minute) of oxytocin are administered in large quantities (eg, over 3 liters) of hypotonic solutions (eg, 5 percent dextrose in water [D5W]) for prolonged periods of time (≥7 hours [74-76]), excessive water retention can occur and result in severe, symptomatic hyponatremia, similar to the syndrome of inappropriate antidiuretic hormone secretion [77-79]. This risk may be as high as 5 percent when the conditions described above are met [78]. Excessive oral, rather than intravenous (IV), intake of hypotonic liquids can have the same effect.

Symptoms of severe acute hyponatremia include headache, anorexia, nausea, vomiting, abdominal pain, lethargy, drowsiness, unconsciousness, grand mal type seizures, and potentially irreversible neurologic injury. (See "Manifestations of hyponatremia and hypernatremia in adults".)

If water intoxication occurs, oxytocin and any hypotonic solutions should be stopped. Correction of hyponatremia must be performed carefully and consists of restricting water intake and careful administration of hypertonic saline if the patient is symptomatic. (See "Overview of the treatment of hyponatremia in adults".)

Hypotension – Because oxytocin relaxes vascular smooth muscle, hypotension and tachycardia can result from rapid IV injection. This has been observed at cesarean birth when large intravenous oxytocin boluses (>5 units) were administered [80-84]. In a randomized trial of 75 patients undergoing cesarean birth and assigned to one of five doses of oxytocin postpartum, the prevalence of hypotension one minute after bolus injection of 0 units of oxytocin was 7 percent (one patient), 20 to 30 percent after bolus injection of 0.5 to 3 units, and 47 percent (seven patients) after bolus injection of 5 units [80].

We found no reports of hypotension with use of contemporary IV oxytocin infusion doses for induction of labor. However, as discussed above, it is prudent to administer oxytocin for induction by infusion pump to optimally control the rate of infusion and avoid adverse cardiovascular effects (arrhythmia, myocardial infarction, hypotension), as well as tachysystole, nausea, vomiting, headache, and flushing [81].

Pain – Whether induced labor is more painful than spontaneous labor is not well understood. The answer is not straightforward given the many factors involved in an individual's labor experience, including the physical circumstances surrounding labor (eg, frequency and strength of uterine contractions, fetal presentation), as well as individual emotional, motivational, cognitive, and social circumstances [85].

Data from randomized trials suggest that intrapartum pain is not worse with induction than expectant management. In a randomized trial comparing over 1700 individuals with postterm inductions with a similar number of expectantly managed/monitored postterm pregnancies, the rate of use of analgesia or anesthesia was similar for both groups (approximately 91 percent) [86]. In a more contemporary randomized trial of induction versus expectant management at 39 weeks among low-risk nulliparous individuals, the induction group had a small reduction in overall and worst pain scores during labor and more perceived control during childbirth; regional analgesia was used in the large majority of both groups and with similar frequency [9].

By comparison, some observational studies have suggested a higher frequency of epidural use among individuals undergoing medically-induced labor, although in many settings its use is common regardless of how labor is initiated [87,88]. Also, whether this finding reflects the presence of greater pain among those being induced is uncertain because of the strong likelihood of selection bias and confounding by indication (eg, those undergoing a medical induction are more likely to have medical circumstances that would predispose to recommendation of neuraxial analgesia). As with other outcomes, it is important to consider the difference between induction versus expectant management in terms of counseling regarding management choices.

Prolonged QT intervalOxytocin can prolong the QT interval, but the dose at which this becomes clinically relevant remains uncertain [89-94]. There is no need to routinely screen individuals with an electrocardiogram before the use of oxytocin; however, clinicians should be aware of the potential for arrythmia in patients with known long QT syndrome [91]. To our knowledge, torsade de pointes has not been reported in a pregnant patient receiving oxytocin. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes" and "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".)

Amniotomy — The combination of amniotomy and oxytocin administration during induction appears to shorten the time to vaginal delivery. Amniotomy may be performed as soon as the head is well apposed to the cervix; if not well apposed, it is delayed to reduce the risk of cord prolapse.

In a meta-analysis of randomized trials of patients undergoing induction (four trials, 1273 patients), early amniotomy after cervical ripening shortened the interval from induction to delivery by approximately five hours (95% CI -8.12 to -1.78) and did not increase the cesarean birth rate (31.1 versus 30.9 percent, RR 1.05, 95% CI 0.71-1.56) compared with usual care (late amniotomy or spontaneous rupture of membranes) [95]. Early amniotomy was defined as artificial rupture of the membranes soon after successful cervical ripening (eg, expulsion of Foley balloon, cervical dilation 3 cm, or favorable Bishop score); late amniotomy was defined as artificial rupture of membranes after the onset of the active phase of labor. A subsequent secondary analysis of data from >2800 nulliparous patients participating in a randomized trial of term labor induction found that amniotomy after oxytocin initiation was associated with either lower or similar odds of cesarean birth and other adverse outcomes compared with no amniotomy [96].

Complications of amniotomy (whether "early" or "late") include rupture of a vasa previa (if present) and umbilical cord prolapse. These complications may occur at the time of spontaneous rupture of the membranes, as well. (See "Velamentous umbilical cord insertion and vasa previa" and "Umbilical cord prolapse".)

COMPLICATIONS OF INDUCTION

Tachysystole

Definition – The American College of Obstetricians and Gynecologists uses the term tachysystole to describe >5 contractions in 10 minutes, averaged over a 30-minute window [97]. The presence or absence of associated fetal heart rate (FHR) changes should also be stated.

When reviewing data on tachysystole, clinicians should be mindful of the different terminologies that have been used in the literature. For example, the term "uterine hyperstimulation without fetal heart rate changes" has been used to describe uterine tachysystole (>5 contractions in 10 minutes for at least 30 minutes) or uterine hypersystole/hypertonus (a contraction lasting at least 2 minutes) with a normal FHR.

Frequency – The reported frequency of tachysystole associated with oxytocin administration varies widely. It is estimated to occur in no more than 5 percent of patients administered prostaglandin preparations for cervical ripening and is usually well tolerated and not associated with an adverse outcome.

Tachysystole occurs more frequently when higher doses of oxytocin or prostaglandins are used [98-101]. It is also thought to occur more often with concurrent administration of oxytocin and a prostaglandin since both drugs carry a risk of this complication, and data from human and animal studies show that prostaglandin administration increases uterine sensitivity to oxytocin [102-106]. Although some studies have not observed a statistically significant increase in excessive uterine activity with concurrent use, this may be due to the small numbers of patients in these studies, differences in methodology (eg, uterine activity was not continuously monitored), and the relatively low frequency of adverse events [107-111]. In one such trial, the frequency of uterine tachysystole with concurrent dinoprostone and oxytocin administration was 14 versus 5 percent with oxytocin alone [107].

Consequences – Since uterine activity causes intermittent interruption of blood flow to the intervillous space, excessive uterine activity for a prolonged time may result in fetal hypoxemia and acidemia [112-116]. Rarely, tachysystole causes uterine rupture; this is more likely to occur in multiparous than nulliparous patients [99,117].

Management – If oxytocin is being infused when tachysystole occurs, the dose should be reduced or discontinued until the tachysystole resolves, even if the FHR is not suggestive of acidemia. If adverse FHR changes are present, standard interventions should be initiated [118,119]. (See "Intrapartum category I, II, and III fetal heart rate tracings: Management", section on 'Selected category II FHR abnormalities' and "Intrapartum category I, II, and III fetal heart rate tracings: Management", section on 'General approach'.)

If oxytocin is discontinued, no studies have evaluated the optimum approach to resuming the drug. One approach resumes oxytocin at one-half the last infusion dose if it has been discontinued for less than 30 minutes and at the initial infusion dose if it has been discontinued for more than 30 minutes [120-122].

Uterine rupture — Induction has been associated with an increased relative risk of uterine rupture, but the absolute risk is very low and most cases occur in patients with a scarred uterus. (See "Uterine rupture: Unscarred uterus", section on 'Risk reduction' and "Cervical ripening and induction of labor in women with a prior cesarean birth".)

In a series including over 226,000 births, 12 of the 14 ruptures in patients with unscarred uteruses occurred in those exposed to oxytocin for induction or augmentation of labor (two of these patients were nulliparous) [123].

Amniotic fluid embolism — Induction (compared with spontaneous labor) appears to be associated with an increased risk of amniotic fluid embolism. In one retrospective series, the adjusted odds ratio was 1.8 (95% CI 1.2-2.7), but the absolute risk difference was small (10.3 per 100,000 births with medical induction versus 5.2 per 100,000 births without medical induction) [124]. Moreover, given that patients were induced for medical indications, it is highly plausible that the amniotic fluid embolism was causally related to these indications and not the induction itself. (See "Amniotic fluid embolism".)

Other issues

Induction of labor at term does not appear to be a risk factor for spontaneous preterm birth in the subsequent pregnancy [125,126].

True allergic reactions to oxytocin are rare [127,128].

There is no consistent evidence from well-designed studies that oxytocin administration is associated with autism spectrum disorder or any other long-term adverse outcomes for the offspring. In a systematic review of observational studies, there was no association between oxytocin use in labor and autism, cognitive impairment, problem behavior, or attention-deficit/hyperactivity disorder in exposed offspring [129]. Confounding by indication and ascertainment bias are among the factors that limit the findings of observational studies.

The best available data in this regard were reported by investigators of a nationwide Swedish epidemiologic study that found no association between labor induction and autism in offspring when adjustments were made for environmental and genetic factors shared by siblings (hazard ratio 0.99, 95% CI 0.88-1.10) [84]. A strength of this study was that comparison of exposure-discordant births to the same patient allowed for better adjustment for unmeasured factors.

OUTCOME

Labor progress — The average duration of the latent phase of labor is longer in induced labor than in spontaneous labor. (See "Labor: Overview of normal and abnormal progression", section on 'Normal progression in induced labors'.)

Once patients who have been induced enter active labor (cervical dilation 6 cm), progression appears to be comparable to that in patients with spontaneous onset active labor [130]. The duration of the second stage is similar in induced and spontaneous labors as well [130-132]. Therefore, active phase and second stage protraction disorders and arrest are diagnosed and managed the same as in patients in spontaneous labor. (See "Labor: Overview of normal and abnormal progression".)

Definition of failed induction — There has not been strong consensus as to the standard for defining a failed induction. We consider a reasonable approach to reserve the term specifically for cesareans that are performed because the latent phase has continued for an extended length of time and, in the clinician's assessment, it is unlikely that the active phase will be reached or that vaginal birth will be achieved [133]. We would not use the term for inductions in which a cesarean is performed to treat active phase protraction or arrest, prolonged second stage, nonreassuring fetal status, or a maternal indication for prompt delivery; instead we use the terms that are typically used for these indications.

A workshop convened by the United States National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, and American College of Obstetricians and Gynecologists attempted to provide evidenced-based criteria for reducing the number of cesarean births performed for failed induction in the latent phase of labor. The group proposed defining failed induction as: failure to generate regular (eg, every 3 minutes) contractions and cervical change after at least 24 hours of oxytocin administration, with artificial membrane rupture as soon as feasible and safe [134]. The time devoted to cervical ripening is not included when calculating the length of induction or diagnosing failed induction [135].

Because rupture of membranes is an important factor in the duration of induced labor, oxytocin generally should be administered for at least 12 hours after membrane rupture before considering the continued presence of the latent phase as an indication for cesarean [133,136-139] given the results of two analyses [133,136]:

For nulliparous patients with an unfavorable cervix, 40 percent who remained in the latent phase after 12 hours of oxytocin administration and membrane rupture gave birth vaginally [136]. Of note, approximately 70 percent exited the latent phase after 6 hours of oxytocin and membrane rupture, 20 percent between 6 and 12 hours, and 5 percent remained in the latent phase more than 12 hours.

For parous patients, the 12-hour criteria essentially eliminated failed labor induction as an indication for cesarean birth [133].

A retrospective review of the Consortium of Safe Labor study, including over 18,000 patients, focused on neonatal morbidity and concluded that in an otherwise uncomplicated induction with membranes ruptured, after initiation of oxytocin, a latent phase of at least 12 hours for nulliparous and 15 hours for multiparous patients is a reasonable criterion for diagnosing a failed induction because neonatal intensive care unit admission rates increased at those thresholds [137]. In an analysis of a multicenter cohort involving over 10,000 nulliparous patients undergoing induction of labor, 96 percent reached the active phase within 15 hours [139]. The authors, members of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, concluded that cesarean should not be performed in the latent phase for an indication of "failed induction" prior to at least 15 hours after oxytocin and rupture of membranes had occurred.

LABOR INDUCTION WITHOUT INITIAL USE OF OXYTOCIN

Amniotomy alone — In patients with a favorable cervix, use of amniotomy alone is an option to initiate labor if the head is well apposed to the cervix; however, the combination of amniotomy and intravenous oxytocin administration is more effective. In a meta-analysis of randomized trials, this combination resulted in a substantial reduction in pregnancies undelivered at 24 hours compared with amniotomy alone (2.1 versus 16.3 percent, relative risk [RR] 0.13, 95% CI 0.04-0.41; two trials with a total of 296 participants) [140].

Prostaglandin E1 or E2 — In patients with unfavorable cervixes, prostaglandins are a proven method of cervical ripening and may initiate labor as a result of their uterotonic effects. (See "Induction of labor: Techniques for preinduction cervical ripening", section on 'Prostaglandins'.)

In patients with favorable cervixes, however, there are inadequate data to determine the safety and efficacy of using prostaglandins instead of oxytocin to initiate induction of labor. Until such data are available, we avoid use of prostaglandins to induce labor in patients with favorable cervixes.

Membrane stripping — Membrane stripping has not been associated with demonstrable improvements in many clinically important outcomes (eg, lower cesarean rates, better perinatal outcomes), and as such, the decision to perform it should be individualized based on patient choice.

Stripping or sweeping of the membranes involves inserting the examiner's finger beyond the internal cervical os and then rotating the finger circumferentially along the lower uterine segment to detach the fetal membranes from the decidua. It is typically performed during an office visit when the cervix is partially dilated and the patient and clinician hope to hasten the onset of spontaneous labor. Thus, it should be performed only in those planning a trial of labor who are at least 39 weeks.

In a 2020 meta-analysis of 40 randomized trials (>6500 participants) comparing membrane sweeping with no or a sham intervention, sweeping modestly reduced the rate of formal labor induction (23 versus 31 percent, RR 0.73, 95% CI 0.56-0.94) and increased the rate of spontaneous onset of labor (72 versus 60 percent, RR 1.21, 95% CI 1.08-1.34) without affecting other maternal or neonatal outcomes [141]. Participants generally felt the benefits outweighed the harms (eg, discomfort) and would recommend it to others.

Group B Streptococcus colonization a contraindication to membrane sweeping as there is no direct evidence of harm. This issue is discussed in more detail separately. (See "Prevention of early-onset group B streptococcal disease in neonates", section on 'Antepartum procedures'.)

Nonstandard approaches — There is a paucity of data regarding the safety and/or efficacy of glucocorticoids, castor oil, hyaluronidase, isosorbide mononitrate, acupuncture, evening primrose oil, herbal preparations, breast stimulation, or sexual intercourse for labor induction, and none of these can be recommended as an evidence-based approach to labor induction [142-152].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cervical ripening and labor induction".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Labor and delivery (childbirth) (The Basics)")

SUMMARY AND RECOMMENDATIONS

Indications for induction

High-risk pregnancies – Induction of labor is indicated when continuation of the pregnancy is thought to be associated with maternal or fetal risks that are at least as great as (if not greater than) labor induction and there is no contraindication to vaginal birth. The risks are influenced primarily by the gestational age and severity of the maternal/fetal conditions, and can rarely be determined with precision. Some of the most common indications are postdate pregnancy, hypertensive disorders, prelabor rupture of membranes, and diabetes. (See 'Medical and obstetric indications' above and 'Contraindications' above.)

Low risk-pregnancies – Induction may be offered to low-risk patients without other medical indication at 39 weeks of gestation (this has been called "elective" induction). The pregnancy should be well dated given the increased risk of neonatal complications prior to 39 weeks. The values and preferences of the pregnant patient and the resources (including personnel) available for an elective procedure need to be considered when making the decision for elective induction. (See '"Elective" induction' above.)

Preinduction evaluation and management – Preinduction evaluation includes reviewing the estimate of gestational age, determining fetal presentation, estimating fetal weight, performing a cervical examination to decide whether a cervical ripening agent is indicated, evaluating the fetal heart rate pattern, and reviewing the patient's pregnancy and medical history for risk factors for potential problems that may develop during labor and delivery. (See 'Preinduction assessment and patient preparation' above.)

Cervical examination/Bishop score – Cervical status immediately before oxytocin administration is a key factor associated with the duration of induction and likelihood of vaginal birth. The Bishop score (table 1) is the best available tool for assessing cervical status. There is no universally accepted definition of favorable or unfavorable cervix. Most obstetricians consider a score ≥6 as favorable and a score ≤3 as unfavorable; scores of 4 or 5 are in a gray zone. (See 'Clinical assessment' above and 'Bishop score' above.)

Cervical ripening – For patients with unfavorable cervixes, preinduction cervical ripening increases the likelihood of a successful induction. There is no one best regimen for ripening, and both pharmacologic and mechanical approaches are reasonable choices unless a patient has a contraindication. (See "Induction of labor: Techniques for preinduction cervical ripening".)

Oxytoxin administration

Role of amniotomy – For patients with favorable cervixes undergoing induction, we suggest administration of oxytocin with amniotomy (preferably "early" rather than "late" in timing) rather than amniotomy alone (Grade 2B). (See 'Amniotomy' above.)

Oxytocin dosing – Oxytocin is administered intravenously by an infusion pump to allow continuous, precise control of the dose administered. A common regimen is to make a solution of 60 units oxytocin in 1000 mL crystalloid (60 milliunits in 1 mL) to allow the infusion pump setting (mL/hour) to match the dose administered (milliunits/minute; ie, a pump infusion rate of 1 mL/hour equals 1 milliunit/minute). (See 'Infusion pump' above.)

Implementation of a standardized oxytocin induction protocol can minimize errors in oxytocin administration. It is unclear whether using a high- versus a low-dose oxytocin regimen (table 2) for labor induction or augmentation results in better outcomes; either approach is acceptable. (See 'High- versus low-dose regimens' above.)

Side effects – The most frequent side effect of oxytocin is tachysystole (>5 contractions in 10 minutes, averaged over a 30-minute window). Rare side effects include hyponatremia and, if administered rapidly (intravenous bolus), hypotension. (See 'Side effects' above and 'Tachysystole' above.)

If tachysystole occurs, the oxytocin dose should be reduced or discontinued. (See 'Tachysystole' above.)

Discontinuation in the active phase – In patients who achieve a desirable labor pattern and progress, there is no consensus about whether oxytocin should be discontinued or continued in the active phase, and either approach is reasonable as long as labor is progressing and the fetal heart rate pattern is reassuring. If discontinued, oxytocin can be restarted if labor progress slows. If continued, continuous FHR monitoring will identify potential tachysystole with FHR changes requiring oxytocin discontinuation or dose reduction. (See 'Should oxytocin be discontinued in the active phase?' above.)

Labor progress – Once a patient undergoing induction has entered active labor (cervical dilation 6 cm), progression appears to be comparable to that with spontaneous active labor. The duration of the second stage is similar in induced and spontaneous labors. Therefore, active phase and second stage protraction and arrest disorders are diagnosed and managed the same as in patients in spontaneous labor. (See 'Labor progress' above.)

Failed induction – Failed induction is defined as failure to generate regular (eg, every 3 minutes) contractions and cervical change after at least 24 hours of oxytocin administration, with artificial membrane rupture as soon as feasible and safe. The time devoted to cervical ripening is not included when calculating the length of induction or diagnosing failed induction. Because rupture of membranes is an important factor in the duration of induced labor, oxytocin generally should be administered for at least 12 hours after membrane rupture before considering the induction to have failed. (See 'Definition of failed induction' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Deborah A Wing, MD, MBA, who contributed to an earlier version of this topic review.

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Topic 4476 Version 151.0

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