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Induction of labor with oxytocin

Author: William Grobman, MD


Section Editor: Charles J Lockwood, MD, MHCM
Deputy Editor: Vanessa A Barss, MD, FACOG

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.

Literature review current through: Jun 2019. | This topic last updated: Jun 26, 2019.

INTRODUCTION

Induction of labor refers to techniques for stimulating uterine contractions to


accomplish delivery prior to the onset of spontaneous labor. The induction of labor
in women with an unscarred uterus will be discussed here. Issues regarding
induction of labor in women who have had a previous cesarean delivery and
methods of cervical ripening are reviewed separately:

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

● (See "Techniques for ripening the unfavorable cervix prior to induction".)

PREVALENCE

Between 1990 and 2012, the overall frequency of labor induction more than
doubled in the United States, rising from 9.5 in 1990 to a high of 23.8 percent in
2010, before declining to 23.3 percent in 2012 [1].

MEDICAL INDICATIONS FOR INDUCTION


Delivery before the onset of labor is indicated when the maternal/fetal risks
associated with continuing the pregnancy are thought to be greater than the
maternal/fetal risks associated with delivery [2]. The relative risk of continuing the
pregnancy versus delivery is influenced primarily by the gestational age and
severity of the maternal/fetal condition and can rarely be determined with
precision.

The only interventions to effect delivery before onset of spontaneous labor are
induction of labor and cesarean delivery. Induction is generally preferred when
there are no contraindications to labor and vaginal birth, given the increased
maternal risks associated with cesarean delivery. (See 'Contraindications' below
and "Cesarean delivery: Postoperative issues".)

Examples of some common conditions where induction is often indicated include,


but are not limited to [2]:

● Postterm pregnancy (see "Postterm pregnancy")

● Prelabor (premature) rupture of membranes (see "Preterm prelabor rupture of


membranes: Clinical manifestations and diagnosis" and "Management of
prelabor rupture of the fetal membranes at term")

● Preeclampsia; eclampsia; hemolysis, elevated liver enzymes, low platelets


(HELLP) syndrome; gestational hypertension; chronic hypertension (see
"Preeclampsia: Management and prognosis" and "Eclampsia" and "HELLP
syndrome" and "Gestational hypertension" and "Management of hypertension
in pregnant and postpartum women", section on 'Management of pregnant
women with chronic (preexisting) hypertension')

● Fetal demise (see "Late fetal death and stillbirth: Maternal care")

● Maternal diabetes (see "Pregestational diabetes mellitus: Obstetrical issues


and management" and "Gestational diabetes mellitus: Obstetrical issues and
management")

● Fetal growth restriction (see "Fetal growth restriction: Evaluation and


management", section on 'Timing delivery')

● Chorioamnionitis (see "Intra-amniotic infection (clinical chorioamnionitis or


triple I)")

● Abruptio placentae (see "Placental abruption: Management")

● Oligohydramnios (see "Oligohydramnios")

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

● Alloimmunization with fetal anemia (see "Management of pregnancy


complicated by Rh(D) alloimmunization" and "Management of non-Rh(D) red
blood cell alloantibodies during pregnancy")

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

Some 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 delivery, and therefore
induction, are greater than the risks associated with cesarean delivery; 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')

● Prior transmural uterine incision entering the uterine cavity (see "Pregnancy in
women with uterine leiomyomas (fibroids)", section on 'Management of
patients with prior myomectomy')

● Active genital herpes 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 "Management of intrapartum category
I, II, and III fetal heart rate tracings", section on 'Category III pattern')

ELECTIVE INDUCTION

An induction is considered "elective" when there is no medical indication that


suggests that the benefits of delivery clearly outweigh the risks.

At 39 weeks or more — Potential advantages of scheduled induction of labor at


full term include reductions in both stillbirth and macrosomia and its
consequences, and the ability to control the time of delivery when this could be
important (eg, women with a history of rapid labor or who live far from the hospital
and thus risk of out-of-hospital delivery) [3-5]. Despite these advantages, elective
induction at ≥39 weeks has been controversial because of concerns that it
increases the chance of cesarean delivery and other adverse maternal outcomes,
as well as cost [6]. This belief was founded upon many retrospective cohort
studies of nulliparous women with singleton cephalic term pregnancies where the
investigators reported that the rate of cesarean delivery was increased
approximately twofold with elective or medical induction compared with
spontaneous labor [7-14]. However, women in spontaneous labor are not an
appropriate comparison group for those undergoing labor induction, as some
women who are not induced (ie, managed expectantly) will have induction or
cesarean delivery recommended later in pregnancy for a medical indication.

ARRIVE trial — When electively induced nulliparous or multiparous women are


compared with the appropriate comparison group (ie, those who are expectantly
managed), there is no convincing evidence that elective induction is associated
with an increase in the rate of cesarean delivery, whether or not the cervix is
favorable [4,15-19]. 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
women across the United States, induction reduced the chances of cesarean
delivery (18.6 versus 22.2 percent; relative risk [RR] 0.84, 95% CI 0.76-0.93),
hypertensive disorders of pregnancy (9.1 versus 14.1 percent; RR 0.64, 95% CI
0.56-0.74), and neonatal respiratory support (3.0 versus 4.2 percent; RR 0.71, 95%
CI 0.55-0.93), and resulted in 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) [20]. However, induction also increased the
median duration of stay on the labor unit (20 versus 14 hours).

Based on the results of this trial, the American College of Obstetricians and
Gynecologists concluded that offering elective induction of labor to low-risk
nulliparous women at 39 weeks of gestation is a reasonable option that should be
a shared decision of a woman and her obstetric provider, with consideration of
available resources [21]. The Society for Maternal-Fetal Medicine also concluded
that it is reasonable to offer elective induction to low-risk nulliparous women who
are ≥39+0 weeks of gestation and recommended that providers who choose this
approach ensure that women meet the eligibility criteria of the ARRIVE trial [22].

Although elective induction is a reasonable option for patients who want to


schedule their delivery date, the differences in outcomes between the two
approaches are small and do not warrant a strong recommendation for one
approach versus the other.

Before 39 weeks — Elective induction before 39 weeks of gestation should be


avoided [23,24]. The morbidity of birth before 37 weeks (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 than
birth at 39 to 40 weeks [25-31].

In order to emphasize the importance of avoiding elective induction prior to 39


weeks ("the 39 week rule"), the National Quality Forum, the Joint Commission, and
the Leapfrog Group made elective delivery prior to 39+0 weeks a maternal
performance measure and collect data from hospitals on elective deliveries
performed at >37 and <39 weeks of gestation [32]. In addition, the American
College of Obstetricians and Gynecologists has stated that maternal anxiety or
discomfort related to normal pregnancy, the distance lived from the hospital, or a
previous pregnancy with shoulder dystocia are not appropriate indications for
early-term induction [23], although they may be appropriate reasons for induction
at ≥39 weeks.

PREINDUCTION ASSESSMENT

The American College of Obstetricians and Gynecologists has published a patient


safety checklist to help with preinduction assessment [33]. A thorough evaluation
of maternal and fetal status is important before undertaking labor induction to
make sure the indication is appropriate and confirm the absence of
contraindications to labor or vaginal delivery. Evaluation includes:

● Reviewing the basis for 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 to assess whether there are clear
indications that the fetus is unlikely to tolerate initiation of labor

● Reviewing the patient's pregnancy and medical history for risk factors for
potential problems that may develop during labor and delivery

PATIENT PREPARATION AND MANAGEMENT OF LABOR

Patient preparation, laboratory studies, and labor management are generally the
same as in women in spontaneous labor (see "Management of normal labor and
delivery"). In addition, the indications for and alternatives to induction, planned
drugs and procedures including side effects and complications, and the possibility
of cesarean delivery or induction over several days should be discussed.

ASSESSING THE CHANCE OF A SUCCESSFUL INDUCTION

Cervical status — Cervical status immediately before oxytocin administration is a


key factor impacting the duration of induction and the likelihood of vaginal
delivery. It should be noted that even a high chance of cesarean at the time of
induction does not necessarily imply that expectant management will result in a
relatively lower chance of cesarean, as women with an unfavorable cervix may
also have a higher chance of cesarean if expectantly managed.

Despite its limitations, the Bishop score appears to be the best available tool for
assessing cervical status. Systematic reviews have concluded that the Bishop
score is as, or more, predictive of successful induction than fetal fibronectin [34]
or sonographic measurement of cervical length [35]. Cervical dilation is
considered to be the most important element of the Bishop score [34].

Bishop score — The Bishop score is the cervical assessment system most


commonly used in clinical practice in the United States [36]. This system tabulates
a score based upon the station of the presenting part and four characteristics of
the cervix: dilation, effacement, consistency, and position (table 1). 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 [37]).

There is no universally accepted definition of favorable or unfavorable cervix.


Higher Bishop scores are associated with a higher chance of vaginal delivery
[10,36,38,39], while lower Bishop scores have been associated with a higher
chance of cesarean delivery [40]. 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 grey zone. If the cervix is favorable, oxytocin is
administered without cervical ripening. If the cervix is unfavorable, cervical
ripening is employed. (See "Techniques for ripening the unfavorable cervix prior to
induction".)

Of note, a simplified Bishop scoring system appears to be as predictive as the


original system. In a cohort of over 5400 nulliparous women 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 delivery [41]. For predicting successful labor induction
(defined as achieving vaginal delivery), 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 (2.34 versus 2.19), and correct classification rate (51.0 versus 47.3 percent)
compared with the conventional Bishop score.

Noncervical factors — In addition to the status of the cervix, the chance of


successful induction is associated with noncervical characteristics of the
population being induced. The chance of vaginal delivery for women in
spontaneous labor is also associated with these characteristics.

Induction is more likely to be successful in [34,40,42,43]:

● Multiparous women

● Women at term gestation

● Women with ruptured membranes

● Women with lower body mass index (BMI)

● Women with taller height

● Women with an infant <4000 g

● Women without 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 delivery (multiparity versus
nulliparity: odds ratio [OR] 6.8, 95% CI 6.4-7.2, n = 6555 women) [44]. Higher
gestational age also was associated with vaginal delivery: Women <34 weeks of
gestation were less likely to deliver vaginally than those ≥34 weeks of gestation;
nevertheless, 57 percent of pregnancies 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 successful vaginal live birth.

The time of day when induction is started does not appear to be a factor in
success [45]. Early administration of neuraxial analgesia also does not appear to
be a factor in success [46]. (See "Adverse effects of neuraxial analgesia and
anesthesia for obstetrics", section on 'Effects on the progress and outcome of
labor'.)

Calculator — One group developed an internet-based calculator to estimate the


risk of cesarean after induction of labor at term in women with an unfavorable
cervix [47]. It incorporates five variables known at the start of induction (maternal
height, BMI, parity, gestational age, and modified Bishop score). The area under
the curve in the external validation cohort was 0.73 (95% CI 0.72-0.74). (Note: A
perfect test has an area under the curve equal to one, whereas a test that
performs no better than chance would have an area under the curve of 0.5.) It
should be noted that the usefulness of this calculator in clinical practice remains
uncertain. For example, it may not indicate which women would have a higher
chance of vaginal delivery if expectant management were to be employed.
Similarly, it may not provide information as to which women would have lower
morbidity by avoiding labor altogether. Thus, before routine introduction into
clinical practice, the benefit of its use should be demonstrated.

PROCEDURE

Preinduction cervical ripening for women with an unfavorable cervix — Because


induction with oxytocin is less likely to be successful in women with an
unfavorable cervix, a ripening process is generally employed prior to administering
oxytocin to these women (see 'Bishop score' above). Most research studies of
cervical ripening agents have limited participation to women with Bishop scores
≤6 [48,49]. (See "Techniques for ripening the unfavorable cervix prior to induction".)
If prostaglandin E2 or E1 is administered to promote cervical ripening, this
approach alone has been reported to initiate labor in up to 50 percent of women
and may obviate the need for oxytocin [50]. Use of prostaglandins for cervical
ripening is discussed in detail separately. (See "Techniques for ripening the
unfavorable cervix prior to induction", section on 'Prostaglandins'.)

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

Uterine and fetal heart rate monitoring — When uterotonic drugs (eg,


prostaglandins, oxytocin) are administered, continuous monitoring of uterine
activity and fetal heart rate (FHR) are important so that the dose can be adjusted
based on uterine activity and the FHR pattern. (See 'Tachysystole' below and
"Management of intrapartum category I, II, and III fetal heart rate tracings".)

Oxytocin administration — Synthetic oxytocin administration is the most common


and proven method of labor induction [51,52]. 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
delivery within 24 hours [48].

Pharmacology — 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 [53]. Increases in myometrial sensitivity are due primarily to increases in
myometrial oxytocin receptor binding sites [54]. Receptor activation triggers
signaling events that stimulate contractions, primarily by elevating intracellular
calcium [55]. 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 [56]. 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 [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 at three to six
minutes [58]. Low-dose oxytocin protocols are based upon 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 and maintenance' below.)

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
[60-62]. (See "Reducing adverse obstetrical 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 titration and maintenance — Some examples of low and high dose


oxytocin infusion protocols are described in the table (table 2). The optimum
dosing regimen for oxytocin administration is controversial, and no protocol has
been subjected to the scientific scrutiny necessary to demonstrate its superiority
in both efficacy and safety over another. Protocols differ as to 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) [60]. In a 2014 systematic review of
nine randomized trials of high- versus low-dose oxytocin regimens for induction of
labor, high-dose oxytocin reduced the induction to delivery interval in high-quality
trials but did not decrease the frequency of cesarean delivery compared with low-
dose therapy [63]. High-dose regimens were associated with a higher rate of
tachysystole than low-dose regimens, but maternal and perinatal complication
rates were similar for both regimens.

In both low and high dose protocols, the dose is typically increased until labor
progress is normal or uterine activity reaches 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). Although there is no evidence-based
optimal upper limit for the oxytocin dose, most protocols will limit the oxytocin
infusion during labor with a live fetus in the third trimester to no more than 40
milliunits/minute.

Clinical indications (eg, types of FHR abnormalities, tachysystole) should lead to


the reduction in oxytocin until they resolve. However, there is no consensus about
whether the oxytocin infusion routinely should be maintained or can be
lowered/discontinued when a desirable labor pattern and progress have been
achieved.

In a systematic review and meta-analysis of randomized trials comparing


discontinuation of oxytocin when the active phase was reached with continuation
until delivery (nine trials, n = 1538 singleton cephalic term pregnancies),
discontinuation resulted in lower rates of cesarean delivery (9.3 versus 14.7
percent; relative risk [RR] 0.64, 95% CI 0.48-0.87) and tachysystole (6.2 versus 13.1
percent; RR 0.53, 95% CI 0.33-0.84) [64]. Discontinuation increased the duration of
the active phase (mean difference 28 minutes, 95% CI 4-51 minutes), but the
duration of the second stage was similar in both groups. Approximately 30 percent
of women had oxytocin restarted because of arrest of labor. A Cochrane review
reported similar findings with regard to cesarean delivery when all participants
were included, but noted that when the analysis was restricted to women who
reached the active phase of labor, the difference in cesarean delivery was no
longer significant (RR 0.92, 95% CI 0.65-1.29) [65]. Both reviews emphasized the
significant design limitations and high risk of bias (including post-randomization
exclusions) among the trials. Based on these findings, it is reasonable for
clinicians to either continue or reduce/discontinue oxytocin during the active
phase until further research to determine the best approach for oxytocin
management clearly establishes evidence for best practice.

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 [66,67]. However, pulsatile administration does
not improve outcomes such as the frequency of cesarean delivery, and 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.

There is no maximum cumulative dose limit for oxytocin that is known to improve
outcomes.

Tolerance — We recommend not routinely discontinuing oxytocin and restarting


infusion for the purpose of improving labor progress. Oxytocin-induced
desensitization of the oxytocin receptor has been demonstrated in vitro, but the
clinical relevance of this finding in women who receive prolonged oxytocin
stimulation is unknown [68-70]. 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 clinical evidence supports this theory.

Side effects

● Tachysystole – (See 'Tachysystole' below.)


● Hyponatremia – Oxytocin 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 [71-73]), excessive
water retention can occur and result in severe, symptomatic hyponatremia,
similar to the syndrome of inappropriate antidiuretic hormone secretion [74-
76]. This risk may be as high as 5 percent when the conditions described
above are met [75]. 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 – Oxytocin relaxes vascular smooth muscle, thus hypotension


and tachycardia can result from rapid IV injection. This has been observed at
cesarean delivery when large oxytocin boluses (>5 units) were given [77-81].
In a randomized trial of 75 women undergoing cesarean delivery and assigned
to one of five doses of oxytocin after delivery, the prevalence of hypotension
one minute after bolus injection of 0 units of oxytocin was 7 percent (1
patient), 20 to 30 percent after bolus injection of 0.5 to 3 units, and 47 percent
(7 patients) after bolus injection of 5 units [77].
We found no reports of hypotension with use of contemporary IV oxytocin
doses for induction or labor. However, it is prudent to administer oxytocin for
induction by infusion pump to best control the rate of infusion avoid adverse
cardiovascular effects (arrhythmia, myocardial infarction, hypotension), as
well as tachysystole, nausea, vomiting, headache, and flushing [78].

Early amniotomy — Early amniotomy may be performed if the head is well


opposed to the cervix; if not, it is delayed until the head descends in order to
reduce the risk of cord prolapse. The combination of early amniotomy and
oxytocin administration during induction appears to shorten the time to vaginal
delivery [82-84]. In a randomized trial of nulliparous women undergoing labor
induction, routine early amniotomy (defined as cervical dilation ≤4 cm) shortened
the time to delivery by approximately 2 hours and increased the proportion of
deliveries within 24 hours (68 versus 56 percent; RR 0.72, 95% CI 0.59-0.89)
compared with "usual care" [82]. In a cohort study of women undergoing labor
induction after cervical ripening with a balloon catheter, those who had amniotomy
within one hour of catheter removal were more likely to have a vaginal delivery
within 24 hours of catheter placement (42.9 versus 33.0 percent) and a shorter
interval to delivery (10.6 versus 13.8 hours) [83]. Other outcomes between groups
were similar.

Complications of amniotomy (whether "early" or "late") include rupture of a vasa


previa 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".)

ALTERNATIVE APPROACHES TO LABOR INDUCTION

Amniotomy alone — In women with a favorable cervix, use of amniotomy alone is


an option for initiation of labor if the head is well opposed to the cervix; however,
the combination of amniotomy and intravenous oxytocin administration is more
effective. In a systematic review of randomized trials, this combination resulted at
least a 60 percent reduction in women undelivered at 24 hours compared with
amniotomy alone (relative risk [RR] 0.13, 95% CI 0.04-0.41) [85].

Prostaglandin E1 or E2 instead of oxytocin — In women with unfavorable cervixes,


prostaglandins are a proven method of cervical ripening and may also initiate
labor as a result of their uterotonic effects (see "Techniques for ripening the
unfavorable cervix prior to induction", section on 'Prostaglandins'). In women 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
women 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.

The efficacy of membrane sweeping was demonstrated in a 2005 meta-analysis of


20 trials in which sweeping of membranes was compared with no treatment [86].
Compared with no intervention, membrane sweeping was associated with reduced
frequency of pregnancy continuing beyond 41 weeks (RR 0.59, 95% CI 0.46-0.74)
and 42 weeks of gestation (RR 0.28, 95% CI 0.15-0.50), and reduced frequency of
labor induction (RR 0.72, 95% CI 0.52-1.00). The rates of maternal fever, maternal
infection, neonatal infection, and cesarean delivery were similar in both groups.

While this meta-analysis found the practice was not associated with an increase in
neonatal infection, Group B Streptococcus (GBS) colonization status was not
specifically addressed. Subsequently, an observational study compared maternal
and neonatal outcomes following membrane stripping among GBS-positive (n =
135), GBS-negative (n = 361), and GBS-unknown (n = 46) women and found no
significant difference in adverse maternal or neonatal outcomes among groups
[87]. Most GBS-positive women received intrapartum GBS antibiotic prophylaxis.
Although these results are reassuring, the study did not have adequate power to
detect modest differences in less frequent outcomes and is subject to the
limitations of an observational design. We believe GBS colonization is not a
contraindication to membrane sweeping as there is no direct evidence of harm.
(See "Neonatal group B streptococcal disease: Prevention", 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 [88-98].

COMPLICATIONS

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 [99]. The presence or absence of associated fetal
heart rate (FHR) changes should also be stated.
Nevertheless, 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. Tachysystole is estimated to occur in no more
than 5 percent of women 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 [100-103]. 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 [104-108]. 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 [109-113]. In one such trial, the
frequency of uterine tachysystole with concurrent dinoprostone and oxytocin
administration was 14 versus 5 percent with oxytocin alone [109].

● 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 [114-118]. Rarely,
tachysystole causes uterine rupture; this is more common in multigravidas
than primigravidas [101,119].
● Management – If oxytocin is being infused when tachysystole occurs, the
dose should be reduced or discontinued until the tachysystole resolves, even
if the FHR suggests fetal well-being. If adverse FHR changes are present,
standard interventions should be instituted [120,121]. (See "Management of
intrapartum category I, II, and III fetal heart rate tracings", section on 'In utero
resuscitation' and "Management of intrapartum category I, II, and III fetal heart
rate tracings", section on 'Selected category II FHR abnormalities'.)

If oxytocin is discontinued, no studies have evaluated the optimum approach


to resuming the drug. One approach resumes oxytocin at one-half the
previous dose if it has been discontinued for less than 30 minutes and at the
initial dose ordered if it has been discontinued for more than 30 minutes [122-
124].

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 women
with a scarred uterus. (See "Uterine rupture: Unscarred uterus", section on 'Use of
uterotonic drugs' and "Cervical ripening and induction of labor in women with a
prior cesarean delivery", section on 'Minimizing risk of uterine rupture during
induction'.)

In a series including over 226,000 births, 12 of the 14 ruptures in women with


unscarred uteruses occurred in women exposed to oxytocics for induction or
augmentation of labor (two of these women were nulliparous) [125].

Amniotic fluid embolism — Induction 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) [126]. Moreover, given that women were induced for medical
indications, it may be 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 [127,128].

● True allergic reactions to oxytocin are rare [129,130].

● Risk of neurodevelopmental disorders in offspring – 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 [131]. Confounding by indication and ascertainment bias
are among the factors that limit the findings of observational studies.

The best available data were reported by 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) [81]. A strength of this
study was that comparison of exposure-discordant births to the same woman
allowed for better adjustment for unmeasured factors shared by siblings.

OUTCOME

Labor progress — The average duration of the latent phase of labor is longer in


induced labor. In two observational studies, the total length of time from
admission to delivery in women who were induced was three to four hours longer
than in those who were expectantly managed (regardless of cervical status)
[132,133].
Once women who have been induced enter active labor (cervical dilation 6 cm),
progression appears to be comparable to progression in women with spontaneous
active labor [134]. The duration of the second stage is similar in induced and
spontaneous labors as well [11,134,135]. Therefore, active phase and second
stage protraction disorders and arrest are diagnosed and managed the same as in
women in spontaneous labor. (See "Normal and abnormal labor 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
delivery will be achieved [136]. We would not use the term for inductions in which
an operative intervention is performed to treat active phase protraction or arrest,
prolonged second stage, nonreassuring fetal status, or a maternal indication for
prompt delivery.

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 deliveries 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 [137]. The time devoted to cervical ripening is not included
when calculating the length of induction or diagnosing failed induction [138].

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 [136,139-142],
given the results of two analyses [136,139]:
● For nulliparous women with an unfavorable cervix, 40 percent who remained
in the latent phase after 12 hours of oxytocin administration and membrane
rupture delivered vaginally [139]. 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 women, the 12 hour criteria essentially eliminated failed labor
induction as an indication for cesarean birth [136].

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 women and 15 hours
for multiparous women is a reasonable criterion for diagnosing a failed induction
[140]. In an analysis of a multicenter cohort involving over 10,000 nulliparous
women undergoing induction of labor, 96 percent reached the active phase of
labor within 15 hours [142]. The authors, members of the National Institute of
Child Health and Human Development Maternal-Fetal Medical Units Network,
concluded that cesarean should not be performed for a failed induction in the
latent phase prior to at least 15 hours after oxytocin and rupture of membranes
had occurred.

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


● Induction of labor is indicated when continuation of the pregnancy is thought
to be associated with greater maternal or fetal risk than intervention to deliver
the pregnancy, and there is no contraindication to vaginal birth. (See 'Medical
indications for induction' above and 'Contraindications' above.)

● If elective induction is offered, women should have well-dated pregnancies


≥39 weeks of gestation, given the increased risk of neonatal complications
prior to 39 weeks. The values and preferences of the pregnant woman and the
resources (including personnel) available for an elective procedure need to be
considered when making the decision for elective induction. Although elective
induction at ≥39 weeks is a reasonable option for patients who want to
schedule their delivery date, the differences in outcomes between elective
induction and expectant management are small and do not warrant a strong
recommendation for one approach versus the other. (See 'Elective induction'
above.)

● The American College of Obstetricians and Gynecologists has published a


patient safety checklist to help with preinduction assessment. 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' above.)

● Cervical status immediately before oxytocin administration is a key factor


associated with the duration of induction and likelihood of vaginal delivery.
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 grey zone. (See 'Cervical status' above
and 'Bishop score' above.)

● For women with favorable cervixes undergoing induction, we suggest


administration of oxytocin with early amniotomy rather than amniotomy alone
(Grade 2B). There is no single oxytocin regimen that has been shown to be
best (table 2). 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 one 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). Implementation of a standardized
oxytocin induction protocol can minimize errors in oxytocin administration.
(See 'Dose titration and maintenance' above.)

● Once the active phase of labor is established, it is reasonable to either


continue or reduce/discontinue oxytocin. (See 'Dose titration and
maintenance' above.)

● For women 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 "Techniques for ripening
the unfavorable cervix prior to induction".)

● 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 a bolus is given, hypotension. (See 'Side effects' above
and 'Tachysystole' above.)

● If tachysystole occurs, the oxytocin dose should be reduced or discontinued.


(See 'Tachysystole' above.)

● Once a woman undergoing induction has entered active labor (cervical


dilation 6 cm), progression appears to be comparable to progression in
women 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 women in spontaneous labor. (See 'Labor progress' above.)

● 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 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. 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 editorial staff at UpToDate would like to acknowledge Deborah A Wing, MD,
MBA, who contributed to an earlier version of this topic review.

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