22.2.1 Obstetrical and Medical Indications

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 early delivery [2]. Induction is generally preferred when there are no contraindications to labor and vaginal birth. The relative risk of delivery versus continuation of pregnancy is influenced by factors such as gestational age, presence/absence of fetal lung maturity, severity of the clinical condition, cervical status, and maternal demographic factors. However, the magnitude of maternal/fetal risk of early delivery can rarely be determined with precision.

Elective or Marginally Indicated Induction at Term Induction of labor without medical indication is termed as elective induction of labor. Sometimes this is done for reasons like previous history of precipitate labor, distance from the hospital, or social reasons. However, the potential advantages are reduction in stillbirth, macrosomia and meconium passage. It is also done to ensure that the delivery occurs at the time when hospital has optimum number of staff. In addition, the risk of delivery en route to the hospital is reduced among patients with a history of rapid labor or who live far from the hospital. However there is insufficient evidence to support this practice as routine. The major concerns associated with elective (“social”) or marginally indicated induction at term are the potential for cesarean delivery in latent phase, the increased length of labor, neonatal morbidity if delivery is before 39 weeks of gestation [3], and cost [4–6].

There is expert consensus that elective induction should not be performed before 39 weeks of gestation because of the increased risk of neonatal morbidity and mortality. In particular, the following clinical scenarios are not indications for early term induction (i.e., at 37–38 weeks): maternal anxiety or discomfort related to normal pregnancy; a previous pregnancy with labor abnormalities, shoulder dystocia, or rapid labor; suspected macrosomia; or the distance the mother lives from the hospital [7].

22.4.1 Pre-Induction Cervical Ripening

Uterine activity and fetal heart rate monitoring are indicated for at least 30 min after administration of prostaglandins for cervical ripening and should be maintained as long as regular uterine activity is present [17].

If labor does not ensue or is not progressing adequately after administering prostaglandins, repeated doses can be given. Alternatively, oxytocin may be initiated, or, if technically possible, amniotomy can be performed and appears to be more effective than repeated dosing with prostaglandin [5].

Prostaglandin E1 (Misoprostol). Misoprostol, a synthetic PGE1 analogue, is an effective drug for induction of labor. It is cheap and stable at room temperature and very useful in developing countries. The American College of Obstetricians and Gynecologists (ACOG) has indicated that use of misoprostol appears safe and efficacious when used as a cervical ripening and/or labor induction agent when utilized judiciously. Though 50 mcg dose is more effective than 25 mcg (e.g., higher rate of vaginal delivery and lower rate of oxytocin use), 25 mcg dose is safer (lower rate of tachysystole, hyperstimulation, cesarean deliveries for non-reassuring fetal heart rate, NICU admissions, and meconium passage) [18]. Therefore, lower doses, such as 25 mcg, should be used initially, with re-dosing intervals of 4–6 h [19–21]. The World Health Organization (WHO) suggests 25 mcg every 6 h [22] maximum up to 150 μg in 24 h. The time interval between the final dose and initiation of oxytocin should be around 4 h because of the potential possibility for uterine tachysystole with concurrent oxytocin and misoprostol administration.

Routes of Administration of Misopristol. Vaginal route is the most preferred route. Oral route is convenient and effective [23]. The concentration of orally administered misoprostol peaks sooner and declines more rapidly than with vaginal administration [24]. Buccal or sublingual administration is a novel approach which avoid first pass hepatic metabolism associated with oral ingestion and may therefore increase bioavailability similar to that achieved with vaginal administration.

Contraindications to Misoprostol. Prostaglandins are not used for cervical ripening or labor induction in term pregnancies with a prior cesarean birth or other prior major uterine surgeries (e.g., extensive myomectomies and hysterotomies) because of the increased risk for uterine rupture [6]. Pre-existing uterine activity is a relative contraindication to use of prostaglandins. Addition of an exogenous uterotonic agent, in the presence of any degree of antecedent uterine activity, will cause excessive uterine activity. For patients having frequent, low-amplitude, painless contractions or ≥2 painful contractions/10 min as baseline uterine activity or who have received one dose of prostaglandin, second dose should be delayed or avoided, as there appears to be cumulative uterotonic effect.

Side effects of misoprostol include tachysystole, hyperstimulation, fever, chills, vomiting, and diarrhea. The frequency of these side effects depends on the type of prostaglandin, dose, and route of administration. Uterine contractile abnormalities are encountered in up to 30% of cases depending on the route of administration; other systemic effects occur in up to 5% of cases.

Prostaglandin E2. Prostaglandin E2 preparation is available for cervical ripening. Intracervical gel contains 0.5 mg of Dinoprostone gel for endocervical administration. The dose can be repeated in 6–12 h if cervical change is inadequate and uterine activity is minimal following the first dose. The manufacturer recommends that the maximum cumulative dose of Dinoprostone not exceed 1.5 mg (i.e., three doses) within a 24-hour period. The time interval between the final dose and initiation of oxytocin should be around 6 h because of the potential for uterine tachysystole with concurrent oxytocin and prostaglandin administration. PGE2 is contraindicated in bronchial asthma and heart disease.

Mechanical Methods. Mechanical methods are among the oldest approaches used to promote cervical ripening. Advantages of these techniques compared with pharmacologic methods include their low cost compared with some drugs, low risk of tachysystole, few systemic side effects, and convenient storage requirements (no refrigeration or expiration, which are issues for some drugs). Disadvantages include a possible small increase in the risk of maternal and neonatal infection from introduction of a foreign body [11], the potential for disruption of a low-lying placenta, some maternal discomfort upon manipulation of the cervix, and frequent need for oxytocin induction of labor.

The most common mechanical method is insertion of a balloon catheter.

These methods likely work, at least in part, by causing the release of prostaglandin F2-alpha from the decidua and adjacent membranes or prostaglandin E2 from the cervix. In addition, insertion of a catheter or dilator directly dilates the cervix.

Under strict aseptic precaution, a 24 F Foley catheter with 30–50 mL bulb is inserted into the cervix and passed into the internal os and into the extraamniotic space. The bulb is then filled with 30–50 mL saline, and the Foley is pulled back gently, so that the bulb rests against the internal os. The catheter is then strapped to the patient’s thigh. The catheter is left in place until it is extruded or for up to 6–12 h.

Mifepristone (RU486) is a progesterone receptor antagonist. The rationale behind its use for induction of labor is that in spontaneous labor, a fall in progesterone is one of the main factors leading to onset of labor. When compared to placebo, it is more effective in increasing the chances of spontaneous labor and reducing the need for prostaglandins. Usually after 48 h, the ripening of the cervix occurs. Dose: tablet 200 mg orally.

22.4.2 Labor Induction

Once the cervix becomes favorable, labor is induced, usually with oxytocin, with or without amniotomy. Prostaglandins used for ripening the cervix may also stimulate uterine contraction, and labor may follow. Mechanical methods of cervical ripening are usually followed by oxytocin to induce labor. Prostaglandins are very effective in ripening, effacing, and dilating the cervix to the extent required for amniotomy. Amniotomy in itself may be ineffective without use of oxytocin, and in any case, it cannot be done unless the cervix is dilated enough to allow the passage of instrument. Oxytocin is most effective when the cervix is already favorable or when membranes have ruptured.

Oxytocin. Oxytocin is a polypeptide hormone produced in the hypothalamus and secreted from the posterior lobe of the pituitary gland in a pulsatile fashion. It is identical to its synthetic analogue, which is among the most potent uterotonic agents.

Synthetic oxytocin administration is a proven method of labor induction [25]. 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 [26]. Increases in myometrial sensitivity are due primarily to increases in myometrial oxytocin binding sites [27]; 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 [28].

Regimen. Oxytocin is most commonly given intravenously. It cannot be administered orally because the polypeptide is degraded into small, inactive forms by gastrointestinal enzymes. The plasma half-life is short, estimated at 3–6 min [29]. Steady-state concentrations are reached within 40 min of initiation or dose change [30].

Infusion pumps are used to allow continuous, precise control of the dose administered. A common contemporary practice is to make a solution of 5 units of oxytocin in 500 mL crystalloid (10 mU in 1 mL). In the absence of infusion pumps, the drops per minute have to be titrated and monitored accurately.

When uterotonic drugs are administered, continuous monitoring of uterine activity and fetal heart rate is important so that the dose can be adjusted up or down if uterine activity is inadequate or excessive. The maximum dose of oxytocin has not been established and the end point is usually the achievement of uterine contractions of at least 3 in 10 min each lasting for 40 s.