Objective
The purpose of this study was to determine whether there is an increase in the cesarean delivery rate in women who undergo induction when oxytocin is discontinued in the active phase of labor.
Study Design
We conducted a prospective randomized controlled trial of women who underwent induction of labor at term; they were assigned randomly to either routine oxytocin use (routine) or oxytocin discontinuation (DC) once in active labor. Analysis was by intention to treat.
Results
Two hundred fifty-two patients were eligible for study analysis: 127 patients were assigned randomly to the routine group and 125 patients were assigned randomly to the DC group. Cesarean delivery rate was similar between the groups (routine, 25.2% [n = 32] vs the DC group, 19.2% [n = 24]; P = .25). There was a higher chorioamnionitis rate and slightly longer active phase in those women who were assigned to the DC group. In adjusted analysis, the rate of chorioamnionitis was not different by randomization group but was explained by the duration of membrane rupture and intrauterine pressure catheter placement.
Conclusion
Discontinuation of oxytocin in active labor after labor induction does not increase the cesarean delivery rate significantly.
Oxytocin is the most common agent used to induce and augment labor. Known benefits of oxytocin include the initiation and/or improvement of contractions to achieve labor, whereas risks include uterine overactivity, water intoxication, and, albeit rare, uterine rupture. Despite its widespread use, optimal protocols for oxytocin use as an induction agent have not been identified.
For Editors’ Commentary, see Contents
See related editorial, page 439
The relationship of oxytocin and its receptor is crucial in obtaining adequate uterine activity. The myometrium contains receptors that are specific to oxytocin, which, when occupied, stimulate myometrial contraction and prostaglandin formation in the decidua. Oxytocin receptors increase with advancing gestation, and uterine sensitivity to oxytocin increases rapidly in spontaneous labor. A lower number of receptors have also been noted in women who have been given larger doses or a longer infusion of oxytocin compared with those who have been given shorter treatments or lower doses, which suggests receptor down-regulation in this environment. As such, prolonged oxytocin use and receptor desensitization may lead to poor uterine contractility, atony, and potential labor dysfunction.
Various oxytocin regimens for the induction of labor have been described, although limited data are available regarding which is superior. Particularly unclear is whether oxytocin should be continued once active labor is achieved. Although traditional thinking is that discontinuation of oxytocin, once labor is achieved, may prolong labor length and/or increase the cesarean delivery rate, given what is known about prolonged oxytocin use, there actually may be benefit to discontinuing oxytocin once active labor is achieved. Studies in populations with a lower cesarean rate suggest that, once active labor is achieved, oxytocin may be discontinued without altering labor progression or the cesarean delivery rate. It is unclear whether oxytocin discontinuation would lead to a higher rate of cesarean delivery in a population such as ours. Thus, the objective of this study was to determine in our population whether there is an increase in the cesarean delivery rate in women who undergo labor induction when oxytocin is discontinued in the active phase of labor. We hypothesized that oxytocin discontinuation, once active labor is achieved, would not increase the risk of labor abnormalities or cesarean delivery.
Materials and Methods
This was a prospective randomized controlled trial of women who underwent induction of labor from February 2009 to August 2011 at Lehigh Valley Health Network. The primary outcome was the rate of cesarean delivery among women for whom oxytocin was either discontinued or continued once in active labor. Institutional review board approval was obtained, and written informed consent was obtained from participants. The trial was registered at ClinicalTrials.gov , ID NCT00957593 .
Our inclusion criterion was a singleton gestation of ≥37 weeks that was scheduled for labor induction, regardless of indication for induction, Bishop score, or parity. Patients were recruited at the time of admission to Labor and Delivery. Exclusion criteria were multiple gestations, previous cesarean delivery, active labor, and documented fetal anomalies. Method of induction was at the provider’s discretion. Cervical ripening before the initiation of oxytocin was allowed in the study protocol. In our institution, women whose induction requires cervical ripening undergo ripening with either misoprostol or intracervical Foley bulb placement with or without oxytocin. Women with a favorable Bishop score are induced with oxytocin alone.
At enrollment, patients were assigned randomly to either routine treatment or discontinuation (DC). The routine group followed a standard institutional oxytocin protocol in which oxytocin is titrated to target 3-5 contractions in a 10-minute period. Usual practice is to continue oxytocin until delivery, unless there is an indication to stop the infusion. The DC group followed an oxytocin protocol by which oxytocin was discontinued once the patient was deemed to be in active labor by the obstetrician. Active labor was defined by the clinician’s assessment of regular uterine contractions with a cervical examination that confirmed dilation of ≥4 cm.
The study’s primary outcome was the difference in the rate of cesarean delivery between the groups. Secondary outcomes included the length of latent and active phases of labor and maternal and neonatal outcomes including chorioamnionitis. Chorioamnionitis was diagnosed by clinical criteria: maternal temperature of ≥100.4°F and maternal tachycardia, fetal tachycardia, or both. The decision to perform a cesarean delivery was according to standard obstetric indications and ultimately was decided by the treating physician, regardless of treatment assignment. The treating physician was able at any time to restart the oxytocin infusion in patients who assigned to the DC group if they believed it was indicated clinically.
Using a power of 80% and an alpha level of .05, we estimated that 304 women (152 in each group) would be needed to show an increase in the cesarean delivery rate from a baseline rate of 25% to 40% for women who had oxytocin discontinuation. Four-block randomization was used that was stratified for parity. For statistical analysis, we used Stata software (version 9.0 SE; StataCorp, College Station, TX). Comparisons were made with the Student t test or the Mann Whitney U test for continuous variables and χ 2 analysis or Fisher exact test for categoric variables. Multinomial logistic regression models, controlled for confounding, were developed; adjusted relative risk ratios (RRR) with 95% confidence interval (CI) were derived from the models. Statistical analysis was by intention to treat.
Results
Three hundred three patients agreed to enroll in the study ( Figure ); 38 women did not complete the enrollment process, and 13 pregnancies were screen failures, allowing 252 patients for enrollment and participation in the study. Enrollment was stopped after 30 months primarily because of enrollment challenges. One hundred twenty-seven women (50.4%) were randomly assigned to the routine group, and 125 women (49.6%) were randomly assigned to the DC group once active labor was achieved. Demographic and antepartum characteristics were similar between the routine group and DC groups ( Table 1 ). There was no difference in indication for induction or method of induction between groups ( Table 2 ). Most women were induced initially with oxytocin (77.2% in the routine group vs 72.0% in the DC group; P = .26). The use of Foley bulb ripening was also similar between the groups ( P = .10; Table 2 ).
| Group | ||
|---|---|---|
| Characteristic | Routine (n = 127) | Oxytocin discontinuation (n = 125) |
| Maternal age, y a | 27.1 ± 5.6 | 27.7 ± 5.7 |
| Nulliparity, n (%) | 63 (49.6) | 64 (51.2) |
| Marital status, n (%) | ||
| Married | 56 (44.1) | 66 (52.8) |
| Divorced/widow | 1 (0.8) | 1 (0.8) |
| Never married | 70 (55.1) | 58 (46.4) |
| Race/ethnicity, n (%) | ||
| White | 86 (67.7) | 82 (65.6) |
| African American | 8 (6.3) | 7 (5.6) |
| Latina | 27 (21.3) | 30 (24.0) |
| Other | 6 (4.7) | 6 (4.8) |
| Insurance, n (%) | ||
| Government | 52 (41.0) | 45 (36.0) |
| Private | 60 (47.2) | 61 (48.8) |
| Self-pay | 15 (11.8) | 19 (15.2) |
| Private service vs resident service, n (%) | 70 (55.1) | 67 (53.6) |
| Tobacco use, n (%) | 17 (13.4) | 18 (14.4) |
| Alcohol use, n (%) | 0 | 1 (0.8) |
| Drug use, n (%) | 0 | 2 (1.6) |
| Body mass index (kg/m 2 ) a | 31.7 ± 7.3 | 31.0 ± 7.4 |
| Obesity: body mass index ≥30, n (%) | 75 (59.1) | 64 (51.2) |
| Pregestational diabetes mellitus, n (%) | 1 (0.8) | 1 (0.8) |
| Gestational diabetes mellitus, n (%) | 14 (11.0) | 17 (13.6) |
| Essential hypertension, n (%) | 5 (3.9) | 6 (4.8) |
| Gestational hypertension or preeclampsia, n (%) | 46 (36.2) | 41 (32.8) |
| Any comorbidity, n (%) | 89 (70.6) | 82 (65.6) |
| History of preterm birth, n (%) | 3 (2.4) | 8 (6.4) |
| Gestational age at first prenatal visit, wk a | 12.5 ± 6.7 | 12.2 ± 6.1 |
| Group B streptococcus, n (%) | 34 (27.4) | 24 (19.4) |
| Group | |||
|---|---|---|---|
| Characteristic | Routine (n = 127) | Oxytocin discontinuation (n = 125) | P value |
| Gestational age at admission, wk a | 39.8 ± 1.3 | 40.0 ± 1.0 | .18 |
| Indication for induction of labor, n (%) | .52 | ||
| Prolonged pregnancy | 32 (25.2) | 36 (28.8) | |
| Premature rupture of membranes | 6 (4.7) | 9 (7.2) | |
| Nonreassuring antenatal testing | 14 (11.0) | 5 (4.0) | |
| Oligohydramnios | 14 (11.0) | 12 (9.6) | |
| Gestational hypertension or preeclampsia | 21 (16.5) | 19 (15.2) | |
| Intrauterine growth restriction | 1 (0.8) | 1 (0.8) | |
| Diabetes mellitus, any | 10 (7.9) | 13 (10.4) | |
| Elective | 19 (15.0) | 15 (12.0) | |
| Other b | 10 (7.9) | 15 (12.0) | |
| First method of induction, n (%) | .26 | ||
| Misoprostol | 22 (17.3) | 21 (16.8) | |
| Oxytocin | 98 (77.2) | 90 (72.0) | |
| Foley bulb and oxytocin | 7 (5.5) | 14 (11.2) | |
| Cervical ripening, n (%) | 29 (22.8) | 35 (28.0) | .35 |
| Bishop score c | 5 (0–10) | 5 (0–10) | .84 |
| Bishop score >4, n (%) | 81 (63.8) | 80 (64.0) | .97 |
| Membrane status, n (%) | .84 | ||
| Amniotomy | 103 (81.1) | 101 (80.8) | |
| Spontaneous rupture of membranes | 15 (11.8%) | 13 (10.4%) | |
| Premature rupture of membranes | 9 (7.1%) | 11 (8.8%) | |
a Data are expressed as mean ± SD;
b Other indications included conditions such as intrahepatic cholestasis of pregnancy, essential hypertension, renal disease, history of abruptio placentae, history of fetal death, history of deep venous thromboembolism;
The primary outcome, cesarean delivery, was similar between groups (25.2% in the routine group vs 19.2% in the DC group (RR, 0.76; 95% CI, 0.48–1.21; P = .25; Table 3 ). The difference in the rate of cesarean delivery for an arrest disorder (arrest of the active phase or arrest of descent) was not significant by randomization (59.4% in the routine group vs 70.8% in the DC group; RR, 1.19; 95% CI, 0.81–1.75; P = .38; Table 3 ). Although intrapartum complications, as a whole, were similar by randomization, the rate of chorioamnionitis was higher among those who were assigned randomly to the DC group (5.5% in the routine group vs 12.8% in the DC group; P = .05; Table 4 ). Postpartum complications were similar among randomized groups ( Table 4 ).
| Group | |||
|---|---|---|---|
| Characteristic | Routine (n = 127) | Oxytocin discontinuation (n = 125) | P value |
| Cesarean delivery, n (%) | 32 (25.2) | 24 (19.2) | .25 |
| Indications for cesarean delivery, n (%) | .74 | ||
| Nonreassuring fetal heart tracing | 8 (25.0) | 7 (29.2) | |
| Arrest of the active phase | 12 (37.5) | 11 (45.8) | |
| Arrest of descent | 7 (21.9) | 6 (25.0) | |
| Failed induction of labor | 2 (6.3) | 0 | |
| Malpresentation | 2 (6.3) | 0 | |
| Other | 1 (3.1) | 0 | |
| Latent phase of labor, hr a , b | n = 114 7.7 (1.3–54.6) | n = 117 10.4 (0.3–23.7) | .05 |
| Active phase of labor, hr a , b | n = 102 3.0 (0.1–15.3) | n = 107 3.9 (0.1–15.5) | .01 |
| Second stage of labor, hr a , b | n = 95 0.5 (0–6.7) | n = 101 0.5 (0–6.5) | .97 |
| Ruptured membranes, hr a | n = 127 6.1 (0.1–32.7) | n = 125 8.0 (0–37.4) | .01 |
a Data are expressed as median (range);
b The lengths of the first and second stages of labor were calculated for those patients who completed each phase or stage.
| Group | |||
|---|---|---|---|
| Characteristic | Routine (n = 127) | Oxytocin discontinuation (n = 125) | P value |
| Oxytocin dose in active labor, mU/min a | 9.8 ± 5.4 | 10.8 ± 6.2 | .23 |
| Maximum oxytocin dose, mU/min a | 13.0 ± 6.8 | 13.1 ± 6.6 | .87 |
| Cervical dilation once diagnosed in active labor, cm b | 5 (3–7) | 5 (3–9.5) | < .001 |
| Use of intrauterine pressure catheter, n (%) | 42 (33.1) | 42 (33.6) | .93 |
| Cervical examinations, n b | 7 (1–17) | 7 (2–13) | .03 |
| Epidural anesthesia, n (%) | 122 (96.1) | 118 (94.4) | .54 |
| Intrapartum complications, n (%) | .24 | ||
| Preeclampsia | 5 (3.9) | 3 (2.4) | |
| Chorioamnionitis | 7 (5.5) | 16 (12.8) | |
| Abruptio placentae | 1 (0.8) | 1 (0.8) | |
| Other | 12 (9.5) | 8 (6.4) | |
| Postpartum complications, n (%) | |||
| Postpartum hemorrhage | 8 (6.3) | 8 (6.4) | |
| Preeclampsia diagnosed after delivery | 1 (0.8) | 0 | |
| Endometritis | 0 | 1 (0.8) | |
| Acute blood loss anemia | 10 (7.9) | 17 (13.6) | |
| Other | 2 (1.6) | 3 (2.4) | .48 |
a Data are expressed as mean ± SD;
The median active phase of labor was longer among women who were assigned randomly to the DC group by 1 hour (3.0 hours in the routine group vs 3.9 hours in the DC group; P = .01; Table 3 ). Duration of ruptured membranes was also higher in women assigned randomly to the DC group (median, 6.1 hours in the routine group vs 8.0 hours in the DC group; P = .01; Table 3 ). Latent phase and second stage of labor duration were similar ( Table 3 ), as were neonatal outcomes ( Table 5 ).
| Group | |||
|---|---|---|---|
| Characteristic | Routine (n=127) | Oxytocin discontinuation (n = 125) | P value |
| Male sex, n (%) | 70 (55.1) | 66 (52.8) | .71 |
| Apgar score | |||
| At 1 min a | 8 (1–9) | 8 (1–9) | .27 |
| At 5 min a | 9 (6–10) | 9 (8–10) | .27 |
| Neonatal weight, g a | 3475 (2345–4495) | 3475 (2715–4650) | .55 |
| Arterial cord pH a | 7.26 (6.94–7.64) | 7.27 (7.08–7.68) | .21 |
| Neonatal resuscitation, n (%) | 9 (7.1) | 7 (5.6) | .63 |
| Admission to neonatal intensive care unit, n (%) | 10 (7.95) | 9 (7.25) | .84 |
| Neonatal antibiotic use, n (%) | 9 (7.1) | 16 (12.8) | .13 |
| Length of stay, d a | 3 (2–7) | 3 (2–8) | .79 |
Thirty-one participants (24.8%) in the DC group had the oxytocin infusion continued once active labor was achieved, despite randomization to the DC group ( Figure ). Data regarding rationale for this occurrence were not always available. Discussion with participating nurses and providers identified reasons for this likely to be provider preference to continue the infusion, provider being unaware that the patient was enrolled in the DC group, or a short active phase. Oxytocin was restarted in an additional 58 patients from the DC group (46.4%), which was allowed by the study protocol. Restarting oxytocin was mostly due to a lack of cervical change (44.8%) or a decrease in contraction frequency (39.7%). Among the 58 patients whose infusion was restarted, 51 women delivered vaginally (87.9%). Of the remaining 36 patients from the DC group, 9 women never achieved active labor; 2 women achieved active labor after undergoing cervical ripening alone, and 25 women never had the oxytocin infusion restarted, of whom 84% (n = 21) delivered vaginally.
Because of the number of patients in the DC group who had oxytocin infusion continued, analyses were performed by actual treatment received ( Table 6 ). Cesarean delivery rates were similar by actual treatment received (22.8% in those treated as routine vs 21.3% in those treated as DC; P = .78); the median active phase of labor was prolonged in the discontinuation group when analyzed by actual treatment received (3.0 hours when oxytocin was continued vs 4.2 hours in the group where oxytocin was discontinued; P = .004).
