Objective
The purpose of this study was to estimate the association between epidural dosing and the risk of uterine rupture in women who attempt vaginal birth after cesarean delivery (VBAC).
Study Design
A nested case-control study within a multicenter retrospective cohort of >25,000 women with previous cesarean delivery compared cases of uterine rupture with women without rupture (control subjects) while attempting VBAC with epidural anesthesia. Dose timing, frequency, and quantity were compared. Time-to-event analyses were performed to estimate the association between epidural dosing and risk for uterine rupture while accounting for labor duration.
Results
Of 804 women in the nested case-control study, 504 women (62.7%) had epidural anesthesia, with no statistical difference in epidural usage rates between cases and control subjects (70.4% vs 62.4%; P = .09). Cox-regression analysis revealed a dose-response relationship between the number of epidural doses and uterine rupture risk: 1 dose (hazard ratio, 2.8; 95% confidence interval [CI], 1.4–5.7), 2 doses (hazard ratio, 3.1; 95% CI, 2.2–6.2), 3 doses (hazard ratio, 6.7; 95% CI, 3.8–12.1), ≥4 doses (hazard ratio, 8.1; 95% CI, 5.4–18.2).
Conclusion
Clinical suspicion for uterine rupture should be high in women who require frequent epidural dosing during a VBAC trial.
Attempting vaginal delivery after previous cesarean (VBAC) remains an important delivery option for women with such a history. Optimization of patient selection and management of VBAC attempts maximizes the chances for success and minimizes morbidity. Despite this, the rare risk of uterine rupture remains. Physicians who manage VBAC attempts take great care to identify the classically described signs and symptoms of uterine rupture, which includes fetal heart rate abnormalities, pain, vaginal bleeding, loss of fetal station, and maternal hemodynamic instability. However, in the setting of epidural use, it is possible that maternal pain from uterine rupture may be blunted and may result in the loss of this objective measure.
No published data exist to describe the relationship between epidural use and dosing and the risk of uterine rupture in women who attempt VBAC. We undertook this study to test the hypothesis that dosing patterns were related directly to the risk of uterine rupture, and specifically that women who attempt VBAC with epidural anesthesia still sense pain that can be measured by an increase in the number of epidural doses before rupture.
Methods
A nested case-control study was conducted between 1999 and 2005 within a 17-center retrospective cohort study of pregnant women with at least 1 previous cesarean delivery. The parent cohort study was designed to estimate the maternal risks that are associated with attempted VBAC, specifically the risk of uterine rupture. To further identify factors that are associated with VBAC success and those factors that are associated with uterine rupture, all the cases (women who attempted VBAC and experienced uterine rupture) were matched on hospital site with 5 control subjects who attempted VBAC but did not sustain a uterine rupture. Control subjects were chosen at random by a random number generator that was applied to the study number of all women who attempted VBAC without experiencing a rupture. The women who attempted VBAC with epidural anesthesia were eligible for this secondary study. Institutional review board approval was obtained from all study sites. A detailed description of the parent study has been previously published; a brief description follows.
International Classification of Disease, 9th revision , codes for “previous cesarean delivery, delivered” were used to identify eligible participants. The accuracy of these codes for the identification of patients who attempt VBAC had been validated previously. Patients were included if they carried a single or twin gestation and had a previous cesarean birth and were excluded if their previous uterine incision was not low transverse or their pregnancy was complicated by a known fetal anomaly. Dedicated, trained research nurses extracted the charts of all patients who were included in the parent cohort study in detail, which included information on sociodemographics; obstetric, medical, and surgical history; pregnancy course, and delivery outcomes. Data for patients who were selected for the case-control study were reextracted for further detail, which included all procedure, medication and dosing, and examination details in 15-minute time increments throughout labor.
The primary outcome, uterine rupture , was defined explicitly a priori as full-thickness uterine wall disruption that was accompanied by clinical sign(s) of uterine rupture that included at least 1 of the following events: nonreassuring fetal heart rate tracing immediately preceding surgery, hemoperitoneum at the type of peritoneal entry, or signs of maternal hemorrhage (including systolic blood pressure <70 mm Hg, diastolic blood pressure <40 mm Hg, or heart rate >120 beats/min). This definition distinguished cases from incidental findings of “uterine windows” and asymptomatic scar separation, the clinical significance of which is unknown.
For this analysis, women who attempted VBAC were identified as having epidural anesthetic during labor by a directly extracted dichotomous variable for “epidural” and were verified by the epidural medication list and route of delivery. In women who had epidural anesthetic, cases (uterine rupture) were compared with control subjects (no uterine rupture) with respect to baseline characteristics. Dichotomous variables were compared with the use of χ 2 or Fisher’s exact tests, as appropriate. The distribution of continuous variables was tested with the use of the Shapiro-Wilk test and then compared between groups with the use of the Student t test and Mann-Whitney U test, as appropriate. The incidence of epidural use and number of doses were estimated within the parent cohort and within the case-control sample and then compared between cases and control subjects. Sensitivity analyses were performed to compare the control patients with those patients in the parent cohort who underwent VBAC and did not experience a uterine rupture on baseline characteristics and relevant confounders to assure that the patients who were chosen at random for this nested analysis were representative.
Time-to-event analysis was used to estimate the association between number of epidural doses and the risk of uterine rupture. Patients were classified as having the event of interest (uterine rupture) or were censored (delivered). Time zero was defined as the beginning of the active phase of labor, which was defined as either the time at 4-cm dilation or at admission for patients who were admitted at ≥4 cm dilation. Imputed values were not used because data were nearly complete; 0-1.8% of fields were missing for any given variable. The number of epidural doses that were required in the final 90 minutes before the event or censor was used to create a dummy categoric variable for epidural dosing, with zero doses required in that period as the reference. Kaplan-Meier plots were used to illustrate graphically the risk of uterine rupture over time by stratum of epidural doses. Bivariate analyses were used to identify potentially confounding effects of the epidural dose-uterine rupture risk relationship. Cox proportional hazard regression was used to model the effect of number of epidural doses on risk of uterine rupture; adjustment was made for relevant potentially confounding effects that were identified in the bivariate analyses and those historically proposed. The proportional hazards assumption was tested with the global test of Grambsch. All statistical analyses were completed with the STATA software package (version 10, special edition; Stata Corporation, College Station, TX).
Results
Of 25,005 women with a history of at least 1 previous low-transverse cesarean delivery, 13,706 women attempted VBAC, and 11,299 women elected repeat cesarean delivery. Cases were 134 women who experienced a uterine rupture, and 670 women who did not experience a uterine rupture while attempting VBAC were chosen randomly to be control subjects. Cases and control subjects with epidural anesthesia were statistically similar on average with respect to maternal age, number of previous pregnancies, gestational age at delivery, infant birthweight, incidence of maternal comorbidities, or delivery hospital type. Women who experienced a uterine rupture were less likely to deliver postterm or have had a previous vaginal delivery than those women who did not experience a uterine rupture. Additionally, patients who experienced a uterine rupture were more likely to have been exposed to oxytocin and to have had a history of >1 previous cesarean delivery than control patients ( Table 1 ).
| Characteristic | Case (n = 93) | Control subject (n = 411) | P value |
|---|---|---|---|
| Maternal age, y a | 31.1 ± 4.8 | 31.0 ± 5.5 | .17 |
| Gravidity, n a | 3.1 ± 1.4 | 3.3 ± 1.6 | .46 |
| Gestational age at delivery, wk a | 39.0 ± 2.0 | 38.7 ± 2.7 | .26 |
| Delivery <34 wk, % | 1.2 | 2.8 | .41 |
| Delivery >41 wk, % | 8.4 | 18.8 | .02 |
| Birthweight, g a | 3452 ± 665.2 | 3430 ± 635.5 | .76 |
| >1 previous cesarean delivery, % | 18.1 | 9.5 | .02 |
| Previous vaginal delivery, % | 16.7 | 32.6 | < .01 |
| Induction of labor, % | 43.4 | 35.6 | .18 |
| Oxytocin exposure, % | 65.8 | 46.1 | < .01 |
| Gestational diabetes mellitus, % | 4.3 | 5.1 | .74 |
| Pregestational diabetes mellitus, % | 0.7 | 0.9 | .39 |
| Chronic hypertension, % | 2.1 | 4.9 | .25 |
| Preeclampsia, % | 2.5 | 1.8 | .67 |
| Black race, % | 16.9 | 24.1 | .16 |
| University hospital, % | 66.9 | 68.2 | .91 |
| Obstetrics/gynecology residency, % | 26.2 | 34.5 | .11 |
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