Maternal outcomes, stratified by both history of vaginal delivery and type of labor, are presented in Table 2. There was no maternal mortality in the entire cohort. Regardless of history of vaginal delivery, women who underwent induction of labor were significantly less likely to have a vaginal delivery. Aside from the outcome of vaginal delivery, however, statistically significant differences in maternal outcomes between those women who underwent induction and those who labored spontaneously were limited to the primiparous cohort. Specifically, primiparous women who underwent induction were more likely to experience a uterine rupture, transfusion, venous thromboembolism, and hysterectomy.
Perinatal outcomes stratified by history of vaginal delivery and type of labor are presented in Table 3. Regardless of the history of vaginal delivery, no measure of perinatal morbidity significantly differed between women who were and were not induced.
Data regarding the cervical examination at initiation of labor induction were available for 1,494 primiparous women (87.8%) and 1,374 women (88.2%) with a prior vaginal delivery. After further stratification by cervical ripeness, the maternal outcome variables that were significantly different between women who spontaneously labored and those who underwent induction are summarized in Table 4. Vaginal delivery was significantly more likely when induction was initiated with a favorable cervix than with an unfavorable cervix regardless of whether women had a prior vaginal delivery. The frequency of uterine rupture for primiparous women, however, was similar regardless of cervical status at initiation of labor. The frequency of other maternal morbidities did not differ on the basis of initial cervical status at labor induction.
Last, multivariable logistic regression was used to determine the independent association of labor induction with outcome after attempted VBAC. In this analysis, dichotomous variables representing “induction with a favorable cervix” and “induction with an unfavorable cervix” were entered as independent variables into the same regression and compared with “spontaneous labor.” After controlling for differences in maternal age, race, body mass index at delivery, prior cesarean delivery for arrest of progress or descent, and birth weight, an induction with an unfavorable cervix in primiparous women decreased the chance of a successful VBAC when compared with spontaneous labor (adjusted odds ratio 0.46, 95% confidence interval [CI] 0.39–0.53). However, primiparous women with favorable cervices undergoing induction of labor experienced the same success rate for VBAC as women in spontaneous labor (adjusted odds ratio 1.19, 95% CI 0.93–1.53). Results were similar for women with a prior vaginal delivery (adjusted odds ratio 0.50, 95% CI 0.40–0.62; odds ratio 1.24, 95% CI 0.90–1.71, respectively). As in univariable analysis, both uterine rupture (adjusted odds ratio 1.82, 95% CI 1.07–3.08) and the composite measure of other maternal morbidity (adjusted odds ratio 1.98, 95% CI 1.29–3.04) were significantly associated with induction of labor in women with no prior vaginal delivery.
The appropriateness of a labor induction for women attempting a VBAC remains controversial. The continuing controversy exists, to a large degree, because of the conflicting results from studies that have examined the health outcomes of induction of labor in women with a prior cesarean delivery.7–14 Several methodologic reasons may account for these inconsistent results. Many study groups have included women with different numbers of prior cesarean deliveries, different types of cesarean incisions, and different histories with regard to vaginal delivery. 7–12 Thus, the independent effect of an induction of labor in a specific circumstance, such as in a woman whose only prior birth was through a low-transverse cesarean incision, was not possible to discern from these studies. While other investigators have analyzed more specific study populations, retrospective data collection has been a cause for concern. For example, Lydon-Rochelle and colleagues,14 who assessed the chance of uterine rupture after labor induction in women with one prior cesarean delivery, based the diagnosis of uterine rupture on International Classification of Diseases, 9th revision, coding alone, a method with known potential for ascertainment bias.17 Additionally, retrospective analyses have not been able to account for other potentially influential factors, such as cervical status at initiation of induction, and frequently have studied intermediate endpoints.3,13,14
In the present analysis, we restricted the study population to women with a singleton gestation at term and one prior low-transverse cesarean delivery. We chose this group because it represents the majority of women undergoing a trial of labor and limits potentially confounding effects of other factors. In an effort to further ensure that the association of labor induction with trial of labor outcomes was not affected by other potentially confounding factors, the analysis was stratified by history of vaginal delivery and cervical ripeness at the initiation of labor induction. The possibility of ascertainment bias was minimized by the prospective study design, the use of trained abstractors for all data collection, and the reconfirmation of certain health outcomes, such as uterine rupture, by confirmatory chart reviews. Finally, in addition to assessing outcomes such as successful VBAC and uterine rupture, we have examined a more extended set of maternal and neonatal morbidity.
The results of the study indicate that a broad conclusion regarding the appropriateness of labor induction for women with one prior cesarean delivery is unlikely to be a useful approach. Instead, counseling with regard to labor induction will need to take into account certain characteristics, such as whether a woman has had a prior vaginal delivery. Although the overall chance of successful VBAC is greater in women with a prior vaginal birth, these women as well as those without a prior vaginal birth have a decreased chance of a successful VBAC after induction of labor is initiated with an unfavorable cervix.18 In contrast, as demonstrated in the multivariable analysis, an induction of labor with a favorable cervix has a similar rate of successful VBAC in comparison to spontaneous labor in women with one prior cesarean, regardless of prior vaginal delivery.
Whereas labor induction, compared with spontaneous labor, increases the risk of uterine rupture in primiparous women, no significant association between labor induction and uterine rupture was found in women with a prior vaginal delivery. This difference in the association of labor induction with uterine rupture as a function of history of vaginal delivery has not been well documented previously. Few studies have specifically examined the outcome of uterine rupture after induced labors in women with both a prior cesarean delivery and a prior vaginal delivery.19–21 Investigators who have examined this specific subgroup have each analyzed fewer than 100 women with a prior vaginal delivery, thus limiting any conclusions that could be drawn. In the present study, which contains more than 1,500 women with a prior vaginal delivery and an induced labor, there is much greater power to have found a difference. It should be noted that even with this number of women analyzed, the possibility remains that there could be a small absolute increase in uterine rupture with labor induction that would not have been discerned.
With regard to the primiparous women, there has previously been controversy as to the circumstances that predispose a woman to an increased risk of rupture during labor induction. Some investigators have found this increased risk with oxytocin, some have found it with prostaglandin only, and others have determined that an increased risk exists only when prostaglandin and oxytocin are used in combination. 4,12–14,22 The disparity of these results may be due to several disparities in the underlying methodology of these studies. The study by Lydon-Rochelle et al14 that implicated prostaglandin, for example, did not have information as to whether the prostaglandin was used alone or in combination with other agents. In contrast, after analyzing the data by specific circumstance of prostaglandin use and including only women who received intravaginal prostaglandin, Macones et al22 did not find a strong association between prostaglandin agents and uterine rupture, with a small increased risk only when prostaglandin was used sequentially with oxytocin. Neither study accounted for cervical status at initiation of induction, raising the possibility that induction with an unfavorable cervix, which would predispose to use of ripening agents such as prostaglandin, could be the factor underlying any increased risk attributed to prostaglandin.
Our results call into question the supposition that the status of the cervix, rather than the induction agent itself, may be the actual factor associated with an increased risk of uterine rupture, as there was no evidence that rupture or other maternal morbidity was increased in women with an unfavorable cervix at initiation of induction. Also, there was no evidence that prostaglandin agents, either alone or in combination with oxytocin, were associated with a significantly elevated risk of uterine rupture greater than induction undertaken with oxytocin alone. However, given the relatively few patients who received prostaglandin agents, there is limited power in this study to assess this association.
One issue that has been raised with regard to prior studies that have evaluated labor induction after prior cesarean delivery is that the health outcomes usually examined, namely successful VBAC and uterine rupture, are intermediate outcomes, and that the actual association of labor induction with other maternal and perinatal morbidity remains uncertain.3 The present study, which did examine an extended number of these morbidities, allows several conclusions to be drawn. As with uterine rupture, several measures of maternal morbidity are statistically increased in association with labor induction, although only in primiparous women. The frequency of these outcomes does not appear to be highly dependent on whether induction occurs with a favorable or unfavorable cervix. Also, although several measures of maternal morbidity were statistically increased, the attributable risk was small, as no increase greater than 0.9% was seen in either the rates of transfusion, venous thromboembolism, or hysterectomy. Given that this was an observational study, the chance remains that the outcome differences were not due to the labor induction itself, but to other differences in women who undergo labor induction. In an effort to limit this possibility, we performed multivariable regression to adjust for possible confounding variables.
Labor induction was not associated with a statistically significant increase for any measure of perinatal morbidity. For some outcomes, this finding should be reassuring for women who desire a VBAC, but are confronted with the need to iatrogenically initiate labor. For example, this study has 80% power to detect an increase as small as 2.5% in the frequency of special care nursery admission among primiparous women. Even with the present sample size, however, the infrequency of some outcomes, such as hypoxic-ischemic encephalopathy, allows the possibility that an increase in these outcomes could not be discerned in this study.
In this analysis, all women who underwent spontaneous labor, regardless of whether they ultimately received oxytocin augmentation, were compared with those who underwent labor induction. The decision not to stratify separately by augmentation status was made for several reasons. First, augmentation is in and of itself evidence that a labor is not progressing at the same pace as a spontaneous labor. Consequently, finding an increased cesarean delivery rate or maternal complication such as need for transfusion may not be independently associated with the augmentation itself, but the prolonged labor that engendered the augmentation in the first place. Also, this comparison is the relevant comparison from the perspectives of a patient and physician who are discussing whether or not to proceed with labor induction.
Indeed, given the data in this analysis, women who desire a VBAC and are confronted with the decision to undergo labor induction can be counseled that their risk for most serious adverse outcomes is not significantly increased, the adverse outcomes that are increased have a small attributable risk associated with induction, and that even this small attributable risk appears limited to women without a prior vaginal birth. Regardless of history of vaginal delivery, however, women should be aware that induction initiated with an unfavorable cervix may decrease the chance of successful VBAC, and physicians should consider limiting this practice to cases where expectant management is no longer the most reasonable option.
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In addition to the authors, other members of the National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network are as follows:
© 2007 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
- Ohio State University — J. Iams, F. Johnson, S. Meadows, H. Walker
- University of Alabama at Birmingham — J. Hauth, A. Northen, S. Tate
- University of Texas Southwestern Medical Center — S. Bloom, J. Gold, D. Bradford
- University of Utah — M. Belfort, F. Porter, B. Oshiro, K. Anderson, A. Guzman
- University of Chicago — J. Hibbard, P. Jones, M. Ramos-Brinson, M. Moran, D. Scott
- University of Pittsburgh — K. Lain, M. Cotroneo, D. Fischer, M. Luce
- Wake Forest University — P. Meis, M. Swain, C. Moorefield, K. Lanier, L. Steele
- Thomas Jefferson University — A. Sciscione, M. DiVito, M. Talucci, M. Pollock
- Wayne State University — M. Dombrowski, G. Norman, A. Millinder, C. Sudz, B. Steffy
- University of Cincinnati — T. Siddiqi, H. How, N. Elder
- Columbia University — F. Malone, M. D’Alton, V. Pemberton, V. Carmona, H. Husami
- Brown University — H. Silver, J. Tillinghast, D. Catlow, D. Allard
- Northwestern University — A. Peaceman, M. Socol, D. Gradishar, G. Mallett
- University of Miami — G. Burkett, J. Gilles, J. Potter, F. Doyle, S. Chandler
- University of Tennessee — W. Mabie, R. Ramsey
- University of Texas at San Antonio — D. Conway, S. Barker, M. Rodriguez
- University of North Carolina — K. Moise, K. Dorman, S. Brody, J. Mitchell
- University of Texas at Houston — L. Gilstrap, M. Day, M. Kerr, E. Gildersleeve
- Case Western Reserve University — P. Catalano, C. Milluzzi, B. Slivers, C. Santori
- The George Washington University Biostatistics Center — E. Thom, H. Juliussen-Stevenson, M. Fischer
- National Institute of Child Health and Human Development — D. McNellis, K. Howell, S. Pagliaro