By Rebecca H. Allen, MD, MPH, Editor
SYNOPSIS: In this retrospective cohort study among patients who underwent second trimester induction of labor for fetal demise or pregnancy termination, those with two or more prior cesarean deliveries had an increased risk of uterine rupture (6.25%) compared to those with one prior cesarean delivery (0%) or no prior cesarean delivery (0%) (P = 0.004).
SOURCE: Latta K, Barker E, Kendall P, et al. Complications of second trimester induction for abortion or fetal demise for patients with and without cesarean delivery. Contraception 2022;117:55-60.
Whether multiple prior cesarean deliveries increase the risk of uterine rupture and other complications with second trimester induction of labor is unclear. The authors of this study sought to delineate those risks.
This was a retrospective cohort study of patients who underwent induction of labor for pregnancy termination or fetal demise between 14 weeks 0 days and 23 weeks 6 days of gestation at a hospital system in Chicago from January 2009 to September 2019. Inclusion criteria were induction with misoprostol alone or mifepristone plus misoprostol and indications of preterm premature rupture of membranes (PPROM), fetal anomaly, intrauterine fetal demise, or maternal health condition such as severe preeclampsia. The misoprostol regimen was at the discretion of the clinician but typically used an 800-mcg loading dose followed by 400 mcg every three hours, either vaginally or sublingually. Exclusion criteria were preterm labor (cervical dilation of 2 cm or more), cervical insufficiency, intrauterine infection prior to start of the induction, and oxytocin or osmotic dilator use as the main method of induction.
The authors used the electronic medical record to collect sociodemographic and clinical characteristics. Complications were defined as failed induction, retained placenta, infection, hemorrhage (estimated blood loss 500 mL or more), blood transfusion, intensive care unit (ICU) admission, uterine rupture, death, and hospital readmission. Serious complications included blood transfusion, uterine rupture, ICU admission, hospital readmission, and death. Three groups were compared: patients with no prior cesarean deliveries, patients with one prior cesarean delivery, and patients with two or more prior cesarean deliveries.
Over the 10-year study period, 510 patients met inclusion criteria. Among this sample, 411 women had no prior cesarean, 77 had one prior cesarean, and 32 had two or more prior cesareans. Of the 32 patients with two or more prior cesareans, 25 patients had two cesarean deliveries only, six patients had three prior low-transverse cesarean deliveries, and one patient had four prior low-transverse cesarean deliveries. In the entire sample, 11 patients had a prior classical cesarean delivery, eight had one prior classical cesarean delivery, and three had one prior low-transverse and one prior classical cesarean delivery.
The most common indications for induction were fetal demise (41%), fetal anomaly (37.5%), PPROM (23.8%), and maternal health (4.2%). A total of 138 (26.5%) patients had mifepristone pretreatment prior to their misoprostol induction. This was similar among the three groups (P = 0.72). In the study, 82 patients received a fetal injection of potassium chloride; this was no different in the three groups (P = 0.42).
Serious complications were more common among those with two or more cesarean deliveries compared to the other groups (18.75% vs. 7.79% vs. 6.08%; P = 0.04). This was driven by their rates of experiencing uterine rupture (6.25% vs. 0% vs. 0%; P = 0.004) and ICU admission (6.45% vs. 1.3% vs. 0.49%; P = 0.02). The other individual complications showed no difference among the three groups.
The two patients with uterine rupture each had two prior low-transverse cesarean deliveries and had received potassium chloride injections at 22 weeks of gestation. One patient received a total of 1,600 mcg of misoprostol and the other a total of 2,400 mcg of misoprostol. There was one death in the group in a patient with one prior cesarean, which was presumed to be the result of an amniotic fluid embolism. In multivariable analysis that controlled for age, obesity, gravidity, gestational age of 20 weeks or more, indication for induction, and use of mifepristone, patients with two or more prior cesarean deliveries had increased odds of a complication compared to those with no prior cesarean delivery (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.30-7.02) and one prior cesarean delivery (aOR, 2.71; 95% CI, 1.09-6.86). There was no difference between the one prior cesarean delivery group and the no prior cesarean delivery group in the multivariable analysis (aOR, 1.11; 95% CI, 0.64-1.89). Mifepristone was used in 26.4% of the subjects equally between the three groups and was associated with a reduced rate of retained placenta requiring surgery.
COMMENTARY
This large retrospective cohort study suggests that patients with two or more prior cesarean deliveries are at an increased risk of complications with induction of labor in the second trimester, particularly uterine rupture and ICU admission. The study was limited by the variations in misoprostol dosing regimens and the use of mifepristone. Induction of labor for uterine evacuation in the second trimester is an option for patients who either desire that treatment route or when there is no dilation and evacuation provider available. The addition of mifepristone to misoprostol regimens previously has been shown to reduce the interval to delivery and retained placenta rates, as this study shows. The American College of Obstetricians and Gynecologists recommends mifepristone 200 mg orally 24 to 48 hours prior to the misoprostol induction, with an 800-mcg loading dose followed by 400 mcg every three hours either vaginally, buccally, or sublingually for a maximum of five doses.1 The new U.S. Food and Drug Administration regulations allowing retail pharmacies to dispense mifepristone may make this regimen more accessible compared to misoprostol-only regimens.2
Uterine rupture is possible with second trimester induction, although it is not common. There are two systematic reviews evaluating the issue. One showed that the incidence of uterine rupture with second trimester misoprostol induction of labor was 0.4% (2/461) in women with one prior low-transverse cesarean delivery, 0% (0/46) in those with two prior low-transverse cesarean deliveries, and 50% (1/2) in those with a prior classical cesarean delivery.3 However, the authors thought that the numbers in those with multiple prior cesarean deliveries or classical cesarean deliveries were too small to reach conclusions.
Another systematic review demonstrated that the use of misoprostol in second trimester induction in patients with a prior cesarean delivery resulted in a risk of uterine rupture of 0.28% compared to 0.04% without a prior cesarean delivery.4 This study did not specify the type or number of prior cesarean deliveries. Nevertheless, this risk is comparable to the risk for uterine rupture during trial of labor after cesarean (< 1%) and generally is considered acceptable. Interestingly, in the current study, there were no uterine ruptures among patients with prior classical cesarean deliveries. The overall rate of rupture among women with one or more prior cesarean delivery in this study was 1.8% (2/109), which is higher than reported in the systematic reviews mentioned earlier. However, even in this large cohort, the numbers were small in the group of two or more prior cesarean deliveries (n = 32).
This study adds to the literature regarding uterine rupture rates in this setting. It is a difficult topic to study because, thankfully, it is a rare event. More information still is needed to guide clinicians and patients in this setting. I speculate that adding mifepristone to the misoprostol regimen likely is helpful, since it will reduce the amount of misoprostol needed to achieve delivery, which, in turn, would reduce the risk of rupture. It may be that the doses of misoprostol should be adjusted in women with multiple prior cesarean deliveries, but, unfortunately, we do not have good evidence to guide us. Of the patients who had a uterine rupture in this study, one had the 800-mcg loading dose, and one did not. Overall, second trimester labor induction among women with prior cesarean deliveries is safe and something that should be offered to patients and, ideally, dilation and evacuation also should be considered and available as an option.
REFERENCES
- [No authors listed]. ACOG Practice Bulletin No. 135: Second-trimester abortion. Obstet Gynecol 2013;121:1394-1406.
- Belluck P. Abortion pills can now be offered at retail pharmacies, F.D.A. says. The New York Times. Published Jan. 3, 2023. https://www.nytimes.com/2023/01/03/health/abortion-pill-cvs-walgreens-pharmacies.html
- Berghella V, Airoldi J, O’Neill AM, et al. Misoprostol for second trimester pregnancy termination in women with prior caesarean: A systematic review. BJOG 2009;116:1151-1157.
- Goyal V. Uterine rupture in second-trimester misoprostol-induced abortion after cesarean delivery: A systematic review. Obstet Gynecol 2009;113:1117-1123.
