obstetric outcomes associated with induction of labor

Accepted Manuscript

Obstetric outcomes associated with induction of labor after two prior cesareandeliveries

Emily S. Miller, MD MPH, William A. Grobman, MD MBA

PII: S0002-9378(15)00125-8

DOI: 10.1016/j.ajog.2015.02.003

Reference: YMOB 10262

To appear in: American Journal of Obstetrics and Gynecology

Received Date: 12 November 2014

Revised Date: 8 January 2015

Accepted Date: 9 February 2015

Please cite this article as: Miller ES, Grobman WA, Obstetric outcomes associated with induction oflabor after two prior cesarean deliveries, American Journal of Obstetrics and Gynecology (2015), doi:10.1016/j.ajog.2015.02.003.

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http://dx.doi.org/10.1016/j.ajog.2015.02.003

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Obstetric outcomes associated with induction of labor after two prior cesarean deliveries

Emily S MILLER, MD MPH

William A GROBMAN, MD MBA

Chicago, IL

Northwestern University Feinberg School of Medicine

Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine

The authors report no conflict of interest.

To be presented February 5th, 2015 at the Society for Maternal Fetal Medicine, San

Diego CA

Corresponding author:

Emily S Miller

250 E. Superior St, Suite 05-2191, Chicago, IL 60611

Phone 312-472-4685

Fax 312-472-4687

[email protected]

Reprints not available

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Condensation

Women with two cesareans undergoing induction have similar obstetric outcomes to

women with one cesarean undergoing induction and women with two cesareans

undergoing a repeat cesarean.

Short Title

Induction in women with multiple cesareans

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Abstract

Objective: To determine whether, in the setting of induction, obstetric outcomes differ

based on the number of prior cesarean deliveries (CD) and to determine whether

women with two cesareans undergoing induction face increased risks of adverse

outcomes compared to women undergoing a repeat CD.

Study Design: This is a secondary analysis of a 4-year multi-center prospective cohort.

Women with one or two CD were included. Frequencies of vaginal birth after cesarean

(VBAC) as well as maternal and neonatal complications were compared among women

with one CD undergoing induction, women with two CD undergoing induction, and

women undergoing repeat CD with two cesareans.

Results: Of the 10,262 women included in this study, 4100 (40.0%) underwent an

induction after one CD, 152 (1.5%) underwent an induction after two CD, and 6010

(58.6%) had a repeat CD after two CD. In women undergoing induction, the chance of

VBAC was no different in women with two compared to one prior CD (65% vs 69%,

p=0.28). Similarly, composite maternal (aOR 1.2, 95% CI 0.6-2.3) and neonatal (aOR

1.1, 95% CI 0.7-1.7) outcomes were not different between the two groups. In women

who had two prior CD, undergoing an induction carried similar composite adverse

maternal and neonatal outcomes compared to having a repeat CD (aOR 0.7, 95% CI

0.3-2.0; aOR 1.1, 95% CI 0.6-2.2).

Conclusions: Labor induction outcomes are similar regardless of whether women have

had one or two CD. After two CD, undergoing an induction carries similar maternal and

neonatal risks as having a repeat CD.

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Key Words: vaginal birth after cesarean, trial of labor after cesarean, induction of labor,

multiple cesarean, repeat cesarean

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Introduction

There is significantly increased maternal morbidity associated with each additional

cesarean delivery. For example, the risks of blood transfusion, hysterectomy, operative

injury, and intensive care admission all increase with each cesarean performed.1 The

alternative to having a repeat cesarean is a trial of labor after cesarean (TOLAC), which

is associated with its own maternal and perinatal risks.2 As such, ACOG recommends

that women be counseled about the risks and benefits of each approach to delivery and

decide with their care provider which approach is most preferred.3

Due to the overall rise in cesarean frequency in the United States, an increasing

number of women have had two cesarean deliveries. When rates of maternal

complications for women with two prior cesareans undergoing TOLAC are compared to

those associated with having a repeat cesarean, transfusion, hysterectomy, and febrile

morbidity rates have been reported to be similar.4 Accordingly, ACOG considers women

with two prior low transverse cesareans to be reasonable candidates for TOLAC.3

Nevertheless, in women motivated for TOLAC with two prior cesarean deliveries,

spontaneous labor does not always occur. In this setting, if delivery is required, a

physician is faced with the decision of whether to induce labor or perform a third

cesarean delivery. To our knowledge, there are no existing studies that examine

obstetric outcomes specifically for women with two prior cesarean deliveries who

undergo an induction of labor. Therefore, we sought to estimate the chance of achieving

a vaginal birth after cesarean (VBAC) as well as the maternal and neonatal risks

associated with induction of labor in women with two prior cesarean deliveries.

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Materials and Methods

This is a secondary analysis of an observational study of women at 19 academic

medical centers between 1999 and 2002. The methodology of the primary study has

been described elsewhere.2 Women were included in the present analysis if they had

one or two prior cesarean deliveries, a singleton gestation, and no contraindication to a

vaginal delivery (e.g., placenta previa, breech presentation). Women with anomalous

fetuses or antenatal stillbirths were excluded. Women with prior classical, T or J, or low

vertical incisions also were excluded. Women with an unknown scar were included as it

was assumed they were most likely to have had a low transverse cesarean. Women

were divided into three groups: those with one prior cesarean delivery undergoing

induction of labor, those with two prior cesarean deliveries undergoing induction of

labor, and those with two prior cesarean deliveries undergoing a repeat cesarean

without a TOLAC.

Demographic and clinical characteristics of the population were examined. Student’s t

or chi squared tests were performed for these bivariable comparisons, as appropriate.

Maternal and perinatal outcomes, including the frequency of VBAC and maternal

complications were compared among the three study groups as well. A post-hoc power

calculation demonstrated that this study had 80% power to detect a 10% difference in

the chance of VBAC.

Maternal complications included endometritis, any blood product transfusion,

thromboembolic disease (deep venous thrombosis or pulmonary embolus), operative

injury (broad ligament hematoma, cystotomy, bowel injury, or ureteral injury), uterine

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rupture, uterine dehiscence, hysterectomy, intensive care unit admission, or postpartum

readmission. Uterine rupture was defined as either a disruption of both the myometrium

and serosa or a disruption of only the myometrium but with extension into the bladder or

broad ligament. Uterine dehiscence was defined as disruption of the myometrium alone

without any extension. A composite adverse maternal outcome was created and

documented to be present if any one of the aforementioned complications were present.

Neonatal complications also were analyzed and similar bivariable comparisons made.

Specific neonatal complications examined included a five minute Apgar of less than 7,

neonatal intensive care unit (NICU) admission, hypoxic-ischemic encephalopathy (HIE),

intrapartum stillbirth, and neonatal death. A composite adverse neonatal outcome was

created and documented to be present if any one of the aforementioned complications

were present.

Three multivariable logistic regressions were then performed to compare outcomes of

induction of labor in women with one versus two prior cesareans: one for the dependent

variable of VBAC, one for the dependent variable of the composite maternal outcome,

and one for the dependent variable of the composite neonatal outcome. Independent

variables were added to the equation if they were found to be significant in the

bivariable analysis with a p < 0.05. The presence of two prior cesarean deliveries was

forced into the equation and an adjusted odds ratio calculated to estimate whether the

number of prior cesareans remained associated with the chance of VBAC or adverse

maternal or neonatal outcomes. Multivariable logistic regressions also were used to

determine whether labor induction in the presence of two prior cesarean deliveries was

associated with differences in outcomes compared to scheduled cesarean delivery.

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Analyses were performed using Stata version 13.1 (StataCorp College Station, TX). All

tests were two tailed and a p < 0.05 was used to define statistical significance. As all

data were de-identified prior to analysis, this study was considered IRB exempt.

Results

There were 10,262 women included in this analysis. Of these, 4252 underwent an

induction of labor. One hundred and fifty-two (3.6%) of those undergoing induction had

two prior cesarean deliveries and 6010 (58.6%) had a repeat CD after two prior CD.

Comparisons between women undergoing induction with one or two prior cesareans as

well as comparisons between women with two prior cesareans undergoing induction

versus repeat cesarean without a trial of labor are shown in Table 1. Most notably,

women with two prior cesareans undergoing induction were significantly more likely to

have had a prior VBAC compared to either women with one prior cesarean undergoing

induction or women undergoing a repeat cesarean.

The frequency of VBAC was similar between women undergoing induction of labor with

one versus two prior cesareans. 2840 (69.3%) of women with one prior cesarean

achieved a VBAC compared to 99 (65.1%) of women with two prior cesareans (p=0.28).

Similarly, there were no significant differences in maternal complications for women

undergoing labor induction regardless of the number of prior cesarean deliveries or

approach to delivery (Table 2).

In terms of neonatal outcomes, there were no significant differences in any of the

neonatal outcomes, although the incidence of a five minute Apgar < 7, HIE, intrapartum

stillbirth, or neonatal death was low in all groups (Table 3).

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In the multivariable regressions comparing outcomes in women undergoing induction of

labor, after controlling for potential confounders, having had two prior cesareans did not

affect the odds of achieving a VBAC (Table 4). Similarly, in the multivariable regressions

for composite adverse outcomes, having two prior cesarean deliveries was not

significantly associated with an increased risk of either maternal or neonatal outcomes

(Table 4). In the multivariable regressions comparing outcomes in women with two prior

cesareans, women undergoing induction were no more likely than those undergoing

repeat cesarean to experience composite adverse maternal or neonatal outcomes

(Table 5).

Comment

Compared to women without a prior cesarean, women with two prior cesarean

deliveries are at an increased risk of pregnancy complications regardless of the

intended mode of delivery. Further compounding this issue is the fact that spontaneous

labor does not always occur and induction of labor carries potential additional risks. For

example, in women with one prior cesarean delivery, induction of labor (compared to

spontaneous labor) is associated with a decreased chance of VBAC.5-8 While ACOG

still considers induction of labor a reasonable option in the setting of TOLAC, they

recommend patients be counseled on the decreased chance of achieving VBAC.3

In addition to a decreased chance of VBAC (compared to spontaneous labor), the risk

of complications, such as uterine rupture with its attendant maternal and neonatal risks,

is increased with induction of labor in women with one prior cesarean and no prior

vaginal delivery.7,9-12 Whether the risks of failed TOLAC or other morbidity is further

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increased in women with two prior cesareans undergoing induction has not previously

been studied. Accordingly, ACOG offers no specific recommendations on induction of

labor for women with two prior cesareans.

Women who achieve a VBAC experience less morbidity than women who undergo a

repeat cesarean. Indeed, the majority of the morbidity associated with TOLAC occurs

among women with a failed trial of labor. Accordingly, women who have a 60-70%

chance of TOLAC success have no greater morbidity if they undergo a TOLAC than if

they undergo an elective repeat cesarean delivery.13 Our data suggest that women who

undergo induction with two prior cesareans have a 65% chance of achieving VBAC,

which is similar to that of women with one prior cesarean.

ACOG recommends that the risk of rupture be discussed with women with one prior

cesarean undergoing induction of labor, but that induction of labor is a reasonable

option in the properly selected patient.3 Our data suggest that women undergoing an

induction with two prior cesareans are no more likely to experience either maternal or

neonatal complications compared to women undergoing induction with one prior

cesarean. Thus while discussion about an increased risk compared to spontaneous

labor may be warranted, our data do not indicate that the risks are significantly different

than those experienced by women with one prior cesarean undergoing an induction of

labor. Furthermore, maternal and neonatal risks among women with two prior

cesareans were no different in women undergoing induction compared to women

undergoing a repeat cesarean.

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This study is subject to limitations. While these data are from a large cohort, the number

of women with two prior cesareans undergoing induction of labor was relatively small.

Small but clinically significant differences, particularly for more rare outcomes such as

uterine rupture, may not have been able to be identified. For example, given the

observed incidence of composite morbidities in women with two prior cesareans, the

study had 80% power to detect a two-fold increased risk in maternal morbidity and a

1.7-fold increased risk in neonatal morbidity associated with an induction of labor as

opposed to a repeat cesarean.

Another limitation of this study is its observational design. The women with two prior

cesareans who underwent an induction of labor were significantly different than those

with one prior cesarean who underwent a labor induction and those who underwent a

repeat cesarean. Of particular importance, nearly half of the women with two prior

cesareans had a prior VBAC. However, potential confounding factors were included in

the multivariable regression and did not alter the results obtained from bivariable

analysis.

In this study, we have demonstrated that the chance of a VBAC, as well as maternal

and neonatal morbidities, are similar for women with one or two prior cesarean

deliveries who undergo labor induction. In addition, in women with two prior cesarean

deliveries, induction of labor was not associated with increased maternal or neonatal

risks compared to a repeat cesarean. These data can be used to guide shared decision-

making surrounding intended approach to delivery in women with two prior cesarean

deliveries, and support the notion that induction of labor, when necessary, is an

acceptable option.

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References

1. Silver RM, Landon MB, Rouse DJ, et al. Maternal morbidity associated with

multiple repeat cesarean deliveries. Obstetrics and gynecology 2006;107:1226-32.

2. Landon MB, Hauth JC, Leveno KJ, et al. Maternal and perinatal outcomes

associated with a trial of labor after prior cesarean delivery. The New England journal of

medicine 2004;351:2581-9.

3. American College of O, Gynecologists. ACOG Practice bulletin no. 115: Vaginal

birth after previous cesarean delivery. Obstetrics and gynecology 2010;116:450-63.

4. Tahseen S, Griffiths M. Vaginal birth after two caesarean sections (VBAC-2)-a

systematic review with meta-analysis of success rate and adverse outcomes of VBAC-2

versus VBAC-1 and repeat (third) caesarean sections. BJOG : an international journal

of obstetrics and gynaecology 2010;117:5-19.

5. Delaney T, Young DC. Spontaneous versus induced labor after a previous

cesarean delivery. Obstetrics and gynecology 2003;102:39-44.

6. Landon MB, Leindecker S, Spong CY, et al. The MFMU Cesarean Registry:

factors affecting the success of trial of labor after previous cesarean delivery. American

journal of obstetrics and gynecology 2005;193:1016-23.

7. Ravasia DJ, Wood SL, Pollard JK. Uterine rupture during induced trial of labor

among women with previous cesarean delivery. American journal of obstetrics and

gynecology 2000;183:1176-9.

8. Sims EJ, Newman RB, Hulsey TC. Vaginal birth after cesarean: to induce or not

to induce. American journal of obstetrics and gynecology 2001;184:1122-4.

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9. Grobman WA, Gilbert S, Landon MB, et al. Outcomes of induction of labor after

one prior cesarean. Obstetrics and gynecology 2007;109:262-9.

10. Landon MB, Spong CY, Thom E, et al. Risk of uterine rupture with a trial of labor

in women with multiple and single prior cesarean delivery. Obstetrics and gynecology

2006;108:12-20.

11. Macones GA, Peipert J, Nelson DB, et al. Maternal complications with vaginal

birth after cesarean delivery: a multicenter study. American journal of obstetrics and

gynecology 2005;193:1656-62.

12. Zelop CM, Shipp TD, Repke JT, Cohen A, Caughey AB, Lieberman E. Uterine

rupture during induced or augmented labor in gravid women with one prior cesarean

delivery. American journal of obstetrics and gynecology 1999;181:882-6.

13. Grobman WA, Lai Y, Landon MB, et al. Can a prediction model for vaginal birth

after cesarean also predict the probability of morbidity related to a trial of labor?

American journal of obstetrics and gynecology 2009;200:56 e1-6.

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Table 1: Patient characteristics stratified by number of prior cesareans and approach to delivery

IOL after one

prior

cesarean

n=4100 p

IOL after two

prior

cesareans

n=152 p

Repeat

cesarean

after two prior

cesareans

n=6010

Age at delivery (y) 29.6 ± 5.7 0.008 30.8 ± 5.4 0.046 29.9 ± 5.5

Race 0.039 <0.001

White 2009 (49.0%) 60 (39.5%) 2147 (35.7%)

Black 1365 (33.3%) 65 (42.8%) 1398 (23.3%)

Hispanic 537 (13.1%) 23 (15.1%) 2184 (36.3%)

Other/unknown 189 (4.6%) 4 (2.6%) 281 (4.7%)

Married 2563 (62.5%) 0.021 81 (53.3%) 0.033 3715 (61.8%)

Public insurance 1537 (37.5%) <0.001 79 (52.0%) 0.036 2174 (37.9%)

BMI at delivery (kg/m2) 33.1 ± 7.3 0.044 34.4 ± 6.5 <0.001 33.7 ± 7.1

Tobacco use 621 (15.2%) 0.015 34 (22.4%) 0.001 803 (13.4%)

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Prior vaginal delivery 2036 (49.9%) 0.329 82 (54.0%) <0.001 809 (13.6%)

Prior VBAC 1373 (34.8%) 0.003 67 (46.9%) <0.001 346 (5.9%)

Interval since last cesarean (years) 5.6 ± 3.8 0.175 6.1 ± 4.0 <0.001 4.3 ± 3.1

Gestational age at delivery (weeks) 39.1 ± 2.6 0.056 38.7 ± 4.3 0.33 38.5 ± 2.3

Epidural anesthesia 3395 (86.6%) 0.177 119 (82.6%) --- ---

Cervical dilation on admission (cm) 1.7 ± 1.2 0.188 1.6 ± 1.3 --- ---

Birth weight (grams) 3306 ± 645 0.081 3211 ± 754 0.008 3344 ± 598

IOL = induction of labor; VBAC = vaginal birth after cesarean; BMI = body mass index

Data presented as mean ± standard deviation or n (%).

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Table 2: Maternal complications stratified by number of prior cesareans and approach to delivery

IOL after one

prior

cesarean OR (95% CI)*

IOL after

two prior

cesareans OR (95% CI)**

Cesarean

after two

prior

cesareans

Endometritis 119 (2.9%) 0.90 (0.33-2.48) 4 (2.6%) 1.11 (0.41-3.03) 143 (2.4%)

Transfusion 69 (1.7%) 1.18 (0.36-3.78) 3 (2.0%) 1.13 (0.36-3.61) 105 (1.8%)

Thromboembolic disease 12 (0.3%) 2.26 (0.29-17.46) 1 (0.7%) 5.68 (0.69-46.45) 7 (0.1%)

Operative injury 11 (0.3%) --- 0 (0.0%) --- 28 (0.5%)

Uterine rupture 39 (1.0%) 0.69 (0.09-5.05) 1 (0.7%) 5.68 (0.69-46.45) 7 (0.1%)

Uterine dehiscence 28 (0.7%) --- 0 (0.0%) --- 44 (0.7%)

Hysterectomy 12 (2.4%) --- 0 (0.0%) --- 22 (0.4%)

ICU admission 15 (0.4%) 3.63 (0.82-16.02) 2 (1.3%) 3.80 (0.88-16.36) 21 (0.4%)

Postpartum readmission 56 (1.4%) 0.96 (0.23-3.98) 2 (1.3%) 1.12 (0.24-4.59) 71 (1.2%)

Maternal composite outcome 288 (7.0%) 1.03 (0.55-1.93) 11 (7.2%) 1.03 (0.54-1.96) 386 (6.4%)

IOL = induction of labor; ICU = intensive care unit; OR = odds ratio

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*IOL with two prior cesareans versus with one prior cesarean

**IOL with two prior cesareans versus cesarean delivery after two prior cesareans

Data presented as n (%)

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Table 3: Neonatal complications stratified by number of prior cesareans and intended route of delivery

IOL after

one prior

cesarean OR (95% CI)*

IOL after

two prior

cesareans OR (95% CI)**

Repeat

cesarean

after two prior

cesareans

5 minute Apgar < 7 74 (1.8%) 1.09 (0.34-3.51) 3 (2.0%) 2.35 (0.73-7.62) 51 (0.9%)

NICU admission 580 (15.7%) 1.23 (0.79-1.91) 25 (18.7%) 1.25 (0.81-1.93) 817 (13.6%)

Intrapartum stillbirth 2 (0.1%) --- 0 (0.0%) --- 2 (0.0%)

Neonatal death 11 (0.3%) 2.52 (0.32-19.66) 1 (0.8%) 3.06 (0.40-23.50) 13 (0.2%)

HIE 4 (0.1%) --- 0 (0.0%) --- 2 (0.0%)

Neonatal composite outcome 599 (14.6%) 1.13 (0.78-1.62) 25 (16.5%) 1.20 (0.83-1.72) 826 (13.7%)

IOL = induction of labor; NICU = neonatal intensive care unit; HIE = hypoxic ischemic encephalopathy

Data presented as n (%)

* IOL with two prior cesareans versus with one prior cesarean

**IOL with two prior cesareans versus cesarean delivery after two prior cesareans

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Table 4: Multivariable analyses for women undergoing induction of labor

VBAC

Composite maternal

morbidity

Composite neonatal

morbidity

aOR 95% CI aOR 95% CI aOR 95% CI

Two prior cesareans 0.71 0.48-1.05 1.22 0.64-2.33 1.08 0.68-1.73

Age at delivery (years) 0.98 0.96-0.99 1.01 0.98-1.03 1.03 1.02-1.05

Race

White 1.00 ref 1.00 ref 1.00 ref

Black 0.54 0.44-0.66 3.19 2.20-4.62 1.41 1.09-1.81

Hispanic 0.53 0.42-0.68 2.69 1.75-4.12 1.57 1.16-2.10

Other 0.62 0.43-0.88 3.64 2.14-6.22 1.62 1.06-2.46

Married 1.22 1.00-1.49 0.86 0.62-1.20 0.67 0.53-0.86

Public insurance 0.96 0.78-1.16 1.14 0.84-1.55 1.42 1.13-1.78

BMI at delivery (kg/m2) 0.95 0.94-0.96 1.02 1.00-1.03 1.01 1.00-1.02

Tobacco use 0.86 0.69-1.06 0.73 0.49-1.09 1.02 0.79-1.31

Prior VBAC 5.58 4.62-6.74 0.38 0.28-0.53 0.65 0.53-0.79

VBAC = vaginal birth after cesarean; BMI = body mass index; aOR = adjusted odds ratio

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Table 5: Multivariable analyses for women with two prior cesarean deliveries

Composite maternal

morbidity

Composite neonatal

morbidity

aOR 95% CI aOR 95% CI

Induction of labor 0.72 0.26-2.04 1.14 0.60-2.16

Age at delivery (years) 1.00 0.97-1.02 1.03 1.01-1.04

Race

White 1.00 ref 1.00 ref

Black 0.45 0.32-0.62 1.05 0.82-1.33

Hispanic 0.62 0.46-0.82 0.70 0.55-0.88

Other 0.59 0.33-1.06 0.93 0.61-1.42

Married 0.90 0.69-1.18 0.91 0.74-1.12

Public insurance 0.99 0.99-1.02 1.04 0.86-1.26

BMI at delivery (kg/m2) 1.01 0.80-1.55 1.03 1.02-1.04

Tobacco use 1.12 0.58-1.43 0.81 0.63-1.04

Prior VBAC 0.91 0.93-1.01 1.12 0.82-1.53

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Interval since last cesarean (years) 0.97 0.93-1.01 0.98 0.95-1.00

Birth weight (grams) 1.00 1.00-1.00 1.00 1.00-1.00

VBAC = vaginal birth after cesarean; BMI = body mass index; aOR = adjusted odds ratio

obstetric outcomes associated with induction of labor

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