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Impact of multiple cesarean deliveries on maternal morbidity: a systematic review
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Impact of multiple cesarean deliveries on maternal morbidity: a systematic review Nicole E. Marshall, MD, MCR; Rongwei Fu, PhD; Jeanne-Marie Guise, MD, MPH OBJECTIVE: The purpose of this study was to determine the impact of
increasing numbers of cesarean deliveries on maternal morbidity. This study was performed for the 2010 National Institutes of Health Consensus Development Conference on Vaginal Birth After Cesarean: New Insights. STUDY DESIGN: We conducted a systematic review and metaanalysis of observational studies. RESULTS: Twenty-one studies (2,282,922 deliveries) were included.
The rate of hysterectomy, blood transfusions, adhesions, and surgical injury all increased with increasing number of cesarean deliveries. The
incidence of placenta previa increased from 10/1000 deliveries with 1 previous cesarean delivery to 28/1000 with ⱖ3 cesarean deliveries. Compared with women with previa and no previous cesarean delivery, women with previa and ⱖ3 cesarean deliveries had a statistically significant increased risk of accreta (3.3-4% vs 50-67%), hysterectomy (0.7-4% vs 50-67%), and composite maternal morbidity (15% vs 83%; odds ratio, 33.6; 95% confidence interval, 14.6 –77.4). CONCLUSION: Serious maternal morbidity progressively increased as
the number of previous cesarean deliveries increased. Key words: maternal morbidity, multiple cesarean deliveries, previa
Cite this article as: Marshall NE, Fu R, Guise J-M. Impact of multiple cesarean deliveries on maternal morbidity: a systematic review. Am J Obstet Gynecol 2011;205:262.e1-8.
A
lmost one-third of all births in the United States are by cesarean delivery (CD) and the rate of both primary and repeat cesarean deliveries in the United States continues to rise each year.1 In the last decade, there has been a trend away from vaginal birth after CD (VBAC), with one-third of US hospitals banning VBAC and ⬎90% of women delivering by repeat cesarean.2,3 Counseling patients with previous CD regarding delivery options typically focuses on the risks of a trial of labor on a scarred uterus and the potential for uterine rupture in this pregnancy rather than the risk of repeat CD in future pregnancies. Many women
choose repeat CD or deliver in a facility that does not allow VBAC. After 2 CDs, most women will not be offered VBAC and are destined to deliver by CD for all future pregnancies. CD is not without risk. Maternal morbidity may include adhesion formation, surgical injury, postoperative infection, hemorrhage/transfusion, hysterectomy, abnormal placentation, and death. It is unclear whether the incidence of adverse outcomes changes with increasing numbers of CDs. To provide meaningful counseling, it is important for patients and providers to understand not only the risks of trial of labor but also the risks that are associ-
From the Departments of Obstetrics and Gynecology (Drs Marshall and Guise), Public Health and Preventive Medicine (Drs Fu and Guise), and Medical Informatics and Clinical Epidemiology (Dr Guise) and the Oregon Evidence-Based Practice Center (Dr Guise), Oregon Health & Science University, Portland, OR. Presented at the 31st Annual Meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, Feb. 7-12, 2011. Received March 10, 2011; revised May 2, 2011; accepted June 8, 2011. Reprints: Nicole E. Marshall, MD, Department of Obstetrics & Gynecology, Oregon Health & Science University, mail code L458, 3181 SW Sam Jackson Park Rd., Portland, OR 97239-3098. [email protected]. Conducted for the 2010 National Institutes of Health Consensus Development Conference entitled “Vaginal Birth After Cesarean: New Insights” and was supported by the Agency for Healthcare Research and Quality, Contract no. 290-2007-10057-I, for the Office of Medical Applications of Research at the National Institutes of Health. The authors report no conflicts of interest. 0002-9378/$36.00 • © 2011 Mosby, Inc. All rights reserved. • doi: 10.1016/j.ajog.2011.06.035
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ated with multiple CDs. Similarly, from a policy level, it is important to understand the risks for women with multiple CDs to ensure that hospitals and staff have the resources and skilled personnel required to respond. This systematic review was conducted to inform the 2010 National Institutes of Health Consensus Development Conference: Vaginal Birth After Cesarean: New Insights.3 The objectives were to (1) determine the incidence of adverse maternal outcome with multiple CDs and (2) determine whether the incidence changes with the number of previous CDs.
M ATERIALS AND M ETHODS Search strategy A systematic literature search was conducted in MEDLINE, Database of Abstracts of Reviews of Effectiveness, and the Cochrane Collaboration resources to identify relevant articles from 1980 to September 2009. Search terms used included variations of repeat CD, previous CD, and multiple CD. Additional relevant studies were identified from reference lists of reviews and editorials and by hand-searching key journals and websites, as has been shown to improve study identification in addition to electronic searches.4,5
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FIGURE 1
Search and selection of literature Database searches* downloaded citations 3134
Review titles/abstracts with eligibility criteria 2171 abstracts excluded
963 total full text papers retrieved and reviewed with refined eligibility criteria 37 papers suggested by reviewers and other sources
203 studies met all inclusion criteria, of good or fair quality, and included in results, stratified by topic†
797 full text papers excluded because: Published <1980 <10 subjects From developing or undeveloped country No prior cesarean Twins or abortions
Other Categories TOL & VBAC Rate: Predictors of TOL & VBAC: Scored Models of VBAC: Induction/Augmentation: Maternal Outcomes: Uterine Rupture: Special Considerations: Infant Outcomes:
71 28 14 28 41 28 14 11
Multiple Cesareans 21
The asterisk denotes the databases that were searched and include MEDLINE, Cochrane and DARE; the dagger denotes that many studies were included in ⬎1 topic area. TOL, trial of labor; VBAC, vaginal birth after cesarean delivery. Marshall. Morbidity with multiple cesarean deliveries. Am J Obstet Gynecol 2011.
Study selection Two investigators reviewed a random set of titles and abstracts to select articles for full text review. When an appropriate level of reliability was reached for selection of studies (kappa of ⱖ0.60), the remaining titles and abstracts were divided up and reviewed by 1 investigator. Similarly, 2 investigators screened a random set of articles for inclusion. When an appropriate level of reliability was reached, the remaining articles were divided among the investigators for further screening. Settings that were applicable to a United States population were included. Therefore, non-US studies were included if they originated from a developed country.6 We excluded studies of or with women without a previous CD, nulliparous patients, ⱕ10 subjects, breech delivery, exclusive focus on preterm delivery, low birthweight, and pregnancies that included twins or abortions. We also
excluded studies that were begun or published before the 1980 National Institutes of Health Consensus Conference on VBAC and studies that were limited to patients with particular conditions, such as gestational diabetes mellitus, human immunodeficiency virus, preeclampsia.
Data abstraction Data were extracted from each study and entered directly into evidence tables by a primary reviewer. A second reviewer verified the accuracy and completeness of the data, which was summarized descriptively. Study quality assessment A “best evidence” approach was applied, in which studies with the highest quality and most rigorous design according to predetermined criteria were emphasized.7 Reviewers rated the quality of each study using criteria that were spe-
cific to particular study designs as developed by the US Preventive Services Task Force and the National Health Service Centre for Reviews and Dissemination.8,9 Quality rating categories included maintenance of comparable groups, outcome measures that were reliable and valid, outcome assessor blinding, and adjustment for potential confounders. Details of the methods and results for quality assessments are provided in the evidence review.3 Two reviewers independently quality-rated all studies, with final rating achieved through consensus.10 Studies rated poor quality were excluded from the analyses.
Data synthesis Metaanalyses were conducted, when appropriate, to generate a meaningful combined estimate to summarize rates with STATA software (version 10.1; StataCorp, College Station, TX). A random effects model11 was used to combine the studies while incorporating variations among studies. Statistical heterogeneity was assessed with the standard Q-test and the I2 statistic (the proportion of variation in study estimates because of heterogeneity rather than sampling error). Forest plots were presented to graphically summarize the study results and the pooled results.12
R ESULTS We identified 3134 citations and reviewed 963 articles for inclusion, of which 203 articles met inclusion and were quality rated and 21 articles provided information on the association of maternal morbidity with multiple CDs (Figure 1). For multiple CDs, 69 citations were identified, and 39 full-text articles were quality rated. Eleven studies met inclusion criteria and were rated good or fair quality.13-23 Individual topics were informed in the following manner (Table 1): hysterectomy (7 studies),13,16,17,19,20,22,23 hemorrhage (3 studies),18,19,21 adhesions (3 studies),15,17,19 surgical injury (2 studies),17,22 perioperative infection (4 studies),15,17,20,22 and wound complications (2 studies).17,22 To determine the incidence and outcomes of abnormal placentation (including placental abruption, previa, and accreta) after previous CD, 82 full-text articles were re-
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TABLE 1
Studies of maternal morbidity with multiple cesarean deliveries Study
Design/years/location Aim of study
Bodelon et al, 200913
Case-control/19872006/United States
Population
Exclusion criteria Criteria for diagnosis
To identify factors associated Cases: women undergoing Not reported with peripartum peripartum hysterectomy hysterectomy within 30 days after delivery/control subjects: women without peripartum hysterectomy
ICD-9 codes
To estimate the relationship between previous CD and previa
Documentation on perinatal abstract form and entered in perinatal registry.
Relevant outcomes evaluated Maternal risk factors for peripartum hysterectomy that included placenta abnormalities and delivery method
................................................................................................................................................................................................................................................................................................................................................................................
Gilliam et al, 200228
Case-control/19861989/United States
Cases: multiparous Multiple gestation, women with previa/control no previa with CD subjects: multiparous women with spontaneous vaginal deliveries
Incidence of previous CD and previa
................................................................................................................................................................................................................................................................................................................................................................................
Grobman et al, 200714
Cohort/1999-2002/ United States
To estimate the association between the number of previous CD and pregnancy outcomes in women with previa
Cases: women with previa Antepartum Documentation in and singleton gestation stillbirth, unknown intrapartum record of number of “placenta previa” previous CDs
To investigate the effects of mode of delivery on problems with subsequent births
Women with ⬎1 delivery during the study period, comparison by mode of delivery of first birth
Women with missing information (904 births)
ICD-9 codes
To determine whether multiple previous CDs is associated with higher frequency of previa vs 1 previous CD
Cases: multiparous women with previa/control subjects: multiparous women with no previa
Nulliparous, ⬍2 consecutive deliveries at same institution
Placenta attachment totally or mostly low uterine segment diagnosed by ultrasound evaluation or in labor
Characteristics of women with previa compared with women without previa
To evaluate outcomes in CD that is repeated several times
Cases: women with ⱖ4 CDs/control subjects: women with 1-3 CDs
Number of previous hysterectomies
Maternal morbidity that included adhesions, blood loss ⬎1000 g, placenta previa, abruptio placentae, and major perioperative complication
Maternal morbidity that included placenta accreta, hysterectomy, and composite maternal morbidity
................................................................................................................................................................................................................................................................................................................................................................................
Hemminki et al, 200524
Cohort/1987-1998/ Finland
Prelabor hemorrhage, placental problems at birth, mode of delivery
................................................................................................................................................................................................................................................................................................................................................................................
Hershkowitz et al, Cohort/1985-1992/ 199525 Israel
................................................................................................................................................................................................................................................................................................................................................................................
Juntunen et al, 200415
Case-control/19822002/Finland
Not reported
................................................................................................................................................................................................................................................................................................................................................................................
Knight et al, 200816
Case-control/20052006/United Kingdom
To investigate the incidence of peripartum hysterectomy
Cases: women with peripartum hysterectomy/ control subects: no hysterectomy
Not reported
Women undergoing a Risk and indication of hysterectomy in the same hysterectomy that was clinical episode as associated with previous CD delivery of a fetus or infant
................................................................................................................................................................................................................................................................................................................................................................................
Laughon et al, 200529
Case-control/20002003/United States
To determine whether increased risk of previa at delivery with previous CD results from an increased risk of abnormal implantation or lower likelihood of resolution
Cases: singleton Low-lying pregnancies with previa placentas on second trimester ultrasound evaluation/ control subjects: singleton pregnancies with no previa
Review of computerized database records
To assess the association between first birth CD and second birth placental abruption and previa
Cases: women with second singleton with previous CD/control subjects: women with second singleton and previous vaginal
First birth abruption or previa
Classification on birth certificate or ICD-9 code for “placental abruption” or “placenta previa”
Cases: women with CD after ⱖ2 previous CDs
Not reported
Incidence of placenta previa with previous CD
................................................................................................................................................................................................................................................................................................................................................................................
Lydon-Rochelle et Cohort/1987-1996/ al, 200134 United States
Second-birth maternal complications that included abruption, previa, postpartum hemorrhage, hysterectomy, and infection
................................................................................................................................................................................................................................................................................................................................................................................
Lynch et al, 200317
Case series/1990-1999/ Ireland
To investigate the incidence of maternal morbidity after CD in women with at least 2 previous CDs
Women with elective repeat CD solely because of ⱖ2 previous CDs
Maternal morbidity that included previa, adhesions, hysterectomy, surgical injury, venous thromboembolism, and wound problems
................................................................................................................................................................................................................................................................................................................................................................................
Macones et al, 200518
Cohort/1996-2000/ United States
To compare clinical outcomes in women with previous CD
Cases: women with 2 previous CDs
Classic scar
ICD-9 code “previous cesarean delivery, delivered”
Maternal morbidity that included major operative injuries, transfusion, and postpartum fever
................................................................................................................................................................................................................................................................................................................................................................................
Miller et al, 199732
Case series/1985-1994/ United States
To define clinical risk factors Cases: placenta accreta that are associated with confirmed by histologic placenta previa-accreta examination
Cohort/2000-2005/ Israel
To assess maternal complications after multiple CDs
Not reported
Placenta accreta Clinical risk factors associated confirmed by histology on with placenta accreta hysterectomy specimens
................................................................................................................................................................................................................................................................................................................................................................................
Nisenblat et al, 200619
Cases: women with ⱖ3 CDs/control subjects: second CD
Trial of labor after Women scheduled for CD planned repeat CD
Maternal morbidity that included excessive blood loss, dense adhesions, hysterectomy, surgical injury, and placental abnormalities
................................................................................................................................................................................................................................................................................................................................................................................
Marshall. Morbidity with multiple cesarean deliveries. Am J Obstet Gynecol 2011.
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(continued )
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TABLE 1
Studies of maternal morbidity with multiple cesarean deliveries (continued) Study
Design/years/location Aim of study
Population
Odibo et al, 200727
Retrospective cohort/ 1996-2000/United States
Cases: women with Not reported previous CD and previa or abruption/control subjects: women with previous CD without previa or abruption
To evaluate risk factors that are associated with placenta previa and abruption in women with previous CDs
Exclusion criteria Criteria for diagnosis
Relevant outcomes evaluated
ICD-9 codes for ”previous Placenta previa and abruption cesarean delivery, delivered,” sonographic evidence of placenta covering os in third trimester, separation of the placenta before delivery as reported by physicians
................................................................................................................................................................................................................................................................................................................................................................................
Olive et al, 200533
Case series/1998-2002/ Australia
To determine risk factors and Cases: women with maternal morbidity for placenta previa/control women with placenta previa subjects: women without placenta previa
Vaginal birth or CD for failure to progress
Women with placenta previa delivered by CD at ⬎26 wk gestation
Maternal morbidity that included severe postpartum hemorrhage, hysterectomy, intensive care unit admission, or composite maternal morbidity
................................................................................................................................................................................................................................................................................................................................................................................
Phelan et al, 198720
Cohort/1982-1984/ United States
To evaluate the risks that are Cases: women with 1-2 associated with trial of labor previous CDs who attempted a trial of labor/ control subjects: women with repeat CDs
Classic scar, Patients who accepted multiple gestation, trial of labor malpresentation
To evaluate risks for blood transfusion in women with CD
Not reported
Maternal morbidity that included hysterectomy and abnormal placentation
................................................................................................................................................................................................................................................................................................................................................................................
Rouse et al, 200621
Cohort/1999-2000/ United States
Cases: women with CD and blood transfusion
Transfusion of packed red Characteristics of women with blood cells CD who received a blood intraoperatively or transfusion postoperatively before hospital discharge
................................................................................................................................................................................................................................................................................................................................................................................
Silver et al, 200622
Cohort/1999-2002/ United States
To estimate the magnitude of Cases: women who had a increased maternal morbidity CD without labor that is associated with increasing numbers of CDs
Women in labor
Women undergoing CD without labor
Maternal morbidity that included placenta accreta, previa, hysterectomy, surgical injury, and composite morbidity
To investigate the occurrence Cases: women with of placenta previa after CD previa/control subjects: women without previa
Nonwhite, nulliparous, missing data
Vital records check-box of Incidence of placenta previa previous CD and placenta with previous CD previa
To determine whether the rate of abnormal placentation is increasing in conjunction with CD rate
Cases: abnormal placentation/control subjects: normal placentation, matched by year of delivery
Myomatous uteri, malignancy
Histopathologic diagnosis; Incidence of abnormal difficult manual piecemeal placentation by number of removal; heavy continued previous CDs bleeding from implantation site after CD
Cases: women with emergency peripartum hysterectomy
Elective peripartum hysterectomies
................................................................................................................................................................................................................................................................................................................................................................................
Taylor et al, 199430
Case-control/19841987/United States
................................................................................................................................................................................................................................................................................................................................................................................
Wu et al, 200531
Case-control/19822002/United States
................................................................................................................................................................................................................................................................................................................................................................................
Zelop et al, 199323
Case series/1983-1991/ United States
To evaluate the clinical indications and incidence of emergency peripartum hysterectomy
Peripartum hysterectomy performed during the same hospitalization as the delivery
Clinical indications and incidence of peripartum hysterectomy
................................................................................................................................................................................................................................................................................................................................................................................
CD, cesarean delivery; ICD-9, International Classification of Diseases–9th revision. Marshall. Morbidity with multiple cesarean deliveries. Am J Obstet Gynecol 2011.
viewed. Nineteen articles met inclusion criteria and consisted of 8 good- or fairquality cohort studies,14,19,21,22,24-27 7 fairquality case control studies,13,15,16,28-31 and 4 good- or fair-quality case series.17,23,32,33 Each study provided evidence for ⱖ1 of the sections on abruption (5 studies),19,21,24,27,34 previa (16 studies),14,15,17,19, 21-25,27-30,32-34 and accreta (5 studies).13,16,19,22,32
Multiple CDs Hysterectomy increased with increasing number of CDs in all studies (Table 2).13,16,17,19,20,22,23 The odds ratio (OR) for hysterectomy rose with number of previous CDs from 0.7-2.14 with 1 previous CD, 1.4-7.9 with ⱖ1, and 3.8-18.6 with ⱖ2. The best evidence comes from
Silver et al22 who used the Eunice Kennedy Shriver Maternal-Fetal Medicine Units Network CD registry database and noted a statistically significant increased incidence of hysterectomy with an increasing number of CDs from 0.65%, 0.42%, 0.90%, 2.41%, 3.49%, to 8.99%, with 0 to ⱖ5 CDs. Women with ⱖ5 CDs were 15 times more likely to require hysterectomy (OR, 15.2; 95% confidence interval [CI], 6.9 –33.5) than women with vaginal delivery. Four of 7 studies listed the indication for hysterectomy in women with previous CD. The primary indications were placenta previa/accreta (67%), uterine atony (25%), and uterine rupture/laceration (5%).16,17,19,20 Two studies found that increased parity was
associated with an increased risk of hysterectomy after previous CD, but no other examined risk factors, including maternal body mass index or spontaneous labor, were reported to be associated with an increased risk of hysterectomy. 16,23 Higher rates of hemorrhage, blood transfusion, adhesions, and surgical injury with increasing number of CDs were reported consistently in all studies. No change in perioperative infection or wound complications was noted with increasing CDs.
Abruption The overall incidence of abruption with any previous CD was 1.2-1.5%.21,27 Most studies found no increased incidence of abruption in women with increasing
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TABLE 2
Effect of increasing number of cesarean deliveries on rates of hysterectomy Previous cesarean deliveries Study
0
Bodelon et al, 200913
4.6 (3.5–6.0)a
Knight et al, 200816
7.1 (3.7–13.7)a
1
>1
2
>2
3
4
>4
>5
7.9 (5.8–10.7)a
................................................................................................................................................................................................................................................................................................................................................................................
2.1 (1.4–3.3)a
18.6 (7.7–45.4)a
................................................................................................................................................................................................................................................................................................................................................................................
Silver et al, 200622
40/6,201 (0.7)b
Zelop et al, 199323
19/35,240 (0.05)b
0.7a (0.4–0.97)a
1.4 (0.9–2.1)a
3.8 (2.4–6.0)a
5.6 (2.7–11.6)a
15.2 (6.9–33.5)a
................................................................................................................................................................................................................................................................................................................................................................................
29/4366 (0.7)b
70/6694 (1.0)b
................................................................................................................................................................................................................................................................................................................................................................................
Nisenblat et al, 200619
1/491 (0.2)b
3/277 (1.1)b
................................................................................................................................................................................................................................................................................................................................................................................
Phelan et al, 198720
14/847 (1.7)b
................................................................................................................................................................................................................................................................................................................................................................................
2/170 (1.1)b
Lynch et al, 200317
................................................................................................................................................................................................................................................................................................................................................................................ a
Adjusted odds ratio (95% CI); b Data are given as n/N (%).
Marshall. Morbidity with multiple cesarean deliveries. Am J Obstet Gynecol 2011.
numbers of previous CDs. One casecontrol study reported abruption in 3.4% of women with ⱖ3 CDs, but no abruptions were reported in the 149 control CDs (P ⫽ .024).15 For women with ⱖ1 CDs, the rate of abruption was 10.3-15 per 1000 deliveries and does not appear to increase significantly with increasing numbers of CDs.
Placenta previa Compared with previous normal spontaneous vaginal delivery, previous CD was a statistically significant risk factor for placenta previa in 7 studies (OR, 1.48-3.95).21,25,27-30,33 The ORs for all studies were in the direction of increasing risk with the increasing number of CDs, although not all studies reported a statistically significant difference. The incidence of previa with 1 previous CD was 0.8-1.5%. Compared with women without a previous CD, the OR for previa was 1.2-1.9 and reached statistical significance in 4 of 7 studies.24-26,32 In women with 2 CDs, the incidence of previa was 1.1-2.0% (OR, 1.9-2.0, compared with women with previous normal spontaneous vaginal delivery) and was statistically significant in 3 of 5 studies.22,28,32 Two studies19,25 limited comparisons to women with 1 previous CD vs multiple CDs. No increased risk with additional CDs was noted, although these studies had limited sample size for women with multiple CDs 262.e5
and previa (n ⫽ 7 and ⫽ 20, respectively). The 5 studies15,22,27,28,32 that specifically identified women with ⱖ3 CDs all noted a statistically significant increased rate of previa with increasing CDs, up to 3.7% for women with ⱖ5 CDs.
Metaanalysis The metaanalysis with a random effects model demonstrated absolute risk of previa associated with any number of CDs was 12 per 1000 deliveries (95% CI, 8-15 per 1000). Although significant heterogeneity was detected among studies (I2 ⫽ 96.4%; P ⬍ .001), the absolute risks of previa from the included studies were actually quite consistent, ranging from 8 –14 per 1000 deliveries to provide a meaningful summary estimate for previa risk. This was a case in which unimportant statistical heterogeneity was detected, given the large sample size of the included studies. The risk increased with each additional previous CD (Figure 2) from 10 per 1000 with 1 previous CD (95% CI, 6 –13 per 1000) to 28 per 1000 (95% CI, 18 –37 per 1000) with ⱖ3 CDs. The incidence of hysterectomy rose with the increasing number of previous CDs in women with previa. Women with no CD and previa required hysterectomy in 0.7-4% of cases, compared with 5067% in women with ⱖ3 CDs.14,15,17,23 A history of previous CD increased the likelihood of requiring a blood transfu-
American Journal of Obstetrics & Gynecology SEPTEMBER 2011
sion compared with women with previa without a CD (OR, 15.9; 95% CI, 12.0 –21.0).21 Two studies presented composite major maternal morbidity in women with previous CD and previa.14,33 One study evaluated severe postpartum hemorrhage, acute renal failure, intensive care unit admission, mechanical ventilation, shock, disseminated intravascular coagulopathy, hysterectomy, other procedures to stop bleeding, and/or death.33 Twenty-two percent of women with previous CD and previa experienced major maternal morbidity compared with 11% of women with previa and no CD. A second study combined transfusion, hysterectomy, operative injury, coagulopathy, venous thromboembolism, pulmonary edema, and/or death.14 There was a statistically significant increase in composite major maternal morbidity in women with previa with an increasing number of CDs from 15% with no previous CD to 83% with ⱖ3 CDs (OR, 33.6; 95% CI, 14.6 –77.4).
Placenta accreta The incidence of placenta accreta increased with the increasing number of CDs (Table 3). The increased incidence did not reach statistical significance until women had at least 2 CDs, compared with no previous CD (OR, 8.6-29.8). Women with 1 previous CD had a rate of
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FIGURE 2
TABLE 3
Risk of placenta previa by number of previous cesarean deliveries
Incidence of accreta in women with previa, based on number of previous cesarean deliveries Previous cesarean deliveries, % Study Miller et al, 1997
0 1 32
2
3
4
>5
4 14 23 35 50
........................................................................................................... 22
Silver et al, 2006
3 11 40 61 67 67
...........................................................................................................
Marshall. Morbidity with multiple cesarean deliveries. Am J Obstet Gynecol 2011.
The squares represent the individual study’s point estimate of effect. The diamond represents the combined point estimate of effect. The size of the shape is a reflection of the weight of the study in each metaanalysis. Marshall. Morbidity with multiple cesarean deliveries. Am J Obstet Gynecol 2011.
accreta of 0.3-0.6%. In comparison with women without previous CD, the OR for accreta with 1 previous CD was 1.3-2.16, which was not statistically significant. The incidence of accreta continued to rise with increasing previous CD up to 6.74% for women with ⱖ5 CDs compared with no previous CD, with an OR of 29.8. Two studies noted a statistically significant increase in accreta in women with previa and previous CD.22,32 As the number of previous CDs rose, the presence of placenta previa increased the likelihood of placenta accreta from 3.3-4% in women who underwent their first CD to 50-67% in women with ⱖ4 CDs. The risk of hysterectomy in women with accreta and previous CD was not reported separately, but 2 studies found that, compared with women with normal placentas, accreta was a statistically
significant risk factor for hysterectomy (OR, 43-99.5; 95% CI, 19.0 –⬁).13,16 Additional maternal outcomes such as surgical injury, hemorrhage, transfusion, and death in women with accreta and previous CD were reported inconsistently, such that meaningful analysis was not possible.
C OMMENT Maternal morbidity increases in a dose-response fashion with each additional CD, especially for women with ⱖ3 CDs who are at statistically significant increased risk of previa, accreta, and hysterectomy. Women with previa and previous CD face the highest rates of morbidity, and the risks increase with increasing number of previous CDs. Compared with women with previa and no previous CD, women with ⱖ3 CDs and previa had a statistically sig-
nificant increased risk of accreta (3.3-4% vs 50-67%), hysterectomy (0.7-4% vs 5067%), and composite maternal morbidity (15% vs 83%; OR, 33.6; 95% CI, 14.6 –77.4). The overall incidence of previa is uncommon and ranges from 12 per 1000 deliveries in women with any previous CD to 28 per 1000 in women with ⱖ3 CDs. Unfortunately, all pregnant women are at risk for previa, and there is no known method for determining which women will experience previa in a subsequent pregnancy. Women with previa are at increased risk of maternal morbidity, and the incidence of previa and risk of morbidity increases with the increasing number of CD. This review confirms the increasing incidence of accreta in women with previa depending on number of previous CDs.22,32,35 Although the patient numbers in each individual study were limited, the consistent findings strongly suggest that women with previa and previous CD are at substantially increased risk of placenta accreta. All women with accreta, regardless of history of previous CD, were at statistically significant increased risk of hysterectomy (OR, 4399.5). This has important implications for patients and providers, especially in rural locations that may not have blood bank capabilities to manage the massive hemorrhage that can accompany placenta accreta. This review found increased maternal morbidity with increasing number of CDs, regardless of placental status. Although the overall incidence was uncommon, the rate of blood transfusions, adhesion formation, surgical injury, and
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SMFM Papers hysterectomy all increased with the increasing number of CDs. Abruption and wound complications do not appear to increase with increasing numbers of CDs. One of the major limitations in analyzing studies regarding placental abnormalities was the lack of consistent definitions that were used, especially for abruption, which may have resulted in misclassification. There was also the potential of surveillance bias as women with previous CDs may have had additional ultrasound scans or observation at the time of delivery in anticipation of possible placental complications compared with women without known risk factors. Some of our primary outcomes were not the focus of the original studies; thus, cases may have been underreported. Studies that used histopathologic diagnosis of accreta were limited to hysterectomy patients and would have missed patients who received conservative therapy. Most studies relied on retrospective data analysis and, as such, are limited by the quality and consistency of the original data collection. A strength of this review is the large volume of cases that were available from a variety of countries and practice settings, including the United States, Australia, United Kingdom, and Israel and both academic- and community-based health centers, which increases the generalizability of the results. We included 21 studies that collected data from 2,282,922 deliveries, which included 180,177 repeat CD and 5729 deliveries with ⱖ3 CDs. There were 5823 cases of placenta previa and 743 cases of accreta; 1852 women required hysterectomy. Most women experienced good outcomes, regardless of the number of previous CDs; therefore, these data do not suggest an upper limit to the number of allowable CDs. The data do support an increased risk of major morbidity with an increasing number of CDs, especially in women with previa. Further studies are needed to better evaluate additional risk factors for the development of placenta accreta and surgical management to minimize uterine scarring. Women who desire large families should be counseled about the risks of 262.e7
www.AJOG.org increasing morbidity with multiple CDs. Because future fertility plans are unknown for many women, patients with 1 previous CD should be counseled about the risks and benefits of both VBAC and multiple CDs to assist with informed decision-making. As the rate of CD continues to rise, hospitals and physicians must be prepared to optimize the treatment of women with multiple CDs and minimize f morbidity and death. ACKNOWLEDGMENTS We thank Andrew Hamilton, MLS, MS, for conducting the literature searches, and Miranda Walker, MA, for assistance with manuscript preparation.
REFERENCES 1. Hamilton B, Martin J, Ventura S. Births: preliminary data for 2007: National Vital Statistics Report, web release. Hyattsville, MD: National Center for Vital Statistics; 2009. 2. Guise J-M, Denman M, Emeis C, et al. Vaginal birth after cesarean: new insights on maternal and fetal outcomes. Obstet Gynecol 2010;115:1267-78. 3. Guise J-M, Eden K, Emeis C, et al. Vaginal birth after cesarean: new insights: evidence report/technology assessment no. 191. Rockville, MD: Agency for Healthcare Research and Quality; 2010. 4. Hopewell S, Clarke M, Lefebvre C, Scherer R. Handsearching versus electronic searching to identify reports of randomized trials. Cochrane Database Syst Rev 2007:MR000001. 5. Richards D. Handsearching still a valuable element of the systematic review. Evid Based Dent 2008;9:85. 6. The world factbook 2008. Washington, DC: Central Intelligence Agency; 2008. 7. Slavin RE. Best evidence synthesis: an intelligent alternative to meta-analysis. J Clin Epidemiol 1995;48:9-18. 8. Agency for Healthcare Research and Quality. Methods guide for effectiveness and comparative effectiveness reviews, AHRQ publication no. 10 (11)-EHC063-EF. Rockville, MD: 2011. Available at: www.effectivehealthcare.ahrq. gov. Accessed July 21, 2011. 9. Deeks JJ, Dinnes J, D’Amico R, et al. Evaluating non-randomised intervention studies. Health Technol Assess 2003;7:iii-x, 1-173. 10. Altman DG. Practical statistics for medical research. London: Chapman & Hall; 1991. 11. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88. 12. Lewis S, Clarke M. Forest plots: trying to see the wood and the trees. BMJ 2001; 322:1479-80. 13. Bodelon C, Bernabe-Ortiz A, Schiff MA, Reed SD. Factors associated with peripartum hysterectomy. Obstet Gynecol 2009;114:115-23.
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14. Grobman WA, Gersnoviez R, Landon MB, et al. Pregnancy outcomes for women with placenta previa in relation to the number of prior cesarean deliveries. Obstet Gynecol 2007;110:1249-55. 15. Juntunen K, Makarainen L, Kirkinen P. Outcome after a high number (4-10) of repeated caesarean sections. BJOG 2004;111:561-3. 16. Knight M, Kurinczuk JJ, Spark P, Brocklehurst P, United Kingdom Obstetric Surveillance System Steering C. Cesarean delivery and peripartum hysterectomy. Obstet Gynecol 2008;111:97-105. 17. Lynch CM, Kearney R, Turner MJ. Maternal morbidity after elective repeat caesarean section after two or more previous procedures. Eur J Obstet Gynecol Reprod Biol 2003;106:10-3. 18. Macones GA, Cahill A, Pare E, et al. Obstetric outcomes in women with two prior cesarean deliveries: is vaginal birth after cesarean delivery a viable option? Am J Obstet Gynecol 2005; 192:1223-9. 19. Nisenblat V, Barak S, Griness OB, Degani S, Ohel G, Gonen R. Maternal complications associated with multiple cesarean deliveries. Obstet Gynecol 2006;108:21-6. 20. Phelan JP, Clark SL, Diaz F, Paul RH. Vaginal birth after cesarean. Am J Obstet Gynecol 1987;157:1510-5. 21. Rouse DJ, MacPherson C, Landon M, et al. Blood transfusion and cesarean delivery. [erratum appears in Obstet Gynecol. 2006;108:1556]. Obstet Gynecol 2006;108:891-7. 22. Silver RM, Landon MB, Rouse DJ, et al. Maternal morbidity associated with multiple repeat cesarean deliveries. Obstet Gynecol 2006; 107:1226-32. 23. Zelop CM, Harlow BL, Frigoletto FD Jr, Safon LE, Saltzman DH. Emergency peripartum hysterectomy. Am J Obstet Gynecol 1993; 168:1443-8. 24. Hemminki E, Shelley J, Gissler M. Mode of delivery and problems in subsequent births: a register-based study from Finland. Am J Obstet Gynecol 2005;193:169-77. 25. Hershkowitz R, Fraser D, Mazor M, Leiberman JR. One or multiple previous cesarean sections are associated with similar increased frequency of placenta previa. Eur J Obstet Gynecol Reprod Biol 1995;62:185-8. 26. Lydon-Rochelle M, Holt VL, Easterling TR, Martin DP. Risk of uterine rupture during labor among women with a prior cesarean delivery. N Engl J Med 2001;345:3-8. 27. Odibo AO, Cahill AG, Stamilio DM, Stevens EJ, Peipert JF, Macones GA. Predicting placental abruption and previa in women with a previous cesarean delivery. Am J Perinatol 2007; 24:299-305. 28. Gilliam M, Rosenberg D, Davis F. The likelihood of placenta previa with greater number of cesarean deliveries and higher parity. Obstet Gynecol 2002;99:976-80. 29. Laughon SK, Wolfe HM, Visco AG. Prior cesarean and the risk for placenta previa on second-trimester ultrasonography. Obstet Gynecol 2005;105:962-5.
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www.AJOG.org 30. Taylor VM, Kramer MD, Vaughan TL, Peacock S. Placenta previa and prior cesarean delivery: how strong is the association? Obstet Gynecol 1994;84:55-7. 31. Wu S, Kocherginsky M, Hibbard JU. Abnormal placentation: twenty-year analysis. Am J Obstet Gynecol 2005;192:1458-61.
32. Miller DA, Chollet JA, Goodwin TM. Clinical risk factors for placenta previa-placenta accreta. Am J Obstet Gynecol 1997;177:210-4. 33. Olive EC, Roberts CL, Algert CS, Morris JM. Placenta praevia: maternal morbidity and place of birth. Aust N Z J Obstet Gynaecol 2005; 45:499-504.
34. Lydon-Rochelle M, Holt VL, Easterling TR, Martin DP. First-birth cesarean and placental abruption or previa at second birth. Obstet Gynecol 2001;97:765-9. 35. Clark SL, Koonings PP, Phelan JP. Placenta previa/accreta and prior cesarean section. Obstet Gynecol 1985;66:89-92.
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Impact of multiple cesarean deliveries on maternal morbidity: a systematic review Nicole E. Marshall, MD, MCR; Rongwei Fu, PhD; Jeanne-Marie Guise, MD, MPH OBJECTIVE: The purpose of this study was to determine the impact of
increasing numbers of cesarean deliveries on maternal morbidity. This study was performed for the 2010 National Institutes of Health Consensus Development Conference on Vaginal Birth After Cesarean: New Insights. STUDY DESIGN: We conducted a systematic review and metaanalysis of observational studies. RESULTS: Twenty-one studies (2,282,922 deliveries) were included.
The rate of hysterectomy, blood transfusions, adhesions, and surgical injury all increased with increasing number of cesarean deliveries. The
incidence of placenta previa increased from 10/1000 deliveries with 1 previous cesarean delivery to 28/1000 with ⱖ3 cesarean deliveries. Compared with women with previa and no previous cesarean delivery, women with previa and ⱖ3 cesarean deliveries had a statistically significant increased risk of accreta (3.3-4% vs 50-67%), hysterectomy (0.7-4% vs 50-67%), and composite maternal morbidity (15% vs 83%; odds ratio, 33.6; 95% confidence interval, 14.6 –77.4). CONCLUSION: Serious maternal morbidity progressively increased as
the number of previous cesarean deliveries increased. Key words: maternal morbidity, multiple cesarean deliveries, previa
Cite this article as: Marshall NE, Fu R, Guise J-M. Impact of multiple cesarean deliveries on maternal morbidity: a systematic review. Am J Obstet Gynecol 2011;205:262.e1-8.
A
lmost one-third of all births in the United States are by cesarean delivery (CD) and the rate of both primary and repeat cesarean deliveries in the United States continues to rise each year.1 In the last decade, there has been a trend away from vaginal birth after CD (VBAC), with one-third of US hospitals banning VBAC and ⬎90% of women delivering by repeat cesarean.2,3 Counseling patients with previous CD regarding delivery options typically focuses on the risks of a trial of labor on a scarred uterus and the potential for uterine rupture in this pregnancy rather than the risk of repeat CD in future pregnancies. Many women
choose repeat CD or deliver in a facility that does not allow VBAC. After 2 CDs, most women will not be offered VBAC and are destined to deliver by CD for all future pregnancies. CD is not without risk. Maternal morbidity may include adhesion formation, surgical injury, postoperative infection, hemorrhage/transfusion, hysterectomy, abnormal placentation, and death. It is unclear whether the incidence of adverse outcomes changes with increasing numbers of CDs. To provide meaningful counseling, it is important for patients and providers to understand not only the risks of trial of labor but also the risks that are associ-
From the Departments of Obstetrics and Gynecology (Drs Marshall and Guise), Public Health and Preventive Medicine (Drs Fu and Guise), and Medical Informatics and Clinical Epidemiology (Dr Guise) and the Oregon Evidence-Based Practice Center (Dr Guise), Oregon Health & Science University, Portland, OR. Presented at the 31st Annual Meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, Feb. 7-12, 2011. Received March 10, 2011; revised May 2, 2011; accepted June 8, 2011. Reprints: Nicole E. Marshall, MD, Department of Obstetrics & Gynecology, Oregon Health & Science University, mail code L458, 3181 SW Sam Jackson Park Rd., Portland, OR 97239-3098. [email protected]. Conducted for the 2010 National Institutes of Health Consensus Development Conference entitled “Vaginal Birth After Cesarean: New Insights” and was supported by the Agency for Healthcare Research and Quality, Contract no. 290-2007-10057-I, for the Office of Medical Applications of Research at the National Institutes of Health. The authors report no conflicts of interest. 0002-9378/$36.00 • © 2011 Mosby, Inc. All rights reserved. • doi: 10.1016/j.ajog.2011.06.035
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ated with multiple CDs. Similarly, from a policy level, it is important to understand the risks for women with multiple CDs to ensure that hospitals and staff have the resources and skilled personnel required to respond. This systematic review was conducted to inform the 2010 National Institutes of Health Consensus Development Conference: Vaginal Birth After Cesarean: New Insights.3 The objectives were to (1) determine the incidence of adverse maternal outcome with multiple CDs and (2) determine whether the incidence changes with the number of previous CDs.
M ATERIALS AND M ETHODS Search strategy A systematic literature search was conducted in MEDLINE, Database of Abstracts of Reviews of Effectiveness, and the Cochrane Collaboration resources to identify relevant articles from 1980 to September 2009. Search terms used included variations of repeat CD, previous CD, and multiple CD. Additional relevant studies were identified from reference lists of reviews and editorials and by hand-searching key journals and websites, as has been shown to improve study identification in addition to electronic searches.4,5
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FIGURE 1
Search and selection of literature Database searches* downloaded citations 3134
Review titles/abstracts with eligibility criteria 2171 abstracts excluded
963 total full text papers retrieved and reviewed with refined eligibility criteria 37 papers suggested by reviewers and other sources
203 studies met all inclusion criteria, of good or fair quality, and included in results, stratified by topic†
797 full text papers excluded because: Published <1980 <10 subjects From developing or undeveloped country No prior cesarean Twins or abortions
Other Categories TOL & VBAC Rate: Predictors of TOL & VBAC: Scored Models of VBAC: Induction/Augmentation: Maternal Outcomes: Uterine Rupture: Special Considerations: Infant Outcomes:
71 28 14 28 41 28 14 11
Multiple Cesareans 21
The asterisk denotes the databases that were searched and include MEDLINE, Cochrane and DARE; the dagger denotes that many studies were included in ⬎1 topic area. TOL, trial of labor; VBAC, vaginal birth after cesarean delivery. Marshall. Morbidity with multiple cesarean deliveries. Am J Obstet Gynecol 2011.
Study selection Two investigators reviewed a random set of titles and abstracts to select articles for full text review. When an appropriate level of reliability was reached for selection of studies (kappa of ⱖ0.60), the remaining titles and abstracts were divided up and reviewed by 1 investigator. Similarly, 2 investigators screened a random set of articles for inclusion. When an appropriate level of reliability was reached, the remaining articles were divided among the investigators for further screening. Settings that were applicable to a United States population were included. Therefore, non-US studies were included if they originated from a developed country.6 We excluded studies of or with women without a previous CD, nulliparous patients, ⱕ10 subjects, breech delivery, exclusive focus on preterm delivery, low birthweight, and pregnancies that included twins or abortions. We also
excluded studies that were begun or published before the 1980 National Institutes of Health Consensus Conference on VBAC and studies that were limited to patients with particular conditions, such as gestational diabetes mellitus, human immunodeficiency virus, preeclampsia.
Data abstraction Data were extracted from each study and entered directly into evidence tables by a primary reviewer. A second reviewer verified the accuracy and completeness of the data, which was summarized descriptively. Study quality assessment A “best evidence” approach was applied, in which studies with the highest quality and most rigorous design according to predetermined criteria were emphasized.7 Reviewers rated the quality of each study using criteria that were spe-
cific to particular study designs as developed by the US Preventive Services Task Force and the National Health Service Centre for Reviews and Dissemination.8,9 Quality rating categories included maintenance of comparable groups, outcome measures that were reliable and valid, outcome assessor blinding, and adjustment for potential confounders. Details of the methods and results for quality assessments are provided in the evidence review.3 Two reviewers independently quality-rated all studies, with final rating achieved through consensus.10 Studies rated poor quality were excluded from the analyses.
Data synthesis Metaanalyses were conducted, when appropriate, to generate a meaningful combined estimate to summarize rates with STATA software (version 10.1; StataCorp, College Station, TX). A random effects model11 was used to combine the studies while incorporating variations among studies. Statistical heterogeneity was assessed with the standard Q-test and the I2 statistic (the proportion of variation in study estimates because of heterogeneity rather than sampling error). Forest plots were presented to graphically summarize the study results and the pooled results.12
R ESULTS We identified 3134 citations and reviewed 963 articles for inclusion, of which 203 articles met inclusion and were quality rated and 21 articles provided information on the association of maternal morbidity with multiple CDs (Figure 1). For multiple CDs, 69 citations were identified, and 39 full-text articles were quality rated. Eleven studies met inclusion criteria and were rated good or fair quality.13-23 Individual topics were informed in the following manner (Table 1): hysterectomy (7 studies),13,16,17,19,20,22,23 hemorrhage (3 studies),18,19,21 adhesions (3 studies),15,17,19 surgical injury (2 studies),17,22 perioperative infection (4 studies),15,17,20,22 and wound complications (2 studies).17,22 To determine the incidence and outcomes of abnormal placentation (including placental abruption, previa, and accreta) after previous CD, 82 full-text articles were re-
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TABLE 1
Studies of maternal morbidity with multiple cesarean deliveries Study
Design/years/location Aim of study
Bodelon et al, 200913
Case-control/19872006/United States
Population
Exclusion criteria Criteria for diagnosis
To identify factors associated Cases: women undergoing Not reported with peripartum peripartum hysterectomy hysterectomy within 30 days after delivery/control subjects: women without peripartum hysterectomy
ICD-9 codes
To estimate the relationship between previous CD and previa
Documentation on perinatal abstract form and entered in perinatal registry.
Relevant outcomes evaluated Maternal risk factors for peripartum hysterectomy that included placenta abnormalities and delivery method
................................................................................................................................................................................................................................................................................................................................................................................
Gilliam et al, 200228
Case-control/19861989/United States
Cases: multiparous Multiple gestation, women with previa/control no previa with CD subjects: multiparous women with spontaneous vaginal deliveries
Incidence of previous CD and previa
................................................................................................................................................................................................................................................................................................................................................................................
Grobman et al, 200714
Cohort/1999-2002/ United States
To estimate the association between the number of previous CD and pregnancy outcomes in women with previa
Cases: women with previa Antepartum Documentation in and singleton gestation stillbirth, unknown intrapartum record of number of “placenta previa” previous CDs
To investigate the effects of mode of delivery on problems with subsequent births
Women with ⬎1 delivery during the study period, comparison by mode of delivery of first birth
Women with missing information (904 births)
ICD-9 codes
To determine whether multiple previous CDs is associated with higher frequency of previa vs 1 previous CD
Cases: multiparous women with previa/control subjects: multiparous women with no previa
Nulliparous, ⬍2 consecutive deliveries at same institution
Placenta attachment totally or mostly low uterine segment diagnosed by ultrasound evaluation or in labor
Characteristics of women with previa compared with women without previa
To evaluate outcomes in CD that is repeated several times
Cases: women with ⱖ4 CDs/control subjects: women with 1-3 CDs
Number of previous hysterectomies
Maternal morbidity that included adhesions, blood loss ⬎1000 g, placenta previa, abruptio placentae, and major perioperative complication
Maternal morbidity that included placenta accreta, hysterectomy, and composite maternal morbidity
................................................................................................................................................................................................................................................................................................................................................................................
Hemminki et al, 200524
Cohort/1987-1998/ Finland
Prelabor hemorrhage, placental problems at birth, mode of delivery
................................................................................................................................................................................................................................................................................................................................................................................
Hershkowitz et al, Cohort/1985-1992/ 199525 Israel
................................................................................................................................................................................................................................................................................................................................................................................
Juntunen et al, 200415
Case-control/19822002/Finland
Not reported
................................................................................................................................................................................................................................................................................................................................................................................
Knight et al, 200816
Case-control/20052006/United Kingdom
To investigate the incidence of peripartum hysterectomy
Cases: women with peripartum hysterectomy/ control subects: no hysterectomy
Not reported
Women undergoing a Risk and indication of hysterectomy in the same hysterectomy that was clinical episode as associated with previous CD delivery of a fetus or infant
................................................................................................................................................................................................................................................................................................................................................................................
Laughon et al, 200529
Case-control/20002003/United States
To determine whether increased risk of previa at delivery with previous CD results from an increased risk of abnormal implantation or lower likelihood of resolution
Cases: singleton Low-lying pregnancies with previa placentas on second trimester ultrasound evaluation/ control subjects: singleton pregnancies with no previa
Review of computerized database records
To assess the association between first birth CD and second birth placental abruption and previa
Cases: women with second singleton with previous CD/control subjects: women with second singleton and previous vaginal
First birth abruption or previa
Classification on birth certificate or ICD-9 code for “placental abruption” or “placenta previa”
Cases: women with CD after ⱖ2 previous CDs
Not reported
Incidence of placenta previa with previous CD
................................................................................................................................................................................................................................................................................................................................................................................
Lydon-Rochelle et Cohort/1987-1996/ al, 200134 United States
Second-birth maternal complications that included abruption, previa, postpartum hemorrhage, hysterectomy, and infection
................................................................................................................................................................................................................................................................................................................................................................................
Lynch et al, 200317
Case series/1990-1999/ Ireland
To investigate the incidence of maternal morbidity after CD in women with at least 2 previous CDs
Women with elective repeat CD solely because of ⱖ2 previous CDs
Maternal morbidity that included previa, adhesions, hysterectomy, surgical injury, venous thromboembolism, and wound problems
................................................................................................................................................................................................................................................................................................................................................................................
Macones et al, 200518
Cohort/1996-2000/ United States
To compare clinical outcomes in women with previous CD
Cases: women with 2 previous CDs
Classic scar
ICD-9 code “previous cesarean delivery, delivered”
Maternal morbidity that included major operative injuries, transfusion, and postpartum fever
................................................................................................................................................................................................................................................................................................................................................................................
Miller et al, 199732
Case series/1985-1994/ United States
To define clinical risk factors Cases: placenta accreta that are associated with confirmed by histologic placenta previa-accreta examination
Cohort/2000-2005/ Israel
To assess maternal complications after multiple CDs
Not reported
Placenta accreta Clinical risk factors associated confirmed by histology on with placenta accreta hysterectomy specimens
................................................................................................................................................................................................................................................................................................................................................................................
Nisenblat et al, 200619
Cases: women with ⱖ3 CDs/control subjects: second CD
Trial of labor after Women scheduled for CD planned repeat CD
Maternal morbidity that included excessive blood loss, dense adhesions, hysterectomy, surgical injury, and placental abnormalities
................................................................................................................................................................................................................................................................................................................................................................................
Marshall. Morbidity with multiple cesarean deliveries. Am J Obstet Gynecol 2011.
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(continued )
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TABLE 1
Studies of maternal morbidity with multiple cesarean deliveries (continued) Study
Design/years/location Aim of study
Population
Odibo et al, 200727
Retrospective cohort/ 1996-2000/United States
Cases: women with Not reported previous CD and previa or abruption/control subjects: women with previous CD without previa or abruption
To evaluate risk factors that are associated with placenta previa and abruption in women with previous CDs
Exclusion criteria Criteria for diagnosis
Relevant outcomes evaluated
ICD-9 codes for ”previous Placenta previa and abruption cesarean delivery, delivered,” sonographic evidence of placenta covering os in third trimester, separation of the placenta before delivery as reported by physicians
................................................................................................................................................................................................................................................................................................................................................................................
Olive et al, 200533
Case series/1998-2002/ Australia
To determine risk factors and Cases: women with maternal morbidity for placenta previa/control women with placenta previa subjects: women without placenta previa
Vaginal birth or CD for failure to progress
Women with placenta previa delivered by CD at ⬎26 wk gestation
Maternal morbidity that included severe postpartum hemorrhage, hysterectomy, intensive care unit admission, or composite maternal morbidity
................................................................................................................................................................................................................................................................................................................................................................................
Phelan et al, 198720
Cohort/1982-1984/ United States
To evaluate the risks that are Cases: women with 1-2 associated with trial of labor previous CDs who attempted a trial of labor/ control subjects: women with repeat CDs
Classic scar, Patients who accepted multiple gestation, trial of labor malpresentation
To evaluate risks for blood transfusion in women with CD
Not reported
Maternal morbidity that included hysterectomy and abnormal placentation
................................................................................................................................................................................................................................................................................................................................................................................
Rouse et al, 200621
Cohort/1999-2000/ United States
Cases: women with CD and blood transfusion
Transfusion of packed red Characteristics of women with blood cells CD who received a blood intraoperatively or transfusion postoperatively before hospital discharge
................................................................................................................................................................................................................................................................................................................................................................................
Silver et al, 200622
Cohort/1999-2002/ United States
To estimate the magnitude of Cases: women who had a increased maternal morbidity CD without labor that is associated with increasing numbers of CDs
Women in labor
Women undergoing CD without labor
Maternal morbidity that included placenta accreta, previa, hysterectomy, surgical injury, and composite morbidity
To investigate the occurrence Cases: women with of placenta previa after CD previa/control subjects: women without previa
Nonwhite, nulliparous, missing data
Vital records check-box of Incidence of placenta previa previous CD and placenta with previous CD previa
To determine whether the rate of abnormal placentation is increasing in conjunction with CD rate
Cases: abnormal placentation/control subjects: normal placentation, matched by year of delivery
Myomatous uteri, malignancy
Histopathologic diagnosis; Incidence of abnormal difficult manual piecemeal placentation by number of removal; heavy continued previous CDs bleeding from implantation site after CD
Cases: women with emergency peripartum hysterectomy
Elective peripartum hysterectomies
................................................................................................................................................................................................................................................................................................................................................................................
Taylor et al, 199430
Case-control/19841987/United States
................................................................................................................................................................................................................................................................................................................................................................................
Wu et al, 200531
Case-control/19822002/United States
................................................................................................................................................................................................................................................................................................................................................................................
Zelop et al, 199323
Case series/1983-1991/ United States
To evaluate the clinical indications and incidence of emergency peripartum hysterectomy
Peripartum hysterectomy performed during the same hospitalization as the delivery
Clinical indications and incidence of peripartum hysterectomy
................................................................................................................................................................................................................................................................................................................................................................................
CD, cesarean delivery; ICD-9, International Classification of Diseases–9th revision. Marshall. Morbidity with multiple cesarean deliveries. Am J Obstet Gynecol 2011.
viewed. Nineteen articles met inclusion criteria and consisted of 8 good- or fairquality cohort studies,14,19,21,22,24-27 7 fairquality case control studies,13,15,16,28-31 and 4 good- or fair-quality case series.17,23,32,33 Each study provided evidence for ⱖ1 of the sections on abruption (5 studies),19,21,24,27,34 previa (16 studies),14,15,17,19, 21-25,27-30,32-34 and accreta (5 studies).13,16,19,22,32
Multiple CDs Hysterectomy increased with increasing number of CDs in all studies (Table 2).13,16,17,19,20,22,23 The odds ratio (OR) for hysterectomy rose with number of previous CDs from 0.7-2.14 with 1 previous CD, 1.4-7.9 with ⱖ1, and 3.8-18.6 with ⱖ2. The best evidence comes from
Silver et al22 who used the Eunice Kennedy Shriver Maternal-Fetal Medicine Units Network CD registry database and noted a statistically significant increased incidence of hysterectomy with an increasing number of CDs from 0.65%, 0.42%, 0.90%, 2.41%, 3.49%, to 8.99%, with 0 to ⱖ5 CDs. Women with ⱖ5 CDs were 15 times more likely to require hysterectomy (OR, 15.2; 95% confidence interval [CI], 6.9 –33.5) than women with vaginal delivery. Four of 7 studies listed the indication for hysterectomy in women with previous CD. The primary indications were placenta previa/accreta (67%), uterine atony (25%), and uterine rupture/laceration (5%).16,17,19,20 Two studies found that increased parity was
associated with an increased risk of hysterectomy after previous CD, but no other examined risk factors, including maternal body mass index or spontaneous labor, were reported to be associated with an increased risk of hysterectomy. 16,23 Higher rates of hemorrhage, blood transfusion, adhesions, and surgical injury with increasing number of CDs were reported consistently in all studies. No change in perioperative infection or wound complications was noted with increasing CDs.
Abruption The overall incidence of abruption with any previous CD was 1.2-1.5%.21,27 Most studies found no increased incidence of abruption in women with increasing
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TABLE 2
Effect of increasing number of cesarean deliveries on rates of hysterectomy Previous cesarean deliveries Study
0
Bodelon et al, 200913
4.6 (3.5–6.0)a
Knight et al, 200816
7.1 (3.7–13.7)a
1
>1
2
>2
3
4
>4
>5
7.9 (5.8–10.7)a
................................................................................................................................................................................................................................................................................................................................................................................
2.1 (1.4–3.3)a
18.6 (7.7–45.4)a
................................................................................................................................................................................................................................................................................................................................................................................
Silver et al, 200622
40/6,201 (0.7)b
Zelop et al, 199323
19/35,240 (0.05)b
0.7a (0.4–0.97)a
1.4 (0.9–2.1)a
3.8 (2.4–6.0)a
5.6 (2.7–11.6)a
15.2 (6.9–33.5)a
................................................................................................................................................................................................................................................................................................................................................................................
29/4366 (0.7)b
70/6694 (1.0)b
................................................................................................................................................................................................................................................................................................................................................................................
Nisenblat et al, 200619
1/491 (0.2)b
3/277 (1.1)b
................................................................................................................................................................................................................................................................................................................................................................................
Phelan et al, 198720
14/847 (1.7)b
................................................................................................................................................................................................................................................................................................................................................................................
2/170 (1.1)b
Lynch et al, 200317
................................................................................................................................................................................................................................................................................................................................................................................ a
Adjusted odds ratio (95% CI); b Data are given as n/N (%).
Marshall. Morbidity with multiple cesarean deliveries. Am J Obstet Gynecol 2011.
numbers of previous CDs. One casecontrol study reported abruption in 3.4% of women with ⱖ3 CDs, but no abruptions were reported in the 149 control CDs (P ⫽ .024).15 For women with ⱖ1 CDs, the rate of abruption was 10.3-15 per 1000 deliveries and does not appear to increase significantly with increasing numbers of CDs.
Placenta previa Compared with previous normal spontaneous vaginal delivery, previous CD was a statistically significant risk factor for placenta previa in 7 studies (OR, 1.48-3.95).21,25,27-30,33 The ORs for all studies were in the direction of increasing risk with the increasing number of CDs, although not all studies reported a statistically significant difference. The incidence of previa with 1 previous CD was 0.8-1.5%. Compared with women without a previous CD, the OR for previa was 1.2-1.9 and reached statistical significance in 4 of 7 studies.24-26,32 In women with 2 CDs, the incidence of previa was 1.1-2.0% (OR, 1.9-2.0, compared with women with previous normal spontaneous vaginal delivery) and was statistically significant in 3 of 5 studies.22,28,32 Two studies19,25 limited comparisons to women with 1 previous CD vs multiple CDs. No increased risk with additional CDs was noted, although these studies had limited sample size for women with multiple CDs 262.e5
and previa (n ⫽ 7 and ⫽ 20, respectively). The 5 studies15,22,27,28,32 that specifically identified women with ⱖ3 CDs all noted a statistically significant increased rate of previa with increasing CDs, up to 3.7% for women with ⱖ5 CDs.
Metaanalysis The metaanalysis with a random effects model demonstrated absolute risk of previa associated with any number of CDs was 12 per 1000 deliveries (95% CI, 8-15 per 1000). Although significant heterogeneity was detected among studies (I2 ⫽ 96.4%; P ⬍ .001), the absolute risks of previa from the included studies were actually quite consistent, ranging from 8 –14 per 1000 deliveries to provide a meaningful summary estimate for previa risk. This was a case in which unimportant statistical heterogeneity was detected, given the large sample size of the included studies. The risk increased with each additional previous CD (Figure 2) from 10 per 1000 with 1 previous CD (95% CI, 6 –13 per 1000) to 28 per 1000 (95% CI, 18 –37 per 1000) with ⱖ3 CDs. The incidence of hysterectomy rose with the increasing number of previous CDs in women with previa. Women with no CD and previa required hysterectomy in 0.7-4% of cases, compared with 5067% in women with ⱖ3 CDs.14,15,17,23 A history of previous CD increased the likelihood of requiring a blood transfu-
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sion compared with women with previa without a CD (OR, 15.9; 95% CI, 12.0 –21.0).21 Two studies presented composite major maternal morbidity in women with previous CD and previa.14,33 One study evaluated severe postpartum hemorrhage, acute renal failure, intensive care unit admission, mechanical ventilation, shock, disseminated intravascular coagulopathy, hysterectomy, other procedures to stop bleeding, and/or death.33 Twenty-two percent of women with previous CD and previa experienced major maternal morbidity compared with 11% of women with previa and no CD. A second study combined transfusion, hysterectomy, operative injury, coagulopathy, venous thromboembolism, pulmonary edema, and/or death.14 There was a statistically significant increase in composite major maternal morbidity in women with previa with an increasing number of CDs from 15% with no previous CD to 83% with ⱖ3 CDs (OR, 33.6; 95% CI, 14.6 –77.4).
Placenta accreta The incidence of placenta accreta increased with the increasing number of CDs (Table 3). The increased incidence did not reach statistical significance until women had at least 2 CDs, compared with no previous CD (OR, 8.6-29.8). Women with 1 previous CD had a rate of
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FIGURE 2
TABLE 3
Risk of placenta previa by number of previous cesarean deliveries
Incidence of accreta in women with previa, based on number of previous cesarean deliveries Previous cesarean deliveries, % Study Miller et al, 1997
0 1 32
2
3
4
>5
4 14 23 35 50
........................................................................................................... 22
Silver et al, 2006
3 11 40 61 67 67
...........................................................................................................
Marshall. Morbidity with multiple cesarean deliveries. Am J Obstet Gynecol 2011.
The squares represent the individual study’s point estimate of effect. The diamond represents the combined point estimate of effect. The size of the shape is a reflection of the weight of the study in each metaanalysis. Marshall. Morbidity with multiple cesarean deliveries. Am J Obstet Gynecol 2011.
accreta of 0.3-0.6%. In comparison with women without previous CD, the OR for accreta with 1 previous CD was 1.3-2.16, which was not statistically significant. The incidence of accreta continued to rise with increasing previous CD up to 6.74% for women with ⱖ5 CDs compared with no previous CD, with an OR of 29.8. Two studies noted a statistically significant increase in accreta in women with previa and previous CD.22,32 As the number of previous CDs rose, the presence of placenta previa increased the likelihood of placenta accreta from 3.3-4% in women who underwent their first CD to 50-67% in women with ⱖ4 CDs. The risk of hysterectomy in women with accreta and previous CD was not reported separately, but 2 studies found that, compared with women with normal placentas, accreta was a statistically
significant risk factor for hysterectomy (OR, 43-99.5; 95% CI, 19.0 –⬁).13,16 Additional maternal outcomes such as surgical injury, hemorrhage, transfusion, and death in women with accreta and previous CD were reported inconsistently, such that meaningful analysis was not possible.
C OMMENT Maternal morbidity increases in a dose-response fashion with each additional CD, especially for women with ⱖ3 CDs who are at statistically significant increased risk of previa, accreta, and hysterectomy. Women with previa and previous CD face the highest rates of morbidity, and the risks increase with increasing number of previous CDs. Compared with women with previa and no previous CD, women with ⱖ3 CDs and previa had a statistically sig-
nificant increased risk of accreta (3.3-4% vs 50-67%), hysterectomy (0.7-4% vs 5067%), and composite maternal morbidity (15% vs 83%; OR, 33.6; 95% CI, 14.6 –77.4). The overall incidence of previa is uncommon and ranges from 12 per 1000 deliveries in women with any previous CD to 28 per 1000 in women with ⱖ3 CDs. Unfortunately, all pregnant women are at risk for previa, and there is no known method for determining which women will experience previa in a subsequent pregnancy. Women with previa are at increased risk of maternal morbidity, and the incidence of previa and risk of morbidity increases with the increasing number of CD. This review confirms the increasing incidence of accreta in women with previa depending on number of previous CDs.22,32,35 Although the patient numbers in each individual study were limited, the consistent findings strongly suggest that women with previa and previous CD are at substantially increased risk of placenta accreta. All women with accreta, regardless of history of previous CD, were at statistically significant increased risk of hysterectomy (OR, 4399.5). This has important implications for patients and providers, especially in rural locations that may not have blood bank capabilities to manage the massive hemorrhage that can accompany placenta accreta. This review found increased maternal morbidity with increasing number of CDs, regardless of placental status. Although the overall incidence was uncommon, the rate of blood transfusions, adhesion formation, surgical injury, and
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SMFM Papers hysterectomy all increased with the increasing number of CDs. Abruption and wound complications do not appear to increase with increasing numbers of CDs. One of the major limitations in analyzing studies regarding placental abnormalities was the lack of consistent definitions that were used, especially for abruption, which may have resulted in misclassification. There was also the potential of surveillance bias as women with previous CDs may have had additional ultrasound scans or observation at the time of delivery in anticipation of possible placental complications compared with women without known risk factors. Some of our primary outcomes were not the focus of the original studies; thus, cases may have been underreported. Studies that used histopathologic diagnosis of accreta were limited to hysterectomy patients and would have missed patients who received conservative therapy. Most studies relied on retrospective data analysis and, as such, are limited by the quality and consistency of the original data collection. A strength of this review is the large volume of cases that were available from a variety of countries and practice settings, including the United States, Australia, United Kingdom, and Israel and both academic- and community-based health centers, which increases the generalizability of the results. We included 21 studies that collected data from 2,282,922 deliveries, which included 180,177 repeat CD and 5729 deliveries with ⱖ3 CDs. There were 5823 cases of placenta previa and 743 cases of accreta; 1852 women required hysterectomy. Most women experienced good outcomes, regardless of the number of previous CDs; therefore, these data do not suggest an upper limit to the number of allowable CDs. The data do support an increased risk of major morbidity with an increasing number of CDs, especially in women with previa. Further studies are needed to better evaluate additional risk factors for the development of placenta accreta and surgical management to minimize uterine scarring. Women who desire large families should be counseled about the risks of 262.e7
www.AJOG.org increasing morbidity with multiple CDs. Because future fertility plans are unknown for many women, patients with 1 previous CD should be counseled about the risks and benefits of both VBAC and multiple CDs to assist with informed decision-making. As the rate of CD continues to rise, hospitals and physicians must be prepared to optimize the treatment of women with multiple CDs and minimize f morbidity and death. ACKNOWLEDGMENTS We thank Andrew Hamilton, MLS, MS, for conducting the literature searches, and Miranda Walker, MA, for assistance with manuscript preparation.
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