- Email: [email protected]
Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and metaanalysis
Accepted Manuscript Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and meta-analysis Stéphanie Roberge , MSc Suzanne Demers , MD Vincenzo Berghella , MD Nils Chaillet , PhD Lynne Moore , PhD Emmanuel Bujold , MD, MSc PII:
S0002-9378(14)00575-4
DOI:
10.1016/j.ajog.2014.06.014
Reference:
YMOB 9874
To appear in:
American Journal of Obstetrics and Gynecology
Received Date: 14 March 2014 Revised Date:
28 May 2014
Accepted Date: 5 June 2014
Please cite this article as: Roberge S, Demers S, Berghella V, Chaillet N, Moore L, Bujold E, Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and meta-analysis, American Journal of Obstetrics and Gynecology (2014), doi: 10.1016/j.ajog.2014.06.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and meta-analysis Stéphanie
ROBERGE,
MSc1,
Suzanne
DEMERS,
MD1,2,
Vincenzo
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BERGHELLA, MD3, Nils CHAILLET, PhD4, Lynne MOORE, PhD1, Emmanuel BUJOLD, MD, MSc1,2 1
Department of Social and Preventive Medicine, Faculty of Medicine, Université
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Laval, Quebec, QC, Canada 2
Department of Obstetrics and Gynecology, Faculty of Medicine, Université Laval, Quebec, QC, Canada
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Department of Obstetrics and Gynecology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA
4
Department of Obstetrics and Gynecology, Université de Sherbrooke, Sherbrooke, QC, Canada
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Corresponding author:
Emmanuel Bujold, MD, MSc, FRCSC
Professor, Department of Obstetrics and Gynecology, Faculty of Medicine, Université Laval,
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2705 boulevard Laurier, Québec, QC, Canada G1V 4G2; email: [email protected]
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Word count:
Abstract: 240
Manuscript: 2,114
Disclosure statement All authors report that they have no potential conflicts of interest.
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Short title: Uterine closure and adverse maternal outcomes
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Condensation: This review estimates the effect of single- vs double-layer uterine closure at cesarean on the risk of postoperative complications and uterine scar defect.
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Abstract A systematic review and meta-analysis were performed through electronic
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database searches to estimate the effect of uterine closure at cesarean on the risk of adverse maternal outcome and on uterine scar evaluated by ultrasound. Randomized controlled trials, that compared single vs double layers and locking vs unlocking sutures for uterine closure of low transverse cesarean, were
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included. Outcomes were short-term complications (endometritis, wound infection, maternal infectious morbidity, blood transfusion, duration of surgical
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procedure, length of hospital stay, mean blood loss), uterine rupture or dehiscence at next pregnancy and uterine scar evaluation by ultrasound. Twenty out of 1,278 citations were included in the analysis. We found that all types of closure were comparable for short-term maternal outcomes, except for single-
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layer closure that had shorter operative time (-6.1 minutes, 95% confidence interval (CI) -8.7 to -3.4, p<0.001) than double-layer closure. Single-layer (-2.6 mm, 95% CI -3.1 to -2.1, p<0.001) and locked first layer (mean difference: -2.5
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mm, 95% CI -3.2 to -1.8, p<0.001) were associated with lower residual myometrial thickness. Two studies reported no significant difference between
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single- vs double-layer closure for uterine dehiscence (relative risk; 1.86, 95% CI 0.44-7.90, p=0.40) or uterine rupture (no case). In conclusion, current evidence based on randomized trials does not support a specific type of uterine closure for optimal maternal outcomes and is insufficient to conclude about the risk of uterine rupture. Single-layer closure and locked first layer are possibly coupled with thinner residual myometrium thickness. Keywords: cesarean; uterine scar defect; uterine closure; ultrasound evaluation
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Introduction Cesarean is one of the most frequent surgical procedures around the world, constituting the delivery method in up to 30% of births.1 While it allows safe
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delivery in many situations, it remains associated with a risk of adverse outcomes.2 Short-term complications of cesarean include hemorrhage, wound disruption, infection, and venous thromboembolism. In subsequent pregnancies,
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a previous cesarean significantly increases the risk of 2 major obstetrical complications: uterine rupture and placenta accreta.3,4 Moreover, long-term
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adverse outcomes include pain, abnormal uterine bleeding, intraperitoneal adhesions, infertility and additional risk of complications from future abdominal surgeries, including cesareans and hysterectomies.4-8
A growing body of evidence suggests that the surgical technique for uterus
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closure influences uterine scar healing, but there is still no consensus about optimal uterus closure.6,9-13 Some techniques seem to have the potential to decrease the risk of short-term complications, while others have long-term
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benefits, such as reduced risk of uterine rupture.9,10,14 Recently, interest has
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grown in the impact of single- vs. double-layer closure of hysterotomy on the risk of uterine rupture.9,10 Our recent meta-analysis of observational studies, including randomized and non-randomized trials, suggested that locked, single-layer closure was associated with a significantly increased risk of uterine rupture in the next pregnancy compared to double-layer closure (odds ratio (OR) 4.96, 95% confidence intervals (CI) 2.58-9.52, p<0.001),15 but unlocked single-layer closure was not (OR 0.49, 95% CI 0.21-1.16, p=0.10). However, most studies were 4
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retrospective, and the meta-analyses included only 160 cases of uterine rupture. Therefore, we believe that additional evidence-based literature is required before recommending one technique over another. With growing interest in uterine scar
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evaluation by ultrasound, and numerous publications showing a relationship between uterine scar defects, adverse gynecological outcomes, and uterine rupture.5,16-22 this review and meta-analysis could provide additional evidence
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regarding optimal uterine closure technique for short-term outcomes and scar
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defects in addition to long-term outcomes, such as uterine rupture. Our objective was to compare the effect of single- versus double-layer and locked versus unlocked closure of low transverse cesarean on the risk of adverse maternal outcomes, including uterine rupture and uterine scar defect evaluated
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by ultrasound.
Source
A systematic review and meta-analyses were performed. Only randomized
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controlled trials (RCTs) that compared number of layers (single vs double layers)
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and the use of locking vs unlocking sutures for uterus closure at the time of low transverse cesarean were included. However, there was no other restriction about type of skin incision, abdominal opening, or closure of other layers (fascia, peritoneum or skin). A list of keywords and medical subject headings were combined to search the electronic databases PubMed, Web of Science, Embase, and Cochrane Central Register: “uterus”, “uterine”, “dehiscence”, “rupture”, “separation”, “scar”, “VBAC”, “vaginal birth after cesarean”, “closure”, “cesarean”, 5
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and “cesarean” from 1980 to September 2013. References from other selected articles, reviews or meta-analysis were searched for additional relevant articles. Titles, abstracts and full texts were screened by 2 independent reviewers (S.R.,
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E.B.) for inclusion. No language restriction was applied. Disagreement was resolved by discussion with a third reviewer (S.D.). The quality of studies was evaluated by Cochrane Handbook criteria for judging risk of bias, and studies
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with high risk of bias were evaluated by sensitivity analysis.23,24 The quality and integrity of this review were validated with PRISMA: preferred reporting items for
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systematic reviews and meta-analyses.25
We collected information on the following outcomes: 1) maternal infectious morbidity defined as combination of wound infection, endometritis and post-
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operative febrile morbidity or equivalent; 2) endometritis; 3) wound infection; 4) blood transfusion; 5) mean blood loss; 6) duration of surgical procedure, and 7) length of hospital stay. We collected data regarding long-term adverse outcomes
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during subsequent pregnancies, such as uterine rupture or dehiscence. Uterine rupture is defined as complete separation of the uterine scar with visceral disruption
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peritoneum
or
bladder
rupture,
necessitating
an
emergency
intervention (or equivalent definition).26,27 Uterine dehiscence is defined as partial opening of the uterus with intact visceral peritoneum (or an equivalent definition).26,27
We
collected
all
information
regarding
post-cesarean
ultrasonographic evaluation of uterine scar, including the presence of uterine scar defect (defined as the observation of myometrical loss or deformity at the
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cesarean scar site), residual myometrial thickness (in mm) or residual myometrical thickness less than a specific cut-off determined by the author. In case of multiple ultrasound measures in time, available data or those who were
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close to 6-month evaluation, were analyzed.
Risk ratios (RR) with 95% CI compared binary outcomes (uterine rupture,
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infectious morbidity, endometritis, wound infection, blood transfusion, scar defect) between the 2 closure types, and mean difference with 95% CI compared
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continuous outcomes (duration of procedure, length of hospital stay, mean blood loss, residual myometrial thickness). Heterogeneity between studies was assessed according to Higgins I2 criteria.28 Pooled RR were calculated with fixed effects or with DerSimonian and Laird random effects in the absence and
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presence of heterogeneity (I2 >50%), respectively.29 Sensitivity analysis was conducted to investigate robustness of the findings and to explain heterogeneity between studies, comparing suture type (locked or unlocked), thread type
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(yes or no).
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(synthetic or chromic), region (North America or other), and primary cesarean
Results
Our systematic search identified 1,278 articles which were first screened by title and abstract, including 176 that were kept for further evaluation, 39 that were considered potentially eligible, and 20 (13,086 women) meeting all inclusion criteria (Figure 1).11,30-47 Out of them, 16 (41%) studies reported post-operative
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outcomes, including maternal infectious morbidity, the result encountered most frequently (in 11 trials). Six randomized trials detailed uterine scar evaluation with ultrasound,34,36,38,39,41,47 including 3 that reported the rate of uterine scar defect
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and 3 that observed residual myometrial thickness, but raw data could not be extracted from 1 of them and, consequently, could not be included in the analysis.39 Only 2 studies reported follow-up at the next pregnancy and the risk of
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uterine scar dehiscence or uterine rupture (Table 1).13,47
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We undertook sensitivity analysis for maternal infectious morbidity that was examined in 11 trials. We found no significant difference in any subgroup analysis. The number of studies that evaluated uterine scar defects and uterine
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rupture was too small to allow sensitivity analyses.
Moderate-to-high heterogeneity was observed for most outcomes so random effect analysis was undertaken (Table 1). Accurate evaluation of study
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heterogeneity was not possible for uterine scar defect and uterine rupture because of their small number. Two studies were considered at high risk of bias,
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one for the quality of randomization, and the other for unclear reporting of some outcomes (Figure 2).32,36 Removing both of them from the analysis did not significantly change the results so they were conserved for analyses.
Single- vs double-layer closure
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No difference was observed between single- and double-layer closure for the presence of maternal infectious morbidity, endometritis, wound infection, blood transfusion and hospital stay (Table 2). Nonetheless, single-layer closure was
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associated with shorter operative time (4,722 patients, -6.1 minutes, 95% CI -8.7 to -3.4, p<0.001).
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Single-layer closure was not linked with a significant risk of uterine scar dehiscence (187 patients, RR; 2.38, 95% CI 0.63-8.96, p=0.20) or uterine rupture
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(no case) compared to double-layer closure (Table 3).13,40,47 No trials reported the impact of uterus closure on pelvic adhesion or long-term adverse gynecologic outcomes.
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We observed no significant difference in the risk of uterine scar defect with single-layer closure (193 patients, RR: 0.53, 95% CI 0.24-1.17, p=0.12), compared to double-layer closure, (Table 3). However, we noted lower residual
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myometrial thickness in women with single-layer than in those with double-layer
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closure (240 patients, -2.6 mm, 95% CI -3.1 to -2.2, p<0.001) (Table 3).
Locked vs unlocked sutures We identified 2 randomized trials that compared locked to unlocked sutures.47,48 The first study reported no difference in the risk of uterine scar dehiscence at next cesarean delivery for double-layer suture with the first layer locked (29 participants, RR 2.14, 95% CI 0.22-21.10, p=0.51) compared to double-layer
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suture with unlocked first layer.47 However, it showed decreased myometrial thickness (60 patients, mean difference -2.5, 95% CI -3.2 to -1.8, p<0.001) and increased blood loss (60 patients, mean difference 45.0 ml, 95% CI 21.6-68.4,
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p<0.001) with locking of the first layer.47 The second study reported no difference in terms of proportion of scar defect at ultrasound 6-12 months after cesarean (55 patients, RR 1.16, 95% CI 0.97-1.40, p=0.11), using continuous locked
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single-layer compared to interrupted, unlocked, single-layer suture. However, continuous, locked, single-layer closure was coupled with a larger scar defect
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(p<0.001) on sonographic evaluation.48
Conclusion
Our systematic review and meta-analyses suggest no difference in the risk of
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maternal morbidity or long-term outcomes between single- vs double-layer uterus closure at low transverse cesarean. Data from randomized trials are actually insufficient to conclude about the risk of uterine rupture, dehiscence, or
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gynecological outcomes because of insufficient power. On the other hand, when compared to double-layer, single-layer closure was associated with decreased
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residual myometrial thickness and shorter operative time based on 2 (n=240) and 9 (n=4,722 women) studies, respectively. Few data are available on the impact of locked vs unlocked sutures that actually favor the use of unlocked sutures to obtain a thicker myometrium measured by ultrasound.
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Our study has limitations. Based on current evidence, it is very difficult to recommend 1 or the other type of uterus closure. Single- and double-layer closures are associated with low and comparable adverse maternal outcomes in
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almost 15,000 randomized participants. On the other hand, only 504 women underwent ultrasonographic evaluation of uterine scar after cesarean, including heterogeneous protocols and criteria for uterine scar defect. The fact that
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ultrasonographic evaluation of uterine scar was performed 6 weeks to 6 months after cesarean could have affected the results, since complete scar healing can
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take up to 6 months or longer.49 Ultrasound was sometimes undertaken via a transvaginal, sometimes via a transabdominal approach, which could also have influenced the results. Regarding the type of technique for single- or double-layer closure, we observed heterogeneity between studies in the use of locked,
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unlocked, continuous and interrupted sutures, making comparison between studies even more difficult. While the difference was not significant (p=0.12), the rates of uterine scar defect (single-layer: 25% vs double-layer: 61%) do not seem
respectively,
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to be in agreement with residual myometrium thickness (15.0 mm vs 17.6 mm, p<0.001).
Finally,
participants
were
randomized
for
other
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procedures (type of incision, type of closure for other layers) in some studies, while others specifically combined single or double-layer closure with other specific procedures that could have influenced several outcomes, such as operative time, making meta-analyses even more difficult to interpret. Our sensitivity analysis was unable to give us information on robustness of the
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analysis because of the small number of studies available for the primary outcome.
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Our results are in agreement with the Cochrane Review9 that included 7 RCTs (1,769 patients) and compared single vs. double-layer closure on short-term outcomes. The authors did not observe a significant difference between single-
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and double-layer closure in the risk of blood transfusion (1 study, RR 0.80, 95% CI 0.34-1.92), post-operative febrile morbidity (RR 1.07, 95% CI 0.70-1.64) or
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wound infection (RR 1.27, 95% CI 0.95-1.70).9 However, they found that singlelayer uterus closure was associated with reduction of operative time (4 studies, 7.4 minutes, 95% CI -8.4 to -6.5) and blood loss (3 studies, -70.1 ml, 95% CI 101.6 to -38.6) compared to double-layer closure.9 Relative to the Cochrane
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review, our study added the 2 most recent and large RCTs and provided data regarding the evaluation of scar-healing.11,30
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Based on current randomized trials, we cannot recommend a specific technique for uterus closure. However, data from non-randomized or quasi-randomized
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studies strongly suggest that uterine closure techniques can influence uterine scar healing and the risk of uterine rupture.47,50 Moreover, the presence of uterine scar defects and residual myometrial thickness, evaluated by ultrasound, have been associated with gynecologic outcomes, uterine scar dehiscence and uterine rupture, making them surrogate markers of uterine scar healing.8,21,47,51,52 Therefore, we believe that primary prevention of uterine scar defects and
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optimization of residual myometrial thickness have the potential to improve women’s health after cesarean and to decrease the risk of abnormal uterine bleeding, secondary infertility, and adverse obstetrical outcomes, including
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ectopic scar pregnancy, abnormal placentation, scar dehiscence and uterine rupture.7,53
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Currently, there is increasing interest in uterine scar evaluation by ultrasound after cesarean, and a growing practice of uterine scar surgical repair, even in the
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absence of comparative studies showing the benefits of such procedures.20,54,55 We believe that such enthusiasm should be directed towards the primary prevention of uterine scar defects that affect up to 59% of women.56 Additional retrospective and prospective studies could lead to better identification of risk
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factors for scar defects and to future randomized trials.
In conclusion, data from randomized trials that evaluated types of uterine closure
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at cesarean are limited and do not allow us to recommend a specific suture.
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Acknowledgments: Emmanuel Bujold holds a Clinician Scientist Award from the Canadian Institutes of Health Research (CIHR) and Stéphanie Roberge is the recipient of a PhD Study Award from Fonds de recherche du Québec – Santé
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(FRQS). Suzanne Demers received a MSc Study Award from FRQS and the CIHR. This study was supported by the Jeanne and Jean-Louis Lévesque
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Perinatal Research Chair at Université Laval, Quebec, QC, Canada.
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Bujold E, Mehta SH, Bujold C, Gauthier RJ. Interdelivery interval and uterine rupture. Am. J. Obstet. Gynecol. Nov 2002;187(5):1199-1202.
51.
Fabres C, Arriagada P, Fernandez C, Mackenna A, Zegers F, Fernandez E. Surgical treatment and follow-up of women with intermenstrual bleeding due to cesarean section scar defect. J Minim Invasive Gynecol. Jan-Feb 2005;12(1):25-28.
52.
Feng YL, Li MX, Liang XQ, Li XM. Hysteroscopic treatment of postcesarean scar defect. J Minim Invasive Gynecol. Jul-Aug 2012;19(4):498-502.
53.
Spong CY, Quennan JT. Uterine Scar Assessment : How Should It Be Done Before Trial of Labor After Cesarean Delivery? Obstet Gynecol. 2011;117(3):521-522.
54.
Marotta ML, Donnez J, Squifflet J, Jadoul P, Darii N, Donnez O. Laparoscopic repair of post-cesarean section uterine scar defects diagnosed in nonpregnant women. J Minim Invasive Gynecol. May-Jun 2013;20(3):386-391.
55.
Demers S, Roberge S, Bujold E. Laparoscopic repair of post-cesarean uterine scar defect. J Minim Invasive Gynecol. Jul-Aug 2013;20(4):537.
56.
Roberge S, Boutin A, Chaillet N, et al. Systematic Review of Cesarean Scar Assessment in the Nonpregnant State: Imaging Techniques and Uterine Scar Defect. Am. J. Perinatol. Jun 2012;29(6):465-471.
57.
Caesarean section surgical techniques (CORONIS): a fractional, factorial, unmasked, randomised controlled trial. Lancet. May 24 2013;382(9888):234-248.
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58.
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49.
Sood AK. Single versus double layer closure of low transverse uterine incision and caesarean section. Journal of Obstetrics and Gynaecology of India. 2005;55(3):231-236. http://onlinelibrary.wiley.com/o/cochrane/clcentral/articles/669/CN00582669/frame.html.
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Table 1: Characteristics of included studies N
Inclusion criteria
CORONIS, 2013
8,516
Primary or secondary CS through a planned transverse abdominal incision
Any method
El-Gharib & Awara, 201336
150
Primary CS
Continuous locked
Guyot-Cottrel, 38 2011
70
≥18 years, ≥37 weeks, near 1 of 2 hospitals
Continuous unlocked
Yasmin et al., 201147
90
Repeat CS in a singleton pregnancy.
Continuous locked
CAESAR, 201011
2,727
Primary CS planned through LUS
Continuous, locked or unlocked
Continuous, locked or unlocked
Nabhan, 200842
600
LUS CS
nr
nr
Borowski et al., 200734
64
Primary CS
nr
Hamar et al., 200739
30
Non-urgent primary CS
Banad, 200631
100
Poonam et al., 200643 Batioglu et al., 199832 Sood, 200558
Double layer
Outcomes
Any method
Maternal infectious morbidity, endometritis, wound infection, blood transfusion, operative time, hospital stay RMT
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1st layer continuous locked, 2nd imbricating Continuous unlocked Continuous, locked (group B) or continuous unlocked (group C)
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Single layer
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57
Scar defect, blood transfusion
RMT, operative time, uterine dehiscence
Transvaginal US at 6 weeks post-CS
Continuous locked
1st layer continuous locked, 2nd imbricating
Operative time
US at 48 h, 2 weeks and 6 weeks post-CS
LUS CS
nr
nr
400
CS after 37 weeks’ gestation
nr
118
LTCS
208
LTCS
nr
Continuous unlocked Continuous unlocked
Continuous locked for the 1st layer Continuous unlocked
Continuous
Continuous
Continuous locked Continuous locked
nr Continuous
nr
nr
Maternal infectious morbidity, endometritis, wound infection Maternal infectious morbidity, blood transfusion, operative time, hospital stay Maternal infectious morbidity, endometritis, operative time, hospital stay Maternal infectious morbidity, endometritis, wound infection, operative time, hospital stay Maternal infectious morbidity, endometritis, wound infection, operative time, hospital stay Duration of cesarean Duration of cesarean, hospital stay Maternal infectious morbidity, wound infection, operative time, hospital stay Maternal infectious morbidity, endometritis, wound infection, blood transfusion
LTCS Primary CS Primary CS after 30 weeks’ gestation
339
CS after 37 weeks’ gestation
Wallin & Fall, 199945
72
Elective CS without prior abdominal surgery
Interrupted
Interrupted
Lal & Tsomo, 1998
100
LUS CS
Interrupted
Interrupted
Scar defect
Hauth et al., 199240 Chapman et al.,199713
906 145
LTCS
Continuous locked
1st layer continuous locked, 2nd imbricating
Maternal infectious morbidity, endometritis, blood transfusion, operative time, hospital stay, uterine dehiscence
47
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146 200 158
Yasminet al., 2011
Transabdominal US at 6 weeks post-CS
Scar defect
Chitra et al., 200435 Ferrari et al., 200137 Bjorklund et al., 200033
Ceci et al., 201248
Transabdominal US at 48 h, 2 weeks and 6 weeks post-CS Transvaginal US at 6 weeks post-CS
Maternal infectious morbidity, endometritis, wound infection, blood transfusion, operative time, hospital stay Maternal infectious morbidity, wound infection, blood transfusion
Xavier et al., 200546
41
Scar evaluation
nr
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Study
Locked sutures
Unlocked sutures
60
Non-urgent LUS CS in singleton pregnancy at ≥38 weeks
Locked continuous excluding decidua
Interrupted suture excluding decidua
Scar defect
90
Repeat CS in a singleton pregnancy.
Continuous locked
Continuous unlocked
RMT, operative time, uterine dehiscence
Hysterography at 3 months post-CS
Transvaginal US at 6, 12 and 24 months post-CS Transabdominal US at 6 weeks post-CS
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CS: Cesarean section LUS: Low uterine segment LTCS: Low transverse cesarean section US: ultrasound RMT: Residual myometrial thickness nr: not reported
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Table 2: Impact of single- vs double-layer closure on the risk of maternal outcome
13,815 13,730 14,313 No. of participants 1,025
9
4,722
5
4,063
Double layer (%)
416/2,937 (14.2) 196/6,907 (2.8) 566/6,856 (8.3) 141/7,149 (2.0)
425/2,931 (14.5) 183/6,908 (2.6) 612/6,874 (8.9) 164/7,164 (2.3)
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8 8 7 No. of trials 6
Single layer (%)
P value
0.92 (0.74, 1.15)
0.48 0.76 0.18 0.19
513
1.04 (0.81, 1.34) 0.93 (0.83, 1.04) 0.86 (0.69, 1.08) Mean difference (95% CI) -40 [-110, 29]
33.5
39.7
-6.1 (-8.7, -3.4)
<0.0001
4.2
4.6
-0.3 (-0.7, 0.0)
0.05
Means 473
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5,868
RR (95% CI)
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Mean blood loss (ml) Duration of cesarean (minutes) Hospital stay (days)
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Prevalence
I2 37% 26% 15% 23%
P value 0.26
95% 94% 85%
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Endometritis Wound infection Blood transfusion
No. of participants
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Maternal infectious morbidity
No. of trials
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Outcome
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Table 3: Single- vs double-layer closure on the risk of scar defect and lower uterine segment thickness No. of participants
3 2
193 187
Prevalence Single layer (%)
25/100 (25.0) 4/83 (4.8)
Double layer (%)
57/93 (61.3) 3/104 (2.9)
Means 2
240
15.0
17.6
0.53 (0.24, 1.17) 2.38 (0.63, 8.96) Mean difference (95% CI) -2.6 mm (-3.1, -2.2)
P value
I2
0.12 0.20
67% 0%
<0.0001
0%
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LUS thickness (mm)
RR (95% CI)
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Scar defect evaluated by US Uterine rupture or dehiscence
No. of trials
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Outcome
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LUS: Lower uterine segment US: ultrasound
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Figure legends Figure 1: Study selection process
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Figure 2: Assessment of risk of bias in studies included following the Cochrane Handbook
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Potentially relevant citation identified and screened for research (n=1278)
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Citations not relevant excluded (n=1102)
Trials retrieved for more detailed evaluation (n=176)
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Citations excluded, with reasons (n=137)
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Potentially eligible studies reviewed (n=40)
-Same analysis (6) -Other study design (29) -Inappropriate comparison (23) -Allocation inadequate (1) -Letters, commentary, editorial (18) -<1980 (21) -Review or meta-analysis (24) -Other (15)
Studies included in the analysis (n=20)
Citations excluded, with reasons (n=20) -Quasi-random studies (3) -Other comparison (8) -Not a RCT (4) -No results available (4) -Same study (1)
Random sequence allocation Allocation concealment Blinding of participant and… Blinding of outcome assessment
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Incomplete outcome data
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Low Unclear High
Selective reporting Other bias
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0%
20%
40%
60%
80%
100%
Figure 2 Assessment of risk of bias in studies included following the Cochrane Handbook
S0002-9378(14)00575-4
DOI:
10.1016/j.ajog.2014.06.014
Reference:
YMOB 9874
To appear in:
American Journal of Obstetrics and Gynecology
Received Date: 14 March 2014 Revised Date:
28 May 2014
Accepted Date: 5 June 2014
Please cite this article as: Roberge S, Demers S, Berghella V, Chaillet N, Moore L, Bujold E, Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and meta-analysis, American Journal of Obstetrics and Gynecology (2014), doi: 10.1016/j.ajog.2014.06.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and meta-analysis Stéphanie
ROBERGE,
MSc1,
Suzanne
DEMERS,
MD1,2,
Vincenzo
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BERGHELLA, MD3, Nils CHAILLET, PhD4, Lynne MOORE, PhD1, Emmanuel BUJOLD, MD, MSc1,2 1
Department of Social and Preventive Medicine, Faculty of Medicine, Université
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Laval, Quebec, QC, Canada 2
Department of Obstetrics and Gynecology, Faculty of Medicine, Université Laval, Quebec, QC, Canada
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Department of Obstetrics and Gynecology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA
4
Department of Obstetrics and Gynecology, Université de Sherbrooke, Sherbrooke, QC, Canada
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Corresponding author:
Emmanuel Bujold, MD, MSc, FRCSC
Professor, Department of Obstetrics and Gynecology, Faculty of Medicine, Université Laval,
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2705 boulevard Laurier, Québec, QC, Canada G1V 4G2; email: [email protected]
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Word count:
Abstract: 240
Manuscript: 2,114
Disclosure statement All authors report that they have no potential conflicts of interest.
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Short title: Uterine closure and adverse maternal outcomes
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Condensation: This review estimates the effect of single- vs double-layer uterine closure at cesarean on the risk of postoperative complications and uterine scar defect.
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Abstract A systematic review and meta-analysis were performed through electronic
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database searches to estimate the effect of uterine closure at cesarean on the risk of adverse maternal outcome and on uterine scar evaluated by ultrasound. Randomized controlled trials, that compared single vs double layers and locking vs unlocking sutures for uterine closure of low transverse cesarean, were
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included. Outcomes were short-term complications (endometritis, wound infection, maternal infectious morbidity, blood transfusion, duration of surgical
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procedure, length of hospital stay, mean blood loss), uterine rupture or dehiscence at next pregnancy and uterine scar evaluation by ultrasound. Twenty out of 1,278 citations were included in the analysis. We found that all types of closure were comparable for short-term maternal outcomes, except for single-
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layer closure that had shorter operative time (-6.1 minutes, 95% confidence interval (CI) -8.7 to -3.4, p<0.001) than double-layer closure. Single-layer (-2.6 mm, 95% CI -3.1 to -2.1, p<0.001) and locked first layer (mean difference: -2.5
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mm, 95% CI -3.2 to -1.8, p<0.001) were associated with lower residual myometrial thickness. Two studies reported no significant difference between
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single- vs double-layer closure for uterine dehiscence (relative risk; 1.86, 95% CI 0.44-7.90, p=0.40) or uterine rupture (no case). In conclusion, current evidence based on randomized trials does not support a specific type of uterine closure for optimal maternal outcomes and is insufficient to conclude about the risk of uterine rupture. Single-layer closure and locked first layer are possibly coupled with thinner residual myometrium thickness. Keywords: cesarean; uterine scar defect; uterine closure; ultrasound evaluation
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Introduction Cesarean is one of the most frequent surgical procedures around the world, constituting the delivery method in up to 30% of births.1 While it allows safe
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delivery in many situations, it remains associated with a risk of adverse outcomes.2 Short-term complications of cesarean include hemorrhage, wound disruption, infection, and venous thromboembolism. In subsequent pregnancies,
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a previous cesarean significantly increases the risk of 2 major obstetrical complications: uterine rupture and placenta accreta.3,4 Moreover, long-term
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adverse outcomes include pain, abnormal uterine bleeding, intraperitoneal adhesions, infertility and additional risk of complications from future abdominal surgeries, including cesareans and hysterectomies.4-8
A growing body of evidence suggests that the surgical technique for uterus
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closure influences uterine scar healing, but there is still no consensus about optimal uterus closure.6,9-13 Some techniques seem to have the potential to decrease the risk of short-term complications, while others have long-term
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benefits, such as reduced risk of uterine rupture.9,10,14 Recently, interest has
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grown in the impact of single- vs. double-layer closure of hysterotomy on the risk of uterine rupture.9,10 Our recent meta-analysis of observational studies, including randomized and non-randomized trials, suggested that locked, single-layer closure was associated with a significantly increased risk of uterine rupture in the next pregnancy compared to double-layer closure (odds ratio (OR) 4.96, 95% confidence intervals (CI) 2.58-9.52, p<0.001),15 but unlocked single-layer closure was not (OR 0.49, 95% CI 0.21-1.16, p=0.10). However, most studies were 4
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retrospective, and the meta-analyses included only 160 cases of uterine rupture. Therefore, we believe that additional evidence-based literature is required before recommending one technique over another. With growing interest in uterine scar
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evaluation by ultrasound, and numerous publications showing a relationship between uterine scar defects, adverse gynecological outcomes, and uterine rupture.5,16-22 this review and meta-analysis could provide additional evidence
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regarding optimal uterine closure technique for short-term outcomes and scar
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defects in addition to long-term outcomes, such as uterine rupture. Our objective was to compare the effect of single- versus double-layer and locked versus unlocked closure of low transverse cesarean on the risk of adverse maternal outcomes, including uterine rupture and uterine scar defect evaluated
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by ultrasound.
Source
A systematic review and meta-analyses were performed. Only randomized
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controlled trials (RCTs) that compared number of layers (single vs double layers)
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and the use of locking vs unlocking sutures for uterus closure at the time of low transverse cesarean were included. However, there was no other restriction about type of skin incision, abdominal opening, or closure of other layers (fascia, peritoneum or skin). A list of keywords and medical subject headings were combined to search the electronic databases PubMed, Web of Science, Embase, and Cochrane Central Register: “uterus”, “uterine”, “dehiscence”, “rupture”, “separation”, “scar”, “VBAC”, “vaginal birth after cesarean”, “closure”, “cesarean”, 5
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and “cesarean” from 1980 to September 2013. References from other selected articles, reviews or meta-analysis were searched for additional relevant articles. Titles, abstracts and full texts were screened by 2 independent reviewers (S.R.,
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E.B.) for inclusion. No language restriction was applied. Disagreement was resolved by discussion with a third reviewer (S.D.). The quality of studies was evaluated by Cochrane Handbook criteria for judging risk of bias, and studies
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with high risk of bias were evaluated by sensitivity analysis.23,24 The quality and integrity of this review were validated with PRISMA: preferred reporting items for
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systematic reviews and meta-analyses.25
We collected information on the following outcomes: 1) maternal infectious morbidity defined as combination of wound infection, endometritis and post-
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operative febrile morbidity or equivalent; 2) endometritis; 3) wound infection; 4) blood transfusion; 5) mean blood loss; 6) duration of surgical procedure, and 7) length of hospital stay. We collected data regarding long-term adverse outcomes
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during subsequent pregnancies, such as uterine rupture or dehiscence. Uterine rupture is defined as complete separation of the uterine scar with visceral disruption
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peritoneum
or
bladder
rupture,
necessitating
an
emergency
intervention (or equivalent definition).26,27 Uterine dehiscence is defined as partial opening of the uterus with intact visceral peritoneum (or an equivalent definition).26,27
We
collected
all
information
regarding
post-cesarean
ultrasonographic evaluation of uterine scar, including the presence of uterine scar defect (defined as the observation of myometrical loss or deformity at the
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cesarean scar site), residual myometrial thickness (in mm) or residual myometrical thickness less than a specific cut-off determined by the author. In case of multiple ultrasound measures in time, available data or those who were
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close to 6-month evaluation, were analyzed.
Risk ratios (RR) with 95% CI compared binary outcomes (uterine rupture,
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infectious morbidity, endometritis, wound infection, blood transfusion, scar defect) between the 2 closure types, and mean difference with 95% CI compared
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continuous outcomes (duration of procedure, length of hospital stay, mean blood loss, residual myometrial thickness). Heterogeneity between studies was assessed according to Higgins I2 criteria.28 Pooled RR were calculated with fixed effects or with DerSimonian and Laird random effects in the absence and
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presence of heterogeneity (I2 >50%), respectively.29 Sensitivity analysis was conducted to investigate robustness of the findings and to explain heterogeneity between studies, comparing suture type (locked or unlocked), thread type
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(yes or no).
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(synthetic or chromic), region (North America or other), and primary cesarean
Results
Our systematic search identified 1,278 articles which were first screened by title and abstract, including 176 that were kept for further evaluation, 39 that were considered potentially eligible, and 20 (13,086 women) meeting all inclusion criteria (Figure 1).11,30-47 Out of them, 16 (41%) studies reported post-operative
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outcomes, including maternal infectious morbidity, the result encountered most frequently (in 11 trials). Six randomized trials detailed uterine scar evaluation with ultrasound,34,36,38,39,41,47 including 3 that reported the rate of uterine scar defect
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and 3 that observed residual myometrial thickness, but raw data could not be extracted from 1 of them and, consequently, could not be included in the analysis.39 Only 2 studies reported follow-up at the next pregnancy and the risk of
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uterine scar dehiscence or uterine rupture (Table 1).13,47
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We undertook sensitivity analysis for maternal infectious morbidity that was examined in 11 trials. We found no significant difference in any subgroup analysis. The number of studies that evaluated uterine scar defects and uterine
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rupture was too small to allow sensitivity analyses.
Moderate-to-high heterogeneity was observed for most outcomes so random effect analysis was undertaken (Table 1). Accurate evaluation of study
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heterogeneity was not possible for uterine scar defect and uterine rupture because of their small number. Two studies were considered at high risk of bias,
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one for the quality of randomization, and the other for unclear reporting of some outcomes (Figure 2).32,36 Removing both of them from the analysis did not significantly change the results so they were conserved for analyses.
Single- vs double-layer closure
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No difference was observed between single- and double-layer closure for the presence of maternal infectious morbidity, endometritis, wound infection, blood transfusion and hospital stay (Table 2). Nonetheless, single-layer closure was
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associated with shorter operative time (4,722 patients, -6.1 minutes, 95% CI -8.7 to -3.4, p<0.001).
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Single-layer closure was not linked with a significant risk of uterine scar dehiscence (187 patients, RR; 2.38, 95% CI 0.63-8.96, p=0.20) or uterine rupture
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(no case) compared to double-layer closure (Table 3).13,40,47 No trials reported the impact of uterus closure on pelvic adhesion or long-term adverse gynecologic outcomes.
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We observed no significant difference in the risk of uterine scar defect with single-layer closure (193 patients, RR: 0.53, 95% CI 0.24-1.17, p=0.12), compared to double-layer closure, (Table 3). However, we noted lower residual
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myometrial thickness in women with single-layer than in those with double-layer
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closure (240 patients, -2.6 mm, 95% CI -3.1 to -2.2, p<0.001) (Table 3).
Locked vs unlocked sutures We identified 2 randomized trials that compared locked to unlocked sutures.47,48 The first study reported no difference in the risk of uterine scar dehiscence at next cesarean delivery for double-layer suture with the first layer locked (29 participants, RR 2.14, 95% CI 0.22-21.10, p=0.51) compared to double-layer
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suture with unlocked first layer.47 However, it showed decreased myometrial thickness (60 patients, mean difference -2.5, 95% CI -3.2 to -1.8, p<0.001) and increased blood loss (60 patients, mean difference 45.0 ml, 95% CI 21.6-68.4,
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p<0.001) with locking of the first layer.47 The second study reported no difference in terms of proportion of scar defect at ultrasound 6-12 months after cesarean (55 patients, RR 1.16, 95% CI 0.97-1.40, p=0.11), using continuous locked
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single-layer compared to interrupted, unlocked, single-layer suture. However, continuous, locked, single-layer closure was coupled with a larger scar defect
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(p<0.001) on sonographic evaluation.48
Conclusion
Our systematic review and meta-analyses suggest no difference in the risk of
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maternal morbidity or long-term outcomes between single- vs double-layer uterus closure at low transverse cesarean. Data from randomized trials are actually insufficient to conclude about the risk of uterine rupture, dehiscence, or
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gynecological outcomes because of insufficient power. On the other hand, when compared to double-layer, single-layer closure was associated with decreased
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residual myometrial thickness and shorter operative time based on 2 (n=240) and 9 (n=4,722 women) studies, respectively. Few data are available on the impact of locked vs unlocked sutures that actually favor the use of unlocked sutures to obtain a thicker myometrium measured by ultrasound.
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Our study has limitations. Based on current evidence, it is very difficult to recommend 1 or the other type of uterus closure. Single- and double-layer closures are associated with low and comparable adverse maternal outcomes in
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almost 15,000 randomized participants. On the other hand, only 504 women underwent ultrasonographic evaluation of uterine scar after cesarean, including heterogeneous protocols and criteria for uterine scar defect. The fact that
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ultrasonographic evaluation of uterine scar was performed 6 weeks to 6 months after cesarean could have affected the results, since complete scar healing can
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take up to 6 months or longer.49 Ultrasound was sometimes undertaken via a transvaginal, sometimes via a transabdominal approach, which could also have influenced the results. Regarding the type of technique for single- or double-layer closure, we observed heterogeneity between studies in the use of locked,
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unlocked, continuous and interrupted sutures, making comparison between studies even more difficult. While the difference was not significant (p=0.12), the rates of uterine scar defect (single-layer: 25% vs double-layer: 61%) do not seem
respectively,
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to be in agreement with residual myometrium thickness (15.0 mm vs 17.6 mm, p<0.001).
Finally,
participants
were
randomized
for
other
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procedures (type of incision, type of closure for other layers) in some studies, while others specifically combined single or double-layer closure with other specific procedures that could have influenced several outcomes, such as operative time, making meta-analyses even more difficult to interpret. Our sensitivity analysis was unable to give us information on robustness of the
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analysis because of the small number of studies available for the primary outcome.
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Our results are in agreement with the Cochrane Review9 that included 7 RCTs (1,769 patients) and compared single vs. double-layer closure on short-term outcomes. The authors did not observe a significant difference between single-
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and double-layer closure in the risk of blood transfusion (1 study, RR 0.80, 95% CI 0.34-1.92), post-operative febrile morbidity (RR 1.07, 95% CI 0.70-1.64) or
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wound infection (RR 1.27, 95% CI 0.95-1.70).9 However, they found that singlelayer uterus closure was associated with reduction of operative time (4 studies, 7.4 minutes, 95% CI -8.4 to -6.5) and blood loss (3 studies, -70.1 ml, 95% CI 101.6 to -38.6) compared to double-layer closure.9 Relative to the Cochrane
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review, our study added the 2 most recent and large RCTs and provided data regarding the evaluation of scar-healing.11,30
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Based on current randomized trials, we cannot recommend a specific technique for uterus closure. However, data from non-randomized or quasi-randomized
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studies strongly suggest that uterine closure techniques can influence uterine scar healing and the risk of uterine rupture.47,50 Moreover, the presence of uterine scar defects and residual myometrial thickness, evaluated by ultrasound, have been associated with gynecologic outcomes, uterine scar dehiscence and uterine rupture, making them surrogate markers of uterine scar healing.8,21,47,51,52 Therefore, we believe that primary prevention of uterine scar defects and
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optimization of residual myometrial thickness have the potential to improve women’s health after cesarean and to decrease the risk of abnormal uterine bleeding, secondary infertility, and adverse obstetrical outcomes, including
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ectopic scar pregnancy, abnormal placentation, scar dehiscence and uterine rupture.7,53
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Currently, there is increasing interest in uterine scar evaluation by ultrasound after cesarean, and a growing practice of uterine scar surgical repair, even in the
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absence of comparative studies showing the benefits of such procedures.20,54,55 We believe that such enthusiasm should be directed towards the primary prevention of uterine scar defects that affect up to 59% of women.56 Additional retrospective and prospective studies could lead to better identification of risk
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factors for scar defects and to future randomized trials.
In conclusion, data from randomized trials that evaluated types of uterine closure
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at cesarean are limited and do not allow us to recommend a specific suture.
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Acknowledgments: Emmanuel Bujold holds a Clinician Scientist Award from the Canadian Institutes of Health Research (CIHR) and Stéphanie Roberge is the recipient of a PhD Study Award from Fonds de recherche du Québec – Santé
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(FRQS). Suzanne Demers received a MSc Study Award from FRQS and the CIHR. This study was supported by the Jeanne and Jean-Louis Lévesque
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Perinatal Research Chair at Université Laval, Quebec, QC, Canada.
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References Betran AP, Merialdi M, Lauer JA, et al. Rates of caesarean section: analysis of global, regional and national estimates. Paediatr Perinat Epidemiol. Mar 2007;21(2):98-113.
2.
Liu S, Liston RM, Joseph KS, Heaman M, Sauve R, Kramer MS. Maternal mortality and severe morbidity associated with low-risk planned cesarean delivery versus planned vaginal delivery at term. Cmaj. Feb 13 2007;176(4):455-460.
3.
Jauniaux E, Jurkovic D. Placenta accreta: pathogenesis of a 20th century iatrogenic uterine disease. Placenta. Apr 2012;33(4):244-251.
4.
Silver RM. Delivery after previous cesarean: long-term maternal outcomes. Semin Perinatol. Aug 2010;34(4):258-266.
5.
Fabres C, Aviles G, De La Jara C, et al. The cesarean delivery scar pouch: clinical implications and diagnostic correlation between transvaginal sonography and hysteroscopy. J Ultrasound Med. Jul 2003;22(7):695-700; quiz 701-692.
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Blumenfeld YJ, Caughey AB, El-Sayed YY, Daniels K, Lyell DJ. Singleversus double-layer hysterotomy closure at primary caesarean delivery and bladder adhesions. Bjog. May 2010;117(6):690-694.
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Demers S, Roberge S, Bujold E. Laparoscopic repair of post-cesarean uterine scar defect. J Minim Invasive Gynecol. Jul-Aug 2013;20(4):537.
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Table 1: Characteristics of included studies N
Inclusion criteria
CORONIS, 2013
8,516
Primary or secondary CS through a planned transverse abdominal incision
Any method
El-Gharib & Awara, 201336
150
Primary CS
Continuous locked
Guyot-Cottrel, 38 2011
70
≥18 years, ≥37 weeks, near 1 of 2 hospitals
Continuous unlocked
Yasmin et al., 201147
90
Repeat CS in a singleton pregnancy.
Continuous locked
CAESAR, 201011
2,727
Primary CS planned through LUS
Continuous, locked or unlocked
Continuous, locked or unlocked
Nabhan, 200842
600
LUS CS
nr
nr
Borowski et al., 200734
64
Primary CS
nr
Hamar et al., 200739
30
Non-urgent primary CS
Banad, 200631
100
Poonam et al., 200643 Batioglu et al., 199832 Sood, 200558
Double layer
Outcomes
Any method
Maternal infectious morbidity, endometritis, wound infection, blood transfusion, operative time, hospital stay RMT
RI PT
1st layer continuous locked, 2nd imbricating Continuous unlocked Continuous, locked (group B) or continuous unlocked (group C)
SC
Single layer
M AN U
57
Scar defect, blood transfusion
RMT, operative time, uterine dehiscence
Transvaginal US at 6 weeks post-CS
Continuous locked
1st layer continuous locked, 2nd imbricating
Operative time
US at 48 h, 2 weeks and 6 weeks post-CS
LUS CS
nr
nr
400
CS after 37 weeks’ gestation
nr
118
LTCS
208
LTCS
nr
Continuous unlocked Continuous unlocked
Continuous locked for the 1st layer Continuous unlocked
Continuous
Continuous
Continuous locked Continuous locked
nr Continuous
nr
nr
Maternal infectious morbidity, endometritis, wound infection Maternal infectious morbidity, blood transfusion, operative time, hospital stay Maternal infectious morbidity, endometritis, operative time, hospital stay Maternal infectious morbidity, endometritis, wound infection, operative time, hospital stay Maternal infectious morbidity, endometritis, wound infection, operative time, hospital stay Duration of cesarean Duration of cesarean, hospital stay Maternal infectious morbidity, wound infection, operative time, hospital stay Maternal infectious morbidity, endometritis, wound infection, blood transfusion
LTCS Primary CS Primary CS after 30 weeks’ gestation
339
CS after 37 weeks’ gestation
Wallin & Fall, 199945
72
Elective CS without prior abdominal surgery
Interrupted
Interrupted
Lal & Tsomo, 1998
100
LUS CS
Interrupted
Interrupted
Scar defect
Hauth et al., 199240 Chapman et al.,199713
906 145
LTCS
Continuous locked
1st layer continuous locked, 2nd imbricating
Maternal infectious morbidity, endometritis, blood transfusion, operative time, hospital stay, uterine dehiscence
47
AC C
EP
146 200 158
Yasminet al., 2011
Transabdominal US at 6 weeks post-CS
Scar defect
Chitra et al., 200435 Ferrari et al., 200137 Bjorklund et al., 200033
Ceci et al., 201248
Transabdominal US at 48 h, 2 weeks and 6 weeks post-CS Transvaginal US at 6 weeks post-CS
Maternal infectious morbidity, endometritis, wound infection, blood transfusion, operative time, hospital stay Maternal infectious morbidity, wound infection, blood transfusion
Xavier et al., 200546
41
Scar evaluation
nr
TE D
Study
Locked sutures
Unlocked sutures
60
Non-urgent LUS CS in singleton pregnancy at ≥38 weeks
Locked continuous excluding decidua
Interrupted suture excluding decidua
Scar defect
90
Repeat CS in a singleton pregnancy.
Continuous locked
Continuous unlocked
RMT, operative time, uterine dehiscence
Hysterography at 3 months post-CS
Transvaginal US at 6, 12 and 24 months post-CS Transabdominal US at 6 weeks post-CS
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CS: Cesarean section LUS: Low uterine segment LTCS: Low transverse cesarean section US: ultrasound RMT: Residual myometrial thickness nr: not reported
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Table 2: Impact of single- vs double-layer closure on the risk of maternal outcome
13,815 13,730 14,313 No. of participants 1,025
9
4,722
5
4,063
Double layer (%)
416/2,937 (14.2) 196/6,907 (2.8) 566/6,856 (8.3) 141/7,149 (2.0)
425/2,931 (14.5) 183/6,908 (2.6) 612/6,874 (8.9) 164/7,164 (2.3)
RI PT
8 8 7 No. of trials 6
Single layer (%)
P value
0.92 (0.74, 1.15)
0.48 0.76 0.18 0.19
513
1.04 (0.81, 1.34) 0.93 (0.83, 1.04) 0.86 (0.69, 1.08) Mean difference (95% CI) -40 [-110, 29]
33.5
39.7
-6.1 (-8.7, -3.4)
<0.0001
4.2
4.6
-0.3 (-0.7, 0.0)
0.05
Means 473
SC
5,868
RR (95% CI)
M AN U
Mean blood loss (ml) Duration of cesarean (minutes) Hospital stay (days)
10
Prevalence
I2 37% 26% 15% 23%
P value 0.26
95% 94% 85%
TE D
Endometritis Wound infection Blood transfusion
No. of participants
EP
Maternal infectious morbidity
No. of trials
AC C
Outcome
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Table 3: Single- vs double-layer closure on the risk of scar defect and lower uterine segment thickness No. of participants
3 2
193 187
Prevalence Single layer (%)
25/100 (25.0) 4/83 (4.8)
Double layer (%)
57/93 (61.3) 3/104 (2.9)
Means 2
240
15.0
17.6
0.53 (0.24, 1.17) 2.38 (0.63, 8.96) Mean difference (95% CI) -2.6 mm (-3.1, -2.2)
P value
I2
0.12 0.20
67% 0%
<0.0001
0%
M AN U
LUS thickness (mm)
RR (95% CI)
RI PT
Scar defect evaluated by US Uterine rupture or dehiscence
No. of trials
SC
Outcome
AC C
EP
TE D
LUS: Lower uterine segment US: ultrasound
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Figure legends Figure 1: Study selection process
AC C
EP
TE D
M AN U
SC
RI PT
Figure 2: Assessment of risk of bias in studies included following the Cochrane Handbook
24
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RI PT
Potentially relevant citation identified and screened for research (n=1278)
SC
Citations not relevant excluded (n=1102)
Trials retrieved for more detailed evaluation (n=176)
M AN U
Citations excluded, with reasons (n=137)
AC C
TE D
EP
Potentially eligible studies reviewed (n=40)
-Same analysis (6) -Other study design (29) -Inappropriate comparison (23) -Allocation inadequate (1) -Letters, commentary, editorial (18) -<1980 (21) -Review or meta-analysis (24) -Other (15)
Studies included in the analysis (n=20)
Citations excluded, with reasons (n=20) -Quasi-random studies (3) -Other comparison (8) -Not a RCT (4) -No results available (4) -Same study (1)
Random sequence allocation Allocation concealment Blinding of participant and… Blinding of outcome assessment
TE D
Incomplete outcome data
M AN U
SC
RI PT
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Low Unclear High
Selective reporting Other bias
AC C
EP
0%
20%
40%
60%
80%
100%
Figure 2 Assessment of risk of bias in studies included following the Cochrane Handbook