http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, Early Online: 1–4 ! 2015 Informa UK Ltd. DOI: 10.3109/14767058.2014.998647
ORIGINAL ARTICLE
Wound morbidity with staples compared with suture for cesarean skin closure by diabetic status Joseph L. Fitzwater, Victoria C. Jauk, Dana Figueroa, Joseph R. Biggio, William W. Andrews, and Alan T. N. Tita J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Mcgill University on 02/19/15 For personal use only.
Department of Obstetrics and Gynecology, Center for Women’s Reproductive Health, University of Alabama at Birmingham, Birmingham, AL, USA
Abstract
Keywords
Objective: To determine if the risk of post-cesarean wound morbidity in patients undergoing staple versus suture closure is modified by diabetic status. Methods: Secondary analysis of a randomized trial of skin closure with subcuticular 4-0 monocryl suture or surgical staples after cesarean delivery. The primary outcome was a composite of wound disruption or infection within 4–6 weeks. We compared the association between this outcome and skin closure method by diabetic status (also stratified by gestational or pregestational) using the Breslow–Day test for interaction. Results: Of 350 patients, 179 were randomized to staples and 171 to suture. Of the 67 (19.1%) diabetic patients, 35 were gestational and 32 pregestational. The incidence of composite wound morbidity in non-diabetics was 16.7% for staples and 3.6% for suture (p 0.001, RR: 4.6, 95% CI: 1.8–11.8); it was 5.7% for staples and 15.6% for sutures in diabetics (p ¼ 0.25, RR: 0.4, 95% CI: 0.1–1.7). The corresponding Breslow–Day p value indicated a significant difference between diabetics and non-diabetics (p ¼ 0.002). Stratified further by gestational and pregestational diabetes, the RRs were 0.3 (95% CI: 0.03–2.4) and 0.5 (95% CI: 0.05–5.0) compared to non-diabetics, respectively. Each diabetic sub-group was significantly different from non-diabetics (Breslow–Day p values for homogeneity p ¼ 0.005 and p ¼ 0.045, respectively). Conclusions: The use of staples compared with subcuticular suture for cesarean skin closure is associated with increased wound morbidity. While this is true for non-diabetics, further studies of diabetics are needed to evaluate for a null or opposite effect of closure type.
Cesarean delivery, diabetes mellitus, gestational diabetes, wound disruption
Introduction In 2010, 32.8% of all deliveries in the United States were by cesarean, having increased by nearly 60% since 1996 [1]. Among multiple short- and long-term complications of cesarean deliveries, wound complications, including infection or disruption, are frequent and costly [2]. Prior studies have evaluated the type of skin closure and the associated risk of wound disruption after cesarean delivery and reported increased wound complication rates with staple closure as compared with subcuticular suture [3–5]. However, there is insufficient data to assess the influence of diabetes mellitus on these findings since several trials excluded patients with this risk factor for wound complication [5,6]. Diabetes mellitus is an increasingly common comorbidity or complication of pregnancy, pregestational in up to 3.7% and gestational in another 2–10% of pregnancies in the United States [7]. This comorbidity is even more prevalent in the southeastern United States [8]. Overall, diabetes mellitus is
Address for correspondence: Joseph L. Fitzwater, MD, 176F 10270, 619 19th St S, Birmingham, AL 35249, USA. Tel: 1-205-934-2565. Fax: 1-205-975-4375. E-mail: [email protected]
History Received 10 September 2014 Revised 5 December 2014 Accepted 11 December 2014 Published online 8 January 2015
also associated with increased risk of multiple adverse pregnancy outcomes and cesarean delivery [2,9–11]. Takoudes demonstrated an independently increased risk of 2.5 for cesarean wound complications in patients with diabetes mellitus [12]. Therefore, the objective of our study was to determine if the association between method of skin closure at cesarean delivery and wound complication differed by diabetic status.
Methods We conducted a secondary analysis of data from an IRBapproved, single-center randomized controlled trial conducted at the University Hospital in Birmingham, Alabama, from August 2009 to November 2010. Full details of the trial have been previously published [4]. Briefly, eligible women with viable pregnancies at 24 weeks gestational age or greater who were undergoing primary or repeat cesarean delivery (scheduled or unscheduled) were enrolled. The women were randomized at the time of fascia closure to either surgical metallic staples (Ethicon Endosurgery Promixate PlusMD skin stapler) or absorbable 4-0 Monocryl (Ethicon, Somerville, NJ) according to a predetermined computer-
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Mcgill University on 02/19/15 For personal use only.
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generated and concealed block randomization technique. Subcutaneous tissue was closed with 3-0 vicryl if the subcutaneous layer was greater than 2.0 cm. Staples were removed at postoperative day 3–4 for patients with Pfannenstiel incisions and postoperative day 7–10 for those with vertical skin incisions. Evaluations of the incisions were performed at discharge (days 3–4 postoperatively) as well as 4–6 weeks postpartum. For the current analysis, we examined the primary outcome of composite wound morbidity, defined as wound infection (purulent drainage, cellulitis, abscess or wound requiring drainage/debridement and antibiotics) and/or disruption (subcutaneous or fascial dehiscence) within 4–6 weeks after delivery. We compared the association between the primary outcome and skin closure method in diabetic and non-diabetic patients using the Breslow–Day test to assess homogeneity (interaction). Diabetic status was sub-stratified further to pregestational and gestational diabetes and compared in each case to non-diabetic status. Diagnosis of gestational diabetes was based on a 50 g 1-h glucose challenge test (GCT) 4200 mg/dL or abnormal 100 g 3-h oral glucose tolerance test using the Carpenter–Coustan criteria following a GCT 135 mg/dL. Diabetes diagnosed prior to pregnancy or in the first half of pregnancy was considered pregestational. The data for the primary trial were abstracted from medical records by trained research nurses into data collection forms. The forms were entered into an Access database by trained data entry staff (Access 2007; Microsoft, Redmond, WA). Data checks were implemented on an ongoing basis during the study and prior to the primary data analysis to assure quality. The current data analysis was implemented with SAS, version 9.1 (SAS Institute, Inc., Cary, NC). Categorical data were examined with the chi-square test of association and Fisher’s exact test. The Student t-test and Wilcoxon rank sum test were used to evaluate quantitative measures.
Results In the original study, 350 of the 398 randomized women completed an evaluation at 4–6 weeks postpartum. Of these patients, 179 were randomized to staples and 171 to suture with 35 and 32 diabetic patients in each closure group, respectively. For the 67 (19.1%) diabetic patients, 35 were gestational and 32 pregestational. The baseline characteristics of patients randomized to staples versus those to the suture group stratified by diabetic status (non-diabetic and diabetics) are listed in Table 1. There was no significant difference in any baseline characteristics between women who received suture and those who received staples within diabetic sub-groups. The primary outcome of composite wound morbidity in the original study was identified in 7.1% (n ¼ 14) of patients with staples and 0.5% (n ¼ 1) with sutures at hospital discharge in 398 patients. By 4–6 weeks, the primary outcome was seen in 14.5% (n ¼ 26) with staples and 5.9% (n ¼ 10) with sutures. The primary outcome at 4–6 weeks stratified by diabetic status is depicted in Figure 1. The incidence of composite wound morbidity at 4–6 weeks postpartum was 16.7% (n ¼ 24) for staples versus 3.6% (n ¼ 5) for sutures (p 0.001, RR: 4.6, 95% CI: 1.8–11.8) in non-diabetics and 5.7% (n ¼ 2) for staples versus 15.6% (n ¼ 5) for sutures in diabetics (p ¼ 0.25, RR: 0.4, 95% CI: 0.1–1.7). The Breslow–Day p value for homogeneity between diabetics and non-diabetics indicated that the association between staple closure and wound complications differed by diabetic status (p ¼ 0.002). When diabetic status was stratified further by sub-type gestational and pregestational diabetes, the relative risks for the association of staple closure and the primary outcome were 0.3 (95% CI: 0.03–2.4) in gestational and 0.5 (95% CI: 0.05–5.0) in pregestational diabetics. Furthermore, comparing each diabetic subtype separately with non-diabetics, the p values for homogeneity were significant – p ¼ 0.005 and p ¼ 0.045, respectively.
Table 1. Baseline characteristics for non-diabetic and diabetic patients. Non-diabetics
Characteristic Age BMI Obese (BMI 30) Race African American White Hispanic Other Smoking Primiparous Prior Cesarean Chronic Hypertension HIV Chorioamnionitis Labor or attempted induction Intrapartum antibiotics Intraoperative antibiotics Vertical midline incision Steroids BTL
Diabetics (pregestational or gestational)
Suture (n ¼ 139) n (%)
Staple (n ¼ 144) n (%)
25.9 ± 5.6 35.0 ± 8.3 96 (69.6%)
26.0 ± 6.0 36.1 ± 8.1 108 (75.0%)
0.9738 0.2826 0.3078
(59.7%) (20.1%) (18.0%) (2.2%)
100 22 21 1
(69.4%) (15.3%) (15.6%) (0.7%)
0.3320
18 (13.0%) 45 (32.4%) 74 (53.2%) 11 (7.9%) 0 15 (10.8%) 76 (54.7%) 36 (25.9%) 136 (98.6%) 11 (7.9%) 9 (6.5%) 35 (25.2%)
16 44 65 18 2 16 76 45 141 6 13 43
(11.1%) (30.6%) (45.1%) (12.5%) (1.4%) (11.1%) (52.8%) (31.3%) (97.9%) (4.2%) (9.0%) (29.9%)
0.6344 0.7419 0.1731 0.2034 0.4984 0.9314 0.7488 0.3195 40.999 0.1848 0.4226 0.3783
83 28 25 3
p value
Suture (n ¼ 32) n (%)
Staple (n ¼ 35) n (%)
p value
30.8 ± 5.8 39.6 ± 8.5 28 (87.5%)
29.7 ± 5.7 39.9 ± 7.0 33 (94.3%)
0.4491 0.9064 0.4145
(43.8%) (31.3%) (21.9%) (3.1%)
19 (54.3%) 5 (14.3%) 11 (31.4%) 0
0.2384
3 (8.6%) 13 (40.6%) 14 (43.8%) 9 (28.1%) 0 5 (15.6%) 15 (46.9%) 12 (37.5%) 32 (100%) 4 (12.5%) 4 (12.5%) 12 (37.5%)
3 (9.4%) 11 (31.4%) 19 (54.3%) 6 (17.1%) 0 2 (5.7%) 13 (37.1%) 10 (28.6%) 35 (100%) 9 (25.7%) 2 (5.7%) 17 (48.6%)
40.999 0.4329 0.3889 0.2814 – 0.2456 0.4198 0.4370 – 0.1719 0.4145 0.3609
14 10 7 1
DOI: 10.3109/14767058.2014.998647
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Mcgill University on 02/19/15 For personal use only.
Discussion Our group and others have previously reported a significant increase in post-cesarean wound morbidity with staples as compared with subcuticular suture close of the skin after cesarean delivery [3–5,13]. Our current secondary analysis indicates that although this relationship is true for the majority of patients who are non-diabetic, findings may be different among diabetics (Breslow–Day p value ¼ 0.002). Specifically, the protective point estimate and the range of values within the 95% CI among diabetics, albeit not significant, raise the possibility of not only a null but also perhaps a protective effect of staples as compared with suture use in diabetics. The findings within sub-types of diabetics are consistent with, and reinforce, the overall results. Nevertheless, since this question was not a pre-specified main objective of the trial, these interesting observations are only hypothesis-generating and should be treated as such. Although diabetes mellitus has been considered a potential confounder due to its independent association with wound morbidity, our study suggests there also is an interaction specific to closure type, modifying the effect of closure on wound complications. Traditional practice has advocated interrupted closure in clean-contaminated incisions like cesarean deliveries to avoid trapping infection in the subcutaneous tissue [14]. Staples have been advocated for this purpose and their theoretical advantage in reducing local tissue injury. Removing them at postoperative day 3–4 may reduce any foreign body reaction. Despite this logic, the literature has not borne out these advantages over suture in reducing wound morbidity. Recent clinical trials and meta-analyses instead have found suture closure to be advantageous in reducing wound morbidity despite the shorter surgical times with staples [3,4,13]. A key strength of this study is the availability of highquality, prospectively collected detailed information on the trial cohort including diabetic status since diabetes was excluded in some of the prior trials examining cesarean wound closure [5,15–19]. Two studies that have evaluated the impact of diabetic status on cesarean wounds did not review this in light of closure type, while the trial by Basha et al. did not examine a difference in effect of closure type by diabetic status [3,11,12]. Although the non-obstetric literature differs in patient population and wound location, there are examples
Staple or suture cesarean closure by diabetic status
3
of similar findings to our study. Johnson et al. found a significantly increased risk of wound complications with staple closure after cardiac operations in non-diabetics but not in diabetics [20]. Key study limitations must be emphasized. First, as mentioned above, a difference by diabetic status was not a pre-specified objective of the trial; therefore, the likelihood of a type 1 error is increased. Second, the primary study was not powered to examine the relationship separately by diabetic status. Findings restricted to diabetics are underpowered, but the significant interaction and the point estimates for diabetics, suggest the potential for a beneficial association of staples with wound complication in diabetics. Third, the results may not be applicable to vertical skin incisions as there were too few to draw meaningful conclusions. Fourth, we acknowledge the potential for residual confounding. As listed in Table 1, there were no significant baseline differences between the suture and staple groups for potential confounders, stratified by the presence or absence of diabetes. Thus, given the small numbers and that our findings are hypothesisgenerating, larger studies can further assess this possibility. While the role of chance is an important concern, this study findings are obviously intriguing and deserve further evaluation. Perhaps less-expensive undertakings, such as secondary analyses of other trials including individual patient data meta-anlysis of all trials and retrospective or time series cohort studies, should be promising before commencing any confirmatory trials in diabetic patients. It remains unclear why patients with pregestational or gestational diabetes may react to staple and suture closure differently than nondiabetics. This notion is not implausible, however, since diabetes is known to be associated with immune-inflammatory dysfunction that increases the risk of wound complications as compared with non-diabetics [21]. Fibroblast and endothelial cell proliferation are reduced, delaying wound remodeling and weakening the closure. In addition, wounds are predisposed to infection due to derangement of the host neutrophil response. Pregestational diabetics with microvascular disease may have inadequate tissue perfusion, depriving the wound of vital nutrition and inflammatory cells [22]. It is possible that the subcuticular stitch engenders a reaction that is not completely controlled by host mechanisms predisposing to wound complications. In conclusion, accumulating evidence supports the use of subcuticular suture over staples for skin closure to prevent cesarean wound complications in most patients including diabetics. Nevertheless, our findings suggest a need to further evaluate optimal closure technique in populations with elevated risk for wound disruption such as those with diabetes mellitus.
Acknowledgements
Figure 1. Effect of staples versus suture for cesarean wound closure on composite wound morbidity by diabetic status. This figure shows the relative risk for the primary composite outcome in non-diabetics and diabetics (further stratified by gestational and pregestational) for the use of suture versus staples.
The authors thank Jan Grant, RN, for contributing to data collection in the primary study and the University of Alabama at Birmingham Residents in Obstetrics and Gynecology for assistance with patient enrollment. This research was presented, in part, at the 33rd Annual Meeting of the Society for Maternal-Fetal Medicine in San Francisco, CA 14–16 February 2013.
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References 1. Martin JA, Hamilton BE, Ventura SJ, et al. Births: final data for 2010. National vital statistics reports. Vol 61, no. 1. Hyattsville (MD): National Center for Health Statistics; 2012. 2. Cunningham FG, Leveno KL, Bloom SL, et al. Williams obstetrics. 23rd ed. New York: McGraw-Hill; 2010. 3. Basha SL, Rochon ML, Quin˜ones JN, et al. Randomized controlled trial of wound complication rates of subcuticular suture vs staples for skin closure at cesarean delivery. Am J Obstet Gynecol 2010; 203:285.e1–8. 4. Figueroa D, Jauk VC, Szychowski JM, et al. Surgical staples compared with subcuticular suture for skin closure after cesarean delivery: a randomized controlled trial. Obstet Gynecol 2013;121: 33–8. 5. Mackeen AD, Khlifeh A, Fleisher J, et al. Suture compared with staple skin closure after cesarean delivery. Obstet Gynecol 2014; 123:1169–75. 6. Mackeen AD, Berghella V, Larsen ML. Techniques and materials for skin closure in caesarean section. Cochrane Database Syst Rev 2012;11:CD003577. 7. Centers for Disease Control and Prevention. National Diabetes Fact Sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta (GA): U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2011. 8. Centers for Disease Control and Prevention. Diabetes Report Card 2012. Atlanta (GA): Centers for Disease Control and Prevention, US Department of Health and Human Services; 2012. 9. ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 60. Clinical Management Guidelines for ObstetricianGynecologists. Number 60, March 2005. Pregestational diabetes mellitus. Obstet Gynecol 2005;105:675–85. 10. Committee on Practice Bulletins – Obstetrics. Practice Bulletin No. 137: gestational diabetes mellitus. Obstet Gynecol 2013;122: 406–16. 11. Leth RA, Uldbjerg N, Nørgaard M, et al. Obesity, diabetes, and the risk of infections diagnosed in hospital and post-discharge
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infections after cesarean section: a prospective cohort study. Acta Obstet Gynecol Scand 2011;90:501–9. Takoudes TC, Weitzen S, Slocum J, Malee M. Risk of cesarean wound complications in diabetic gestations. Am J Obstet Gynecol 2004;191:958–63. Tuuli MG, Rampersad RM, Carbone JF, et al. Staples compared with subcuticular suture for skin closure after cesarean delivery: a systematic review and meta-analysis. Obstet Gynecol 2011;117: 682–90. Berghella V, Baxter JK, Chauhan SP. Evidence-based surgery for cesarean delivery. Am J Obstet Gynecol 2005;193: 1607–17. de Graaf IM, Oude Rengerink K, Wiersma IC, et al. Techniques for wound closure at caesarean section: a randomized clinical trial. Eur J Obstet Gynecol Reprod Biol 2012;165:47–52. Gaertner I, Burkhardt T, Beinder E. Scar appearance of different skin and subcutaneous tissue closure techniques in caesarean section: a randomized study. Eur J Obstet Gynecol Reprod Biol 2008;138:29–33. Juergens S, Maune C, Kezze F, et al. A randomized, controlled study comparing the cosmetic outcome of a new wound closure device with Prolene suture closing caesarean wounds. Int Wound J 2011;8:329–35. Murtha AP, Kaplan AL, Paglia MJ, et al. Evaluation of a novel technique for wound closure using a barbed suture. Plast Reconstr Surg 2006;117:1769–80. Rousseau JA, Girard K, Turcot-Lemay L, Thomas N. A randomized study comparing skin closure in cesarean sections: staples vs subcuticular sutures. Am J Obstet Gynecol 2009;200:265.e1–4. Johnson RG, Cohn WE, Thurer RL, et al. Cutaneous closure after cardiac operations: a controlled, randomized, prospective comparison of intradermal versus staple closures. Ann Surg 1997;226: 606–12. Witte MB, Barbul A. General principles of wound healing. Surg Clin North Am 1997;77:509–28. Robson MC, Steed DL, Franz MG. Wound healing: biologic features and approaches to maximize healing trajectories. Curr Probl Surg 2001;38:72–140.
ORIGINAL ARTICLE
Wound morbidity with staples compared with suture for cesarean skin closure by diabetic status Joseph L. Fitzwater, Victoria C. Jauk, Dana Figueroa, Joseph R. Biggio, William W. Andrews, and Alan T. N. Tita J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Mcgill University on 02/19/15 For personal use only.
Department of Obstetrics and Gynecology, Center for Women’s Reproductive Health, University of Alabama at Birmingham, Birmingham, AL, USA
Abstract
Keywords
Objective: To determine if the risk of post-cesarean wound morbidity in patients undergoing staple versus suture closure is modified by diabetic status. Methods: Secondary analysis of a randomized trial of skin closure with subcuticular 4-0 monocryl suture or surgical staples after cesarean delivery. The primary outcome was a composite of wound disruption or infection within 4–6 weeks. We compared the association between this outcome and skin closure method by diabetic status (also stratified by gestational or pregestational) using the Breslow–Day test for interaction. Results: Of 350 patients, 179 were randomized to staples and 171 to suture. Of the 67 (19.1%) diabetic patients, 35 were gestational and 32 pregestational. The incidence of composite wound morbidity in non-diabetics was 16.7% for staples and 3.6% for suture (p 0.001, RR: 4.6, 95% CI: 1.8–11.8); it was 5.7% for staples and 15.6% for sutures in diabetics (p ¼ 0.25, RR: 0.4, 95% CI: 0.1–1.7). The corresponding Breslow–Day p value indicated a significant difference between diabetics and non-diabetics (p ¼ 0.002). Stratified further by gestational and pregestational diabetes, the RRs were 0.3 (95% CI: 0.03–2.4) and 0.5 (95% CI: 0.05–5.0) compared to non-diabetics, respectively. Each diabetic sub-group was significantly different from non-diabetics (Breslow–Day p values for homogeneity p ¼ 0.005 and p ¼ 0.045, respectively). Conclusions: The use of staples compared with subcuticular suture for cesarean skin closure is associated with increased wound morbidity. While this is true for non-diabetics, further studies of diabetics are needed to evaluate for a null or opposite effect of closure type.
Cesarean delivery, diabetes mellitus, gestational diabetes, wound disruption
Introduction In 2010, 32.8% of all deliveries in the United States were by cesarean, having increased by nearly 60% since 1996 [1]. Among multiple short- and long-term complications of cesarean deliveries, wound complications, including infection or disruption, are frequent and costly [2]. Prior studies have evaluated the type of skin closure and the associated risk of wound disruption after cesarean delivery and reported increased wound complication rates with staple closure as compared with subcuticular suture [3–5]. However, there is insufficient data to assess the influence of diabetes mellitus on these findings since several trials excluded patients with this risk factor for wound complication [5,6]. Diabetes mellitus is an increasingly common comorbidity or complication of pregnancy, pregestational in up to 3.7% and gestational in another 2–10% of pregnancies in the United States [7]. This comorbidity is even more prevalent in the southeastern United States [8]. Overall, diabetes mellitus is
Address for correspondence: Joseph L. Fitzwater, MD, 176F 10270, 619 19th St S, Birmingham, AL 35249, USA. Tel: 1-205-934-2565. Fax: 1-205-975-4375. E-mail: [email protected]
History Received 10 September 2014 Revised 5 December 2014 Accepted 11 December 2014 Published online 8 January 2015
also associated with increased risk of multiple adverse pregnancy outcomes and cesarean delivery [2,9–11]. Takoudes demonstrated an independently increased risk of 2.5 for cesarean wound complications in patients with diabetes mellitus [12]. Therefore, the objective of our study was to determine if the association between method of skin closure at cesarean delivery and wound complication differed by diabetic status.
Methods We conducted a secondary analysis of data from an IRBapproved, single-center randomized controlled trial conducted at the University Hospital in Birmingham, Alabama, from August 2009 to November 2010. Full details of the trial have been previously published [4]. Briefly, eligible women with viable pregnancies at 24 weeks gestational age or greater who were undergoing primary or repeat cesarean delivery (scheduled or unscheduled) were enrolled. The women were randomized at the time of fascia closure to either surgical metallic staples (Ethicon Endosurgery Promixate PlusMD skin stapler) or absorbable 4-0 Monocryl (Ethicon, Somerville, NJ) according to a predetermined computer-
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Mcgill University on 02/19/15 For personal use only.
2
J. L. Fitzwater et al.
J Matern Fetal Neonatal Med, Early Online: 1–4
generated and concealed block randomization technique. Subcutaneous tissue was closed with 3-0 vicryl if the subcutaneous layer was greater than 2.0 cm. Staples were removed at postoperative day 3–4 for patients with Pfannenstiel incisions and postoperative day 7–10 for those with vertical skin incisions. Evaluations of the incisions were performed at discharge (days 3–4 postoperatively) as well as 4–6 weeks postpartum. For the current analysis, we examined the primary outcome of composite wound morbidity, defined as wound infection (purulent drainage, cellulitis, abscess or wound requiring drainage/debridement and antibiotics) and/or disruption (subcutaneous or fascial dehiscence) within 4–6 weeks after delivery. We compared the association between the primary outcome and skin closure method in diabetic and non-diabetic patients using the Breslow–Day test to assess homogeneity (interaction). Diabetic status was sub-stratified further to pregestational and gestational diabetes and compared in each case to non-diabetic status. Diagnosis of gestational diabetes was based on a 50 g 1-h glucose challenge test (GCT) 4200 mg/dL or abnormal 100 g 3-h oral glucose tolerance test using the Carpenter–Coustan criteria following a GCT 135 mg/dL. Diabetes diagnosed prior to pregnancy or in the first half of pregnancy was considered pregestational. The data for the primary trial were abstracted from medical records by trained research nurses into data collection forms. The forms were entered into an Access database by trained data entry staff (Access 2007; Microsoft, Redmond, WA). Data checks were implemented on an ongoing basis during the study and prior to the primary data analysis to assure quality. The current data analysis was implemented with SAS, version 9.1 (SAS Institute, Inc., Cary, NC). Categorical data were examined with the chi-square test of association and Fisher’s exact test. The Student t-test and Wilcoxon rank sum test were used to evaluate quantitative measures.
Results In the original study, 350 of the 398 randomized women completed an evaluation at 4–6 weeks postpartum. Of these patients, 179 were randomized to staples and 171 to suture with 35 and 32 diabetic patients in each closure group, respectively. For the 67 (19.1%) diabetic patients, 35 were gestational and 32 pregestational. The baseline characteristics of patients randomized to staples versus those to the suture group stratified by diabetic status (non-diabetic and diabetics) are listed in Table 1. There was no significant difference in any baseline characteristics between women who received suture and those who received staples within diabetic sub-groups. The primary outcome of composite wound morbidity in the original study was identified in 7.1% (n ¼ 14) of patients with staples and 0.5% (n ¼ 1) with sutures at hospital discharge in 398 patients. By 4–6 weeks, the primary outcome was seen in 14.5% (n ¼ 26) with staples and 5.9% (n ¼ 10) with sutures. The primary outcome at 4–6 weeks stratified by diabetic status is depicted in Figure 1. The incidence of composite wound morbidity at 4–6 weeks postpartum was 16.7% (n ¼ 24) for staples versus 3.6% (n ¼ 5) for sutures (p 0.001, RR: 4.6, 95% CI: 1.8–11.8) in non-diabetics and 5.7% (n ¼ 2) for staples versus 15.6% (n ¼ 5) for sutures in diabetics (p ¼ 0.25, RR: 0.4, 95% CI: 0.1–1.7). The Breslow–Day p value for homogeneity between diabetics and non-diabetics indicated that the association between staple closure and wound complications differed by diabetic status (p ¼ 0.002). When diabetic status was stratified further by sub-type gestational and pregestational diabetes, the relative risks for the association of staple closure and the primary outcome were 0.3 (95% CI: 0.03–2.4) in gestational and 0.5 (95% CI: 0.05–5.0) in pregestational diabetics. Furthermore, comparing each diabetic subtype separately with non-diabetics, the p values for homogeneity were significant – p ¼ 0.005 and p ¼ 0.045, respectively.
Table 1. Baseline characteristics for non-diabetic and diabetic patients. Non-diabetics
Characteristic Age BMI Obese (BMI 30) Race African American White Hispanic Other Smoking Primiparous Prior Cesarean Chronic Hypertension HIV Chorioamnionitis Labor or attempted induction Intrapartum antibiotics Intraoperative antibiotics Vertical midline incision Steroids BTL
Diabetics (pregestational or gestational)
Suture (n ¼ 139) n (%)
Staple (n ¼ 144) n (%)
25.9 ± 5.6 35.0 ± 8.3 96 (69.6%)
26.0 ± 6.0 36.1 ± 8.1 108 (75.0%)
0.9738 0.2826 0.3078
(59.7%) (20.1%) (18.0%) (2.2%)
100 22 21 1
(69.4%) (15.3%) (15.6%) (0.7%)
0.3320
18 (13.0%) 45 (32.4%) 74 (53.2%) 11 (7.9%) 0 15 (10.8%) 76 (54.7%) 36 (25.9%) 136 (98.6%) 11 (7.9%) 9 (6.5%) 35 (25.2%)
16 44 65 18 2 16 76 45 141 6 13 43
(11.1%) (30.6%) (45.1%) (12.5%) (1.4%) (11.1%) (52.8%) (31.3%) (97.9%) (4.2%) (9.0%) (29.9%)
0.6344 0.7419 0.1731 0.2034 0.4984 0.9314 0.7488 0.3195 40.999 0.1848 0.4226 0.3783
83 28 25 3
p value
Suture (n ¼ 32) n (%)
Staple (n ¼ 35) n (%)
p value
30.8 ± 5.8 39.6 ± 8.5 28 (87.5%)
29.7 ± 5.7 39.9 ± 7.0 33 (94.3%)
0.4491 0.9064 0.4145
(43.8%) (31.3%) (21.9%) (3.1%)
19 (54.3%) 5 (14.3%) 11 (31.4%) 0
0.2384
3 (8.6%) 13 (40.6%) 14 (43.8%) 9 (28.1%) 0 5 (15.6%) 15 (46.9%) 12 (37.5%) 32 (100%) 4 (12.5%) 4 (12.5%) 12 (37.5%)
3 (9.4%) 11 (31.4%) 19 (54.3%) 6 (17.1%) 0 2 (5.7%) 13 (37.1%) 10 (28.6%) 35 (100%) 9 (25.7%) 2 (5.7%) 17 (48.6%)
40.999 0.4329 0.3889 0.2814 – 0.2456 0.4198 0.4370 – 0.1719 0.4145 0.3609
14 10 7 1
DOI: 10.3109/14767058.2014.998647
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Mcgill University on 02/19/15 For personal use only.
Discussion Our group and others have previously reported a significant increase in post-cesarean wound morbidity with staples as compared with subcuticular suture close of the skin after cesarean delivery [3–5,13]. Our current secondary analysis indicates that although this relationship is true for the majority of patients who are non-diabetic, findings may be different among diabetics (Breslow–Day p value ¼ 0.002). Specifically, the protective point estimate and the range of values within the 95% CI among diabetics, albeit not significant, raise the possibility of not only a null but also perhaps a protective effect of staples as compared with suture use in diabetics. The findings within sub-types of diabetics are consistent with, and reinforce, the overall results. Nevertheless, since this question was not a pre-specified main objective of the trial, these interesting observations are only hypothesis-generating and should be treated as such. Although diabetes mellitus has been considered a potential confounder due to its independent association with wound morbidity, our study suggests there also is an interaction specific to closure type, modifying the effect of closure on wound complications. Traditional practice has advocated interrupted closure in clean-contaminated incisions like cesarean deliveries to avoid trapping infection in the subcutaneous tissue [14]. Staples have been advocated for this purpose and their theoretical advantage in reducing local tissue injury. Removing them at postoperative day 3–4 may reduce any foreign body reaction. Despite this logic, the literature has not borne out these advantages over suture in reducing wound morbidity. Recent clinical trials and meta-analyses instead have found suture closure to be advantageous in reducing wound morbidity despite the shorter surgical times with staples [3,4,13]. A key strength of this study is the availability of highquality, prospectively collected detailed information on the trial cohort including diabetic status since diabetes was excluded in some of the prior trials examining cesarean wound closure [5,15–19]. Two studies that have evaluated the impact of diabetic status on cesarean wounds did not review this in light of closure type, while the trial by Basha et al. did not examine a difference in effect of closure type by diabetic status [3,11,12]. Although the non-obstetric literature differs in patient population and wound location, there are examples
Staple or suture cesarean closure by diabetic status
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of similar findings to our study. Johnson et al. found a significantly increased risk of wound complications with staple closure after cardiac operations in non-diabetics but not in diabetics [20]. Key study limitations must be emphasized. First, as mentioned above, a difference by diabetic status was not a pre-specified objective of the trial; therefore, the likelihood of a type 1 error is increased. Second, the primary study was not powered to examine the relationship separately by diabetic status. Findings restricted to diabetics are underpowered, but the significant interaction and the point estimates for diabetics, suggest the potential for a beneficial association of staples with wound complication in diabetics. Third, the results may not be applicable to vertical skin incisions as there were too few to draw meaningful conclusions. Fourth, we acknowledge the potential for residual confounding. As listed in Table 1, there were no significant baseline differences between the suture and staple groups for potential confounders, stratified by the presence or absence of diabetes. Thus, given the small numbers and that our findings are hypothesisgenerating, larger studies can further assess this possibility. While the role of chance is an important concern, this study findings are obviously intriguing and deserve further evaluation. Perhaps less-expensive undertakings, such as secondary analyses of other trials including individual patient data meta-anlysis of all trials and retrospective or time series cohort studies, should be promising before commencing any confirmatory trials in diabetic patients. It remains unclear why patients with pregestational or gestational diabetes may react to staple and suture closure differently than nondiabetics. This notion is not implausible, however, since diabetes is known to be associated with immune-inflammatory dysfunction that increases the risk of wound complications as compared with non-diabetics [21]. Fibroblast and endothelial cell proliferation are reduced, delaying wound remodeling and weakening the closure. In addition, wounds are predisposed to infection due to derangement of the host neutrophil response. Pregestational diabetics with microvascular disease may have inadequate tissue perfusion, depriving the wound of vital nutrition and inflammatory cells [22]. It is possible that the subcuticular stitch engenders a reaction that is not completely controlled by host mechanisms predisposing to wound complications. In conclusion, accumulating evidence supports the use of subcuticular suture over staples for skin closure to prevent cesarean wound complications in most patients including diabetics. Nevertheless, our findings suggest a need to further evaluate optimal closure technique in populations with elevated risk for wound disruption such as those with diabetes mellitus.
Acknowledgements
Figure 1. Effect of staples versus suture for cesarean wound closure on composite wound morbidity by diabetic status. This figure shows the relative risk for the primary composite outcome in non-diabetics and diabetics (further stratified by gestational and pregestational) for the use of suture versus staples.
The authors thank Jan Grant, RN, for contributing to data collection in the primary study and the University of Alabama at Birmingham Residents in Obstetrics and Gynecology for assistance with patient enrollment. This research was presented, in part, at the 33rd Annual Meeting of the Society for Maternal-Fetal Medicine in San Francisco, CA 14–16 February 2013.
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J. L. Fitzwater et al.
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