By Ahizechukwu C. Eke, MD, PhD, MPH
Associate Professor in Maternal Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore
Povidone-iodine (Betadine) vaginal cleansing prior to an unplanned cesarean delivery for labor-related indications did not lessen the postoperative infectious morbidity, and, therefore, its regular use in women having a cesarean delivery for labor-related indications is not supported.
Temming LA, Frovola AI, Raghuraman N, et al. Vaginal cleansing before unscheduled cesarean delivery to reduce infection: A randomized clinical trial. Am J Obstet Gynecol 2022; Nov 30. doi: 10.1016/j.ajog.2022.11.1300. [Online ahead of print].
Puerperal infectious morbidity after cesarean delivery remains a major cause of maternal morbidity and mortality in the United States.1 Puerperal infections occur in 1% to 3% of vaginal births and up to 27% of cesarean deliveries.2 Although there are numerous causes for puerperal infections (including urinary tract infections, pyelonephritis, mastitis, septic thrombophlebitis, pneumonia, and drug fever), endometritis resulting from ascending infection of anaerobic vaginal bacteria remains the most common cause.3 Endometritis accounts for nearly half of puerperal infections in patients following cesarean delivery in the United States.4 Previous research indicates that cleansing the vagina with an antiseptic solution prior to cesarean delivery significantly lowered the risk for puerperal infections by reducing the burden of vaginal bacteria.5 In two recent systematic review and meta-analyses, vaginal cleansing just prior to cesarean delivery resulted in a significant reduction in postoperative endometritis in laboring pregnant women with and without ruptured membranes.5,6
Both povidone iodine (Betadine) and chlorhexidine-based antiseptics reduced the risk of post-cesarean endometritis compared to saline or no cleansing.5,6 However, the included studies in these meta-analyses were of varying size, quality, and design. Because of the significant heterogeneity in the included studies in these two meta-analyses (I2 > 30%), Temming and colleagues designed this randomized trial and hypothesized that vaginal cleansing with povidone-iodine antiseptic reduces post-cesarean infectious morbidity in laboring pregnant women with ruptured membranes.7
This was an open-label, randomized clinical trial conducted at several centers in the United States. Inclusion criteria were pregnant women with ruptured membranes who underwent cesarean delivery after regular uterine contractions with any cervical dilation. Women were excluded if they had a cesarean delivery with intact membranes in the absence of labor, if they were unable to provide informed consent, or if they had a known or potential allergy to iodine. Participants were randomized in a 1:1 ratio to receive vaginal cleansing (three passes of vaginal cleansing with sponge sticks soaked in 1% povidone-iodine solution) vs. no vaginal cleansing.
The primary outcome included a composite of post-cesarean infectious morbidity comprising endometritis, isolated fever (> 38.0°C more than 12 hours after cesarean delivery), superficial or deep surgical-site infection (as defined by the Centers for Disease Control and Prevention National Safety Network criteria), and other wound complications that do not meet the definition of a surgical-site infection (seroma, hematoma, or separation or dehiscence of the wound greater than 2 cm). Individual outcomes of the composite, length of hospital stay, hospital readmissions, number of outpatient or emergency department visits as the result of infectious morbidity, and empirical treatment for newborn sepsis were secondary outcomes.
A total sample size of at least 608 women (304 in each group) was sufficient to demonstrate a 60% reduction in the rate of the primary outcome (assuming a baseline incidence of a 10% rate of the primary outcome in the control group), and assuming 80% power and a type 1 error rate of 5%. The statistical analysis was performed using intention-to-treat analyses, and differences between the two groups were considered statistically significant if the P value was < 0.05.
From August 2015 to January 2021, 608 pregnant women met inclusion criteria after screening 6,256 women for eligibility. A total of 304 participants received the active treatment (vaginal cleansing with povidone-iodine) and 304 received abdominal cleansing alone. The baseline characteristics were similar in the two groups. The incidence of the primary outcome also was similar between the two groups (11.8% vs. 11.5%), for an adjusted risk ratio (aRR) of 1.0 (95% confidence interval [CI], 0.7 to 1.6; P = 0.90). There were no significant differences between the two groups with respect to all the secondary outcomes. In prespecified and post-hoc subgroup analyses, the primary outcome results did not differ based on obesity, rupture of membranes, presence of chorioamnionitis, use of azithromycin, or dilation ≥ 6 cm at the time of cesarean delivery. Risks for serious adverse events were not different between the two groups.
COMMENTARY
This study demonstrates that the use of povidone-iodine vaginal cleansing prior to an unplanned cesarean delivery for labor-related indications did not reduce postoperative infection morbidity. Preoperative skin antisepsis has long been demonstrated to prevent surgical-site infections.5,6 Several antiseptic solutions are available for preoperative preparation of the vagina prior to cesarean delivery, including iodine-based products (e.g., povidone-iodine), alcohol-containing products (e.g., chlorhexidine-alcohol), and chlorhexidine-based products (e.g., chlorhexidine gluconate). Evidence suggests that cleansing the vagina with antiseptic solutions reduces the risk for puerperal infections in laboring pregnant women when used prior to cesarean delivery.6
Although both iodine-based and chlorhexidine-based antiseptic solutions have broad-spectrum antimicrobial activity, chlorhexidine-based antiseptics have been demonstrated to provide significantly better effectiveness, likely because of their faster onset of action, greater ability to withstand exposure to bodily fluids, and longer-lasting effects (up to six hours).8 These superior effects of chlorhexidine-based antiseptics also have been demonstrated in gynecologic procedures such as vaginal hysterectomy.9 Despite the proven effectiveness of chlorhexidine-based solutions compared to povidone-iodine-based solutions, Temming and colleagues did not provide a rationale for using povidone-iodine in their randomized trial.7 However, it is unclear from current studies whether the efficacy of chlorhexidine-based therapies is the result of the chlorhexidine itself, the alcohol, or a combination of both chlorhexidine and alcohol.10 In addition, the immune modulation in pregnancy and the specific combination of skin and vaginal pathogens in surgical-site infections after cesarean delivery raises questions about the efficacy of one vaginal cleansing agent compared to another.10
Vaginal cleansing usually is combined with abdominal cleansing and preoperative antibiotics prior to cesarean delivery to reduce the risk for puerperal infections. With the recent addition of azithromycin, which has been shown to have modest benefit in lowering postpartum endometritis in pregnant women at highest risk for postpartum infections (those with rupture of fetal membranes and obesity), puerperal infection rates have decreased.11 However, in this study by Temming et al, the rates of the primary outcome did not differ in women who were administered azithromycin compared to those who were not. Although the findings from the study by Temming et al does not support the use of povidone-iodine for vaginal cleansing at the time of cesarean delivery, the American College of Obstetricians and Gynecology (ACOG) recommends vaginal cleansing using either povidone-iodine or chlorhexidine gluconate in laboring patients and in those with ruptured membranes.12 ACOG recommends that pregnant women with a betadine allergy should receive vaginal preparation with 4% chlorhexidine and that pregnant women who need an emergency cesarean delivery should not receive vaginal preparation prior to delivery to expedite delivery and ensure the safety of both mother and fetus.
REFERENCES
- Conroy K, Koenig AF, Yu Y-H, et al. Infectious morbidity after cesarean delivery: 10 strategies to reduce risk. Rev Obstet Gynecol 2012;5:69-77.
- Mackeen AD, Packard RE, Ota E, Speer L. Antibiotic regimens for postpartum endometritis. Cochrance Database Syst Rev 2015;2015:CD001067.
- Dalton E, Castillo E. Post partum infections: A review for the non-OBGYN. Obstet Med 2014;7:98-102.
- Brumfield CG, Hauth JC, Andrews WW. Puerperal infection after cesarean delivery: Evaluation of a standardized protocol. Am J Obstet Gynecol 2000;182:1147-1151.
- Caissutti C, Saccone G, Zullo F, et al. Vaginal cleansing before cesarean delivery: A systematic review and meta-analysis. Obstet Gynecol 2017;130:527-538.
- Haas DM, Morgan S, Contreras K, Kimball S. Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections. Cochrane Database Syst Rev 2020;4:CD007892.
- Temming LA, Frolova AI, Raghuraman N, et al. Vaginal cleansing before unscheduled cesarean delivery to reduce infection: A randomized clinical trial. Am J Obstet Gynecol 2022; Nov 30. doi:10.1016/j.ajog.2022.11.1300. [Online ahead of print].
- Darouiche RO, Wall MJ Jr, Itani KM, et al. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. N Engl J Med 2010;362:18-26.
- Culligan PJ, Kubik K, Murphy M, et al. A randomized trial that compared povidone iodine and chlorhexidine as antiseptics for vaginal hysterectomy. Am J Obstet Gynecol 2005;192:
422-425.
- Tuuli MG, Liu J, Stout MJ, et al. A randomized trial comparing skin antiseptic agents at cesarean delivery. N Engl J Med 2016;374:647-655.
- Tita AT, Szychowski JM, Boggess K, et al. Adjunctive azithromycin prophylaxis for cesarean delivery. N Engl J Med 2016;375:1231-1241.
- Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 199: Use of prophylactic antibiotics in labor and delivery. Obstet Gynecol 2018;132:e103-e119.
