Cost-utility analysis of azithromycin to assist in the prevention of acute cesarean section infection in a Chinese population

Cost-utility analysis of azithromycin to assist in the prevention of acute cesarean section infection in a Chinese population | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cost-utility analysis of azithromycin to assist in the prevention of acute cesarean section infection in a Chinese population Maobai Liu, Caicong You, Jiahao Zhang, Iianying Lei, Xiaoling Zeng, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3159554/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract OBJECTIVE The infection rate of cesarean delivery in China is 7 to 20 times higher than that of vaginal delivery, and the infection rate of nonelective cesarean delivery may be even higher. Therefore, this study aimed to conduct a cost-utility analysis of cefazolin combined with azithromycin versus cefazolin alone for the prevention of nonelective cesarean infection from a society-wide perspective in China, taking into account maternal outcomes of current cesarean deliveries as well as potential pregnancies. METHODS A decision tree model was constructed using TreeAge Pro 2022 to simulate the total cost and lifetime health outcomes of pregnant women in China under two infection prophylaxis regimens. Epidemiological, quality-of-life and cost parameters were obtained from various sources, including published literature, publicly available documents from the Fujian Provincial Bureau of Medical Security, data from www.yaozh.com , and information from the China Bureau of Statistics. The discount rate has been established at 5% annually. The acceptable cost-utility threshold was established at three times China's GDP per capita in 2022. RESULTS An analysis of 800,000 nonelective cesarean deliveries during labor or after rupture of membranes in China estimated that the use of cefazolin combined with azithromycin reduced the incidence of endometritis by 18,400 cases, wound infections by 33,500 cases, sepsis by 24 cases, prevented a rupture of the uterus by 342 cases, hysterectomy by 24 cases, and maternal deaths by 3 cases, compared to the use of cefazolin prophylaxis alone. The baseline analysis indicates that the combination of cefazolin and azithromycin resulted in an increase of 0.00157 quality-adjusted life years and a cost reduction of $769.14, making it the superior regimen. The results of the sensitivity analysis confirmed the robustness of the baseline analysis. Conclusion The prophylactic use of cefazolin combined with azithromycin may result in better cost-effectiveness and health outcomes than cefazolin alone for Chinese pregnant women undergoing nonelective cesarean delivery. cesarean section cefazolin Azithromycin pharmacoeconomic evaluation Cost-utility analysis Figures Figure 1 Figure 2 Figure 3 1. Introduction The rate of cesarean deliveries in China continues to be high, with the yearly occurrence of cesarean deliveries rising from 28.8% in 2008 to 34.9% in 2014 and further to 36.7% in 2018 [ 1 ]. Infection is one of the most significant complications of a cesarean section. The incidence of postoperative morbidity and infection following cesarean delivery is 7–10 times higher than that of vaginal birth in China [ 2 , 3 ]. Mild cases of postpartum infection may present with fever and wound infections, while severe cases can lead to endometritis, sepsis, hemorrhage, and ultimately hysterectomy, shock, or even death. In recent years, China has implemented a policy to encourage natural childbirth and reduce the rate of cesarean deliveries. As a result, maternal awareness has increased, and the rate of elective cesarean deliveries has decreased. In contrast, The proportion of nonelective cesarean deliveries due to various potential maternal emergencies has increased. Nonelective cesarean deliveries now account for 60–70% of total planned deliveries in the United States and 41.13–75.61% in China [ 4 – 13 ]. In particular, maternal conditions such as excessive weight gain, advanced maternal age, premature rupture of membranes, low amniotic fluid, or excessive fetal weight can increase the likelihood of requiring a cesarean delivery during labor [ 14 ]. Nonelective cesarean delivery is associated with emergencies and suddenness for both the mother and fetus, resulting in a higher probability of postoperative infection, more severe complications, and higher medical costs. Therefore, the prophylactic use of appropriate antimicrobial regimens is necessary for nonelective cesarean deliveries. A multicenter randomized controlled trial conducted in the US in 2016 showed that the prophylactic use of cefazolin combined with azithromycin during nonelective cesarean delivery resulted in a lower risk of postoperative infection compared to the use of cefazolin alone [ 15 ]. In the US context, Harper et al. developed a decision analysis model to demonstrate the more significant economic benefit of combining cefazolin with azithromycin [ 16 ]. This treatment's effectiveness, safety, and cost-effectiveness have been confirmed in the United States, but there needs to be more research on its prophylactic use in China. This study evaluates the economic benefits of cefazolin combined with azithromycin compared to cefazolin alone for prophylaxis of nonelective cesarean infections. The study will identify this regimen's inherent advantages and cost-effectiveness and provide a reference for selecting appropriate prophylaxis regimens for nonelective post-cesarean infections in China. 2. Material and methods This study was designed as a cost-utility analysis, and a decision tree model was constructed using TreeAge Pro 2022 software. The cost-utility of using cefazolin alone versus cefazolin combined with azithromycin for preventing nonselective post-cesarean infections was evaluated from a societal perspective in China. 2.1 Model Structure The decision tree model (shown in Fig. 1) begins with completing maternal cesarean delivery. Maternal outcomes are divided into current cesarean delivery outcomes and potential outcomes for future pregnancies. Two studies, a retrospective study by Chen Zhifang in China and a case-control study by Shipp's team, have shown that endometritis or pelvic inflammatory disease is associated with an increased risk of uterine rupture during a potential future trial of labor after cesarean (TOLAC) [17, 18]. Thus, setting potential pregnancy event outcomes and exploring the impact of having a history of endometritis on the overall maternal quality of life level. Current cesarean delivery outcomes may include endometritis, wound infection, sepsis, venous thromboembolism, and maternal mortality. Potential outcomes of a pregnancy event may include elective repeat cesarean delivery, TOLAC, vaginal birth after cesarean (VBAC), cesarean delivery after unsuccessful TOLAC, uterine rupture, hysterectomy, and maternal mortality. 2.2.1 Cost parameters Drug costs were determined based on the azithromycin dosing regimen of 0.5 g and the cefazolin dosing regimen of 2 g, which were used in the Tita study and recommended by the Guidelines for Clinical Use of Antimicrobial Drugs (2015 edition) [15, 19], respectively. The costs of cefazolin sodium and azithromycin drugs were obtained from www.yaozh.com and the median price in each province in China since 2022 was used. The outcome of maternal mortality in terms of the opportunity cost of lost maternal years of work was calculated using the following formula: national per capita disposable income × (female retirement age - average female childbearing age). The average female childbearing age was 28.61 years, the female retirement age was 50, and the national per capita disposable income was set to ¥32,188.8 [20-23]. The average female childbearing age was obtained by taking a weighted average of the age data for having one, two, three, and more children from the China Fertility Report. Other costs related to maternal outcomes include the expenses associated with treating endometritis, wound infections, sepsis, and venous thromboembolism, as reported in the literature [24-27]. The costs in Table 1 were adjusted to 2020 price levels using the Consumer Price Index (CPI) for Medical Services and the CPI for Traditional Chinese Medicine and Healthcare Supplies, as published by the National Bureau of Statistics of China (S1) [23]. Endometritis and venous thromboembolism treatment costs were divided into pharmaceutical and nonpharmaceutical costs. They were therefore adjusted according to the CPI for medical services and the CPI for Traditional Chinese Medicine and Healthcare Supplies. In contrast, the costs of treating sepsis and wound infections were not differentiated and were adjusted solely based on the Consumer Price Index (CPI) for medical services. All other costs related to maternal outcomes were obtained from the "Notice on Announcing the Prices of Some Medical Service Items and Other Related Issues in Provincial Public Hospitals" published by the Medical Security Bureau of Fujian Province, China, in 2022 [28]. The time frame for potential pregnancy events was set to three years later, representing the age difference between women with multiple children and those with only one child in 2020. The cost of treatment for the desired outcome was discounted at the recommended annual rate of 5% according to Chinese pharmacoeconomic evaluation guidelines [20, 21]. The specific cost parameters are presented in Table 1. The range of parameters for the univariate sensitivity analysis was set to ±20% of the baseline value or based on the range reported in the literature. Table 1 Cost parameters in the model (¥) Cost parameters Source Year Baseline value (adjusted） Sensitivity analysis range Source Azithromycin for injection 2022 13.76 7.36~20.21 www.yaozh.com Cefazolin sodium for injection 2022 57.22 18.02~73.41 www.yaozh.com maternal mortality 2020 688518.43 550814.74-826222.12 [20-23] primary cesarean delivery 2022 1343.7 1215-1620 [28] secondary cesarean 2022 1330.31 1261.20-1399.42 [28] secondary cesarean section plus TOLAC 2022 1740.63 1649.93-1831.36 [28] cesarean hysterectomy 2022 1442.61 1364.86-1520.35 [28] Uterine repair 2022 885.43 837.92-932.94 [28] Treatment of endometritis 2013 13137.53 10510.02-15765.03 [24] Treatment of Sepsis 2018 24466.72 14312.10-49409.48 [25] Treatment of venous thromboembolism 2013 18772.63 15018.10-22527.15 [26] Treatment of wound infection 2013 11232.82 8986.25-13479.38 [27] TOLAC, trial of labor after cesarean. 2.2.2 Probability parameters Most of the probabilities for each outcome in the decision tree model were obtained from relevant literature published in Chinese and English databases. Due to the limited research on the effectiveness of cefazolin and cefazolin combined with azithromycin in preventing cesarean infections in China, the study by Tita's team was used to determine their preventive effects [15]. Data from international research were used to calculate the probability of maternal endometritis or wound infection in conjunction with sepsis, as these conditions are rare in China [29, 30]. Maternal mortality rates associated with cesarean delivery were obtained from a retrospective study that analyzed the mode of delivery [31]. The probability of death resulting from sepsis was derived from an epidemiological study conducted in Beijing [25]. The probability of venous thromboembolism was investigated in an observational study on the risk of maternal venous thromboembolism in Hong Kong, China [32]. The probability of maternal death resulting from venous thromboembolism was obtained from a retrospective study that utilized a risk assessment model for patients who experienced combined venous thromboembolism during pregnancy and postpartum [33]. The probability of a woman having another pregnancy was 54.2% based on the proportion of one child versus multiple births in 2020 [20]. For specific potential pregnancy outcomes, the probability of TOLAC from an analysis of maternal outcomes of the vaginal trial of labor after cesarean delivery [34]. The probability of maternal death resulting from cesarean delivery after a failed trial of labor after cesarean (TOLAC) was assumed to be zero [35, 36]. This decision was based on multiple sources in the literature that reported no instances of maternal mortality. The probability of uterine rupture during a trial of labor after cesarean [TOLAC] in pregnant women, with or without a history of endometritis, was determined through a retrospective study that examined the factors influencing complications after secondary cesarean delivery [18]. The probability of needing a hysterectomy after uterine rupture was derived from a multicenter analysis of uterine rupture outcomes in China [37]. The probability of maternal death resulting from hysterectomy was determined based on five retrospective studies, as there is a lack of research on maternal outcomes in women who undergo hysterectomy, and the sample sizes in individual studies are small [38-42]. The probability of VBAC was derived from a retrospective study on factors associated with pregnancy outcomes and uterine rupture [43]. The probability of maternal death for this outcome was assumed to be 0, considering no maternal complications after VBAC. The parameter range for the univariate sensitivity analysis of each outcome probability was determined based on the range reported in the literature or set to a baseline value of ±20%. As the probability of maternal death resulting from cesarean delivery after failed TOLAC and maternal death after successful vaginal birth was set to zero, it was not feasible to establish the parameter range to the baseline value ± 20%. Therefore, the upper limit of the parameter range for the former was determined based on the maternal mortality rate (13.16/100,000) from a Meta-analysis on maternal and infant safety of TOLAC, and the upper limit of the parameter range for the latter was set to the maternal mortality rate in 2021 (16.1/100,000). The lower limit for both was zero [35, 44]. The probability parameters for specific outcomes are presented in Table 2. Table 2 Probability of maternal outcomes Probability parameters Baseline value Sensitivity analysis range Source Endometritis: cefazolin 0.061 0.05-0.1 [15] Endometritis: cefazolin azithromycin 0.038 0.02-0.06 [15] Wound infection: cefazolin 0.066 0.05-0.1 [15] Wound infection: cefazolin azithromycin 0.024 0.02-0.07 [15] Probability of endometritis combined with sepsis 0.000682 0-0.033 [29, 30] Probability of wound infection combined with sepsis 0.000345 0-0.000345 [29, 30] Probability of venous thromboembolism 0.0004 0-0.00138 [32] Maternal mortality due to cesarean delivery 0.0004 0.00032-0.00048 [31] Maternal mortality due to sepsis 0.174 0.1392-0.2088 [25] Maternal mortality due to venous thromboembolism 0.007 0.0056-0.0084 [33] Probability of potential pregnancy 0.542 0.4336-0.6504 [20] Probability of TOLAC 0.2962 0.2381-0.3939 [34] Maternal mortality due to cesarean delivery after failed TOLAC 0 0-0.0001316 [35, 36] Probability of uterine rupture during TOLAC in pregnant women with a history of endometritis 0.1379 0.1103-0.1655 [18] Probability of uterine rupture during TOLAC in pregnant women without a history of endometritis 0.02193 0.01754-0.02632 [18] Probability of needing hysterectomy after uterine rupture 0.071 0.0568-0.0852 [37] Maternal mortality due to hysterectomy 0.05115 0.04092-0.06138 [38-42] Probability of VBAC 0.05656 0-0.0641 [43] Maternal mortality after VBAC 0 0-0.0000161 [44] TOLAC, trial of labor after cesarean; VBAC, vaginal birth after cesarean. 2.2.3 Utility parameters Health outcomes were measured using utility values to adjust life years for health-related quality of life, resulting in quality-adjusted life years (QALYs). We used a maternal utility of 0.6309 for Hysterectomy, 0.52 for maternal infection, 0.2 for maternal infection combined with sepsis, and 0.96 for Venous thromboembolism [45-48]. The health utility values for the combined states were obtained by multiplying the health utility values of each state. Life cycle by status from China Bureau of Statistics data, a prospective study of menopausal status in Chinese women, and a retrospective study on treatment duration by outcome status [24, 25, 27, 48-50]. The length of hospital stay for the combined state outcomes was determined by taking the most extended mean length of stay from both groups. These parameters were obtained from published studies. The specific utility parameters are presented in Table 3. Table 3 Utility values for each outcome Utility Parameters Baseline Value Sensitivity analysis range Source Health utility value Hysterectomy 0.6309 0.5507-0.8100 [45] Endometritis 0.52 0.416-0.624 [46] Wound infection 0.52 0.416-0.624 [46] Wound infection or endometritis combined with sepsis 0.2 0.16-0.24 [46, 47] Maternal death 0 - - Venous thromboembolism 0.96 0.768-1 [48] Sepsis combined with venous thromboembolism 0.192 0.1536-0.2304 [47, 48] Endometritis or wound infection combined with venous thromboembolism 0.4492 0.3594-0.5390 [46, 48] Time parameters for each endpoint (years) mean length of hospital stay for endometritis 0.01671 0.01370-0.01973 [24] mean length of hospital stay for sepsis 0.03013 0.01644-0.04932 [25] mean length of hospital stay for wound infection 0.03789 0.02896-0.04682 [27] mean length of hospital stay for venous thromboembolism 0.01370 0.01-0.0174 [48] remaining years of childbearing 9.59 5.19-13.99 [49] maternal remaining life expectancy 52.27 41.816-62.724 [50] "-" means not set. The QALYs for each outcome were set as follows: QALYs for maternal hysterectomy = 1 × (maternal remaining life expectancy - remaining years of childbearing) + hysterectomy utility value × remaining years of childbearing (remaining years of childbearing = mean female menopause - mean female childbearing age, with the health utility value of hysterectomy discounted at an annual rate of 5%). QALYs for maternal sepsis combined with venous thromboembolism = 1 × (maternal remaining life expectancy - mean length of hospital stay for sepsis combined with venous thromboembolism) + utility value for sepsis combined with venous thromboembolism × mean length of hospital stay. QALYs for maternal wound infection or endometritis combined with sepsis = 1 × (maternal life remaining - mean length of hospital stay for wound infection or endometritis combined with sepsis) + utility value for wound infection or endometritis combined with sepsis × mean length of hospital stay. QALYs for maternal endometritis or wound infection combined with venous thromboembolism = 1 × (maternal life remaining - mean length of hospital stay for endometritis or wound infection combined with venous thromboembolism) + utility value for endometritis or wound infection combined with venous thromboembolism × mean length of hospital stay. QALYs for maternal venous thromboembolism = 1 × (maternal life remaining - mean length of hospital stay for venous thromboembolism) + venous thromboembolism utility value × mean length of hospital stay. QALYs for successful maternal pregnancy with no complications = 1 × remaining maternal life expectancy. 2.3 Analysis method This study constructed a cost-utility model using TreeAge Pro 2022 software. The collected model parameters were utilized to conduct a cost-utility analysis. First, a basic analysis was conducted to estimate the lifetime health output (measured in QALYs), total cost, and incremental cost-effectiveness ratio (ICER) of using a prophylactic regimen consisting of cefazolin combined with azithromycin and cefazolin alone. Second, the aim is to estimate the cesarean section outcomes for 800,000 women by calculating the incidence of each outcome. Approximately 800,000 women undergo nonselective cesarean deliveries during labor and delivery in China each year. This estimate is based on the following formula: the number of public hospital discharges for cesarean delivery in 2021 [44] × proportion of nonselective cesarean to total cesarean deliveries (54.90%, as reported in the literature) [7-14]. Third, a one-way sensitivity analysis was conducted to evaluate the influence of uncertainty in each parameter on cost utility. The parameter range was obtained from the literature or set to baseline values with a variation of ±20% interval. Fourth to conduct probabilistic sensitivity analysis, we generated 1000 iterations for all variables with uncertainty within the 95% confidence interval (CI). The cost parameters were assumed to follow a Gamma distribution, while the probability and quality of life parameters followed a Beta distribution. The standard deviation was fixed at 25%. The willingness-to-pay cost was determined using the World Health Organization's recommended cost-utility acceptability threshold of ¥257,094, three times the 2022 GDP per capita (¥85,698) [51]. 3. Results 3.1 Basic analysis results As presented in Table 4, the overall cost of the infection prophylaxis regimen combining cefazolin and azithromycin was lower than that of the cefazolin-only regimen. Moreover, the quality-adjusted life years (QALYs) associated with the former were higher than those of the latter. These findings suggest that cefazolin combined with an azithromycin infection prophylaxis regimen is superior. Table 4 Results of cost-utility analysis Decision Cost (¥） Cost (¥) QALY QALY ICER(¥/QALY) cefazolin azithromycin 3410.78 - 52.2297 - - cefazolin 4179.94 769.17 52.22813 -0.00157 -488453.22 QALY, quality-adjusted life year; ICER, incremental cost-effect ratio. Outcomes were estimated for 800,000 women who underwent nonselective cesarean delivery in China, and differences in outcomes were compared between cefazolin alone and cefazolin combined with azithromycin (Table 5). The cefazolin combined with azithromycin prophylaxis regimen reduced all maternal outcomes, with outcome estimates showing a reduction of 18,400 cases of endometritis, 33,500 cases of wound infection, 24 cases of sepsis, prevention of 342 cases of uterine rupture, 24 cases of hysterectomy, and a reduction of 3 maternal deaths in current and potential pregnancies. Table 5 Summary of Estimated Outcomes of Nonselective Cesarean Delivery for 800,000 Pregnant Women (Persons) Outcomes cefazolin azithromycin cefazolin Result Difference Endometritis 30400 48800 -18400 Wound infection 19200 52800 -33600 Sepsis 27 51 -24 Potential pregnancy with uterine rupture 3388 3730 -342 Hysterectomy 241 265 -24 Maternal death 561 564 -3 3.2 Univariate sensitivity analysis Univariate sensitivity analyses were performed for all probability, cost, time, and utility parameters. Fig. 2 storm plots omitted some parameters that had no significant effect on the results of the underlying analysis. The probability of endometritis combined with sepsis had the most excellent effect on the results of the underlying analysis, followed by the cost of treating wound infections and the length of hospital stay. At the same time, other parameters also affected the results. 3.3 Probabilistic sensitivity analysis A Monte Carlo simulation (MCS) was run 1,000 times to generate ICER scatter plots. The willingness to pay the cost (WTP) was set to ¥ 257,094. The results are shown in Fig. 3, which shows that 76.1% of the scatter of ICER values in 1000 MCS is below the maternal WTP line. Therefore, the probability that the cefazolin combined with azithromycin prophylaxis regimen is cost-effective is 76.1%, validating the robustness of the ICER values of the underlying analysis. 4. Discussion In this study, we constructed a decision tree model to compare the economic outcomes of two prophylaxis regimens - cefazolin + azithromycin and cefazolin - for nonselective cesarean infections. The model was based on a societal perspective and aimed to assist pregnant women in choosing the most cost-effective prophylaxis regimen for their nonselective cesarean delivery. The current clinical study by Tita, Ward, et al. abroad, and the study by Suttion, skeith et al. comparing the costs associated with these two intervention options demonstrate the effectiveness and economy of cefazolin combined with azithromycin for the prevention of cesarean infection [ 15 , 16 , 52 – 55 ]. However, there is a dearth of clinical studies in China that correspond to this topic, and no pharmacoeconomic studies have been published to date regarding the use of cefazolin combined with azithromycin protocols for preventing nonselective cesarean infections. The model parameters used in this study were obtained from various sources, including published literature, documents from the Fujian Provincial Bureau of Medical Security, information from Drugwise.com, and data from the National Bureau of Statistics. Additionally, some parameters were discounted at a 5% annual rate. The results of this study indicate that the cefazolin and azithromycin prophylaxis regimen had a lower total cost and higher health output than cefazolin alone, making it the superior strategy. The robustness of the underlying analysis was verified through one-way sensitivity analysis and Monte Carlo simulation. The results showed a 76.1% probability that the combination of cefazolin and azithromycin was cost-effective. It is understood that this study is the first pharmacoeconomic evaluation in China that integrates maternal outcomes of current cesarean deliveries and potential pregnancies to construct a decision tree model for data analysis of two infection prevention regimens: cefazolin combined with azithromycin and cefazolin alone. The potential pregnancy event outcomes were constructed in the decision tree model so that maternal outcomes could be simulated and the overall maternal quality of life could be analyzed as much as possible. Moreover, this study estimated maternal outcomes for approximately 800,000 nonselective cesarean deliveries in China, which can more visually demonstrate the benefits of using cefazolin combined with azithromycin prophylaxis regimens for this population. This study has some limitations due to the absence of specific clinical trials. There are fewer studies in China on the combination of azithromycin in standard antibiotics for preventing nonselective cesarean infection, and no relevant, high-quality articles have been published, so clinical data on the efficacy of the combination of azithromycin in preventing infection in US studies were used. There is a question as to whether combining azithromycin with standard antibiotics is similarly effective in the Chinese population. Tita et al. suggested that the role of azithromycin in infection prevention may be due to, but not limited to, its inhibitory effect on ureaplasma organisms, so Author searched for the detection rate of ureaplasma organisms in the Chinese population and the resistance of ureaplasma organisms to azithromycin in some parts of China. The results showed that maternal ureaplasma urealyticum detection rates were high, up to 82% in a region of northern China, and several studies analyzing Ureaplasma urealyticum resistance in the northwest, northern and eastern China showed that Ureaplasma urealyticum resistance to azithromycin ranged from 2 to 15% [ 56 – 59 ]. Furthermore, in a meta-analysis and systematic evaluation, this study collected relevant clinical trials from around the world and demonstrated that the risk of infection is decreased when azithromycin is added to the standard prophylactic regimen for cesarean infection [ 60 ]. It was therefore hypothesized that combining azithromycin with standard antibiotics would have a similar effect on the Chinese population. Health utility values for each condition were mainly assessed using Non-Chinese quality of life assessments. Considering that the data sources for some of the parameters were foreign studies, there may be some differences with domestic real-world maternal data. The researcher's bias during the parameter collection may also affect the analysis results. Therefore, larger intervals of parameter variation were set in the probabilistic sensitivity analysis to determine the model's robustness. In conclusion, the prophylactic use of a cefazolin and azithromycin regimen during nonselective cesarean delivery can improve maternal postoperative indicators and potentially lead to better pregnancy outcomes. Therefore, conducting clinical studies in China on preventing nonelective or elective cesarean infections using standard antibiotics combined with azithromycin is worthwhile. This regimen could also be used as an effective means of preventing nonelective planarian infections in China. 5. Conclusion From a societal perspective in China, combining cefazolin with azithromycin for infection prophylaxis in pregnant women undergoing acute cesarean delivery may have better cost-effectiveness and health outcomes than using cefazolin alone for infection prophylaxis. Abbreviations TOLAC, trial of labor after cesarean; VBAC, vaginal birth after cesarean; CD, cesarean delivery; VTE, venous thromboembolism; MD, maternal death; UR, uterine rupture; C hyst, cesarean hysterectomy; CPI, Consumer Price Index; QALYs, quality-adjusted life years; ICER, incremental cost-effectiveness ratio. Declarations Ethics approval and consent to participate：This is a data analysis type of study and does not involve human or animal testing, and case reports. All data in the literature were obtained from publicly available online data and published literature, therefore ethical approval and consent to participate did not apply to this study. Competing interests：Not applicable. Availability of data and materials' section of your manuscript：The datasets supporting the conclusions of this article are included within the article. Conflicts of Interest statement: No financial support was received for this project. There are no conflicts of interest. Funding information: This study did not receive specific funding. Author Contributions statement: Concept and design: Liu, Li. Acquisition, analysis, or interpretation of data: Liu, You, Li, Zhang, Lei, Zeng, Chen. Drafting of the manuscript: Liu, You. Critical revision of the manuscript for important intellectual content: Liu, Li, Chen, Zhang, Lei, Zeng. Statistical analysis: You. Administrative, technical, or material support: Liu, Li, Chen. Supervision: Liu, Li. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Acknowledgments ： Fujian Medical University Union Hospital, China, provided valuable information for the analytical model. References Li HT, Hellerstein S, Zhou YB, Liu JM, Blustein J. Trends in Cesarean Delivery Rates in China, 2008–2018. JAMA. 2020;323(1):89–91. Ye HF. Pougongchanshu de shiyingzheng yu bingfazheng [Indications and complications of cesarean section] (in Chinese). Chin J Obstet Gynecol. 1994(08):494–7. Riskin-Mashiah S. Maternal morbidity associated with vaginal versus cesarean delivery. Obstet Gynecol. 2004;104(3):633. author reply. Thigpen BD, Hood WA, Chauhan S et al. 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Shen RR, Wang XD. 430 li banhen zigong zaici renshen fenmian fangshi tantao [Exploration of the mode of delivery in 430 cases of re-pregnancy in scarred uterus] (in Chinese). Guide of China Medicine. 2012;10(10):155–6. Liu Z, Yang HX, Xin H, Cui SH, Qi HB, Zhang WS. Current status of uterine rupture: a multi-center survey in China. Chin J Obstet Gynecol. 2019;54(6):363–8. Liu L. Chanke linchuang zhong de zigongqiechushu fenxi [Analysis of hysterectomy in obstetric clinics] (in Chinese). Guide of China Medicine. 2017;15(02):61. Li HJ, Jin GX. Chanke linchuang zhong de zigongqiechushu fenxi [Analysis of hysterectomy in obstetric clinics] (in Chinese). China Health Standard Management. 2014;5(11):26–7. Zhang XL. Chanke linchuang zhong de zigongqiechushu fenxi [Analysis of hysterectomy in obstetric clinics] (in Chinese). Guide of China Medicine. 2015;13(23):79–80. Chen WZ. Zigong qiechushu chanke linchuang fenxi [Clinical analysis of hysterectomy obstetrics] (in Chinese). Capital Food Medicine. 2010;17(12):28–9. Dai MH, Shao JZ, Lu L. Maternal mortality after peripartum hysterectomy for postpartum hemorrhage. Chin J Woman Child Health. 2019;30(07):855–8. Wan S, Yang M, Pei J, Zhao X, Zhou C, Wu Y, et al. Pregnancy outcomes and associated factors for uterine rupture: an 8 years population-based retrospective study. BMC Pregnancy Childbirth. 2022;22(1):91. China Health Care Statistics Yearbook. 2022. Available online at:https: https://www.yearbookchina.com/navibooklist-n3022110202-2.html (Accessed April 15, 2023). Smith KJ, Tsevat J, Ness RB, Wiesenfeld HC, Roberts MS. Quality of life utilities for pelvic inflammatory disease health states. Sex Transm Dis. 2008;35(3):307–11. Tengs TO, Wallace A. One thousand health-related quality-of-life estimates. Med Care. 2000;38(6):583–637. Talmor D, Greenberg D, Howell MD, Lisbon A, Novack V, Shapiro N. The costs and cost-effectiveness of an integrated sepsis treatment protocol. Crit Care Med. 2008;36(4):1168–74. Huang LM. Preventive Value of Accelerated Rehabilitation Surgery Combined with Low Molecular Weight Heparin Sodium on Venous Thromboembolism after Cesarean Section. Heilongjiang Med J. 2021;34(03):542–4. Wang M, Gan W, Kartsonaki C, Guo Y, Lv J, Chen Z, et al. Menopausal status, age at natural menopause and risk of diabetes in China: a 10-year prospective study of 300,000 women. Nutr Metab (Lond). 2022;19(1):7. Final Statistical Monitoring Report of the China Women's Development Pro-gram. (2011–2020). Available online at: https://www.gov.cn/xinwen/2021-12/21/content_5663667.htm (Accessed April 15, 2023). Statistical Bulletin on National Economic and Social Development of the People's Republic of China. 2022. Available online at: http://www.stats.gov.cn/sj/zxfb/202302/t20230228_1919011.html (Accessed April 17, 2023). Tita AT, Hauth JC, Grimes A, Owen J, Stamm AM, Andrews WW. Decreasing incidence of postcesarean endometritis with extended-spectrum antibiotic prophylaxis. Obstet Gynecol. 2008;111(1):51–6. Ward E, Duff P. A comparison of 3 antibiotic regimens for prevention of postcesarean endometritis: an historical cohort study. Am J Obstet Gynecol. 2016;214(6):751e1–4. Sutton AL, Acosta EP, Larson KB, Kerstner-Wood CD, Tita AT, Biggio JR. Perinatal pharmacokinetics of azithromycin for cesarean prophylaxis. Am J Obstet Gynecol. 2015;212(6):812e1–6. Skeith AE, Niu B, Valent AM, Tuuli MG, Caughey AB. Adding Azithromycin to Cephalosporin for Cesarean Delivery Infection Prophylaxis: A Cost-Effectiveness Analysis. Obstet Gynecol. 2017;130(6):1279–84. Zheng j, Guo YY. Analysis of prevalence of ureaplasma urealyticum infection and drug resistance in female genital tracts. J North China Univ Sci Technology(Health Sci Edition). 2019;21(06):471–5. Jie J, Liu WK, Li B, Fan Y, Chen HN, Li L. Detection and Drug Resistance of Mycoplasma in Vaginal Secretions of Gynecological Patients in Xi'an. J Mod Lab Med. 2017;32(06):118–21. Huang YF, Lan HH, Zou HQ. The investigation on urogenital mycoplasma infection and drug resistance variation from 2013 to 2018. Mod Practical Med. 2019;31(06):764–5. Ma T. Urogenital Tract Mycoplasma Infection and Drug Sensitivity Analysis. World Latest Medicine Information. 2018;18(A3):51–2. Yang M, Yuan F, Guo Y, Wang S. Efficacy of adding azithromycin to antibiotic prophylaxis in caesarean delivery: a meta-analysis and systematic review. Int J Antimicrob Agents. 2022;59(3):106533. Additional Declarations No competing interests reported. Supplementary Files SupportingInformation.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3159554","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":224815893,"identity":"6f17581d-ec00-437b-b26d-04cbd0932004","order_by":0,"name":"Maobai Liu","email":"","orcid":"","institution":"Fujian Medical University Union Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maobai","middleName":"","lastName":"Liu","suffix":""},{"id":224815895,"identity":"3d70ed52-103a-4a97-a8bc-71316a6eb49c","order_by":1,"name":"Caicong You","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Caicong","middleName":"","lastName":"You","suffix":""},{"id":224815897,"identity":"c72fea3e-cfb5-4129-ab3f-08103bf2dc16","order_by":2,"name":"Jiahao Zhang","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jiahao","middleName":"","lastName":"Zhang","suffix":""},{"id":224815899,"identity":"5a55452e-43fc-420c-8b7f-77efa01e76c6","order_by":3,"name":"Iianying Lei","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Iianying","middleName":"","lastName":"Lei","suffix":""},{"id":224815901,"identity":"e75fccf2-6786-4ade-8f44-d4f4f968c48a","order_by":4,"name":"Xiaoling Zeng","email":"","orcid":"","institution":"The Second Hospital of Zhangzhou City","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaoling","middleName":"","lastName":"Zeng","suffix":""},{"id":224815903,"identity":"279e5f3e-185f-48fb-bdd4-aab4414f3b26","order_by":5,"name":"Ling Chen","email":"","orcid":"","institution":"Fujian Medical University Union Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ling","middleName":"","lastName":"Chen","suffix":""},{"id":224815905,"identity":"1dbb9256-96dc-4f4a-9701-0cac74ec716a","order_by":6,"name":"Na Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYBAC9oYDbAwPDBgY2NibDz/4YMMGFpXAp4XnAFBLAlALH8+xNMMZaURpYQBqATLkJHIMpHnSGIjQwnjG7EFCwR15Nom0BGObBL5ogwPMB2/zMNjl4dTCcCzdIMHgmWEbz+MDj3MS2HI3HGBLtuZhSC7GpcWe4fAxiQSDw4xt7EBbcn+AtPCYSfMwHEhswGnLwTaQFvs2BqBfLMC28H8joAViS2IbB1ALA1gLDxsBLcfSQFqS20CB3APUMvMwm7HlHINk3FokzphJfPhz2HZ+OzAqfyQcy+073vzwxpsKO5xaGCQOoHCPMTAwg2gDXOqBgB/VsBo8SkfBKBgFo2CkAgAvjlonp6AC4QAAAABJRU5ErkJggg==","orcid":"","institution":"Fujian Medical University Union Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Na","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2023-07-11 09:14:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3159554/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3159554/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":41543256,"identity":"1005a299-8710-4fd2-8b2d-d62dbe298fb7","added_by":"auto","created_at":"2023-08-14 15:24:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":66425,"visible":true,"origin":"","legend":"\u003cp\u003eDecision tree model\u003c/p\u003e\n\u003cp\u003e“+” indicates that subsequent branches of the tree are hidden to facilitate display; these branches are similar to the ones displayed. CD, cesarean delivery; VTE, venous thromboembolism; MD, maternal death; TOLAC, trial of labor after cesarean; UR, uterine rupture; C hyst, cesarean hysterectomy; VBAC, vaginal birth after cesarean.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3159554/v1/f0dd731618d2bc3c34fd345a.png"},{"id":41542214,"identity":"920059c5-fe2e-43c1-9cb0-74daf34b3258","added_by":"auto","created_at":"2023-08-14 15:16:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":141734,"visible":true,"origin":"","legend":"\u003cp\u003eResults of univariate sensitivity analysis\u003c/p\u003e\n\u003cp\u003er_se, probability of endometritis combined with sepsis; c_w, cost of treating wound infections; t_W, time to treat wound infection; u_w, utility of wound infection; r_w2, probability of wound infection in patients in the cefazolin +azithromycin group; t_sy, remaining years of childbearing; c_e, cost of treating endometritis; r_TOLAC, probability of trial of labor after cesarean; t_L, maternal remaining life expectancy; r_UR1, probability of uterine rupture during TOLAC in pregnant women with a history of endometritis; r_sw, probability of wound infections combined with sepsis; u_ch, utility of hysterectomy; r_ChUR, probability of needing a cesarean hysterectomy after uterine rupture; r_e2, probability of endometritis in patients in the cefazolin+ azithromycin group; r_sd, Maternal mortality due to sepsis; r_e1, probability of endometritis in patients in the cefazolin group; u_e, utility of endometritis; r_w1, probability of wound infections in patients in the cefazolin group; t_E, ; r_UR0, probability of uterine rupture during TOLAC in pregnant women without a history of endometritis; c_a, Cost of Azithromycin.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3159554/v1/4fbf27b2f6e8af271dd912d3.png"},{"id":41542212,"identity":"cdc26fc3-1b23-40e9-950f-ac61edbadc7a","added_by":"auto","created_at":"2023-08-14 15:16:14","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":114788,"visible":true,"origin":"","legend":"\u003cp\u003eProbabilistic sensitivity analyses for cefazolin combined with azithromycin infection prevention regimen vs cefazolin infection prevention regimen.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3159554/v1/f928cc6bc54a080f2bc957f0.png"},{"id":52396660,"identity":"dc8d9cbe-8a6f-4113-ab5d-2cf4a6d11554","added_by":"auto","created_at":"2024-03-11 05:28:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":495255,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3159554/v1/ee3c1b2c-7e64-4a49-871f-81cd7a3bd8fc.pdf"},{"id":41542215,"identity":"c2c55d86-0f19-436c-9b9a-2d7bf066192a","added_by":"auto","created_at":"2023-08-14 15:16:14","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":14720,"visible":true,"origin":"","legend":"","description":"","filename":"SupportingInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-3159554/v1/83a014388d9301f4fc1b3bdd.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cost-utility analysis of azithromycin to assist in the prevention of acute cesarean section infection in a Chinese population","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe rate of cesarean deliveries in China continues to be high, with the yearly occurrence of cesarean deliveries rising from 28.8% in 2008 to 34.9% in 2014 and further to 36.7% in 2018 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Infection is one of the most significant complications of a cesarean section. The incidence of postoperative morbidity and infection following cesarean delivery is 7\u0026ndash;10 times higher than that of vaginal birth in China [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Mild cases of postpartum infection may present with fever and wound infections, while severe cases can lead to endometritis, sepsis, hemorrhage, and ultimately hysterectomy, shock, or even death. In recent years, China has implemented a policy to encourage natural childbirth and reduce the rate of cesarean deliveries. As a result, maternal awareness has increased, and the rate of elective cesarean deliveries has decreased. In contrast, The proportion of nonelective cesarean deliveries due to various potential maternal emergencies has increased. Nonelective cesarean deliveries now account for 60\u0026ndash;70% of total planned deliveries in the United States and 41.13\u0026ndash;75.61% in China [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In particular, maternal conditions such as excessive weight gain, advanced maternal age, premature rupture of membranes, low amniotic fluid, or excessive fetal weight can increase the likelihood of requiring a cesarean delivery during labor [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Nonelective cesarean delivery is associated with emergencies and suddenness for both the mother and fetus, resulting in a higher probability of postoperative infection, more severe complications, and higher medical costs. Therefore, the prophylactic use of appropriate antimicrobial regimens is necessary for nonelective cesarean deliveries.\u003c/p\u003e \u003cp\u003eA multicenter randomized controlled trial conducted in the US in 2016 showed that the prophylactic use of cefazolin combined with azithromycin during nonelective cesarean delivery resulted in a lower risk of postoperative infection compared to the use of cefazolin alone [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In the US context, Harper et al. developed a decision analysis model to demonstrate the more significant economic benefit of combining cefazolin with azithromycin [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This treatment's effectiveness, safety, and cost-effectiveness have been confirmed in the United States, but there needs to be more research on its prophylactic use in China. This study evaluates the economic benefits of cefazolin combined with azithromycin compared to cefazolin alone for prophylaxis of nonelective cesarean infections. The study will identify this regimen's inherent advantages and cost-effectiveness and provide a reference for selecting appropriate prophylaxis regimens for nonelective post-cesarean infections in China.\u003c/p\u003e"},{"header":"2. Material and methods","content":"\u003cp\u003eThis study was designed as a cost-utility analysis, and a decision tree model was constructed using TreeAge Pro 2022 software. The cost-utility of using cefazolin alone versus cefazolin combined with azithromycin for preventing nonselective post-cesarean infections was evaluated from a societal perspective in China.\u003c/p\u003e\n\u003cp\u003e2.1 Model Structure\u003c/p\u003e\n\u003cp\u003eThe decision tree model (shown in Fig. 1) begins with completing maternal cesarean delivery. Maternal outcomes are divided into current cesarean delivery outcomes and potential outcomes for future pregnancies. Two studies, a retrospective study by Chen Zhifang in China and a case-control study by Shipp\u0026apos;s team, have shown that endometritis or pelvic inflammatory disease is associated with an increased risk of uterine rupture during a potential future trial of labor after cesarean (TOLAC) [17, 18]. Thus, setting potential pregnancy event outcomes and exploring the impact of having a history of endometritis on the overall maternal quality of life level. Current cesarean delivery outcomes may include endometritis, wound infection, sepsis, venous thromboembolism, and maternal mortality. Potential outcomes of a pregnancy event may include elective repeat cesarean delivery, TOLAC, vaginal birth after cesarean (VBAC), cesarean delivery after unsuccessful TOLAC, uterine rupture, hysterectomy, and maternal mortality.\u003c/p\u003e\n\u003cp\u003e2.2.1 Cost parameters\u003c/p\u003e\n\u003cp\u003eDrug costs were determined based on the azithromycin dosing regimen of 0.5 g and the cefazolin dosing regimen of 2 g, which were used in the Tita study and recommended by the Guidelines for Clinical Use of Antimicrobial Drugs (2015 edition) [15, 19], respectively. The costs of cefazolin sodium and azithromycin drugs were obtained from www.yaozh.com and the median price in each province in China since 2022 was used.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe outcome of maternal mortality in terms of the opportunity cost of lost maternal years of work was calculated using the following formula: national per capita disposable income \u0026times; (female retirement age - average female childbearing age). The average female childbearing age was 28.61 years, the female retirement age was 50, and the national per capita disposable income was set to \u0026yen;32,188.8 [20-23]. The average female childbearing age was obtained by taking a weighted average of the age data for having one, two, three, and more children from the China Fertility Report.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOther costs related to maternal outcomes include the expenses associated with treating endometritis, wound infections, sepsis, and venous thromboembolism, as reported in the literature\u0026nbsp;[24-27]. The costs in Table 1 were adjusted to 2020 price levels using the Consumer Price Index (CPI) for Medical Services and the CPI for Traditional Chinese Medicine and Healthcare Supplies, as published by the National Bureau of Statistics of China (S1) [23]. Endometritis and venous thromboembolism treatment costs were divided into pharmaceutical and nonpharmaceutical costs. They were therefore adjusted according to the CPI for medical services and the CPI for Traditional Chinese Medicine and Healthcare Supplies. In contrast, the costs of treating sepsis and wound infections were not differentiated and were adjusted solely based on the Consumer Price Index (CPI) for medical services. All other costs related to maternal outcomes were obtained from the \u0026quot;Notice on Announcing the Prices of Some Medical Service Items and Other Related Issues in Provincial Public Hospitals\u0026quot; published by the Medical Security Bureau of Fujian Province, China, in 2022 [28]. The time frame for potential pregnancy events was set to three years later, representing the age difference between women with multiple children and those with only one child in 2020. The cost of treatment for the desired outcome was discounted at the recommended annual rate of 5% according to Chinese pharmacoeconomic evaluation guidelines [20, 21]. The specific cost parameters are presented in Table 1.\u003c/p\u003e\n\u003cp\u003eThe range of parameters for the univariate sensitivity analysis was set to \u0026plusmn;20% of the baseline value or based on the range reported in the literature.\u003c/p\u003e\n\u003cp\u003eTable 1 Cost parameters in the model (\u0026yen;)\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"560\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003eCost parameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003eSource Year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003eBaseline value (adjusted）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003eSensitivity analysis range\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\"\u003e\n \u003cp\u003eSource\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003eAzithromycin for injection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003e13.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003e7.36~20.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\"\u003e\n \u003cp\u003ewww.yaozh.com\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003eCefazolin sodium for injection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003e57.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003e18.02~73.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\"\u003e\n \u003cp\u003ewww.yaozh.com\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003ematernal mortality\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003e688518.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003e550814.74-826222.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\"\u003e\n \u003cp\u003e[20-23]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003eprimary cesarean delivery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003e1343.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003e1215-1620\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\"\u003e\n \u003cp\u003e[28]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003esecondary cesarean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003e1330.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003e1261.20-1399.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\" valign=\"top\"\u003e\n \u003cp\u003e[28]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003esecondary cesarean section plus TOLAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003e1740.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003e1649.93-1831.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\"\u003e\n \u003cp\u003e[28]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003ecesarean hysterectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003e1442.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003e1364.86-1520.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\" valign=\"top\"\u003e\n \u003cp\u003e[28]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003eUterine repair\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003e885.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003e837.92-932.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\" valign=\"top\"\u003e\n \u003cp\u003e[28]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003eTreatment of endometritis\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003e2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003e13137.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003e10510.02-15765.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\"\u003e\n \u003cp\u003e[24]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003eTreatment of Sepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003e24466.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003e14312.10-49409.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\"\u003e\n \u003cp\u003e[25]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003eTreatment of venous thromboembolism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003e2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003e18772.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003e15018.10-22527.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\"\u003e\n \u003cp\u003e[26]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.305903398926656%\"\u003e\n \u003cp\u003eTreatment of wound infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37567084078712%\"\u003e\n \u003cp\u003e2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.132379248658319%\"\u003e\n \u003cp\u003e11232.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.86583184257603%\"\u003e\n \u003cp\u003e8986.25-13479.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.32021466905188%\"\u003e\n \u003cp\u003e[27]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTOLAC, trial of labor after cesarean.\u003c/p\u003e\n\u003cp\u003e2.2.2 Probability parameters\u003c/p\u003e\n\u003cp\u003eMost of the probabilities for each outcome in the decision tree model were obtained from relevant literature published in Chinese and English databases. Due to the limited research on the effectiveness of cefazolin and cefazolin combined with azithromycin in preventing cesarean infections in China, the study by Tita\u0026apos;s team was used to determine their preventive effects [15]. Data from international research were used to calculate the probability of maternal endometritis or wound infection in conjunction with sepsis, as these conditions are rare in China [29, 30]. Maternal mortality rates associated with cesarean delivery were obtained from a retrospective study that analyzed the mode of delivery [31]. The probability of death resulting from sepsis was derived from an epidemiological study conducted in Beijing [25]. The probability of venous thromboembolism was investigated in an observational study on the risk of maternal venous thromboembolism in Hong Kong, China [32]. The probability of maternal death resulting from venous thromboembolism was obtained from a retrospective study that utilized a risk assessment model for patients who experienced combined venous thromboembolism during pregnancy and postpartum [33]. The probability of a woman having another pregnancy was 54.2% based on the proportion of one child versus multiple births in 2020 [20]. For specific potential pregnancy outcomes, the probability of TOLAC from an analysis of maternal outcomes of the vaginal trial of labor after cesarean delivery [34]. The probability of maternal death resulting from cesarean delivery after a failed trial of labor after cesarean (TOLAC) was assumed to be zero [35, 36]. This decision was based on multiple sources in the literature that reported no instances of maternal mortality. The probability of uterine rupture during a trial of labor after cesarean [TOLAC] in pregnant women, with or without a history of endometritis, was determined through a retrospective study that examined the factors influencing complications after secondary cesarean delivery [18]. The probability of needing a hysterectomy after uterine rupture was derived from a multicenter analysis of uterine rupture outcomes in China [37]. The probability of maternal death resulting from hysterectomy was determined based on five retrospective studies, as there is a lack of research on maternal outcomes in women who undergo hysterectomy, and the sample sizes in individual studies are small [38-42]. The probability of VBAC was derived from a retrospective study on factors associated with pregnancy outcomes and uterine rupture [43]. The probability of maternal death for this outcome was assumed to be 0, considering no maternal complications after VBAC.\u003c/p\u003e\n\u003cp\u003eThe parameter range for the univariate sensitivity analysis of each outcome probability was determined based on the range reported in the literature or set to a baseline value of \u0026plusmn;20%. As the probability of maternal death resulting from cesarean delivery after failed TOLAC and maternal death after successful vaginal birth was set to zero, it was not feasible to establish the parameter range to the baseline value \u0026plusmn; 20%. Therefore, the upper limit of the parameter range for the former was determined based on the maternal mortality rate (13.16/100,000) from a Meta-analysis on maternal and infant safety of TOLAC, and the upper limit of the parameter range for the latter was set to the maternal mortality rate in 2021 (16.1/100,000). The lower limit for both was zero [35, 44]. The probability parameters for specific outcomes are presented in Table 2.\u003c/p\u003e\n\u003cp\u003eTable 2 Probability of maternal outcomes\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"577\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eProbability parameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003eBaseline value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003eSensitivity analysis range\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003eSource\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eEndometritis: cefazolin\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.05-0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e[15]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eEndometritis: cefazolin\u0026nbsp;azithromycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.02-0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e[15]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eWound infection: cefazolin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.066\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.05-0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e[15]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eWound infection: cefazolin\u0026nbsp;azithromycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.02-0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e[15]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eProbability of endometritis combined with sepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.000682\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0-0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[29, 30]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eProbability of wound infection combined with sepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.000345\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0-0.000345\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[29, 30]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eProbability of venous thromboembolism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.0004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0-0.00138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[32]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eMaternal mortality due to cesarean delivery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.0004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.00032-0.00048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[31]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eMaternal mortality due to sepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.1392-0.2088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[25]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eMaternal mortality due to venous thromboembolism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.0056-0.0084\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[33]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eProbability of potential pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.542\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.4336-0.6504\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[20]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eProbability of TOLAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.2962\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.2381-0.3939\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[34]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eMaternal mortality due to cesarean delivery after failed TOLAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0-0.0001316\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[35, 36]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eProbability of uterine rupture during TOLAC in pregnant women with a history of endometritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.1379\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.1103-0.1655\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[18]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eProbability of uterine rupture during TOLAC in pregnant women without a history of endometritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.02193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.01754-0.02632\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[18]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eProbability of needing hysterectomy after uterine rupture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.0568-0.0852\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[37]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eMaternal mortality due to hysterectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.05115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0.04092-0.06138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[38-42]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eProbability of VBAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0.05656\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0-0.0641\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[43]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.56944444444444%\"\u003e\n \u003cp\u003eMaternal mortality after VBAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.756944444444445%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0-0.0000161\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e[44]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTOLAC, trial of labor after cesarean; VBAC, vaginal birth after cesarean.\u003c/p\u003e\n\u003cp\u003e2.2.3 Utility parameters\u003c/p\u003e\n\u003cp\u003eHealth outcomes were measured using utility values to adjust life years for health-related quality of life, resulting in quality-adjusted life years (QALYs). We used a maternal utility of 0.6309 for Hysterectomy, 0.52 for maternal infection, 0.2 for maternal infection combined with sepsis, and 0.96 for Venous thromboembolism [45-48]. The health utility values for the combined states were obtained by multiplying the health utility values of each state.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLife cycle by status from China Bureau of Statistics data, a prospective study of menopausal status in Chinese women, and a retrospective study on treatment duration by outcome status [24, 25, 27, 48-50]. The length of hospital stay for the combined state outcomes was determined by taking the most extended mean length of stay from both groups. These parameters were obtained from published studies. The specific utility parameters are presented in Table 3.\u003c/p\u003e\n\u003cp\u003eTable 3 Utility values for each outcome\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003eUtility Parameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003eBaseline Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003eSensitivity analysis range\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003eSource\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003eHealth utility value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003eHysterectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e0.6309\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e0.5507-0.8100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[45]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003eEndometritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e0.416-0.624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[46]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003eWound infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e0.416-0.624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[46]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003eWound infection or endometritis combined with sepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e0.16-0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[46, 47]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003eMaternal death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003eVenous thromboembolism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e0.768-1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[48]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003eSepsis combined with venous thromboembolism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e0.192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e0.1536-0.2304\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[47, 48]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003eEndometritis or wound infection combined with venous thromboembolism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e0.4492\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e0.3594-0.5390\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[46, 48]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003eTime parameters for each endpoint (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003emean length of hospital stay for endometritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e0.01671\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e0.01370-0.01973\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[24]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003emean length of hospital stay for sepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e0.03013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e0.01644-0.04932\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[25]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003emean length of hospital stay for wound infection\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e0.03789\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e0.02896-0.04682\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[27]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003emean length of hospital stay for venous thromboembolism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e0.01370\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e0.01-0.0174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[48]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003eremaining years of childbearing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e9.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e5.19-13.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[49]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.974729241877256%\"\u003e\n \u003cp\u003ematernal remaining life expectancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\"\u003e\n \u003cp\u003e52.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.43682310469314%\"\u003e\n \u003cp\u003e41.816-62.724\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.440433212996389%\"\u003e\n \u003cp\u003e[50]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026quot;-\u0026quot; means not set.\u003c/p\u003e\n\u003cp\u003eThe QALYs for each outcome were set as follows:\u003c/p\u003e\n\u003cp\u003eQALYs for maternal hysterectomy = 1 \u0026times; (maternal remaining life expectancy - remaining years of childbearing) + hysterectomy utility value \u0026times; remaining years of childbearing (remaining years of childbearing = mean female menopause - mean female childbearing age, with the health utility value of hysterectomy discounted at an annual rate of 5%).\u003c/p\u003e\n\u003cp\u003eQALYs for maternal sepsis combined with venous thromboembolism = 1 \u0026times; (maternal remaining life expectancy - mean length of hospital stay for sepsis combined with venous thromboembolism) + utility value for sepsis combined with venous thromboembolism \u0026times; mean length of hospital stay.\u003c/p\u003e\n\u003cp\u003eQALYs for maternal wound infection or endometritis combined with sepsis = 1 \u0026times; (maternal life remaining - mean length of hospital stay for wound infection or endometritis combined with sepsis) + utility value for wound infection or endometritis combined with sepsis \u0026times; mean length of hospital stay.\u003c/p\u003e\n\u003cp\u003eQALYs for maternal endometritis or wound infection combined with venous thromboembolism = 1 \u0026times; (maternal life remaining - mean length of hospital stay for endometritis or wound infection combined with venous thromboembolism) + utility value for endometritis or wound infection combined with venous thromboembolism \u0026times; mean length of hospital stay.\u003c/p\u003e\n\u003cp\u003eQALYs for maternal venous thromboembolism = 1 \u0026times; (maternal life remaining - mean length of hospital stay for venous thromboembolism) + venous thromboembolism utility value \u0026times; mean length of hospital stay.\u003c/p\u003e\n\u003cp\u003eQALYs for successful maternal pregnancy with no complications = 1 \u0026times; remaining maternal life expectancy.\u003c/p\u003e\n\u003cp\u003e2.3 Analysis method\u003c/p\u003e\n\u003cp\u003eThis study constructed a cost-utility model using TreeAge Pro 2022 software. The collected model parameters were utilized to conduct a cost-utility analysis. First, a basic analysis was conducted to estimate the lifetime health output (measured in QALYs), total cost, and incremental cost-effectiveness ratio (ICER) of using a prophylactic regimen consisting of cefazolin combined with azithromycin and cefazolin alone. Second, the aim is to estimate the cesarean section outcomes for 800,000 women by calculating the incidence of each outcome. Approximately 800,000 women undergo nonselective cesarean deliveries during labor and delivery in China each year. This estimate is based on the following formula: the number of public hospital discharges for cesarean delivery in 2021 [44] \u0026times; proportion of nonselective cesarean to total cesarean deliveries (54.90%, as reported in the literature) [7-14]. Third, a one-way sensitivity analysis was conducted to evaluate the influence of uncertainty in each parameter on cost utility. The parameter range was obtained from the literature or set to baseline values with a variation of \u0026plusmn;20% interval. Fourth to conduct probabilistic sensitivity analysis, we generated 1000 iterations for all variables with uncertainty within the 95% confidence interval (CI). The cost parameters were assumed to follow a Gamma distribution, while the probability and quality of life parameters followed a Beta distribution. The standard deviation was fixed at 25%. The willingness-to-pay cost was determined using the World Health Organization\u0026apos;s recommended cost-utility acceptability threshold of \u0026yen;257,094, three times the 2022 GDP per capita (\u0026yen;85,698) [51].\u0026nbsp;\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e3.1 Basic analysis results\u003c/p\u003e\n\u003cp\u003eAs presented in Table 4, the overall cost of the infection prophylaxis regimen combining cefazolin and azithromycin was lower than that of the cefazolin-only regimen. Moreover, the quality-adjusted life years (QALYs) associated with the former were higher than those of the latter. These findings suggest that cefazolin combined with an azithromycin infection prophylaxis regimen is superior.\u003c/p\u003e\n\u003cp\u003eTable 4 Results of cost-utility analysis\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"527\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.022727272727273%\"\u003e\n \u003cp\u003eDecision\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.393939393939394%\"\u003e\n \u003cp\u003eCost (\u0026yen;）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.393939393939394%\"\u003e\n \u003cp\u003e\u0026nbsp;Cost (\u0026yen;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.393939393939394%\"\u003e\n \u003cp\u003eQALY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.393939393939394%\"\u003e\n \u003cp\u003e\u0026nbsp;QALY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.401515151515152%\"\u003e\n \u003cp\u003eICER(\u0026yen;/QALY)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.022727272727273%\"\u003e\n \u003cp\u003ecefazolin\u0026nbsp;\u0026nbsp;azithromycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.393939393939394%\"\u003e\n \u003cp\u003e3410.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.393939393939394%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.393939393939394%\"\u003e\n \u003cp\u003e52.2297\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.393939393939394%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.401515151515152%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.022727272727273%\"\u003e\n \u003cp\u003ecefazolin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.393939393939394%\"\u003e\n \u003cp\u003e4179.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.393939393939394%\"\u003e\n \u003cp\u003e769.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.393939393939394%\"\u003e\n \u003cp\u003e52.22813\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.393939393939394%\"\u003e\n \u003cp\u003e-0.00157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.401515151515152%\"\u003e\n \u003cp\u003e-488453.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eQALY, quality-adjusted life year; ICER, incremental cost-effect ratio.\u003c/p\u003e\n\u003cp\u003eOutcomes were estimated for 800,000 women who underwent nonselective cesarean delivery in China, and differences in outcomes were compared between cefazolin alone and cefazolin combined with azithromycin (Table 5). The cefazolin combined with azithromycin prophylaxis regimen reduced all maternal outcomes, with outcome estimates showing a reduction of 18,400 cases of endometritis, 33,500 cases of wound infection, 24 cases of sepsis, prevention of 342 cases of uterine rupture, 24 cases of hysterectomy, and a reduction of 3 maternal deaths in current and potential pregnancies.\u003c/p\u003e\n\u003cp\u003eTable 5 Summary of Estimated Outcomes of Nonselective Cesarean Delivery for 800,000 Pregnant Women (Persons)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.305605786618443%\"\u003e\n \u003cp\u003eOutcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.08137432188065%\"\u003e\n \u003cp\u003ecefazolin\u0026nbsp;\u0026nbsp;azithromycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.466546112115733%\"\u003e\n \u003cp\u003ecefazolin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.146473779385172%\"\u003e\n \u003cp\u003eResult Difference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.305605786618443%\" valign=\"top\"\u003e\n \u003cp\u003eEndometritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.08137432188065%\"\u003e\n \u003cp\u003e30400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.466546112115733%\"\u003e\n \u003cp\u003e48800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.146473779385172%\"\u003e\n \u003cp\u003e-18400\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.305605786618443%\" valign=\"top\"\u003e\n \u003cp\u003eWound infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.08137432188065%\"\u003e\n \u003cp\u003e19200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.466546112115733%\"\u003e\n \u003cp\u003e52800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.146473779385172%\"\u003e\n \u003cp\u003e-33600\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.305605786618443%\" valign=\"top\"\u003e\n \u003cp\u003eSepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.08137432188065%\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.466546112115733%\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.146473779385172%\"\u003e\n \u003cp\u003e-24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.305605786618443%\" valign=\"top\"\u003e\n \u003cp\u003ePotential pregnancy with uterine rupture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.08137432188065%\"\u003e\n \u003cp\u003e3388\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.466546112115733%\"\u003e\n \u003cp\u003e3730\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.146473779385172%\"\u003e\n \u003cp\u003e-342\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.305605786618443%\" valign=\"top\"\u003e\n \u003cp\u003eHysterectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.08137432188065%\"\u003e\n \u003cp\u003e241\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.466546112115733%\"\u003e\n \u003cp\u003e265\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.146473779385172%\"\u003e\n \u003cp\u003e-24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.305605786618443%\" valign=\"top\"\u003e\n \u003cp\u003eMaternal death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.08137432188065%\"\u003e\n \u003cp\u003e561\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.466546112115733%\"\u003e\n \u003cp\u003e564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.146473779385172%\"\u003e\n \u003cp\u003e-3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e3.2 Univariate sensitivity analysis\u003c/p\u003e\n\u003cp\u003eUnivariate sensitivity analyses were performed for all probability, cost, time, and utility parameters. Fig. 2 storm plots omitted some parameters that had no significant effect on the results of the underlying analysis. The probability of endometritis combined with sepsis had the most excellent effect on the results of the underlying analysis, followed by the cost of treating wound infections and the length of hospital stay. At the same time, other parameters also affected the results.\u003c/p\u003e\n\u003cp\u003e3.3 Probabilistic sensitivity analysis\u003c/p\u003e\n\u003cp\u003eA Monte Carlo simulation (MCS) was run 1,000 times to generate ICER scatter plots. The willingness to pay the cost (WTP) was set to \u0026yen; 257,094. The results are shown in Fig. 3, which shows that 76.1% of the scatter of ICER values in 1000 MCS is below the maternal WTP line. Therefore, the probability that the cefazolin combined with azithromycin prophylaxis regimen is cost-effective is 76.1%, validating the robustness of the ICER values of the underlying analysis.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this study, we constructed a decision tree model to compare the economic outcomes of two prophylaxis regimens - cefazolin\u0026thinsp;+\u0026thinsp;azithromycin and cefazolin - for nonselective cesarean infections. The model was based on a societal perspective and aimed to assist pregnant women in choosing the most cost-effective prophylaxis regimen for their nonselective cesarean delivery. The current clinical study by Tita, Ward, et al. abroad, and the study by Suttion, skeith et al. comparing the costs associated with these two intervention options demonstrate the effectiveness and economy of cefazolin combined with azithromycin for the prevention of cesarean infection [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR53 CR54\" citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. However, there is a dearth of clinical studies in China that correspond to this topic, and no pharmacoeconomic studies have been published to date regarding the use of cefazolin combined with azithromycin protocols for preventing nonselective cesarean infections. The model parameters used in this study were obtained from various sources, including published literature, documents from the Fujian Provincial Bureau of Medical Security, information from Drugwise.com, and data from the National Bureau of Statistics. Additionally, some parameters were discounted at a 5% annual rate. The results of this study indicate that the cefazolin and azithromycin prophylaxis regimen had a lower total cost and higher health output than cefazolin alone, making it the superior strategy. The robustness of the underlying analysis was verified through one-way sensitivity analysis and Monte Carlo simulation. The results showed a 76.1% probability that the combination of cefazolin and azithromycin was cost-effective.\u003c/p\u003e \u003cp\u003eIt is understood that this study is the first pharmacoeconomic evaluation in China that integrates maternal outcomes of current cesarean deliveries and potential pregnancies to construct a decision tree model for data analysis of two infection prevention regimens: cefazolin combined with azithromycin and cefazolin alone. The potential pregnancy event outcomes were constructed in the decision tree model so that maternal outcomes could be simulated and the overall maternal quality of life could be analyzed as much as possible. Moreover, this study estimated maternal outcomes for approximately 800,000 nonselective cesarean deliveries in China, which can more visually demonstrate the benefits of using cefazolin combined with azithromycin prophylaxis regimens for this population.\u003c/p\u003e \u003cp\u003eThis study has some limitations due to the absence of specific clinical trials. There are fewer studies in China on the combination of azithromycin in standard antibiotics for preventing nonselective cesarean infection, and no relevant, high-quality articles have been published, so clinical data on the efficacy of the combination of azithromycin in preventing infection in US studies were used. There is a question as to whether combining azithromycin with standard antibiotics is similarly effective in the Chinese population. Tita et al. suggested that the role of azithromycin in infection prevention may be due to, but not limited to, its inhibitory effect on ureaplasma organisms, so Author searched for the detection rate of ureaplasma organisms in the Chinese population and the resistance of ureaplasma organisms to azithromycin in some parts of China. The results showed that maternal ureaplasma urealyticum detection rates were high, up to 82% in a region of northern China, and several studies analyzing Ureaplasma urealyticum resistance in the northwest, northern and eastern China showed that Ureaplasma urealyticum resistance to azithromycin ranged from 2 to 15% [\u003cspan additionalcitationids=\"CR57 CR58\" citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. Furthermore, in a meta-analysis and systematic evaluation, this study collected relevant clinical trials from around the world and demonstrated that the risk of infection is decreased when azithromycin is added to the standard prophylactic regimen for cesarean infection [\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]. It was therefore hypothesized that combining azithromycin with standard antibiotics would have a similar effect on the Chinese population. Health utility values for each condition were mainly assessed using Non-Chinese quality of life assessments. Considering that the data sources for some of the parameters were foreign studies, there may be some differences with domestic real-world maternal data. The researcher's bias during the parameter collection may also affect the analysis results. Therefore, larger intervals of parameter variation were set in the probabilistic sensitivity analysis to determine the model's robustness.\u003c/p\u003e \u003cp\u003eIn conclusion, the prophylactic use of a cefazolin and azithromycin regimen during nonselective cesarean delivery can improve maternal postoperative indicators and potentially lead to better pregnancy outcomes. Therefore, conducting clinical studies in China on preventing nonelective or elective cesarean infections using standard antibiotics combined with azithromycin is worthwhile. This regimen could also be used as an effective means of preventing nonelective planarian infections in China.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eFrom a societal perspective in China, combining cefazolin with azithromycin for infection prophylaxis in pregnant women undergoing acute cesarean delivery may have better cost-effectiveness and health outcomes than using cefazolin alone for infection prophylaxis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eTOLAC, trial of labor after cesarean; VBAC, vaginal birth after cesarean; CD, cesarean delivery; VTE, venous thromboembolism; MD, maternal death; UR, uterine rupture; C hyst, cesarean hysterectomy; CPI, Consumer Price Index; QALYs, quality-adjusted life years; ICER, incremental cost-effectiveness ratio.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate：This is a data analysis type of study and does not involve human or animal testing, and case reports. All data in the literature were obtained from publicly available online data and published literature, therefore ethical approval and consent to participate did not apply to this study.\u003c/p\u003e\n\u003cp\u003eCompeting interests：Not applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials' section of your manuscript：The datasets supporting the conclusions of this article are included within the article.\u003c/p\u003e\n\u003cp\u003eConflicts of Interest statement: No financial support was received for this project. There are no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eFunding information: This study did not receive specific funding.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions statement:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConcept and design: Liu, Li.\u003c/p\u003e\n\u003cp\u003eAcquisition, analysis, or interpretation of data: Liu, You, Li, Zhang, Lei, Zeng, Chen.\u003c/p\u003e\n\u003cp\u003eDrafting of the manuscript: Liu, You.\u003c/p\u003e\n\u003cp\u003eCritical revision of the manuscript for important intellectual content: Liu, Li, Chen, Zhang, Lei, Zeng.\u003c/p\u003e\n\u003cp\u003eStatistical analysis: You.\u003c/p\u003e\n\u003cp\u003eAdministrative, technical, or material support: Liu, Li, Chen.\u003c/p\u003e\n\u003cp\u003eSupervision: Liu, Li.\u003c/p\u003e\n\u003cp\u003eEthics approval: Not applicable.\u003c/p\u003e\n\u003cp\u003eConsent to participate: Not applicable.\u003c/p\u003e\n\u003cp\u003eConsent for publication: Not applicable.\u003c/p\u003e\n\u003cp\u003eAcknowledgments\u003cstrong\u003e：\u003c/strong\u003e Fujian Medical University Union Hospital, China, provided valuable information for the analytical model.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eLi HT, Hellerstein S, Zhou YB, Liu JM, Blustein J. 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Int J Antimicrob Agents. 2022;59(3):106533.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"cesarean section, cefazolin, Azithromycin, pharmacoeconomic evaluation, Cost-utility analysis","lastPublishedDoi":"10.21203/rs.3.rs-3159554/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3159554/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eOBJECTIVE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe infection rate of cesarean delivery in China is 7 to 20 times higher than that of vaginal delivery, and the infection rate of nonelective cesarean delivery may be even higher. Therefore, this study aimed to conduct a cost-utility analysis of cefazolin combined with azithromycin versus cefazolin alone for the prevention of nonelective cesarean infection from a society-wide perspective in China, taking into account maternal outcomes of current cesarean deliveries as well as potential pregnancies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMETHODS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA decision tree model was constructed using TreeAge Pro 2022 to simulate the total cost and lifetime health outcomes of pregnant women in China under two infection prophylaxis regimens. Epidemiological, quality-of-life and cost parameters were obtained from various sources, including published literature, publicly available documents from the Fujian Provincial Bureau of Medical Security, data from \u003ca href=\"http://www.yaozh.com\" target=\"_blank\"\u003ewww.yaozh.com\u003c/a\u003e, and information from the China Bureau of Statistics. The discount rate has been established at 5% annually. The acceptable cost-utility threshold was established at three times China's GDP per capita in 2022.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRESULTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn analysis of 800,000 nonelective cesarean deliveries during labor or after rupture of membranes in China estimated that the use of cefazolin combined with azithromycin reduced the incidence of endometritis by 18,400 cases, wound infections by 33,500 cases, sepsis by 24 cases, prevented a rupture of the uterus by 342 cases, hysterectomy by 24 cases, and maternal deaths by 3 cases, compared to the use of cefazolin prophylaxis alone. The baseline analysis indicates that the combination of cefazolin and azithromycin resulted in an increase of 0.00157 quality-adjusted life years and a cost reduction of $769.14, making it the superior regimen. The results of the sensitivity analysis confirmed the robustness of the baseline analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe prophylactic use of cefazolin combined with azithromycin may result in better cost-effectiveness and health outcomes than cefazolin alone for Chinese pregnant women undergoing nonelective cesarean delivery.\u003c/p\u003e","manuscriptTitle":"Cost-utility analysis of azithromycin to assist in the prevention of acute cesarean section infection in a Chinese population","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-08-14 15:16:09","doi":"10.21203/rs.3.rs-3159554/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"06ef9b02-755c-459c-98c3-16f96211b7e6","owner":[],"postedDate":"August 14th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-11T05:20:28+00:00","versionOfRecord":[],"versionCreatedAt":"2023-08-14 15:16:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3159554","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3159554","identity":"rs-3159554","version":["v1"]},"buildId":"wLkW0s4AflPzk-lpfg-fK","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}