Tranexamic acid for the treatment of postpartum hemorrhage: a cost-effectiveness analysis.

BACKGROUND: Postpartum hemorrhage is a leading cause of pregnancy-related morbidity and mortality. Recent data have demonstrated that tranexamic acid reduces death because of bleeding when used as a treatment for postpartum hemorrhage. The World Health Organization now recommends tranexamic acid as a first-line treatment for postpartum hemorrhage; however, data are not yet available on the frequency of use in the United States, where tranexamic acid is currently recognized as an adjunct treatment for postpartum hemorrhage. OBJECTIVE: We aimed to strengthen the current evidence that tranexamic acid should be recognized as a first-line treatment for postpartum hemorrhage, even in high-resource countries. Furthermore, we aimed to determine whether early administration of tranexamic acid (within 3 hours of diagnosis) is a cost-effective strategy for reducing maternal morbidity and mortality from postpartum hemorrhage in the United States. STUDY DESIGN: A decision-analytical model was designed to compare the outcomes and costs of the administration of tranexamic acid in the treatment of postpartum hemorrhage. Moreover, this model was used to compare outcomes for early administration with those of routine use. The interventions compared were 1 g of intravenous tranexamic acid or matching placebo. The risks analyzed in the model were death because of hemorrhage and laparotomy to control bleeding. Probabilities, utilities, and costs were derived from literature. Quality-adjusted life-years were calculated using a discounted life expectancy rate of 3%. Cost-effectiveness was determined on the basis of a willingness-to-pay threshold of $100,000 per quality-adjusted life year. RESULTS: The administration of tranexamic acid to a theoretical cohort of 100,000 women would prevent 11 maternal deaths, 6 postpartum laparotomies after vaginal delivery, and 112 reoperations after cesarean delivery. This would lead to an increase in 329 quality-adjusted life years and a total cost savings of $15.39 million. Furthermore, if tranexamic acid were administered early (within 3 hours of postpartum hemorrhage diagnosis) to the same theoretical cohort, 16 maternal deaths owing to hemorrhage, 9 laparotomies, and 155 reoperations would be prevented. This amounts to an increase in 438 quality-adjusted life years and an annual cost savings of $23.15 million. A sensitivity analysis showed that the administration of tranexamic acid was the dominant strategy at all probabilities of maternal death owing to hemorrhage >0.00002. When the cost of tranexamic acid was varied, the administration of tranexamic acid remained dominant up to a cost of $267 per administration in the United States if given within the first 3 hours. Furthermore, in a Monte Carlo probabilistic sensitivity analysis, the early administration of tranexamic acid remained the dominant strategy (both lowered costs and improved outcomes) in 99.8% of models. CONCLUSION: Early administration of tranexamic acid was a cost-effective strategy for reducing maternal morbidity and mortality owing to postpartum hemorrhage in the United States.

Maternal body-mass-index and neonatal brachial plexus palsy in a California cohort.

OBJECTIVE: To evaluate risk factors and describe the association between maternal pre-pregnancy body-mass-index (BMI) and neonatal brachial plexus palsy (BPP) in vaginal deliveries with and without shoulder dystocia. METHODS: This is a retrospective cohort study of singleton, non-anomalous, term vaginal deliveries in California (2007-2011). Deliveries were classified as with or without shoulder dystocia. Our primary outcome was BPP and the independent variable of interest was maternal pre-pregnancy BMI, which was categorized as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obesity I (30-34.9 kg/m2), obesity II (35-39.9 kg/m2) and obesity III (≥40 kg/m2). We evaluated demographics, maternal, labor, and neonatal characteristics using chi-squared tests and assessed the association of pre-pregnancy BMI with BPP using multivariable logistic regression models. RESULTS: In our cohort of 1,395,761 women, there were 21,463 deliveries with shoulder dystocia and 1,374,298 deliveries without shoulder dystocia. Among deliveries with shoulder dystocia, BPP was observed more frequently in neonates born to women with BMI categorized as overweight (32% vs. 29%; p < .001), obesity I (22% vs. 14%; p < .001), obesity II (10% vs. 6%; p < .001), and obesity III (8% vs. 3%; p < .001). After adjusting for confounders, the odds of BPP in deliveries with shoulder dystocia was significantly higher for women who were overweight (aOR = 1.65; 95% CI: 1.35-2.01), obesity I (aOR = 2.33; 95% CI: 1.86-2.90), obesity II (aOR = 2.56; 95% CI: 1.92-3.40), and obesity III (aOR = 3.80; 95% CI: 2.75-5.25). In deliveries without shoulder dystocia, BPP was more common in women with a BMI that was overweight (29% vs. 25%; p < .001), obesity I (17% vs. 11%; p < .001), obesity II (9% vs. 4%; p < .001), and obesity III (8% vs. 2%; p < .001). In this cohort, multivariable regression model showed similar results in women with a BMI that was overweight (aOR = 1.47; 95% CI: 1.19-1.81), obesity I (aOR = 1.99; 95% CI: 1.55-2.54), obesity II (aOR = 2.79; 95% CI: 2.04-3.83), and obesity III (aOR = 5.05; 95% CI: 3.63-7.03). CONCLUSION: Rising maternal pre-pregnancy BMI is associated with an increased risk of BPP in vaginal deliveries with and without shoulder dystocia. Preconception interventions targeting weight management may be beneficial in reducing BPP in all deliveries.

First trimester fasting plasma glucose screen in advanced maternal age women: a cost-effectiveness analysis.

BACKGROUND: The prevalence of preexisting type 2 diabetes mellitus (T2DM) in the United States is on the rise. Women of advanced maternal age (AMA, ≥35 years) are more likely to have preexisting T2DM in pregnancy because glucose intolerance increases with age. Diabetes in pregnancy is associated with significant maternal and neonatal morbidity and mortality, and earlier treatment initiation improves pregnancy outcomes. However, maternal age is not currently recognized as an independent risk factor that warrants diabetes screening prior to the traditional screen at 24-28 weeks gestation. OBJECTIVE: To evaluate the cost-effectiveness of screening all AMA women with a first trimester fasting plasma glucose (FPG) test for earlier diagnosis and management of preexisting T2DM. STUDY DESIGN: A decision-analytic model was created to compare pregnancy outcomes in AMA women who undergo a first trimester FPG test vs third trimester oral glucose tolerance test alone. Probabilities were obtained from the literature. Outcomes examined included preeclampsia, preterm delivery, macrosomia, shoulder dystocia, brachial plexus injury (BPI), intrauterine fetal demise (IUFD), cerebral palsy, and neonatal death. The cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio of the first trimester screening strategy were examined as well. Sensitivity analyses and a Monte Carlo simulation were performed to test the model's robustness. RESULTS: In AMA women, screening for preexisting T2DM in the first trimester with an FPG test resulted in fewer cases of preeclampsia, preterm delivery, BPI, IUFD, cerebral palsy, and neonatal death compared to performing a third trimester oral glucose tolerance test alone, and is cost-effective. Monte Carlo analysis incorporating the distribution of all probabilities showed that first trimester FPG screening remained cost-effective as long as the incremental cost of initiating diabetes treatment in the first trimester was less than $150,000 and the cost of the FPG screen was less than $2700. CONCLUSION: Compared to third trimester oral glucose tolerance test alone, performing a first trimester FPG screen in AMA women is cost-saving and more effective.

Extending the second stage of labor in nulliparous women with epidural analgesia: a cost-effectiveness analysis.

The objective of this study was to evaluate maternal outcomes with an extended second stage of labor and determine if an extended second stage is cost effective. This theoretical model evaluated expectant management to 4 h compared to delivery at 3 h in the setting of a prolonged second stage of labor in nulliparous women with epidural analgesia. In our theoretical cohort of 165,000 women, we found that an extended second stage resulted in 53,268 more spontaneous vaginal deliveries, 14,163 fewer operative vaginal deliveries, and 39,105 fewer cesarean deliveries. This approach also resulted in 1 fewer instance of maternal death. An extended second stage, however, led to 14,025 more cases of chorioamnionitis, 1699 more episodes of postpartum hemorrhage requiring transfusion, and 119 more severe perineal lacerations, suggesting that while an extended second stage of labor results in overall improved maternal outcomes, there are tradeoffs. Expectant management to 4 h was the dominant strategy in the model, as it saved over $114 million US dollars and resulted in 4000 additional QALYs over our theoretical cohort. Sensitivity analysis indicated that expectant management until 4 h was cost-effective as long as the probability of cesarean delivery at 4 h was below 41.8%, and was the dominant strategy below 38.2% (baseline input: 19.5%). Multivariable sensitivity analysis demonstrated that the model was robust over a wide range of assumptions. Expectant management of the second stage of labor until 4 h is a cost-effective strategy to prevent primary cesarean deliveries, decrease costs, and improve some maternal outcomes, despite tradeoffs.

Vaginal preparation with povidone-iodine or chlorhexidine before hysterectomy: a propensity score matched analysis.

BACKGROUND: Antiseptic vaginal preparation is recommended before gynecologic surgery; however, there is a lack of data regarding the effectiveness of different agents. OBJECTIVE: To compare rates of postoperative infectious complications and hospital utilization with preoperative vaginal preparation using povidone-iodine or chlorhexidine before hysterectomy. STUDY DESIGN: This was a retrospective analysis of patients who underwent hysterectomy for gynecologic indications at 70 hospitals in a statewide surgical collaborative between January 2017 and December 2019. The primary outcome was postoperative infectious complications (including urinary tract infection, surgical site infections involving superficial, deep, or organ space tissues, or cellulitis) within 30 days of surgery. To adjust for confounding, propensity score matching, 1:1 without replacement and with a caliper of.005 was performed to create cohorts that had vaginal preparation with either povidone-iodine or chlorhexidine and did not differ in observable characteristics. We compared the rates of infectious morbidity and hospital utilization (emergency department visits, readmission, reoperation) in the matched cohorts. RESULTS: In the statewide collaborative, there were 18,184 patients who received povidone-iodine and 3018 who received chlorhexidine. After propensity score matching of 2935 pairs, the povidone-iodine and chlorhexidine groups did not differ in demographics, comorbidities, choice of preoperative antibiotics, benign vs malignant surgical indication, and surgical approach. Povidone-iodine was associated with a lower rate of infectious morbidity (3.0% vs 4.3%; P=.01), urinary tract infection (1.1% vs 1.7%; P=.03) and emergency department visits (7.9% vs 9.7%; P=.01) than with chlorhexidine. There were nonsignificant trends of lower rates of surgical site infection (2.0% vs 2.7%; P=.07) and reoperation (1.6% vs 2.1%; P=.18). CONCLUSION: This propensity score matched analysis provides evidence that povidone-iodine is preferable to chlorhexidine for vaginal preparation before hysterectomy because of lower rates of infectious morbidity and fewer emergency department visits. However, the absolute differences in infectious morbidity rates were approximately 1%, and in the event of an iodine allergy, chlorhexidine appears to be a reasonable alternative.

History of adolescent birth and diabetes in adulthood: a cross-sectional study of a nationally representative sample of American women.

Background: In the USA, 12-14% have type 2 diabetes mellitus and the incidence is rising. Adolescent birth has been shown to be associated with significant gestational weight gain and obesity in adulthood.Objective: We sought to evaluate the association between the history of adolescent birth and diabetes in adulthood.Study design: We conducted a cross-sectional study of the National Health and Nutrition Examination Survey (NHANES) data, examining 2-year cycles from 2005 to 2014. In a population of adult women who had experienced at least one live birth and who were not currently pregnant, we examined the prevalence of type 2 diabetes mellitus by the history of adolescent birth (live birth prior to 20 years of age). Sample characteristics were compared using survey-weighted chi-square tests. Multivariate logistic regression was used to examine the association between diabetes mellitus and adolescent birth history, with progressive adjustments for birth cohort, race/ethnicity, education level, and body mass index (BMI).Results: In a survey sample of 6507 individuals, we found that 38% of the women had experienced adolescent birth. Significant differences were found between those who had experienced adolescent birth and those who had not by birth cohort, race/ethnicity, federal poverty level, education attainment, parity, and BMI (p < .001 for all). The prevalence of type 2 diabetes was higher in women with a history of adolescent birth in adulthood than in women without a history of adolescent birth (17.2 versus 12.1%, p < .001; BMI-adjusted odds ratio = 1.27; 95% confidence interval, 1.03-1.58, p = .03).Conclusion: American women with a history of adolescent birth are at a significantly higher risk of type 2 diabetes mellitus in adulthood. Greater attention must be paid to preventing metabolic disease in women who experience early parity.

Maternal and Neonatal Hospitalization Costs Associated With Elective Induction of Labor at Term in California, 2007-2011.

OBJECTIVE: To compare hospitalization costs of pregnancies managed by elective induction of labor to those with spontaneous labor in a large cohort of pregnant women. METHODS: We conducted a retrospective cohort study of women with singleton, nonanomalous births in California from 2007 to 2011. We excluded women with placenta previa, breech presentation, prior cesarean delivery, planned cesarean delivery, medically indicated induction of labor, gestational age less than 37 weeks or at or greater than 41 weeks, and stillbirths. We adjusted hospital charges using a cost-to-charge ratio and costs included hospitalization costs for admission for delivery only. We estimated the difference in costs between elective induction of labor (resulting in a vaginal or cesarean delivery) and spontaneous labor for both women and neonates, stratified by mode of delivery, parity, gestational age at delivery and geographic location. We conducted analyses using Kruskal-Wallis equality-of-populations rank tests with a significance level of 0.05. RESULTS: In a California cohort of 1,278,151 women, 190,409 (15%) had an elective induction of labor. Median maternal hospitalization costs were $10,175 (interquartile range: $7,284-$14,144) with induction of labor and $9,462 (interquartile range: $6,667-$13,251) with spontaneous labor (P<.01) for women who had a vaginal delivery, and $20,294 (interquartile range: $15,367-$26,920) with induction of labor and $18,812 (interquartile range: $13,580-$25,197) with spontaneous labor (P<.01) for women who had a cesarean delivery. Maternal median hospitalization costs were significantly higher in the setting of elective induction of labor regardless of parity, mode of delivery, and gestational age at delivery. Alternatively, median hospitalization costs for neonates of women who had an elective induction of labor were significantly lower. CONCLUSION: Further research regarding approaches to induction of labor is necessary to determine whether strategies to reduce health care costs without affecting or even improving outcomes could help curb costs associated with induction of labor.

Cost-effectiveness of second curettage for treatment of low-risk non-metastatic gestational trophoblastic neoplasia.

OBJECTIVE: Low-risk non-metastatic gestational trophoblastic neoplasia (GTN) has been treated with single agent chemotherapy, but second curettage is emerging as an alternative strategy with reported cure rates of 40%. We sought to estimate the cost-effectiveness of second curettage as the first line treatment of low-risk GTN. METHODS: A decision-analytic model was created using TreeAge software to compare costs and outcomes for women with WHO staged low-risk GTN undergoing treatment with 5-day methotrexate (MTX), biweekly pulsed actinomycin-D, or second curettage. Probabilities were derived from the literature. Outcomes of interest included side effects from chemotherapy, need for additional agents, hemorrhage, uterine perforation, and cure rates. Utilities were applied to discounted life expectancy at a rate of 3% to generate quality adjusted life years (QALYs). Sensitivity analyses were then performed in order to assess the robustness of our assumptions. RESULTS: Of the three treatment arms, MTX was associated with the lowest cost and had similar QALYs to the other studied modalities. Second curettage was associated with 49 additional cures when applied to a theoretic cohort of 1000 women, as well as an additional 83 hemorrhages and 17 uterine perforations. Sensitivity analysis on the cure rate of second curettage revealed that second curettage was not cost-effective over MTX unless its probability of cure was 98%. CONCLUSION: Our study found 5-day MTX was the cost-effective strategy for treatment of women with low-risk, non-metastatic GTN when compared to second curettage and actinomycin-D. In a carefully selected patient population, second curettage may be an additional treatment strategy.

Induction of labor at 39 weeks of gestation versus expectant management for low-risk nulliparous women: a cost-effectiveness analysis.

BACKGROUND: A large, recent multicenter trial found that induction of labor at 39 weeks for low-risk nulliparous women was not associated with an increased risk of cesarean delivery or adverse neonatal outcomes. OBJECTIVE: We sought to examine the cost-effectiveness and outcomes associated with induction of labor at 39 weeks vs expectant management for low-risk nulliparous women in the United States. STUDY DESIGN: A cost-effectiveness model using TreeAge software was designed to compare outcomes in women who were induced at 39 weeks vs expectantly managed. We used a theoretical cohort of 1.6 million women, the approximate number of nulliparous term births in the United States annually that are considered low risk. Outcomes included mode of delivery, hypertensive disorders of pregnancy, macrosomia, stillbirth, permanent brachial plexus injury, and neonatal death, in addition to cost and quality-adjusted life years for both the woman and neonate. Model inputs were derived from the literature, and a cost-effectiveness threshold was set at $100,000/quality-adjusted life years. RESULTS: In our theoretical cohort of 1.6 million women, induction of labor resulted in 54,498 fewer cesarean deliveries and 79,152 fewer cases of hypertensive disorders of pregnancy. We also found that induction of labor resulted in 795 fewer cases of stillbirth and 11 fewer neonatal deaths, despite 86 additional cases of brachial plexus injury. Induction of labor resulted in increased costs but increased quality-adjusted life years with an incremental cost-effectiveness ratio of $87,691.91 per quality-adjusted life year. In sensitivity analysis, if the cost of induction of labor was increased by $180, elective induction would no longer be cost effective. Similarly, we found that if the rate of cesarean delivery was the same in both strategies, elective induction of labor at 39 weeks would not be a cost-effective strategy. In probabilistic sensitivity analysis via Monte Carlo simulation, we found that induction of labor was cost effective only 65% of the time. CONCLUSION: In our theoretical cohort, induction of labor in nulliparous term women at 39 weeks of gestation resulted in improved outcomes but increased costs. The incremental cost-effectiveness ratio was marginally cost effective but would lead to an additional 2 billion dollars of healthcare costs. Whether individual clinicians and healthcare systems offer routine induction of labor at 39 weeks will need to depend on local capacity, careful evaluation and allocation of healthcare resources, and patient preferences. KEY WORDS: cesarean delivery, decision analysis, healthcare resources, induction of labor, low-risk nulliparous women, mode of delivery, obstetric outcomes.

Association of a Health Care Provider Review Meeting With Cesarean Delivery Rates: A Quality Improvement Program.

OBJECTIVE: To examine the association of a quality improvement effort that was mediated through weekly review of all criteria for cesarean delivery on cesarean delivery prevalence and indications. METHODS: We conducted a retrospective cohort study using a natural experiment model that compared two timeframes, from 2009 to 2013, at a single institution. We introduced a weekly retrospective review conference to discuss all cesarean deliveries in 2010 that continued over time. The conferences were attended by obstetric care providers, anesthesiology, and labor and delivery nurses. Date of delivery was dichotomized by those delivering before July 1, 2010, and those delivering after. We included women with term singleton vertex gestations in our study population and then examined the rates of cesarean delivery by date of delivery. We then examined indications for the cesarean deliveries during the study period based on surgeon documentation. χ tests were used for statistical comparisons and a P value of <.05 was used to indicate statistical significance. RESULTS: There were 5,541 term singleton cephalic births during the study period. The rate of cesarean delivery declined significantly after our intervention in all women (22.2% vs 27.4%, P<.001) and nulliparous women (23.3% vs 30.9%, P<.001). The adjusted odds ratio of cesarean delivery in all women as related to time cohort is 0.68 (95% CI 0.58-0.79) and 0.56 (95% CI 0.44-0.70) in nulliparous women. We examined indications for the 1,315 cesarean deliveries during the study period by date of delivery. The indications of active-phase arrest, second-stage arrest, failed induction, repeat cesarean delivery, and maternal request decreased significantly between delivery cohorts in all women (P<.001) and in nulliparous women specifically (P<.001). Between delivery cohorts, we found that the prevalence of labored indications for cesarean delivery decreased more than nonlabored indications. CONCLUSION: Implementation of a weekly review conference was associated with a reduction in both overall cesarean delivery prevalence and labored indications at our institution.

Twenty-Week Abortion Bans on Pregnancies With a Congenital Diaphragmatic Hernia: A Cost-Effectiveness Analysis.

OBJECTIVE: To estimate the effect of 20-week abortion bans on maternal and consequent neonatal health outcomes and costs in the setting of fetal congenital diaphragmatic hernia. METHODS: A decision-analytic model was built using TreeAge software to evaluate the effect of a 20-week ban on abortion in a theoretical cohort of 921 women diagnosed with fetal congenital diaphragmatic hernia. Probabilities, utilities, and costs were derived from the literature. The cohort size was based on the annual rate of prenatal diagnoses of congenital diaphragmatic hernia and live births among the 20 states with bans. The threshold for cost-effectiveness was set at $100,000 per quality-adjusted life-year. Analysis was completed from the maternal perspective. Clinical outcomes included mode of delivery, maternal death, intrauterine fetal death, neonatal death, neurodevelopmental disability, and use of extracorporeal membrane oxygenation. One-way sensitivity analysis was used on all variables and Monte Carlo simulation was performed. RESULTS: A policy restricting termination was associated with higher costs, at an additional $158,419,623, with decreased quality of life and 674 fewer quality-adjusted life-years. With 20-week bans in place, 60 women would travel out of state to obtain abortions. There would be 158 more live births affected by congenital diaphragmatic hernia. Of these births, 45 neonates would die before 28 days after birth and an additional 37 would have long-term neurodevelopmental disability. CONCLUSION: In this model, bans that limit abortions beyond 20 weeks of gestation were associated with worse health outcomes and increased costs for women with pregnancies complicated by congenital diaphragmatic hernia. The restriction of health care access should be considered in terms of the long-term outcomes and economic effect on individuals and society.

Adding Azithromycin to Cephalosporin for Cesarean Delivery Infection Prophylaxis: A Cost-Effectiveness Analysis.

OBJECTIVE: To investigate the cost-effectiveness of adding azithromycin to standard cephalosporin regimens of cesarean delivery prophylaxis by considering the maternal outcomes in the current and potential subsequent pregnancies. METHODS: A cost-effectiveness model was created using TreeAge to compare the outcomes of using azithromycin-cephalosporin with cephalosporin alone in a theoretical cohort of 700,000 women, the approximate number of nonelective cesarean deliveries annually in the United States that occur during labor or after membrane rupture. Outcomes examined included endometritis, wound infection, sepsis, venous thromboembolism, and maternal death in the current pregnancy and uterine rupture, cesarean hysterectomy, and maternal death in subsequent pregnancies, including cost and quality-adjusted life-years for both pregnancies. Probabilities, utilities, and costs were derived from the literature, and a cost-effectiveness threshold was set at $100,000 per quality-adjusted life-year. Sensitivity analyses were used to determine the robustness of our results. RESULTS: Compared with cephalosporin alone for prophylaxis, our model showed 16,100 fewer cases of endometritis, 17 fewer cases of sepsis, eight fewer cases of venous thromboembolism, and one fewer maternal death with azithromycin-cephalosporin. Additionally, this strategy prevented 36 uterine ruptures and four cesarean hysterectomies in the subsequent pregnancy. Overall, the addition of azithromycin led to both lower costs and higher quality-adjusted life-years when compared with standard cephalosporin prophylaxis. In sensitivity analysis, we found that as long as the cost of azithromycin remained below $930 (baseline cost $27), it was cost-effective. CONCLUSION: For women who undergo cesarean delivery in labor or after membrane rupture, compared with cephalosporin alone, the addition of azithromycin to cesarean delivery infection prophylaxis is less costly and leads to better maternal outcomes in the index delivery and subsequent deliveries. These findings support the use of prophylactic azithromycin at the time of cesarean delivery.