Third stage of labor: evidence-based practice for prevention of adverse maternal and neonatal outcomes.

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term "active management of the third stage of labor" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term "active management of the third stage of labor" as a combined intervention no longer be used. Instead, we recommend that "third stage care" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate.

Analysis of Obstetric Outcomes by Hospital Location, Volume, and Teaching Status Associated With Non-Medically Indicated Induction of Labor at 39 Weeks.

Importance: Non-medically indicated induction of labor has been demonstrated to potentially improve some obstetric outcomes, such as decreasing cesarean birth. It has been reported that rates of cesarean birth and other obstetric outcomes vary among hospitals with different characteristics. Objective: To assess whether obstetric outcomes differ between nulliparous individuals with low-risk pregnancies managed with non-medically indicated induction of labor compared with expectant management in different types of hospitals. Design, Setting, and Participants: This retrospective cohort study included non-medically indicated induction of labor at 39 weeks' gestation compared with expectant management of singleton, nonanomalous, births in nulliparous women with low-risk pregnancies in California between January 1, 2007, and December 31, 2011. The initial analysis of these data was performed in 2021. Outcomes were assessed by 3 hospital characteristics: location (urban vs rural), obstetric volume, and teaching (academic vs community) status. Volume was categorized based on the average number of births per year and grouped into low (<1200 births per year), medium (1200-2399 births per year), and high (≥2400 births per year). Births with previous or planned cesarean delivery were excluded, and non-medically indicated induction of labor was defined as induction of labor without a specific medical indication. Testing with χ2 and multivariable logistic regression analyses was used for statistical comparisons with a cutoff level of P = .01. Exposure: Non-medically indicated induction of labor at 39 weeks' gestation. Main Outcomes and Measures: The primary outcome was cesarean birth, and numerous secondary perinatal outcomes were also assessed. Results: There were 455 044 births included in this study. When stratified by hospital variables, a number of sociodemographic characteristics were significantly different, such as race and ethnicity, age, body mass index, and insurance type. The adjusted odds ratios (aORs) of cesarean birth were significantly lower in all settings with induction of labor except for low-volume hospitals, in which there was no significant difference (aOR, 0.95; 95% CI, 0.82-1.09). Chorioamnionitis and postpartum hemorrhage were lower with induction of labor among nearly every hospital when stratified by hospital characteristics. Neonatal outcomes were improved in all settings with induction of labor compared with expectant management. Conclusions and Relevance: These findings suggest that non-medically indicated induction of labor may be associated with a lower rate of cesarean births and some maternal and neonatal adverse outcomes in a range of hospital settings.

Considering Criteria for Active Phase Labor Management of Nulliparous Women: A Cost-Effectiveness Analysis.

OBJECTIVE: The aim of the study is to evaluate differences in maternal and neonatal outcomes based on updated criteria for defining active labor at 6 cm of cervical dilation and to determine if these recommendations are cost-effective. STUDY DESIGN: A decision-analytic model was built using TreeAge Pro 2020 software. We included maternal outcomes of mode of delivery, endometritis, postpartum hemorrhage requiring transfusion, and death. Neonatal outcomes included rates of shoulder dystocia and permanent brachial plexus injury. Costs and quality-adjusted life years (QALYs) were included from the maternal and infant perspectives. We used a willingness-to-pay threshold of $100,000 per QALY and all model inputs were subjected to sensitivity analysis. RESULTS: In a theoretical cohort of 1.4 million women, a threshold of 6 cm to define active labor resulted in 373,668 fewer cesarean deliveries, 33,181 fewer cases of endometritis, 143 fewer postpartum hemorrhages requiring transfusions, and seven fewer maternal deaths when compared with a threshold of 4 cm. However, there were higher rates of adverse neonatal outcomes, including 484 more cases of shoulder dystocia and 17 more instances of permanent brachial plexus injury. Using 6 cm as the threshold resulted in lower costs and greater effectiveness, making it a dominant strategy. Multivariate sensitivity analysis demonstrated the model was robust over a wide range of assumptions. CONCLUSION: In this model, considering 6 cm of cervical dilation as the threshold for the active phase of labor compared with 4 cm was a cost-effective strategy to prevent primary cesarean deliveries, lower costs, and improve maternal outcomes, despite associated increased adverse neonatal outcomes. KEY POINTSG: · Cervical dilation of 6 cm should be considered the threshold for the active phase of labor. This is a change from the prior definition of 4 cm.. · We built a theoretical model to compare outcomes and costs associated with the new active phase definition of 6 cm.. · Using a 6-cm threshold is a cost-effective strategy for decreasing primary cesarean deliveries..

Outcomes among Nulliparous Women Undergoing Nonmedically Indicated Induction of Labor at 39 Weeks Compared with Expectant Management Differ by Maternal Age.

OBJECTIVE: Prior studies have demonstrated the potential benefit of nonmedically indicated induction of labor for nulliparous women at 39 weeks of gestation, yet few have studied the impact of this management strategy in different maternal age groups on obstetric outcomes. We sought to assess whether obstetric outcomes among women undergoing nonmedically indicated induction of labor at 39 weeks of gestation as compared with expectant management vary based on maternal age. STUDY DESIGN: This was a retrospective cohort study of singleton, nonanomalous, deliveries between 2007 and 2012 in California. We defined nonmedically indicated induction of labor as induction of labor without a specific medical indication, and women with planned cesarean sections were excluded. We compared induction of labor with expectant management beyond the gestational age of induction and examined this comparison in different maternal age groups. Numerous maternal and neonatal outcomes were examined. Chi-squared and multivariable logistic regression analyses were used for statistical comparisons and a p-value of less than 0.05 was used to indicate statistical significance. RESULTS: A total of 630,485 women-infant dyads met our inclusion criteria and were included in this study. At 39 weeks' gestation, 6% of women underwent nonmedically indicated induction of labor and 94% underwent expectant management. Women 20 to 34 and ≥35 years old had lower odds of cesarean delivery if they underwent induction of labor. Women of all ages undergoing nonmedically indicated induction of labor had higher odds of operative vaginal delivery. Neonatal outcomes were better with nonmedically indicated induction of labor, including lower odds of neonatal intensive care unit admission and neonatal respiratory distress. CONCLUSION: Our study demonstrated that obstetric outcomes vary among women undergoing nonmedically indicated induction of labor compared with expectant management when stratified by maternal age. These findings illustrate the importance of understanding age-related differences in outcomes associated with nonmedically indicated induction of labor. KEY POINTS: · Outcomes are different by age with nonmedically indicated induction of labor (IOL).. · The odds of cesarean delivery with IOL decreases with increasing maternal age compared with expectant management.. · Neonatal outcomes were improved with IOL compared with expectant management..

Association of perinatal outcomes among pregnant patients with gestational diabetes receiving benefits from the Special Supplemental Nutrition Program for Women, Infants, and Children.

BACKGROUND: Treatment of gestational diabetes mellitus has been demonstrated to improve perinatal outcomes. However, the role of the Special Supplemental Nutrition Program for Women, Infants, and Children in maternal and neonatal outcomes for qualifying patients with gestational diabetes mellitus is less understood. OBJECTIVE: The objective of this study is to observe the relationship of enrollment in the Special Supplemental Nutrition Program for Women, Infants, and Children with pregnancy outcomes in patients with gestational diabetes. STUDY DESIGN: This was a retrospective cohort study using National Vital Statistics Birth Data of pregnant persons diagnosed with gestational diabetes mellitus between 2014 and 2018. The study population was composed of patients who had Medicaid coverage for maternity care; patients with Medicaid are automatically qualified for the Special Supplemental Nutrition Program for Women, Infants, and Children. The study groups were defined as those who enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children vs those who did not enroll. In addition, maternal and neonatal outcomes for these groups were analyzed. Univariate and multivariable logistic regression analyses adjusted for significant covariates were performed. RESULTS: Of 460,377 pregnant persons with pregnancies complicated by gestational diabetes mellitus, 73% were enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children, and 27% were not. Pregnant persons with gestational diabetes mellitus enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children had decreased odds of preterm delivery before 34 and 37 weeks of gestation. Although the Special Supplemental Nutrition Program for Women, Infants, and Children group had higher odds of large-for-gestational-age neonates and cesarean delivery, the overall rates of these outcomes in both cohorts were high. CONCLUSION: The Special Supplemental Nutrition Program for Women, Infants, and Children provides a resource for perinatal support, supplemental food, and nutritional education. The decrease in the rates of preterm deliveries in pregnant persons with gestational diabetes mellitus that enroll in the Special Supplemental Nutrition Program for Women, Infants, and Children, Infants, and Children relative to those that qualified for the program but did not enroll suggested that having access to available education and food sources may influence perinatal outcomes.

Soluble concentrations of the terminal complement complex C5b-9 correlate with end-organ injury in preeclampsia.

OBJECTIVE: We sought to determine if soluble levels of C5b-9, the terminal complement complex, correlate with end-organ injury in preeclampsia. STUDY DESIGN: Project COPA (Complement and Preeclampsia in the Americas), a multi-center observational study in Colombia from 2015 to 2016, enrolled hypertensive pregnant women into four groups: chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia with severe features. Trained coordinators collected clinical data, blood and urine. End-organ injury was defined by serum creatinine ≥ 1.0 mg/dl, aspartate transaminase ≥ 70U/L, platelet count < 150,000/µl, or lactate dehydrogenase ≥ 500 U/L. Data were analyzed by χ2 or Fisher's exact test with significance at P < 0.05. MAIN OUTCOME MEASURE: C5b-9 concentrations in plasma and urine, using enzyme linked immunosorbent assays. RESULTS: In total, 298 hypertensive participants were enrolled. Plasma and urine C5b-9 levels were measured in all participants and stratified by quartile (Q1-4), from lowest to highest C5b-9 concentration. Participants with low plasma C5b-9 levels (Q1) were more likely to have end-organ injury compared to those with higher levels (Q2-Q4) [platelet count < 150,000/µl (20.8% vs. 8.4%, P = 0.01); elevated serum creatinine ≥ 1.0 mg/dl (14.9% vs. 4.5%, P = 0.009)]. In contrast, participants with high urinary C5b-9 levels (Q4) were more likely to have end-organ injury compared to those with lower levels (Q1-Q3) [platelet count < 150,000/µl (19.7% vs. 7.4%, P = 0.003); elevated serum creatinine ≥ 1.0 mg/dl (12.3% vs. 4.4%, P = 0.025)]. CONCLUSION: We identified a pattern of increased urine and low plasma C5b-9 levels in patients with preeclampsia and end-organ injury. Soluble C5b-9 levels may be used to identify complement-mediated end-organ injury in preeclampsia.

In vitro fertilization with preimplantation genetic testing for monogenetic diseases versus unassisted conception with prenatal diagnosis for Huntington disease: a cost-effectiveness analysis.

OBJECTIVE: To investigate if in vitro fertilization (IVF) with preimplantation genetic testing for monogenic disease is cost effective for heterozygous individuals with Huntington disease vs. unassisted conception with prenatal diagnosis. DESIGN: Cost-effectiveness analysis in a theoretical cohort of 3,851 couples, where one individual is heterozygous for Huntington disease. SETTING: N/A. PATIENTS/ANIMALS: None. INTERVENTION: In vitro fertilization preimplantation genetic testing for couples attempting conception. MAIN OUTCOME MEASURES: Outcomes included cost and quality-adjusted life years (QALYs) for both parents in addition to secondary outcomes of procedure-related loss, spontaneous abortion, termination of pregnancy, and early/normal/late-onset Huntington disease. A willingness-to-pay threshold was set at $100,000/QALY. RESULTS: In vitro fertilization preimplantation genetic testing is lower in cost and higher in effectiveness compared to unassisted conception with prenatal diagnosis among couples with one heterozygous Huntington disease individual, making it the dominant strategy. In vitro fertilization preimplantation genetic testing was associated with 77 more QALYs and a cost savings of $46,394,268. All measured outcomes were lower in the IVF preimplantation genetic testing strategy, including 39 fewer procedure-related losses, 39 fewer spontaneous abortions, and 462 fewer terminations of pregnancy. Most notably, in our theoretical cohort of couples, IVF preimplantation genetic testing resulted in 1,079 fewer Huntington disease-affected offspring. Our results were robust over a wide range of assumptions. CONCLUSION: In vitro fertilization preimplantation genetic testing is a cost-effective conception strategy compared to unassisted conception with prenatal diagnosis when one individual is heterozygous for Huntington disease. Not only can morbidity and mortality incurred by Huntington disease be mitigated for the offspring with the use of IVF preimplantation genetic testing, but this study demonstrates the cost-effectiveness of using IVF preimplantation genetic testing for those with Huntington disease.

Prevention of perinatal depression with counseling in adolescents: a cost-effectiveness analysis.

OBJECTIVE: The US Preventive Services Task Force recently recommended that clinicians refer all pregnant and postpartum individuals at increased risk of perinatal depression to a counseling intervention. Adolescents are considered a high-risk group for perinatal depression. Therefore, we examined whether it is cost effective for all pregnant adolescents to be referred for preventive counseling. STUDY DESIGN: We developed a decision-analytic model using TreeAge Pro software to compare outcomes in pregnant adolescents who received versus did not receive counseling interventions. We used a theoretical cohort of 180,000 individuals, which is the estimated annual number of births to persons ≤ 19 years in the US. Outcomes included perinatal depression, chronic depression, maternal suicide attributed to depression, preterm delivery, neonatal death, cerebral palsy, and sudden infant death syndrome (SIDS), in addition to cost and quality-adjusted life years (QALYs). The willingness-to-pay (WTP) threshold was set to $100,000/QALY. We derived model inputs from the literature, and sensitivity analyses were used to assess robustness of the model. RESULTS: A strategy of referral to counseling interventions was cost effective in our theoretical cohort, with 8935 fewer cases of perinatal depression, 1606 fewer cases of chronic depression, 166 fewer preterm deliveries, 4 fewer neonatal deaths, 1 fewer case of cerebral palsy, 20 fewer cases of SIDS. In total, there were 21,976 additional QALYs and cost savings of $223,549,872, making it the dominant strategy (better outcomes with lower costs). We found that counseling interventions remained cost saving until the annual direct and indirect cost of chronic, severe depression was set below $30,000, at which point it became cost effective (baseline input: $182,309). CONCLUSION: We found it was cost effective to refer all pregnant adolescents for preventive counseling interventions. Clinicians should develop approaches to identify and refer pregnant adolescents for behavioral counseling to prevent perinatal depression.

Antenatal corticosteroids for pregnant women with COVID-19 infection and preterm prelabor rupture of membranes: a decision analysis.

BACKGROUND: While antenatal corticosteroids are routinely used to decrease adverse neonatal outcomes following preterm delivery, corticosteroids are also associated with worse outcomes in patients with viral respiratory infections. Currently in the setting of the COVID-19 pandemic, it is unclear whether antenatal corticosteroids for infant benefit outweigh the potential harm to a pregnant woman with a COVID-19 infection. OBJECTIVE: To determine at which gestational ages administering antenatal corticosteroids is the optimal management strategy for hospitalized women with preterm prelabor rupture of membranes (PPROM) who have a COVID-19 infection. METHODS: We designed a decision-analytic model to assess the maternal and infant outcomes associated with antenatal corticosteroid administration for risk of preterm delivery following rupture of membranes in the setting of a COVID-19 infection. We used a theoretical cohort of 10,000 women at each gestational age between 24 and 32 weeks who were hospitalized with PPROM and found to be COVID-19 positive. Maternal outcomes included intensive care unit admission and death related to COVID-19 infection. The infant outcomes of interest included respiratory distress syndrome, intraventricular hemorrhage, neurodevelopmental delay, and death, and were assessed along with maternal and infant quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were used to evaluate model assumptions. RESULTS: In our theoretical cohort of 10,000 women with COVID-19 infection and preterm prelabor rupture of membrane between 24 and 32 weeks, corticosteroid administration resulted in 2,200 women admitted to the ICU and 110 maternal deaths at each gestational age. No antenatal corticosteroid use resulted in 1,500 ICU admissions and 75 maternal deaths at each gestational age. Antenatal corticosteroid administration also resulted in fewer cases of respiratory distress syndrome, intraventricular hemorrhage, and infant death. Overall, we found that between 24 and 30 weeks of gestation, administering antenatal corticosteroids was the optimal management strategy as it resulted in higher combined QALYs than no corticosteroid use. For 31 and 32 weeks of gestation, antenatal corticosteroid administration resulted in lower combined QALYs. On sensitivity analyses, we found that with increasing gestational age, the probability which antenatal corticosteroids was the optimal management strategy decreased. CONCLUSION: Administration of antenatal corticosteroids was an effective management strategy compared to no corticosteroid administration at gestational ages less than 31 weeks. These results provide data for clinicians to utilize when counseling pregnant patients hospitalized with PPROM and have a COVID-19 infection.

Timing of active phase labor arrest diagnosis in nulliparous women: a cost-effectiveness analysis.

BACKGROUND: Recommendations from the American College of Obstetricians and Gynecologists for the safe prevention of primary cesarean deliveries propose that cesarean delivery for active phase arrest in the first stage of labor should be performed only if women fail to progress despite four hours of adequate uterine activity and no cervical change. This is a change in recommendation from a two-hour threshold. OBJECTIVE: To determine the economic and clinical implications of waiting four hours compared to two hours for cervical progression before diagnosing active phase labor arrest. STUDY DESIGN: We designed a cost-effectiveness analysis using TreeAge Pro 2020 software with model inputs derived from the literature. We used a theoretical cohort of 1.4 million women, the approximate number of nulliparous U.S. women reaching four centimeters in spontaneous labor. We compared maternal and neonatal outcomes and costs associated with defining active phase arrest after four hours of no cervical progression versus two hours. As a baseline assumption, active labor was defined at four centimeters. It was assumed that women with active phase arrest were delivered via cesarean delivery. In addition to cost and maternal quality-adjusted life years (QALY), outcomes included mode of delivery, endometritis, postpartum hemorrhage requiring transfusion, and maternal deaths. Neonatal outcomes included rates of shoulder dystocia and permanent brachial plexus injury. The willingness-to-pay threshold was set at $100,000/QALY. RESULTS: In a theoretical cohort of 1.4 million women, waiting four hours instead of two hours led to 322,253 fewer cesarean deliveries, 6 fewer maternal deaths, 123 fewer postpartum hemorrhages requiring transfusions, and 28,615 fewer episodes of endometritis. There were 418 more instances of neonatal shoulder dystocia and 14 more cases of permanent brachial plexus injuries with a four-hour threshold. A four-hour threshold leads to 56% more women having a vaginal delivery in our theoretical cohort. Results from our model show that waiting four hours versus two hours to diagnose active phase labor arrest led to increased total QALYs with increased costs, with an incremental cost effectiveness ratio (ICER) below our willingness-to-pay threshold of $100,000 per QALY. Thus, it was cost effective to wait for at least four hours in the diagnosis of active phase arrest. Multivariable sensitivity analysis demonstrated the model was robust over a wide range of assumptions. CONCLUSIONS: Increasing the time threshold from two to four hours for diagnosing active phase labor arrest beyond four centimeters is a cost-effective strategy, resulting in fewer primary cesarean deliveries and improved maternal outcomes, despite a small increase in adverse neonatal outcomes.

Maternal and infant hospitalization costs associated with hypertensive disorders of pregnancy in a California cohort.

BACKGROUND: The United States has higher health care costs than other developed nations. Hypertensive disorders of pregnancy are increasingly common, and longer hospital admissions and utilization of additional therapies are costly. OBJECTIVE: We sought to estimate maternal and neonatal hospital costs in a large cohort of pregnant women with and without hypertensive disorders of pregnancy. STUDY DESIGN: This was a retrospective cohort study of women in California with singleton, non-anomalous births with gestational ages between 23-42 weeks. Women were categorized into seven mutually exclusive groups: no hypertension, chronic hypertension (HTN), chronic HTN with superimposed preeclampsia, gestational HTN, mild preeclampsia, severe preeclampsia, and eclampsia. Hospitalization costs were estimated for women and neonates separately and included the cost for admission for delivery only. We used Chi squared and Kruskal-Wallis equality-of-populations rank tests for statistical analysis with a significance level of 0.05. RESULTS: In a California cohort of 1,918,482 women, 16,208 (0.8%) had chronic HTN, 5,912 (0.3%) had chronic HTN with superimposed preeclampsia, 39,558 (2.1%) had gestational HTN, 33,462 (1.7%) had mild preeclampsia, 17,184 (0.9%) had severe preeclampsia and 1252 (0.1%) had eclampsia. Median hospitalization costs and length-of-stays were statistically significantly different for women in each group (p<.001). Women with eclampsia had the highest median hospitalization costs ($25,437, IQR: $16,893-$37,261) and women without any hypertensive disorder of pregnancy had the lowest ($11,720, IQR: $8019-$17,530). Costs were significantly different between groups based on gestational age and mode of delivery, and with severe maternal morbidity and neonatal intensive care unit admission status (p<.001). CONCLUSIONS: We found that hospitalization costs of hypertensive disorders of pregnancy were significantly higher than women without hypertension in pregnancy. These results highlight the economic burden of hypertensive disorders of pregnancy.

Therapeutic hypothermia in severe hypoxic-ischemic encephalopathy: a cost-effectiveness analysis.

BACKGROUND: The incidence of hypoxic-ischemic encephalopathy (HIE) is 0.5 per 1,000 live births. Current standard treatment is therapeutic hypothermia (cooling) begun within 6 hours of life. In infants with severe HIE, this results in fewer deaths; however, more infants survive with major neurodevelopmental disability. OBJECTIVE: We sought to determine whether cooling is cost-effective compared to no cooling in cases of severe HIE, and to compare it to the cost-effectiveness of cooling in cases of moderate HIE. STUDY DESIGN: A decision analytic model using TreeAge Pro (2020) software was designed comparing cooling to no cooling in a cohort of 5,800 term neonates with HIE. Model inputs were derived from the literature. Utilities were applied to life expectancy to generate quality-adjusted life years (QALYs). All costs and QALYs were discounted at an annual rate of 3%. The strategy was considered cost-effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-to-pay threshold of $100,000 per QALY. Sensitivity analyses were conducted to assess the robustness of the results. RESULTS: Cooling for the management of severe HIE resulted in increased costs and increased QALYs, with an ICER of 6,864. In our theoretical cohort, cooling resulted in 835 fewer neonatal deaths, but 52 additional cases of severe neurological disability with cooling due to increased survival. When varying the probability of a healthy child with cooling in univariate sensitivity analysis, cooling was found to be the cost-effective strategy across all ranges and the dominant (lower costs, higher QALYs) strategy above 68% (baseline estimate: 63%). Multivariate sensitivity analysis found cooling was the cost-effective strategy 99.7% of the time. CONCLUSION: Cooling is the cost-effective intervention with improved outcomes for neonates with severe perinatal hypoxic-ischemic encephalopathy over a wide range of assumptions. Despite the increased cost, more neonates survive morbidity free when compared with no cooling.

Cost effectiveness of buprenorphine vs. methadone for pregnant people with opioid use disorder.

OBJECTIVE: To assess the cost effectiveness of buprenorphine versus methadone in the management of opioid use disorder (OUD) during pregnancy. METHODS: We designed a decision-analytic model to evaluate the costs and outcomes associated with buprenorphine compared to methadone for pregnant people with OUD. We used a theoretical cohort of 22,400 pregnant people, which is an estimation of pregnancies affected by OUD per year in the United States. Outcomes included maternal retention in maintenance treatment, neonatal opioid withdrawal syndrome, preterm birth, fetal growth restriction, cerebral palsy, and maternal overdose in addition to cost and quality-adjusted life-years (QALYs). We used a willingness-to-pay threshold of $100,000/QALY. All model inputs were derived from the literature and varied in sensitivity analyses to assess the robustness of our baseline inputs. RESULTS: In our theoretical cohort, treatment of OUD with buprenorphine during pregnancy resulted in 2413 fewer cases of neonatal opioid withdrawal syndrome, 1089 fewer preterm births, 299 fewer cases of fetal growth restriction, 32 fewer stillbirths, and 13 fewer cases of cerebral palsy compared to methadone treatment. Despite lower rates of retention, buprenorphine treatment saved nearly 123 million healthcare dollars and resulted in 558 additional QALYs, making it the dominant strategy compared to methadone treatment. Our findings were robust over a wide range of assumptions. CONCLUSION: Our data suggest that buprenorphine should be considered a cost effective treatment option for OUD in pregnancy, as it is associated with improved neonatal outcomes compared to methadone despite the risk of treatment discontinuation.

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.

Maternal and infant hospitalization costs associated with maternal pre-pregnancy body mass index in California, 2007-2011.

BACKGROUND: In the United States, the number of pregnant women who are overweight or obese is increasing. While such individuals are at increased risk of pregnancy complications, data regarding costs associated with pre-pregnancy body mass index (BMI) and maternal and infant outcomes are lacking. OBJECTIVE: To estimate maternal and infant costs associated with pre-pregnancy BMI in a large cohort of pregnant women. MATERIALS AND METHODS: We conducted a retrospective cohort study of women with singleton, non-anomalous births in California from 2007 to 2011. Women with preexisting diabetes mellitus and chronic hypertension were excluded. Hospitalization costs were estimated separately for women and infants using hospital charges adjusted using a cost-to-charge ratio. These costs included hospitalization costs for admission for delivery only. We estimated the differences in median costs between seven categories of pre-pregnancy BMIs, including underweight (BMI <18.5), normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), class I obesity (BMI 30.0-34.9), class II obesity (BMI 35.0-39.9), class III obesity (BMI 40.0-49.9) and obesity with BMI ≥50.0. We also performed stratified analyses by mode of delivery and gestational age at delivery. We examined the length of stay for women and infants and estimated the gestational age at delivery. Analyses were conducted utilizing Kruskal-Wallis equality-of-populations rank tests with a significance cutoff of 0.05. RESULTS: In a California cohort of 1,722,840 women, 787,790 (45.7%) had a pre-pregnancy BMI that was considered overweight or obese. The median maternal and infant costs of each pre-pregnancy BMI strata were significantly different when compared to other strata, with underweight and normal weight women having the lowest median costs ($11,581 and $11,721, respectively) and the most obese category (BMI ≥50) having the highest costs ($15,808). When stratified by mode of delivery and gestational age at delivery, this remained true. Hospitalization costs for women and infants with severe maternal morbidity were also significantly different based on maternal BMI. COMMENT: The hospitalization costs associated with each strata of BMI were significantly different when compared to each other and when stratified by mode of delivery and prematurity. This analysis allows for a greater understanding of the health care costs associated with different maternal pre-pregnancy BMI classes.

Cost-effectiveness of influenza vaccination during pregnancy.

OBJECTIVE: To assess the cost-effectiveness of influenza vaccination for all pregnant patients in the United States. METHODS: We designed a cost-effectiveness model to compare outcomes and costs in pregnant patients who received the inactivated, trivalent influenza vaccine to those who did not. We used a theoretical cohort of 4 million patients, the number of individuals giving birth in the United States per year. We assumed that H1N1 and A or B type influenza were of equal incidence based on seasonal variation from the past ten years. Our outcomes include acquiring H1N1, acquiring A or B type influenza, maternal death, stillbirth, infant death, preterm birth, and cerebral palsy in addition to cost and quality-adjusted life years (QALYs). Probabilities were derived from the literature and QALYs generated at a discount rate of 3%. Sensitivity analyses were performed to assess the robustness of our model. RESULTS: In our theoretical cohort of 4 million pregnant patients, the influenza vaccination strategy was associated with 1632 fewer stillbirths (24,332 in the vaccine strategy vs. 25,964 in the no vaccine strategy), 120 fewer maternal deaths (284 vs. 404), 340 fewer infant deaths (5608 vs. 5948), 32,856 fewer preterm births (403,896 vs. 436,752), and 641 fewer cases of moderate cerebral palsy (12,388 vs. 13,029). Additionally, the vaccination strategy corresponded to savings of $3.7 billion ($63.3 billion vs. $67.0 billion) and increased QALYs of 81,696 (226,852,076 vs 226,770,380). Therefore, it was considered a dominant strategy. Univariate sensitivity analysis demonstrated that the vaccine is cost saving until vaccine cost passes $900, far above the current cost of $12.16. In addition, we used sensitivity analysis to vary seasonal proportions of H1N1 to A or B type influenza. The vaccine was cost saving and increased QALYs for any proportion of H1N1 to A or B type influenza including when H1N1 was absent. CONCLUSION: We demonstrate that in a cohort of 4 million patients, the influenza vaccine may save $3.7 billion per year, improve maternal and infant outcomes, and reduce morbidity and mortality. Our study provides further evidence that providers should strongly recommend that pregnant patients receive their annual influenza vaccine.

Adverse pregnancy outcomes associated with maternal syphilis infection.

BACKGROUND: Syphilis infections affect many pregnant women worldwide every year. The increasing rates of maternal and congenital syphilis infections in recent years in the United States necessitates further investigation into the adverse effects of syphilis infection on maternal and neonatal health. OBJECTIVE: We sought to examine the association of maternal syphilis infection with adverse pregnancy and perinatal outcomes. METHODS: We performed a retrospective cohort study of women with singleton pregnancies who delivered between 23 and 42 weeks in California between 2007 and 2011. We compared demographic characteristics and pregnancy outcomes between pregnant women with syphilis and without syphilis. Maternal outcomes of interest included gestational hypertension, pre-eclampsia, gestational diabetes, preterm delivery, cesarean delivery, induction of labor, and severe maternal morbidity. Neonatal outcomes included neonatal intensive care unit admission, congenital anomaly, congenital syphilis, small for gestational age, stillbirth, neonatal death, infant death. Descriptive statistics were assessed using chi-square/Fisher's Exact tests. Multivariable logistic regression was used to estimate the association between syphilis and adverse pregnancy and perinatal outcomes. Statistical comparisons with a p-value of less than .05 and 95% CI that did not cross the null were considered statistically significant. RESULTS: Among a cohort of 2,566,246 women, there were 991 pregnancies complicated by maternal infection with syphilis (0.04%). We found during multivariable logistic regression that syphilis infection was significantly associated with preterm delivery (aOR: 1.27, 95% CI: 1.05-1.54), NICU admission >24 h (aOR: 2.54, 95% CI: 2.13-3.04) and stillbirth (aOR: 5.01, 95% CI: 3.16-7.92) after adjusting for a number of potential confounders including maternal age, race/ethnicity, education, parity, prenatal visits, body mass index, smoking and insurance status. CONCLUSION: Maternal syphilis infection in pregnancy is associated with specific adverse pregnancy outcomes, even after adjusting for potential confounders. These data can be used to counsel patients with syphilis in pregnancy, and in developing approaches to clinical care. Due to the increased risk of stillbirth, perhaps such patients should receive antenatal testing. Further research is necessary to investigate the mechanisms of morbidity.

Obstetric management for stillbirth complicated by a prior cesarean delivery: a cost-effectiveness analysis.

BACKGROUND: The primary concern for a trial of labor after cesarean (TOLAC) is a uterine rupture leading to neonatal injury or mortality and maternal mortality. In individuals who have a term stillbirth, the neonatal concern is absent, yet repeat cesarean delivery remains common in this setting. Given the increased maternal risks from cesarean, it is important to evaluate obstetric management options in the population of women who have a term stillbirth and prior cesarean delivery (CD). OBJECTIVES: To examine the outcomes and costs of a TOLAC via induction of labor verses a repeat CD for cases of stillbirth occurring near term. STUDY DESIGN: A decision-analytic model incorporating the current and a subsequent delivery using TreeAge software was designed to compare outcomes in women induced for a TOLAC to those undergoing repeat CD in the setting of stillbirth at 34-41 weeks' gestation. We used a theoretical cohort of 6000 women, the estimated annual number of women a prior cesarean who experience a stillbirth in the United States. Outcomes included quality-adjusted life years (QALY) for both modes of delivery with consideration of future pregnancy risks. Future pregnancy risks included uterine rupture, hysterectomy, placenta accreta, maternal death, neonatal death, and neonatal neurological deficits. Probabilities were derived from the literature, and a cost-effectiveness threshold was set at $100,000/QALY. RESULTS: In our theoretical cohort of 6000 women with a prior CD and current stillbirth, induction of labor resulted in 4836 fewer cesarean deliveries during stillbirth management, 1040 fewer cesarean deliveries in the subsequent pregnancy, and 14 fewer cases of placenta accreta in the subsequent pregnancy, despite 29 additional uterine ruptures across both pregnancies. Induction of labor was found to be the dominant strategy, resulting in decreased costs and increased QALYs. Univariate sensitivity analyses demonstrated that induction of labor was cost effective until the risk of uterine rupture in the first delivery exceeded 0.83% (baseline estimate: 0.38%). Additional univariate sensitivity analyses found that induction of labor was cost effective until the risk of IOL failure in the first delivery exceeded 64% (baseline estimate: 19%). CONCLUSION: In our theoretical cohort, induction of labor for TOLAC in the setting of a stillbirth with a history of prior CD is cost effective compared to a repeat CD. The results of this analysis demonstrate the benefit of induction of labor among women in this scenario who desire a future pregnancy.

A cost-effectiveness analysis of universal hepatitis C screening in all United States pregnancies.

OBJECTIVE: To evaluate the cost-effectiveness of universal screening for HCV among all pregnant women in the United States. METHODS: We designed a decision-analytic model to evaluate the cost-effectiveness and outcomes associated with universal HCV screening in pregnancy compared to no screening. A theoretical cohort of 3.9 million women, the approximate number of annual live births in the United States was used. Outcomes included hepatocellular carcinoma, decompensated cirrhosis, liver transplant and death, in addition to cost and quality-adjusted life years (QALYs). Model inputs were derived from the literature and the willingness-to-pay threshold was $100,000 per QALY. Sensitivity analysis were conducted to evaluate the robustness of the results. RESULTS: In a theoretical cohort of 3.9 million women, universal HCV screening resulted in 3003 fewer cases of hepatocellular carcinoma, 1484 fewer decompensated cirrhosis, 46 fewer liver transplants and 2665 fewer deaths from HCV when compared to no screening. Universal HCV screening was found to be the dominant strategy, meaning it resulted in lower costs and higher QALYs. Sensitivity analyses showed our model was robust over a wide range of assumptions. CONCLUSION: Among pregnant women in the United States, universal HCV screening is cost effective compared with no screening.