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.

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..

Does obesity influence the preferred treatment approach for early-stage cervical cancer? A cost-effectiveness analysis.

OBJECTIVE: Abdominal radical hysterectomy in early-stage cervical cancer has higher rates of disease-free and overall survival compared with minimally invasive radical hysterectomy. Abdominal radical hysterectomy may be technically challenging at higher body mass index levels resulting in poorer surgical outcomes. This study sought to examine the influence of body mass index on outcomes and cost effectiveness between different treatments for early-stage cervical cancer. METHODS: A Markov decision-analytic model was designed using TreeAge Pro software to compare the outcomes and costs of primary chemoradiation versus surgery in women with early-stage cervical cancer. The study used a theoretical cohort of 6000 women who were treated with abdominal radical hysterectomy, minimally invasive radical hysterectomy, or primary chemoradiation therapy. We compared the results for three body mass index groups: less than 30 kg/m2, 30-39.9 kg/m2, and 40 kg/m2 or higher. Model inputs were derived from the literature. Outcomes included complications, recurrence, death, costs, and quality-adjusted life years. An incremental cost-effectiveness ratio of less than $100 000 per quality-adjusted life year was used as our willingness-to-pay threshold. Sensitivity analyses were performed broadly to determine the robustness of the results. RESULTS: Comparing abdominal radical hysterectomy with minimally invasive radical hysterectomy, abdominal radical hysterectomy was associated with 526 fewer recurrences and 382 fewer deaths compared with minimally invasive radical hysterectomy; however, abdominal radical hysterectomy resulted in more complications for each body mass index category. When the body mass index was 40 kg/m2 or higher, abdominal radical hysterectomy became the dominant strategy because it led to better outcomes with lower costs than minimally invasive radical hysterectomy. Comparing abdominal radical hysterectomy with primary chemoradiation therapy, recurrence rates were similar, with more deaths associated with surgery across each body mass index category. Chemoradiation therapy became cost effective when the body mass index was 40 kg/m2 or higher. CONCLUSION: When the body mass index is 40 kg/m2 or higher, abdominal radical hysterectomy is cost saving compared with minimally invasive radical hysterectomy and primary chemoradiation is cost effective compared with abdominal radical hysterectomy. Primary chemoradiation may be the optimal management strategy at higher body mass indexes.

What is the Cost-Effective Treatment for Melanoma Patients with a Positive Sentinel Node?

BACKGROUND: Survival for positive sentinel lymph node (SLN) patients does not differ between completion lymph node dissection (CLND) and nodal observation (OBS). However, treating these patients with CLND and checkpoint inhibitors, such as pembrolizumab (PEM), improves outcomes. This study evaluated the cost-effectiveness of OBS, CLND, and CLND with PEM (CLND-PEM) treatments. METHODS: A Markov model was designed to simulate treatment for a theoretical cohort of 1000 positive SLN patients per therapy with a 5-year follow-up period. An intervention was cost-effective if its incremental cost-effectiveness ratio among therapies was below the willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY). RESULTS: Compared with CLND or CLND-PEM, OBS resulted in fewer lymphedema cases but in more disease recurrences. Compared with OBS, CLND had higher costs and lower QALYs. Although CLND-PEM had a lower number of recurrences and deaths than OBS or CLND, it had higher costs and lower QALYs than OBS, and thus was not cost-effective. However, with the effects of CLND from CLND-PEM removed, allowing evaluation of PEM effects alone (PEM alone), the resulting QALYs were the highest, but PEM alone still was not cost-effective compared with OBS ($1.2 million per QALY). By reducing the drug cost to less than $14,404 per patient, PEM alone would become cost-effective. CONCLUSIONS: Compared with CLND, CLND-PEM, and PEM alone, OBS was cost-effective for managing positive SLN patients. Although CLND-PEM and PEM alone result in fewer recurrences and deaths, these therapies were not cost-effective due to the quality-of-life decrement of CLND and the current high drug cost of PEM.

Pharmacists' perspectives and experience prescribing hormonal contraception in rural and urban New Mexico.

BACKGROUND: Pharmacist prescription of contraception is becoming increasingly common in the United States (US). Limited information exists on whether this is improving access to contraception in underserved areas, including rural America. OBJECTIVE: We sought to determine whether there were differences by rural location in pharmacists' willingness to prescribe hormonal contraception and perceived barriers to doing so. METHODS: We conducted a cross-sectional survey of pharmacists eligible to prescribe hormonal contraception in New Mexico in March and May 2020. The survey consisted of demographic data, pharmacists' experience prescribing hormonal contraception, and questions regarding perceived barriers to pharmacist-prescribed hormonal contraception. Descriptive statistics assessed differences in survey responses between rural and urban pharmacists. We used multivariable logistic regression to estimate the association between rural practice and prescribing hormonal contraception. RESULTS: Our sampling frame consisted of 822 licensed pharmacists. We received 256 responses, for a response rate of 31.1%. We found that rural pharmacists were as likely as their urban counterparts to prescribe hormonal contraception (adjusted odds ratio 1.22 [95% CI 0.56-2.68], P = 0.50). Five main barriers included a need for additional training, reimbursement for services, liability concerns, corporate policies, and shortage of staff. No difference in barriers were identified by rural location or staff role. CONCLUSION: Pharmacy access has the potential to improve access to contraception across New Mexico, including underserved rural areas.

Isolated echogenic intracardiac foci and the role of cell-free fetal DNA: A cost-effectiveness analysis.

OBJECTIVES: Cell-free fetal DNA (cfDNA) has been increasingly incorporated into prenatal aneuploidy screening paradigms given its relatively high sensitivity for Down syndrome (DS). This is often the case when fetal ultrasonographic soft markers are present, such as the relatively common echogenic intracardiac focus (EIF). We sought to evaluate the cost-effectiveness of a screening strategy that included cfDNA screening when an isolated EIF is identified in a low-risk population with prior aneuploidy screening. METHODS: A decision-analytic model was constructed using TreeAge software with probabilities derived from the literature. Our model compared cfDNA screening following isolated EIF detection in women less than 35 years with prior reassuring first trimester screen compared to a strategy of no further aneuploidy screening. Strategies were compared to generate an incremental cost-effectiveness ratio with a threshold of $100 000/quality-adjusted life year (QALY) and applied to a theoretical cohort. RESULTS: The cfDNA strategy resulted in 21 fewer DS births and 52 additional QALYs, however, increased costs by $51.3 million. This yielded an incremental cost-effectiveness ratio of $986 503; therefore, it was not a cost-effective strategy. CONCLUSION: In a low-risk population with prior reassuring aneuploidy screening, it is not cost effective to offer cfDNA after identification of an isolated EIF.

Cost-Effectiveness of Implantable Cardioverter-Defibrillators in Children with Cardiac Conditions Associated with Risk for Sudden Cardiac Death.

Children at high risk for sudden cardiac death (SCD) receive implantable cardioverter-defibrillators (ICD) for prevention, but the cost effectiveness of ICDs in children at intermediate risk is unclear. Our objective was to create a cost-effectiveness model to compare costs and outcomes in children at risk of SCD, with and without ICD. Utilizing hypertrophic cardiomyopathy as the proxy disease, a theoretical cohort of 8150 children was followed for 69 years. Model inputs were derived from the literature, with an incremental cost-effectiveness ratio (ICER) willingness-to-pay threshold of $100,000/quality-adjusted life year (QALY) used to delineate cost effectiveness. Outcomes included prevalence of severe neurological morbidity (SNM), SCD, cost, and QALYs. In children at intermediate risk of SCD (4-6% over 5 years), ICD resulted in 56 fewer cases of SNM, 2686 fewer deaths. In children at high risk (> 6% over 5 years), ICD placement resulted in 74 fewer cases of SNM and 3663 fewer deaths from cardiac causes. The costs of ICD were higher, but placement was cost effective with an ICER of $3009 per QALY in intermediate risk children, but ICD therapy was a dominant strategy in high-risk children. Sensitivity analysis demonstrated ICD placement was cost-effective until the annual probability of SCD was < 0.22%. The model was robust over a wide range of values. For children at risk of SCD, prophylactic ICD implantation is cost effective, resulting in improved outcomes and increased QALYs, despite increased costs. These findings highlight the economic benefits of ICD utilization in this population.

Antenatal Corticosteroids for Pregnant Women at High Risk of Preterm Delivery with COVID-19 Infection: A Decision Analysis.

OBJECTIVE: Antenatal corticosteroids given prior to preterm deliveries reduce the risk of adverse neonatal outcomes. However, steroid administration in the setting of a viral respiratory infection can worsen maternal outcomes. Therefore, the decision to administer corticosteroids must balance the neonatal benefits with the potential harm to the mother if she is infected with the novel coronavirus disease 2019 (COVID-19). This study aimed to determine the gestational ages for which administering antenatal corticosteroids to women at high risk of preterm labor with concurrent COVID-19 infection results in improved combined maternal and infant outcomes. STUDY DESIGN: A decision-analytic model using TreeAge (2020) software was constructed for a theoretical cohort of hospitalized women with COVID-19 in the United States. All model inputs were derived from the literature. Outcomes included maternal intensive care unit (ICU) admission and death, along with infant outcomes of death, respiratory distress syndrome, intraventricular hemorrhage, and neurodevelopmental delay. Quality-adjusted life years (QALYs) were assessed from the maternal and infant perspectives. Sensitivity analyses were performed to determine if the results were robust over a range of assumptions. RESULTS: In our theoretical cohort of 10,000 women delivering between 24 and 33 weeks of gestation with COVID-19, corticosteroid administration resulted in 2,200 women admitted to the ICU and 110 maternal deaths. No antenatal corticosteroid use resulted in 1,500 ICU admissions and 75 maternal deaths. Overall, we found that corticosteroid administration resulted in higher combined QALYs up to 31 weeks of gestation in all hospitalized patients, and up to 29 weeks of gestation in ICU patients. CONCLUSION: Administration of antenatal corticosteroids at less than 32 weeks of gestation for hospitalized patients and less than 30 weeks of gestation for patients admitted to the ICU resulted in higher combined maternal and infant outcomes compared with expectant management for women at high risk of preterm birth with COVID-19 infection. These results can guide clinicians in their counseling and management of these pregnant women. KEY POINTS: · Antenatal steroids reduce adverse neonatal outcomes.. · Steroids worsen maternal outcomes in COVID-19.. · Steroids given < 32 weeks result in improved outcomes..

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 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.

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.

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.

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.

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.

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.

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.

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.

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.