Cell-free fetal DNA screening for detection of microdeletion syndromes: a cost-effectiveness analysis.

OBJECTIVE: Fetuses with genetic copy number variants are poorly detected through traditional prenatal screening. Microdeletions and duplications are clearly identified with diagnostic testing through chromosomal microarray, and screening of a select number of microdeletions has become available with cell-free DNA (cfDNA). Our study compares the costs and outcomes of cfDNA for five pathogenic microdeletions and aneuploidy to cfDNA for aneuploidy alone in conjunction with ultrasound. METHODS: A decision-analytic model was constructed using TreeAge software to compare cfDNA with microdeletions versus traditional cfDNA in a theoretical cohort of 4,000,000 pregnancies that would also be screened with ultrasound. Probabilities, costs, and utilities were derived from literature. The primary outcomes were the incremental cost per quality-adjusted life-year (QALY), terminations, and procedure-related losses. Because the microdeletion results are available, but not reported, on all cfDNA testing we set the incremental cost of the cfDNA microdeletion screening test to zero at baseline and varied the cost in sensitivity analysis. RESULTS: Screening with cfDNA for microdeletions among all pregnant women would result in 83 fewer anomalous neonates compared to traditional cfDNA with ultrasound. This reduction is due to increased diagnosis and termination of fetuses with microdeletions in this group. Routine use of cfDNA with microdeletions resulted in more procedure-related losses. cfDNA with microdeletions would improve effectiveness by 977 QALYs and decrease costs by $90,991,784. When we varied the specificity of the screening test, we found that it remained cost-effective down to a specificity of 91%. With a threshold of $100,000/QALY, microdeletion screening is cost-effective to an incremental increase in cost over cfDNA for aneuploidy alone of $47.10. CONCLUSION: For detection of fetal subchromosomal abnormalities, use of cfDNA with microdeletions is a cost-effective strategy compared to cfDNA for aneuploidy alone in conjunction with ultrasound. Cell-free DNA for microdeletions is not currently recommended as routine screening for low-risk obstetric populations by the American College of Obstetrics and Gynecologists or the Society for Maternal-Fetal Medicine. The test characteristics of cfDNA with microdeletions require greater examination before being routinely recommended.

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..

Type-2 diabetes mellitus: does prenatal care affect outcomes?

OBJECTIVE: To determine if prenatal care affects adverse perinatal outcomes in pregnant women with Type-2 diabetes mellitus (T2DM). STUDY DESIGN: This was a retrospective cohort study of pregnant women with pregestational diabetes mellitus pregnancies in the state of California between 1997 and 2006, using vital statistics data linked to birth certificates. Women were stratified by time of presentation to care and we compared those who presented in the first trimester, third trimester, and those who had no prenatal care prior to delivery. Perinatal outcomes looked at included: preeclampsia, macrosomia, preterm delivery, cesarean delivery, and intrauterine fetal demise (IUFD). The two groups were compared with chi-squared testing to determine statistical significance. RESULTS: In women with pregestational diabetes those who presented at time of delivery had an 11.3% risk of IUFD compared to 0.9% in those who presented in the first trimester. There was also an increased rate of preterm birth in the late presentation cohort (29.4% at time of delivery versus 21.0% in the first trimester). After adjusting for possible confounding variables using logistic regression models, rates of IUFD and preterm delivery were still found to be statistically significant with adjusted odds ratios of 11.37 (95% CI: 6.10-21.16) and 1.55 (95% CI: 1.03-2.32), respectively. There were no differences in rates of macrosomia or preeclampsia between the three cohorts. CONCLUSIONS: Treatment of T2DM throughout pregnancy leads to improved maternal and neonatal outcomes.

Social media and the intrauterine device: a YouTube content analysis.

BACKGROUND: YouTube's online archive of video testimonials related to health information are more commonly viewed than those developed by clinicians and professional groups, suggesting the importance of the patient experience to viewers. We specifically sought to examine the accuracy of information on, and projected acceptability of, the intrauterine device (IUD) from these YouTube testimonials. METHODS: We searched YouTube for videos about individual uploaders' IUD experiences, using the search terms 'intrauterine device', 'IUD', 'Mirena' and 'Paragard'. Given interest in user testimonials, we excluded professional and instructional videos belonging to commercial or non-profit entities. Two reviewers independently analysed the videos using a structured guide, with attention to inaccurate information. RESULTS: Of 86 identified videos, four videos featured clinicians and were excluded; 62 met inclusion criteria. Interrater agreement on IUD portrayal was good (K=0.73). Young (mean age 25, range 19-38, years), white (75%), nulliparous (61%) women primarily uploaded content. Most described placement of the LNG-IUS (65%), were posted within 1 month of insertion (45%), and mentioned side effects (66%) - bleeding, pain, and partner sensation of the strings. About one-third of videos contained inaccurate information (34%) and were thought to project an overall negative experience (30%). Videos portraying IUDs negatively were associated with inaccurate information and/or mention of side effects. CONCLUSION: While one-third of IUD user testimonials on YouTube contained inaccurate information, the majority of IUD experiences were perceived by our study viewers to be positive.

The Evolution of the Laborist.

The laborist movement was introduced as a means to improve the quality of care patients receive in the labor suite and decrease physician burnout and malpractice claims. This model of care has rapidly expanded, and there is evidence of its potential role in improving labor outcomes. This article outlines the different models of laborist care, reviews the evidence for its potential impact on labor outcomes, and discusses the economic impact the employment of laborists can have.

A recurrent endometrial stromal sarcoma harbors the novel fusion JAZF1-BCORL1.

•Genomic alterations may improve diagnostic certainty and subsequent treatment of endometrial stromal sarcoma.•Novel JAZF1-BCORL1 mutation was identified.•Targeted therapeutics to down-stream targets may improve survival benefit in these patients.

Cost-Effectiveness Analysis of Latent versus Active Labor Hospital Admission for Medically Low-Risk, Term Women.

OBJECTIVE: To assess the outcomes and costs of hospital admission during the latent versus active phase of labor. Latent labor hospital admission has been consistently associated with elevated maternal risk for increased interventions, including epidural anesthesia and cesarean delivery, longer hospital stay, and higher utilization of hospital resources. METHODS: A cost-effectiveness model was built to simulate a theoretic cohort of 3.2 million term, medically low-risk women either being admitted in latent labor (< 4 cm dilation) or delaying admission until active labor (≥ 4 cm dilation). Outcomes included epidural use, mode of delivery, stillbirth, maternal death, and costs of care. All probability, cost, and utility estimates were derived from the literature, and total quality-adjusted life years were calculated. Sensitivity analyses and a Monte Carlo simulation were used to investigate the robustness of model assumptions. RESULTS: Delaying admission until active labor would result in 672,000 fewer epidurals, 67,232 fewer cesarean deliveries, and 9.6 fewer maternal deaths in our theoretic cohort as compared to admission during latent labor. Additionally, delaying admission results in a cost savings of $694 million annually in the United States. Sensitivity analyses indicated the model was robust within a wide range of probabilities and costs. Monte Carlo simulation found that delayed admission was the optimal strategy in 76.79 percent of trials. CONCLUSION: Delaying admission until active labor is a dominant strategy, resulting in both better outcomes and lower costs. Issues related to clinical translation of these findings are explored.

Intrahepatic cholestasis of pregnancy and timing of delivery.

OBJECTIVE: We examined the morbidities from delivery at earlier gestational ages versus intrauterine fetal demise (IUFD) for women with intrahepatic cholestasis of pregnancy (ICP) to determine the optimal gestational age for delivery. METHODS: A decision-analytic model was created to compare delivery at 35 through 38 weeks gestation for different delivery strategies: (1) empiric steroids; (2) steroids if fetal lung maturity (FLM) negative; (3) wait a week and retest if FLM negative; or (4) deliver immediately. Literature review identified 18 studies that estimated IUFD in ICP; we used the mean rate, 1.74%, and assumed a uniform distribution from 34 to 40 weeks gestation. Large cohort data was used to calculate neonatal morbidity rates at each gestational age. Maternal and neonatal quality-adjusted life years (QALYs) were combined. Univariate sensitivity and Monte Carlo analyses were performed to test for robustness. RESULTS: Immediate delivery at 36 weeks without FLM testing and steroid administration was the optimal strategy as compared to delivery at 36 weeks with steroids (+47 QALYs) and as compared to immediate delivery at 35 weeks (+210 QALYs). Our results were robust up to a 30% increase in the rate of IUFD. CONCLUSION: Immediate delivery at 36 weeks in women with ICP is the optimal delivery strategy.

Resuscitation of neonates at 23 weeks' gestational age: a cost-effectiveness analysis.

OBJECTIVE: Resuscitation of infants at 23 weeks' gestation remains controversial; clinical practices vary. We sought to investigate the cost effectiveness of resuscitation of infants born 23 0/7-23 6/7 weeks' gestation. DESIGN: Decision-analytic modeling comparing universal and selective resuscitation to non-resuscitation for 5176 live births at 23 weeks in a theoretic U.S. cohort. Estimates of death (77%) and disability (64-86%) were taken from the literature. Maternal and combined maternal-neonatal utilities were applied to discounted life expectancy to generate QALYs. Incremental cost-effectiveness ratios were calculated, discounting costs and QALYs. Main outcomes included number of survivors, their outcome status and incremental cost-effectiveness ratios for the three strategies. A cost-effectiveness threshold of $100 000/QALY was utilized. RESULTS: Universal resuscitation would save 1059 infants: 138 severely disabled, 413 moderately impaired and 508 without significant sequelae. Selective resuscitation would save 717 infants: 93 severely disabled, 279 moderately impaired and 343 without significant sequelae. For mothers, non-resuscitation is less expensive ($19.9 million) and more effective (127 844 mQALYs) than universal resuscitation ($1.2 billion; 126 574 mQALYs) or selective resuscitation ($845 million; 125 966 mQALYs). For neonates, both universal and selective resuscitation were cost-effective, resulting in 22 256 and 15 134 nQALYS, respectively, versus 247 nQALYs for non-resuscitation. In sensitivity analyses, universal resuscitation was cost-effective from a maternal perspective only at utilities for neonatal death <0.42. When analyzed from a maternal-neonatal perspective, universal resuscitation was cost-effective when the probability of neonatal death was <0.95. CONCLUSIONS: Over wide ranges of probabilities for survival and disability, universal and selective resuscitation strategies were not cost-effective from a maternal perspective. Both strategies were cost-effective from a maternal-neonatal perspective. This study offers a metric for counseling and decision-making for extreme prematurity. Our results could support a more permissive response to parental requests for aggressive intervention at 23 weeks' gestation.

Handheld ultrasound versus physical examination in patients referred for transthoracic echocardiography for a suspected cardiac condition.

OBJECTIVES: The purpose of this study was to test the hypothesis that handheld ultrasound (HHU) provides a more accurate diagnosis than physical examination in patients with suspected cardiovascular abnormalities and that its use thus reduces additional testing and overall costs. BACKGROUND: Despite the limitations of physical examination and the demonstrated superiority of HHU for detecting cardiac abnormalities, it is not routinely used for the bedside diagnosis of cardiac conditions. METHODS: Patients referred for a standard echocardiogram for common indications (cardiac function, murmur, stroke, arrhythmias, and miscellaneous) underwent physical examination and HHU by different cardiologists, who filled out a form that also included suggestions for additional testing, if necessary, based on their findings. RESULTS: Of 250 patients, 142 had an abnormal finding on standard echocardiogram. Of these, HHU correctly identified 117 patients (82%), and physical examination correctly identified 67 (47%, p < 0.0001). HHU was superior to physical examination (p < 0.0001) for both normal and abnormal cardiac function. It was also superior to physical examination in correctly identifying the presence of substantial valve disease (71% vs. 31%, p = 0.0003) and in identifying miscellaneous findings (47% vs. 3%, p < 0.0001). Of 108 patients without any abnormalities on standard echocardiography, further testing was suggested for 89 (82%) undergoing physical examination versus only 60 (56%) undergoing HHU (p < 0.0001). Cost modeling showed that HHU had an average cost of $644.43 versus an average cost of $707.44 for physical examination. This yielded a savings of $63.01 per patient when HHU was used versus physical examination. CONCLUSIONS: When used by cardiologists, HHU provides a more accurate diagnosis than physical examination for the majority of common cardiovascular abnormalities. The finding of no significant abnormality on HHU is also likely to result in less downstream testing and thus potentially reduce the overall cost for patients being evaluated for a cardiovascular diagnosis.

Prohibiting consent: what are the costs of denying permanent contraception concurrent with abortion care?

OBJECTIVE: Oregon and federal laws prohibit giving informed consent for permanent contraception when presenting for an abortion. The primary objective of this study was to estimate the number of unintended pregnancies associated with this barrier to obtaining concurrent tubal occlusion and abortion, compared with the current policy, which limits women to obtaining interval tubal occlusion after abortion. The secondary objectives were to compare the financial costs, quality-adjusted life years, and the cost-effectiveness of these policies. STUDY DESIGN: We designed a decision-analytic model examining a theoretical population of women who requested tubal occlusion at time of abortion. Model inputs came from the literature. We examined the primary and secondary outcomes stratified by maternal age (>30 and <30 years). A Markov model incorporated the possibility of multiple pregnancies. Sensitivity analyses were performed on all variables and a Monte Carlo simulation was conducted. RESULTS: For every 1000 women age <30 years in Oregon who did not receive requested tubal occlusion at the time of abortion, over 5 years there would be 1274 additional unintended pregnancies and an additional $4,152,373 in direct medical costs. Allowing women to receive tubal occlusion at time of abortion was the dominant strategy. It resulted in both lower costs and greater quality-adjusted life years compared to allowing only interval tubal occlusion after abortion. CONCLUSION: Prohibiting tubal occlusion at time of abortion resulted in an increased incidence of unintended pregnancy and increased public costs.