Cost-effectiveness of BRCA1 testing at time of obstetrical prenatal carrier screening for cancer prevention.

BACKGROUND: Improved technologies paired with an increase in access to genetic testing have led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time when precancer screening, chemoprevention, and/or risk-reducing surgery may be beneficial. OBJECTIVE: This study aimed to inform clinical decision-making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective. STUDY DESIGN: A decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years were used to simulate the lifespan of patients. The setting was obstetrical clinics in the United States, and the participants were a theoretical cohort of 1,429,074 pregnant patients who annually underwent expanded carrier screening. RESULTS: Among our cohort, BRCA1 testing resulted in the identification of an additional 3716 BRCA1-positive patients, the prevention of 1394 breast and ovarian cancer cases, and 1084 fewer deaths. BRCA1 testing was a cost-effective strategy compared with no BRCA1 testing with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life years. In a 1-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0.00% to 20.00% and found that BRCA1 testing continued to be the cost-effective strategy until the prevalence rate was reduced to 0.16%. Multiple additional sensitivity analyses did not substantially affect the cost-effectiveness. CONCLUSION: The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing.

Procalcitonin levels in pregnancy: A systematic review and meta-analysis of observational studies.

BACKGROUND: The utility of procalcitonin to identify obstetric sepsis is unknown. OBJECTIVE: To calculate the mean (range) procalcitonin in pregnancy among healthy women not in labor (group 1), healthy women in labor (group 2), and women with preterm prelabor rupture of membranes (PPROM) without clinical chorioamnionitis (group 3). SEARCH STRATEGY: NLM PubMed, Elsevier Embase, and Wiley Cochrane Central Register of Controlled Trials from inception to February 21, 2022. SELECTION CRITERIA: Ten or more pregnant women with procalcitonin reported at more than 20 weeks of pregnancy, with information on labor, PPROM, and infection. Exclusions were major medical comorbidities. DATA COLLECTION AND ANALYSIS: Each abstract and full-text review was independently reviewed by the same two authors. Quality was reviewed using the Newcastle-Ottawa Scale. A meta-analysis was performed using a random effects model. MAIN RESULTS: The systematic review included 25 studies: 10 (40%) of good quality and 15 (60%) of poor quality. The meta-analysis included 21 studies. Mean procalcitonin in group 1 was 0.092 ng/mL (range 0.036-0.049 ng/mL), in group 2 it was 0.130 ng/mL (range 0.049-0.259 ng/mL), and in group 3 it was 0.345 ng/mL (range 0.005-1.292 ng/mL). CONCLUSIONS: Among healthy pregnant women not in labor, procalcitonin levels are comparable to those in non-pregnant adults and may be useful in identifying infection. Procalcitonin levels in other groups overlap abnormal values of procalcitonin in non-pregnant adults, and may not discriminate infection among women in labor or with obstetric comorbidities. PROSPERO: CRD42020157376, registered 4/28/2020.

Association between programmed frozen embryo transfer and hypertensive disorders of pregnancy.

Dissociation of embryo transfer from the ovarian stimulation cycle has afforded patients increased flexibility for genetic testing and fertility preservation. Although frozen embryo transfer (FET) has largely been demonstrated to be safe and effective compared with fresh transfer, programmed FET cycles, where a corpus luteum is absent, have come under increasing scrutiny. In observational trials, programmed FET protocols appear to be associated with an increased risk of ineffective decidualization and impaired placental function. Together with the appropriate preexisting risk factors, this additive risk may potentiate hypertensive disorders of pregnancy later in gestation. Efforts to understand the reasons for this apparent risk may afford us opportunities to better individualize the FET cycle type offered to patients with cryopreserved embryos. Randomized controlled trials will help us to understand whether the apparent risk is due to patient factors, which influence protocol choice, or a characteristic of the protocol itself, such as the absence of the corpus luteum or suboptimal replacement of estradiol and progesterone.

Challenges in Interpreting the Ob/Gyn Literature: Studies of Screening.

Screening tests are critical to patient care. Screening tests must meet ten criteria established by the World Health Organization in order to be considered effective. Common types of studies on screening tests include those that establish test characteristics, such as sensitivity, specificity, positive predictive value, and negative predictive value, as well as cost-effective analyses. In this paper, we review the criteria for effective screening tests, and discuss the strengths and pitfalls of common study designs evaluating screening tests.

Universal Hepatitis B Antibody Screening and Vaccination in Pregnancy: A Cost-Effectiveness Analysis.

OBJECTIVE: To evaluate the cost effectiveness of universal screening for hepatitis B immunity and vaccination among pregnant women in the United States. METHODS: We designed a decision-analytic model to evaluate the outcomes, costs, and cost effectiveness associated with universal hepatitis B virus (HBV) immunity screening in pregnancy with vaccination of susceptible individuals compared with no screening. A theoretical cohort of 3.6 million women, the approximate number of annual live births in the United States, was used. Outcomes included cases of HBV, 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 $50,000 per QALY. Univariate sensitivity analyses and Monte Carlo simulation models were performed to evaluate the robustness of the results. RESULTS: In a theoretical cohort of 3.6 million women, universal HBV immunity screening and vaccination resulted in 1,702 fewer cases of HBV, seven fewer cases of decompensated cirrhosis, four fewer liver transplants, and 11 fewer deaths over the life expectancy of a woman after pregnancy. Universal screening and vaccination were found to be cost effective, with an incremental cost-effectiveness ratio of $1,890 per QALY. Sensitivity analyses demonstrated the model was robust even when the prevalence of HBV immunity was high and the annual risk of HBV acquisition low. CONCLUSION: Among pregnant women in the United States, universal HBV immunity screening and vaccination of susceptible persons is cost effective compared with not routinely screening and vaccinating.

Impact of Tobacco and Marijuana on Infertility and Early Reproductive Wastage.

Reducing exposure to tobacco and marijuana during preconception and early pregnancy is a critical area of intervention for obstetricians, gynecologists, and other reproductive health care professionals. Beyond the deleterious personal health effects, both substances have been extensively associated with short-term and long-term detrimental effects to gametogenesis, fecundity, as well as tissue level effects in the reproductive tracts. When tobacco and marijuana do not impair the ability to achieve pregnancy, an increasing body of literature suggests either may be associated with increased risk of early pregnancy loss and reproductive wastage. In this review, we will discuss what is known about how tobacco and marijuana affect the male and female reproductive systems and highlight how these consequences may impair attempts at successful conception and pregnancy continuation beyond the first trimester.

Association between low fetal fraction and hypertensive disorders of pregnancy in in vitro fertilization-conceived pregnancies.

BACKGROUND: Fetal fraction from noninvasive prenatal screening has been used as a predictive marker for hypertensive disorders of pregnancy in spontaneous pregnancies. OBJECTIVE: We aimed to determine whether fetal fraction from noninvasive prenatal screening predicts hypertensive disorders of pregnancy in pregnancies conceived by assisted reproductive technology, stratified by fresh and frozen embryo transfer. STUDY DESIGN: Retrospective cohort study of women with singleton pregnancies who underwent fresh or frozen embryo transfer, had noninvasive prenatal screening, and had a live birth >20 weeks at a single institution from 2013 to 2019. Women with major anomalies, nonreportable noninvasive prenatal screening, or chronic hypertension were excluded. Fetal fraction was corrected for gestational age, noninvasive prenatal screening platform, and defined as low if it is less than fifth percentile for the study population. The primary outcome was hypertensive disorders of pregnancy during delivery hospitalization, stratified by fresh vs frozen embryo transfer. We performed multivariable logistic regression analyses to determine whether low fetal fraction predicts hypertensive disorders of pregnancy for fresh and frozen embryo transfer, controlling for age, prepregnancy body mass index, heparin use, low-dose aspirin use, estradiol level if fresh embryo transfer, and trophectoderm biopsy and cycle type if frozen embryo transfer. RESULTS: We included 81 women with low fetal fraction and 847 women with normal fetal fraction. The adjusted prevalence of hypertensive disorders of pregnancy in women with low fetal fraction was 24.9% in fresh embryo transfer and 34.5% in frozen embryo transfer. In fresh embryo transfer pregnancies, the odds of hypertensive disorders of pregnancy were higher among women with low fetal fraction (adjusted odds ratio, 2.46; 95% confidence interval, 1.07-5.30; P=.026). In frozen embryo transfer pregnancies, there was no association between low fetal fraction and hypertensive disorders of pregnancy (adjusted odds ratio, 1.43; 95% confidence interval, 0.69-2.88; P=.321). CONCLUSION: Low fetal fraction is associated with hypertensive disorders of pregnancy in women who conceive by fresh embryo transfer. Fetal fraction may represent a clinically useful marker for screening for hypertension and allow clinicians to target risk reduction strategies, such as low-dose aspirin, in pregnancies conceived by fresh embryo transfer.

Society for Maternal-Fetal Medicine Consult Series #57: Evaluation and management of isolated soft ultrasound markers for aneuploidy in the second trimester: (Replaces Consults #10, Single umbilical artery, October 2010; #16, Isolated echogenic bowel diagnosed on second-trimester ultrasound, August 2011; #17, Evaluation and management of isolated renal pelviectasis on second-trimester ultrasound, December 2011; #25, Isolated fetal choroid plexus cysts, April 2013; #27, Isolated echogenic intracardiac focus, August 2013).

Soft markers were originally introduced to prenatal ultrasonography to improve the detection of trisomy 21 over that achievable with age-based and serum screening strategies. As prenatal genetic screening strategies have greatly evolved in the last 2 decades, the relative importance of soft markers has shifted. The purpose of this document is to discuss the recommended evaluation and management of isolated soft markers in the context of current maternal serum screening and cell-free DNA screening options. In this document, "isolated" is used to describe a soft marker that has been identified in the absence of any fetal structural anomaly, growth restriction, or additional soft marker following a detailed obstetrical ultrasound examination. In this document, "serum screening methods" refers to all maternal screening strategies, including first-trimester screen, integrated screen, sequential screen, contingent screen, or quad screen. The Society for Maternal-Fetal Medicine recommends the following approach to the evaluation and management of isolated soft markers: (1) we do not recommend diagnostic testing for aneuploidy solely for the evaluation of an isolated soft marker following a negative serum or cell-free DNA screening result (GRADE 1B); (2) for pregnant people with no previous aneuploidy screening and isolated echogenic intracardiac focus, echogenic bowel, urinary tract dilation, or shortened humerus, femur, or both, we recommend counseling to estimate the probability of trisomy 21 and a discussion of options for noninvasive aneuploidy screening with cell-free DNA or quad screen if cell-free DNA is unavailable or cost-prohibitive (GRADE 1B); (3) for pregnant people with no previous aneuploidy screening and isolated thickened nuchal fold or isolated absent or hypoplastic nasal bone, we recommend counseling to estimate the probability of trisomy 21 and a discussion of options for noninvasive aneuploidy screening through cell-free DNA or quad screen if cell-free DNA is unavailable or cost-prohibitive or diagnostic testing via amniocentesis, depending on clinical circumstances and patient preference (GRADE 1B); (4) for pregnant people with no previous aneuploidy screening and isolated choroid plexus cysts, we recommend counseling to estimate the probability of trisomy 18 and a discussion of options for noninvasive aneuploidy screening with cell-free DNA or quad screen if cell-free DNA is unavailable or cost-prohibitive (GRADE 1C); (5) for pregnant people with negative serum or cell-free DNA screening results and an isolated echogenic intracardiac focus, we recommend no further evaluation as this finding is a normal variant of no clinical importance with no indication for fetal echocardiography, follow-up ultrasound imaging, or postnatal evaluation (GRADE 1B); (6) for pregnant people with negative serum or cell-free DNA screening results and isolated fetal echogenic bowel, urinary tract dilation, or shortened humerus, femur, or both, we recommend no further aneuploidy evaluation (GRADE 1B); (7) for pregnant people with negative serum screening results and isolated thickened nuchal fold or absent or hypoplastic nasal bone, we recommend counseling to estimate the probability of trisomy 21 and discussion of options for no further aneuploidy evaluation, noninvasive aneuploidy screening through cell-free DNA, or diagnostic testing via amniocentesis, depending on clinical circumstances and patient preference (GRADE 1B); (8) for pregnant people with negative cell-free DNA screening results and isolated thickened nuchal fold or absent or hypoplastic nasal bone, we recommend no further aneuploidy evaluation (GRADE 1B); (9) for pregnant people with negative serum or cell-free DNA screening results and isolated choroid plexus cysts, we recommend no further aneuploidy evaluation, as this finding is a normal variant of no clinical importance with no indication for follow-up ultrasound imaging or postnatal evaluation (GRADE 1C); (10) for fetuses with isolated echogenic bowel, we recommend an evaluation for cystic fibrosis and fetal cytomegalovirus infection and a third-trimester ultrasound examination for reassessment and evaluation of growth (GRADE 1C); (11) for fetuses with an isolated single umbilical artery, we recommend no additional evaluation for aneuploidy, regardless of whether results of previous aneuploidy screening were low risk or testing was declined. We recommend a third-trimester ultrasound examination to evaluate growth and consideration of weekly antenatal fetal surveillance beginning at 36 0/7 weeks of gestation (GRADE 1C); (12) for fetuses with isolated urinary tract dilation A1, we recommend an ultrasound examination at ≥32 weeks of gestation to determine if postnatal pediatric urology or nephrology follow-up is needed. For fetuses with urinary tract dilation A2-3, we recommend an individualized follow-up ultrasound assessment with planned postnatal follow-up (GRADE 1C); (13) for fetuses with isolated shortened humerus, femur, or both, we recommend a third-trimester ultrasound examination for reassessment and evaluation of growth (GRADE 1C).

Universal Screening and Vaccination for Hepatitis B in Pregnancy: The Time Is Now.

Recommendations for screening for hepatitis B immunity in pregnancy and vaccinating susceptible women vary among professional societies. The American College of Obstetricians and Gynecologists recommends vaccinating high-risk women for hepatitis B. However, only one fourth of U.S. adults have received a complete hepatitis B vaccination series. Because two thirds of individuals with chronic hepatitis B are unaware of their diagnosis, risk-based screening for immunity followed by vaccination of susceptible women may not identify and protect all women at risk. Acquisition of hepatitis B poses short-term and long-term risks to maternal and fetal health, an outcome that can be prevented by vaccination. Hepatitis B vaccination in pregnancy is safe and efficacious and can be completed during the course of prenatal care. Universal screening for hepatitis B immunity and vaccination of susceptible women in pregnancy should be a priority during prenatal care. Cost-effectiveness studies are needed to validate this approach.

Postoperative Opioid Consumption After Scheduled Compared With Unscheduled Cesarean Delivery.

OBJECTIVE: To identify characteristics associated with high inpatient daily opioid consumption after cesarean delivery. METHODS: This is a retrospective cohort study of all cesarean deliveries performed under neuraxial anesthesia with neuraxial morphine, at a single institution from January 1, 2015, to December 31, 2015. Women with preoperative opioid use disorder or chronic opioid use were excluded. Sociodemographic data, medical comorbidities, use of anxiolytics or antidepressants, smoking history, nonopioid substance use, intrapartum and cesarean delivery characteristics, and opioid consumption data (converted to morphine milligram equivalents) were abstracted. We defined high opioid use as a mean daily opioid consumption, standardized to the postoperative length of stay (excluding the first 24 postoperative hours to account for neuraxial morphine), greater than the 75th percentile of all opioid consumption. We used multivariable Poisson regression, stratified by whether or not cesarean delivery was scheduled, to identify characteristics associated with high opioid consumption. RESULTS: Among 949 women who underwent cesarean delivery, the mean (SD) and median (interquartile range) daily opioid consumption was 48.6 (22.8) and 44.6 (36.6-66.6) morphine milligram equivalents, respectively. Among those women with high opioid consumption, the mean (SD) and median (interquartile range) daily opioid consumption was 78.8 (8.5) and 78.3 (72.9-83.5) morphine milligram equivalents, respectively. Daily opioid consumption among those with high consumption was similar among women with scheduled compared with unscheduled cesarean delivery. Sociodemographic characteristics were similar among women with and without high opioid consumption. No sociodemographic, antepartum, or intrapartum characteristics were associated with high opioid consumption for either women having unscheduled or scheduled cesarean deliveries. CONCLUSION: For a quarter of women undergoing cesarean delivery, daily consumption of opioids is equivalent to 10 tablets of oxycodone 5 mg daily. No characteristics were associated with high opioid use for women having a scheduled or unscheduled cesarean delivery. Understanding opioid consumption after cesarean delivery is critical to managing women's postoperative pain while decreasing opioid exposure and risks of long-term opioid use disorder.

Opioid dispensing patterns after oocyte retrieval.

OBJECTIVE: To study opioid dispensing patterns following oocyte retrieval. DESIGN: Retrospective cohort. SETTING: Not applicable. PATIENT(S): Women undergoing oocyte retrieval with a maximum of 1 opioid prescription in the 12 weeks prior to the procedure, without an opioid use or other substance use disorder. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We measured the frequency of opioids dispensed within 3 days of oocyte retrieval, most common opioids dispensed; and quantity dispensed, in median (interquartile range [IQR] and 10th-90th percentile ranges) oral morphine milligram equivalents (MME). Multivariate regression analyses were used to calculate odds ratios and 95% confidence intervals (CI) to examine the association between patient characteristics and the occurrence of an opioid dispensing. RESULT(S): In total, 61,463 women with an oocyte retrieval met the criteria for analysis. After oocyte retrieval, 11.9% were dispensed an opioid, most commonly hydrocodone (48.5%), codeine (23.0%), and oxycodone (17.7%). The median (IQR; 10th-90th percentile) oral MME dose dispensed after retrieval was 90 (50-125; 50-207). Women with mood disorders (adjusted odds ratio [aOR] 1.17, 95% CI 1.00-1.36), tobacco use (aOR 1.67, 95% CI 1.18-2.37), or anti-depressant use (aOR 1.62, 95% CI 1.47-1.80) were more likely to fill an opioid prescription, compared to those without these diagnoses. CONCLUSION(S): Although only a small proportion of women fill a prescription for opioids after oocyte retrieval, there is substantial variation in the amount dispensed. Patients with a concurrent mood disorder or those taking anti-depressants were more likely to fill an opioid prescription.

Perioperative pain management strategies among women having reproductive surgeries.

This review presents opioid-sparing strategies for perioperative pain management among women undergoing reproductive surgeries and procedures. Recommendations are provided regarding the use of nonsteroidal anti-inflammatory drugs, acetaminophen, other adjunctive medications, and regional anesthetic blocks. Additional considerations for chronic opioid users or patients using opioid replacement or antagonist therapy are discussed.

Development of World Health Organization (WHO) recommendations for appropriate clinical trial endpoints for next-generation Human Papillomavirus (HPV) vaccines.

The World Health Organization (WHO) serves as a key organization to bring together experts along the continuum of vaccine development and regulatory approval, among its other functions. Using the revision of WHO's guidelines on prophylactic human papillomavirus (HPV) vaccine as an example, we describe the process by which (1) a need to revise the guidelines was identified; (2) a group of stakeholders with complementary expertise and key questions were identified; (3) a scientific review was conducted; (4) consensus on revisions was achieved; (5) guidelines were updated, reviewed widely, and approved. This multi-year process resulted in the consensus that regulatory agencies could consider additional endpoints, such as persistent HPV infection or immune equivalence, depending on the design of the HPV vaccine trials. Updating the guidelines will now accelerate vaccine development, reduce costs of clinical trials, and lead to faster regulatory approval.

A captive audience: bringing the WISEWOMAN program to South Dakota prisoners.

PURPOSE: This analysis compares the baseline heart disease risk profile of WISEWOMAN participants screened in the South Dakota Women's Prison with the general WISEWOMAN population in South Dakota and explores the potential benefits of lifestyle intervention programs to reduce heart disease risk factors among women during incarceration. METHODS: Using baseline data for WISEWOMAN participants in South Dakota, we compared participants who were enrolled in prison (n = 261) with nonincarcerated participants enrolled throughout the state (n = 1,427). Using regression analysis and adjusting for demographics, we assessed differences in baseline prevalence of risk factors (hypertension, high cholesterol, smoking, and obesity), awareness and treatment of hypertension and high cholesterol, and attendance at lifestyle intervention sessions. RESULTS: Incarcerated participants had significantly lower (p < .01) total cholesterol (183 mg/dL) than nonincarcerated participants (199 mg/dL). However, a significantly higher (p < .03) percentage of incarcerated women (85%) than nonincarcerated women (54%) with high cholesterol were unaware of their condition. Despite the smoke-free status of the prison, 24% of incarcerated participants reported smoking. Attendance at lifestyle intervention sessions was significantly higher among incarcerated participants than among nonincarcerated participants with intervention take-up rates of 53% among incarcerated versus 23% among nonincarcerated women (p < .01) and intervention completion rates of 43% and 4% (p < .01). CONCLUSIONS: The results illustrate the need for screening and education programs in prisons. WISEWOMAN screenings helped identify undiagnosed cases of abnormal blood pressure and cholesterol, and educational interventions provided women with opportunities to improve their health. Such programs may also improve discharge planning and linkages between released women and community health providers.