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.

Society for Maternal-Fetal Medicine Statement: RhD immune globulin after spontaneous or induced abortion at less than 12 weeks of gestation.

Guidelines for the management of first-trimester spontaneous and induced abortion vary in terms of rhesus factor D (RhD) testing and RhD immune globulin (RhIg) administration. These existing guidelines are based on limited data that do not convincingly demonstrate the safety of withholding RhIg for first-trimester abortions or pregnancy losses. Given the adverse fetal and neonatal outcomes associated with RhD alloimmunization, prevention of maternal sensitization is essential in RhD-negative patients who may experience subsequent pregnancies. In care settings in which RhD testing and RhIg administration are logistically and financially feasible and do not hinder access to abortion care, we recommend offering both RhD testing and RhIg administration for spontaneous and induced abortion at <12 weeks of gestation in unsensitized, RhD-negative individuals. Guidelines for RhD testing and RhIg administration in the first trimester must balance the prevention of alloimmunization with the individual- and population-level harms of restricted access to abortion.

Society for Maternal-Fetal Medicine Consult Series #69: Hepatitis B in pregnancy: updated guidelines.

More than 290 million people worldwide, and almost 2 million people in the United States, are infected with hepatitis B virus, which can lead to chronic hepatitis B, a vaccine-preventable communicable disease. The prevalence of chronic hepatitis B infection in pregnancy is estimated to be 0.7% to 0.9% in the United States, with >25,000 infants born annually at risk for chronic infection due to perinatal transmission. Given the burden of disease associated with chronic hepatitis B infection, recent national guidance has expanded both the indications for screening for hepatitis B infection and immunity and the indications for vaccination. The purpose of this document is to aid clinicians caring for pregnant patients in screening for hepatitis B infection and immunity status, discuss the perinatal risks of hepatitis B infection in pregnancy, determine whether treatment is indicated for maternal or perinatal indications, and recommend hepatitis B vaccination among susceptible patients. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend triple-panel testing (hepatitis B surface antigen screening, antibody to hepatitis B surface antigen, and total antibody to hepatitis B core antigen) at the initial prenatal visit if not previously documented or known to have been performed (GRADE 1C); (2) we recommend universal hepatitis B surface antigen screening alone at the initial prenatal care visit for all pregnancies where there has been a previously documented negative triple-panel test (GRADE 1B); (3) we recommend that individuals with unknown hepatitis B surface antigen screening status be tested on any presentation for care in pregnancy; we also recommend that those with clinical hepatitis or those with risk factors for acute hepatitis B infection be tested at the time of admission to a birthing facility when delivery is anticipated (GRADE 1B); (4) we do not recommend altering routine intrapartum care in individuals chronically infected with hepatitis B; administration of neonatal immunoprophylaxis is standard of care in these situations (GRADE 1B); (5) we do not recommend cesarean delivery for the sole indication of reducing perinatal hepatitis B virus transmission (GRADE 1B); (6) we recommend that individuals with HBV infection can breastfeed as long as the infant has received immunoprophylaxis at birth (GRADE 1C); (7) we suggest individuals with hepatitis B infection who desire invasive testing may have the procedure performed after an informed discussion on risks and benefits in the context of shared decision-making and in the context of how testing will affect clinical care (GRADE 2C); (8) in individuals with hepatitis viral loads >200,000 IU/mL (>5.3 log 10 IU/mL), we recommend antiretroviral therapy with tenofovir (tenofovir alafenamide at 25 mg daily or tenofovir disoproxil fumarate at 300 mg daily) in the third trimester (initiated at 28-32 weeks of gestation) as an adjunctive strategy to immunoprophylaxis to reduce perinatal transmission (GRADE 1B); (9) we recommend administering hepatitis B vaccine and hepatitis B immunoglobin within 12 hours of birth to all newborns of hepatitis B surface antigen-positive pregnant patients or those with unknown or undocumented hepatitis B surface antigen status, regardless of whether antiviral therapy has been given during the pregnancy to the pregnant patient (GRADE 1B); and (10) we recommend hepatitis B vaccination in pregnancy for all individuals without serologic evidence of immunity or documented history of vaccination (GRADE 1C).

Society of Family Planning Clinical Recommendation: Medication abortion between 14 0/7 and 27 6/7 weeks of gestation.

OBJECTIVE: The objective of this Clinical Recommendation is to review relevant literature and provide evidence-based recommendations for medication abortion between 14 0/7-27 6/7 weeks of gestation, with focus on mifepristone-misoprostol and misoprostol-only regimens. METHODS: We systematically reviewed PubMed articles published between 2008 and 2022 and reviewed reference lists of included articles to identify additional publications. See Search Strategy for more details. RESULTS/CONCLUSIONS: Several randomized trials of medication abortion between 14 0/7-27 6/7 weeks of gestation demonstrate that mifepristone 200 mg orally before misoprostol increases effectiveness (complete abortion at 24 or 48 hours) compared to misoprostol only. Studies continue to evaluate different doses, routes, and dosing intervals for misoprostol. If mifepristone is unavailable, several misoprostol regimens with individual doses of at least 200 mcg or more are effective. Adjunctive osmotic dilators are of limited benefit. It is important to individualize care, with consideration to reducing misoprostol dose in low resources settings or at 24 0/7 weeks of gestation or later (or equivalent uterine size). Misoprostol in the setting of two or more previous cesarean sections is associated with increased risk of uterine rupture compared to one or none, but risk remains low. Most contraceptives can be started during or immediately following abortion. Appropriately trained and credentialed advanced practice clinicians can provide medication abortion between 14 0/7-27 6/7 weeks of gestation with appropriate backup within the confines of local regulations and licensure.

Society of Family Planning Clinical Recommendation: Medication abortion between 14 0/7 and 27 6/7 weeks of gestation: Jointly developed with the Society for Maternal-Fetal Medicine.

The objective of this Clinical Recommendation is to review relevant literature and provide evidence-based recommendations for medication abortion between 14 0/7 and 27 6/7 weeks of gestation, with a focus on mifepristone-misoprostol and misoprostol-only regimens. We systematically reviewed PubMed articles published between 2008 and 2022 and reviewed reference lists of included articles to identify additional publications. See Search Strategy for more details. Several randomized trials of medication abortion between 14 0/7 and 27 6/7 weeks of gestation demonstrate that mifepristone 200 mg orally before misoprostol increases effectiveness (complete abortion at 24 or 48 hours) compared to misoprostol only. Studies continue to evaluate different doses, routes, and dosing intervals for misoprostol. If mifepristone is unavailable, several misoprostol regimens with individual doses of at least 200 mcg or more are effective. Adjunctive osmotic dilators are of limited benefit. It is important to individualize care, with consideration to reducing misoprostol dose in low-resource settings or at 24 0/7 weeks of gestation or later (or equivalent uterine size). Misoprostol in the setting of two or more previous cesarean sections is associated with increased risk of uterine rupture compared to one or none, but risk remains low. Most contraceptives can be started during or immediately following abortion. Appropriately trained and credentialed advanced practice clinicians can provide medication abortion between 14 0/7 and 27 6/7 weeks of gestation with appropriate backup within the confines of local regulations and licensure.

SARS-CoV-2 vaccination, booster, and infection in pregnant population enhances passive immunity in neonates.

The effects of heterogeneous infection, vaccination and boosting histories prior to and during pregnancy have not been extensively studied and are likely important for protection of neonates. We measure levels of spike binding antibodies in 4600 patients and their neonates with different vaccination statuses, with and without history of SARS-CoV-2 infection. We investigate neutralizing antibody activity against different SARS-CoV-2 variant pseudotypes in a subset of 259 patients and determined correlation between IgG levels and variant neutralizing activity. We further study the ability of maternal antibody and neutralizing measurements to predict neutralizing antibody activity in the umbilical cord blood of neonates. In this work, we show SARS-CoV-2 vaccination and boosting, especially in the setting of previous infection, leads to significant increases in antibody levels and neutralizing activity even against the recent omicron BA.1 and BA.5 variants in both pregnant patients and their neonates.

Alliance for Innovation on Maternal Health: Consensus Bundle on Sepsis in Obstetric Care.

Sepsis in obstetric care is one of the leading causes of maternal death in the United States, with Black, Asian/Pacific Islander, and American Indian/Alaska Native obstetric patients experiencing sepsis at disproportionately higher rates. State maternal mortality review committees have determined that deaths are preventable much of the time and are caused by delays in recognition, treatment, and escalation of care. The "Sepsis in Obstetric Care" patient safety bundle provides guidance for health care teams to develop coordinated, multidisciplinary care for pregnant and postpartum people by preventing infection and recognizing and treating infection early to prevent progression to sepsis. This is one of several core patient safety bundles developed by AIM (the Alliance for Innovation on Maternal Health) to provide condition- or event-specific clinical practices that should be implemented in all appropriate care settings. As with other bundles developed by AIM, the "Sepsis in Obstetric Care" patient safety bundle is organized into five domains: Readiness, Recognition and Prevention, Response, Reporting and Systems Learning, and Respectful, Equitable, and Supportive Care. The Respectful, Equitable, and Supportive Care domain provides essential best practices to support respectful, equitable, and supportive care to all patients. Further health equity considerations are integrated into the elements of each domain.

Is magnesium sulfate therapy warranted in all cases of late postpartum severe hypertension? A suggested approach to a clinical conundrum.

Magnesium sulfate reduces the risk for eclamptic seizures antepartum, intrapartum, and in the immediate postpartum period, however, there are no studies that have evaluated the benefits and risks of magnesium sulfate among women with late postpartum severe hypertension only. Juxtaposed on this clinical uncertainty is the increased incidence of severe hypertension owing to a rise in pregnancies complicated by advanced maternal age, obesity, chronic hypertension, diabetes, and recent protocols for intensive monitoring of blood pressure in the postpartum period. These factors have led to a significant increase in postpartum presentations for the evaluation and management of severe hypertension, in some cases leading to postpartum readmissions for administration of antihypertensive therapy and magnesium sulfate without data demonstrating clear clinical benefit. Postpartum readmissions can have several negative consequences, including interfering with early bonding with a newborn, breastfeeding, and use of scarce healthcare resources. In addition, magnesium sulfate is associated with risks for serious cardiorespiratory depression and bothersome side effects and can delay determining the optimal antihypertensive regimen, which is typically the most pressing clinical need during postpartum presentations of late-postpartum severe hypertension. Eclampsia that occurs more than 48 hours after delivery is rare (constitutes 16% of all cases of eclampsia) and is most commonly preceded by headaches or other cerebral symptoms. In this commentary, we propose an approach to evaluating and managing patients with late postpartum severe hypertension aimed at identifying those women at highest risk for end-organ injury. We recommend that the short- and long-term focus for all patients with severe hypertension should be the optimal management of blood pressures with a goal of close outpatient monitoring when logistically feasible and clinically appropriate. We suggest reserving magnesium sulfate therapy for the subset of patients with neurologic symptoms who may be at highest risk for an eclamptic seizure.

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.

Coronavirus Disease 2019 (COVID-19) Vaccination in Pregnancy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with significant maternal morbidity and mortality, and its risks can be mitigated with coronavirus disease 2019 (COVID-19) vaccination. Vaccination against COVID-19 in pregnancy results in protection against both maternal and neonatal SARS-CoV-2 infection, as well as maternal critical illness. Vaccination during pregnancy is safe, with no documented risks of pregnancy loss, preterm delivery, congenital anomalies, or other adverse perinatal outcomes. For these reasons, COVID-19 vaccination is recommended in pregnancy by the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine, as well as other national and international professional organizations. In this review, we will summarize the published literature demonstrating the benefit and safety of these vaccines.

Longitudinal antibody response kinetics following SARS-CoV-2 messenger RNA vaccination in pregnant and nonpregnant persons.

BACKGROUND: For some vaccine-preventable diseases, the immunologic response to vaccination is altered by a pregnant state. The effect of pregnancy on SARS-CoV-2 vaccine response remains unclear. OBJECTIVE: We sought to characterize the peak and longitudinal anti-S immunoglobulin G, immunoglobulin M, and immunoglobulin A responses to messenger RNA-based SARS-CoV-2 vaccination in pregnant persons and compare them with those in nonpregnant, reproductive-aged persons. STUDY DESIGN: We conducted 2 parallel prospective cohort studies among pregnant and nonpregnant persons who received SARS-CoV-2 messenger RNA vaccinations. Blood was collected at the time of first and second vaccine doses, 2 weeks post second dosage, and with serial longitudinal follow-up up to 41.7 weeks post vaccination initiation. Anti-S immunoglobulin M, immunoglobulin G, and immunoglobulin A were analyzed by enzyme-linked immunosorbent assay. We excluded those with previous evidence of SARS-CoV-2 infection by history or presence of antinucleocapsid antibodies. In addition, for this study, we did not include individuals who received a third or booster vaccine dosage during the study period. We also excluded pregnant persons who were not fully vaccinated (14 days post receipt of the second vaccine dosage) by time of delivery and nonpregnant persons who became pregnant through the course of the study. We studied the effect of gestational age at vaccination on the anti-S response using Spearman correlation. We compared the peak anti-S antibody responses between pregnant and nonpregnant persons using a Mann-Whitney U test. We visualized and studied the longitudinal anti-S antibody response using locally weighted scatterplot smoothing, Mann-Whitney U test, and mixed analysis of variance test. RESULTS: Data from 53 pregnant and 21 nonpregnant persons were included in this analysis. The median (interquartile range) age of the pregnant and nonpregnant participants was 35.0 (33.3-37.8) years and 36.0 (33.0-41.0) years, respectively. Six (11.3%) participants initiated vaccination in the first trimester, 23 (43.3%) in the second trimester, and 24 (45.3%) in the third trimester, with a median gestational age at delivery of 39.6 (39.0-40.0) weeks. The median (interquartile range) follow-up time from vaccine initiation to the last blood sample collected was 25.9 (11.9) weeks and 28.9 (12.9) weeks in the pregnant and nonpregnant cohort, respectively. Among pregnant persons, anti-S immunoglobulin G, immunoglobulin A, and immunoglobulin M responses were not associated with gestational age at vaccine initiation (all P>.05). The anti-S immunoglobulin G response at 2 weeks post second dosage was not statistically different between pregnant and nonpregnant persons (P>.05). However, the anti-S immunoglobulin M and immunoglobulin A responses at 2 weeks post second dosage were significantly higher in nonpregnant persons (P<.001 for both). The anti-S immunoglobulin G and immunoglobulin M levels 6 to 8 months after vaccine initiation fell to comparable proportions of the peak 2 weeks post second dosage antibody levels between pregnant and nonpregnant persons (immunoglobulin G P=.77; immunoglobulin M P=.51). In contrast, immunoglobulin A levels 6 to 8 months after vaccine initiation fell to statistically significantly higher proportions of peak 2 weeks post second dosage antibody levels in pregnant compared with nonpregnant persons (P=.002). Maternal anti-S immunoglobulin G levels were strongly correlated with umbilical cord anti-S immunoglobulin G levels (R=0.8, P<.001). CONCLUSION: The anti-S immunoglobulin A, immunoglobulin M, and immunoglobulin G response to SARS-CoV-2 vaccination in pregnancy is independent of gestational age of vaccine initiation. Maintenance of the immunoglobulin G response is comparable between pregnant and nonpregnant persons. The differential peak response of immunoglobulin M and immunoglobulin A and the differential decline of anti-S immunoglobulin A between pregnant and nonpregnant persons requires further investigation.

Innovating Evaluation and Treatment of Intrapartum Fevers: Where Do We Go from Here?

As intrapartum fevers are not always infectious in origin, determining whether antibiotics are indicated is challenging. We previously sought to create a point-of-care calculator using clinical data available at the time of an intrapartum fever to identify the subset of women who require antibiotic treatment to avoid maternal and neonatal morbidity. Despite the use of a comprehensive dataset from our institutions, we were unable to propose a valid and highly predictive model. In this commentary, we discuss why our model failed, as well as future research directions to identify and treat true intraamniotic infection. Developing a risk-stratification model is paramount to minimizing maternal and neonatal exposure to unnecessary antibiotics while allowing for early identification of women and babies at risk for infectious morbidity. KEY POINTS: · Determining whether antibiotics are indicated in intrapartum fever is challenging.. · Developing a risk-stratification model for febrile laboring women is critical to decreasing harm.. · A point-of-care calculator based on clinical and biomarker data is the necessary approach..

Placental pathology, neonatal birth weight, and Apgar score in acute and distant SARS-CoV-2 infection.

Background: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy has been on acute infections with limited data on the effect of distant infection. Aim: We examined placental pathology and neonatal outcomes in distant SARS-CoV-2 infection earlier in pregnancy compared to acute infections late in pregnancy/at birth and to non-SARS-CoV-2 infected patients with other placental pathologies/clinical presentations. Methods: Placentas birthed to unvaccinated patients with SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) testing and serology testing results from time of delivery were included in this study. A total of 514 singleton placentas between April 18, 2020, and July 26, 2021, were included: 77 acute SARS-CoV-2 infection (RT-PCR positive and serology negative); 222 distant SARS-CoV-2 infection (RT-PCR negative but serology IgG-positive); and 215 non-SARS-Cov-2 infected (RT-PCR negative, serology negative, and history negative) with other placental pathologies: preeclampsia/hypertension, intrauterine growth restriction (IUGR), diabetes, chorioamnionitis, and meconium. Placental pathology findings, Apgar scores, and neonatal birth weights were compared. Results: Placentas from the acute group had significantly more villous agglutination (10.4%, P = 0.015) and eosinophilic T-cell vasculitis (5.2%, P = 0.004) compared to placentas from the distant group (2.7% and 0%) and non-SARS-CoV-2 placentas (1.9% and 0.9%). One acute case showed SARS-CoV-2 placentitis and resulted in preterm delivery at 25 weeks. Both the preeclampsia/hypertension and the IUGR groups showed significantly more maternal vascular malperfusion findings compared to the acute (6.5%, 6.5% and 1.3%) and distant (7.7%, 7.7%, and 3.2%) groups. Fetal vascular malperfusion findings such as thrombosis of fetal vessels (17.4% P = 0.042) and intramural fibrin deposition (21.7% P = 0.026) were significantly higher in the IUGR group compared to acute (7.8%; 2.6%) and distant (3.6%; 8.1%) infection. Many neonates born to patients infected with SARS-CoV-2 had birth weights outside of 95% confidence range of observed birth weights. There was no association of Apgar scores with infection status or placental pathology. Conclusion: Acute and distant SARS-CoV-2 infections present differing placental pathology. Relevance for Patients: SARS-CoV-2 infection during pregnancy has demonstrable effects on the placenta with potential significant impacts for maternal and fetal health. Prevention of maternal SARS-CoV-2 infection, primarily through vaccination, remains the best mitigation strategy to prevent sequelae of maternal SARS-CoV-2 infection.

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.

Cytokine response over the course of COVID-19 infection in pregnant women.

OBJECTIVE: To study how severity and progression of coronavirus disease (COVID-19) affect cytokine profiles in pregnant women. MATERIALS AND METHODS: 69 third-trimester, pregnant women were tested for COVID-19 infection and SARS-CoV-2 specific IgM and IgG antibodies. Patients were stratified according to SARS-CoV-2 Reverse Transcriptase-PCR (RT-PCR) status and serology (IgM and IgG) status. Cytokines G-CSF, HGF, IL-18, IL-1Ra, IL-2Ra, IL-8, and IP-10 were measured via ELISA. Retrospective chart review for COVID-19 symptoms and patient vitals was conducted, and cytokine levels were compared between SARS-CoV-2 positive and negative cohorts, by seronegative and seropositive infection, by time course since onset of infection, and according to NIH defined clinical severity. RESULTS: IL-18, IL-1Ra, and IP-10 increased in the 44 RT-PCR positive pregnant women compared to the 25 RT-PCR negative pregnant controls. Elevated cytokine levels were found in early infections, defined by positive RT-PCR and seronegative status, and higher cytokine levels were also associated with more severe disease. By IgM seroconversion, IL-8 and IP-10 returned to levels seen in uninfected patients, while IL-18 levels remained significantly elevated. CONCLUSION: Cytokine profiles of third-trimester pregnant women vary with the time course of infection and are correlated with clinical severity.

Inflammatory responses in the placenta upon SARS-CoV-2 infection late in pregnancy.

The effect of SARS-CoV-2 infection on placental function is not well understood. Analysis of placentas from women who tested positive at delivery showed SARS-CoV-2 genomic and subgenomic RNA in 22 out of 52 placentas. Placentas from two mothers with symptomatic COVID-19 whose pregnancies resulted in adverse outcomes for the fetuses contained high levels of viral Alpha variant RNA. The RNA was localized to the trophoblasts that cover the fetal chorionic villi in direct contact with maternal blood. The intervillous spaces and villi were infiltrated with maternal macrophages and T cells. Transcriptome analysis showed an increased expression of chemokines and pathways associated with viral infection and inflammation. Infection of placental cultures with live SARS-CoV-2 and spike protein-pseudotyped lentivirus showed infection of syncytiotrophoblast and, in rare cases, endothelial cells mediated by ACE2 and Neuropilin-1. Viruses with Alpha, Beta, and Delta variant spikes infected the placental cultures at significantly greater levels.

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.