Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

Importance: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER- Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. Methods: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. Discussion: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. Registration: NCT05172024.

Antihypertensives in Pregnancy.

Hypertensive disorders of pregnancy (HDP) can result in significant maternal morbidity and even mortality. Available data suggest that many antihypertensives can be safely used in pregnant patients, albeit with close supervision of parameters like fetal growth and amniotic fluid volume. This article summarizes current guidelines on the diagnosis and treatment of hypertension in pregnancy and provides an in-depth guide to the available safety and efficacy data for antihypertensives during pregnancy and postpartum.

Choice Architecture to Assist Clinicians with Appropriate COVID-19 Test Ordering.

BACKGROUND: Despite improving supplies, SARS-CoV-2 nucleic acid amplification tests remain limited during surges and more so given concerns around COVID-19/influenza co-occurrence. Matching clinical guidelines to available supplies ensures resources remain available to meet clinical needs. We report a change in clinician practice after an electronic health record (EHR) order redesign to impact emergency department (ED) testing patterns. METHODS: We included all ED visits between December 1, 2021 and January 18, 2022 across a hospital system to assess the impact of EHR order changes on provider behavior 3 weeks before and after the change. The EHR order redesign included embedded symptom-based order guidance. Primary outcomes were the proportion of COVID-19 + flu/respiratory syncytial virus (RSV) testing performed on symptomatic, admitted, and discharged patients, and the proportion of COVID-19 + flu testing on symptomatic, discharged patients. RESULTS: A total of 52 215 ED visits were included. For symptomatic, discharged patients, COVID-19 + flu/RSV testing decreased from 11.4 to 5.8 tests per 100 symptomatic visits, and the rate of COVID-19 + flu testing increased from 7.4 to 19.1 before and after the intervention, respectively. The rate of COVID-19 + flu/RSV testing increased from 5.7 to 13.1 tests per 100 symptomatic visits for symptomatic patients admitted to the hospital. All changes were significant (P < 0.0001). CONCLUSIONS: A simple EHR order redesign was associated with increased adherence to institutional guidelines for SARS-CoV-2 and influenza testing amidst supply chain limitations necessitating optimal allocation of scarce testing resources. With continually shifting resource availability, clinician education is not sufficient. Rather, system-based interventions embedded within exiting workflows can better align resources and serve testing needs of the community.

Neonatal outcomes by delivery indication after administration of antenatal late preterm corticosteroids.

Background: Antenatal corticosteroids, specifically betamethasone, administered to patients at risk for late preterm delivery have been associated with reduced rates of neonatal respiratory complications. However, whether these risks vary by delivery indication among betamethasone-exposed, late-preterm infants is not known. Objective: This study aimed to evaluate if spontaneous preterm labor or preterm prelabor rupture of membranes, compared with indicated late preterm delivery, is associated with better neonatal respiratory outcomes after accounting for betamethasone administration in the late preterm period. Study Design: This was a secondary analysis of the Antenatal Late Preterm Steroids trial, a multicenter, placebo-controlled trial in which patients with singleton pregnancies at risk for delivery at 34 0/7 to 36 5/7 weeks of gestation were randomized to a single course of antenatal corticosteroids (betamethasone) or placebo. Patients were eligible if they had spontaneous preterm labor, preterm prelabor rupture of membranes, or if they were undergoing indicated late preterm delivery. The primary outcome was a composite of need for respiratory support, stillbirth, or neonatal death within 72 hours after delivery. Secondary outcomes included individual neonatal morbidities. Bivariate analyses were performed, and multivariable logistic regression models were used to control for potential confounders. Using the indicated preterm delivery group as the reference group, adjusted odds ratios and 95% confidence intervals were calculated for the outcomes by delivery indication. Subgroup analyses separately examined the treatment and placebo groups to determine the odds of the primary outcome by delivery indication. Results: Of 2827 participants at high risk for late preterm delivery, 1427 (50.5%) received betamethasone. There were 790 (27.9%) infants born after preterm labor, 620 (21.9%) born after preterm prelabor rupture of membranes, and 1417 (50.1%) born after indicated preterm delivery. Compared with indicated preterm delivery, the odds of the primary outcome were lower among those born after preterm labor (7.3% vs 16.4%; adjusted odds ratio, 0.57; 95% confidence interval, 0.40-0.82) and among those born after preterm prelabor rupture of membranes (12.4% vs 16.4%; adjusted odds ratio, 0.49; 95% confidence interval, 0.35-0.69). Preterm labor had lower odds of all neonatal complications except feeding problems, and preterm prelabor rupture of membranes had lower odds of all neonatal complications except newborn intensive care unit admission for ≥3 days when compared with indicated preterm delivery. For the placebo group, the odds of the primary outcome were lower for the preterm labor group (8.2% vs 18.5%; adjusted odds ratio, 0.55; 95% confidence interval, 0.34-0.91) and the preterm prelabor rupture of membranes group (13.2% vs 18.5%; adjusted odds ratio, 0.46; 95% confidence interval, 0.29-0.73) than for the indicated preterm delivery group. For those exposed to betamethasone, the odds of the primary outcome remained lower for the preterm labor group (6.5% vs 14.3%; adjusted odds ratio, 0.58; 95% confidence interval, 0.34-0.99) and the preterm prelabor rupture of membranes group (11.7% vs 14.3%, adjusted odds ratio, 0.56; 95% confidence interval, 0.34-0.91) than for the indicated preterm delivery group. Conclusion: Compared with indicated preterm delivery, preterm labor and preterm prelabor rupture of membranes were associated with reduced odds of neonatal respiratory complications irrespective of betamethasone exposure in the late preterm period.

Pilot Implementation of a Health Equity Checklist to Improve the Identification of Equity-Related Adverse Events.

OBJECTIVE: To establish a sustainable and trackable process to delineate the role of social determinants of health, bias, and racism in adverse gynecologic events. METHODS: The existing process entails monthly reviews of adverse events. Each case is assessed for preventability, harm, and standards of care. The equity-focused process consists of: 1) creation of a standardized health equity checklist; 2) application of the checklist to each gynecologic adverse event beginning on September 1, 2020; 3) collection of event review data in a secure central digital repository; 4) review of the cases to understand apparent causes of the event; 5) exploration of areas for improvement by using standard fields; and 6) identification of specific ideas for change. RESULTS: Within 15 months, 46 safety events were identified by standard criteria. Twenty-four of the cases were deemed preventable. Of the 24, there were 12 cases in which social determinants of health or bias or both social determinants of health and bias were identified playing a role. Diagnostic delays and care delays were attributed to social determinants of health and implicit bias. Our process has mapped areas of infrastructure as well as the need for culture improvement and has also highlighted the need for restorative work on addressing implicit bias and improving approaches to shared decision making. CONCLUSION: Through the use of a health equity checklist, we have illustrated the feasibility of creating a systematic and trackable process to begin delineating the role of social determinants of health, bias, and racism in adverse gynecologic events.

Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons.

Background: The SARS-CoV-2 Omicron variant became a global concern due to its rapid spread and displacement of the dominant Delta variant. We hypothesized that part of Omicron's rapid rise was based on its increased ability to cause infections in persons that are vaccinated compared to Delta. Methods: We analyzed nasal swab PCR tests for samples collected between December 12 and 16, 2021, in Connecticut when the proportion of Delta and Omicron variants was relatively equal. We used the spike gene target failure (SGTF) to classify probable Delta and Omicron infections. We fitted an exponential curve to the estimated infections to determine the doubling times for each variant. We compared the test positivity rates for each variant by vaccination status, number of doses, and vaccine manufacturer. Generalized linear models were used to assess factors associated with odds of infection with each variant among persons testing positive for SARS-CoV-2. Findings: For infections with high virus copies (Ct < 30) among vaccinated persons, we found higher odds that they were infected with Omicron compared to Delta, and that the odds increased with increased number of vaccine doses. Compared to unvaccinated persons, we found significant reduction in Delta positivity rates after two (43.4%-49.1%) and three vaccine doses (81.1%), while we only found a significant reduction in Omicron positivity rates after three doses (62.3%). Conclusion: The rapid rise in Omicron infections was likely driven by Omicron's escape from vaccine-induced immunity. Funding: This work was supported by the Centers for Disease Control and Prevention (CDC).

Adherence to Definitions of Labor Arrest Influence on Primary Cesarean Delivery Rate.

OBJECTIVE: The cesarean delivery rate in the United States is 31.9%. One of the leading indications for primary cesarean delivery is labor arrest. A modern understanding of the labor curve supports more time prior to the diagnosis of labor arrest. We conducted this study to examine the impact of adherence to the modern criteria for labor arrest and failed induction on rates of primary cesarean delivery and to identify predictors of meeting these criteria. STUDY DESIGN: We analyzed rates of primary cesarean deliveries overall and primary cesarean deliveries occurring due to arrest of dilation, arrest of descent, and failed induction among the 17,877 live births at a large academic center from 2010 through 2013. Multiple logistic regression modeling identified predictors of meeting the new criteria for these indications based on guidelines published by the 2012 National Institute of Child Health and Human Development. RESULTS: The primary cesarean delivery rate decreased from 23.5 to 21.1% (p = 0.026) from 2010 to 2013. Primary cesarean delivery rate for labor arrest and failed induction decreased from 8.5 to 6.7% (p = 0.005). The percentage of primary cesarean deliveries meeting the 2012 criteria for labor arrest increased from 18.8 to 34.9% (p = 0.002), and the rate of primary cesarean deliveries due to arrest of dilation decreased from 5.1 to 3.4% (p < 0.0005). The percentage of cases meeting the 2012 criteria for arrest of descent increased from 57.8 to 71.0% (p < 0.007), while primary cesarean delivery rate due to arrest of descent remained relatively unchanged, 3.1 to 2.6% (p = 0.330). CONCLUSION: A decrease in the primary cesarean rate was attributable to a decrease in cesarean for arrest of dilation in the setting of a significant increase in meeting the 2012 criteria for arrest of dilation. At the end of the study period, 65.2% of cesareans still did not meet the criteria for arrest of dilation. Greater rates of adherence to these guidelines may yield further reductions in the cesarean rate. KEY POINTS: · Primary cesarean delivery for labor arrest was decreased.. · Meeting criteria for labor arrest increased.. · A hospitalist provider increased odds of meeting criteria..

Society for Maternal-Fetal Medicine Special Statement: A critique of postpartum readmission rate as a quality metric.

Hospital readmission is considered a core measure of quality in healthcare. Readmission soon after hospital discharge can result from suboptimal care during the index hospitalization or from inadequate systems for postdischarge care. For many conditions, readmission is associated with a high rate of serious morbidity and potentially avoidable costs. In obstetrics, for postpartum care specifically, hospitals and payers can easily track the rate of maternal readmission after childbirth and may seek to incentivize obstetricians, maternal-fetal medicine specialists, or provider groups to reduce the rate of readmission. However, this practice has not been shown to improve outcomes or reduce harm. There are major concerns with incentivizing providers to reduce postpartum readmissions, including the lack of a standardized metric, a baseline rate of 1% to 2% that is too low to accurately discriminate between random variation and controllable factors, the need for risk adjustment that greatly complicates rate calculations, the potential for bias depending on the duration of the follow-up interval, the potential for the "gaming" of the metric, the lack of evidence that obstetrical providers can influence the rate, and the potential for unintended harm in the vulnerable postpartum population. Until these problems are adequately addressed, maternal readmission rate after a childbirth hospitalization currently has limited utility as a metric for quality or performance improvement or as a factor to adjust provider reimbursement.

Mass severe acute respiratory coronavirus 2 (SARS-CoV-2) testing of asymptomatic healthcare personnel.

Mass asymptomatic SARS-CoV-2 nucleic acid amplified testing of healthcare personnel (HCP) was performed at a large tertiary health system. A low period-prevalence of positive HCP was observed. Of those who tested positive, half had mild symptoms in retrospect. HCP with even mild symptoms should be isolated and tested.

Society for Maternal-Fetal Medicine Consult Series #54: Assessing the risk of maternal morbidity and mortality.

The rates of maternal morbidity and mortality in the United States demand a comprehensive approach to assessing pregnancy-related risks. Numerous medical and nonmedical factors contribute to maternal morbidity and mortality. Reducing the number of women who experience pregnancy morbidity requires identifying which women are at greatest risk and initiating appropriate interventions early in the reproductive life course. The purpose of this Consult is to educate all healthcare practitioners about factors contributing to a high-risk pregnancy, strategies to assess maternal health risks due to pregnancy, and the importance of risk assessment across the reproductive spectrum in reducing maternal morbidity and mortality.

Society for Maternal-Fetal Medicine Consult Series #53: Intrahepatic cholestasis of pregnancy: Replaces Consult #13, April 2011.

Intrahepatic cholestasis of pregnancy is a hepatic disorder characterized by pruritus and an elevation in serum bile acid levels. Although intrahepatic cholestasis of pregnancy poses little risk for women, this condition carries a significant risk for the fetus, including complications such as preterm delivery, meconium-stained amniotic fluid, and stillbirth. The purpose of this Consult is to review the current literature on intrahepatic cholestasis of pregnancy and provide recommendations based on the available evidence. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we recommend measurement of serum bile acid and liver transaminase levels in patients with suspected intrahepatic cholestasis of pregnancy (GRADE 1B); (2) we recommend that ursodeoxycholic acid be used as the first-line agent for the treatment of maternal symptoms of intrahepatic cholestasis of pregnancy (GRADE 1A); (3) we suggest that patients with a diagnosis of intrahepatic cholestasis of pregnancy begin antenatal fetal surveillance at a gestational age when delivery would be performed in response to abnormal fetal testing results or at the time of diagnosis if the diagnosis is made later in gestation (GRADE 2C); (4) we recommend that patients with total bile acid levels of ≥100 µmol/L be offered delivery at 36 0/7 weeks of gestation, given that the risk of stillbirth increases substantially around this gestational age (GRADE 1B); (5) we recommend delivery between 36 0/7 and 39 0/7 weeks of gestation for patients with intrahepatic cholestasis of pregnancy and total bile acid levels of <100 µmol/L (GRADE 1C); (6) we recommend administration of antenatal corticosteroids for fetal lung maturity for patients delivering before 37 0/7 weeks of gestation if not previously administered (GRADE 1A); (7) we recommend against preterm delivery at <37 weeks of gestation in patients with a clinical diagnosis of intrahepatic cholestasis of pregnancy without laboratory confirmation of elevated bile acid levels (GRADE 1B).

Coronavirus disease 2019 pregnancy outcomes in a racially and ethnically diverse population.

Background: Older age and medical comorbidities are identified risk factors for developing severe coronavirus disease 2019. However, there are limited data on risk stratification, clinical and laboratory course, and optimal management of coronavirus disease 2019 in pregnancy. Objective: Our study aimed to describe the clinical course of coronavirus disease 2019, effect of comorbidities on disease severity, laboratory trends, and pregnancy outcomes of symptomatic and asymptomatic severe acute respiratory syndrome coronavirus 2-positive pregnant women. Study Design: This is a case series of pregnant and postpartum women who received positive test results for severe acute respiratory syndrome coronavirus 2 between March 3, 2020, and May 11, 2020, within 3 hospitals of the Yale New Haven Health delivery network. Charts were reviewed for basic sociodemographic and prepregnancy characteristics, coronavirus disease 2019 course, laboratory values, and pregnancy outcomes. Results: Of the 1567 tested pregnant and postpartum women between March 3, 2020, and May 11, 2020, 9% (n=141) had a positive severe acute respiratory syndrome coronavirus 2 result. Hispanic women were overrepresented in the severe acute respiratory syndrome coronavirus 2-positive group (n=61; 43.8%). In addition, Hispanic ethnicity was associated with a higher rate of moderate and severe diseases than non-Hispanic (18% [11/61] vs 3.8% [3/78], respectively; odds ratio, 5.5; 95% confidence interval, 1.46-20.7; P=.01). Of note, 44 women (31.2%) were asymptomatic, 37 of whom (26.2%) were diagnosed on universal screening upon admission for delivery. Moreover, 59% (n=83) were diagnosed before delivery, 36% (n=51) upon presentation for childbirth, and 5% (n=7) after delivery. Severe disease was diagnosed in 6 cases (4.3%), and there was 1 maternal death. Obese women were more likely to develop moderate and severe diseases than nonobese women (16.4% [9/55] vs 3.8% [3/79]; odds ratio, 4.96; 95% confidence interval, 1.28-19.25; P=.02). Hypertensive disorders of pregnancy were diagnosed in 22.3% of women (17/77) who delivered after 20 weeks' gestation. Higher levels of C-reactive protein during antepartum coronavirus disease 2019-related admission were more common in women with worse clinical course; however, this association did not reach statistical significance. Conclusion: Coronavirus disease 2019 in pregnancy may result in severe disease and death. Hispanic women were more likely to receive a positive test result for severe acute respiratory syndrome 2 than other ethnic groups. Obesity and Hispanic ethnicity represent risk factors for moderate and severe diseases.