Pregnancy alters interleukin-1 beta expression and antiviral antibody responses during severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied. OBJECTIVE: This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women. STUDY DESIGN: Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood. RESULTS: Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.

Dysregulated immunity in SARS-CoV-2 infected pregnant women.

IMPORTANCE: The effects of SARS-CoV-2 infection on immune responses during pregnancy have not been systematically evaluated. OBJECTIVE: To assess the impact of SARS-CoV-2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to SARS-CoV-2 among pregnant and non-pregnant women. DESIGN: Immune responses to SARS-CoV-2 were analyzed using samples from pregnant and non-pregnant women who had either tested positive or negative for SARS-CoV-2. We measured, proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) receptor expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we measured anti-spike (S) IgG, anti-S-receptor binding domain (RBD) IgG, and neutralizing antibody (nAb) responses to SARS-CoV-2 in serum or plasma collected from non-pregnant women, pregnant women, and cord blood. SETTING: Johns Hopkins Hospital (JHH). PARTICIPANTS: Pregnant women were recruited through JHH outpatient obstetric clinics and the JHH Labor & Delivery unit. Non-pregnant women were recruited after receiving outpatient SARS-CoV-2 testing within Johns Hopkins Health System, USA. Adult non-pregnant women with positive RT-PCR results for SARS-CoV-2, within the age range of 18-48 years, were included in the study. EXPOSURES: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Participant demographic characteristics, antibody titers, cytokine mRNA expression, and FcRn receptor expression. RESULTS: SARS-COV-2 positive pregnant women expressed more IL1ß , but not IL6 , in blood samples collected within 14 days versus > 14 days after a confirmed SARS-CoV-2 test, with similar patterns observed in the fetal side of placentas, particularly among asymptomatic pregnant women. Pregnant women with confirmed SARS-CoV-2 infection also had reduced anti-S-RBD IgG titers and were less likely to have detectable nAb as compared with non-pregnant women. Although SARS-CoV-2 infection did not disrupt FcRn expression in the placenta, maternal transfer of nAb was inhibited by SARS-CoV-2 infection during pregnancy. CONCLUSIONS AND RELEVANCE: SARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.

A Mentorship Program for Academic Obstetrician Gynecologists that Improved Publication and Overall Confidence for Success.

This article aims to evaluate the impact of a mentorship program to enhance the training of clinical and research scientists in obstetrics and gynecology (OBGYN). A departmental course was developed for junior faculty and fellows based on their areas of interest. The research was IRB-approved. The curriculum consisted of monthly interactive workshops for an interdisciplinary group of trainees in OBGYN. Themes included research, education, and leadership in academic OBGYN. There was a strong emphasis on participatory exercises. Examples of curriculum topics included manuscript publication and review, grant writing, working with an IRB, promotion, and time management. Pre- and post-course questionnaires assessed participants' confidence in skills related to the course topics. Generalized linear models were used to assess changes in post-course response, using each question as the dependent variable and an indicator for post-course as the predictor variable. The control group was composed of junior faculty and fellows before the course was initiated. Outcome measures included the number and impact factor of published manuscripts. A Wilcoxon rank-sum test was used to assess outcome measures. Of the 118 attendees, 26 (22.0%) were junior faculty, 35 (29.66%) were clinical fellows, and 28 (23.7%) were research fellows, other research staff, or students. For each 3-year course series, an average of 20 participants completed the post-course surveys, of which 72% were clinical fellows, 22% were assistant professors, and 5% were instructors. The data revealed a statistically significant change in the participant's overall confidence in skills related to research, education, and leadership when comparing the cumulative results from the pre-to-post course surveys (p < 0.001). Specifically, participants noted improved confidence in their skills related to clinical and translation research (p < 0.001) and leadership and academic career advancement (p = 0.001). Additionally, junior faculty and clinical fellows who attended the course had a higher number of publications during the course period compared with controls (p = 0.003 and p = 0.008, respectively). This subspecialty-tailored, departmental training program was effective in increasing junior faculty and clinical fellows' confidence in skills related to career advancement and research and in the number of peer-reviewed publications.

Simulation in Obstetrics.

Simulation in obstetrics is a widely accepted and valuable tool that benefits all levels of learners from medical students to maternal-fetal medicine subspecialists. What began as an adjunct to medical education now has a rapidly expanding role in acquisition of new and innovative procedures, team and unit training, and safety and quality initiatives. The number of obstetric simulation peer-reviewed reports has increased exponentially in recent years, yet only a small percentage of reports primarily addresses clinical outcomes. Studies link simulation to a reduction in neonatal brachial plexus injury, maternal trauma related to forceps delivery, response to postpartum hemorrhage, efficiency in performing emergent cesarean delivery, and neonatal mortality. Simulation is a required component in accredited obstetrics and gynecology residency training programs. Obstetric simulation has a role in the certification of physicians, and simulation hands-on courses may be used to meet maintenance of certification requirements. As simulation platforms are validated, they are likely to be incorporated into the certification process as a means of assessing technical and communication skills. Accrediting, certifying, professional, quality, and safety organizations have invested in simulation committees, interest groups, curricula, and continuing medical education courses. Support for research, including large multicenter trials, are needed to inform further implementation. Research and development should lead to lower costs and improved simulators. As the public, government, licensing, and credentialing institutions explore means of improving patient safety, expansion of simulation in obstetrics is inevitable.

Simulation Training in Obstetrics.

Simulation now permeates all levels of training in obstetrics and maternal-fetal medicine. We will review the role of obstetric simulation through the continuum of training and practice. Simulation allows learners to acquire skills in a nonthreatening environment while avoiding harm to patients. Simulation in obstetrics evolved from a learning tool for students and residents, to a method for experienced physicians to learn new procedures and reenter the full breadth and depth of practice. Specialty boards and credentialing organizations recognize simulation training as an innovative approach to assess and assure technical, clinical, and teamwork skills.

Implementation of a multicenter shoulder dystocia injury prevention program.

Although the evidence for supporting the effectiveness of many patient safety practices has increased in recent years, the ability to implement programs to positively impact clinical outcomes across multiple institutions is lagging. Shoulder dystocia simulation has been shown to reduce avoidable patient harm. Neonatal injury from shoulder dystocia contributes to a significant percentage of liability claims. We describe the development and the process of implementation of a shoulder dystocia simulation program across five academic medical centers and their affiliated hospitals united by a common insurance carrier. Key factors in successful roll out of this program included the following: involvement of physician and nursing leadership from each academic medical center; administrative and logistic support from the insurer; development of consensus on curriculum components of the program; conduct of gap and barrier analysis; financial support from insurer to close necessary gaps and mitigate barriers; and creation of dashboards and tracking performance of the program.

Early Postpartum Glucose Testing in Women with Gestational Diabetes Mellitus.

Objective Given that most women with gestational diabetes mellitus (GDM) never undergo the recommended 6 to 12 weeks postpartum glucose tolerance test (GTT), we assessed the feasibility of performing GTTs on postpartum day 2. Study Design Women with abnormal postpartum day 2 results were similar to women with normal postpartum day 2 results except that more women with abnormal results required medicine to treat their GDM (Table 1). [corrected]. We assessed the feasibility of this GTT and compared the results to the standard of care GTT at 6 to 12 weeks postpartum. We also evaluated maternal and pregnancy characteristics of women who return for 6 to 12 weeks GTTs compared with those lost to follow-up. Results In this study, 98 of 106 participants (92%) completed the postpartum day 2 GTT; 59% had normal glucose values at that time. Only 49 women returned at 6 to 12 weeks postpartum. Among women who had testing at both time points, the 2 days postpartum GTT were 100% sensitive and 94% specific for diabetes mellitus but less sensitive and specific for milder forms of abnormal glucose. Women who did not return for testing at 6 to 12 weeks postpartum were more likely to have less education, have Medicaid, and to have GDM previously (Table 2). [corrected]. Conclusion Performing GTTs on postpartum day 2 is feasible and should be further investigated as an alternative postpartum testing regimen in GDM.

Clinical Communities at Johns Hopkins Medicine: An Emerging Approach to Quality Improvement.

BACKGROUND: Clinical communities are an emerging approach to quality improvement (QI) to which several large-scale projects have attributed some success. In 2011 the Armstrong Institute for Patient Safety and Quality established clinical communities as a core strategy to connect frontline providers from six different hospitals to improve quality of care, patient safety, and value across the health system. CLINICAL COMMUNITIES: Fourteen clinical communities that presented great opportunity for improvement were established. A community could focus on a clinical area, a patient population, a group, a process, a safety-related issue, or nearly any health care issue. The collaborative spirit of the communities embraced interdisciplinary membership and representation from each hospital in each community. Communities engaged in team-building activities and facilitated discussions, met monthly, and were encouraged to meet in person to develop relationships and build trust. After a community was established, patients and families were invited to join and share their perspectives and experiences. ENABLING STRUCTURES: The clinical community structure provided clinicians access to resources, such as technical experts and safety and QI researchers, that were not easily otherwise accessible or available. Communities convened clinicians from each hospital to consider safety problems and their resolution and share learning with workplace peers and local unit safety teams. CONCLUSION: The clinical communities engaged 195 clinicians from across the health system in QI projects and peer learning. Challenges included limited financial support and time for clinicians, timely access to data, limited resources from the health system, and not enough time with improvement experts.

Developing a program, a curriculum, a scenario.

Simulation in obstetrics and maternal-fetal medicine is an educational tool that can be employed to address local and national learning objectives for residents and fellows. Simulation may also be incorporated as part of a comprehensive patient safety program to improve maternal and neonatal outcomes. Our objective is to identify steps in designing an effective simulation program, curricula, and scenario using available evidence and drawing on experience. Identification of needs, leadership, and financial and logistic resources is the first step in program design. An appropriate curriculum may be crafted with the intended audience and clear learning objectives in mind. Simulation scenario design is best achieved in a stepwise, layered fashion and must incorporate time for debriefing, feedback, and didactics. Simulation programs of any size, budget, and scope can be successfully implemented at the local, regional, and national levels to enhance education and improve patient safety.

Warm-up on a simulator improves residents' performance in laparoscopic surgery: a randomized trial.

INTRODUCTION AND HYPOTHESIS: Our aim was to assess the impact of immediate preoperative laparoscopic warm-up using a simulator on intraoperative laparoscopic performance by gynecologic residents. METHODS: Eligible laparoscopic cases performed for benign, gynecologic indications were randomized to be performed with or without immediate preoperative warm-up. Residents randomized to warm-up performed a brief set of standardized exercises on a laparoscopic trainer immediately before surgery. Intraoperative performance was scored using previously validated global rating scales. Assessment was made immediately after surgery by attending faculty who were blinded to the warm-up randomization. RESULTS: We randomized 237 residents to 47 minor laparoscopic cases (adnexal/ tubal surgery) and 44 to major laparoscopic cases (hysterectomy). Overall, attendings rated upper-level resident performances (postgraduate year [PGY-3, 4]) significantly higher on global rating scales than lower-level resident performances (PGY-1, 2). Residents who performed warm-up exercises prior to surgery were rated significantly higher on all subscales within each global rating scale, irrespective of the difficulty of the surgery. Most residents felt that performing warm-up exercises helped their intraoperative performances. CONCLUSION: Performing a brief warm-up exercise before a major or minor laparoscopic procedure significantly improved the intraoperative performance of residents irrespective of the difficulty of the case.

Obesity management in gynecologic cancer survivors: provider practices and attitudes.

OBJECTIVE: Obesity is associated with the development and risk of death from several women's cancers. The study objective was to describe and compare oncologic providers' attitudes and practices as they relate to obesity counseling and management in cancer survivors. STUDY DESIGN: Society of Gynecologic Oncology members (n = 924) were surveyed with the use of a web-based, electronic questionnaire. χ(2) and Fisher exact tests were used to analyze responses. RESULTS: Of the 240 respondents (30%), 92.9% were practicing gynecologic oncologists or fellows, and 5.1% were allied health professionals. Median age was 42 years; 50.8% of the respondents were female. Of the respondents, 42.7% reported that they themselves were overweight/obese and that ≥50% of their survivor patients were overweight/obese. Additionaly, 82% of the respondents believed that discussing weight would not harm the doctor-patient relationship. Most of the respondents (95%) agreed that addressing lifestyle modifications with survivors is important. Respondents believed that gynecologic oncologists (85.1%) and primary care providers (84.5%) were responsible for addressing obesity. More providers who were ≤42 years old reported undergoing obesity management training (P < .001) and were more likely to believe that survivors would benefit from obesity education than providers who were >42 years old (P = .017). After initial counseling, 81.5% of the respondents referred survivors to other providers for obesity interventions. CONCLUSION: Oncology provider respondents believe that addressing obesity with cancer survivors is important. Providers believed themselves to be responsible for initial counseling but believed that obesity interventions should be directed by other specialists. Further research is needed to identify barriers to care for obese cancer survivors and to improve physician engagement with obesity counseling in the "teachable moment" that is provided by a new cancer diagnosis.

Strenuous exercise during pregnancy: is there a limit?

OBJECTIVE: The purpose of this study was to evaluate fetal responses to strenuous exercise in physically active and inactive women. STUDY DESIGN: Forty-five healthy women (15 who were nonexercisers, 15 who were regularly active, 15 who were highly active) underwent a peak treadmill test at 28 weeks' gestation to 32 weeks 6 days' gestation. Fetal well-being (umbilical artery Doppler indices, fetal heart tracing/rate, biophysical profile [BPP]) was evaluated before and after exercise. Uterine artery Doppler scans were also obtained. RESULTS: Umbilical and uterine artery Doppler indices were similar among activity groups and did not change with exercise (P > .05). BPP and fetal heart tracings were reassuring in all groups. However, subgroup analyses showed transient fetal heart rate decelerations after exercise and elevated umbilical and uterine artery Doppler indices in 5 highly active women. After this, BPP and fetal heart tracings were reassuring. CONCLUSION: Overall fetal well-being is reassuring after short-duration, strenuous exercise in both active and inactive pregnant women. A subset of highly active women experienced transient fetal heart rate decelerations and Doppler changes immediately after exercise. Athletes may push beyond a threshold intensity at which fetal well-being may be compromised. However, potential impact on neonatal outcomes is unknown.

Exercise during pregnancy: fetal responses to current public health guidelines.

OBJECTIVE: To evaluate acute fetal responses to individually prescribed exercise according to existing guidelines (U.S. Department of Health and Human Services) in active and inactive pregnant women. METHODS: Forty-five healthy pregnant women (15 nonexercisers, 15 regularly active, 15 highly active) were tested between 28 0/7 and 32 6/7 weeks of gestation. After a treadmill test to volitional fatigue, target heart rates were calculated for two subsequent 30-minute treadmill sessions: 1) moderate intensity (40-59% heart rate reserve); and 2) vigorous intensity (60-84%). All women performed the moderate test; only active women performed the vigorous test. Fetal well-being measures included umbilical artery Dopplers, fetal heart tracing and rate, and biophysical profile. Measures were obtained at rest and immediately postexercise. RESULTS: Groups were similar in age, body mass index, and gestational age. Maternal resting heart rate in the highly active group (61.6 ± 7.2 beats per minute [bpm]) was significantly lower than the nonexercise (79.0 ± 11.6 bpm) and regularly active (71.9 ± 7.4 bpm) groups (P<.001). Treadmill time was longer in highly active (22.3 ± 2.9 minutes) than regularly active (16.6 ± 3.4) and nonexercise (12.1 ± 3.6) groups (P<.001), reflecting higher fitness. With moderate exercise, all umbilical artery Doppler indices were similar pre-exercise and postexercise among groups. With vigorous exercise, Dopplers were similar in regularly and highly active women with statistically significant decreases postexercise (P<.05). The group × time interaction was not significant. Postexercise fetal heart tracings met criteria for reactivity within 20 minutes after all tests. Biophysical profile scores were reassuring. CONCLUSION: This study supports existing guidelines indicating pregnant women may begin or maintain an exercise program at moderate (inactive) or vigorous (active) intensities.