COVID-19 critical illness in pregnancy.

Although the pregnant population was affected by early waves of the COVID-19 pandemic, increasing transmission and severity due to new viral variants has resulted in an increased incidence of severe illness during pregnancy in many regions. Critical illness and respiratory failure are relatively uncommon occurrences during pregnancy, and there are limited high-quality data to direct management. This paper reviews the current literature on COVID-19 management as it relates to pregnancy, and provides an overview of critical care support in these patients. COVID-19 drug therapy is similar to that used in the non-pregnant patient, including anti-inflammatory therapy with steroids and IL-6 inhibitors, although safety data are limited for antiviral drugs such as remdesivir and monoclonal antibodies. As both pregnancy and COVID-19 are thrombogenic, thromboprophylaxis is essential. Endotracheal intubation is a higher risk during pregnancy, but mechanical ventilation should follow usual principles. ICU management should be directed at optimizing maternal well-being, which in turn will benefit the fetus.

Adapting obstetric and neonatal services during the COVID-19 pandemic: a scoping review.

BACKGROUND: The provision of care to pregnant persons and neonates must continue through pandemics. To maintain quality of care, while minimizing physical contact during the Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV2) pandemic, hospitals and international organizations issued recommendations on maternity and neonatal care delivery and restructuring of clinical and academic services. Early in the pandemic, recommendations relied on expert opinion, and offered a one-size-fits-all set of guidelines. Our aim was to examine these recommendations and provide the rationale and context to guide clinicians, administrators, educators, and researchers, on how to adapt maternity and neonatal services during the pandemic, regardless of jurisdiction. METHOD: Our initial database search used Medical subject headings and free-text search terms related to coronavirus infections, pregnancy and neonatology, and summarized relevant recommendations from international society guidelines. Subsequent targeted searches to December 30, 2020, included relevant publications in general medical and obstetric journals, and updated society recommendations. RESULTS: We identified 846 titles and abstracts, of which 105 English-language publications fulfilled eligibility criteria and were included in our study. A multidisciplinary team representing clinicians from various disciplines, academics, administrators and training program directors critically appraised the literature to collate recommendations by multiple jurisdictions, including a quaternary care Canadian hospital, to provide context and rationale for viable options. INTERPRETATION: There are different schools of thought regarding effective practices in obstetric and neonatal services. Our critical review presents the rationale to effectively modify services, based on the phase of the pandemic, the prevalence of infection in the population, and resource availability.

Clinical decision analysis of elective delivery vs expectant management for pregnant individuals with COVID-19-related acute respiratory distress syndrome.

BACKGROUND: Pregnant individuals are vulnerable to COVID-19-related acute respiratory distress syndrome. There is a lack of high-quality evidence on whether elective delivery or expectant management leads to better maternal and neonatal outcomes. OBJECTIVE: This study aimed to determine whether elective delivery or expectant management are associated with higher quality-adjusted life expectancy for pregnant individuals with COVID-19-related acute respiratory distress syndrome and their neonates. STUDY DESIGN: We performed a clinical decision analysis using a patient-level model in which we simulatedpregnant individuals and their unborn children. We used a patient-level model with parallel open-cohort structure, daily cycle length, continuous discounting, lifetime horizon, sensitivity analyses for key parameter values, and 1000 iterations for quantification of uncertainty. We simulated pregnant individuals at 32 weeks of gestation, invasively ventilated because of COVID-19-related acute respiratory distress syndrome. In the elective delivery strategy, pregnant individuals received immediate cesarean delivery. In the expectant management strategy, pregnancies continued until spontaneous labor or obstetrical decision to deliver. For both pregnant individuals and neonates, model outputs were hospital or perinatal survival, life expectancy, and quality-adjusted life expectancy denominated in years, summarized by the mean and 95% credible interval. Maternal utilities incorporated neonatal outcomes in accordance with best practices in perinatal decision analysis. RESULTS: Model outputs for pregnant individuals were similar when comparing elective delivery at 32 weeks' gestation with expectant management, including hospital survival (87.1% vs 87.4%), life-years (difference, -0.1; 95% credible interval, -1.4 to 1.1), and quality-adjusted life expectancy denominated in years (difference, -0.1; 95% credible interval, -1.3 to 1.1). For neonates, elective delivery at 32 weeks' gestation was estimated to lead to a higher perinatal survival (98.4% vs 93.2%; difference, 5.2%; 95% credible interval, 3.5-7), similar life-years (difference, 0.9; 95% credible interval, -0.9 to 2.8), and higher quality-adjusted life expectancy denominated in years (difference, 1.3; 95% credible interval, 0.4-2.2). For pregnant individuals, elective delivery was not superior to expectant management across a range of scenarios between 28 and 34 weeks of gestation. Elective delivery in cases where intrauterine death or maternal mortality were more likely resulted in higher neonatal quality-adjusted life expectancy, as did elective delivery at 30 weeks' gestation (difference, 1.1 years; 95% credible interval, 0.1 - 2.1) despite higher long-term complications (4.3% vs 0.5%; difference, 3.7%; 95% credible interval, 2.4-5.1), and in cases where intrauterine death or maternal acute respiratory distress syndrome mortality were more likely. CONCLUSION: The decision to pursue elective delivery vs expectant management in pregnant individuals with COVID-19-related acute respiratory distress syndrome should be guided by gestational age, risk of intrauterine death, and maternal acute respiratory distress syndrome severity. For the pregnant individual, elective delivery is comparable but not superior to expectant management for gestational ages from 28 to 34 weeks. For neonates, elective delivery was superior if gestational age was ≥30 weeks and if the rate of intrauterine death or maternal mortality risk were high. We recommend basing the decision for elective delivery vs expectant management in a pregnant individual with COVID-19-related acute respiratory distress syndrome on gestational age and likelihood of intrauterine or maternal death.

Feasibility of establishing a Canadian Obstetric Survey System (CanOSS) for severe maternal morbidity: a study protocol.

INTRODUCTION: Severe maternal morbidity (SMM)-an unexpected pregnancy-associated maternal outcome resulting in severe illness, prolonged hospitalisation or long-term disability-is recognised by many, as the preferred indicator of the quality of maternity care, especially in high-income countries. Obtaining comprehensive details on events and circumstances leading to SMM, obtained through maternity units, could complement data from large epidemiological studies and enable targeted interventions to improve maternal health. The aim of this study is to assess the feasibility of gathering such data from maternity units across Canadian provinces and territories, with the goal of establishing a national obstetric survey system for SMM in Canada. METHODS AND ANALYSIS: We propose a sequential explanatory mixed-methods study. We will first distribute a cross-sectional survey to leads of all maternity units across Canada to gather information on (1) Whether the unit has a system for reviewing SMM and the nature and format of this system, (2) Willingness to share anonymised data on SMM by direct entry using a web-based platform and (3) Respondents' perception on the definition and leading causes of SMM at a local level. This will be followed by semistructured interviews with respondent groups defined a priori, to identify barriers and facilitators for data sharing. We will perform an integrated analysis to determine feasibility outcomes, a narrative description of barriers and facilitators for data-sharing and resource implications for data acquisition on an annual basis, and variations in top-5 causes of SMM. ETHICS AND DISSEMINATION: The study has been approved by the Mount Sinai and Hamilton Integrated Research Ethics Boards. The study findings will be presented at annual scientific meetings of the Society of Obstetricians and Gynaecologists of Canada, North American Society of Obstetric Medicine, and International Network of Obstetric Survey Systems and published in an open-access peer-reviewed Obstetrics and Gynaecology or General Internal Medicine journal.

Tocilizumab for coronavirus disease 2019 in pregnancy and lactation: a narrative review.

BACKGROUND: Tocilizumab is a monoclonal antibody that interrupts interleukin-6 signalling, reducing downstream effects on inflammation and the innate immune response. It was shown to reduce mortality in patients with severe or critical coronavirus disease 2019 (COVID-19). Pregnant and breastfeeding people were largely excluded from clinical trials and hence, the extent to which results can be applied to these populations is not clear. OBJECTIVES: To synthesize published data on tocilizumab in pregnancy and lactation, highlight important knowledge gaps, and help inform clinical decision-making about tocilizumab's use in these populations with COVID-19. SOURCES: PubMed was searched for studies evaluating tocilizumab in pregnancy and lactation for COVID-19 and other indications. Literature on pharmacokinetics and reproductive/fetal safety of monoclonal antibodies in general was also sought. The US Food and Drug Administration and the European Medicines Agency guidance for the industry and regulatory approval documents were reviewed. CONTENT: Published data on tocilizumab in pregnancy include 610 cases (n = 20 with COVID-19) together with seven mother-infant breastfeeding pairs. Higher rates of spontaneous abortion and premature birth have been reported compared with the general population, but multiple confounding variables limit interpretation. There is little data on tocilizumab exposure in the second and third trimesters when transplacental transport is highest. The effects of tocilizumab on the developing immune system are unclear. Pregnant patients with COVID-19 who received tocilizumab were often critically ill and corticosteroid use was uncommon. Neonatal follow up was limited. Tocilizumab appears to be compatible with breastfeeding. IMPLICATIONS: Although the available data do not raise serious safety signals, they have significant limitations and are not sufficient to delineate the complete spectrum of potential adverse outcomes that may be associated with tocilizumab exposure during pregnancy and lactation. Diligent follow up and documentation of pregnancy outcomes will be important moving forward. A more effective regulatory framework to ensure equitable inclusion of pregnant people in research is clearly needed.

Physician Perspectives on Including Pregnant Women in Covid-19 Clinical Trials: Time for a Paradigm Change.

Excluding pregnant people from Covid-19 clinical trials may lead to unintended harmful consequences. For this study, an online questionnaire was sent to physicians belonging to Canadian professional medical associations in order to evaluate their perspectives on the participation of pregnant women in Covid-19 clinical trials. The majority of respondents expressed support for including pregnant women in Covid-19 trials (119/165; 72%), especially those investigating therapies with a prior safety record in pregnancy (139/164; 85%). The main perceived barriers to inclusion identified were unwillingness of pregnant patients to participate and of treating teams to offer participation, the burden of regulatory approval, and a general "culture of exclusion" of pregnant women from trials. We describe why some physicians may be reluctant to include pregnant individuals in trials, and we identify barriers to the appropriate participation of pregnant people in clinical research.

A review of remdesivir for COVID-19 in pregnancy and lactation.

Mounting evidence suggests that pregnant people have an elevated risk of severe COVID-19-related complications compared with their non-pregnant counterparts, underscoring the need for effective prevention and treatment strategies. However, despite progress in innovative and flexible trial designs during the COVID-19 pandemic, regressive policies excluding pregnant and breastfeeding people from biomedical research persist. Remdesivir, a broad-spectrum antiviral, was the first drug licensed for the treatment of COVID-19, based on data showing it reduced the time to recovery in hospitalized patients. Pregnant and breastfeeding people were specifically excluded from all clinical trials of remdesivir in COVID-19, but data are accumulating from post-marketing registries, compassionate use programmes and case series/reports. In this review we synthesize these data and highlight key knowledge gaps to help inform clinical decision-making about its use in pregnancy and lactation.