Serotonin Syndrome After Treatment of Nausea and Vomiting in Pregnancy.

BACKGROUND: Nausea and vomiting in pregnancy often require pharmacotherapy for symptom management. Serotonin syndrome is a rare clinical entity that can be precipitated by the medications used to treat nausea and vomiting in pregnancy. CASE: A 35-year-old pregnant individual with a history of hyperemesis gravidarum in an earlier pregnancy requiring prolonged hospitalization presented with nausea and vomiting at 7 weeks of gestation. She was incidentally found to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection when she was universally screened at the time of admission. She required pharmacotherapy, including prochlorperazine and ondansetron for treatment of nausea as well as sumatriptan for migraine. She developed acute spasticity, autonomic dysfunction, and temperature rise, precipitated by antiemetic therapy, consistent with serotonin syndrome. The syndrome resolved with supportive care and benzodiazepines. CONCLUSION: Serotonin syndrome is a serious clinical entity that can be provoked by the pharmacotherapy given to treat nausea and vomiting in pregnancy. This medical emergency requires early recognition and prompt management.

Cardiovascular Complications of Pregnancy-Associated COVID-19 Infections.

Cardiovascular complications are frequently present in coronavirus-2019 (COVID-19) infection. These include microvascular and macrovascular thrombotic complications such as arterial and venous thromboembolism, myocardial injury or inflammation resulting in infarction, heart failure, and arrhythmias. Data suggest increased risk of adverse outcomes in pregnant compared with nonpregnant women of reproductive age with COVID-19 infection, including need for intensive care unit admission, mechanical ventilation, and extracorporeal membrane oxygenation utilization. Current statements addressing COVID-19-associated cardiac complications do not include pregnancy complications that may mimic COVID-19 complications such as peripartum cardiomyopathy, spontaneous coronary artery dissection, and preeclampsia. Unique to pregnancy, COVID-19 complications can result in preterm delivery and modify management of the pregnancy. Moreover, pregnancy has often been an exclusion criterion for enrollment in research studies. In this review, we summarize what is known about pregnancy-associated COVID-19 cardiovascular complications.

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.

Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial.

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

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.

Severe and critical COVID-19 in pregnancy: A case series from Montreal.

BACKGROUND: Optimal obstetric management for women with coronavirus disease (COVID-19) is not known. We describe the management of six pregnant women requiring in-hospital care for severe COVID-19. METHODS: A retrospective chart review was conducted to identify pregnant women who tested positive for Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) between 15 March and 30 June 2020. A subset of women meeting criteria for severe COVID-19 was included. RESULTS: Four women required non-invasive supplemental oxygen therapy and two required mechanical ventilation. Four women were discharged from hospital undelivered and two required preterm delivery. One woman had a pulmonary embolism, and two required re-admission for worsening symptoms. CONCLUSION: Management of pregnant women with severe COVID-19 is complex and should involve multidisciplinary expertise. Avoiding early delivery may be a safe option. We recommend an individualized approach to care, including careful consideration of the expected risks and benefits of expectant obstetric management versus delivery.

Obstetrical and Newborn Outcomes Among Patients With SARS-CoV-2 During Pregnancy.

We report on the perinatal outcomes of pregnant patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 2 hospitals in Montréal, Québec. Outcomes of 45 patients with SARS-CoV-2 during pregnancy were compared with those of 225 patients without infection. Sixteen percent of patients with SARS-CoV-2 delivered preterm, compared with 9% of patients without (P = 0.28). Median gestational age at delivery (39.3 (interquartile range [IQR] 37.7-40.4) wk vs. 39.1 [IQR 38.3-40.1] wk) and median birth weight (3250 [IQR 2780-3530] g vs. 3340 [IQR 3025-3665] g) were similar between groups. The rate of cesarean delivery was 29% for patients with SARS-CoV-2. Therefore, we did not find important differences in outcomes associated with SARS-CoV-2. Our findings may be limited to women with mild COVID-19 diagnosed in the third trimester.

Screening and Testing Pregnant Patients for SARS-CoV-2: First-Wave Experience of a Designated COVID-19 Hospitalization Centre in Montréal.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) may present asymptomatically in a large proportion of cases in endemic areas. Accordingly, universal testing has been suggested as a potential strategy for reducing transmission in the obstetrical setting. We describe the clinical characteristics of patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy at a designated COVID-19 hospitalization centre in Montréal, Québec. METHODS: A single-centre retrospective cohort was constructed to include all pregnant patients who tested positive for SARS-CoV-2 between March 22 and July 31, 2020, and received care at the Jewish General Hospital. Initially, testing was restricted to at-risk patients, identified through the use of a screening questionnaire. Beginning on May 15, 2020, universal testing was implemented, and all pregnant patients admitted to the hospital were tested. Data were collected through chart review. RESULTS: Of 803 patients tested for SARS-CoV-2 during the study period, 41 (5%) tested positive. Among those patients who were symptomatic, the most commonly reported symptoms were cough (53%), fever (37%), dyspnea (30%), and anosmia and/or ageusia (20%). Before the implementation of universal testing, 13% (3 of 24) of patients with SARS-CoV-2 were asymptomatic. After implementation of universal testing, 80% (8 of 10) of patients with SARS-CoV-2 were asymptomatic. CONCLUSION: Our findings suggest that most pregnant patients with SARS-CoV-2 are asymptomatic or have mild symptoms of COVID-19. Particularly in endemic areas, universal testing of pregnant patients presenting to the hospital should be strongly considered as an important measure to prevent in-hospital and community transmission of COVID-19.

A critical review of the pathophysiology of thrombotic complications and clinical practice recommendations for thromboprophylaxis in pregnant patients with COVID-19.

Those who are infected with Severe Acute Respiratory Syndrome-related CoronaVirus-2 are theoretically at increased risk of venous thromboembolism during self-isolation if they have reduced mobility or are dehydrated. Should patients develop coronavirus disease (COVID-19) pneumonia requiring hospital admission for treatment of hypoxia, the risk for thromboembolic complications increases greatly. These thromboembolic events are the result of at least two distinct mechanisms - microvascular thrombosis in the pulmonary system (immunothrombosis) and hospital-associated venous thromboembolism. Since pregnancy is a prothrombotic state, there is concern regarding the potentially increased risk of thrombotic complications among pregnant women with COVID-19. To date, however, pregnant women do not appear to have a substantially increased risk of thrombotic complications related to COVID-19. Nevertheless, several organizations have vigilantly issued pregnancy-specific guidelines for thromboprophylaxis in COVID-19. Discrepancies between these guidelines reflect the altruistic wish to protect patients and lack of high-quality evidence available to inform clinical practice. Low molecular weight heparin (LMWH) is the drug of choice for thromboprophylaxis in pregnant women with COVID-19. However, its utility in non-pregnant patients is only established against venous thromboembolism, as LMWH may have little or no effect on immunothrombosis. Decisions about initiation and duration of prophylactic anticoagulation in the context of pregnancy and COVID-19 must take into consideration disease severity, outpatient vs inpatient status, temporal relation between disease occurrence and timing of childbirth, and the underlying prothrombotic risk conferred by additional comorbidities. There is currently no evidence to recommend the use of intermediate or therapeutic doses of LMWH in thromboprophylaxis, which may increase bleeding risk without reducing thrombotic risk in pregnant patients with COVID-19. Likewise, there is no evidence to comment on the role of low-dose aspirin in thromboprophylaxis or of anti-cytokine and antiviral agents in preventing immunothrombosis. These unanswered questions are being studied within the context of clinical trials.