ABSTRACT
Objectives: Excluding pregnant persons from COVID-19 trials of intervention may lead to unintended harmful consequences. Beliefs and attitudes of clinicians have the potential to shape clinical research involving pregnant women. This study evaluates the current perspectives of Canadian physicians on the participation of pregnant women in COVID-19 clinical trials. Methods: An anonymous 22-item online questionnaire was sent to Canadian physicians belonging to four Canadian professional associations. Physicians were surveyed regarding the inclusion of pregnant women in COVID-19 trials using a semi-quantitative approach with multiple choice and open-ended questions. Descriptive statistics were performed. Themes from free-text answers were extracted using a semi-inductive approach. Results: 202 physicians agreed to participate, 168 of which completed the survey. 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%). In addition, 66% (107/161) of physicians responded that including pregnant women in COVID-19 trials was urgent. The main barriers to including pregnant women in COVID-19 trials were perceived unwillingness of pregnant patients to take part in clinical trials, perceived unwillingness of treating teams to offer participation, burden of regulatory approval, and a general ‘culture of exclusion’ of pregnant women from clinical trials. Conclusions: Most physicians surveyed were supportive of the inclusion of pregnant women in COVID-19 trials of intervention. Importantly, we describe why some physicians may be reluctant to include pregnant women in clinical trials and identify important barriers to be addressed for the appropriate participation of pregnant women in clinical research.
ABSTRACT
In this review, we summarize evidence regarding the use of routine and investigational pharmacologic interventions for pregnant and lactating patients with coronavirus disease 2019 (COVID-19). Antenatal corticosteroids may be used routinely for fetal lung maturation between 24 and 34 weeks' gestation, but decisions in those with critical illness and those < 24 or > 34 weeks' gestation should be made on a case-by-case basis. Magnesium sulfate may be used for seizure prophylaxis and fetal neuroprotection, albeit cautiously in those with hypoxia and renal compromise. There are no contraindications to using low-dose aspirin to prevent placenta-mediated pregnancy complications when indicated. An algorithm for thromboprophylaxis in pregnant patients with COVID-19 is presented, which considers disease severity, timing of delivery in relation to disease onset, inpatient vs outpatient status, underlying comorbidities and contraindications to the use of anticoagulation. Nitrous oxide may be administered for labor analgesia while using appropriate personal protective equipment. Intravenous remifentanil patient-controlled analgesia should be used with caution in patients with respiratory depression. Liberal use of neuraxial labor analgesia may reduce the need for emergency general anesthesia which results in aerosolization. Short courses of non-steroidal anti-inflammatory drugs can be administered for postpartum analgesia, but opioids should be used with caution due to the risk of respiratory depression. For mechanically ventilated pregnant patients, neuromuscular blockade should be used for the shortest duration possible and reversal agents should be available on hand if delivery is imminent. To date, dexamethasone is the only proven and recommended experimental treatment for pregnant patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen. Although hydroxycholoroquine, lopinavir/ritonavir and remdesivir may be used during pregnancy and lactation within the context of clinical trials, data from non-pregnant populations have not shown benefit. The role of monoclonal antibodies (tocilizumab), immunomodulators (tacrolimus), interferon, inhaled nitric oxide and convalescent plasma in pregnancy and lactation needs further evaluation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.