Anick Bérard1,2,3, Odile Sheehy1, Jin-Ping Zhao1, Evelyne Vinet4, Caroline Quach1,5, Behrouz Kassai3, Sasha Bernatsky4. 1. Research Center, CHU Sainte-Justine, Montreal, Quebec, Canada. 2. Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada. 3. Faculty of Medicine, Université Claude Bernard, Lyon, France. 4. Faculty of Medicine, McGill University, Montreal, Quebec, Canada. 5. Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
Abstract
BACKGROUND: Medications already available to treat other conditions are presently being studied in clinical trials as potential treatments for COVID-19. Given that pregnant women are excluded from these trials, we aimed to investigate their safety when used during pregnancy within a unique population source. METHODS: Using the population-based Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn (1998-2015). Taking potential confounders into account including indications for use, the risk of prematurity, low birth weight (LBW), small for gestational age (SGA), and major congenital malformation (MCM) associated with COVID-19 repurposed drug use during pregnancy were quantified using generalized estimation equations. RESULTS: Of the 231,075 eligible pregnancies, 107 were exposed to dexamethasone (0.05%), 31 to interferons (0.01%), 1,398 to heparins (0.60%), 24 to angiotensin-receptor blockers (ARB) (0.01%), 182 to chloroquine (0.08%), 103 to hydroxychloroquine (0.05%), 6,206 to azithromycin (2.70%), 230 to oseltamivir (0.10%), and 114 to HIV medications (0.05%). Adjusting for potential confounders, we observed an increased risk of prematurity related to dexamethasone (aOR 1.92, 95%CI 1.11-3.33; 15 exposed cases), anti-thrombotics (aOR 1.58, 95%CI 1.31-1.91; 177 exposed cases), and HIV medications (aOR 2.04, 95%CI 1.01-4.11; 20 exposed cases) use. An increased risk for LBW associated with anti-thrombotics (aOR 1.72, 95%CI 1.41-2.11; 152 exposed cases), and HIV medications (aOR 2.48, 95%CI 1.25-4.90; 21 exposed cases) use were also found. Gestational exposure to anti-thrombotics (aOR 1.20, 95%CI 1.00-1.44; 176 exposed cases), and HIV medications (aOR 2.61, 95%CI 1.51-4.51; 30 exposed cases) were associated with SGA. First-trimester dexamethasone (aOR 1.66, 95%CI 1.02-2.69; 20 exposed cases) and azithromycin (aOR 1.10, 95%CI 1.02-1.19; 747 exposed cases) exposures were associated with MCM. CONCLUSIONS: Many available medications considered as treatments for COVID-19 are associated with adverse pregnancy outcomes. Caution is warranted when considering these medications during the gestational period.
BACKGROUND: Medications already available to treat other conditions are presently being studied in clinical trials as potential treatments for COVID-19. Given that pregnant women are excluded from these trials, we aimed to investigate their safety when used during pregnancy within a unique population source. METHODS: Using the population-based Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn (1998-2015). Taking potential confounders into account including indications for use, the risk of prematurity, low birth weight (LBW), small for gestational age (SGA), and major congenital malformation (MCM) associated with COVID-19 repurposed drug use during pregnancy were quantified using generalized estimation equations. RESULTS: Of the 231,075 eligible pregnancies, 107 were exposed to dexamethasone (0.05%), 31 to interferons (0.01%), 1,398 to heparins (0.60%), 24 to angiotensin-receptor blockers (ARB) (0.01%), 182 to chloroquine (0.08%), 103 to hydroxychloroquine (0.05%), 6,206 to azithromycin (2.70%), 230 to oseltamivir (0.10%), and 114 to HIV medications (0.05%). Adjusting for potential confounders, we observed an increased risk of prematurity related to dexamethasone (aOR 1.92, 95%CI 1.11-3.33; 15 exposed cases), anti-thrombotics (aOR 1.58, 95%CI 1.31-1.91; 177 exposed cases), and HIV medications (aOR 2.04, 95%CI 1.01-4.11; 20 exposed cases) use. An increased risk for LBW associated with anti-thrombotics (aOR 1.72, 95%CI 1.41-2.11; 152 exposed cases), and HIV medications (aOR 2.48, 95%CI 1.25-4.90; 21 exposed cases) use were also found. Gestational exposure to anti-thrombotics (aOR 1.20, 95%CI 1.00-1.44; 176 exposed cases), and HIV medications (aOR 2.61, 95%CI 1.51-4.51; 30 exposed cases) were associated with SGA. First-trimester dexamethasone (aOR 1.66, 95%CI 1.02-2.69; 20 exposed cases) and azithromycin (aOR 1.10, 95%CI 1.02-1.19; 747 exposed cases) exposures were associated with MCM. CONCLUSIONS: Many available medications considered as treatments for COVID-19 are associated with adverse pregnancy outcomes. Caution is warranted when considering these medications during the gestational period.
Authors: Anick Bérard; Padma Kaul; Sherif Eltonsy; Brandace Winquist; Dan Chateau; Steven Hawken; Ann Sprague; Mark Walker; Sasha Bernatsky; Michal Abrahamowicz; Cristiano Soares de Moura; Évelyne Vinet; Bruce Carleton; Gillian Hanley; Tim Oberlander; Odile Sheehy; Yessica Haydee Gomez; Jessica Gorgui; Anamaria Savu Journal: PLoS One Date: 2022-09-20 Impact factor: 3.752