Available medications used as potential therapeutics for COVID-19: What are the known safety profiles in pregnancy

PLoS One. 2021 May 19;16(5):e0251746. doi: 10.1371/journal.pone.0251746. eCollection 2021.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects*
  • COVID-19 Drug Treatment*
  • Cohort Studies
  • Drug Repositioning / methods*
  • Female
  • Humans
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Live Birth / epidemiology
  • Pregnancy / drug effects*
  • Pregnancy Outcome / epidemiology
  • Premature Birth / chemically induced
  • Premature Birth / epidemiology
  • Quebec / epidemiology
  • Risk Factors
  • SARS-CoV-2 / drug effects

Substances

  • Antiviral Agents

Grants and funding

AB. Grant number 132750. Canadian Institutes of Health Research (CIHR) – CAN-AIM. AB. Grant number 30962. Fonds de la recherche du Québec – Santé (FRQS) - Réseau de recherche sur les médicaments. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.