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

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.

The Canadian Mother-Child Cohort Active Surveillance Initiative (CAMCCO): Comparisons between Quebec, Manitoba, Saskatchewan, and Alberta

“…Alberta and Quebec systematically reported higher annual rates of malformations, 16.4% and 10.4%, respectively. This is consistent with Quebec’s founders’ effect [ 16 ] (i.e. a relatively small number of French settlers were ancestors of a large number of families in France), and Zhao et al [ 17 ]; it could also be explained in part by the fact that women of lower socio-economic status have poorer health or poor lifestyle habits.…”

Chloroquine and Hydroxychloroquine Use During Pregnancy and the Risk of Adverse Pregnancy Outcomes Using Real-World Evidence

“…QPC data on prescriptions filled ( Zhao et al, 2017 ), MCM ( Blais et al, 2013 ), gestational age ( Vilain et al, 2008 ) and birth weight ( Vilain et al, 2008 ) have been validated. We have adjusted for all known and measurable potential confounding variables for unfavorable pregnancy outcomes, including maternal chronic comorbidities, indications for study medication uses, lifestyles variables including the use of alcohol, tobacco, illicit substances, and high dose folic acid; adjustment was also made on health care utilization, which is considered as a proxy for diseases severity ( Bérard et al, 2021 ).…”

“…Both the PPV and NPV for medication use were high within the QPC. Because we only included pregnant women covered by the Quebec prescription drug insurance plan, generalizability of results to those covered by private medication insurance could be affected ( Bérard et al, 2021 ). However, validation studies have shown that publicly insured pregnant women have similar characteristics and co-morbidities with those who have private drug insurance plans ( Bérard and Lacasse, 2009 ).…”

Pregnancy, peripartum, and COVID-19: An updated literature review

“…Although, compared to prednisolone, methylprednisolone achieves higher lungs concentrations [156], based on the RECOVERY trial findings, oral prednisolone, and intravenous hydrocortisone are recommended for moderate to severe cases of COVID-19 [157]. WHO recommends oral dexamethasone or intravenous hydrocortisone in severe cases of COVID-19, but studies have recommended against dexamethasone during pregnancy, which is linked with an increased risk of prematurity and adversely affects skeletogenesis [158,159]. Limited data support dexamethasone in postpartum patients; therefore, methylprednisolone is recommended instead [160].…”