Placental transfer and safety in pregnancy of medications under investigation to treat COVID-19

Louchet, Margaux; Sibiude, Jeanne; Peytavin, Gilles; Picone, Olivier; Tréluyer, Jean-Marc; Mandelbrot, Laurent

Abstract Background Treatment of COVID-19 is mostly symptomatic, but a wide range of medications are under investigation against SARS-CoV-2. Although pregnant women are excluded from clinical trials, they will inevitably receive therapies whenever they appear effective in non-pregnant patients and even under compassionate use. Method We conducted a review of the literature on placental transfer and pregnancy safety data of drugs under current investigation for COVID-19. Results Regarding remdesivir, there are no data in pregnant women. Several other candidates already have safety data in pregnant women, since they are repurposed drugs already used for their established indications. They may thus be used in pregnancy, although their safety in the context of COVID-19 may differ from conventional use. These include the HIV protease inhibitors such as lopinavir/ritonavir which have low placental transfer; interferon which does not cross the placental barrier, and (hydroxy) chloroquine, which have high placental transfer. There are also pregnancy safety and placental transfer data for colchicine, steroids, oseltamivir and azithromycin, as well as some monoclonals. However, some drugs are strictly prohibited in pregnancy due to known teratogenicity (thalidomide) or fetal toxicities (renin-angiotensin system blockers). Other candidates including tocilizumab and other IL-6 inhibitors, umifenovir and favipiravir have insufficient data on pregnancy outcomes. Conclusion In life-threatening cases of COVID-19, the potential risks of therapy to the fetus may be more than offset by the benefit of curing the mother. While preclinical and placental transfer studies are required for a number of potential anti-SARS CoV2 drugs, several medications can already be used in pregnant women.