mRNA COVID-19 Vaccination Early in Pregnancy and Risk of Spontaneous Abortion in an International Pregnancy Registry

Background: Messenger RNA (mRNA) Coronavirus disease 2019 (COVID-19) vaccines are used in pregnant populations whether advertently or inadvertently. However, evidence on the safety of these vaccines during pregnancy is limited as pregnant women were excluded from preapproval clinical trials.

Objective: To evaluate the effect of Comirnaty (Pfizer-BioNTech) and Spikevax (Moderna) vaccination during the first 20 weeks of gestation on the risk of spontaneous abortion (SAB)

Objectives: To evaluate the effect of Comirnaty (Pfizer-BioNTech) and Spikevax (Moderna) vaccination during the first 20 weeks of gestation on the risk of spontaneous abortion (SAB)

Methods: All pregnant women who received at least one dose of Comirnaty or Spikevax and enrolled in the COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER) early in pregnancy were prospectively followed from enrollment until 20 weeks of gestation, SAB, or loss to follow-up. Baseline demographics, vaccination information, and pregnancy outcomes were collected via monthly online self-administered questionnaires, vaccination certificates, and medical records. Life tables were used to calculate the cumulative risk of SAB. Cox regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) comparing the two vaccines

Results: Among 6,739 participants who received at least one dose of Comirnaty or Spikevax at any time in pregnancy between Jan-Sep, 2021 in C-VIPER, 2,133 met the inclusion criteria (1,579 received Comirnaty and 554 Spikevax). The two groups were balanced in terms of baseline characteristics. However, the median gestational age (GA) at vaccination was earlier for Spikevax than for Comirnaty (4.6 vs. 7.3 weeks), and Spikevax was most common in the US. There were 44 SABs, with a 13.5% (95% CI 9.3%, 17.7%) estimated cumulative risk of SAB by 20 weeks of gestation. The crude HR of SAB comparing Spikevax to Comirnaty was 1.99 (95% CI 1.08, 3.70). The HR was reduced to 1.49 (95% CI 0.73, 3.04) after stratifying by country and GA at vaccination

Conclusions: In a large, international COVID-19 vaccine pregnancy registry, the risk of SAB among women who received an mRNA vaccine early in pregnancy was consistent with that expected in the general population (10-20%). We observed a higher risk of SAB in study participants vaccinated with Spikevax compared to Comirnaty, which was partially explained by imbalances in the GA at vaccination. Adjusted results were most compatible with HRs from 0.73 to 3.04. Accumulation of data will allow more precise estimation