mRNA COVID‐19 vaccination early in pregnancy and the risk of spontaneous abortion in an international pregnancy registry

Abstract

Purpose: mRNA COVID-19 vaccines are used in pregnant populations whether advertently or inadvertently. However, evidence on the safety of these vaccines during pregnancy is limited. The objective of this study is to evaluate the effect of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (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 BNT162b2 or mRNA-1273 and enrolled in the COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER) 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 selfadministered 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) comparing the two vaccines groups stratified by country of residence and gestational age at enrollment.Results: Among 6840 participants who received at least one dose of BNT162b2 or mRNA-1273 at any time in pregnancy between Jan-Sep, 2021, 2129 met the inclusion criteria (1576 received BNT162b2 and 553 mRNA-1273). The two groups were balanced in terms of baseline characteristics. There were 37 SABs, with an overall 13.4% estimated cumulative risk by 20 weeks of gestation, which is similar to the expected risk in the population. The HR of SAB comparing mRNA-1273 to BNT162b2 was 1.46 (95% CI: 0.66, 3.22). Conclusion:The C-VIPER data show no evidence that mRNA COVID-19 vaccines increase the risk of SAB.

Safety of Monoclonal Antibodies Inhibiting PCSK9 in Pregnancy: Disproportionality Analysis in VigiBase®

“…These included eight events of spontaneous abortion, two live newborn, one fetal death, one premature baby (with maternal pre‐existing diabetes as alternative cause), 12 and a congenital central nervous system anomaly (with alprazolam as coreported drug and potential alternative cause) 13 . Two safety reports of spontaneous abortion had alternative potential causes: maternal age > 35 years 14 and coreported drugs elasomeran and fluoxetine, respectively 15,16 …”

“…13 Two safety reports of spontaneous abortion had alternative potential causes: maternal age > 35 years 14 and coreported drugs elasomeran and fluoxetine, respectively. 15,16 Disproportionality analyses for spontaneous abortion Spontaneous abortion was the only pregnancy outcome reported in more than five safety reports for which disproportionality analysis could be performed. Reporting of spontaneous abortion with alirocumab evolocumab was similar to that within the full database (ROR 0.06, 95% CI 0.03-0.12).…”

Miscarriage after SARS‐CoV‐2 vaccination: A population‐based cohort study

“…Further, misclassification of exposure by the estimated date of conception was partly mitigated by applying a validated algorithm for estimating gestational age within the first trimester of pregnancy, 13 and by the additional analyses shifting the date of conception by 2 weeks. Lastly, the current study identified a miscarriage or induced abortion as that occurring up to 19 completed weeks’ gestation, a convention used by others in the study of SARS‐CoV‐2 vaccination early in pregnancy 21 . While this same time‐point is used in Canada 22 and in major clinical reviews, 23 other jurisdictions, such as the UK, consider miscarriage as that occurring up to 23 completed weeks’ gestation 24…”

“…Lastly, the current study identified a miscarriage or induced abortion as that occurring up to 19 completed weeks' gestation, a convention used by others in the study of SARS-CoV-2 vaccination early in pregnancy. 21 While this same timepoint is used in Canada 22 and in major clinical reviews, 23 other jurisdictions, such as the UK, consider miscarriage as that occurring up to 23 completed weeks' gestation. 24…”