Maternal and Infant Outcomes Following Exposure to SPIKEVAX During Pregnancy: An Observational Database Study

Background: Pregnant women face a higher risk of COVID-19 complications, including hospitalization or death. Adverse neonatal outcomes have also been reported among infants born to mothers infected with COVID-19. COVID-19 vaccines, including Spikevax by Moderna, became available in December 2020 and are recommended during pregnancy.

Objectives: This study evaluated the risk of pregnancy complications, adverse pregnancy outcomes, and adverse neonatal outcomes in pregnancies exposed to Spikevax (mRNA SARS-CoV-2 vaccine developed by Moderna) compared to unexposed pregnancies.

Methods: Using the HealthCare Integrated Research Database, we identified women of childbearing age between December 1, 2019, and January 1, 2023. We compared adverse pregnancy and neonatal outcomes between pregnant women exposed to Spikevax and three reference groups: women unvaccinated with any COVID-19 vaccines from 60 days prior to LMP throughout pregnancy (unexposed), exposed to Spikevax before 60 days prior to LMP (distantly exposed), and women with COVID-19 during pregnancy. Spikevax exposure was determined through medical and pharmacy claims and state immunization data. Exposure windows were defined based on the timing of specific outcomes, such as the first trimester for major congenital malformations (MCM). Generalized linear regression models and inverse probability of exposure (propensity score) weighting were employed to adjust for confounding factors.

Results: The study included 22,622 women exposed to Spikevax, 246,383 unexposed to any COVID-19 vaccine, and 8,282 distantly exposed. Additionally, 27,285 unvaccinated women were diagnosed with COVID-19 during pregnancy.
Among live births, the proportion of infants with MCMs was similar among women exposed to Spikevax as unexposed women (RR: 1.10; 95% CI: 0.91 - 1.36), distantly exposed women (RR: 0.96; 95% CI: 0.75-1.21), and less than that among women who had COVID-19 during pregnancy (RR:0.74; 95% CI: 0.55-0.99). Similarly, most secondary outcomes were not associated with Spikevax exposure during pregnancy. When comparing outcomes with each reference group, Spikevax-exposed women had a reduced risk of stillbirth, preterm birth, and spontaneous abortion and a slightly elevated risk of preeclampsia (vs. unexposed: RR: 1.18; 95% CI: 1.12-1.25; vs. distantly exposed RR: 1.13; 95% CI: 1.01-1.26).

Conclusions: Spikevax exposure during pregnancy was linked to a reduced risk of stillbirth, preterm birth, and spontaneous abortion and a slightly elevated risk of preeclampsia. Notably, infants of Spikevax recipients had fewer MCMs than infants of unvaccinated mothers who contracted COVID-19 during pregnancy.