Moderna Spikevax® Post-Authorisation Safety Study – Pregnancy

Background: Coronavirus disease 2019 (COVID-19) in pregnancy is associated with increased risks of adverse maternal and neonatal outcomes. Moderna mRNA-1273 vaccine was authorised in the European Union and in the United Kingdom (UK) in early 2021 and subsequently recommended for use in pregnancy.

Objectives: To assess whether mRNA-1273 during pregnancy is associated with an elevated risk of adverse pregnancy outcomes; major congenital malformations (MCMs); or adverse birth and neonatal outcomes.

Methods: This multi-database study used secondary healthcare data from national registries (Denmark and Norway), SIDIAP database (Catalonia, Spain), and CPRD Aurum (UK). Study population included pregnancies ending in 2021-2023 and their linkable offspring. Depending on population and outcome types, cohort, prevalence, or cross-sectional designs were used. Exposure was 1+ dose of mRNA-1273 vs. no COVID-19 vaccines during pregnancy, time-varying where appropriate. For the MCM outcomes, only first-trimester exposure was assessed. Local data were harmonised into the ConcePTION common data model and analysed in a federated manner. Country-specific results were pooled using random-effects meta-analysis.

Results: For pregnancy hypertensive disorders, bleeding, and gestational diabetes, adjusted hazard ratios (aHR) (95% confidence interval [CI]) were 0.54 (0.47-0.61), 0.90 (0.76-1.08) and 0.50 (0.46-0.54). For foetal death and elective termination, aHRs (95% CI) were 1.17 (0.91-1.49) and 1.18 (0.91-1.54). For pregnancy-related death and postpartum haemorrhage, aHR (95% CI) were 0.76 (0.23-2.59) and 1.14 (0.96-1.35). For any MCM, adjusted prevalence ratio (aPR) (95% CI) was 1.00 (0.91-1.10). For specific MCMs, most aPR (95% CI) were consistent with a null association, ranging from 0.63 (0.12-3.31) for respiratory MCM to 1.41 (0.88-2.25) for "other" MCMs.

Adjusted PRs (95% CI) were 0.89 (0.84-0.94) for preterm birth, 0.81 (0.76-0.87) for low birth weight, 0.95 (0.80-1.13) for small for gestational age (SGA) defined by birth weight >2 standard deviations below the mean, 0.92 (0.79-1.08) for SGA defined by < 10th centile of birth weight, and 0.88 (0.72-1.09) for low 5-minute Apgar score. For neonatal death, adjusted risk ratio (95% CI) was 0.70 (0.41-1.20).

Conclusions: This study does not indicate an association between receipt of mRNA-1273 vaccine (regardless of other COVID-19 vaccination during pregnancy) and an elevated risk of adverse pregnancy, birth, or neonatal outcomes compared with no COVID-19 vaccination. Limitations include potential selection bias due to prevalent design, incomplete mother-offspring linkage, confounding by indication, healthy vaccinee bias, and imprecise estimates for certain outcomes.