Preterm birth and stillbirth after COVID-19 vaccination during pregnancy: a nationwide retrospective cohort study in the Netherlands

COVID-19 vaccination during pregnancy was recommended in the Netherlands between April 2021 and March 2024. To help assess the safety and potential protective benefits of COVID-19 vaccination during pregnancy, we aimed to estimate the effect of COVID-19 vaccination during pregnancy on the risk of preterm birth and stillbirth. This nationwide register-based cohort study included live and stillborn singleton births ≥ 24 weeks of gestation in the Netherlands between September 2021 and December 2022. Cox proportional hazard models were used to estimate the effect (hazard ratio (HR) with 95% confidence interval (CI)) of COVID-19 vaccination during pregnancy on preterm birth (24–36 completed weeks of gestation) and stillbirth. The models were stratified by estimated conception week and adjusted for maternal age, country of origin, medical risk group, parity and education level using inverse probability of treatment weighting. Secondary analyses stratified by pre-pregnancy vaccination and infection status and by trimester of vaccination were performed. The effect of COVID-19 vaccination during pregnancy on very preterm birth (24–31 weeks of gestation) was estimated as a secondary outcome. Out of 135,123 births, 7,452 (5.5%) were preterm and 340 (0.3%) were stillborn. COVID-19 vaccination during pregnancy was not associated with preterm birth or stillbirth (HR = 1.00 (95%CI: 0.95–1.06) and HR = 1.00 (95%CI: 0.76–1.32), respectively). These results did not differ significantly by trimester of vaccination or pre-pregnancy vaccination and infection status and no significant effect on very preterm birth was observed (HR = 0.88 (95%CI: 0.76–1.02)). COVID-19 vaccination during pregnancy was not associated with preterm birth or stillbirth, which further adds to the existing evidence that COVID-19 vaccination is safe during pregnancy. These findings are relevant for healthcare workers and individuals with a medical indication who may consider getting vaccinated during pregnancy in the Netherlands and for women in countries where COVID-19 vaccination continues to be recommended for all pregnant women.