Covid-19 vaccine safety in pregnancy, a nested case-control study in births from April 2021 to March 2022, England
Authors: Mensah Anna A , Stowe Julia , Jardine Jennifer E , Kirsebom Freja C M , Clare Tom , Kall Meaghan , Campbell Helen , Lopez-Bernal Jamie , Andrews Nick 
Published: October 2023

AbstractIntroductionVaccine safety in pregnancy is always of paramount importance. Current evidence of COVID-19 vaccine safety in pregnancy has been reassuring with no association found with negative maternal and neonatal outcomes. However, very few safety studies are conducted on a national level and investigate dosage, timing of vaccination as well as vaccine manufacturer. To fill this knowledge gap, we conducted a population based COVID-19 vaccine safety evaluation in England, including timing of vaccination by trimester, dosage and vaccine manufacturer received in pregnancy.MethodA matched case control study nested in a retrospective cohort where adverse maternal and neonatal pregnancy outcomes were compared across several COVID-19 vaccine exposures using conditional multivariable logistic regression, adjusting for a range of demographic and health characteristics. Eligible participants were identified from the national maternity services dataset (MSDS) and records were linked to hospital admission, national COVID-19 vaccine and COVID-19 testing databases. Matching criteria differed by outcome but included participant’s age and estimated week of conception.Results514,013 pregnant individuals aged between 18 and 50 years were identified during the study period (births from 16th of April 2021-31st March 2022). Receiving at least one dose of COVID-19 vaccine during pregnancy conferred lower odds of giving birth to a baby who was low birthweight (aOR=0.86, 95% CI: 0.79 – 0.93), preterm (aOR=0.89, 95% CI: 0.85 - 0.92) or who had an Apgar score less than 7 at five mins of age (aOR=0.89, 95% CI: 0.80 - 0.98). There was no association between vaccination in pregnancy and stillbirth (aOR=0.90, 95% CI: 0.76 - 1.07), neonatal death (aOR=1.27, 95% CI: 0.91 - 1.77) perinatal death (aOR=0.98, 95% CI: 0.83 - 1.16), and maternal venous thromboembolism in pregnancy (aOR=0.82, 95% CI: 0.43 - 1.56). The odds of maternal admission to intensive care unit were lower in vaccinated pregnant women (aOR=0.85, 95% CI: 0.76 - 0.95).ConclusionCOVID-19 vaccines are safe to use in pregnancy and they confer protection against SARS-CoV-2 infection which can lead to adverse outcomes for both the mother and the infant. Our findings generated important information to communicate to pregnant women and health professionals to support COVID-19 maternal vaccination programmes.What is already known on this topicCurrent evidence shows that COVID-19 vaccines are safe to use in pregnancy. However, few studies investigate the timing of vaccination in pregnancy including the first trimester for late pregnancy outcomes. Most studies are geographically limited, and few are population based allowing inclusion of participants representative of the country’s inhabitants.What this study addsThis is the first population-based study in England investigating COVID-19 vaccine safety in pregnancy. We used the national maternity services dataset and national English health services data enabling inclusion of a huge numbers of participants across the country. As such, we were able to investigate relevant safety research questions such as the timing of vaccine administration in pregnancy by trimester and before pregnancy, the number of doses received and vaccine manufacturer.How this study might affect research, practice or policyThis national study adds to further existing evidence demonstrating that all COVID-19 vaccines are safe to use in pregnancy at any point in time and gives pregnant individuals confidence in the COVID-19 maternal vaccine programme. We demonstrated that receiving multiple doses of COVID-19 vaccine in pregnancy is not associated with adverse pregnancy outcomes and additionally it was reassuring that there was no evidence of an increased risk by vaccine type.