COVID-19 can cause serious illness in pregnant women. Since April 2021, all pregnant women in the UK have been routinely advised to receive COVID-19 vaccination together with the rest of the population, according to their age and underlying health conditions. Because mRNA vaccines have been given in pregnancy in the United States with reassuring findings from safety surveillance, these have been the preferred vaccines to offer to pregnant women in England. It is important to study the safety of new COVID-19 vaccination during pregnancy in England, to add to the available evidence internationally on the safety of COVID-19 vaccination in pregnancy, and to support appropriate confidence in vaccination.
We will compare the outcomes of pregnant women who were vaccinated against COVID during pregnancy to those of women who were pregnant before the COVID-19 pandemic, and to women who were pregnant during the COVID-19 pandemic but who were not vaccinated during pregnancy. We will look at venous blood clots during pregnancy, stillbirth, premature birth, death of the mother, death of a baby soon after birth, and major birth defects.
This study will inform advice to pregnant women by the UK Health Security Agency (formerly Public Health England) and the Medicines and Healthcare products Regulatory Agency.
Pregnant women are at risk of severe outcomes from COVID-19 infection and are recommended COVID-19 vaccination in the UK and other countries. Safety surveillance to date has been reassuring. However, there is a need for epidemiological studies of COVID-19 vaccination safety during pregnancy to add to the international evidence base and to support appropriate public confidence in vaccination.
The study will use a matched cohort study design to examine whether there is any association between COVID-19 vaccination during pregnancy and adverse maternal, foetal or infant outcomes (maternal venous thromboembolism, stillbirth, maternal death, neonatal death, premature birth, and major congenital anomalies).
The CPRD Pregnancy Register will be used to define a cohort of eligible pregnant women. The main analysis will compare adverse outcomes among women vaccinated in pregnancy to historical controls who were pregnant prior to the COVID-19 pandemic, matched on maternal age. Multivariable Cox regression models will be used to adjust for confounding by gestational age for analyses of venous thromboembolism, stillbirth, maternal death and preterm delivery, and to adjust for ascertainment increasing with length of follow up for major congenital anomalies. A multivariable logistic regression model will be used for analysis of neonatal mortality. A secondary analysis will compare women vaccinated in pregnancy to unvaccinated concurrent pregnant controls, matched on maternal age and expected delivery date (by month).
The study will be conducted in two analysis stages, with a first analysis in early 2022 focused on mRNA platform vaccines to provide indicative results swiftly for policy-makers (maternal outcomes will be followed by infant outcomes if the mother-baby link is not initially available), followed by more precise estimates and secondary analyses (such as brand-specific analysis and analysis by trimester of vaccination) once there is greater power and follow-up time available in late 2022.
Primary: Stillbirth; maternal death; maternal venous thromboembolism; preterm delivery; neonatal death; major congenital malformations.
Secondary: extended perinatal death (stillbirth or neonatal death)
Jemma Walker - Chief Investigator - MHRA
Helen McDonald - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Jemma Walker - Collaborator - MHRA
Jennifer Campbell - Collaborator - CPRD
Katherine Donegan - Collaborator - MHRA
Maria Peppa - Collaborator - University College London ( UCL )
Nick Andrews - Collaborator - Public Health England
CPRD Mother-Baby Link;HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation;Pregnancy Register