The novel coronavirus (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and has led to a global pandemic. The COVID-19 vaccine Spikevax, developed by Moderna, was approved for use in the UK on 8th January 2021 to prevent COVID-19 in the general population. Initially approved for adults (ages ≥18 years), use was later approved for ages ≥6 years and pregnant/breastfeeding women. Sometimes vaccine use is associated with side effects known as adverse events. As COVID-19 vaccines have been developed urgently, they require ongoing safety monitoring to examine these side effects.
Use of Spikevax in pregnancy and its effect on the mother and newborn are not fully understood. This UK study, as part of several studies in Europe, will use information from UK primary care electronic health records to determine the safety of Spikevax in pregnancy. The aim is to determine whether receiving the Spikevax vaccine during pregnancy is related to a higher chance of pregnancy problems including high levels of blood sugar during pregnancy, high blood pressure disorders or bleeding during pregnancy and pregnancy related death; adverse pregnancy outcomes such as foetal death, termination of pregnancy for foetal problems and any chosen pregnancy termination; as well as negative outcomes for the baby within 28-days of birth including birth before 37-weeks, growth problems, low birth weight, deformity that developed in the womb and death within 28 days of birth. It will also describe the use of Spikevax and other Moderna vaccines developed for different versions of the COVID-19 infection in pregnancy.
Spikevax, an mRNA-1273 vaccine, was developed by Moderna, Inc., and the United States National Institute of Allergy and Infectious Diseases (NIAID). Spikevax and a newer Moderna variant vaccine (Spikevax bivalent Original/Omicron BA.1) have been authorised across the European Union and UK to prevent COVID-19 in individuals aged 6+ years, including pregnant/breastfeeding women. Spikevax bivalent Original/Omicron BA.4-5 (UK approval given November 2022) is authorised for use in those aged 12+ years, including pregnant/breastfeeding women.
As COVID-19 vaccines have been developed urgently, they require ongoing safety monitoring to examine side effects. Pregnant women were not eligible to participate in US Phase 3 trials for the Spikevax vaccine. However, preliminary findings from an observational study in the US were not indicative of obvious safety signals among pregnant persons who received mRNA COVID-19 vaccines. However use of Spikevax in pregnancy and its effect on the mother and neonate are not fully understood, and the need for longitudinal follow-up in a large number of pregnant women remains. Therefore, this post-authorisation safety study (PASS) aims to describe use of Spikevax and Moderna variant vaccines in pregnancy and determine whether exposure during pregnancy is associated with an increased risk of pregnancy complications, adverse pregnancy outcomes, major congenital malformations in the offspring (overall and organ-specific if feasible) and/or adverse neonatal outcomes. The prevalence of each outcome will be compared for exposed vs. unexposed pregnancies according to predefined exposure categories using, plausible exposure risk-windows as necessary. Crude and adjusted measures of association will compare the exposed vs the unexposed (prevalence ratios, risk ratios, mortality rate ratios).
Aggregate results from the CPRD UK analyses will be pooled with aggregate results provided by other European Data Access Providers (using a Digital Research Environment) for which CPRD approval has previously been obtained (Query Reference number 00077310).
Primary outcomes
- Pregnancy complications including hypertensive disorders of pregnancy (preeclampsia, eclampsia, gestational hypertension); gestational diabetes; bleeding during pregnancy; postpartum haemorrhage and pregnancy-related death.
- Adverse pregnancy outcomes including foetal death (spontaneous abortion or stillbirth); termination of pregnancy for foetal anomaly; any elective pregnancy termination and ectopic pregnancy.
- Adverse neonatal outcomes including foetal growth restriction/small for gestational age (SGA); preterm birth (<37 full gestational weeks); low birth weight (<2500 g); major congenital malformations; microcephaly (based on head circumference); low 5-minute Apgar score and neonatal death (death within 28 days of birth).
Secondary outcomes
Characteristics of Spikevax utilisation according to the following predefined exposure categories: number and prevalence of exposed pregnancies/births any time during pregnancy/gestation; number and prevalence of pregnancies/births with one dose/two doses/more than two doses; number and prevalence of exposed pregnancies/births in each of the trimesters; trimester of first dose and maternal and newborn characteristics according to the exposure to Spikevax.
Characteristics of Spikevax bivalent Original/Omicron BA.1 utilisation according to predefined exposure categories: number and prevalence of exposed pregnancies/births any time during pregnancy/gestation; and if feasible without reporting personal data (as number of exposed pregnancies may be small), maternal and newborn characteristics according to the exposure to Spikevax bivalent Original/Omicron BA.1.
Debabrata Roy - Chief Investigator - Drug Safety Research Unit
Denise Morris - Corresponding Applicant - Drug Safety Research Unit
Catherine Fry - Collaborator - Drug Safety Research Unit
Kathryn Morton - Collaborator - Drug Safety Research Unit
Miranda Davies - Collaborator - Drug Safety Research Unit
Saad Shakir - Collaborator - Drug Safety Research Unit
Samantha Lane - Collaborator - Drug Safety Research Unit
Sandeep Dhanda - Collaborator - Drug Safety Research Unit
Taylor Aurelius - Collaborator - Drug Safety Research Unit
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation;CPRD Aurum Mother-Baby Link;CPRD Aurum Pregnancy Register