In a recent study posted to the medRxiv* preprint server, researchers evidenced that messenger ribonucleic acid (mRNA)-based coronavirus disease 2019 (COVID-19) vaccines are safe in pregnancy, with lower rates of significant adverse event following immunization (AEFIs) in pregnant women than non-pregnant females.
Multiple research works have published positive recommendations for mRNA-based COVID-19 vaccines in pregnancy, based on the evidence of high efficacy in pre-authorization clinical trials. However, in the absence of a contemporaneous control group to enable comparison with background rates of AEFIs and comparisons based solely on historical rates of AEFIs, apprehensions surrounding the safety of mRNA vaccines during pregnancy are still lurking around.
The Canadian National Vaccine Safety (CANVAS) Network, established during the 2009 influenza pandemic, has been monitoring COVID-19 vaccine safety in Canada since the vaccine rollout in December 2020 to provide rapid, real-time safety data.
The CANVAS actively follow-up individuals with significant health events and actively enrolls control group(s) to enable comparisons with unvaccinated individuals in a similar time frame.
About the study
In the present study, researchers recruited pregnant and non-pregnant females aged 15-49 years, as of 4 November 2021, under the ‘vaccinated’ and ‘control’ cohorts in Canada to evaluate the safety profile of mRNA-based COVID-19 vaccines.
The females in the vaccinated cohort had received the first dose of a vaccine within seven days before enrolling for the study. They had an active email address and telephone number and could communicate in English or French. They reported the occurrence of AEFIs over an email after seven days following each dose of the COVID-19 vaccine and at seven months after their first vaccine dose. The control group participants were unvaccinated and reported significant health events that occurred seven days, 28 days, and six months after enrolling in the study.
All the participants had to report injection site reactions; however, only those who indicated having a significant health event had to provide further details.
The researchers analyzed two types of exposures for the study analysis:
- vaccination status among pregnant people;
- pregnancy status among vaccinated people.
Two endpoints were analyzed, including ‘significant’ and ‘serious’ health events, including common and uncommon symptoms following the first and second doses of COVID-19 vaccines. The former is defined as a new or worsening of a health event sufficient to cause work/school absenteeism or medical consultation in the previous seven days, and the latter describes any event resulting in hospitalization.
Likewise, they analyzed three vaccine groups:
- mRNA-1273, and
- any mRNA vaccine.
They also examined associations between the outcomes and the exposures, using two sets of univariate/multivariate (MV) logistic regression models. When fitting MV models, they adjusted known or expected covariates such as age group, prior COVID-19 infection, and trimester of pregnancy, as appropriate.
Lastly, they conducted two sensitivity analyses to evaluate the robustness of the findings.
Significant health events were lower in pregnant people than in age-matched non-pregnant vaccine recipients. Among pregnant females, AEFI was higher in those who received the second dose of the mRNA-1273 vaccine. However, there was no difference in AEFIs after either dose of the BNT162b2 vaccine.
Initial clinical trials of the mRNA-1273 and BNT162b2 vaccines have reported relatively high rates of AEFIs compared with most routinely used vaccines, including higher rates for dose two than dose one.
The current study analysis revealed similar patterns among pregnant females. Although the analysis specifically quantified the significant and serious AEFI rates in this population for each of the mRNA vaccines, the lower rate of significant AEFIs among pregnant people, compared with vaccinated non-pregnant females, revealed interesting insights.
During pregnancy, dynamic immunologic adaptations occur, for instance, a skewed response towards a T helper cell 2 (Th2)-dominant state. Since mRNA vaccines have specifically elicited a Th1-biased immune response, the Th2-bias during pregnancy may be partially responsible for this lower rate of significant AEFIs.
Considering the high rate of complications related to COVID-19 in pregnancy, it is crucial to maximize vaccine coverage in this at-high risk population for the protection of both the pregnant female and her young infant. Immunized mothers pass on antigen-specific immunoglobulin G (IgG) antibodies against SARS-CoV-2 via placenta or breast milk.
Overall, the study data appropriately informed about the reactogenicity of COVID-19 vaccines during pregnancy. This information should be considered alongside effectiveness and immunogenicity data to make appropriate recommendations about the best use of COVID-19 vaccines in pregnancy. The long-term data from this cohort following a six-month follow-up, when available, could also prove quite useful. Similar data from countries where the ChAdOx-S vaccines are used could provide a complete overview of the safety of COVID-19 vaccines in pregnancy.
In the future, research studies should identify whether the observed reduced reactogenicity of non-COVID-19 mRNA vaccines in pregnant people in this study is a feature of the vaccine platform or these specific vaccines.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.