In a recent study posted to the Preprints with The Lancet* SSRN preprint server, researchers evaluated the safety of currently administered coronavirus disease 2019 (COVID-19) vaccines in child-bearing women.
The distinct physiological changes in the cardiopulmonary and immune systems occurring in pregnancy increase the susceptibility of pregnant women to severe outcomes [intensive care unit (ICU) admissions and ventilation requirements) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. However, the safety data of SARS-CoV-2 vaccines during pregnancy is lacking and needs to be further evaluated to guide advisory and public committees and aid in developing health policies.
Study: Safety of COVID-19 Vaccines During Pregnancy: A Systematic Review and Meta-Analysis. Image Credit: Marina Demidiuk / Shutterstock
About the study
In the present study, researchers conducted a meta-analysis to assess COVID-19 vaccine safety (including components and platforms used for other maternal vaccines) during gestation. This study was conducted for the COVID-19 Vaccines Global Access-Maternal Immunization Working Group (COVAX-MIWG).
Data were searched from inception up to September 15, 2021, in the databases such as the Cochrane Library, EMBASE, MEDLINE, Latin American and Caribbean Health Sciences Literature (LILACS), China Network Knowledge Information (CNKI), World Health Organization’s (WHO) Database of publications on SARS CoV-2, Science Citation Index Expanded (SCI-EXPANDED), TOXLine. Additionally, preprint servers such as bioRxiv, arXiv, medRxiv, and search.bioPreprint, and COVID-19 pregnancy websites such as Maternal and Child Health, PregCOV-19LSR, Nutrition: John Hopkins Centre for Humanitarian health and the LOVE database were also searched.
The reference lists of relevant primary studies in active COVID-19 pregnancy registries and systematic reviews with data on vaccination of pregnant women were also assessed. The United States Food and Drug Administration (US FDA), the European Medicines Agency (EMA), and clinical trial websites were also searched. Additionally, the team contacted articles’ authors and experts for clarification or to obtain additional information.
The studies included were comparative and non-comparative studies for pregnant women (direct population). Case series were only included if they reported greater than 50 exposed pregnant women. Experimental analyses on exposed pregnant animals (indirect population) were also included. Narrative and systematic reviews were excluded, but their reference lists were investigated as an additional primary data source. Passive surveillance studies without clear denominators and articles whose full text was unavailable were also excluded. No geographical or language restrictions were applied.
The interventions or exposures of interest were vaccination with COVID-19 vaccines authorized by the World Health Organization (WHO) and/or authorized by national regulatory authorities up to December 2021 (direct products) or with other maternal vaccines (indirect products) using the platforms (nucleic acid/mRNA-LNP, protein/subunit, or vectored) or components (construct, antigen, vehicle, adjuvants, lipid nanoparticles) that are used by COVID-19 vaccines, including the aluminum, AS03, Matrix-M or CpG 1018 adjuvants.
The studies were independently reviewed by two reviewers and the bias risks of each study were assessed.
A total of 8,837 studies were retrieved, of which 71 studies – 10 and 61 non-clinical and clinical, respectively, involving 17,719,495 child-bearing women and 389 child-bearing animals – were included in the study. The final analyses included two preclinical trials, nine COVID-19 vaccine studies, and seven studies including 309,164 pregnant women, of which most were administered messenger ribonucleic acid (mRNA) vaccines. The majority (94%) of the studies were cohort studies (51%) undertaken in high-income nations. Only a few (<15%) had high bias risks.
The most frequently administered non-SARS-CoV-2 vaccines were the aluminum adjuvants (five preclinical and 31 clinical studies) and the AS03 adjuvant (23 studies).
The meta-analysis showed no association between maternal SARS-CoV-2 vaccines or non-SARS-CoV-2 vaccine adjuvants (with aluminum or AS03) and adverse events (AEs), irrespective of the vaccine type or the pregnancy trimester in which the vaccine was administered.
The pregnancy outcomes observed by the team were hypertension (2.4 to 4%); prenatal bleeds (0.4%); pregnancy diabetes (2.6% to 7.7%); spontaneous miscarriage/abortion (5% to 12%); stillbirths (0.1% to 0.2%); death of fetus (0.8% to 1.4%); growth restrictions of fetus (0.5% to 0.9%); premature delivery (5.5% to 5.6%); low neonatal birth weight (3.7% to 6.8%); small fetus according to the gestational age (6.8% to 12%); developmental anomalies (2.3% to 5%); neonatal infections (3.2% to 7.2%); brain damage of newborn (0·2%); neonatal pulmonary distress syndromes (1.2% to 1.8%); and death of newborns (0.1% to 0.4%).
Medically attended AEs (34%) and serious AEs (12.3%) were only observed for exposure to aluminum-based non-COVID-19 adjuvants. Neither reactogenicity nor pregnancy outcomes were more significant than that expected with the lone exception being postpartum hemorrhage post-SARS-CoV-2 vaccination (10.4%) which was reported in two studies. However, when compared to non-exposed child-bearing women in one study, the differences were not statistically significant.
Overall, the study results showed that COVID-19 vaccines were safe during pregnancy. Further real-world evidence and experimental data must expand the findings of the present study that reinforce existing recommendations on vaccinating pregnant women with currently authorized COVID-19 vaccines. Safety data for non-mRNA-based COVID-19 vaccines are urgently required.
Preprints with The Lancet / SSRN First Look 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.
- Ciapponi, Agustin and Berrueta, Mabel and Bardach, Ariel and Mazzoni, Agustina and Anderson, Steven A. and Argento, Fernando J. and Ballivian, Jamile and Bok, Karin and Comandé, Daniel and Goucher, Erin and Kampmann, Beate and Parker, Edward and Rodriguez Cairoli, Federico and Santa María, María Victoria and Stergachis, Andy and Voss, Gerald and Xiong, Xu and Zamora, Natalia and Buekens, Pierre M. and Zaraa, Sabra, Safety of COVID-19 Vaccines During Pregnancy: A Systematic Review and Meta-Analysis. Available at SSRN: https://ssrn.com/abstract=4072487, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4072487