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Review
. 2023 Jun 7;41(25):3688-3700.
doi: 10.1016/j.vaccine.2023.03.038. Epub 2023 Mar 27.

Safety of COVID-19 vaccines during pregnancy: A systematic review and meta-analysis

Agustín Ciapponi  1 , Mabel Berrueta  2 , Edward P K Parker  3 , Ariel Bardach  4 , Agustina Mazzoni  5 , Steven A Anderson  6 , Fernando J Argento  7 , Jamile Ballivian  8 , Karin Bok  9 , Daniel Comandé  10 , Erin Goucher  11 , Beate Kampmann  12 , Flor M Munoz  13 , Federico Rodriguez Cairoli  14 , Victoria Santa María  8 , Andy S Stergachis  15 , Gerald Voss  16 , Xu Xiong  17 , Natalia Zamora  8 , Sabra Zaraa  18 , Pierre M Buekens  19
Affiliations
Review

Safety of COVID-19 vaccines during pregnancy: A systematic review and meta-analysis

Agustín Ciapponi et al. Vaccine. .

Abstract

Background: Assessment of COVID-19 vaccines safety during pregnancy is urgently needed.

Methods: We conducted a systematic review and meta-analysis to evaluate the safety of COVID-19 vaccines, including their components and technological platforms used in other vaccines during pregnancy and animal studies to complement direct evidence. We searched literature databases from its inception to September 2021 without language restriction, COVID-19 vaccine websites, and reference lists of other systematic reviews and the included studies. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42021234185).

Results: We retrieved 8,837 records from the literature search; 71 studies were included, involving 17,719,495 pregnant persons and 389 pregnant animals. Most studies (94%) were conducted in high-income countries, were cohort studies (51%), and 15% were classified as high risk of bias. We identified nine COVID-19 vaccine studies, seven involving 309,164 pregnant persons, mostly exposed to mRNA vaccines. Among non-COVID-19 vaccines, the most frequent exposures were AS03 and aluminum-based adjuvants. A meta-analysis of studies that adjusted for potential confounders showed no association with adverse outcomes, regardless of the vaccine or the trimester of vaccination. Neither the reported rates of adverse pregnancy outcomes nor reactogenicity exceeded expected background rates, which was the case for ASO3- or aluminum-adjuvanted non-COVID-19 vaccines in the proportion meta-analyses of uncontrolled studies/arms. The only exception was postpartum hemorrhage after COVID-19 vaccination (10.40%; 95% CI: 6.49-15.10%), reported by two studies; however, the comparison with non-exposed pregnant persons, available for one study, found non-statistically significant differences (adjusted OR 1.09; 95% CI 0.56-2.12). Animal studies showed consistent results with studies in pregnant persons.

Conclusion: We found no safety concerns for currently administered COVID-19 vaccines during pregnancy. Additional experimental and real-world evidence could enhance vaccination coverage. Robust safety data for non-mRNA-based COVID-19 vaccines are still needed.

Keywords: Adjuvant; COVID-19; Meta-analysis; Pregnancy; Systematic review; Vaccine safety.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Pierre M. Buekens reports financial support was provided by Bill & Melinda Gates Foundation].

Figures

Fig. 1
Fig. 1
Study flow diagram.
Fig. 2
Fig. 2
Forest plots of pregnancy outcomes comparing exposure with no exposure to COVID-19 vaccines.
See this image and copyright information in PMC

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