mRNA Covid-19 vaccines in pregnancy: A systematic review

  1. Nando Reza Pratama
  2. Ifan Ali Wafa
  3. David Setyo Budi
  4. Manesha Putra
  5. Manggala Pasca Wardhana
  6. Citrawati Dyah Kencono Wungu

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Abstract

Pregnancy is a known risk factor for severe Coronavirus disease 2019. It is important to develop safe vaccines that elicit strong maternal and fetal antibody responses.

Methods

Registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the European Union Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, Springer, medRxiv, and bioRxiv) were systematically searched in June 20–22, 2021, for research articles pertaining to Covid-19 and pregnancy. Manual searches of bioRxiv and medRxiv were also conducted. Inclusion criteria were studies that focused on Covid-19 vaccination among pregnant women, while review articles and non-human studies were excluded. Infection rate, maternal antibody response, transplacental antibody transfer, and adverse events were described.

Results

There were 13 observational studies with a total of 48,039 pregnant women who received mRNA vaccines. Of those, three studies investigated infection rate, six studies investigated maternal antibody response, seven studies investigated antibody transfer, three studies reported local adverse events, and five studies reported systemic adverse events. The available data suggested that the mRNA-based vaccines (Pfizer–BioNTech and Moderna) can prevent future SARS-CoV-2 infection. These vaccines did not show clear harm in pregnancy. The most commonly encountered adverse reactions were pain at the injection site, fatigue, and headache, but these were transient. Antibody responses were rapid after the first vaccine dose. After the booster, antibody responses were stronger and associated with better transplacental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and a better antibody transfer ratio.

Conclusions

The SARS-CoV-2 mRNA vaccines are encouraged for pregnancy. These vaccines can be a safe option for pregnant women and their fetuses. Two vaccine doses are recommended for more robust maternal and fetal antibody responses. Longer latency is associated with higher fetal antibody responses. Further research about its long-term effect on pregnancy is needed.

Systematic review registration

PROSPERO ( CRD42021261684 ).

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  1. Version published to 10.1371/journal.pone.0261350
  2. ScreenIT

    SciScore for 10.1101/2021.07.04.21259985: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableThe authors screened the title and abstract of independently for eligible studies based on the following criteria: (1) pregnant women; (2) adult (≥18 years) female study population; (3) the study involved Covid-19 vaccine of interest; (4) the study compared the intervention group with control (non-pregnant women, unvaccinated, or none); (5) eligible studies should have reported at least one of our outcomes of interest; (6) English language.
    RandomizationEligibility criteria: We accepted any study (retrospective, prospective, cohort, randomized controlled trials (RCT), case series, case control, cross-sectional, crossover) to be included in the review.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search strategy and selection of studies: The authors comprehensively conducted keyword searching of articles published in trial registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the EU Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, and Springer) up until June 20, 2021.
    Cochrane Library
    suggested: (Cochrane Library, RRID:SCR_013000)
    Proquest
    suggested: (ProQuest, RRID:SCR_006093)
    Manual search, including in BioRxiv and MedRxiv, and the bibliographical search were also conducted to obtain additional evidence.
    BioRxiv
    suggested: (bioRxiv, RRID:SCR_003933)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Strength and limitation: To the best of our knowledge, this systematic review used the most recent evidence to describe the efficacy, safety and immunogenicity of Covid-19 mRNA vaccine in pregnancy. All studies included in this review were assessed as high quality studies. However, studies are all observational studies due to no RCTs reports of Covid-19 vaccination for pregnant women yet currently available. These studies reported only from mRNA type vaccines. Moreover, all available studies that were included were only from the United States and Israel.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.07.04.21259985v1 on medRxiv