Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2023 Oct;8(10):e012376.
doi: 10.1136/bmjgh-2023-012376.

Are maternal vaccines effective and safe for mothers and infants? A systematic review and meta-analysis of randomised controlled trials

Odette de Bruin  1   2 , Emily Phijffer  3 , Fariba Ahmadizar  2 , Nicoline van der Maas  4 , Joanne Wildenbeest  3 , Miriam Sturkenboom  2 , Louis Bont  3 , Kitty Bloemenkamp  5
Affiliations
Meta-Analysis

Are maternal vaccines effective and safe for mothers and infants? A systematic review and meta-analysis of randomised controlled trials

Odette de Bruin et al. BMJ Glob Health. 2023 Oct.

Abstract

Introduction: Maternal vaccination is a promising strategy to reduce the burden of vaccine-preventable diseases for mothers and infants. We aimed to provide an up-to-date overview of the efficacy and safety of all available maternal vaccines.

Methods: We searched PubMed, Embase, CENTRAL and ClinicalTrials.gov on 1 February 2022, for phase III and IV randomised controlled trials (RCTs) that compared maternal vaccination against any pathogen with placebo or no vaccination. Primary outcomes were laboratory-confirmed or clinically confirmed disease in mothers and infants. Secondary safety outcomes included intrauterine growth restriction, stillbirth, maternal death, preterm birth, congenital malformations and infant death. Random effects meta-analysis were used to calculate pooled risk ratio's (RR). Quality appraisal was performed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE).

Results: Six RCTs on four maternal vaccines, influenza, tetanus, diphtheria and pertussis (Tdap), pneumococcal and respiratory syncytial virus (RSV) were eligible. The overall risk of bias and certainty of evidence varied from low to high. Maternal influenza vaccination significantly reduced the number of laboratory-confirmed influenza cases (RR 0.58, 95% CI 0.42 to 0.79, event rate 57 vs 98, 2 RCTs, n=6003, I2=0%), and clinically confirmed influenza cases in mothers (RR 0.88, 95% CI 0.78 to 0.99, event rate 418 vs 472, 2 RCTs, n=6003, I2=0%), and laboratory-confirmed influenza in infants (RR 0.66, 95% CI 0.52 to 0.85, event rate 98 vs 148, 2 RCTs, n=5883, I2=0%), although this was not significant for clinically confirmed influenza in infants (RR 0.99, 95% CI 0.94 to 1.05, event rate 1371 vs 1378, 2 RCTs, n=5883, I2=0%). No efficacy data were available on maternal Tdap vaccination. Maternal pneumococcal vaccination did not reduce laboratory-confirmed and clinically confirmed middle ear disease (RR 0.49, 95% CI 0.24 to 1.02, event rate 9 vs 18, 1 RCT, n=133 and RR 0.88 95% CI 0.69 to 1.12, event rate 42 vs 47, 1 RCT, n=133, respectively), and clinically confirmed lower-respiratory tract infection (LRTI) (RR 1.08, 95% CI 0.82 to 1.43, event rate 18 vs 34, 1 RCT, n=70) in infants. Maternal RSV vaccination did not reduce laboratory-confirmed RSV LRTI in infants (RR 0.75, 95% CI 0.56 to 1.01, event rate 103 vs 71, 1 RCT, n=4527). There was no evidence of a significant effect of any of the maternal vaccines on the reported safety outcomes.

Conclusions: The few RCTs with low event rates suggest that, depending on the type of maternal vaccine, the vaccine might effectively prevent disease and within its size does not show safety concerns in mothers and infants.

Prospero registration number: CRD42021235115.

Keywords: Child health; Immunisation; Maternal health; Systematic review; Vaccines.

PubMed Disclaimer

Conflict of interest statement

Competing interests: JW participated in the advisory board of Janssen with fees paid to UMCU. MS leads a department that conducts studies on COVID-19 vaccines for the European Medicines Agency, Pfizer, AstraZeneca and Janssen. All according to the ENCePP code of conduct. KB is principal investigator of a phase 3 clinical trial on maternal RSV vaccination funded by Pfizer and of work package three of the Consign study funded by EMA. LJB has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. UMCU has received major funding (>€100 000 per industrial partner) for investigator initiated studies from AbbVie, MedImmune, Janssen, the Bill and Melinda Gates Foundation, Nutricia (Danone) and MeMed Diagnostics. UMCU has received major cash or in kind funding as part of the public private partnership IMI-funded RESCEU project from GSK, Novavax, Janssen, AstraZeneca, Pfizer and Sanofi. UMCU has received major funding by Julius Clinical for participating in the INFORM study sponsored by MedImmune. UMCU has received minor funding for participation in trials by Regeneron and Janssen from 2015 to 2017 (total annual estimate less than €20 000). UMCU received minor funding for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, Novavax, Pfizer, Janssen (total annual estimate less than €20 000). LJB is the founding chairman of the ReSViNET Foundation. All other authors have nothing to disclose (OB, EP, FA and NvdM).

Figures

Figure 1
Figure 1
Study selection. RSV, respiratory syncytial virus.
Figure 2
Figure 2
Forest plots comparing maternal influenza vaccination with control. M-H, Mantel-Haenszel.
Figure 3
Figure 3
Forest plots comparing maternal Tdap vaccination with control. M-H, Mantel-Haenszel; Tdap, tetanus, diphtheria and pertussis.
Figure 4
Figure 4
Forest plots comparing maternal pneumococcal vaccination with control. M-H, Mantel-Haenszel.
Figure 5
Figure 5
Forest plots comparing maternal RSV vaccination with control. M-H, Mantel-Haenszel; RSV, respiratory syncytial virus.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Vojtek I, Dieussaert I, Doherty TM, et al. . Maternal immunization: where are we now and how to move forward Ann Med 2018;50:193–208. 10.1080/07853890.2017.1421320 - DOI - PubMed
    1. Abu-Raya B, Michalski C, Sadarangani M, et al. . Maternal immunological adaptation during normal pregnancy. Front Immunol 2020;11:575197. 10.3389/fimmu.2020.575197 - DOI - PMC - PubMed
    1. Bergin N, Murtagh J, Philip RK. Maternal vaccination as an essential component of life-course immunization and its contribution to preventive neonatology. Int J Environ Res Public Health 2018;15:847. 10.3390/ijerph15050847 - DOI - PMC - PubMed
    1. Furuta M, Sin J, Ng ESW, et al. . Efficacy and safety of pertussis vaccination for pregnant women - a systematic review of randomised controlled trials and observational studies. BMC Pregnancy Childbirth 2017;17:390. 10.1186/s12884-017-1559-2 - DOI - PMC - PubMed
    1. Vygen-Bonnet S, Hellenbrand W, Garbe E, et al. . Safety and effectiveness of acellular pertussis vaccination during pregnancy: a systematic review. BMC Infect Dis 2020;20:136. 10.1186/s12879-020-4824-3 - DOI - PMC - PubMed

Substances