(264) Are maternal vaccines effective and safe in mothers and infants? A systematic review and meta-analysis of randomized controlled trials

Publication Number: 1254

Background: Maternal vaccination is a promising strategy to reduce the burden of vaccine-preventable diseases for mothers and infants.

Objectives: To provide an up-to-date overview of the efficacy and safety of all available maternal vaccines.

Methods: We performed a systematic review by searching PubMed, Embase, CENTRAL and ClinicalTrials.gov on February 1, 2022. We included phase III and IV randomised controlled trials (RCTs) that compared maternal vaccination against any pathogen with placebo or no vaccination. Primary outcomes were laboratory- or clinically confirmed disease. Secondary outcomes included intra-uterine growth restriction (IUGR), stillbirth, preterm birth, congenital abnormalities, infant death and maternal death. Quality appraisal was performed using the GRADE approach. We used random effects meta-analysis to calculate overall risk ratios (RR) with 95%CI.

Results: Nine studies (n=11674) representing data from 6 phase III and IV RCTs on 4 maternal vaccines (Influenza, TdaP, pneumococcal, RSV) were eligible for meta-analysis. 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 (RR 0.58, 95%CI 0.42–0.79, 2 RCTs, n=6003, I2=0%), and clinically confirmed influenza in mothers (RR 0.88, 95%CI 0.78–0.99, 2 RCTs, n=6003, I2=0%), and laboratory-confirmed influenza in infants (RR 0.66, 95%CI 0.52–0.85, 2 RCTs, n=5833, I2=0%), albeit this was not significant for clinically confirmed influenza in infants (RR 0.99, 95%CI 0.94–1.05, 2 RCTs, n=5833, I2=0%). No efficacy data was available on maternal Tdap vaccination. Maternal pneumococcal vaccination did not reduce laboratory-confirmed middle ear disease (RR 0.49, 95%CI 0.24–1.02, 1 RCT, n=133), clinically confirmed middle ear disease (RR 0.88, 95%CI 0.69–1.12, 1 RCT, n=133), or clinically confirmed lower respiratory tract infection (LRTI) in infants (RR 1.08, 95%CI 0.82–1.43, 1 RCT, n=70). Maternal RSV vaccination probably does not reduce laboratory-confirmed RSV LRTI in infants (RR 0.75 95%CI 0.56–1.01, 1 RCT, n=4527). There was no significant effect of any of the maternal vaccines on the reported safety outcomes.

Conclusions: Our results are based on few RCTs with low event rates and 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. Future research should promptly strive to update available data by performing clinical trials with greater sample sizes, high-risk populations, concomitant vaccinations, administration during various time points of gestation, long-term follow-up, and consistent outcome definitions and time point measurements.