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

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, I(2)=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, I(2)=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, I(2)=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, I(2)=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.