Effects of maternal influenza vaccination on adverse birth outcomes: A systematic review and Bayesian meta-analysis

BACKGROUND: Although pregnant women are a priority group for influenza vaccination, its effect on birth outcomes has long been debated. Numerous observational studies and a few randomized controlled studies have been conducted, with inconsistent results. OBJECTIVES: To evaluate the association of influenza vaccination in pregnancy with adverse birth outcomes. DATA SOURCE: The Cochrane Library, PubMed, EMBASE, Web of Science, and Scopus were searched. STUDY ELIGIBILITY CRITERIA: This analysis included randomized placebo-controlled studies, cohort studies, and case-control studies, in which inactivated influenza vaccination was given during pregnancy and fetal adverse birth outcomes were assessed. PARTICIPANTS & INTERVENTION: Women who received inactivated influenza vaccine during pregnancy and their offspring. STUDY APPRAISAL AND SYNTHESIS: Two independent reviewers and a third reviewer collaborated in study selection and data extraction. A Bayesian 3-level random-effects model was utilized to assess the impact of maternal influenza vaccination on birth outcomes, which were presented as odds ratios (ORs) with 95% credible interval (CrIs). Bayesian outcome probabilities (P) of an OR<1 were calculated, and values of at least 90% (0.9) were deemed to indicate a significant result. RESULTS: Among the 6,249 identified publications, 48 studies were eligible for the meta-analysis, including 2 randomized controlled trials, 41 cohort studies, and 5 case-control studies. The risk of none of the following adverse birth outcomes decreased significantly: preterm birth (OR = 0.945, 95% CrI: 0.736-1.345, P = 73.3%), low birth weight (OR = 0.928, 95% CrI: 0.432-2.112, P = 76.7%), small for gestational age (OR = 0.971, 95% CrI: 0.249-4.217,P = 63.3%), congenital malformation (OR = 1.026, 95% CrI: 0.687-1.600, P = 38.0%), and fetal death (OR = 0.942, 95% CrI: 0.560-1.954, P = 61.6%). Summary estimates including only cohort studies showed significantly decreased risks for preterm birth, small for gestational age and fetal death. However, after adjusting for season at the time of vaccination and countries' income level, only fetal death remained significant. CONCLUSION: This Bayesian meta-analysis did not find a protective effect of maternal influenza vaccination against adverse birth outcomes, as reported in previous studies. In fact, our results showed evidence of null associations between maternal influenza vaccination and adverse birth outcomes.