Trivalent influenza vaccination randomized control trial of pregnant women and adverse fetal outcomes

INTRODUCTION: The purpose of this study was to evaluate the association of influenza vaccine during pregnancy and adverse fetal outcomes. Preventing fetal death, low birth weight, small for gestational age birth and preterm birth are important potential effects of antenatal maternal influenza immunization for which there are conflicting data. MATERIALS AND METHODS: A double-blind, randomized, placebo-controlled clinical trial of trivalent inactivated influenza vaccine was conducted in South Africa from March 2011 until after the 2012 influenza season when the infants born had reached the age of 24 weeks. Mothers were administered the vaccine or placebo during pregnancy at a gestation of 20 to 36 weeks. A comparison of rates of fetal death, low birth weight, small for gestational age birth, and preterm birth, between vaccinated and placebo groups was made. Fetal outcome differences between the groups were measured using Student’s t-tests, vaccine efficacy with 95% confidence intervals, and Poisson regression for incidence rates. All analyses except fetal death excluded mothers who were administered vaccine or placebo after 34 weeks gestational age. RESULTS: There were 2116 HIV-uninfected pregnant women age 18 to 38 years in the trial; 2005 infants were born to mothers where vaccine or placebo had been administered ≥ 14 days prior to delivery, and there were 6 miscarriages and 23 stillbirths. There was no significant vaccine efficacy (with [95% confidence interval]) on fetal death (−21.2% [−150.8, 41.4]), low birth weight (−11.1% [−42.3, 12.5]), small for gestational age birth (−9.9% [−35.6, 11.0]), or preterm birth (−21.3% [−60.5, 8.3]). Neither was vaccine efficacy demonstrated when the analysis was restricted to infants of mothers who were exposed to an influenza season (1832 outcomes available). CONCLUSION: We did not find a beneficial effect of trivalent inactivated influenza vaccine during pregnancy on adverse fetal outcomes.