Efficacy of Maternal Influenza Vaccination Against All-Cause Lower Respiratory Tract Infection Hospitalizations in Young Infants: Results From a Randomized Controlled Trial

Background Influenza immunization of pregnant women protects their young infants against laboratory-confirmed influenza infection. Influenza infection might predispose to subsequent bacterial infections that cause severe pneumonia. In a secondary analysis of a randomized clinical trial (RCT), we evaluated the effect of maternal vaccination on infant hospitalizations for all-cause acute lower respiratory tract infection (ALRI). Methods Infants born to women who participated in a double-blind placebo-controlled RCT in 2011 and 2012 on the efficacy of trivalent inactivated influenza vaccine (IIV) during pregnancy were followed during the first 6 months of life. Results The study included 1026 infants born to IIV-recipients and 1023 born to placebo- recipients. There were 52 ALRI hospitalizations (median age 72 days). The incidence (per 1,000 infant-months) of ALRI hospitalizations was lower in infants born to IIV-recipients (3.4 [95%CI: 2.2, 5.4], 19 cases) compared to placebo-recipients (6.0 [95%CI: 4.3, 8.5], 33 cases) with a vaccine efficacy of 43.1% (p=0.050). Thirty of the ALRI hospitalizations occurred during the first 90 days of life, 9 in the IIV-group (3.0 [95%CI: 1.6, 5.7]) and 21 in the placebo-group (7.0 [95%CI: 4.6, 10.8]; incidence rate ratio: 0.43 [95%CI: 0.19, 0.93]) for a vaccine efficacy of 57.5% (p=0.032). The incidence of ALRI hospitalizations was similar in the IIV- and placebo-group for infants older than 3 months. Forty-four of the hospitalized infants were tested for influenza virus infection and one tested positive. Conclusion Using a RCT as a vaccine-probe, influenza vaccination during pregnancy decreased all-cause ALRI hospitalization during the first 3 months of life, suggesting possible protection against subsequent bacterial infections that influenza infection might predispose to.