Maternal Influenza Immunization and Prevention of Severe Clinical Pneumonia in Young Infants: Analysis of Randomized Controlled Trials Conducted in Nepal, Mali and South Africa

Abstract

Background: To evaluate the effect of antenatal influenza vaccination on all-cause severe infant pneumonia, we performed pooled analysis of 3 randomized controlled trials conducted in Nepal, Mali and South Africa.

Methods: The trials were coordinated from the planning phase. The follow-up period was 0-6 months postpartum in Nepal and Mali and 0-24 weeks in South Africa. Pregnant women with gestational age 17-34 weeks in Nepal, ≥28 weeks in Mali and 20-36 weeks in South Africa were enrolled. Trivalent inactivated influenza vaccine (IIV) was compared with either saline placebo (Nepal and South Africa) or quadrivalent meningococcal conjugate vaccine (Mali). In South Africa, cases were hospitalized and were therefore considered to have severe pneumonia. In Nepal and Mali, severe infant pneumonia diagnosis was based on the WHO Integrated Management of Childhood Illness definition.

Results: A total of 10,002 mothers and 9801 live-born eligible infants were included in the present analysis. There was a 31% lower incidence rate of severe pneumonia in the IIV group compared with the control group in Nepal [incidence rate ratio (IRR): 0.69; 95% CI: 0.50-0.94; ]. In South Africa, there was a 43% lower incidence rate of severe pneumonia in the IIV group versus the control group (IRR: 0.57; 95% CI: 0.33-1.0). There was no difference in incidence rates between the IIV group and the control group in Mali. Overall, incidence rate of severe pneumonia was 20% lower in the IIV group compared with the control group (IRR: 0.80; 95% CI: 0.66-0.99; P = 0.04). Protection was highest in the high influenza circulation period (IRR: 0.44; 95% CI: 0.23-0.84).

Conclusions: Maternal influenza immunization may reduce severe pneumonia episodes among infants-particularly those too young to be completely vaccinated against Streptococcus pneumoniae and influenza.

Trial registration: ClinicalTrials.gov NCT01430689 NCT01034254 NCT02465190.