Vertical Vaccination Against Infant Influenza Hospitalization in a Tropical Setting.

Importance: Maternal influenza vaccination effectively reduces risk of influenza among infants younger than 6 months, who are too young to receive influenza vaccination, in temperate countries with well-demarcated influenza seasons. However, evidence is limited supporting the clinical effectiveness of seasonal maternal influenza vaccination in tropical regions with year-round influenza transmission. Objective: To identify the clinical effectiveness of maternal influenza vaccination in reducing the risk of infant influenza hospitalization in a tropical setting. Design, Setting, and Participants: This cohort study was conducted in Singapore, a tropical country with year-round influenza transmission. Participants included all infants (citizens or permanent residents of Singapore) born between May 1, 2017, and December 1, 2023, who had complete sociodemographic information for both children and their mothers derived from national administrative databases and survived at least 2 weeks after birth. Statistical analysis was performed from May 1, 2017, to April 30, 2024. Exposure: Receipt of influenza vaccination during pregnancy. Maternal vaccination status was classified using the National Immunization Registry and was linked to infant outcomes via the national birth registry. Main Outcome and Measures: The main outcome was infant influenza hospitalization from birth until 6 months of age, recorded in the national health care claims database. Hazard ratio (HR) of infant influenza hospitalizations was contrasted among infants with vaccinated mothers (received influenza vaccination during pregnancy) vs unvaccinated mothers (did not receive influenza vaccination during pregnancy), using overlap-weighted Cox proportional hazards regression model. Vaccine effectiveness (VE) was calculated as 1 - HR. Results: A total of 221 185 infants (113 625 males [51.4%]) were included. Overall, 25.9% of infants were born to vaccinated mothers. Infants were followed up from birth until an influenza hospitalization, 6 months of age, or death, whichever occurred first. The mean (SD) follow-up time was 181.9 (5.6) days for infants born to vaccinated mothers and 182.3 (5.0) days for infants born to unvaccinated mothers. Risk of influenza hospitalization was significantly lower in infants born to vaccinated mothers (adjusted HR [AHR], 0.59; 95% CI, 0.45-0.77). Maternal influenza vaccination was associated with significant VE estimates among infants (VE against hospitalization, 41%; 95% CI, 23%-55%). The VE estimate was statistically significant regardless of trimester timing (VE against hospitalization, first trimester: 52% [95% CI, 20%-71%]; second trimester: 37% [95% CI, 12%-56%]; third trimester: 41% [95% CI, 8%-64%). Maternal influenza vaccination remained protective regardless of season timing (VE against hospitalization, current season: 41% [95% CI, 12%-61%]; prior season: 41% [95% CI, 19%-58%]). Conclusions and Relevance: In this retrospective cohort study in a tropical region with year-round influenza transmission, a strategy of immunizing mothers at any point during their pregnancy was associated with reduced risk of infant influenza hospitalization.