Real-Worl Effectiveness of Maternal Influenza Vaccination During Pregnancy on Risk of Infant Influenza During the First 6 Months of Life

Background: Pregnant persons and infants are at increased risk of complications from influenza. Vaccination is the most effective ways to prevent influenza and its complications, however, infants less than 6 months are not eligible for vaccination. Randomized clinical trials and observational studies have reported that maternal influenza vaccination during pregnancy protects infants against infection and severe disease before they are eligible for vaccination.

Objectives: To evaluate the real-world effectiveness of influenza vaccination during pregnancy and its timing to protect infants against influenza infection during the first 6 months of life using causal inference methodology for trial emulation with electronic health record data.

Methods: We conducted a cohort study among pregnant persons and their infants born at Kaiser Permanente Northern California from 2006 – 2018. The exposure was maternal influenza vaccination anytime between the first prenatal visit (index date) and 14 days before the end of pregnancy. The outcome was influenza infection in infants, defined as any positive influenza test by polymerase chain reaction during the first 6 months of life. Four two-arm randomized trials were emulated to compare outcome risk without vaccination to either 1) vaccination at any time, or vaccination during 2) the first, 3) second, or 4) third trimester of pregnancy.
We used inverse probability weighting to adjust the relative risk for baseline and time-varying confounding and attrition bias. Vaccine effectiveness was calculated as 100% (1 – adjusted relative risk).

Results: For the estimation of the effectiveness of vaccination anytime during pregnancy, the emulated trial included 210,659 pregnant persons and their singleton infants. Less than half of pregnant persons (40.4%) were vaccinated during pregnancy. A higher proportion of infants of unvaccinated mothers tested influenza positive compared with infants of vaccinated mothers (0.33% vs. 0.10%). After adjusting for covariates, maternal vaccination anytime during pregnancy significantly reduced the risk of the infant influenza by 57.7% (95% confidence interval [CI] 44.7% - 67.7%). Vaccine effectiveness against infant influenza was 60.0% (95% CI 22.5% - 79.3%) when mothers were vaccinated during the first trimester, 92.2% (95% CI 73.5%, 97.7%) when vaccinated during the second trimester and 36.9% (-87.3%,78.7%) when vaccinated during the third trimester.

Conclusions: Influenza vaccination during pregnancy protected infants from influenza infection during the vulnerable first six months of life. All eligible pregnant persons should get vaccinated to protect their infants.