Influenza Activity and Preterm Birth in the Atlanta Metropolitan Area: A Time-Series Analysis from 2010 to 2017

Annual influenza epidemics lead to a substantial public health burden, and pregnant people are vulnerable to severe outcomes. Influenza during pregnancy is hypothesized to increase the risk of adverse birth outcomes, but population-based epidemiologic evidence remains limited and inconsistent. We conducted a time-series analysis to estimate short-term associations between community-level seasonal influenza activity and daily counts of preterm births in Atlanta, United States from October 17, 2010 to July 10, 2017. We defined weekly influenza exposures four ways: (1) percent test-positive from virologic surveillance, (2) percent of patients with symptoms of influenza-like illness (ILI) in outpatient settings, (3) a composite measure of percent test-positive and ILI, and (4) influenza hospitalization rates. We used Poisson log-linear models to estimate associations, adjusting for time-varying confounders and ongoing at-risk pregnancies. We further examined associations by influenza type and exposure lags and effect modification by maternal characteristics. We studied a total of 316,253 births. We found consistent positive associations between influenza activity and preterm birth across different exposure measures and exposure lags. An interquartile range increase in a composite measure of ILI activity and percent test-positive was associated with a 1.014 (95% confidence interval: 1.001-1.027) increase in preterm birth during the same week. In stratified analyses, associations were more pronounced among married, non-Black, and Hispanic pregnant people. Periods of high influenza activity were associated with an increased risk of preterm birth.