Dai, Nichole2026-01-052026-01-052026-01-05http://hdl.handle.net/10393/51214https://doi.org/10.20381/ruor-31641Background: Influenza illness during pregnancy has been associated with severe maternal adverse outcomes, including stillbirth. Despite recommendations from Canada’s National Advisory Committee on Immunization (NACI) for influenza vaccination during pregnancy, coverage remains suboptimal, with only 45% of pregnant individuals vaccinated. Existing studies demonstrate inconsistent evidence regarding the association between maternal influenza and adverse outcomes, particularly for seasonal influenza and stillbirth. Methods: We conducted a population-based retrospective cohort study using administrative health data housed at ICES in Ontario, Canada, between April 1, 2006, and March 31, 2020. Adjusted hazard ratios for stillbirth were estimated using an extended Cox proportional hazards model, accounting for time-varying exposure to medically attended influenza illness and adjusted for confounders. Two subgroup analyses were conducted: (1) exploring the acute infection of influenza using risk windows and (2) examining the effects of infection in high-risk individuals with pre-existing maternal medical conditions. Results: We identified 1,646,864 pregnancies, of which 8227 (0.50%) resulted in stillbirths. 16,286 (0.99%) pregnant individuals were diagnosed with medically attended influenza illness during pregnancy. There was a significant association between influenza illness during pregnancy and stillbirth when the seasonal epidemics and the 2009/2010 H1N1 pandemic were pooled for analysis (adjusted HR [95% CI]: 1.30 [1.03,1.62]). When analyzed separately, there was a significant association during seasonal epidemics with the highest hazard when medically attended influenza was diagnosed in the second trimester (adjusted HR [95% CI]: 1.52 [1.09,2.22]) but no association was observed for pandemic influenza. The risk of stillbirth was highest during the two weeks after medically attended influenza infection, with an adjusted HR of 3.70 [95% CI 2.19, 6.25], 2.69 [95% CI 1.73, 4.17] during the four weeks following infection, and 1.96 [95% CI 1.29, 2.97] during the six weeks following infection. In the high-risk population with pre-existing conditions, there was a higher risk of medically attended influenza illness during pregnancy and stillbirth, but the association was not statistically significant (adjusted HR [95% CI]: 1.48 [0.96,2.67]). Conclusion: The findings of our study demonstrate that there is a significant association between medically attended influenza illness during pregnancy and the risk of stillbirth, especially during seasonal epidemics. Importantly, it highlights the need to strengthen vaccination efforts to protect pregnant individuals from obstetrical complications and adverse perinatal outcomes associated with influenza illness.enstillbirthinfluenzapregnancycohortpopulation-basedThesis