biostudies-literatureGonzato EMinistero dell'Università e della RicercaMinistero dell’Università e della Ricerca30827https://www.ebi.ac.uk/biostudies/studies/S-EPMC12371090biostudies-literatureUnknown15(1)In survival analysis, models typically assess the impact of a single Time-Varying Exposure (TVE), where the exposure status can change over time. However, situations with multiple TVEs frequently arise, and adequate statistical handling remains an area of active research. To apply multiple time-varying approaches and to compare estimates derived from different models using an application with real-world data in the paediatric field. The Italian national paediatric database Pedianet was used to identify children aged between six months and 14 years at the beginning of the epidemiological season (October 1, 2017, to May 31, 2018). Influenza vaccine administrations and antibiotic prescriptions were modeled using both time-fixed and time-varying approaches. Cox proportional-hazard models with Scientific reportsHandling multiple time-varying exposures in survival analysis using real-world pediatric data from the pedianet database.PMC12371090H53D23007460001Annicchiarico LCantarutti ADi Chiara CRigamonti VValentini DGonzato EfalseHandling multiple time-varying exposures in survival analysis using real-world pediatric data from the pedianet database.In survival analysis, models typically assess the impact of a single Time-Varying Exposure (TVE), where the exposure status can change over time. However, situations with multiple TVEs frequently arise, and adequate statistical handling remains an area of active research. To apply multiple time-varying approaches and to compare estimates derived from different models using an application with real-world data in the paediatric field. The Italian national paediatric database Pedianet was used to identify children aged between six months and 14 years at the beginning of the epidemiological season (October 1, 2017, to May 31, 2018). Influenza vaccine administrations and antibiotic prescriptions were modeled using both time-fixed and time-varying approaches. Cox proportional-hazard models with 2025-01-01T00:00:00Z2025 Aug2026-05-08T10:42:18.268Z2026-04-07T23:46:44.538ZS-EPMC123710904084157010.1038/s41598-025-14849-5