Sepsis continues to be a major contributor to morbidity and mortality among hospitalized patients globally, especially within intensive care and emergency departments, where rapid recognition is essential for improving survival through timely treatment. In recent years, machine learning approaches have gained attention for their ability to predict sepsis onset using routinely collected electronic health record data. This systematic review, conducted in accordance with PRISMA 2020 guidelines, synthesizes evidence from studies published between 2017 and 2025, focusing on model architectures, feature selection and engineering strategies, prediction time horizons, and validation methodologies. Searches across major biomedical and informatics databases identified 67 eligible studies. The included literature shows that logistic regression, ensemble tree-based algorithms, and deep learning models are most frequently applied for sepsis prediction tasks. However, the majority of studies rely on retrospective datasets with internal validation, while only a limited number incorporate prospective or real-world validation frameworks. Overall, although reported model performance is often strong in retrospective analyses, a consistent decline in accuracy is observed when models are evaluated in real clinical environments. These findings highlight that prospective validation and improved generalizability are still underdeveloped areas, underscoring the need for future research to emphasize real-time deployment and robust external validation before clinical integration.
Clinical Intelligence Research Press