Computational signal preprocessing is a prerequisite for developing data-driven predictive models for clinical decision support. Thus, identifying the best practices that adhere to clinical principles is critical to ensure transparency and reproducibility to drive clinical adoption. It further fosters reproducible, ethical, and reliable conduct of studies. This procedure is also crucial for setting up a software quality management system to ensure regulatory compliance in developing software as a medical device aimed at early preclinical detection of clinical deterioration. This scoping review focuses on the neonatal intensive care unit setting and summarizes the state-of-the-art computational methods used for preprocessing neonatal clinical physiological signals; these signals are used for the development of machine learning models to predict the risk of adverse outcomes. Five databases (PubMed, Web of Science, Scopus, IEEE, and ACM Digital Library) were searched using a combination of keywords and MeSH (Medical Subject Headings) terms. A total of 3585 papers from 2013 to January 2023 were identified based on the defined search terms and inclusion criteria. After removing duplicates, 2994 (83.51%) papers were screened by title and abstract, and 81 (0.03%) were selected for full-text review. Of these, 52 (64%) were eligible for inclusion in the detailed analysis. Of the 52 articles reviewed, 24 (46%) studies focused on diagnostic models, while the remainder (n=28, 54%) focused on prognostic models. The analysis conducted in these studies involved various physiological signals, with electrocardiograms being the most prevalent. Different programming languages were used, with MATLAB and Python being notable. The monitoring and capturing of physiological data used diverse systems, impacting data quality and introducing study heterogeneity. Outcomes of interest included sepsis, apnea, bradycardia, mortality, necrotizing enterocolitis, and hypoxic-ischemic encephalopathy, with some studies analyzing combinations of adverse outcomes. We found a partial or complete lack of transparency in reporting the setting and the methods used for signal preprocessing. This includes reporting methods to handle missing data, segment size for considered analysis, and details regarding the modification of the state-of-the-art methods for physiological signal processing to align with the clinical principles for neonates. Only 7 (13%) of the 52 reviewed studies reported all the recommended preprocessing steps, which could have impacts on the downstream analysis. The review found heterogeneity in the techniques used and inconsistent reporting of parameters and procedures used for preprocessing neonatal physiological signals, which is necessary to confirm adherence to clinical and software quality management system practices, usefulness, and choice of best practices. Enhancing transparency in reporting and standardizing procedures will boost study interpretation and reproducibility and expedite clinical adoption, instilling confidence in the research findings and streamlining the translation of research outcomes into clinical practice, ultimately contributing to the advancement of neonatal care and patient outcomes.
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