Aim: To systematically summarise the current evidence of employing clinical decision support algorithms (CDSAs) using non-invasive parameters for sepsis prediction in neonates. Methods: A comprehensive search in PubMed, CENTRAL and EMBASE was conducted. Screening, data extraction and risk of bias were performed by two authors. The certainty of the evidence was assessed using GRADE. PROSPERO ID: CRD42020205143. Results: After abstract and full-text screening, 36 studies comprising 18,096 infants were included. Most CDSAs evaluated heart rate (HR)-based parameters. Two publications derived from one randomised-controlled trial assessing HR characteristics reported significant reduction in 30-day septicaemia-related mortality. Thirty-four non-randomised studies found promising yet inconclusive results. Conclusion: Heart rate-based parameters are reliable components of CDSAs for sepsis prediction, particularly in combination with additional vital signs and demographics. However, inconclusive evidence and limited standardisation restricts clinical implementation of CDSAs outside of a controlled research environment. Further experimentation and comparison of parameter combinations and testing of new CDSAs are warranted.

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<p> In this original study, we investigate the performances of machine learning algorithms on a neonatal sepsis detection task. We consider this work to be of great interest to both engineers and clinicians, as it uses non-invasive, already existing, vital signs monitoring signals in a population of very low birth weight infants at high risk of sepsis. Vital sign variability may indeed represent a general indicator of health and wellbeing and be helpful in the early detection of systematic inflammation such as sepsis. We used state of the art feature extraction technics and evaluate a large variety of binary classification models among which a neural network based generative model. The models were chosen from two main families: discriminative and generative. This enables a comprehensive study of different kinds of traditional and advanced binary classification algorithms.</p> <p> Our study reveals that advanced machine learning models are more robust to changes in the feature extraction pipeline, although linear classifiers have a comparable performance when the feature extraction is tuned. The advanced model performing the best is a neural network based generative model which is a hybrid generative and discriminative model. A large window length when computing the features is beneficial to almost all algorithms, indicating the relevance of frequency domain related features for the neonatal sepsis detection task.</p> <p> Overall we obtain a classification AUROC above 0.85, which makes our prediction models potentially relevant in clinical practice. This will enable earlier therapeutic interventions and thereby reduce morbidity and mortality in infants.</p>