Continuous prediction and clinical alarm management of late-onset sepsis in preterm infants using vital signs from a patient monitor

Background and Objective: Continuous prediction of late-onset sepsis (LOS) could be helpful for improving clinical outcomes in neonatal intensive care units (NICU). This study aimed to develop an artificial intelligence (AI) model for assisting the bedside clinicians in successfully identifying infants at risk for LOS using non-invasive vital signs monitoring. Methods: In a retrospective study from the NICU of the M <acute accent>axima Medical Center in Veldhoven, the Netherlands, a total of 492 preterm infants less than 32 weeks gestation were included between July 2016 and December 2018. Data on heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO 2 ) at 1 Hz were extracted from the patient monitor. We developed multiple AI models using 102 extracted features or raw time series to provide hourly LOS risk prediction. Shapley values were used to explain the model. For the best performing model, the effect of different vital signs and also the input type of signals on model performance was tested. To further assess the performance of applying the best performing model in a real-world clinical setting, we performed a simulation using four different alarm policies on continuous real-time predictions starting from three days after birth. Results: A total of 51 LOS patients and 68 controls were finally included according to the patient inclusion and exclusion criteria. When tested by seven-fold cross-validations, the mean (standard deviation) area under the receiver operating characteristic curve (AUC) six hours before CRASH was 0.875 (0.072) for the best performing model, compared to the other six models with AUC ranging from 0.782 (0.089) to 0.846 (0.083). The best performing model performed only slightly worse than the model learning from raw physiological waveforms (0.886 [0.068]), successfully detecting 96.1 % of LOS patients before CRASH. When setting the expected alarm window to 24 h and using a multi-threshold alarm policy, the sensitivity metric was 71.6 %, while the positive predictive value was 9.9 %, resulting in an average of 1.15 alarms per day per patient. Conclusions: The proposed AI model, which learns from routinely collected vital signs, has the potential to assist clinicians in the early detection of LOS. Combined with interpretability and clinical alarm management, this model could be better translated into medical practice for future clinical implementation.