Prediction of Late-Onset Sepsis in Preterm Infants Using Monitoring Signals and Machine Learning.

OBJECTIVES: Prediction of late-onset sepsis (onset beyond day 3 of life) in preterm infants, based on multiple patient monitoring signals 24 hours before onset. DESIGN: Continuous high-resolution electrocardiogram and respiration (chest impedance) data from the monitoring signals were extracted and used to create time-interval features representing heart rate variability, respiration, and body motion. For each infant with a blood culture-proven late-onset sepsis, a Cultures, Resuscitation, and Antibiotics Started Here moment was defined. The Cultures, Resuscitation, and Antibiotics Started Here moment served as an anchor point for the prediction analysis. In the group with controls (C), an "equivalent crash moment" was calculated as anchor point, based on comparable gestational and postnatal age. Three common machine learning approaches (logistic regressor, naive Bayes, and nearest mean classifier) were used to binary classify samples of late-onset sepsis from C. For training and evaluation of the three classifiers, a leave-k-subjects-out cross-validation was used. SETTING: Level III neonatal ICU. PATIENTS: The patient population consisted of 32 premature infants with sepsis and 32 age-matched control patients. INTERVENTIONS: No interventions were performed. MEASUREMENTS AND MAIN RESULTS: For the interval features representing heart rate variability, respiration, and body motion, differences between late-onset sepsis and C were visible up to 5 hours preceding the Cultures, Resuscitation, and Antibiotics Started Here moment. Using a combination of all features, classification of late-onset sepsis and C showed a mean accuracy of 0.79 ± 0.12 and mean precision rate of 0.82 ± 0.18 3 hours before the onset of sepsis. CONCLUSIONS: Information from routine patient monitoring can be used to predict sepsis. Specifically, this study shows that a combination of electrocardiogram-based, respiration-based, and motion-based features enables the prediction of late-onset sepsis hours before the clinical crash moment.

Predicting Neonatal Sepsis Using Features of Heart Rate Variability, Respiratory Characteristics, and ECG-Derived Estimates of Infant Motion.

This study in preterm infants was designed to characterize the prognostic potential of several features of heart rate variability (HRV), respiration, and (infant) motion for the predictive monitoring of late-onset sepsis (LOS). In a neonatal intensive care setting, the cardiorespiratory waveforms of infants with blood-culture positive LOS were analyzed to characterize the prognostic potential of 22 features for discriminating control from sepsis-state, using the Naïve Bayes algorithm. Historical data of the subjects acquired from a period sufficiently before the clinical suspicion of LOS was used as control state, whereas data from the 24 h preceding the clinical suspicion of LOS were used as sepsis state (test data). The overall prognostic potential of all features was quantified at three-hourly intervals for the period corresponding to test data by calculating the area under the receiver operating characteristics curve. For the 49 infants studied, features of HRV, respiration, and movement showed characteristic changes in the hours leading up to the clinical suspicion of sepsis, namely, an increased propensity toward pathological heart rate decelerations, increased respiratory instability, and a decrease in spontaneous infant activity, i.e., lethargy. While features characterizing HRV and respiration can be used to probe the state of the autonomic nervous system, those characterizing movement probe the state of the motor system-dysregulation of both reflects an increased likelihood of sepsis. By using readily interpretable features derived from cardiorespiratory monitoring, opportunities for pre-emptively identifying and treating LOS can be developed.