Abstract

Heart rate (HR) patterns can inform on central nervous system dysfunction. We previously used highly comparative time series analysis (HCTSA) to identify HR patterns predicting mortality among patients in the neonatal intensive care unit (NICU) and now use this methodology to discover patterns predicting cerebral palsy (CP) in preterm infants. We studied NICU patients <37 weeks' gestation with archived every-2-s HR data throughout the NICU stay and with or without later diagnosis of CP (n = 57 CP and 1119 no CP). We performed HCTSA of >2000 HR metrics and identified 24 metrics analyzed on HR data from two 7-day periods: week 1 and 37 weeks' postmenstrual age (week 1, week 37). Multivariate modeling was used to optimize a parsimonious prediction model. Week 1 HR metrics with maximum AUC for CP prediction reflected low variability, including "RobustSD" (AUC 0.826; 0.772-0.870). At week 37, high values of a novel HR metric, "LongSD3," the cubed value of the difference in HR values 100 s apart, were added to week 1 HR metrics for CP prediction. A combined birthweight + early and late HR model had AUC 0.853 (0.805-0.892). Using HCTSA, we discovered novel HR metrics and created a parsimonious model for CP prediction in preterm NICU patients. We discovered new heart rate characteristics predicting CP in preterm infants. Using every-2-s HR from two 7-day periods and highly comparative time series analysis, we found a measure of low variability HR week 1 after birth and a pattern of recurrent acceleration in HR at term corrected age that predicted CP. Combined clinical and early and late HR features had AUC 0.853 for CP prediction.

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