Sample entropy correlates with intraventricular hemorrhage and mortality in premature infants early in life

Pediatr Res. 2024 Feb 16. doi: 10.1038/s41390-024-03075-w. Online ahead of print.


Background: Mortality and intraventricular hemorrhage (IVH) are common adverse outcomes in preterm infants and are challenging to predict clinically. Sample entropy (SE), a measure of heart rate variability (HRV), has shown predictive power for sepsis and other morbidities in neonates. We evaluated associations between SE and mortality and IVH in the first week of life.

Methods: Participants were 389 infants born before 32 weeks of gestation for whom bedside monitor data were available. A total of 29 infants had IVH grade 3 or 4 and 31 infants died within 2 weeks of life. SE was calculated with the PhysioNet open-source benchmark. Logistic regressions assessed associations between SE and IVH and/or mortality with and without common clinical covariates over various hour of life (HOL) censor points.

Results: Lower SE was associated with mortality by 4 HOL, but higher SE was very strongly associated with IVH and mortality at 24-96 HOL. Bootstrap testing confirmed SE significantly improved prediction using clinical variables at 96 HOL.

Conclusion: SE is a significant predictor of IVH and mortality in premature infants. Given IVH typically occurs in the first 24-72 HOL, affected infants may initially have low SE followed by a sustained period of high SE.

Impact: SE correlates with IVH and mortality in preterm infants early in life. SE combined with clinical factors yielded ROC AUCs well above 0.8 and significantly outperformed the clinical model at 96 h of life. Previous studies had not shown predictive power over clinical models. First study using the PhysioNet Cardiovascular Toolbox benchmark in young infants. Relative to the generally accepted timing of IVH in premature infants, we saw lower SE before or around the time of hemorrhage and a sustained period of higher SE after. Higher SE after acute events has not been reported previously.