Nonstationary Coupling Between Heart Rate And Perfusion Index In Extremely Preterm Infants In The First Day Of Life

Objective. Adaptation to the extra-uterine environment presents many challenges for infants born less than 28 weeks of gestation. Quantitative analysis of readily available physiological signals at the cotside could provide valuable information during this critical time. We aim to assess the time-varying coupling between heart rate (HR) and perfusion index (PI) over the first 24 h after birth and relate this coupling to gestational age (GA), inotropic therapy, and short-term clinical outcome. Approach. We develop new nonstationary measures of coupling to summarise both frequency- and direction-dependent coupling. These measures employ a coherence measure capable of measuring time-varying Granger casuality using a short-time information partial-directed coherence function. Measures are correlated with GA, inotropic therapy (yes/no), and outcome (adverse/normal). Main results. In a cohort of 99 extremely preterm infants (<28 weeks of gestation), we find weak but significant coupling in both the HR -> PI and PI -> HR directions (P < 0.05). HR -> PI coupling increases with maturation (correlation r = 0.26; P = 0.011). PI -> HR coupling increases with inotrope administration (r = 0.27; P = 0.007). And nonstationary features of PI -> HR coupling are associated with adverse outcome (r = 0.27; P = 0.009). Significance. Nonstationary features are necessary to distinguish different coupling types for complex biomedical systems. Time-varying directional coupling between PI and HR provides objective and independent biomarkers of adverse outcome in extremely preterm infants.