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 hours after birth and relate this coupling to gestational age, 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 gestational age, 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-to-PI and PI-to-HR directions (P<0.05). HR-to-PI coupling increases with maturation (correlation r=0.26; P=0.011); PI-to-HR coupling increases with inotrope administration (r=0.27; P=0.007). And nonstationary features of PI-to-HR coupling are associated with (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.