Maturational physiology in preterm infants: morbidity impact and 2-year neurodevelopmental outcome

Preterm birth may disrupt autonomic maturation. This study examines maturational patterns in physiological signals and heart rate variability (HRV) of preterm infants with and without major morbidity (MM), and their association with 2-year neurodevelopmental outcome. 251 preterm infants (< 30 weeks’ gestation) were enrolled: 125 with MM and 126 without MM. Follow-up was available for 50% with and 63% without MM. Analysis included heart rate (HR), respiration frequency (RF), oxygen saturation (SpO₂) and HRV features. Comparisons were made across gestational age (sub)groups and between infants with and without MM over postnatal ages. Infants without MM showed three distinct maturational phases: transitional phase in week 1–2 with increasing HR and HRV; a mid‑stable phase in week 3–4, except for a decrease in HR; and a later consolidation phase with continued HR decline and increasing HRV. This trajectory was consistent when infants without MM and normal developmental outcomes were included. In contrast, infants with MM exhibited disrupted maturation patterns, and motor and cognitive impairments were two to three times more frequent in this group. Preterm infants without MM show three distinct maturational phases. MM disrupts physiological development, suggesting early detection through physiological monitoring may support timely diagnosis or intervention. This study characterizes the maturation of heart rate, heart rate variability, respiratory frequency, and oxygen saturation in very preterm infants. Typical developmental trajectories were identified and deviations associated with major morbidities were observed. Physiological parameters may serve as early indicators of abnormal development during NICU stay. Typical values for vital signs are necessary for the development of early warning algorithms.