The effect of apnea length on vital parameters in apnea of prematurity - Hybrid observations from clinical data and simulation in a mathematical model

Apnea of prematurity (AOP) is a critical condition for preterm infants which can lead to several adverse outcomes. Despite its relevance, mechanisms underlying AOP are still unclear. In this work we aimed at improving the understanding of AOP and its physiologic responses by analyzing and comparing characteristics of real infant data and model-based simulations of AOP. We implemented an existing algorithm to extract apnea events originating from the central nervous system from a population of 26 premature infants (1248 h of data in total) and investigated oxygen saturation (SpO2) and heart rate (HR) of the infants around these events. We then extended a previously developed cardio-vascular model to include the lung mechanics and gas exchange. After simulating the steady state of a preterm infant, which successfully replicated results described in previous literature studies, the extended model was used to simulate apneas with different lengths caused by a stop in respiratory muscles. Apneas identified by the algorithm and simulated by the model showed several similarities, including a far deeper decrease in SpO2, with the minimum reached later in time, in case of longer apneas. Results also showed some differences, either due to how measures are performed in clinical practice in our neonatal intensive care unit (e.g. delayed detection of decline in SpO2 after apnea onset due to signal averaging) or to the limited number of very long apneas (≥80 s) identified in our dataset.