Understanding Cardiovascular Remodelling Related to Preterm Birth: A Clinical and Computational Modelling Study

Abstract

Background: Globally, one in ten children are born preterm. Babies born prematurely may suffer from cardiovascular instability and also have an increased lifetime cardiovascular risk. Our aim was two-fold: to collect ultrasound data on the structure and function of the developing cardiovascular system in healthy late preterm newborns and term controls; and to develop newborn clinical digital twins: personalisable anatomical computational models of the neonatal cardiovascular system. Methods: Single-centre, prospective, observational cohort study recruiting term (born ≥37+0 weeks’ gestation) and late preterm (born between 34+0 and 36+6 weeks’ gestation) healthy babies. Ultrasound data were collected within 48 hours of birth and again three to six weeks later. These data inform personalised 0D closed-loop bond graph models that simulate blood pressure and flows in the newborn cardiovascular system. Results: 15 term and 10 preterm babies were assessed on day 2 of life and 12 (80%) term and 7 (70%) preterm babies underwent a second assessment at median post-menstrual age 295 days (25 days old for term group and 38 days old for preterm group). We found no evidence that late preterm birth is associated with structural cardiovascular changes in early life, however, there were differences in postnatal growth velocities. This suggests a window for intervention to prevent cardiovascular remodelling in preterm babies through careful monitoring of growth and nutrition. In keeping with the clinical data, our computational modelling outputs were similar for the term and preterm groups. We found that although the term and preterm models had similar lower body resistances at birth, by three to six weeks of age, the preterm group showed evidence of greater vascular resistance. This is a reasonable mechanistic finding in keeping with previous pre-clinical and clinical literature and highlights a possible mechanism of cardiovascular remodelling in late preterm neonates. Conclusion: This thesis presents our newborn cardiovascular digital twins: the first and largest patient-specific computational modelling study of the cardiovascular system in early life. These can provide deeper insights into the complex physiology of cardiovascular remodelling related to preterm birth through the synthesis of clinical data and computational modelling than either on its own.