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.