Novel Models for Haemodynamics and Transport in Complex Media: Towards Precision Healthcare for Placental Disorders

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Pre-term and stillbirths affect up to 10% of all deliveries, including in developed countries, such as the UK. Among these complications, pre-eclampsia, or the compromised supply of blood between mother and fetus via the placenta, costs over £1.2 billion each year in neonatal and infant care to the NHS and public sector services in the UK alone.The human placenta is a vital life-support system for the developing fetus. The supply of oxygen and nutrients by the mother's blood has to be well orchestrated within a complex fetal blood vessel network. There are two reasons for our limited progress in the understanding of the interaction of the structure and the function of the placenta: on the one hand, the human placenta has an extraordinarily complex structure; on the other hand, the structure and physiology of the human placenta are unique and therefore animal studies are of limited use. A direct consequence of the lack of understanding are very limited options for clinical management of pregnancy diseases such as pre-eclampsia and fetal growth restriction. Furthermore, placental insufficiency does not only result in stillbirth or premature delivery, but it has also been associated with a higher risk of heart attack, stroke, diabetes or neurological disorders later in adult life.Recognition of these challenges has resulted in a recent surge of research interest world-wide and in establishing the $41M US Human Placenta Project and the EU Placentology Network for experimental and theoretical testing of chemicals' safety in pregnancy. Moreover, a recent breakthrough in 'artificial placenta' design for life-support of extremely premature infants offers new opportunities for design optimisation by systematic 'reverse engineering' of the normal human placenta. Thus, the UK needs a critical mass of expertise in placental technologies to match the US and EU capacities and to remain an active player in international collaborations in this important area.Based on our research to date, we hypothesise that blood flow and nutrient transport in the placenta are altered in pre-eclampsia and fetal growth restriction. In this project, we propose an interdisciplinary and innovative approach harnessing our theoretical and experimental expertise to deliver precision medicine for obstetrics and neonatal critical care. We will develop and validate a framework for image-based modelling and simulation of blood flow and nutrient transport in patient-specific placentas. Thanks to existing datasets describing the structure of both healthy and diseased placentas, we will be able to explore which anatomical changes in the placenta are associated with compromised nutrient transport. This will establish a sound theoretical basis for the development of interventions and artificial solutions for the treatment of pre-eclampsia and fetal growth restriction. The long-term translational impacts include (i) model-based patient-specific treatment with drugs avoiding placental dysfunction in high-risk pregnancies and (ii) design optimisation of an 'artificial placenta' for the support of extremely premature babies.