Lewandowski Group: Developmental Systems Physiology

adam.lewandowski@cardiov.ox.ac.uk

Cardiovascular Clinical Research Facility Division of Cardiovascular Medicine Oxford Centre for Clinical Magnetic Resonance Research

Our group focuses on understanding how alterations to early human development affect long-term disease risk and how to reduce risk through nutritional and lifestyle interventions. Disruptions to normal development, including exposure to pregnancy complications such as being born preterm, are risk factors for early heart failure, stroke and cardiovascular events. To study early developmental changes, we use multi-modality imaging, activity monitoring, questionnaire data and birth records, as well as blood sample collection to study cellular pathways in fetal through to young adult human cohorts.

EARLY DEVELOPMENT AND NOVEL RISK FACTORS

Our major area of focus has been on preterm birth (born less than 37 weeks’ gestation) and associated pregnancy and postnatal complications. Preterm birth affects 1 in 10 births worldwide and clinical advancements in the past 30 years have meant that survival rates are now regularly higher than 90% globally. Epidemiological studies have identified that preterm birth is an independent risk factor for cardiac disease and hypertension by adult life. Indeed, our group has found that people born early have differences in cardiac structure and function in adult life compared to people born at term with an abnormal cardiac response to physiological stress, suggestive of a reduced myocardial functional reserve. Current studies are ongoing to better define myocardial tissue changes in the preterm adult heart.

More recently, we discovered that cardiac changes seen in adults born preterm present themselves in the first few months after birth. This is a particularly sensitive period of growth for preterm-born neonates because they are exposed to environmental stressors and clinical conditions during a period where they would normally be developing in utero. We are now beginning a study looking at how these cardiac changes seen in the first months of life progress into childhood.

Part of our work has also highlighted the importance of early life nutrition for long-term cardiac size and function by showing that exclusive human milk feeding in the first weeks of life associates with normalisation of cardiac changes in young adulthood. We are now planning a study to look in greater detail at early life nutritional interventions, myocardial tissue characterisation and physiological stress response. Our group is also conducting a trial assessing whether prescribed aerobic exercise training can preferentially modify phenotypic alterations in young adults born preterm.

The next phase of research in this area is primarily funded by the British Heart Foundation as part of Dr Lewandowski’s Intermediate Research Fellowship: ‘Cardiac remodeling in preterm-born offspring: defining the importance of early postnatal changes and potential for neonatal dietary interventions to reduce long-term risk’.