Novel strategies for improving respiratory support and outcomes for very preterm babies

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Very premature birth is the commonest cause of illness and death in newborn babies, making it one of the most serious and costly issues in perinatal medicine. The major problem suffered by very premature babies is lung immaturity and its associated harmful effects on brain development. Most very premature babies require resuscitation followed by ventilatory support,often for several weeks. This is extremely expensive and places an enormous financial burden on health care systems. Furthermore, it increases the risks of respiratory illnesses, including bronchopulmonary dysplasia and chronic lung disease which can impair breathing and increase susceptibility to respiratory disease such as asthma later in life. The overall aim of this program is to improve outcomes for very premature babies, including less lung injury, better respiratory health and shorter stays in hospitals. In order to reduce the health burden caused by very premature birth on the community we need to know more about how it alters the normal development of the lungs in the newborn period and into later life. In particular, we need to understand the cellular and molecular processes involved in lung development so that we can identify gene networks and developmental processes that are disrupted by severe premature birth. Such knowledge is necessary to provide a more rational, scientific basis for managing and treating the alterations in lung structure and function caused by premature birth. We also need to develop better ways of resuscitating and ventilating these infants so that lung injury is minimized.The research team is led by two neonatologists and three biomedical research scientists with a proven record of effective collaboration. This team is internationally unique in that it includes practicing neonatologists, respiratory physiologists and molecular biologists who have collaborated together productively and are regarded as world leaders in their respective fields. New talents have been brought into the team to provide expertise in pulmonary stem cell biology, the design of novel steroid drugs, and clinical follow-up. Together, this team has the potential (a) to greatly enhance the understanding of the impact of very premature birth on the developing lung, (b) to improve resuscitation and ventilation techniques, and (c) to translate the new knowledge into clinical practice to improve the outcome for prematurely born babies. Using well characterized animal models we will determine gene networks involved in fetal lung development and how these are altered by premature birth. The successful transition from fetal to postnatal life is critical for survival at birth but more information is needed. Using newborn lambs and rabbits, we will trial novel strategies for enhancing the transformation of the immaturelung into an effective gas exchange organ at birth. New data on lung aeratio