Improving Immediate and Longer Term Outcomes of Preterm Infants

The Preclinical Intensive Care Research Unit (PICRU) is an exciting new initiative of The University of Western Australia aiming to provide an exceptional national and international collaborative research facility that will enhance the understanding and treatment of infants born preterm. Innovative research evaluating the long-term outcomes of existing controversial and emerging promising therapies will be evaluated  in the PICRU using the preterm lamb model in an environment reflecting contemporary neonatal care.  The PICRU will also provide vital clinical and scientific training facilities for physicians and biomedical research students and staff.

The main PICRU project from 2014-6 aims to resolve a major controversy regarding the cost:benefit of postnatal steroids. Dexamethasone is a proven effective treatment for rescue of preterm infants with severe lung disease, facilitating weaning and extubation from mechanical ventilation to independent respiration. However, clinical concerns about potential adverse consequences of postnatal steroids, particularly impaired neurodevelopmental outcomes, results in withholding or delay in giving steroids to babies who are most likely to benefit. Without postnatal steroid treatment, preterm infants often endure prolonged periods of mechanical ventilation.  However, mechanical ventilation itself is also associated with impaired neurological outcomes and development of a chronic lung disease called bronchopulmonary dysplasia.  An additional factor contributing to poor outcome is the presence of fetal inflammatory response syndrome (FIRS).

The current funded research program will study lambs with and without antenatal exposure to inflammation, who are randomised to either invasive or non-invasive respiratory support.  In a randomised, double-blind study, lambs will be given either glucocorticoid or saline at 72 h postnatal age. Different glucocorticoids (dexamethasone and hydrocortisone) and different steroid doses will be evaluated.  Lambs  will be followed through to a pre-adolescent stage.

Functional study outcomes will include longitudinal measurements of immunological, lung, heart and respiratory muscle function, memory, executive function, motor activity/co-ordination, behaviour and stress. Imaging will evaluate structural developmental outcomes in the brain and eye. Extensive sampling undertaken at study completion will allow complete evaluation of each study group with respect to the effect of the treatment combinations on all organ outcomes.

Functional and structural evaluation techniques include oscillatory mechanics, multiple breath washout, echocardiography, doppler, ultrasound, magnetic resonance imaging, elastography, optical coherence tomography, fluorescence spectroscopy.

Studies are complemented by a longitudinal study of functional and structural outcomes in preterm infants conducted at King Edward and Princess Margaret Hospitals.

Collaborator/s

  • Professor Kurt Albertine, University of Utah
  • Professor Bela Suki, Boston University
  • Professor Raffaele Dellaca, Polytechnico di Milano, University of Milan