A Prospective Study Of The Development Of Innate Immunity In Preterm Infants And Susceptibility To Neonatal Infection
Funder
National Health and Medical Research Council
Funding Amount
$377,773.00
Summary
Life-threatening infection is extremely common in preterm infants, affecting at least 25% of those born before 28 weeks. Infection results in huge human and economic costs. There is currently no way of predicting which preterm infants will develop infection. This project will enrol preterm infants at birth and track the development of their protective immune system over the period of greatest vulnerability. This will lead to development of targeted treatement for those at greatest risk.
International Neonatal Immunotherapy Study (INIS): A Randomised Trial Of Intravenous Immunoglobulin For Neonatal Sepsis
Funder
National Health and Medical Research Council
Funding Amount
$1,151,250.00
Summary
There is promising evidence that treatment of serious infection in babies with a product naturally occuring in blood, intravenous immunoglobulin (IVIG), may reduce deaths by 40% and reduce brain damage in survivors. This would reduce the social, emotional and financial burden of disability on families, health services and society. In financial terms alone, caring for a severely disabled child costs an extra $50,000 per year. However, more evidence is needed before IVIG can be introduced as routi ....There is promising evidence that treatment of serious infection in babies with a product naturally occuring in blood, intravenous immunoglobulin (IVIG), may reduce deaths by 40% and reduce brain damage in survivors. This would reduce the social, emotional and financial burden of disability on families, health services and society. In financial terms alone, caring for a severely disabled child costs an extra $50,000 per year. However, more evidence is needed before IVIG can be introduced as routine treatment for serious infection in the newborn. The International Neonatal Immunotherapy Study (INIS) is a randomised trial to study the potential benefits of IVIG in 5,000 newborn babies in 150 centres world wide. 26 centres are in Australia and New Zealand, whose expected contribution of 1,500 babies will be vital to the success of the study. INIS is supported by the Commonwealth Government and Australian Red Cross Blood Service, who will oversee the supply and distribution of IVIG, and the NHMRC Clinical Trials Centre, who will coordinate the study. Infants will have a detailed specialist assessment at 2 years of age and a parent questionnaire will be completed, to assess their development. An economic evaluation will be performed to estimate the long-term savings to Australian Health Services and families associated with the IVIG therapy. The IVIG product to be used in Australia is Intragam P, manufactured by CSL, who have an unrivalled safety record. CSL has been making IVIG since 1989 and no transmission of HIV or hepatitis viruses has ever been reported. CSL estimate the risk of transmission of these viruses by IVIG is under 1 in 10 million treatments. INIS will provide reliable evidence about IVIG, a treatment with minimum known risk that may benefit thousands of Australian children and millions more worldwide.Read moreRead less
Innate Immunity In Premature Infants: The Role Of Toll Like Receptors In Susceptibility To Infection
Funder
National Health and Medical Research Council
Funding Amount
$440,312.00
Summary
Premature infants are extremely vulnerable to severe infection in early life. This study will examine how well premature infants mount an initial immune response against infection (innate immunity) compared to infants born on time and adults. This study will also look at factors that affect this response and whether we can predict which babies will develop severe infection or other complications. This information will help develop new strategies to treat and prevent infections in these infants.
Differences In Neonatal Immune Regulation In The Developing And Developed World: Implications For Neonatal Vaccinations?
Funder
National Health and Medical Research Council
Funding Amount
$332,083.00
Summary
This project will study the effect of adverse living conditions such as high microbial exposure, malnutrition, environmental tobacco smoke and malaria infection on the development of a newborn's immune system,by comparing immune response between newborns in Papua New Guinea and in Western Australia. This study will help us to understand the high susceptibility of children in the developing world for infectious diseases and to develop better prevention strategies.
Role Of The Thymus In T Cell Homeostasis During Foetal And Postnatal Life In Sheep
Funder
National Health and Medical Research Council
Funding Amount
$264,750.00
Summary
The mature T cell pool can arise from only two sources, either thymic export or expansion of the peripheral T cell pool or a mixture of both. The lifespan of either cell type, i.e. recent thymic emigrants or mature T cells, has considerable implications for the development of a pool of T cells able to respond to a large number of infections. Recent thymic emigrants represent a wide diversity of positively selected thymocytes exhibiting newly arising T cell specificities, but mature T cell pool e ....The mature T cell pool can arise from only two sources, either thymic export or expansion of the peripheral T cell pool or a mixture of both. The lifespan of either cell type, i.e. recent thymic emigrants or mature T cells, has considerable implications for the development of a pool of T cells able to respond to a large number of infections. Recent thymic emigrants represent a wide diversity of positively selected thymocytes exhibiting newly arising T cell specificities, but mature T cell pool expansion results in reduced diversity because of a predominant expansion of a limited number of clones. It follows that a mixing of the pool of older mature T cells with new ones just released from the thymus will introduce more variability, and hence greater adaptability into the immune system. We have developed techniques for labeling the thymus in vivo and the entire blood leukocyte pool in vivo using the long-term lymphocyte tracking dye CFSE. We can establish a cohort of labeled cells and we can, for the first time in any experimental system, track directly the survival, death or division of recent thymic emigrants and mature cells and their progeny together with their tissue homing properties and surface markers for periods of many months. This will enable us to determine the way in which the pool of mature T cells is built up during the formation of the foetal immune system and the way the mature T cell population is established and maintained in postnatal life.Read moreRead less
Inter-hospital Variations In Outcomes Of Very Preterm Infants Admitted To Neonatal Intensive Care Units
Funder
National Health and Medical Research Council
Funding Amount
$130,440.00
Summary
Most babies who are born very preterm (less than 32 weeks' gestation; ie more than 2 months early) are admitted to a neonatal intensive care unit (NICU). These babies stay in hospital for 2 to 4 months and need lots of care (using vast amounts of the available health resources). When compared to babies born at term, these very preterm babies are much more likely to die or to suffer from a range of poor outcomes that impact on their long-term development and quality of life. The Australian and Ne ....Most babies who are born very preterm (less than 32 weeks' gestation; ie more than 2 months early) are admitted to a neonatal intensive care unit (NICU). These babies stay in hospital for 2 to 4 months and need lots of care (using vast amounts of the available health resources). When compared to babies born at term, these very preterm babies are much more likely to die or to suffer from a range of poor outcomes that impact on their long-term development and quality of life. The Australian and New Zealand Neonatal Network (ANZNN) is a collaboration of clinical staff in all 29 NICUs in the region, whose aim is to improve the care of high-risk newborn infants and their families in Australia and New Zealand through collaborative audit and research. This audit has reported considerable differences in the rates of death and poor outcomes between NICUs. Other networks have reported similar variations. Variations in outcomes could be due to 1) differences in the way the diagnosis is made in each unit, 2) differences in how small or ill the babies are when admitted, or 3) different quality of care in each NICU. We need to take account of the first two possibilities before we can compare NICUs fairly and allow them to work towards achieving the best outcomes for very premature babies. To do this, our project will use advanced statistical techniques to look at the risk factors associated with death and poor outcome in very preterm babies. We will then be able to 'predict' outcomes and see if the differences between NICUs are real or not. If the variation between units is explained by differences in clinical practices, then this has enormous potential for quality improvement within the NICUs and through the development of new policy guidelines for clinical practice. The statistical models developed during this project will be useful for clinicians in other health areas and in other countries.Read moreRead less
Generating And Applying Clinical Research To Improve The Outcomes Of Neonatal Intensive Care
Funder
National Health and Medical Research Council
Funding Amount
$568,892.00
Summary
Birth is a complex process and sometimes babies require help to make the transition to independent life. Professor Peter Davis is conducting research into how best to support this transition. This involves helping the lungs to work efficiently and supporting the changes in circulation of the blood to the brain and to the rest of the body. His work aims to quickly identify babies who need help and then provide better treatments to make sure they have the best chance of a healthy life.
Optimising Early Respiratory Support For Preterm Infants: The HIPSTER Trial
Funder
National Health and Medical Research Council
Funding Amount
$696,791.00
Summary
Premature babies who need breathing support are often given ‘nasal continuous positive airway pressure’ (NCPAP) via large nasal prongs. It works well but is uncomfortable. A newer, popular support is ‘high flow’ (HF) which uses smaller nose prongs and may be more comfortable, but HF has not been well studied. The HIPSTER trial will compare these systems in 750 premature babies, at random half will have NCPAP, half will have HF. We will assess whether babies do equally well with each system.
Respiratory failure at birth is a major cause of death and disease in newborn infants. At birth the airways must be cleared of liquid to allow the inhalation of air, but, little is known about the process of lung aeration, because it has not been possible to observe or measure it. We have developed imaging and analytical techniques to observed and measure lung aeration. We will determine ventilation procedures that promote uniform lung aeration and minimise lung injury in ventilated infants.