Postnatal Dexamethasone In Tiny Babies: Does It Do More Good Than Harm?
Funder
National Health and Medical Research Council
Funding Amount
$394,688.00
Summary
The survival rate for tiny or very premature babies has improved dramatically in recent times, from below 10% in the 1960s to greater than 70% in the 1990s. However, some of these babies require prolonged periods of help with breathing and oxygen treatment to survive, and many develop a form of chronic lung disease in the newborn period. A powerful group of drugs, known as corticosteroids, have been used to treat or prevent this chronic lung disease in newborn babies, with some success in shorte ....The survival rate for tiny or very premature babies has improved dramatically in recent times, from below 10% in the 1960s to greater than 70% in the 1990s. However, some of these babies require prolonged periods of help with breathing and oxygen treatment to survive, and many develop a form of chronic lung disease in the newborn period. A powerful group of drugs, known as corticosteroids, have been used to treat or prevent this chronic lung disease in newborn babies, with some success in shortening the time that the babies need help with breathing. However, corticosteroids have the potential to cause long-term harm to the developing baby's brain, and may cause lifelong problems with thinking, walking, talking, seeing or hearing. We want to test in a clinical trial if corticosteroids, specifically dexamethasone, can reduce the need for help with breathing and the rate of chronic lung disease without causing long-term problems to the developing baby's brain. Babies who are very tiny (born weighing less than 1000 g), or born very early (born before 28 weeks of pregnancy, or more than 12 weeks premature) will be eligible for this study if they still need help with their breathing after one week of age from a machine called a respirator, and their doctor considers that corticosteroids might be helpful to the baby's breathing. Some babies will receive dexamethasone and other babies will be treated with a harmless placebo - chance will decide which treatment the baby receives. All other aspects of the babies' care will continue as normally. Children who survive to 2 years of age will be assessed fully to determine if they have any problems with their health, including problems with their thinking, walking, talking, seeing or hearing. We will determine if dexamethasone is helpful or not for very tiny or very premature babies who have breathing problems after the first week of life. We will also measure the economic impact of dexamethasone treatment in these babies.Read moreRead less
SCHOOL-AGE OUTCOME FOR VERY TINY/PRETERM CHILDREN BORN IN VICTORIA IN 1991-92
Funder
National Health and Medical Research Council
Funding Amount
$252,956.00
Summary
The survival rate for tiny or very premature babies has improved dramatically in recent times, from below 10% in the 1960s to greater than 70% in the 1990s. Several new treatments have helped to improve their survival rate, but some have the potential to cause long-term harm to the developing baby's brain or lung, and may cause lifelong problems with thinking, walking, talking, seeing, hearing, growth or breathing. Babies who are very tiny (born weighing less than 1000 g), or born very early (bo ....The survival rate for tiny or very premature babies has improved dramatically in recent times, from below 10% in the 1960s to greater than 70% in the 1990s. Several new treatments have helped to improve their survival rate, but some have the potential to cause long-term harm to the developing baby's brain or lung, and may cause lifelong problems with thinking, walking, talking, seeing, hearing, growth or breathing. Babies who are very tiny (born weighing less than 1000 g), or born very early (born before 28 weeks of pregnancy, or more than 12 weeks premature) will be assessed long term (to 8-9 years of age), as broadly as possible, and in comparison with normal birthweight (NBW, birthweight >2499 g) children. Outcomes will encompass academic progress and behaviour, brain function, general health, growth, and respiratory health. We will compare the outcomes for very tiny-preterm children who were treated with several of these new therapies with those who were not so treated. We will assess whether alternative measures of long term outcome that assess the quality of life are applicable to very tiny-preterm children. If so, these measures could be used much more widely, since they are cheaper and less time-consuming.Read moreRead less
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.
Nasal CPAP For Very Preterm Infants At Birth: Does It Improve Outcome? A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$460,604.00
Summary
Neonatal respiratory distress syndrome (RDS) is the major cause of morbidity and mortality in preterm infants. Many of these infants need ventilatory support to keep them alive. In 1996 and 1997, 10,471 infants in Australia and New Zealand needed ventilatory support for a total of 72,544 days. This treatment is a great physical burden for the infants and an enormous emotional stress for their parents. Each day of treatment costs about A$2000 so their hospital treatment costs about $72 million a ....Neonatal respiratory distress syndrome (RDS) is the major cause of morbidity and mortality in preterm infants. Many of these infants need ventilatory support to keep them alive. In 1996 and 1997, 10,471 infants in Australia and New Zealand needed ventilatory support for a total of 72,544 days. This treatment is a great physical burden for the infants and an enormous emotional stress for their parents. Each day of treatment costs about A$2000 so their hospital treatment costs about $72 million a year. Of infants born less than 29 weeks' gestational age, about 40% of the survivors subsequently developed chronic lung disease (CLD). This condition is defined as prolonged dependence on supplementary oxygen therapy. CLD is associated with further costs and increased lung problems and readmissions to hospital in the first year of life. Thus, CLD is an expensive and time-consuming condition that has a high social cost. This project will determine whether treating these very premature babies from birth simply by applying oxygen under a low continuous positive pressure (CPAP) into their nose rather than the present treatment of placing a tube in the windpipe (known as intubation) and ventilation will reduce the incidence and severity of neonatal respiratory distress syndrome and subsequent chronic lung disease. The project will involve 600 babies from different, high quality neonatal intensive care units. Babies who are born at less than 29 weeks' gestation and who show signs of breathing at birth will be randomly allocated to be treated with either nasal CPAP or intubation and ventilation. This project will determine whether CPAP treatment at birth improves survival and reduces the severity of the RDS and subsequent CLD, or has no long term beneficial effect. If the trial is successful, this will be one of the most useful new treatments in neonatal medicine because it is simple to use, easier for the babies, and cheaper than ventilation.Read moreRead less
Mucopolysaccharidoses (MPS) are a related group of 11 debilitating genetic disorders affecting children. They result from a reduction or total deficiency of an enzyme required for the removal of carbohydrate structures called glycosaminoglycans (gags). Gag degradation occurs inside the cell in specific organelles termed lysosomes and in the absence of the appropriate enzyme, undegraded gag accumulates in the cell. This leads to a range of clinical symptoms and multiple tissue failure. Symptoms c ....Mucopolysaccharidoses (MPS) are a related group of 11 debilitating genetic disorders affecting children. They result from a reduction or total deficiency of an enzyme required for the removal of carbohydrate structures called glycosaminoglycans (gags). Gag degradation occurs inside the cell in specific organelles termed lysosomes and in the absence of the appropriate enzyme, undegraded gag accumulates in the cell. This leads to a range of clinical symptoms and multiple tissue failure. Symptoms common to more than one MPS type include mental deterioration, blindness, abdominal organ enlargement and bone growth problems leading to short stature and bone loss. My laboratory has had a long-term interest in developing treatment for MPS and our research led to the clinical implementation of enzyme replacement therapy (ERT) for MPS VI in 2005. While providing the first effective, multi-tissue treatment for MPS, our research showed that several tissues were not responsive to ERT. These are the brain, cartilage and cornea, thus children on ERT regimens will still suffer from mental retardation, arthritis and blindness. With the goal of treating these particular tissues we have developed a new approach to MPS therapy called substrate deprivation therapy (SDT). Instead of adding back the missing enzyme, SDT acts by decreasing gag production which in turn reduces the level of accumulated gag in cells. SDT results in the correction of MPS cells in culture and reduces several key clinical symptoms in the mouse model of MPS IIIA. In this proposal we will extend our research to evaluate the effect of SDT on brain and bone-joint pathology. Evaluation of efficacy will take place in the MPS VII mouse which exhibits both brain and bone disease and in a new model of MPS IVA developed specifically for this study which exhibits a joint pathology unique amongst the MPS disorders.Read moreRead less
Skeletal disease is a major problem for children with mucopolysaccharidoses (MPS). Patients suffer from early onset osteoporosis and osteoarthritis, severely affecting their quality of life. We will evaluate a lentiviral gene therapy vector developed in-house for its capacity to transduce bone, cartilage, synovial and ligament cells in a mouse model of MPS VI. Our goal is to generate high level, sustained expression of the deficient MPS enzyme and alter the course of skeletal disease in MPS.
Therapy For CNS Degeneration In MPS Disorders That Targets Both Glycosaminoglycan And Ganglioside Storage.
Funder
National Health and Medical Research Council
Funding Amount
$368,043.00
Summary
Children with seven of the eleven types of mucopolysaccharidosis (MPS) disorders exhibit a profound, irreversible neurological deterioration that manifests in infancy. This results from the continual buildup of undegraded sugar and fat in brain cells. The goal of this proposal is to prevent the accumulation of lipid alone or both lipid and sugar in the brain in order to alter the progression of neurological disease. Treatment will be assessed in mouse models of MPS.
Hepatic Fibrogenesis In Paediatric Cholestatic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is bili ....Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is biliary atresia. It develops at, or shortly after birth with progressive destruction of the bile ducts, responsible for transporting bile out of the liver. Without early diagnosis and surgery these infants develop progressive liver scarring leading to liver failure and death or liver transplantation within 1-2 years. It is the commonest reason for liver transplantation in children (55-60%) in the Western world. Even with successful surgery, most, if not all patients will come to liver transplantation over the subsequent 25 years because of ongoing, but slower, scar formation. In older children, diseases like cystic fibrosis cause bile duct blockages leading to progressive liver scarring that is slower and unpredictable, contributing to ill health in up to 20% of patients and death from end stage liver disease or liver transplantation in 5%. Using liver tissue from children with these two disorders we have been able to identify the key cells that control the liver scar process, the Hepatic Stellate Cell. We now need to investigate the role of bile constituents on the scar-forming process in these two diseases. We will utilise a well characterised animal model to investigate the influence of bile constituents on cells isolated from this model and apply these findings back to patient samples to determine their role in paediatric cholestatic liver disease. This will help us to better understand the disease process and importantly, develop more effective and earlier treatment.Read moreRead less
RCT Of The Intragastric Balloon And Lifestyle Intervention Versus Lifestyle Intervention Alone In Obese Adolescents
Funder
National Health and Medical Research Council
Funding Amount
$598,976.00
Summary
For the first time in adolescents, Perth researchers will trial placement of a fluid-filled silicone balloon in the stomach. It will be used in conjunction with a lifestyle intervention, and so is expected to increase weight loss. The balloons are safe, effective at adult weight loss and an alternative to invasive surgery. Adolscent obesity rates are rising and treatment options are limited. The non-surgical balloon may be the alternative for adolescents who would previously had to have surgery.