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
DOES TREATMENT REVERSE THE NEUROCOGNITIVE AND CARDIOVASCULAR SEQUELAE OF SLEEP DISORDERED BREATHING IN CHILDREN?
Funder
National Health and Medical Research Council
Funding Amount
$519,826.00
Summary
Studies in children have shown that disruption to normal sleep patterns resulting from sleep disordered breathing (SDB) has severe consequences for both the cardiovascular system and neurocognition. To date there have been no studies in children to investigate whether treatment of SDB with adenotonsillectomy, which has been shown to reduce sleep fragmentation and neurocognition, also reduces blood pressure.
Repeated Prenatal Corticosteroids: Effects On Childhood Development, Behaviour, Growth And Health
Funder
National Health and Medical Research Council
Funding Amount
$718,055.00
Summary
Infants born preterm are at high risk of needing help with their breathing to survive. Corticosteroids given to the mother prior to preterm birth can substantially reduce these risks, although the beneficial effects of these drugs only seem to last seven days. Because of this there has been a tendancy to repeat the dose of prenatal steroids after seven days in women who remain at continued risk of very preterm birth. There has been no formal assessment of whether or not repeating the dose of pre ....Infants born preterm are at high risk of needing help with their breathing to survive. Corticosteroids given to the mother prior to preterm birth can substantially reduce these risks, although the beneficial effects of these drugs only seem to last seven days. Because of this there has been a tendancy to repeat the dose of prenatal steroids after seven days in women who remain at continued risk of very preterm birth. There has been no formal assessment of whether or not repeating the dose of prenatal corticosteroids is beneficial or harmful. In this clinical trial we will test what effect, if any, repeat doses of corticosteroids given to women who remain at risk of pretermbirth, have on children at the age of two years Women are eligible for the trial if at of less than 32 weeks of pregnancy, they have received corticosteroids seven or more days ago, and they are considered to be at continued risk of preterm birth. Women are randomised to one of the two treatment groups. Half the women will receive a weekly intramuscular injection of corticosteroids up to the time of birth or 32 weeks gestation, whichever is earlier, whilst the risk of very preterm birth remains. The other half of the women will receive a saline placebo injection. Chance will decide which treatment the women receives. In this study all children who survive to 2 years corrected age will be assessed to see if they have any problems with their health, growth and development. In particular we will assess how well they can walk, talk, understand, see and hear. The trial will be able to assess whether repeat doses of prenatal corticosteroids are helpful or not for infants at risk of being born very preterm by comparing the short term effects on infant health after birth and whilst in hospital with the effects on the child's later health, growth and development. An economic assessment of repeat doses of prenatal corticosteroids will be made in these children.Read moreRead less
Clinical Trial Of Minimally-invasive Surfactant Therapy
Funder
National Health and Medical Research Council
Funding Amount
$1,172,978.00
Summary
This proposal is for funding of a clinical trial investigating a new and less-invasive technique of giving surfactant to improve lung function in preterm babies born between 25 and 28 weeks gestation. The trial will examine whether giving surfactant using the less invasive method results in better outcomes, including a reduction in time on respiratory support, and higher survival without chronic oxygen dependency.
DEVELOPMENT OF CARDIOVASCULAR CONTROL DURING SLEEP IN HUMAN INFANTS AFTER PRETERM BIRTH
Funder
National Health and Medical Research Council
Funding Amount
$358,537.00
Summary
Infants spend the major part of their life in sleep, and the period between birth and 6 months of age sees dramatic changes in their sleep organisation. Coincidently, there are dramatic developmental changes in the infant's heart and blood pressure control systems, and the ability to compensate for stress such as falls of blood pressure (hypotension) or in the level of oxygen in the blood (hypoxaemia). In infants born preterm, the risks of hypoxaemia, and even death are significantly greater dur ....Infants spend the major part of their life in sleep, and the period between birth and 6 months of age sees dramatic changes in their sleep organisation. Coincidently, there are dramatic developmental changes in the infant's heart and blood pressure control systems, and the ability to compensate for stress such as falls of blood pressure (hypotension) or in the level of oxygen in the blood (hypoxaemia). In infants born preterm, the risks of hypoxaemia, and even death are significantly greater during sleep than during wakefulness, but why this is so is uncertain. This study will examine the ability of infants to respond to stress during sleep. Four groups of infants will be examined: healthy infants born at normal gestation; healthy infants born prematurely (preterm); preterm infants who have experienced mild hypoxaemia soon after birth; and preterm infants who have suffered more severe hypoxaemia because of lung disease. Infants will be studied in a sleep laboratory during day-time sleep, and their ability to control blood pressure will be determined. By contrasting the effectiveness of blood pressure control between the infant groups we aim to determine whether preterm infants have lasting problems as a result of their premature birth, or their exposure to hypoxaemia. By contrasting infants in sleep and wakefulness, we aim to assess whether the risks of poorer blood pressure control are greater in sleep.Read moreRead less
RCT Of Headbox Oxygen Vs CPAP For Neonatal Respiratory Distress In Non-tertiary Hospitals
Funder
National Health and Medical Research Council
Funding Amount
$225,500.00
Summary
Each year in NSW hundreds of babies are transferred from local general hospital nurseries to a hospital with Neonatal Intensive Care Unit (NICU) because of breathing difficulties. Frequently, mothers are unable to accompany their babies at the time of transfer, leading to stress. When a mother is eventually transferred she is often separated from her partner and local supports causing further anxiety. In addition, if a baby has to be transferred, invasive procedures may be needed to ensure safet ....Each year in NSW hundreds of babies are transferred from local general hospital nurseries to a hospital with Neonatal Intensive Care Unit (NICU) because of breathing difficulties. Frequently, mothers are unable to accompany their babies at the time of transfer, leading to stress. When a mother is eventually transferred she is often separated from her partner and local supports causing further anxiety. In addition, if a baby has to be transferred, invasive procedures may be needed to ensure safety. Currently, babies who need oxygen in a local hospital are placed in a crib with a clear plastic box around their head and oxygen is run into the box (headbox oxygen). There is an alternative method of providing oxygen called CPAP (Continuous Positive Airway Pressure). This involves giving the oxygen directly into the baby's nose via soft rubber prongs. CPAP has been used since the 1970's. It is the main form of respiratory support for infants in many NICUs in Australia and the world. There is some evidence that death and lung disease may be reduced. However, the babies in these studies are sicker and smaller than babies in local hospital nurseries. CPAP is used in some local nurseries in New Zealand, however no studies have been done to see if CPAP reduces the need for inter-hospital transfer. The study will involve hospitals that have been selected because of their level of on site medical and nursing staff. These hospitals will have support and advice from two NICUs that use CPAP as their main form of respiratory support. Babies who need oxygen will be randomly allocated to either have headbox oxygen or CPAP. If the baby becomes so unwell such that certain preset criteria are met, the baby will be transferred to a NICU in the usual way. If CPAP safely reduces the need for inter-hospital transfer, many parents will be saved the anxiety associated with transfer, and the separation it often causes.Read moreRead less
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