DHA For The Improvement Of Neurodevelopmental Outcome In Preterm Infants: The DINO Trial
Funder
National Health and Medical Research Council
Funding Amount
$631,875.00
Summary
The incidence of neurological problems that occur in children born prematurely is higher than for those born at term. The earlier that a baby is born, the greater chance it has of having some developmental delay and general inability to cope at school. This has implications for the child, the families and the health system. One of the many dietary factors implicated in the development of neural abilities in premature infants is an omega-3 fatty acid called DHA. This compound is present in breast ....The incidence of neurological problems that occur in children born prematurely is higher than for those born at term. The earlier that a baby is born, the greater chance it has of having some developmental delay and general inability to cope at school. This has implications for the child, the families and the health system. One of the many dietary factors implicated in the development of neural abilities in premature infants is an omega-3 fatty acid called DHA. This compound is present in breast milk and most preterm formulas and is found in high concentrations in the brain and retina. In the last third of pregnancy the developing baby would normally accumulate DHA at a rapid rate. So it seems reasonable to assume that a baby outside the mother, that is born premature, would also need to accumulate DHA at this same rate. The problem is that none of the milks currently given to premature infants have DHA in high enough concentration to supply this amount of DHA to the baby. For example, breast milk and preterm formulas contain only a third of the DHA required. In order to provide this amount for the premature infant, breast milk containing DHA at about 1% of the total fat is required. Fortunately the level of DHA in breast milk can be increased to this level by supplementing the mothers diet with fish or olis like tuna oil. This study hopes to show that premature babies who receive DHA in amounts similar to that supplied in the womb will develop better than babies who receive low amounts of DHA.Read moreRead less
Improving The Efficacy Of Retinoid Therapy In Childhood Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$295,336.00
Summary
Cancer is still the commonest disease causing death in chilhood. Childhood neuroblastoma is a cancer of the nerve tissue which presents usually as a widely spread malignancy, which responds poorly to conventional therapy, indicating the need for novel treatment approaches. Vitamin A derivatives, or retinoids, given in addition to conventional therapy improves the cure rate for children with advanced neuroblastoma to 50%. We have shown that one likely mechanism of retinoid resistance is a deficie ....Cancer is still the commonest disease causing death in chilhood. Childhood neuroblastoma is a cancer of the nerve tissue which presents usually as a widely spread malignancy, which responds poorly to conventional therapy, indicating the need for novel treatment approaches. Vitamin A derivatives, or retinoids, given in addition to conventional therapy improves the cure rate for children with advanced neuroblastoma to 50%. We have shown that one likely mechanism of retinoid resistance is a deficiency of retinoic acid receptor beta, which is a necessary factor in the neuroblastoma cell for converting the retinoid anti-cancer signal into an irreversible cellular change. In this project we will define why some neuroblastoma cells express low levels of this protein and test new retinoid therapies.Read moreRead less
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