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The Effects Of Maternal Glucocorticoid Administration In Growth Restricted Fetuses.
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
Antenatal administration of glucocorticoids to pregnant women at risk of preterm delivery has been shown to enhance fetal lung maturation. However, glucocorticoids such as betamethasone have a range of potentially deleterious non-pulmonary effects, which include significant alterations in fetal cardiovascular function. This is important because intrauterine growth restricted (IUGR) fetuses constitute a significant proportion of pregnancies in Australia, are at risk of preterm delivery and are th ....Antenatal administration of glucocorticoids to pregnant women at risk of preterm delivery has been shown to enhance fetal lung maturation. However, glucocorticoids such as betamethasone have a range of potentially deleterious non-pulmonary effects, which include significant alterations in fetal cardiovascular function. This is important because intrauterine growth restricted (IUGR) fetuses constitute a significant proportion of pregnancies in Australia, are at risk of preterm delivery and are therefore likely to receive maternal betamethasone. From both human observations and animal studies, it is well documented that IUGR fetuses demonstrate a range of cardiovascular adaptations that ensure maintenance of oxygen delivery to vital organs despite reduced placental perfusion. However, in recent clinical and experimental studies we have demonstrated that administration of betamethasone to IUGR fetuses induces changes in fetal blood flow that may be detrimental to the IUGR fetus. Specifically, we believe that glucocorticoids may increase the risk of both cardivascular and cerebral damage in the growth restricted fetus. The significance of these findings and the mechanisms regulating these changes remain unclear but they have clear implications for future clinical management. This proposal represents the further development of preliminary experimental studies to examine the effects of betamethasone in the ovine IUGR fetus with future clinical care in mind.Read moreRead less
DEVELOPMENT OF FOLDING IN THE FETAL CEREBRAL CORTEX – IDENTIFYING FUNDAMENTAL MECHANISMS AND THEIR SUSCEPTIBILITY TO DISRUPTION IN NORMAL AND ABNORMAL PREGNANCY
Funder
National Health and Medical Research Council
Funding Amount
$607,742.00
Summary
During pregnancy, the surface of the fetal brain gradually develops the ridges, valleys, and folds that are the characteristic feature of our highly developed brain. However, this process can be disturbed if birth occurs prematurely, the unborn baby suffers oxygen starvation in the uterus, or the mother consumes alcohol. In this project we are determining how cell migration results in the development of brain surface folding, and how hypoxia and maternal alcohol consumption affect these importan ....During pregnancy, the surface of the fetal brain gradually develops the ridges, valleys, and folds that are the characteristic feature of our highly developed brain. However, this process can be disturbed if birth occurs prematurely, the unborn baby suffers oxygen starvation in the uterus, or the mother consumes alcohol. In this project we are determining how cell migration results in the development of brain surface folding, and how hypoxia and maternal alcohol consumption affect these important processes.Read moreRead less
Contribution Of Disturbed Blood Flow And Cerebral Metabolism To White Matter Damage In The Perinatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$369,375.00
Summary
It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral ....It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral palsy. Such outcomes are often associated with the presence of asphyxia and infection during pregnancy, leading to the belief that the damage first arises while the baby is still in utero. In this application we suggest that asphyxia and-or infection during pregnancy cause prolonged disturbances in the regulation of blood flow and integrity of the blood-brain barrier in the developing brain, together with changes in metabolism that result in accumulation of prostaglandins and the toxic hydroxyl radical, leading irreversibly to cell death. If this series of events proves to be true, we have suggested and will test several protocols for protecting the fetal brain, which should be readily translatable to clinical practice.Read moreRead less
Understanding The Impact Of Preterm Birth On Development: Improving Outcomes For Preterm Infants.
Funder
National Health and Medical Research Council
Funding Amount
$823,008.00
Summary
Approximately 10% of babies are born prematurely and many suffer long-term health problems. Our aim is to understand how premature birth affects the development of the cardiovascular, respiratory and central nervous systems. This understanding will help to improve the long-term health outcomes for premature infants. By working with medical practitioners treating premature babies we are well placed to translate our findings on preventing and treating developmental injury into clinical practice.
Carbon Dioxide As A Treatment For Seizures In The Newborn
Funder
National Health and Medical Research Council
Funding Amount
$878,389.00
Summary
This study aims to introduce a simple and effective treatment to prevent brain damage from seizures in babies using CO2. Neonatal seizures remain a major clinical problem worldwide and are associated with poor brain outcomes and significant risk of death. Recent trials in human adult epileptics show rapid and effective seizure suppression following the use of CO2. This therapy will significantly impact long-term outcomes for affected babies and reduce the burden of care for families and society.
Creatine, A Multi-organ Protectant Against Hypoxic Injury In The Neonate
Funder
National Health and Medical Research Council
Funding Amount
$524,802.00
Summary
The WHO estimates that up to 9 million babies suffer birth hypoxia each year, leading to 29% of global neonatal deaths, and significant rates of severe disability. We hypothesise that creatine, given as a supplement to the mothers diet during pregnancy, will protect her babies organs should low oxygen around the time of birth occur. The low cost of creatine is particularly relevant for rural and remote communities and the developing world where, currently, there are no effective therapies.
Injury to the developing brain, whether sustained during pregnancy or at birth, is the underlying cause of many cognitive and motor disabilities, including cerebral palsy. This project will identify the cellular pathways that cause developmental brain injury in preterm and term infants, and then administer umbilical cord blood stem cells at different timepoints to assess their efficacy at reducing brain injury. This project will inform treatment with cord blood stem cells in high risk infants.
The exposure of infants to adverse events both before and after birth can cause death or permanent disability (eg cerebral palsy) for the infant. Our primary research objective is to minimize the impact and improve outcomes for infants exposed to adverse events before and/or after birth. We will use a multi-disciplinary approach that aims to understand the science and to develop new treatments, thereby representing true “bench to bedside” research.
Treatment Of Cerebral Palsy - An Experimental Approach
Funder
National Health and Medical Research Council
Funding Amount
$589,544.00
Summary
Cerebral palsy is characterised by disordered movement evident early in life leading to lifelong disability. The motor disorder arises from an abnormality within the white-matter of the brain that is non-progressive and is identifiable soon after birth. In humans and experimental models of fetal infection there is an increase in markers of inflammation. We will use induce ovine fetal infection and white matter injury to examine if anti-inflammatory treatments can prevent fetal brain damage.