Antagonist Of Corticotrophin Releasing Hormone As Therapeutic Agents For The Prevention Of Premature Birth In Humans
Funder
National Health and Medical Research Council
Funding Amount
$376,650.00
Summary
In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow ....In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow the extension of pregnancy term The development of protocols that will in turn reduce neonatal mortality. Additionally we believe that these new agents will be useful in preventing the onset of labour after fetal surgery. Currently there are no effective treatments capable of substantially changing delivery dates. Available therapeutics delay the onset of labour, at best, 24 hours. However, recent exciting results from our laboratories show that rising concentrations of the placental peptide Corticotrophin Releasing Hormone (CRH) are associated with the onset of labour. Further, we have also delayed the onset of labour in pregnant sheep by infusing a relatively insoluble CRH antagonist into the sheep fetus. Labour commenced ONLY AFTER the drug was withdrawn from the mother. This project builds upon an interdisciplinary team: medicinal chemists, molecular modellers, pharmacologists and endocrinologists, to further develop an exciting Australian discovery. Successful completeion of this research will, for the first time, allow the control of pregnancy duration MAXIMISING the benefits to mother and child, reducing mortality and later life morbidities typically associated with premature birth.Read moreRead less
Understanding The Myometrial Transition At Term And Preterm Labour To Guide Tocolysis
Funder
National Health and Medical Research Council
Funding Amount
$808,447.00
Summary
This grant seeks to understand how the muscle cells of the uterus transform at the time of labour. We propose that this transformation is organised by enzymes that modify the histones around key genes. We will test if a similar pathway operates in cases of preterm labour. The results will guide the development of new ways of treating premature labour that will use targeted nanoparticles to deliver siRNA directly to the muscle cells of the uterus.
Multicentre Trial Of Calcium Channel Blocker Versus Calcium Channel Blocker Plus Cox2 Inhibitor In Preterm Labour
Funder
National Health and Medical Research Council
Funding Amount
$644,130.00
Summary
Preterm birth is a major problem in our society, and has enormous consequences for parents and children. It also has a major impact on scarce financial resources. When women present in preterm labor, current therapies have only limited success in stopping contractions and postponing birth. They have not been shown to reduce the rates of the serious neonatal problems associated with prematurity. This project will be coordinated in Newcastle, N.S.W., and will involve major perinatal centres throug ....Preterm birth is a major problem in our society, and has enormous consequences for parents and children. It also has a major impact on scarce financial resources. When women present in preterm labor, current therapies have only limited success in stopping contractions and postponing birth. They have not been shown to reduce the rates of the serious neonatal problems associated with prematurity. This project will be coordinated in Newcastle, N.S.W., and will involve major perinatal centres throughout Australia, along with overseas centres. It will test a new combination of drugs for their ability to postpone delivery in women presenting with preterm labour. It is postulated that the combination of drugs will be more effective than existing therapies. The drugs used in the trial are Nifedipine and Rofecoxib. Complications of prematurity include neonatal death, cerebral palsy, visual and hearing impairment, and chronic lung disease. These complications are most significant in extremely premature infants - in particular, those under 28 weeks gestation at the time of their delivery. For this reason, the study will focus only on women presenting in labour below 28 weeks. The ability to stop labour is important, but the main aim of any treatment for preterm labour is to reduce the rates of neonatal death and handicap. Babies born to women enrolled in this study will be followed for a period of one year after birth to assess their outcomes. It is our hypothesis that the combination of Rofecoxib and Nifedipine will result in lower rates of death and handicap in babies than Nifedipine alone. In addition, we will examine the rates of side effects in women receiving therapy. Currently used therapies, including intravenous ventolin, have high rates of maternal side effects. Nifedipine and Rofecoxib have both been shown to have low rates of maternal side effects.Read moreRead less
Motor problems, ranging from clumsiness to cerebral palsy, are one of the most common adverse outcomes in children born early. This study will investigate the motor development of children born <30 weeks’ gestation compared with peers born at term from birth to 5 years. We will determine whether early clinical evaluations or neuroimaging in the newborn period can predict later motor impairment at 5 years to be able to identify those who will benefit most from early intervention.
Defining Epigenetic Predictors Of Long-term Outcomes Of Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$409,408.00
Summary
On average, those born premature do worse health-wise than those born at term. However, some do worse than others. Our aim is to identify these people at birth to better help doctors and parents to closely monitor their health. For this, we will be “reading the diary of pregnancy” in the molecules added to chromosomes in blood during pregnancy in young adults with will characterised states of health. We will analyse DNA from blood that we will extract from stored heel prick spots.
Air Pollution And Mortality And Morbidity In Adult Australians (APMMA Study): A Large Population Based Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$1,041,410.00
Summary
This study will investigate the link between respiratory and cardiovascular disease and mortality and exposure to long-term air pollution. We will use cutting edge methods to assign neighbourhood air pollution levels to a large cohort of NSW adults (n>265,000) previously recruited in the 45 and Up Study. The study results will be of utmost importance in setting outdoor air pollution standards and informing cost benefit analyses of air pollution control strategies.
Rapidly giving intravenous fluid to prevent or treat shock (fluid resuscitation) is one of the commonest treatments given to critically ill patients. Current guidelines recommend crystalloid solutions but it is unknown whether any particular crystalloid is better than others. This trial will determine whether the use of one of two crystalloid fluids, saline or PlasmaLyte, reduces the risk of organ injuries, such as kidney failure, and improves patients chances of surviving critically illness.
Demographic and social dimensions of migrant ageing and wellbeing in Australia. This project aims to examine the deterioration of health and wellbeing in migrant communities in Australia over time. Some migrant groups suffer higher mortality and morbidity in older age, despite having better health than non-migrants upon arrival in the host country. By consolidating and analysing a wide range of quantitative data and conducting qualitative fieldwork among ten migrant groups in Australia, the proj ....Demographic and social dimensions of migrant ageing and wellbeing in Australia. This project aims to examine the deterioration of health and wellbeing in migrant communities in Australia over time. Some migrant groups suffer higher mortality and morbidity in older age, despite having better health than non-migrants upon arrival in the host country. By consolidating and analysing a wide range of quantitative data and conducting qualitative fieldwork among ten migrant groups in Australia, the project aims to produce new estimates of healthy life expectancy and investigate how social capital sustains health throughout the ageing process. The project will inform government policymakers, migrant aged care service providers, and migrant communities in supporting quality of life outcomes.Read moreRead less
Putting death in its place. The project aims to link 890,000 population records to place of residence from 1838 to 1930, to examine the relationships between where people live, mortality, life expectancy and health. Where people live impacts their life-course outcomes. Using novel matching techniques, the project expects to identify intergenerational changes and the spatial dynamics of inequality and social mobility. Expected outcomes include the creation of a public resource of linked data and ....Putting death in its place. The project aims to link 890,000 population records to place of residence from 1838 to 1930, to examine the relationships between where people live, mortality, life expectancy and health. Where people live impacts their life-course outcomes. Using novel matching techniques, the project expects to identify intergenerational changes and the spatial dynamics of inequality and social mobility. Expected outcomes include the creation of a public resource of linked data and a better understanding of long-run health and inequality. These should provide economic and social benefits by informing policy aimed at contemporary social and health challenges, enhancing our understanding of Australian history, and developing public resources.Read moreRead less
Intergenerational Transmission of Inequality. There is a growing interest in the ways in which biological and socioeconomic heritage can shape vulnerabilities to disease. Once viewed as primarily a product of recent conditions such as lifestyle choices, it is now evident that health outcomes can also be shaped by intergenerational mechanisms. Analysis of these in current populations is impractical given the considerable time it would take for a prospective study to unfold. The analysis of histor ....Intergenerational Transmission of Inequality. There is a growing interest in the ways in which biological and socioeconomic heritage can shape vulnerabilities to disease. Once viewed as primarily a product of recent conditions such as lifestyle choices, it is now evident that health outcomes can also be shaped by intergenerational mechanisms. Analysis of these in current populations is impractical given the considerable time it would take for a prospective study to unfold. The analysis of historical populations, however, presents an opportunity to circumvent this obstacle. Using data for male and female convicts and their descendants, this project seeks to determine the extent to which disadvantage experienced by one generation impacted on the life expectancy of those that followed.Read moreRead less