Development Of A Multiplex Assay For The Identification Of Women At Risk Of Preterm Labour.
Funder
National Health and Medical Research Council
Funding Amount
$202,350.00
Summary
Preterm birth (ie birth before the 37th week of gestation) is the most significant problem facing contemporary clinical obstetrics in the developed world and occurs in approximately 5% to 12% of all deliveries. Being born too early is the major cause of perinatal morbidity and mortality. Data from Australia indicate that each year, more than 17,000 babies will be born prematurely. Of these infants, over 10,000 will suffer respiratory complications and about 1300 will die during the first 21 days ....Preterm birth (ie birth before the 37th week of gestation) is the most significant problem facing contemporary clinical obstetrics in the developed world and occurs in approximately 5% to 12% of all deliveries. Being born too early is the major cause of perinatal morbidity and mortality. Data from Australia indicate that each year, more than 17,000 babies will be born prematurely. Of these infants, over 10,000 will suffer respiratory complications and about 1300 will die during the first 21 days of life. The sickest and most premature of these infants require admission to a Neonatal Intensive Care Unit in a tertiary hospital. Aside from the medical implications of premature delivery, there is also a considerable fiscal challenge to society. While treatments for the prevention of labour have improved considerably over the past decade, current screening tests of preterm labour (ie Fetal Fibronectin test) are unreliable and have poor positive predictive values. The principal objective of this project is to develop and deliver a multiplex assay for the prediction and diagnosis of human preterm labour. Through the successful application of our own proteomic discovery programmes using both ovine and human cervico-vaginal fluid samples, we have identified several new protein markers of labour. Having completed this Phase 1 biomarker trial and established proof-of-concept, we are now well positioned to initiate a Phase 2 biomarker trial to determine reliable estimates of assay sensitivity and specificity. This project targets the development of a new diagnostic to meet a recognised market gap. Delivery of such a test will create a new market in pregnancy-based clinical diagnostics and significantly impact on improving health care and quality of life for many preterm babies. Should the project be completed as detailed and mitigate some of the risk of commercial development, it would then be realistic to seek substantial funding from the private sector.Read moreRead less
The Role And Regulation Of Phospholipase Isozymes In The Initiation Of Human Labour
Funder
National Health and Medical Research Council
Funding Amount
$462,589.00
Summary
Being born too early is the most significant problem facing contemporary clinical obstetrics in the developed world. Preterm birth is the major cause of ill-health and death in newborns, accounting for 85% of all early infant deaths, not secondary to genetic abnormality. In Australia in 1998, more than 17,000 babies were born too early, of these over 10,000 suffered respiratory complications and 1300 died during the first 21 days of life. Even though the likelihood of a premature baby surviving ....Being born too early is the most significant problem facing contemporary clinical obstetrics in the developed world. Preterm birth is the major cause of ill-health and death in newborns, accounting for 85% of all early infant deaths, not secondary to genetic abnormality. In Australia in 1998, more than 17,000 babies were born too early, of these over 10,000 suffered respiratory complications and 1300 died during the first 21 days of life. Even though the likelihood of a premature baby surviving doubles for every two weeks that birth is delayed (between 23 and 28 weeks of gestation), currently there is no treatment available that reliably delays or prevents premature birth. In order to develop clinically useful treatments and improve pregnancy outcome and the well-being of our newborn, it is essential to understand the mechanisms that start the process of labour and delivery. Thus, the overall aim of this project is to increase our understanding of how human labour is initiated and to identify processes that may be manipulated to delay premature birth. In particular, this project focuses on the role and regulation, of what we believe is, a central and common pathway involved in triggering the birth process. This pathway is a known regulator of inflammatory process in the body. Intriguingly, the process of birth displays many of the hallmarks of an inflammatory reaction. Our pilot studies suggest that this pathway is involved in activation many of the events that occur at the time of birth and that further investigation of its role will provide valuable insights in to what triggers human birth. The specific aims of this project are (i) to develop a better understanding of the mechanisms that initiate human labour and (ii) to identify more effectively ways of prevent preterm birth.Read moreRead less
Metabolic And Molecular Determinants Of Embryo Viability
Funder
National Health and Medical Research Council
Funding Amount
$551,321.00
Summary
We know that our health as adults is influenced by the lifestyle of our mothers during pregnancy. In particular, increased risk of adult-onset diseases such as diabetes and cardiovascular disease occurs when small and lean infants at birth are raised in conditions where nutrient intake is not restricted and obesity occurs. This concept of fetal programming is now widely accepted. Our laboratory is leading research in a new concept, that of embryonic programming. We have extensive animal data dem ....We know that our health as adults is influenced by the lifestyle of our mothers during pregnancy. In particular, increased risk of adult-onset diseases such as diabetes and cardiovascular disease occurs when small and lean infants at birth are raised in conditions where nutrient intake is not restricted and obesity occurs. This concept of fetal programming is now widely accepted. Our laboratory is leading research in a new concept, that of embryonic programming. We have extensive animal data demonstrating that exposure of embryos to physiological perturbations alters fetal development, similarly to that occurring in nutrient restriction during pregnancy. Furthermore, there is data from IVF-derived children that their birth-weight is lower than expected, possibly due to the conditions used for conception in the laboratory. How does the response by eggs and embryos, at the time of conception, affect subsequent development? There has been some focus on changes to DNA that are not related to mutations, but structural changes in the DNA that alters gene expression. We call this epigenetics and epigenetic changes are found in embryos, including human embryos following IVF. However, no one knows how such epigenetic changes occur as a result of this stress response by the egg or embryo. Our proposal is to determine the mechanism of how epigenetic alterations take place in eggs and embryos. Our theory is that the mitochondria, the energy producing packages within all cells, are sending signals to the embryo's nucleus. When the egg or embryo finds itself in adverse conditions, the signals change as a result of changes in the energy balance. This in turn changes the activity of enzymes in the nucleus that regulates DNA structure. If we can prove that this relationship occurs, then we can assess these changes in human embryos that are excess to a patient's requirements and learn if programming takes place in human embryos.Read moreRead less
Preterm birth, a birth before the 37th week of pregnancy occurs for fewer than 8% of mothers but is associated with two-thirds of all fetal deaths and deaths of liveborn infants in the first month after birth. In the late 1990s those deaths are concentrated among very preterm births i.e. births before the 32nd week of pregnancy. Infants born very preterm are very likely to need neonatal intensive care, quite likely to have had major respiratory, infectious or other problems after birth, and to n ....Preterm birth, a birth before the 37th week of pregnancy occurs for fewer than 8% of mothers but is associated with two-thirds of all fetal deaths and deaths of liveborn infants in the first month after birth. In the late 1990s those deaths are concentrated among very preterm births i.e. births before the 32nd week of pregnancy. Infants born very preterm are very likely to need neonatal intensive care, quite likely to have had major respiratory, infectious or other problems after birth, and to need readmission to hospital in the first year after birth. Surviving infants are more likely to have major impairments, minor impairments, and school difficulties than infants born at term. There is a substantial impact on families, health services and society of very preterm birth.There has been no reduction in the proportion of births which are preterm, or very preterm in the last 20 years, though advances in treatment and care have markedly improved the survival of preterm and very preterm infants. This study will investigate the role of previous pregnancies which did not result in births (miscarriages and terminations), together with other procedures such as D and C (dilatation and curettage), in subsequent preterm birth. As these previous pregnancy losses are all fairly common experiences any associated risk is important and this particular factor has not been studied in this way before. There is preliminary evidence that they may be associated with preterm birth and the study will be able to measure the associations while taking into account all the other known risk factors. Other possible risk factors such as experiencing violence in pregnancy or social factors acting at a neighbourhood level will also be included. If it is found that previous pregnancy losses are independently associated with preterm birth it will be possible to develop and test preventive strategies.Read moreRead less