This project will test if the ratio of the two different estrogens found in the blood of pregnant women is the critical factor in determining the onset of contractions in the uterus at labour. The studies will also determine the role of a newly discovered receptor for estrogens in allowing powerful contractions at labour. Results will allow development of new treatments to prevent premature birth that block the actions of estrogen at this new receptor or change the ratio of the two estrogens.
We aim to predict neurodevelopmental disability in babies born very preterm, earlier and more accurately than currently possible, by identifying structural and functional connectivity features that correlate with clinical measures of motor and neurodevelopmental functions. To do this we will use brain magnetic resonance imaging (MRI), dense array electroencephalography (EEG) and structured clinical neurodevelopmental assessments to provide a cutting edge view of the state of brain development.
Epigenetic Regulation Of Inflammatory Genes In The Fetal Membranes: Role In Term And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$468,534.00
Summary
Preterm birth is the leading cause of death among newborns and the biggest contributor to disability among infants. Here we propose research to define the mechanism that controls the length of pregnancy and is disrupted in preterm birth. Specifically, we will determine what causes the repression of the labour-promoting inflammatory genes in the uterus during pregnancy and what activates them at labour. We will identify new targets for interventions to block or prevent preterm birth.
Premature birth is a major cause of neonatal death and intellectual and other handicaps among the survivors. While neonatal intensive care has improved the survival of premature babies, there has been no reduction in the number of premature babies born, in fact the numbers are increasing. Our inability to reduce premature birth is partly related to our lack of knowledge of the physiological processes that lead to normal labour. As a result many of our drugs for women in premature labour are not ....Premature birth is a major cause of neonatal death and intellectual and other handicaps among the survivors. While neonatal intensive care has improved the survival of premature babies, there has been no reduction in the number of premature babies born, in fact the numbers are increasing. Our inability to reduce premature birth is partly related to our lack of knowledge of the physiological processes that lead to normal labour. As a result many of our drugs for women in premature labour are not very effective. We have recently identified a novel pathway that regulates the activity of the muscle cells that form the uterus. This project seeks to understand the biochemical processes that change a muscle cell so that it begins to contract actively at the end of pregnancy. Specifically the project will examine two proteins called HSP20 and HSP27. These proteins have recently been reported to play a critical role in the contraction and relaxation of smooth muscle cells in the heart and blood vessels. We have identified for the first time that these proteins are also present in the muscle of the human uterus. It is likely that they play a critical role in regulating the contractions of the uterus. By understanding this process better we may be able to design better treatments to prevent premature birth.Read moreRead less
Premature birth is a major cause of neonatal death and intellectual and other handicaps among the survivors. While neonatal intensive care has improved the survival of premature babies, there has been no reduction in the number of premature babies born, in fact the numbers are increasing. Our inability to reduce premature birth is partly related to our lack of knowledge of the physiological processes that lead to normal labour. As a result many of our drugs for women in premature labour are not ....Premature birth is a major cause of neonatal death and intellectual and other handicaps among the survivors. While neonatal intensive care has improved the survival of premature babies, there has been no reduction in the number of premature babies born, in fact the numbers are increasing. Our inability to reduce premature birth is partly related to our lack of knowledge of the physiological processes that lead to normal labour. As a result many of our drugs for women in premature labour are not very effective. Our work has shown that a hormone called corticotrophin releasing hormone (CRH) made in the placenta plays a critical role in determining the length of a pregnancy. We have measured the levels of this hormone in the blood of pregnant women and shown that it increases more rapidly than normal in women who deliver prematurely and more slowly than normal in women who deliver late. It acts as a kind of clock to determine the length of pregnancy. What is not known is how this hormone acts to bring on labour. What is particularly puzzling is that some of the actions of the CRH seem likely to cause the uterus to relax rather than to contract. We wish to test the idea that the rapidly rising levels of this hormone in late pregnancy cause changes in the uterus that stop the pathways to relaxation and lead to contraction. To perform these studies we will use small pieces of uterus donated with informed consent from women undergoing caesarean section. The results of these studies may allow us to design better ways of preventing premature birth and prevent many cases of cerebral palsy and intellectual handicap.Read moreRead less
Preterm birth is a major cause of neonatal death and cerebral palsy. This grant will provide proof-of-concept that a computer program can be developed to predict a pregnant woman�s risk of preterm birth. There is a large market (4M US and 8M Europe), there are no competing technologies. This is a unique collaboration between Biomedical Engineering and an Australian centre with an international reputation in preterm birth, assisted by a pathology company.
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
Optimising Non-invasive Ventilation At Birth For Preterm Infants
Funder
National Health and Medical Research Council
Funding Amount
$735,912.00
Summary
Infants born very premature require respiratory support at birth to make the transition to newborn life. As these infants are very immature and prone to injury, modern respiratory care strategies utilise the least invasive approaches mainly applied using a facemask. However, we have discovered that the larynx is closed at birth and thereby prevents air from entering the lung. This application is focussed on optimising the efficiency of facemask ventilation at birth and stimulating breathing.
Mental Health Across Generations: Pre-and Post Conception Predicators Of Early Life Risks
Funder
National Health and Medical Research Council
Funding Amount
$666,231.00
Summary
In 2003, mental illnesses were among the ten leading causes of disease burden in Australia, accounting for 13% of the total burden of disease, according to the Australian Institute of Health and Welfare. Mental health problems and mental illness are among the greatest causes of disability, diminished quality of life, and reduced productivity. People affected by mental health problems often have high levels of morbidity and mortality, experiencing poorer general health and higher rates of death f ....In 2003, mental illnesses were among the ten leading causes of disease burden in Australia, accounting for 13% of the total burden of disease, according to the Australian Institute of Health and Welfare. Mental health problems and mental illness are among the greatest causes of disability, diminished quality of life, and reduced productivity. People affected by mental health problems often have high levels of morbidity and mortality, experiencing poorer general health and higher rates of death from a range of causes, including suicide. These conditions are significant in terms of prevalence and disease burden, and have far-reaching impacts for families, carers and others in the community. Mental health problems commonly cluster in families. However, few studies have previously been able to investigate the range of ways in which mental disorders may pass from one generation to another. Further, evidence suggests that influences that arise prior to conception may have major effects on early life risks such as development in utero, birth outcomes and early maternal infant bonding. Mental Health across Generations: Pre- and post-conception predictors of early life risks is a unique study that will examine antenatal maternal mental health and risk behaviours during pregnancy. The study will also examine the links between prior maternal mental health and later birth outcomes, and post natal maternal infant bonding. The risk processes to be tested will include genetic, epigenetic (changes in gene expression), physiological and psycho-social parameters.Read moreRead less
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.