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.
Regulation Of Progesterone Action In Human Parturition.
Funder
National Health and Medical Research Council
Funding Amount
$314,983.00
Summary
Premature birth is the leading cause of neonatal death and sickness, and numbers are increasing due to our ignorance of the biology of labour. Progesterone maintains pregnancy and its withdrawal results in birth, but how this is achieved in humans is unknown. This project will determine the molecular mechanisms by which progesterone action is regulated during the transition from pregnancy to birth. This data will guide new strategies to prevent premature birth.
Understanding The Regulation Of HERG Potassium Channel In The Myometrium At The Time Of Labour
Funder
National Health and Medical Research Council
Funding Amount
$597,661.00
Summary
We have shown that a potassium channel known as hERG falls precipitously at the time of term labour and that blocking this channel causes powerful uterine contractions. This grant will determine how the expression of this channel is regulated in the myometrium and whether changes in hERG channels also occur in premature labour.
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.
Optimising Future Human Health By Optimising Birth Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$876,005.00
Summary
Laureate Professor Smith received an AM for his research on human pregnancy and contributions to Indigenous maternal health. His research has dramatically expanded in the last 5 years to include stillbirth, viral infections during pregnancy, early detection of renal disease, the development of targeted nanoparticles for delivery of therapeutics to the uterus, and data-linkage to test the impact of antenatal care. His research seeks to optimise the health of pregnant women and their children.
Second Trimester Intra-amniotic Treatment For Early Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$392,420.00
Summary
Preterm birth is the leading cause of neonatal death and disability in Australia today, with those born before 32 weeks' completed gestation at the highest risk. Preventing these early preterm births requires treatment of the causative uterine infection. This proposal is to conduct the first study of direct intraamniotic antibiotic treatment of uterine Ureaplasma infection in a clinically relevant, large animal model of second trimester pregnancy.
The Cellular And Molecular Mechanisms In The Initaition Of Human Labour
Funder
National Health and Medical Research Council
Funding Amount
$460,904.00
Summary
Being born too early is the major cause of perinatal morbidity and mortality and accounts for the majority of neonatal deaths. The aim of this project is to gain a better understanding of the mechanisms involved in premature birth with a view to future development of clinically useful interventions to reduce the high rates of mortality and long-term disability.
Achieving Targeted Delivery Of Drugs To Uterine Muscle In Women For The Prevention Of Preterm Labour
Funder
National Health and Medical Research Council
Funding Amount
$469,008.00
Summary
We have patented liposomes targeted to the uterus, which enable us to deliver drugs specifically to the muscle cells of the uterus, increasing safety. The liposomes can be loaded with drugs that either block or promote contractions, creating a versatile drug delivery system that could treat premature labour or postpartum haemorrhage which are major clinical problems. We seek support to demonstrate their effectiveness in mouse and primate models of preterm labour prior to human studies.
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
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