Regulation Of Prostaglandin Endoperoxide Synthase-2 In The Human Fetal Membranes At Birth
Funder
National Health and Medical Research Council
Funding Amount
$249,750.00
Summary
Preterm birth with the resulting immaturity of babies is the leading cause of death and disease among newborns. Early birth occurs in 6 to 11% of pregnancies, and its rate is slowly increasing in industrialized countries. We need a much better knowledge of the regulation of the parturition process to find ways to reverse this trend. Prostaglandins are hormonal substances that stimulate uterine contractions, cervical dilatation and membrane rupture. Intrauterine tissues produce prostaglandins, an ....Preterm birth with the resulting immaturity of babies is the leading cause of death and disease among newborns. Early birth occurs in 6 to 11% of pregnancies, and its rate is slowly increasing in industrialized countries. We need a much better knowledge of the regulation of the parturition process to find ways to reverse this trend. Prostaglandins are hormonal substances that stimulate uterine contractions, cervical dilatation and membrane rupture. Intrauterine tissues produce prostaglandins, and an increase of prostaglandin levels in the uterus is likely responsible for inducing labour both normally and preterm. We have previously identified an enzyme protein in the fetal membranes, called prostaglandin synthase-2, that has a key role in the synthesis of intrauterine prostaglandins during pregnancy. This enzyme is increasingly expressed before labour onset. In the present application, we propose studies to determine what causes the increased expression. We hypothesize that the gene encoding this enzyme is specifically activated in the fetal membranes in preparation for labour. We will define the mechanism of regulation by determining the activity of the gene in tissues from women who deliver either spontaneously or without labour at term and preterm. Further, we will determine the interaction of regulatory proteins with the prostaglandin synthase-2 gene in these pregnancies in order to understand the mechanisms of regulation at the molecular level. Finally, we will conduct cell culture studies to experimentally manipulate prostaglandin synthase-2 gene activity in fetal membrane cells. As an overall outcome of this work, new targets may be identified for drugs to disrupt prostaglandin synthase-2 gene activation specifically in the fetal membranes. The long term perspective is to block prostaglandin synthesis in the uterus in order to suppress preterm labour and prevent preterm birth.Read moreRead less
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
The Early Origins Of Obsteric Diseases: Biological Investigations And Biomarker Discovery
Funder
National Health and Medical Research Council
Funding Amount
$282,290.00
Summary
Recent evidence has pointed to the beginning of pregnancy as the time when biological cascades begin that cause common diseases of pregnancy. This opens the door to developing bloods test in early pregnancy predicting who will develop problems, and to hunt for novel proteins in the bloodstream that are causing the illnesses. 'Proteomic technology' will be used, a new cutting edge tool that can scan the entire protein pool in mum's blood in a single experiment.
This project seeks to identify blood borne biomarkers that may be used, at the first antenatal visit, to identify women at risk of developing complications of pregnancy, If women at risk can be identified early opportunity is afforded to improve outcome for both mother and baby.
Transplantation of frozen ovarian tissue is being used by young patients at risk of losing ovarian function. This study aims to maximize the likelihood that patients who have ovarian tissue collected, frozen and returned will acheive the desired outcome of returning ovarian hormonal cyclicity, ovulation, or fertility.
Control Of Uterine Contraction: Role Of Interstitial Cells
Funder
National Health and Medical Research Council
Funding Amount
$587,206.00
Summary
Being born premature may increase risk of below average IQ, poor performance at school and behavioural difficulties in the child, and increased obesity and blood pressure as an adult, predisposing to life long socio-economic disadvantage. We have come up with a new approach to understanding the control of uterine contraction, namely, that cells other than muscle cells, recently identified in the uterine wall, are essential for inducing forceful and orderly muscle cell contraction during labour.
Vitamin D In Pregnancy And Growth Of The Offspring.
Funder
National Health and Medical Research Council
Funding Amount
$168,550.00
Summary
Vitamin D is a potent steroid hormone required for bone growth and mineralisation, and there is evidence that it regulates cell proliferation. Insufficiency in pregnant women is a cause for concern. The role of vitamin D in human fetal development has been little investigated. At the severe end of the maternal vitamin D insufficiency spectrum, a very small number of deficient neonates have congenital rickets. Low maternal vitamin D status has also been associated with neonatal hypocalcaemia and ....Vitamin D is a potent steroid hormone required for bone growth and mineralisation, and there is evidence that it regulates cell proliferation. Insufficiency in pregnant women is a cause for concern. The role of vitamin D in human fetal development has been little investigated. At the severe end of the maternal vitamin D insufficiency spectrum, a very small number of deficient neonates have congenital rickets. Low maternal vitamin D status has also been associated with neonatal hypocalcaemia and defective tooth enamel. Randomised trials have shown that giving vitamin D to deficient women significantly improves their offspring's birth size and length at a year of age, in one study even though all infants were given vitamin D supplements post-natally. We do not understand the nature of the relationship between maternal vitamin D status and offspring growth. There could be a continuous association, or a threshold vitamin D level below which offspring growth is impaired. If the latter is the case, that threshold value needs to be known. Furthermore, we do not know whether maternal vitamin D level in early or late gestation is most influential in terms of fetal and infant growth. Raised maternal parathyroid hormone (PTH) level is a marker of disturbed vitamin D metabolism. There is evidence that offspring are shorter with increasing level of maternal PTH. In a study in Geelong, 63% of 20-45 year old women tested in winter, and 32% tested in summer, had vitamin D levels in the range where PTH rises. Thus a significant proportion of women may have insufficient vitamin D, in early or late pregnancy, to sustain optimal fetal growth. These issues are important for the health of mothers and their offspring, and there are public health implications, in terms of maternal health and possibly later health of the offspring. These issues have not been investigated in Australia or elsewhere, and this is a novel and important study.Read moreRead less
Yr 4 & 5 Of A Randomised Controlled Trial Of An Intensive Intervention To Reduce Smoking Among Pregnant Indigenous Women
Funder
National Health and Medical Research Council
Funding Amount
$324,665.00
Summary
Rates of smoking in pregnancy are significantly higher among Indigenous women than other Australian women (65% vs 20%). This application is to continue the first ever trial of an intensive program of smoking cessation advice provided to women and their major family supports designed to reduce smoking rates among Indigenous women in pregnancy. This project has already been running sucessfully for two years, however, further funds are required to complete years four and five of the project.
Limiting Weight Gain In Overweight And Obese Women During Pregnancy To Improve Health Outcomes - A Randomised Trial.
Funder
National Health and Medical Research Council
Funding Amount
$1,541,444.00
Summary
Being overweight or obese is a major health issue for women during pregnancy and childbirth in Australia. There are well documented risks associated with obesity during pregnancy for both the mother and her baby. This randomised trial will assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese pregnancy women to limit weight gain during pregnancy is effective in improving health outcomes for women and their babies.