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
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.