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Identifying Risk For Second And Subsequent Pregnancies: A Longitudinal Record Linkage Study
Funder
National Health and Medical Research Council
Funding Amount
$586,129.00
Summary
Interventions (eg. induction of labour) or conditions (eg bleeding) in one pregnancy may affect outcomes in the next pregnancy (eg. risk of complications). These relationships are under-investigated. Using population data on over 194,000 women we can look at repeat pregnancies experienced by individual women. We will use this data to investigate whether interventions in one pregnancy affect subsequent birth outcomes (for mother or baby) and whether particular conditions are likely to recur.
Antenatal Insulin-like Growth Factor-I And Perinatal Growth, Survival And Function Of The Growth Restricted Fetus.
Funder
National Health and Medical Research Council
Funding Amount
$150,370.00
Summary
Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUG ....Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUGR in Australia in non-Aboriginal communities and between 7 to 17% in Aboriginal communities. Despite these adverse consequences for health of the individual throughout life, we do not currently have any effective therapies to treat IUGR. Small infants are mostly a result of an inadequate supply of oxygen and nutrients before birth, due to an impaired capacity of the mother to acquire these for the placenta to deliver them to the growing fetus or due to poor functioning of the placenta itself. This intrauterine malnutrition not only slows growth, but impairs the development of a range of body functions leading to the increased risk of illness and death in IUGR. Therapies to be used before birth to treat IUGR need to either restore supply of oxygen and nutrients or to promote growth and functional development. We have discovered that administration of a major growth promoting hormone, insulin-like growth factor-I (IGF-I), to the IUGR fetus, which has low levels of IGF-I, increases its growth. This project will therefore determine if directly giving this hormone in the IUGR fetus will restore development as well as growth before birth, improving function and hence survival and health after birth. If successful, the first effective approach to the antenatal treatment of IUGR will have been identified and would provide the essential knowledge for the design of a range of therapies to best restore the abundance of IGF within the IUGR fetus to improve perinatal and later outcomes.Read moreRead less
Evaluation Of Novel Antenatal Biomarkers For The Detection Of Adverse Pregnancy Outcomes: A Record Linkage Study
Funder
National Health and Medical Research Council
Funding Amount
$580,997.00
Summary
Although most pregnancies are associated with the birth of a healthy baby to a healthy mother, adverse pregnancy outcomes such as fetal growth restriction, stillbirth and preeclampsia continue to impose a heavy burden on families and the community. We will use a novel application of health record linkage to investigate maternal serum biomarkers for predicting adverse pregnancy outcomes. Intervention studies and preventative strategies will be developed for highly predictive biomarkers.
Comparison Of Pregnancy Outcomes Following Transferring One Or Two Embryos In A Selected Group Of Infertility Patients.
Funder
National Health and Medical Research Council
Funding Amount
$120,302.00
Summary
Assisted reproductive technology (ART) deals with issues of fundamental importance to individuals involved, and society as a whole. Despite major advances, ART continues to be very costly in many regards. A major reason for this is the relatively low rate of pregnancy, which averages 25% per procedure. The common response to the problem of low pregnancy rates is to return several embryos to uterus. A dilemma associated with this strategy is the high risk of multiple pregnancy, which is associate ....Assisted reproductive technology (ART) deals with issues of fundamental importance to individuals involved, and society as a whole. Despite major advances, ART continues to be very costly in many regards. A major reason for this is the relatively low rate of pregnancy, which averages 25% per procedure. The common response to the problem of low pregnancy rates is to return several embryos to uterus. A dilemma associated with this strategy is the high risk of multiple pregnancy, which is associated with adverse consequences for mother and fetus(es). Compared to singleton births; fetal, neonatal, and perinatal mortality rates are 3-6 times higher in twins, and 5-15 times higher in multiple births of a higher order. Cerebral palsy rates among survivors are six times higher in twins and twenty times higher in triplets. The increase in the incidence of adverse outcomes related to multiple pregnancy has been well documented in ART. We propose a randomised controlled study to assess single embryo transfer (SET) compared to double embryo transfer (DET). Infertility women with a high risk of multiple pregnancy will be randomly allocated to receive one or two embryos, which is the usual treatment at present. We shall then examine the rates of single and multiple pregnancies, and the success of those pregnancies in this group of patients. Potential benefits to the community from this project are very substantial, as it has the capacity to substantially reduce the number of multiple births. Patients will also benefit by having more accurate information with which to make an informed choice during treatment.Read moreRead less
Characterisation Of Abnormal Placental Stem Cells In A Human Pregnancy Disorder
Funder
National Health and Medical Research Council
Funding Amount
$487,969.00
Summary
The placenta is a rich source of stem cells. We have discovered that stem cells from placentae affected by fetal growth restriction (FGR), a clinically significant pregnancy disorder, are morphologically and functionally different to normal placental stem cells. We predict that abnormal stem cells contribute to FGR. We will carry out gene expression and functional studies to further characterise the abnormal stem cells. The work may lead to new types of treatments for FGR in future.
The Role Of Placental Transcription Factors In The Pathogenesis Of Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$601,582.00
Summary
We must understand the role of growth control genes in the growth of the human placenta. The reason is that in several significant placental disorders, placental formation is abnormal and prevents the placenta from functioning efficiently. This in turn, impacts on the growth of the developning fetus. A variety of established and innovative methods described in this project will determine the functions of the placental growth control genes and may lead to novel therapeutic targets.
Mechanisms Of Escape From Progesterone-induced Suppression: Role In Normal And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Prematurity caused by preterm birth is the leading cause of death and disease among newborns in Australia. Here we will define how the length of pregnancy is determined by the opposing actions of progesterone, which maintains pregnancy, and prostaglandins, which induce labour. We will demonstrate the mechanism by which the actions of the two hormones are balanced in normal pregnancy and disrupted in preterm labour. We will show that preterm birth can be prevented by correcting the disorder.
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
Does Place Of Birth Influence A Healthy Start To Life?
Funder
National Health and Medical Research Council
Funding Amount
$343,050.00
Summary
There are over 255,000 births in Australia each year and a major challenge in terms of planning and provision is to ensure that these babies are born in hospitals with the appropriate facilities to care for them. International studies suggest that transferring the mother before birth results in better infant outcomes than transferring the baby after birth. In Australia births occur in a range of hospitals, from small rural hospitals to tertiary obstetric and neonatal centres. However, few Austra ....There are over 255,000 births in Australia each year and a major challenge in terms of planning and provision is to ensure that these babies are born in hospitals with the appropriate facilities to care for them. International studies suggest that transferring the mother before birth results in better infant outcomes than transferring the baby after birth. In Australia births occur in a range of hospitals, from small rural hospitals to tertiary obstetric and neonatal centres. However, few Australian studies have looked at infant outcomes based on place of birth. This study will use existing population health data sets to evaluate the provision of care prior to and at birth and the impact it has on infant outcomes up to one year of age. It will also describe for the first time the hospital care utilisation associated with birth and infant health. Information will be obtained from routinely-collected birth, death and birth defect registers, and hospital, midwives and perinatal death review data. Variations in health outcomes for babies may be due to factors that occur before or during pregnancy, or may be due to differences in the care provided at birth. We need to take account of maternal factors to comprehensively assess the role of level of care at birth. We will use statistical techniques to 'predict' infant health outcomes and see if differences between places of birth are real or not. If variations are explained by different levels of care then there is enormous potential for improvement in the provision of pregnancy and newborn services. We will also compare the benefits and consequences of maternal versus neonatal transfer, and assess hospital costs. The results of this study could be applied to direct health services policy and organisational changes to improve pregnancy care and optimise infant outcomes for a healthy start to life.Read moreRead less