Pathways Of Neurosteroid-mediated Protection Following Compromised Pregnancy And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$565,785.00
Summary
The hormonal environment of pregnancy is essential for normal development of the fetal brain. Levels of key hormones fall following premature birth and are further suppressed if the fetus is small or subjected to stress. This leads developmental problems in infants from the pregnancies. This project will examine effectiveness of replacement and supplementation treatments with critical neurosteroid hormones in reversing the adverse neurological effects of these complications of pregnancy.
Creatine Supplementation In Pregnancy: Utilising Cells’ “Built-In” Energy Buffering System
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Through pregnancy, the placenta transfers oxygen and nutrients from the mother to the baby. When a placenta doesn’t function properly a baby’s health is compromised. This can lead to morbidity or death. Creatine is the “back-up generator” of all cells and could help the failing placenta increase nutrient and oxygen delivery to the baby. This study will develop creatine as a potential new therapeutic, to improve the survival of babies of complicated pregnancies.
The Effects Of Maternal Glucocorticoid Administration In Growth Restricted Fetuses.
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
Antenatal administration of glucocorticoids to pregnant women at risk of preterm delivery has been shown to enhance fetal lung maturation. However, glucocorticoids such as betamethasone have a range of potentially deleterious non-pulmonary effects, which include significant alterations in fetal cardiovascular function. This is important because intrauterine growth restricted (IUGR) fetuses constitute a significant proportion of pregnancies in Australia, are at risk of preterm delivery and are th ....Antenatal administration of glucocorticoids to pregnant women at risk of preterm delivery has been shown to enhance fetal lung maturation. However, glucocorticoids such as betamethasone have a range of potentially deleterious non-pulmonary effects, which include significant alterations in fetal cardiovascular function. This is important because intrauterine growth restricted (IUGR) fetuses constitute a significant proportion of pregnancies in Australia, are at risk of preterm delivery and are therefore likely to receive maternal betamethasone. From both human observations and animal studies, it is well documented that IUGR fetuses demonstrate a range of cardiovascular adaptations that ensure maintenance of oxygen delivery to vital organs despite reduced placental perfusion. However, in recent clinical and experimental studies we have demonstrated that administration of betamethasone to IUGR fetuses induces changes in fetal blood flow that may be detrimental to the IUGR fetus. Specifically, we believe that glucocorticoids may increase the risk of both cardivascular and cerebral damage in the growth restricted fetus. The significance of these findings and the mechanisms regulating these changes remain unclear but they have clear implications for future clinical management. This proposal represents the further development of preliminary experimental studies to examine the effects of betamethasone in the ovine IUGR fetus with future clinical care in mind.Read moreRead less
The Role Of Proteoglycans In Contributing To Placental Thrombosis And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$368,269.00
Summary
Fetal growth restriction (FGR) is a pregnancy complication in which the baby doesn�t grow properly in the womb. Growth restricted babies are much more likely to be stillborn. These babies are also at risk of problems later in life such as obesity, diabetes and heart disease. This study investigates molecules in the placenta that may be responsible for causing FGR. If we can understand how these molecules cause the problem of FGR, we may be able to find better ways of treating or preventing it.
My research is primarily aimed at understanding the physiology and pathophysiology of lung development; in particular, how lung development is affected by the fetal and neonatal environment such that adult lung function and respiratory health are impaired. In addition to the lung my research examines the effects of the prenatal environment on development of the brain and cardiovascular system.
Preventing Impaired Beta-cell Plasticity, Insulin Secretion And Diabetes After IUGR
Funder
National Health and Medical Research Council
Funding Amount
$760,611.00
Summary
Babies who are born small are at increased risk of later diabetes, partly because restricting growth before birth also impairs development of insulin-secreting cells in the pancreas, impairing later insulin secretion and contributing to diabetes. We will define the mechanisms underlying impaired insulin secretion in a well-established animal model of fetal growth restriction. Importantly, we will also test interventions to improve insulin secretion after intrauterine growth restriction.
Preventing Insulin Resistance And Obesity Following Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$923,510.00
Summary
Babies who are born small are at increased risk of diabetes and obesity in later life, partly because restricting growth before birth decreases the insulin sensitivity of muscle and diverts nutrients to fat deposition. We will define the mechanisms underlying impaired insulin sensitivity in fetal growth restriction. Importantly, we will also test interventions to improve insulin sensitivity after intrauterine growth restriction.
Functional And Epigenetic Consequences Of Maternal Folate Deficiency, Supplementation And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$545,183.00
Summary
Growing slowly before birth or being born early and premature are very common. Both conditions greatly increase the risk of illness or death around birth and of the infant developing major conditions such as diabetes and cardiovascular disease in later life. Despite their importance, we understand little of what causes fetal growth failure or prematurity or why they influence an individual's health throughout life. Recent findings suggest that low levels of folate in the mother, due to either di ....Growing slowly before birth or being born early and premature are very common. Both conditions greatly increase the risk of illness or death around birth and of the infant developing major conditions such as diabetes and cardiovascular disease in later life. Despite their importance, we understand little of what causes fetal growth failure or prematurity or why they influence an individual's health throughout life. Recent findings suggest that low levels of folate in the mother, due to either dietary or genetic factors, may be involved in their origins and their long-term outcomes. Folate is a nutrient required regularly in small amounts for growth and maintenance of health. Folate supplementation in women is currently recommended before and in early pregnancy, but may have a role throughout the whole of pregnancy in promoting growth and health of the infant. Using experimental models, this project will determine if too little or too much maternal folate modifies the genetic code of the infant (called epigenetic changes), which leads to later metabolic disease and high blood pressure. These epigenetic changes are mild and subtle chemical modifications of DNA that persist in the cells of the infant altering their function. The efficacy of maternal folate supplementation in improving these outcomes for the small baby will also be tested in the models. Finally, the effect of folate status in the normal and small human infant on the epigenetic state of their placenta, cord blood white blood cells and mucous cells of the mouth will be tested. These outcomes will enable the design and testing of interventions with folate and related nutrients in the mother to improve the health of their babies before birth and subsequently throughout their lives. Because these pregnancy complications of being born small or early are common and account for much of the diabetes that occurs in later life, the health benefits from development of effective interventions may be large.Read moreRead less
Investigation Of A New Hypothesis That Increased TGF? Activity In Developing Fetal Organs Predisposes A Women To Polycystic Ovary Syndrome And Associated Metabolic Disorders
Funder
National Health and Medical Research Council
Funding Amount
$583,015.00
Summary
Have you ever wondered why some people get fat and other do not, no matter how much they eat? The answer could lie in what happened before they were born. This project investigates a new hypothesis that was developed from discoveries on polycystic ovary syndrome. Women with this syndrome are at increased risk of becoming overweight and diabetic. If the hypotheses prove correct it might be possible to reduce the incidence of these metabolic disorders in the longer term.