Fetal Cardiovascular Development And The Impact Of Chronic Hypoxia And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$307,232.00
Summary
Low birth weight occurs in 7% of Australian babies and is associated with an increased risk of cardiovascular disease in adult life. Understanding the mechanisms underlying heart and blood vessel development in low birth weight babies will lead to improved identification and intervention in those individuals at risk of cardiovascular disease in adult life, improving heart health for Australians. Reducing cardiovascular disease will improve both quality and quantity of life for Australians.
I am a reproductive biologist specialised in the cell and molecular biology of placental development in pregnancy. I focus on determining the molecular mechanisms that govern placental invasion, growth and function and how these are altered in defective placentation which underlies common complications of pregnancy that can be life threatening to the mother and her baby compromising a healthy start to life. I am developing screening tests to identify couples at risk to improve patient care.
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
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.
The Role Of Oxygen Sensing In The Regulation Of Trophoblast Invasion
Funder
National Health and Medical Research Council
Funding Amount
$404,323.00
Summary
Normal fetal development requires the placenta to successfully invade the mother's uterus so that the baby can be appropriately nourished. It is well known that a failure of normal placental development is associated with two major complications of pregnancy: pre-eclampsia and intrauterine growth restriction. This study is designed to discover whether placental cells have special oxygen sensing mechanisms that help them home in to areas where there is high oxygen.
Optimising Lung Surfactant Protein Production In The IUGR Fetus At Risk Of Preterm Delivery
Funder
National Health and Medical Research Council
Funding Amount
$463,853.00
Summary
Pregnant women at risk of preterm labour after 24 weeks gestation are increasingly administered glucocorticoids in Australian hospitals in order to promote fetal lung maturation and a successful transition to extrauterine life. Antenatal glucocorticoid treatment reduces overall neonatal mortality, the risk of respiratory distress syndrome and the need for respiratory support. Babies that are born small may not benefit from this treatment in the same way that average size babies benefit.
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
VULNERABILITY OF THE INTRAUTERINE GROWTH RESTRICTED HEART AND KIDNEY TO ELEVATIONS IN BLOOD GLUCOSE LEVELS IN ADULTHOOD
Funder
National Health and Medical Research Council
Funding Amount
$58,288.00
Summary
It is proposed that the hearts and kidneys of subjects that were born small for gestational age are particularly vulnerable to the pathophysiological changes induced by hyperglycemia, even when blood glucose levels are only mildly elevated. In the present project, this concept will be investigated. The outcomes of this study will be particularly relevant to the Australian Aboriginal population, as they have a higher incidence than normal of low birth weight and impaired glucose metabolism.
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.