MECHANISMS OF ABNORMAL EXPRESSION OF THE IGF2 GENE IN DISORDERS AFFECTING FOETAL GROWTH
Funder
National Health and Medical Research Council
Funding Amount
$560,434.00
Summary
The IGF2 gene is crucial for foetal growth. Only the copy inherited from the father is active, a phenomenon named parental imprinting. In some children with foetal overgrowth or growth retardation, the deregulation of imprinting of the IGF2 gene during the first days of foetal development will influence subsequent growth and will also have major implications in post-natal and adult life. We will investigate the mechanisms resulting in abnormal imprinting of the IGF2 early in development.
Differential Effects On Fetal Growth And Development Of Repeated Fetal Or Maternal Corticosteroid Treatments
Funder
National Health and Medical Research Council
Funding Amount
$356,849.00
Summary
Injections of synthetic hormones (corticosteroids) to women at risk of early preterm birth reduce the rate of respiratory illness and death in the newborn infant. It is standard clinical practice prior to early preterm birth to give corticosteroids by intramuscular injection to the mother. For many women, however, preterm birth does not occur as expected and it has become common practice to give repeated courses of corticosteroids to women in whom the risk of preterm delivery recurs or continues ....Injections of synthetic hormones (corticosteroids) to women at risk of early preterm birth reduce the rate of respiratory illness and death in the newborn infant. It is standard clinical practice prior to early preterm birth to give corticosteroids by intramuscular injection to the mother. For many women, however, preterm birth does not occur as expected and it has become common practice to give repeated courses of corticosteroids to women in whom the risk of preterm delivery recurs or continues. Using the sheep model, we have shown that repeated doses of corticosteroids, given intramuscularly to the mother, are of benefit to newborn lung function, but also reduce the rate of fetal growth and adversely affect brain development. Evidence from the Western Australian Preterm Infant Cohort Study suggests that birthweight in humans is similarly affected by repeated corticosteroids and is followed by behavioral disorders in childhood. Using sheep, we have shown that repeated injections of corticosteroids given directly to the fetus cause no reduction in birthweight although maturation is still enhanced. This finding of a differential effect of corticosteroids by different routes of administration raises several exciting opportunities and questions. First is the possibility that direct fetal treatment may be of use in humans, if current human trials show that repeated doses cause effects similar to those we have seen in sheep. Secondly, the finding challenges our current understanding of how an individual may be programmed for subsequent health or illness by prenatal events. The proposed study will attempt to explain why corticosteroids given to the mother, but not the fetus, restrict fetal growth. Our hypothesis is that these hormones, when given repeatedly to the mother, adversely affect the ability of the placenta to transfer essential nutrients to the fetus. We will test this hypothesis using pregnant sheep in which catheters have been implanted surgically.Read moreRead less
A Randomised Controlled Trial Of A Decision Aid For Prenatal Screening And Diagnosis
Funder
National Health and Medical Research Council
Funding Amount
$269,625.00
Summary
Prenatal screening is becoming increasingly available to pregnant women in many countries, including Australia, to test for Down syndrome and other chromosomal disorders as well as neural tube defects. Almost half the pregnant women in Victoria are now undergoing prenatal screening. Inherent in all screening tests is the possibility of false positive or false negative results. More than 5% of all women undergoing prenatal screening are likely to receive false positive results and must decide whe ....Prenatal screening is becoming increasingly available to pregnant women in many countries, including Australia, to test for Down syndrome and other chromosomal disorders as well as neural tube defects. Almost half the pregnant women in Victoria are now undergoing prenatal screening. Inherent in all screening tests is the possibility of false positive or false negative results. More than 5% of all women undergoing prenatal screening are likely to receive false positive results and must decide whether to put the pregnancy at risk of miscarriage, or a possible pregnancy termination, as a result of the necessary follow-up invasive diagnostic test. Many women do not realise they may have to face this decision. Others are not aware that their baby may be born with undiagnosed problems even if they have the screening test. One aspect of care that is likely to have a crucial influence on women's experience of screening is how much they are informed about a test prior to undergoing it. Most women visit a GP early in the first trimester of pregnancy. This visit provides an opportunity for information provision about prenatal screening. Decision aids have been developed as adjuncts to practitioners' counselling to prepare patients for decision-making. In this project we will be developing a decision aid for women considering their prenatal screening options. A randomised controlled trial will compare the efficacy of a general educational pamphlet to that of a tailored decision aid in preparing women for decision-making about prenatal screening. A total of 500 women who are less than 11 weeks pregnant and are attending one of 50 GPs will be included. Self-report questionnaires will be used to assess women immediately after use of the educational materials and then again at 24 weeks of pregnancy. The impact of the educational materials on informed choice, decisional conflict, anxiety, depression and uptake of prenatal screening tests will be compared.Read moreRead less
Maternal Anxiety In Pregnancy And Infant Bio-behavioural Regulation: Testing The Fetal Programming Hypothesis
Funder
National Health and Medical Research Council
Funding Amount
$577,896.00
Summary
Recent research shows that maternal anxiety in pregnancy is associated with emotional and behaviour problems in childhood. This project examines the impact of anxiety during pregnancy on infant capacity to regulate behaviour, sleep and physiological response to stress and also considers possible genetic contributions. Findings address the earliest origins of mood and behaviour disorders in children and will inform evidence-based interventions during the perinatal period.
Inherited Muscle Disorders - Gene Discovery, Pathobiology And Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$1,750,277.00
Summary
The project proposed by Professors Nigel Laing and Kathryn North and Dr Kristen Nowak is based upon the results of their successful identification of disease genes for genetic muscle diseases. The project is divided into three parts. In the first part of the project, the research team will identify further novel disease genes, some of which they are already close to finding. In the second part of the project the team will determine how the mutations they have identified in the disease genes actu ....The project proposed by Professors Nigel Laing and Kathryn North and Dr Kristen Nowak is based upon the results of their successful identification of disease genes for genetic muscle diseases. The project is divided into three parts. In the first part of the project, the research team will identify further novel disease genes, some of which they are already close to finding. In the second part of the project the team will determine how the mutations they have identified in the disease genes actually cause the diseases. The aim of this work is to discover targets that may ultimately lead to new therapies for these muscle diseases. In the third and final part of the project, the team will pursue one possible therapeutic approach, which is based upon the understanding of the diseases the researchers have gained from their previous studies. There are currently no cures for these muscle diseases, though symptoms can be treated. The team will determine whether heart actin can replace muscle actin in skeletal muscle and thus might treat the muscle disease.Read moreRead less