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.
In the last ten years, a remarkable series of public health studies have shown that reduced birth weight is associated with an increased prevalence of high blood pressure, coronary heart disease, diabetes and obesity in adult life. These associations are independent of adult lifestyle or current size, are dependent on events initiated prenatally and are present in cohorts which have a birth weight distribution typical of urban and rural Australia. In all societies, the incidence of low birth wei ....In the last ten years, a remarkable series of public health studies have shown that reduced birth weight is associated with an increased prevalence of high blood pressure, coronary heart disease, diabetes and obesity in adult life. These associations are independent of adult lifestyle or current size, are dependent on events initiated prenatally and are present in cohorts which have a birth weight distribution typical of urban and rural Australia. In all societies, the incidence of low birth weight babies has remained above 5% and in some developing countries, it is greater than 30%. The hormonal responses which help the fetus survive periods of growth restriction in utero, result in a permanent reprogramming of the development of key fetal organs and tissues and the subsequent emergence of high blood pressure in later life. The fetal hormones which have been implicated in causing high blood pressure in adult life are known as glucocorticoids. Fetuses may be exposed to excess glucocorticoids through stress in the womb or through increased transfer of glucocorticoids across the placenta. Currently 85% of Australian obstetricians prescribe repeat courses of antenatal corticosteroids in pregnancies in which the risk of preterm birth persists or recurs. The specific long term outcomes of fetal exposure to excess glucocorticoids are unknown and may depend on the timing, route, dose and type of glucocorticoids involved. We propose to define the mechanisms by which high levels of glucocorticoids act to result in high blood pressure and hormonal disturbances in adult life.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
In the last decade there has been a substantial increase in the number of overweight and obese individuals. Obesity is now a major public health issue in Australia and, along with its associated disorders of type 2 diabetes and heart disease, incurs significant health care costs. There is a widespread awareness of the problem, but it has proved difficult to bring this obesity epidemic under control, and unless we can understand the underlying causes, the trend seems set to continue. This researc ....In the last decade there has been a substantial increase in the number of overweight and obese individuals. Obesity is now a major public health issue in Australia and, along with its associated disorders of type 2 diabetes and heart disease, incurs significant health care costs. There is a widespread awareness of the problem, but it has proved difficult to bring this obesity epidemic under control, and unless we can understand the underlying causes, the trend seems set to continue. This research proposal seeks to define the mechanisms which lead to the development of obesity. Evidence from a large range of clinical and population-based studies has shown that infants who are exposed to an increased supply of nutrients before birth have an increased risk of being overweight or obese as children and adults. It is not however, fully understood why this occurs. In normal adults, factors released by fat cells play an important role in the maintenance of energy balance, and changes in the levels of these factors in the fat cell or in the circulation can lead to increased weight gain and the development of poor sensitivity of the body's tissues to the actions of hormones, such as insulin. Fat cells develop before birth, and therefore changes in nutrient supply to the fetus have the potential to alter the functional properties of fat cells for life. In this proposal, we will investigate the effect of being exposed to an increased supply of nutrients in fetal life on the properties of fat cells after birth and define how such changes explain the development of obesity in these individuals. Understanding the mechanisms which link the risk of obesity to events before birth will allow clinicians of the future to provide children who are born to overweight, glucose-intolerant or diabetic mothers with a healthy start to life.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.