Early Detection And Intervention For Infants At High Risk Of Motor Impairments
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
My proposed research program involves several distinct yet related projects addressing i) early detection and ii) early intervention for infants at high risk of movement problems including cerebral palsy. This research will provide the highest quality evidence base that is needed to identify those children most at risk early in development and improve our understanding of which interventions are most effective, so that scare health care resources can be targeted appropriately.
Improving Neurodevelopmental Outcomes Of Preterm Infants
Funder
National Health and Medical Research Council
Funding Amount
$312,085.00
Summary
In Australia over 20,000 babies are born preterm each year. Preterm babies are at risk of long term developmental problems including movement, learning and behavioural impairments. This research will examine both neurodevelopment and brain development of very preterm (born <30 weeksÍ gestation) and late preterm (32-36 weeksÍ gestation) babies from birth to into early childhood so that we can understand how gestational age at birth relates to development, brain growth and interventions.
Periconceptional Nutrition And The Programming Of Obesity
Funder
National Health and Medical Research Council
Funding Amount
$468,879.00
Summary
Mothers who enter pregnancy with a high body mass index are at risk of developing diabetes in pregnancy and of having a large baby who will be at increased risk of developing obesity in childhood and later life. Heavy mothers therefore have heavy babies and these babies go on to become heavy adults. This grant will determine the separate contributions of exposure of the embryo to high nutrition and exposure of the fetus in late gestation to high maternal nutrition.
Novel Methods For Early Bedside Detection And Prognosis Of Preterm Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$630,880.00
Summary
Quick and robust assessments of preterm brain activity are critical for identifying early markers of brain injuries. We need to predict poor outcomes before they develop in order to give clinicians the best chance of helping sick infants. This project will develop and validate new non-invasive methods for assessing early brain activity in preterm infants at risk of developing poor neurodevelopmental outcomes.
Perinatal And Intergenerational Influences On Adult Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$438,520.00
Summary
The aim of this project is to determine the effects of restriction of nutrient supply before and after birth on growth and the development of adult onset diabetes. Being born small and its associated neonatal catch-up growth independently predict adult diabetes. Placental restriction is a major cause of reduced nutrition and growth before birth and is implicated in this programming of disease. Our novel findings suggest that placental compromise increases appetite but also impairs milk quality a ....The aim of this project is to determine the effects of restriction of nutrient supply before and after birth on growth and the development of adult onset diabetes. Being born small and its associated neonatal catch-up growth independently predict adult diabetes. Placental restriction is a major cause of reduced nutrition and growth before birth and is implicated in this programming of disease. Our novel findings suggest that placental compromise increases appetite but also impairs milk quality and supply which limits overfeeding and catch-up growth initially, but on weaning, may independently lead to diabetes. We will determine if this is a direct result of poor nutrition and made worse by overfeeding in response to restored nutrition. We hypothesize that placental compromise permanently reduces an individual's metabolic capacity and that the extent of availability of nutrition after birth determines the consequences for insulin action and increased body fat. Manipulations of postnatal nutrition (by cross-fostering) and fat oxidation will be performed, which are pivotal to understanding the roles of catch-up growth and increased food intake in disease onset. We have found that cross-fostering small rat pups at birth onto mothers with normal lactation improves growth during lactation. The proposed studies will establish the cross-fostering effect on the development of diabetes and identify a developmental stage during which nutritional or other manipulations may have beneficial consequences for the health of the breastfeeding small infant. We propose to determine whether adult females, exposed to placental restriction as a fetus, produce offspring that develop diabetes, and establish whether this effect is caused by programming before conception and-or an altered fetal environment. Identification of critical periods after birth, rather than before, would offer a greater likelihood that practical public health interventions can be developed to improve adult health.Read moreRead less
Prenatal Placental And Postnatal Mammary Programming Of Cardiovascular And Renal Diseases
Funder
National Health and Medical Research Council
Funding Amount
$503,776.00
Summary
Being born small and the associated catch-up growth, independently predict adult hypertension. Reduced placental blood flow is a major cause of fetal growth restriction and is implicated in programming adult disease. We are the first to demonstrate that placental compromise in rats also adversely affects breast development, milk quality and supply, which further impair growth during lactation. This is followed by accelerated growth after weaning, programming more adverse outcomes. Using a rat mo ....Being born small and the associated catch-up growth, independently predict adult hypertension. Reduced placental blood flow is a major cause of fetal growth restriction and is implicated in programming adult disease. We are the first to demonstrate that placental compromise in rats also adversely affects breast development, milk quality and supply, which further impair growth during lactation. This is followed by accelerated growth after weaning, programming more adverse outcomes. Using a rat model, we will determine for the first time if restricted nutrition before birth via the placenta or after birth via lactation increases the risk of developing high blood pressue and kidney and blood vessel dysfunction. Manipulations of nutrition after birth will be achieved by cross-fostering studies. We will establish whether a reduction in the number of functioning units (nephrons) in the kidney, alterations in key genes involved in kidney development and changes in blood vessel reactivity are associated with developing hypertension. We will manipulate the renin-angiotensin system (RAS), which is important in determining kidney function, to define its role in hypertension in this model. We propose that a common lifestyle insult, such as modest elevation in dietary salt, will evoke exaggerated responses in adult offspring who were born small. These studies will identify the mechanisms by which the kidney, vasculature and RAS contribute to the programming of hypertension and the relative roles of the prenatal and postnatal environments. Defining the underlying mechanisms responsible will provide insight into early life interventions that may lessen these adverse consequences for longer-term health. Identification of critical periods after birth, rather than before, would offer a greater likelihood that practical public health interventions can be developed to improve adult health in this emerging field.Read moreRead less
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.
Contrary to traditional belief few cases of cerebral palsy are due to problems at birth. Most have earlier origins. Sophisticated new methods have found that many developmental brain disorders e.g. autism, intellectual disability and epilepsy are associated with submicroscopic but genetically large alterations in the genetic code of these children. This novel study will seek these alterations in a large group of Australian cerebral palsy families. The pilot data show novel and exciting findings.
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.