Regulation Of Eicosanoid Production In The Fetal Placenta In Preterm Labour
Funder
National Health and Medical Research Council
Funding Amount
$256,980.00
Summary
Prostaglandins are fatty substances made within the body and they are what causes the pregnant uterus to contract and push out the fetus. At present we can't control preterm birth because we don't understand well enough how prostaglandin synthesis is controlled. New discoveries in our lab have suggested an exciting new possibility- that prostaglandins partially regulate their own synthesis. If we find this is so, there may be far-reaching implications for the ways in which anti-inflammatory drug ....Prostaglandins are fatty substances made within the body and they are what causes the pregnant uterus to contract and push out the fetus. At present we can't control preterm birth because we don't understand well enough how prostaglandin synthesis is controlled. New discoveries in our lab have suggested an exciting new possibility- that prostaglandins partially regulate their own synthesis. If we find this is so, there may be far-reaching implications for the ways in which anti-inflammatory drugs are used, not only in prevention of premature birth, but in inflammatory diseases too. Most research in this area has been directed toward understanding what controls the overall synthesis of prostaglandins, but there are several types of prostaglandins with different functions. we are now in a position to study, for the first time, how the synthesis of the specific prostaglandins is regulated in the pregnant uterus and how this changes during normal and preterm birth.Read moreRead less
The fovea is a specialized part of the retina which enables us to see fine detail. The fovea is characterised by an extremely high concentration of photoreceptor cells in a small, prescribed area to detect detail in the pattern of light reaching the retina. Each of these photoreceptor cells is connected to at least four other cells within the retina, which further refine the information coded by the photoreceptors. Because this circuitry involves so many cells, the retina has a tendency to be th ....The fovea is a specialized part of the retina which enables us to see fine detail. The fovea is characterised by an extremely high concentration of photoreceptor cells in a small, prescribed area to detect detail in the pattern of light reaching the retina. Each of these photoreceptor cells is connected to at least four other cells within the retina, which further refine the information coded by the photoreceptors. Because this circuitry involves so many cells, the retina has a tendency to be thick at the specialized area. However, in development the cells connected to the foveal photoreceptors move away from the central concentration of photoreceptors, still keeping their contacts with them. This results in thinning of the retina locally, so it has a volcanoe-like formation at the fovea, in which photoreceptors are concentrated within the crater and the displaced cells are accumulated on the rim. The events which trigger these cell displacements that form the fovea are unknown. We propose to investigate growth factors which signal between the fovea and the developing blood supply, and the relationship between the formation of the fovea and neuronal activity. This study will provide a new perspective on factors which affect central visual function and its vulnerability to insult in premature infants and in aging.Read moreRead less
Mechanisms Of Escape From Progesterone-induced Suppression: Role In Normal And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Prematurity caused by preterm birth is the leading cause of death and disease among newborns in Australia. Here we will define how the length of pregnancy is determined by the opposing actions of progesterone, which maintains pregnancy, and prostaglandins, which induce labour. We will demonstrate the mechanism by which the actions of the two hormones are balanced in normal pregnancy and disrupted in preterm labour. We will show that preterm birth can be prevented by correcting the disorder.
Does Caffeine Affect The Development Of The Very Immature Brain: Dose Response Relationship?
Funder
National Health and Medical Research Council
Funding Amount
$668,386.00
Summary
Premature birth is a major health problem worldwide. Preterm babies often develop apnoea of prematurity (AOP), which is commonly treated with caffeine. Trials indicate that preterm babies treated with low dose caffeine have less neurodevelopmental disabilities at 18 months. Higher doses of caffeine are often needed to reduce AOP but the risk of this is unknown. We will study the short and long-term effects of increasing doses of caffeine on the developing brain in a long-gestation species.
Which Oxygen Saturation Level Should We Use For Very Premature Infants? A Randomised Controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$2,215,600.00
Summary
Retinopathy of prematurity (ROP) is a serious complication of premature birth, and is a major cause of preventable blindness. Babies who are born before 28 weeks gestation are at greatest risk for developing severe ROP. Oxygen is one of the most common therapies used daily to care for premature babies, but high oxygen levels are one of multiple factors that can disrupt normal eye development and contribute to ROP. The current dilemma is that doctors and nurses do not know what level of oxygenati ....Retinopathy of prematurity (ROP) is a serious complication of premature birth, and is a major cause of preventable blindness. Babies who are born before 28 weeks gestation are at greatest risk for developing severe ROP. Oxygen is one of the most common therapies used daily to care for premature babies, but high oxygen levels are one of multiple factors that can disrupt normal eye development and contribute to ROP. The current dilemma is that doctors and nurses do not know what level of oxygenation is both safe and most effective for these babies. Whilst higher oxygen levels may increase ROP and other respiratory problems, it is possible that lower oxygen levels may affect other long-term outcomes. Because there is no definitive evidence regarding appropriate oxygenation, a wide spectrum of opinion and practice currently exist. Australia is conducting The Benefits of Oxygen Saturation Targeting Trial (BOOST II), a research study to solve this dilemma. BOOST II is a randomised, double blind, clinical trial, which will study the effects of using two ranges of oxygen saturation, 85-89% versus a higher range 91-95% for infants born before 28 weeks gestation. Both of these oxygen level ranges are currently used in normal practice. Patient safety will be monitored closely, and each infant will have their development, vision and health assessed by specialists at 18-24 months of age (plus the number of weeks premature), to see whether there is difference in survival free of major disability between the two groups. 1200 Australian infants will participate. This study will answer important questions about the benefits and risks of higher versus lower oxygen levels, and will improve the care of thousands of Australian children and millions more worldwide.Read moreRead less
DEVELOPMENT OF CARDIOVASCULAR CONTROL DURING SLEEP IN HUMAN INFANTS AFTER PRETERM BIRTH
Funder
National Health and Medical Research Council
Funding Amount
$358,537.00
Summary
Infants spend the major part of their life in sleep, and the period between birth and 6 months of age sees dramatic changes in their sleep organisation. Coincidently, there are dramatic developmental changes in the infant's heart and blood pressure control systems, and the ability to compensate for stress such as falls of blood pressure (hypotension) or in the level of oxygen in the blood (hypoxaemia). In infants born preterm, the risks of hypoxaemia, and even death are significantly greater dur ....Infants spend the major part of their life in sleep, and the period between birth and 6 months of age sees dramatic changes in their sleep organisation. Coincidently, there are dramatic developmental changes in the infant's heart and blood pressure control systems, and the ability to compensate for stress such as falls of blood pressure (hypotension) or in the level of oxygen in the blood (hypoxaemia). In infants born preterm, the risks of hypoxaemia, and even death are significantly greater during sleep than during wakefulness, but why this is so is uncertain. This study will examine the ability of infants to respond to stress during sleep. Four groups of infants will be examined: healthy infants born at normal gestation; healthy infants born prematurely (preterm); preterm infants who have experienced mild hypoxaemia soon after birth; and preterm infants who have suffered more severe hypoxaemia because of lung disease. Infants will be studied in a sleep laboratory during day-time sleep, and their ability to control blood pressure will be determined. By contrasting the effectiveness of blood pressure control between the infant groups we aim to determine whether preterm infants have lasting problems as a result of their premature birth, or their exposure to hypoxaemia. By contrasting infants in sleep and wakefulness, we aim to assess whether the risks of poorer blood pressure control are greater in sleep.Read moreRead less
A Novel Treatment For Ameliorating Retinal Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$366,685.00
Summary
Retinal vascular disease is a leading cause of blindness and is currently treated by laser photocoagulation surgery. Although successful, this treatment is associated with serious side effects. Recently, Ellex Pty has developed a novel laser called the 2RT laser that is likely to be effective without the accompanying side effects. This study will allow examine the effect of the 2RT laser in animal models of retinal vascular disease so as to complete preclinical development of this laser.
Development Of A Multiplex Assay For The Identification Of Women At Risk Of Preterm Labour.
Funder
National Health and Medical Research Council
Funding Amount
$202,350.00
Summary
Preterm birth (ie birth before the 37th week of gestation) is the most significant problem facing contemporary clinical obstetrics in the developed world and occurs in approximately 5% to 12% of all deliveries. Being born too early is the major cause of perinatal morbidity and mortality. Data from Australia indicate that each year, more than 17,000 babies will be born prematurely. Of these infants, over 10,000 will suffer respiratory complications and about 1300 will die during the first 21 days ....Preterm birth (ie birth before the 37th week of gestation) is the most significant problem facing contemporary clinical obstetrics in the developed world and occurs in approximately 5% to 12% of all deliveries. Being born too early is the major cause of perinatal morbidity and mortality. Data from Australia indicate that each year, more than 17,000 babies will be born prematurely. Of these infants, over 10,000 will suffer respiratory complications and about 1300 will die during the first 21 days of life. The sickest and most premature of these infants require admission to a Neonatal Intensive Care Unit in a tertiary hospital. Aside from the medical implications of premature delivery, there is also a considerable fiscal challenge to society. While treatments for the prevention of labour have improved considerably over the past decade, current screening tests of preterm labour (ie Fetal Fibronectin test) are unreliable and have poor positive predictive values. The principal objective of this project is to develop and deliver a multiplex assay for the prediction and diagnosis of human preterm labour. Through the successful application of our own proteomic discovery programmes using both ovine and human cervico-vaginal fluid samples, we have identified several new protein markers of labour. Having completed this Phase 1 biomarker trial and established proof-of-concept, we are now well positioned to initiate a Phase 2 biomarker trial to determine reliable estimates of assay sensitivity and specificity. This project targets the development of a new diagnostic to meet a recognised market gap. Delivery of such a test will create a new market in pregnancy-based clinical diagnostics and significantly impact on improving health care and quality of life for many preterm babies. Should the project be completed as detailed and mitigate some of the risk of commercial development, it would then be realistic to seek substantial funding from the private sector.Read moreRead less
The Significance Of Glial Dysfunction In Retinopathy Of Prematurity
Funder
National Health and Medical Research Council
Funding Amount
$311,567.00
Summary
Abnormalities in cells at the back of the eye called photoreceptors are associated with at least 50% of all cases of blindness in this country.This project will determine whether substances released from dying photoreceptors cause the death of neighbouring cells. In addition we will examine whether treatments that block the actions of these released substances can prevent the death of photoreceptors, thereby providing a novel therapeutic agent for the treatment of devastating eye diseases.