Mechanisms Contributing To Long-term Neuronal Loss After Hypoxia-ischemia In The Premature Neonate Brain.
Funder
National Health and Medical Research Council
Funding Amount
$432,535.00
Summary
A lack of oxygen (hypoxia) and blood flow to the brain (ischemia) around the time of birth can cause brain injury that perists into adulthood. The burdens on financial, educational and healthcare resources are enormous. We will improve our understanding of what parts of the brain are injured and the mechanisms contributing to on-going brain injury after hypoxia-ischemia.This is important to devise treatments and to provide a healthy start to life for neonates.
International Neonatal Immunotherapy Study (INIS): A Randomised Trial Of Intravenous Immunoglobulin For Neonatal Sepsis
Funder
National Health and Medical Research Council
Funding Amount
$1,151,250.00
Summary
There is promising evidence that treatment of serious infection in babies with a product naturally occuring in blood, intravenous immunoglobulin (IVIG), may reduce deaths by 40% and reduce brain damage in survivors. This would reduce the social, emotional and financial burden of disability on families, health services and society. In financial terms alone, caring for a severely disabled child costs an extra $50,000 per year. However, more evidence is needed before IVIG can be introduced as routi ....There is promising evidence that treatment of serious infection in babies with a product naturally occuring in blood, intravenous immunoglobulin (IVIG), may reduce deaths by 40% and reduce brain damage in survivors. This would reduce the social, emotional and financial burden of disability on families, health services and society. In financial terms alone, caring for a severely disabled child costs an extra $50,000 per year. However, more evidence is needed before IVIG can be introduced as routine treatment for serious infection in the newborn. The International Neonatal Immunotherapy Study (INIS) is a randomised trial to study the potential benefits of IVIG in 5,000 newborn babies in 150 centres world wide. 26 centres are in Australia and New Zealand, whose expected contribution of 1,500 babies will be vital to the success of the study. INIS is supported by the Commonwealth Government and Australian Red Cross Blood Service, who will oversee the supply and distribution of IVIG, and the NHMRC Clinical Trials Centre, who will coordinate the study. Infants will have a detailed specialist assessment at 2 years of age and a parent questionnaire will be completed, to assess their development. An economic evaluation will be performed to estimate the long-term savings to Australian Health Services and families associated with the IVIG therapy. The IVIG product to be used in Australia is Intragam P, manufactured by CSL, who have an unrivalled safety record. CSL has been making IVIG since 1989 and no transmission of HIV or hepatitis viruses has ever been reported. CSL estimate the risk of transmission of these viruses by IVIG is under 1 in 10 million treatments. INIS will provide reliable evidence about IVIG, a treatment with minimum known risk that may benefit thousands of Australian children and millions more worldwide.Read moreRead less
A Randomised Controlled Trial Of Whole Body Cooling On The Outcome Of Term Infants With Hypoxic Ischaemic Encephalopathy
Funder
National Health and Medical Research Council
Funding Amount
$386,732.00
Summary
The aim of this project is to investigate whether the brain damage caused by a serious lack of oxygen around the time of birth can be prevented or reduced by cooling the baby's temperature to 34C for 72 hours. The consequences, of a lack of oxygen, to the brain, around the time of birth can be devastating. Over 30% of those babies with abnormal brain function soon after birth either die or survive with severe permanent brain damage. There is no specific treatment for these infants. Evidence from ....The aim of this project is to investigate whether the brain damage caused by a serious lack of oxygen around the time of birth can be prevented or reduced by cooling the baby's temperature to 34C for 72 hours. The consequences, of a lack of oxygen, to the brain, around the time of birth can be devastating. Over 30% of those babies with abnormal brain function soon after birth either die or survive with severe permanent brain damage. There is no specific treatment for these infants. Evidence from studies in animals, as well as human adults and a small number of newborn infants, suggests that moderate body cooling started soon after birth in babies with serious abnormal brain function might prevent or reduce brain damage. This project is a multicentre trial, where infants who have suffered from a severe lack of oxygen around birth, are randomised to body cooling to 34C for 72 hours. This will be started as soon as possible after birth at their hospital of birth. If the baby needs to be transported this will be started when the newborn transport team collects the baby for transfer to a newborn intensive care unit. This new treatment will be compared with maintaining the baby's temperature at 37C. This project will investigate a new, simple and pragmatic treatment that might reduce brain damage. If it finds that cooling infants who have been severely deprived of oxygen is an effective and safe treatment, the information will be applicable to any of the very large number of babies around the world who suffer from a serious lack of oxygen around the time of birth.Read moreRead less
Developmental Changes In Cerebral Oxygenation After Term And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$445,306.00
Summary
Approximately 10% of all births are preterm and the numbers of infants surviving are increasing. We have previously found that infants born preterm have lower blood pressure over the first 6 months after term equivalent age than infants born at term. We will use new technology to examine how preterm birth affects brain oxygenation and how this is altered with gestational age, sleep states and sleeping position, to provide insights into their increased risk for SIDS.
Extracellular Acidosis And PH-modulating Drugs As Novel Therapies For Neuroprotection In Hypoxia/ischemia In The Newborn
Funder
National Health and Medical Research Council
Funding Amount
$452,310.00
Summary
Approximately 4 out of every 1000 babies suffer severe perinatal asphyxia (a period of a shortage of oxygen) during the birth process which carries with it a high risk of brain damage or death. Those babies surviving with a severe disability cost Australia $500,000,000 per annum in lifelong costs. With currently available methods, the presence of asphyxia is difficult to detect and hence prevention is often not possible. At present, there are no effective medications to treat asphyxia-related br ....Approximately 4 out of every 1000 babies suffer severe perinatal asphyxia (a period of a shortage of oxygen) during the birth process which carries with it a high risk of brain damage or death. Those babies surviving with a severe disability cost Australia $500,000,000 per annum in lifelong costs. With currently available methods, the presence of asphyxia is difficult to detect and hence prevention is often not possible. At present, there are no effective medications to treat asphyxia-related brain damage in babies. This study brings together a multi-disciplinary team driven by the clinical need to develop suitable strategies for neuroprotection in the developing brain. We will investigate the neuroprotective properties of the clinically relevant factor of acidosis and determine how acidosis influences neuroprotectant drugs. In the future, it is envisaged that this study will lead to rationally-based clinical trials aimed at improving neurodevelopmental outcomes for babies who suffer asphyxia and for infants who are victims of near-drowning or head trauma.Read moreRead less
DETERMINING THE MECHANISMS LEADING TO LONG-TERM IMPAIRMENT IN VERY PRETERM CHILDREN: THE VIBeS LONGITUDINAL STUDY.
Funder
National Health and Medical Research Council
Funding Amount
$1,061,733.00
Summary
Approximately 50% of children born very preterm will develop significant problems. The objective of this project is to determine the mechanisms leading to these problems. We will do this by assessing at school-age a unique and valuable cohort of very preterm infants (VIBeS cohort) who had state-of-the-art brain scans shortly after birth and neurobehaviour assessments across early childhood. This school-age follow-up will involve repeat brain scans and detailed neuropsychological assessments.
Novel Approaches To Assessing Cerebral Circulation And Oxygenation In Preterm Human Infants.
Funder
National Health and Medical Research Council
Funding Amount
$489,145.00
Summary
In the first few days after birth, some premature babies develop low blood pressure. It is thought that this meant that the amount of blood and oxygen going to the brain would also fall. If blood pressure became very low, this could injure the brain. Drugs are used to prevent low blood pressure, but their effect on blood flow and oxygen in the brain is uncertain. This study aims to develop simple cotside monitoring procedures that allow neonatologists to monitor oxygen supply and blood flow in t ....In the first few days after birth, some premature babies develop low blood pressure. It is thought that this meant that the amount of blood and oxygen going to the brain would also fall. If blood pressure became very low, this could injure the brain. Drugs are used to prevent low blood pressure, but their effect on blood flow and oxygen in the brain is uncertain. This study aims to develop simple cotside monitoring procedures that allow neonatologists to monitor oxygen supply and blood flow in the brain in tiny babies who weigh less than 1000gm, and what happens within the brain when drugs are given to raise blood pressure. We will employ a new instrument that generates low intensity near infrared light which passes safely into the brain and is absorbed according to the amount of oxygen present in very small blood vessels. As the methodology is new, we intend to first validate the measurement in immature lambs. The instrument will then be applied in studies of babies undergoing intensive care and at risk for low pressure and brain injury, as many as 5000 babies each year in Australia.Read moreRead less
The Relationship Between Cognition And Interictal Discharges: Language Organization And Spike Localisation In BECTS
Funder
National Health and Medical Research Council
Funding Amount
$216,500.00
Summary
Benign epilepsy with centro-temporal spikes (BECTS, rolandic epilepsy) is a common cause of seizures in primary school children. Despite this it is poorly understood. Although seizures are infrequent, brainwave recordings (electroencephalography, EEG) reveal striking abnormalities present much of the time. Large, sharply contoured brain waves (spikes) are seen frequently, increasing during sleep. The pattern of the spikes, and the characteristic nature of seizures have suggested the epilepsy ari ....Benign epilepsy with centro-temporal spikes (BECTS, rolandic epilepsy) is a common cause of seizures in primary school children. Despite this it is poorly understood. Although seizures are infrequent, brainwave recordings (electroencephalography, EEG) reveal striking abnormalities present much of the time. Large, sharply contoured brain waves (spikes) are seen frequently, increasing during sleep. The pattern of the spikes, and the characteristic nature of seizures have suggested the epilepsy arises near the face area of the motor cortex, but this remains unproven. Functional magnetic resonance imaging (fMRI) is a safe and non-invasive way of imaging cerebral function, to reveal the brain at work . The technology is contributing to major advances in understanding of basic human functions such as language. Recent developments at the Brain Research Institute in Melbourne mean it is now possible to record EEG during fMRI. This has permitted visualisation of spike activity in the brain. The BRI is the only centre in Australia, and one of only a handful in the world that is able to perform such studies. One purpose of this study is reveal the location of spikes in BECTS. Recent studies have revealed subtle language and learning difficulties in BECTS children. Our preliminary EEG-fMRI studies have suggested spikes arise from brain regions adjacent to important language areas. It is possible that the frequent spikes of BECTS are interfering with adjacent cognitive processes. In addition to spike mapping, we will perform functional imaging of language to look for interactions between spike and language areas, and compare with patterns of language activation seen in normal children. The demonstration of spike related affects on cognition may lead to a reassessment of current epilepsy management strategies, which focus predominately on seizure control. This study, with researchers in Cairns and Melbourne, shares the benefits of world class research with regional Australia.Read moreRead less