I am a perinatal physiologist who specializes in determining the factors that cause fetal and neonatal brain damage, and in devising treatments to prevent this for application in pregnant women and the neonate.
Newborn babies are at risk of becoming short of oxygen during delivery. Death or brain damage may result. In the days after birth, when the brain is attempting to recover from the lack of oxygen, seizures (also called fits) are common. Seizures may cause further damage to the brain because they release damaging chemicals such as glutamate or because they make extra energy demands on the brain that cannot be met. It is difficult to be certain whether unusual movements or twitches are seizures or ....Newborn babies are at risk of becoming short of oxygen during delivery. Death or brain damage may result. In the days after birth, when the brain is attempting to recover from the lack of oxygen, seizures (also called fits) are common. Seizures may cause further damage to the brain because they release damaging chemicals such as glutamate or because they make extra energy demands on the brain that cannot be met. It is difficult to be certain whether unusual movements or twitches are seizures or not. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain that can be measured from the scalp using small stick on electrodes. It is difficult to measure EEG, particularly for longer periods, because the electrodes may fall off, the baby may move excessively or electrical interference may ruin the recording. We are proposing to measure EEG for 48 hours in babies who have suffered a lack of oxygen during delivery. We will develop, optimise and implement a new method of automatically detecting seizures, building upon 6 years of fundamental signal processing research work that we have done in the newborn. We will test this system against the 'gold standard' to determine how accurate it will be in detecting seizures. We will also try to find out whether damage in particular areas of the brain or in particular cell types within the brain is most likely to be associated with seizures. The anticipated outcome is that we will be able to accurately identify seizures. This is a major step on the path to being able to prevent injury to the brain and to monitor the effectiveness of new experimental treatments.Read moreRead less
I am a perinatal paediatrician undertaking clinically-focussed research on brain development, brain disorders, brain therapies, neurodevelopmental outcomes and the development, application and evaluation of new technology to clinical problems.
Neuroactive Steroids In The Developing Brain: Potential For Preventing Perinatal Brain Damage
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown tha ....Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown that protective neuroactive steroids are present in very large amounts in the fetal brain. Steroids produced by the placenta are converted to these neuroactive products by enzymes in the brain leading to the high levels that are seen during fetal life. Certain adverse conditions during pregnancy as well as preterm birth may cause marked changes in the balance of steroids that could increase susceptibility to brain injury. We have found that areas of the brain, where damage most often occurs, normally contain the highest amount of protective steroids, but only in late pregnancy. This suggests that disturbances that lower steroid production in these areas could contribute to the death of cells, particularly in mid-pregnancy and after premature birth. In the proposed studies, we will examine whether a toxic balance of steroids develops following adverse events in pregnancy as well as the areas of the brain where this is most pronounced. We will examine the changes in the expression of enzymes that can potentially cause the accumulation of protective steroids in the brain. We will then examine treatments that can raise the concentration of steroids and determine which combination of steroids best reduces cell death and brain injury following complications during pregnancy. The findings of this work will indicate the best therapeutic approach that may be adopted to modify the concentration of certain steroids so as to reduce the risk of brain damage in the fetus and neonate.Read moreRead less
Neurosteroid Mediated Protection After Birth: Approaches For Maximising Protective Steroid Levels In The Neonatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$450,703.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the levels of these protective steroids are remarkably high in the ....Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the levels of these protective steroids are remarkably high in the fetal brain and levels rise further in response to fetal stress. The placenta contributes steroid precursors that help maintain these high neurosteroid levels. This placenta-fetal brain interaction comprises an internal mechanism that protects the fetal brain from adverse events during pregnancy. At birth, however, there is a dramatic decline in neurosteroid concentrations in the brain after the loss of the placental precursor supply. The fall in concentrations is even greater in animals that are born growth restricted. This suggests that newborns, particularly those from compromised pregnancies, are at increased risk of brain damage due to low neurosteroid levels. We believe that certain commonly used steroid therapies may also lower steroid levels in the brain and result in increased vulnerability to brain damage during birth or in the early neonatal period. Alternatively, we propose that replacement of neurosteroid precursors in the newborn may raise brain neurosteroid levels and protect against brain damage. In the proposed studies we will evaluate treatments that can raise the concentration of steroids and determine the best strategy for reducing brain injury following complications during pregnancy, at birth and during the early newborn period. This work will determine the best therapeutic approaches for maximising neurosteroid-induced brain protection and for reducing the risk of brain damage.Read moreRead less
Improved Respiratory Support And Outcomes For Very Preterm Babies
Funder
National Health and Medical Research Council
Funding Amount
$9,185,907.00
Summary
Premature babies are born with lungs that are not developed enough to sustain their breathing needs after birth. As a result, they need intensive care which is the most costly and challenging problem in newborn medicine as these infants can suffer life-long diseases because of their early birth. This programs study will help to understand the causes of lung disease in premature babies and develop better ways of caring for them to improve their chances of survival without ongoing illness and disa ....Premature babies are born with lungs that are not developed enough to sustain their breathing needs after birth. As a result, they need intensive care which is the most costly and challenging problem in newborn medicine as these infants can suffer life-long diseases because of their early birth. This programs study will help to understand the causes of lung disease in premature babies and develop better ways of caring for them to improve their chances of survival without ongoing illness and disabilityRead moreRead less
Potential For Creatine Or Melatonin As Dietary Supplements In Pregnancy To Prevent Perinatal Brain Damage
Funder
National Health and Medical Research Council
Funding Amount
$483,217.00
Summary
Brain damage in the newborn - particularly in prematurely born infants - remains a significant health problem. At present there are very few treatments that can be used to minimize damage when it becomes apparent in the newborn, and none that can be used PROSPECTIVELYduring pregnancy to protect the developing brain from damage. The most likely cause of damage to the fetal brain during pregnancy or at birth is global ASPHYXIA, either by itself or in association with other problems of pregnancy su ....Brain damage in the newborn - particularly in prematurely born infants - remains a significant health problem. At present there are very few treatments that can be used to minimize damage when it becomes apparent in the newborn, and none that can be used PROSPECTIVELYduring pregnancy to protect the developing brain from damage. The most likely cause of damage to the fetal brain during pregnancy or at birth is global ASPHYXIA, either by itself or in association with other problems of pregnancy such as infection, preterm birth, or fetal growth retardation. In this project we propose that providing extra amounts of the dietary constituent creatine, or of the hormone melatonin, to the pregnant animal in late gestation, will provide NEUROPROTECTION to the developing brain in the face of an asphyxial challenge that otherwise causes damage. We will use pregnant sheep to investigate the effects of asphyxia in utero on the fetal brain using techniques that allow us to monitor metabolic changes within the brain in real time. In addition, we will use the pregnant Spiny Mouse to investigate the effects of birth asphyxia on the postnatal brain structure and behavioral development. We will study groups of animals fed a normal diet, and compare then to animals that receive additional amounts of creatine or melatonin. We expect to determine if either of these treatments have the potential to protect the developing brain from asphyxial damage, and to recommend if similar treatments could be used in pregnant women where the obstetrician suspects the baby's brain is at risk of damage.Read moreRead less