Repeated Prenatal Corticosteroids: Effects On Childhood Development, Behaviour, Growth And Health
Funder
National Health and Medical Research Council
Funding Amount
$265,900.00
Summary
Infants born preterm are at high risk of needing help with their breathing to survive. Corticosteroids given to the mother prior to preterm birth can substantially reduce these risks, although the beneficial effects of these drugs only seem to last seven days. Because of this there has been a tendancy to repeat the dose of prenatal steroids after seven days in women who remain at continued risk of very preterm birth. There has been no formal assessment of whether or not repeating the dose of pre ....Infants born preterm are at high risk of needing help with their breathing to survive. Corticosteroids given to the mother prior to preterm birth can substantially reduce these risks, although the beneficial effects of these drugs only seem to last seven days. Because of this there has been a tendancy to repeat the dose of prenatal steroids after seven days in women who remain at continued risk of very preterm birth. There has been no formal assessment of whether or not repeating the dose of prenatal corticosteroids is beneficial or harmful. In this clinical trial we will test what effect, if any, repeat doses of corticosteroids given to women who remain at risk of preterm birth, have on children at the age of two years Women are eligible for the trial if at of less than 32 weeks of pregnancy, they have received corticosteroids seven or more days ago, and they are considered to be at continued risk of preterm birth. Women are randomised to one of the two treatment groups. Half the women will receive a weekly intramuscular injection of corticosteroids up to the time of birth or 32 weeks gestation, whichever is earlier, whilst the risk of very preterm birth remains. The other half of the women will receive a saline placebo injection. Chance will decide which treatment the women receives. In this study all children who survive to 2 years corrected age will be assessed to see if they have any problems with their health, growth and development. In particular we will assess how well they can walk, talk, understand, see and hear. The trial will be able to assess whether repeat doses of prenatal corticosteroids are helpful or not for infants at risk of being born very preterm by comparing the short term effects on infant health after birth and whilst in hospital with the effects on the child's later health, growth and development. An economic assessment of repeat doses of prenatal corticosteroids will be made in these children.Read moreRead less
Early School-Age Outcomes After Exposure To Repeat Prenatal Corticosteroids - A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,083,964.00
Summary
AIMS OF THE RESEARCH We have recently concluded a large clinical trial in Australia and New Zealand of repeat dose of antenatal corticosteroids given to women who were likely to deliver their baby too early (before 34 weeks of pregnancy). We have been able to show that repeat doses of corticosteroids before birth significantly reduces the risk of the baby developing respiratory difficulties after birth from 41.4% to 32.8%. However, we are not sure if this potentially important improvement will t ....AIMS OF THE RESEARCH We have recently concluded a large clinical trial in Australia and New Zealand of repeat dose of antenatal corticosteroids given to women who were likely to deliver their baby too early (before 34 weeks of pregnancy). We have been able to show that repeat doses of corticosteroids before birth significantly reduces the risk of the baby developing respiratory difficulties after birth from 41.4% to 32.8%. However, we are not sure if this potentially important improvement will translate into better outcomes for the children as they grow older and reach school-age. As there are many examples of treatments given around the time of birth that have been shown to have some short-term benefits, but substantial long-term harms, we must be as certain as we can be that any advance in one small area of health is not counterbalanced by disadvantages in other health areas. This is particularly important to find out for repeat antenatal corticosteroids given the earlier conflicting reports from non-randomised studies. We plan to assess the 1085 survivors from our earlier clinical trial of repeat dose of prenatal corticosteroids when they are of early school age. We will assess their movement and other important areas of their brain function, as well as their school progress, blood pressure, lung function and general health and growth. EXPECTED OUTCOMES OF THE RESEARCH If we find important improvements in health outcomes at school-age in children exposed to repeat corticosteroids, without any substantial couterbalancing adverse effects, repeat steroids will be recommended standard therapy in women who are likely to give birth to their baby very early. This will lead to a reduction in the burden of ill health.Read moreRead less
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.
What Role Do Cerebral Hypoxia And Sleep Disruption Play In The Neurocognitive Effects Of Paediatric Sleep Disordered Breathing?
Funder
National Health and Medical Research Council
Funding Amount
$558,957.00
Summary
Sleep disordered breathing (SDB) describes a spectrum of disorders caused by obstruction of the upper airway during sleep from simple primary snoring (PS) to obstructive sleep apnoea (OSA). Findings of our recently studies have provided strong evidence that all levels of SDB severity including PS are associated with neurocognitive and behavioural deficits. In this study we will investigate the mechanisms of which underpin these deficits.
Enhancing The Neuroprotective Benefit Of Hypothermia With Melatonin In The Asphyxiated Neonate
Funder
National Health and Medical Research Council
Funding Amount
$785,331.00
Summary
During labour, asphyxic episodes which cause a severe reduction in oxygen supply can become prolonged and result in perinatal brain injury, termed Hypoxic Ischemic Encephalopathy, which may underlie cerebral palsy. Presently, newborn infants with suspected encephalopathy are cooled, which modestly protects the brain against cellular injury. We propose that the administration of melatonin to the newborn, in addition to cooling, will decrease the post-asphyxic formation of oxygen free radicals, th ....During labour, asphyxic episodes which cause a severe reduction in oxygen supply can become prolonged and result in perinatal brain injury, termed Hypoxic Ischemic Encephalopathy, which may underlie cerebral palsy. Presently, newborn infants with suspected encephalopathy are cooled, which modestly protects the brain against cellular injury. We propose that the administration of melatonin to the newborn, in addition to cooling, will decrease the post-asphyxic formation of oxygen free radicals, thereby reducing the progression of brain damage.Read moreRead less
Metabolic Complications Of Obstructive Sleep Apnea During Early Development
Funder
National Health and Medical Research Council
Funding Amount
$320,375.00
Summary
Adults with OSA are known to have increased risk for heart disease. We will study children with OSA, and an animal model of the disease during early development, to help clarify how this disease of adulthood actually has its origins in childhood. We have already shown that obese children with obstructive sleep apnea (OSA) are more prone to diabetes (metabolic problems) than those without OSA. More recently, we found that this is also true for children who are not overweight. This early diabetes ....Adults with OSA are known to have increased risk for heart disease. We will study children with OSA, and an animal model of the disease during early development, to help clarify how this disease of adulthood actually has its origins in childhood. We have already shown that obese children with obstructive sleep apnea (OSA) are more prone to diabetes (metabolic problems) than those without OSA. More recently, we found that this is also true for children who are not overweight. This early diabetes is known to be to show a future risk for heart disease. This study will examine why OSA in children is linked to metabolic problems. First, we will continue our study in children who are not overweight. We need to study more children to be sure that OSA is truly linked to metabolic problems - whether or not a child is overweight, because this means that children with OSA are at risk for metabolic and future cardiac problems, whether they are overweight or not. Since weight does not usually change after treatment of OSA, we will also study children again, after they have been treated for OSA. We expect to show that treatment of OSA resolves the metabolic problems. Since hypoxia (low oxygen) occurs in OSA we believe that this is the fundamental cause of the metabolic problems. To test whether this is true, we will look for metabolic problems in piglets exposed to similar, low levels of oxygen as those seen in children with OSA, comparing them to piglets that have not been so exposed. We believe that the tendency to develop OSA and diabetes is inherited. To test this, we will study the genes of a very large family whose members have OSA and-or diabetes, and try to find which genes are associated with OSA and with diabetes. This will help determine if the two genes are linked in some way.Read moreRead less
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
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.