Early Identification Of Infants Who Will Benefit From Neural Rescue Treatment
Funder
National Health and Medical Research Council
Funding Amount
$206,320.00
Summary
Lack of oxygen supply before, during or immediately after birth can lead to severe disability or death. This occurs in about 1 in every 500 births and is one of the most important but unsolved problems in pediatrics. The costs (financial and other) to both the individuals involved, and the community in general, is very high. However the outlook for those affected by this condition is improving. Recent research has focused on the development of neural rescue therapies, which may decrease the exte ....Lack of oxygen supply before, during or immediately after birth can lead to severe disability or death. This occurs in about 1 in every 500 births and is one of the most important but unsolved problems in pediatrics. The costs (financial and other) to both the individuals involved, and the community in general, is very high. However the outlook for those affected by this condition is improving. Recent research has focused on the development of neural rescue therapies, which may decrease the extent of disabilities suffered by these children. The same treatments may also be helpful in children following near drowning and head trauma. Neural rescue therapies must be applied less than 24 hours following the event which has caused the reduction in oxygen supply. Thus, before these treatments can be tested, it is necessary to find a way to quickly tell which babies may benefit from the treatments. This study will trial a new method which is inexpensive and can be used without moving the baby away from its incubator. This technique involves a new application of an established technology to detect the redistribution of water within the brain one of the earliest signs of impending brain cell death. The research team consists of medical personnel from the intensive care nurseries of both the Royal Women's Hospital and the Mater Mother s Hospital, as well as scientific staff experienced in the use of this technology. If this technique is effective, it will enable babies to receive maximum benefit from new treatments and reduce long-term difficulties suffered by these children and their families.Read moreRead less
Repeated Prenatal Corticosteroids: Effects On Childhood Development, Behaviour, Growth And Health
Funder
National Health and Medical Research Council
Funding Amount
$718,055.00
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 pretermbirth, 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
Factor V Leiden Mutation: A Contributory Factor For Cerebral Palsy?
Funder
National Health and Medical Research Council
Funding Amount
$72,595.00
Summary
Cerebral palsy is the commonest physical disability in childhood. It has a major impact on individuals and families. In a significant proportion of cases, the cause is unknown so further research is essential to define the reasons for this condition, and thereby develop preventative strategies. Two mutations have been identified that predispose carriers to develop blood clots (called thrombosis). These mutations are the Factor V Leiden mutation and the coagulation gene for prothrombin (also know ....Cerebral palsy is the commonest physical disability in childhood. It has a major impact on individuals and families. In a significant proportion of cases, the cause is unknown so further research is essential to define the reasons for this condition, and thereby develop preventative strategies. Two mutations have been identified that predispose carriers to develop blood clots (called thrombosis). These mutations are the Factor V Leiden mutation and the coagulation gene for prothrombin (also known as the G20210A mutation). If blood clots form in, or travel to the brain (embolism), they can obstruct the blood supply causing damage that may result in cerebral palsy in young children. Our research will investigate both mothers of children with cerebral palsy, and the children themselves. The study of the mothers will determine whether those that are carriers of these mutations are at an increased risk of having children with cerebral palsy. Factors that may precipitate the development of blood clots, such as smoking during pregnancy, will be investigated. The children with cerebral palsy will be studied to determine whether they carry the mutations, and if so, whether they have brain scan evidence of previous blood clots. Children will be tested for the mutation using the blood spot taken routinely early in life. These blood spots are stored on cards (Guthrie cards) and are available for research following parental consent. The mothers will be tested for the mutation by using a saliva sample and will also be interviewed to obtain details of their pregnancies. As a result of this project, useful information will be provided for families and health care providers. It will be established whether these mutations play a role in the genesis of cerebral palsy. In addition, data about possible factors which may increase the risk in carrier mothers, such as smoking, will be provided.Read moreRead less
The Effect Of Very Premature Birth On Brain Development
Funder
National Health and Medical Research Council
Funding Amount
$517,975.00
Summary
The neurological outcome of the premature infant is of major importance. Approximately 2,600 premature infants weighing less than 1500 grams are born annually in Australasia. Of the approximate 2,400 survivors between 5-15% will have a more major cerebral palsy, i.e. around 200 children per annum. A greater proportion of 25-50%, i.e., upto 1200 children will have a developmental disability that will adversely affect their school perfomance requiring special assistance or repeating grades. With a ....The neurological outcome of the premature infant is of major importance. Approximately 2,600 premature infants weighing less than 1500 grams are born annually in Australasia. Of the approximate 2,400 survivors between 5-15% will have a more major cerebral palsy, i.e. around 200 children per annum. A greater proportion of 25-50%, i.e., upto 1200 children will have a developmental disability that will adversely affect their school perfomance requiring special assistance or repeating grades. With an increasing number of very prematurely born infants surviving, the absolute number of affected children will continue to rise. Prevention of these disabilities will require an understanding of the cause. The educational and social implications of these high rates of neuro-developmental disability are enormous and the focus of wide international concern. Magnetic Resonance Imaging : It is a major challenge for neonatologists to be able to understand the impact of their therapies and managements on the developing brain. A window into the newborn brain can be seen utilising advanced magnetic resonance imaging techniques in-vivo to investigate these key issues: 1. What is the nature of brain injury in the prematurely born infant? 2. What are the risk factors for brain injury in the prematurely born infant - and are they able to be altered to reduce this risk - e.g. blood pressure management, steroid therapy 3. Is the brain of a prematurely born infant different from that of a full term born infant at TERM equivalent - if so, how is it different? 4. Are there certain postnatal therapies that relate to any alteration in brain structure and chemistry - e.g. postnatal nutrition, modes of ventilation, pharmacological therapies? 5. How does the brain structure relate to function on long term neuro-developmental follow up of our infants at 2 years?Read moreRead less
Improving The Outcome Of Premature Infants- A Randomised Trial Of Preventive Care At Home
Funder
National Health and Medical Research Council
Funding Amount
$633,375.00
Summary
The high rate of adverse neurodevelopmental outcomes of very premature infants is of major concern. In Australia there are approximately 2600 very low birthweight (VLBW, birthweight <1500 g) or very premature (<30 weeks' gestational age) survivors per annum. A large proportion of these infants (40%-50%) will later develop motor incoordination, cognitive impairment, attention deficits or behavioural problems (up to 1300 new cases per year). There is little research to test the efficacy of e ....The high rate of adverse neurodevelopmental outcomes of very premature infants is of major concern. In Australia there are approximately 2600 very low birthweight (VLBW, birthweight <1500 g) or very premature (<30 weeks' gestational age) survivors per annum. A large proportion of these infants (40%-50%) will later develop motor incoordination, cognitive impairment, attention deficits or behavioural problems (up to 1300 new cases per year). There is little research to test the efficacy of early preventive care programs geared to changing the infant's environment (physical management, behavioural regulation, maternal factors). In the proposed study we aim to use a low cost preventive care program at home conducted by physiotherapists and psychologists that has been shown to have utility and efficacy in pilot work, with follow up until 2 years of age. In subsequent studies we would aim to follow this cohort to school age, to determine if there are any lasting benefits of early intervention accompanied by measures of brain growth and structural development using advanced imaging techniques. Any new health care program should result not only in improvements in health, but should be affordable to implement so an economic evaluation will also be undertaken. This study will also utilise novel and advanced MRI brain imaging techniques to understand the complex interaction between brain injury and altered brain development in these infants with the risk and the repsonse to this program of care. In this way the changes in brain connectivity, structure and biochemistry can be formally defined to undertsnad the pathway of any potential benefit from this program.Read moreRead less
Postnatal Dexamethasone In Tiny Babies: Does It Do More Good Than Harm?
Funder
National Health and Medical Research Council
Funding Amount
$394,688.00
Summary
The survival rate for tiny or very premature babies has improved dramatically in recent times, from below 10% in the 1960s to greater than 70% in the 1990s. However, some of these babies require prolonged periods of help with breathing and oxygen treatment to survive, and many develop a form of chronic lung disease in the newborn period. A powerful group of drugs, known as corticosteroids, have been used to treat or prevent this chronic lung disease in newborn babies, with some success in shorte ....The survival rate for tiny or very premature babies has improved dramatically in recent times, from below 10% in the 1960s to greater than 70% in the 1990s. However, some of these babies require prolonged periods of help with breathing and oxygen treatment to survive, and many develop a form of chronic lung disease in the newborn period. A powerful group of drugs, known as corticosteroids, have been used to treat or prevent this chronic lung disease in newborn babies, with some success in shortening the time that the babies need help with breathing. However, corticosteroids have the potential to cause long-term harm to the developing baby's brain, and may cause lifelong problems with thinking, walking, talking, seeing or hearing. We want to test in a clinical trial if corticosteroids, specifically dexamethasone, can reduce the need for help with breathing and the rate of chronic lung disease without causing long-term problems to the developing baby's brain. Babies who are very tiny (born weighing less than 1000 g), or born very early (born before 28 weeks of pregnancy, or more than 12 weeks premature) will be eligible for this study if they still need help with their breathing after one week of age from a machine called a respirator, and their doctor considers that corticosteroids might be helpful to the baby's breathing. Some babies will receive dexamethasone and other babies will be treated with a harmless placebo - chance will decide which treatment the baby receives. All other aspects of the babies' care will continue as normally. Children who survive to 2 years of age will be assessed fully to determine if they have any problems with their health, including problems with their thinking, walking, talking, seeing or hearing. We will determine if dexamethasone is helpful or not for very tiny or very premature babies who have breathing problems after the first week of life. We will also measure the economic impact of dexamethasone treatment in these babies.Read moreRead less
School-Age Outcomes Of Very Preterm Infants And Antenatal Magnesium Sulphate Therapy - A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$675,050.00
Summary
Despite recent major advances in care around the time of birth that have led to large increases in the survival rates for very preterm babies, the rate of adverse long-term health problems has not diminished in survivors, and remains too high compared with children not born very preterm. In particular they have higher rates of substantial problems with the way their brain works, particularly affecting their movement, vision, hearing, thinking and talking. We have just concluded a large clinical ....Despite recent major advances in care around the time of birth that have led to large increases in the survival rates for very preterm babies, the rate of adverse long-term health problems has not diminished in survivors, and remains too high compared with children not born very preterm. In particular they have higher rates of substantial problems with the way their brain works, particularly affecting their movement, vision, hearing, thinking and talking. We have just concluded a large clinical trial in Australia and New Zealand of magnesium sulphate which was given to mothers who were likely to deliver their baby too early (before 30 weeks of pregnancy). We have been able to show, for the first time, that magnesium sulphate was able to halve the rate of substantial problems with movement in 2 year old survivors, from 6% to 3%. 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. We plan to assess the 1061 survivors from our earlier clinical trial of magnesium sulphate therapy at ages from 7-8 years, when they are at school. We will assess their movement and other important areas of their brain function, as well as their school progress and general health and growth. If we find important improvements in health at school-age of these children caused by magnesium sulphate therapy, without any substantial counterbalancing side-effects, magnesium sulphate will probably become standard therapy in mothers who are likely to deliver their baby very early. This will lead to a reduction in the burden of illness in the community caused by being born too early.Read moreRead less
SCHOOL-AGE OUTCOME FOR VERY TINY/PRETERM CHILDREN BORN IN VICTORIA IN 1991-92
Funder
National Health and Medical Research Council
Funding Amount
$252,956.00
Summary
The survival rate for tiny or very premature babies has improved dramatically in recent times, from below 10% in the 1960s to greater than 70% in the 1990s. Several new treatments have helped to improve their survival rate, but some have the potential to cause long-term harm to the developing baby's brain or lung, and may cause lifelong problems with thinking, walking, talking, seeing, hearing, growth or breathing. Babies who are very tiny (born weighing less than 1000 g), or born very early (bo ....The survival rate for tiny or very premature babies has improved dramatically in recent times, from below 10% in the 1960s to greater than 70% in the 1990s. Several new treatments have helped to improve their survival rate, but some have the potential to cause long-term harm to the developing baby's brain or lung, and may cause lifelong problems with thinking, walking, talking, seeing, hearing, growth or breathing. Babies who are very tiny (born weighing less than 1000 g), or born very early (born before 28 weeks of pregnancy, or more than 12 weeks premature) will be assessed long term (to 8-9 years of age), as broadly as possible, and in comparison with normal birthweight (NBW, birthweight >2499 g) children. Outcomes will encompass academic progress and behaviour, brain function, general health, growth, and respiratory health. We will compare the outcomes for very tiny-preterm children who were treated with several of these new therapies with those who were not so treated. We will assess whether alternative measures of long term outcome that assess the quality of life are applicable to very tiny-preterm children. If so, these measures could be used much more widely, since they are cheaper and less time-consuming.Read moreRead less