Nasal CPAP For Very Preterm Infants At Birth: Does It Improve Outcome? A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$460,604.00
Summary
Neonatal respiratory distress syndrome (RDS) is the major cause of morbidity and mortality in preterm infants. Many of these infants need ventilatory support to keep them alive. In 1996 and 1997, 10,471 infants in Australia and New Zealand needed ventilatory support for a total of 72,544 days. This treatment is a great physical burden for the infants and an enormous emotional stress for their parents. Each day of treatment costs about A$2000 so their hospital treatment costs about $72 million a ....Neonatal respiratory distress syndrome (RDS) is the major cause of morbidity and mortality in preterm infants. Many of these infants need ventilatory support to keep them alive. In 1996 and 1997, 10,471 infants in Australia and New Zealand needed ventilatory support for a total of 72,544 days. This treatment is a great physical burden for the infants and an enormous emotional stress for their parents. Each day of treatment costs about A$2000 so their hospital treatment costs about $72 million a year. Of infants born less than 29 weeks' gestational age, about 40% of the survivors subsequently developed chronic lung disease (CLD). This condition is defined as prolonged dependence on supplementary oxygen therapy. CLD is associated with further costs and increased lung problems and readmissions to hospital in the first year of life. Thus, CLD is an expensive and time-consuming condition that has a high social cost. This project will determine whether treating these very premature babies from birth simply by applying oxygen under a low continuous positive pressure (CPAP) into their nose rather than the present treatment of placing a tube in the windpipe (known as intubation) and ventilation will reduce the incidence and severity of neonatal respiratory distress syndrome and subsequent chronic lung disease. The project will involve 600 babies from different, high quality neonatal intensive care units. Babies who are born at less than 29 weeks' gestation and who show signs of breathing at birth will be randomly allocated to be treated with either nasal CPAP or intubation and ventilation. This project will determine whether CPAP treatment at birth improves survival and reduces the severity of the RDS and subsequent CLD, or has no long term beneficial effect. If the trial is successful, this will be one of the most useful new treatments in neonatal medicine because it is simple to use, easier for the babies, and cheaper than ventilation.Read moreRead less
EVALUATION OF THE EFFECTIVENESS OF EXPANDED NEWBORN SCREENING BY TANDEM MASS SPECTROMETRY
Funder
National Health and Medical Research Council
Funding Amount
$375,250.00
Summary
Newborn babies in Australia are routinely tested for certain treatable disorders. Testing began in the 1960's with systematic testing for phenylketonuria, a rare amino acid enzyme defect. It causes severe mental retardation which can only be prevented if treatment is begun in the first few weeks of life. By 1997, only three other disorders, congenital hypothyroidism, cystic fibrosis, and galactosaemia, had been added to the testing protocol as tests became available. Using the new technology of ....Newborn babies in Australia are routinely tested for certain treatable disorders. Testing began in the 1960's with systematic testing for phenylketonuria, a rare amino acid enzyme defect. It causes severe mental retardation which can only be prevented if treatment is begun in the first few weeks of life. By 1997, only three other disorders, congenital hypothyroidism, cystic fibrosis, and galactosaemia, had been added to the testing protocol as tests became available. Using the new technology of tandem mass spectrometry (MSMS) it is now possible to screen for up to 30 extremely rare, treatable metabolic disorders simultaneously and cheaply, but it is not clear how effective this is. A formal trial of MSMS screening, randomly assigning babies to be tested or not tested, does not seem feasible because of the rarity of the individual disorders (most with a birth prevalence much less than 1: 50,000). Huge numbers would be needed in the trial for statistical significance. We began MSMS screening in NSW April 1998 and in South Australia in February 1999. Victoria is proposing to start screening now, but there are as yet no plans for this screening in the other states. We would like to assess the effectiveness of MSMS newborn screening using the best possible evidence drawn from all data available in the whole of Australia. We plan to undertake an economic evaluation, comparing costs and benefits such as development, hospitalisations, medical complications and other outcome measures, in screened and unscreened babies and also assess harms from screening. Because only 6 specialised laboratories in Australia, in Brisbane (2), Sydney, Melbourne, Adelaide, and Perth can diagnose these disorders, we are confident that we know of all diagnosed cases of the disorders in question. We hope to be able to show whether or not there is a benefit to affected babies by implementing newborn screening tests for these rare diseases.Read moreRead less
The Significance Of Human Metapneumovirus In The Australian Paediatric Population
Funder
National Health and Medical Research Council
Funding Amount
$457,625.00
Summary
A newly discovered paramyxovirus, human metapneumovirus (hMPV), shows clinical and virological charcteristics very similar to those of human respiratory syncytial virus (hRSV). Human RSV is the major cause of acute lower respiratory illness in infants and accounts for more than 1 million deaths world wide annually. Most infants are infected in their first year of life, and re-infection is common. Genetic variation of the virus is thought to play a critical role in its ability to escape the immun ....A newly discovered paramyxovirus, human metapneumovirus (hMPV), shows clinical and virological charcteristics very similar to those of human respiratory syncytial virus (hRSV). Human RSV is the major cause of acute lower respiratory illness in infants and accounts for more than 1 million deaths world wide annually. Most infants are infected in their first year of life, and re-infection is common. Genetic variation of the virus is thought to play a critical role in its ability to escape the immune response and establish multiple sequential infections in the same host. Currently, we have no knowledge of the extent that hMPV exists in the Australian population, nor do we know if hMPV is a significant respiratory pathogen in paediatric patients. This research aims to determine the importance of hMPV as a respiratory agent, and will establish the rate, age of exposure, and incidence of hMPV infection in Australian children. In addition, we will identify the hMPV strains (genotypes) that infect local children, and the difference, if any, between these and virus strains detected in children from other community groups, and from overseas. Such data is invaluable in devising a future vaccine strategy for hMPV, and the study of the genetic variability among Australian strains will have profound implications for public health. This research project is a preliminary study into the clinical and virological significance of hMPV, in children, and will form a basis for future research projects. Once this preliminary data is obtained, further studies are possible to determine the cellular immune response to hMPV infection and its role in long-term protection. Also,it is likely that hMPV, like hRSV, may prove to be an agent associated with long-term decreased pulmonary function and airflow limitation perhaps developing to asthma.Read moreRead less
The Use Of Probiotics To Reduce The Incidence Of Sepsis In Premature Infants.
Funder
National Health and Medical Research Council
Funding Amount
$808,733.00
Summary
Currently, premature infants are born without the normal immune defenses of infants born at the correct time because the protective factors that normally pass from the mother to the baby during the last few months of pregnancy have not had time to do so. In addition the tiny premature infants are at risk because they need the expertise of intensive care and are therefore separated from their parents and their parents' organisms which healthy term infants normally pick up from the birth canal and ....Currently, premature infants are born without the normal immune defenses of infants born at the correct time because the protective factors that normally pass from the mother to the baby during the last few months of pregnancy have not had time to do so. In addition the tiny premature infants are at risk because they need the expertise of intensive care and are therefore separated from their parents and their parents' organisms which healthy term infants normally pick up from the birth canal and their parents skin. The infants commonly develop infections from organisms living on their skin surfaces or inside their lungs, stomach or bowels. The babies are living in a hospital environment which they need to survive, but they may pick up particularly unhealthy organisms (pathogens) that produce toxins, which are difficult to treat even with antibiotics. These infections are so severe that one-fifth of the babies die, even in Australia where facilities for premature infants are excellent. Two recent studies overseas have shown that giving premature babies special preparations of certain probiotic organisms decreases the chance of babie developing infections. Probiotics are organisms that have health benefits. Probiotics tighten the spaces between cells to stop bacteria getting into the body, produce substances that kill other bacteria and promote the production of immunoglobulin A by the baby's own cells. Immunoglobulin A is a substance that lines the bowel wall and protects the baby from invasion by bacteria. This study will offer this probiotic product to very premature babies in a trial to see if it produces additional benefits for our babies in Victoria. Around five hundred babies will be given the product and five hundred will be given the placebo ( a harmless inert product which will look just like the real probiotic). Currently 23% of our babies get the serious infections and this study is powerful enough to see if we can reduce the number by one third.Read moreRead less
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
Cancer is still a major cause of mortality in adults and children. Several lines of evidence suggest that some childhood cancers may arise due to factors, which interfere with the normal process of early development in embryonal tissues. The nature of the molecular factors which derail normal embryogenesis, their mechanism and timing, is vital information for efforts to generate novel pharmaceuticals. Moreover, factors which are necessary for tumour initiation, might be very good targets for a c ....Cancer is still a major cause of mortality in adults and children. Several lines of evidence suggest that some childhood cancers may arise due to factors, which interfere with the normal process of early development in embryonal tissues. The nature of the molecular factors which derail normal embryogenesis, their mechanism and timing, is vital information for efforts to generate novel pharmaceuticals. Moreover, factors which are necessary for tumour initiation, might be very good targets for a cancer prevention strategy. If entirely successful, our experiments will show that the MYCN oncoprotein is a key factor in the very earliest stages of neuroblastoma tumour formation, we will define the mechanism of the MYCN effect on the normal process of neural crest development, and, we will provide a basis for future cancer prevention strategies in children with this disease.Read moreRead less
Health-Related Quality Of Life In Intractable Paediatric Epilepsy: Using A New Measure To Improve Management
Funder
National Health and Medical Research Council
Funding Amount
$252,940.00
Summary
Until recently there was no adequate measure to assess the quality of life of children with epilepsy. Our Australian centre was the first to develop, validate and publish such an instrument; the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). We now aim to collect more data using the QOLCE to gain further understanding of the effects of epilepsy and its treatment on the quality of life of children. We will determine if surgery in children stops seizures and improves quality of life. ....Until recently there was no adequate measure to assess the quality of life of children with epilepsy. Our Australian centre was the first to develop, validate and publish such an instrument; the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). We now aim to collect more data using the QOLCE to gain further understanding of the effects of epilepsy and its treatment on the quality of life of children. We will determine if surgery in children stops seizures and improves quality of life. We also aim to find out if children with different types of epilepsies have unique quality of life issues. Finally, we aim to determine if the quality of a child's life depends on how well they are thinking and learning or how often they are having seizures. We will conduct this study in children with difficult epilepsy recruited from three major children's hospitals (Sydney Children's Hospital, the Children's Hospital, Westmead, Miami Children's Hospital, Florida USA) using a well designed methodology. Each child will have their particular type of epilepsy characterised using video and brain wave analysis. Each parent and older child will receive a quality of life package including the QOLCE to assess life function. In addition, all children will have an assessment of their thinking and learning by a child psychologist. At the completion of this project we will have established whether surgical treatment in children with epilepsy stops seizures and improves quality of life. This will allow clinicians and parents to better understand the effects of surgical treatment in this population. In addition, we will determine if problems in quality of life are associated with specific types of epilepsy. This information can be used to counsel families and tailor interventions and treatments. Finally, we will know whether a child's quality of life is determined by problems with thinking and learning and-or seizures.Read moreRead less
Efficacy And Safety Of Methylxanthines In Very Low Birth Weight Infants
Funder
National Health and Medical Research Council
Funding Amount
$221,136.00
Summary
With improving technologies and medications the numbers of very premature babies surviving to leave hospital has increased over the last two decades. However these babies are at increased risk of having brain damage in the form of mental retardation and cerebral palsy. These problems impose a major burden on the individuals, their families and society at large. This study attempts to identify whether or not a commonly used drug is safe in these babies or whether it contributes to brain damage in ....With improving technologies and medications the numbers of very premature babies surviving to leave hospital has increased over the last two decades. However these babies are at increased risk of having brain damage in the form of mental retardation and cerebral palsy. These problems impose a major burden on the individuals, their families and society at large. This study attempts to identify whether or not a commonly used drug is safe in these babies or whether it contributes to brain damage in some cases. Many premature babies have difficulty breathing by themselves because their brain does not send regular messages to their lungs telling them to expand. A class of drugs which includes caffeine has been shown to stimulate breathing in babies and has been thought to reduce the amount of support these babies require from a ventilator in the first weeks of life. The safety of these drugs has not been adequately demonstrated in premature babies and there is some evidence from animal studies that they may disrupt the developing brain. Results in human babies are inconclusive and concerns remain regarding the long term effects of caffeine. The question of whether caffeine usage increases the risk of mental retardation or cerebral palsy is a very important one given the almost universal usage of this or similar drugs in premature babies. We will find out whether babies given caffeine as newborns perform as well at 18 months of age as babies not given the drug.Read moreRead less
The Genitofemoral Nerve And Gubernaculum In Testicular Descent And Inguinal Hernia
Funder
National Health and Medical Research Council
Funding Amount
$339,750.00
Summary
This project examines the mechanism of descent of the testis, which when abnormal, leads to the common anomaly in infant boys of undescended testes. In addition, the tunnel through the abdominal wall which permits testicular descent very commonly fails to close afterwards, allowing the intestines to protrude through the hole to cause an inguinal hernia, which is a tender lump in the groin,and requires surgery to resolve. Our long-term aim is to understand testicular descent and inguinal closure ....This project examines the mechanism of descent of the testis, which when abnormal, leads to the common anomaly in infant boys of undescended testes. In addition, the tunnel through the abdominal wall which permits testicular descent very commonly fails to close afterwards, allowing the intestines to protrude through the hole to cause an inguinal hernia, which is a tender lump in the groin,and requires surgery to resolve. Our long-term aim is to understand testicular descent and inguinal closure well enough to develop non-surgical treatments for these two conditions, which are the two commonest abnormalities in children requiring surgery. We will examine how male hormones control descent of the testis indirectly by altering the anatomy and function of a specific nerve suplying the groin and scrotum. A simple and safe treatment that avoided surgery would be a major advance for infants in the developing world.Read moreRead less
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