Preventing Preterm Lung Disease - A Cell Therapy Approach.
Funder
National Health and Medical Research Council
Funding Amount
$460,610.00
Summary
Due to improvements in medical care, the survival of very premature babies has greatly improved over the past 20 years. However, many of these children are surviving with disability due to severe chronic lung disease of prematurity. Currently, there are no effective treatments for this lung disease. This project explores the use of placental stem cells as a lung repair and regeneration therapy - a therapy that can be given to the baby in the days immediately following its birth.
A small number of babies die unexpectedly while still in the womb: the numbers are much higher than those dying from Sudden Infant Death Syndrome (SIDS). Some of these babies slow their movements down in the days before death. It would be very helpful to be able to accurately monitor babies' movements in the womb so that we could help the few babies who need it, and so prevent poor outcomes. Mothers feel their babies moving, but it's often hard for them to pick up all the movements that do occur ....A small number of babies die unexpectedly while still in the womb: the numbers are much higher than those dying from Sudden Infant Death Syndrome (SIDS). Some of these babies slow their movements down in the days before death. It would be very helpful to be able to accurately monitor babies' movements in the womb so that we could help the few babies who need it, and so prevent poor outcomes. Mothers feel their babies moving, but it's often hard for them to pick up all the movements that do occur. The best way of measuring babies' movements is during an ultrasound. However, that's expensive and means that the pregnant mother needs to lie still for about half an hour to have this testing done. We are developing a way of recording babies' movements, which still lets the pregnant woman continue with her normal activities. We will do this using an AMBULATORY FETAL ACTIVITY MONITOR, which is an accelerometer, like an advanced pedometer. The ambulatory fetal activity monitor will measure the activity of the unborn baby during pregnancy, looking at the number of times s-he moves and how simple or complex the movements are. We expect that the unborn baby who is not getting enough nutrition during the pregnancy will have fewer movements than other unborn babies. This project involves checking that movements picked up by the ambulatory fetal activity monitor are the same as movements seen on an ultrasound. We will then monitor a large number of pregnant women with healthy and possibly unhealthy babies, to help identify the babies who need help. Once we have this information, we will be able to use it in the future to possibly prevent poor outcomes in those babies who do need help.Read moreRead less
Differential Effects On Fetal Growth And Development Of Repeated Fetal Or Maternal Corticosteroid Treatments
Funder
National Health and Medical Research Council
Funding Amount
$356,849.00
Summary
Injections of synthetic hormones (corticosteroids) to women at risk of early preterm birth reduce the rate of respiratory illness and death in the newborn infant. It is standard clinical practice prior to early preterm birth to give corticosteroids by intramuscular injection to the mother. For many women, however, preterm birth does not occur as expected and it has become common practice to give repeated courses of corticosteroids to women in whom the risk of preterm delivery recurs or continues ....Injections of synthetic hormones (corticosteroids) to women at risk of early preterm birth reduce the rate of respiratory illness and death in the newborn infant. It is standard clinical practice prior to early preterm birth to give corticosteroids by intramuscular injection to the mother. For many women, however, preterm birth does not occur as expected and it has become common practice to give repeated courses of corticosteroids to women in whom the risk of preterm delivery recurs or continues. Using the sheep model, we have shown that repeated doses of corticosteroids, given intramuscularly to the mother, are of benefit to newborn lung function, but also reduce the rate of fetal growth and adversely affect brain development. Evidence from the Western Australian Preterm Infant Cohort Study suggests that birthweight in humans is similarly affected by repeated corticosteroids and is followed by behavioral disorders in childhood. Using sheep, we have shown that repeated injections of corticosteroids given directly to the fetus cause no reduction in birthweight although maturation is still enhanced. This finding of a differential effect of corticosteroids by different routes of administration raises several exciting opportunities and questions. First is the possibility that direct fetal treatment may be of use in humans, if current human trials show that repeated doses cause effects similar to those we have seen in sheep. Secondly, the finding challenges our current understanding of how an individual may be programmed for subsequent health or illness by prenatal events. The proposed study will attempt to explain why corticosteroids given to the mother, but not the fetus, restrict fetal growth. Our hypothesis is that these hormones, when given repeatedly to the mother, adversely affect the ability of the placenta to transfer essential nutrients to the fetus. We will test this hypothesis using pregnant sheep in which catheters have been implanted surgically.Read moreRead less