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
Improving The Prediction And Detection Of Contributors To Term Stillbirth
Funder
National Health and Medical Research Council
Funding Amount
$570,358.00
Summary
Stillbirths are a global human tragedy, with 1 in 130 of all pregnancies in Australia ending in stillbirth. We propose to use ultrasound and blood markers to improve the detection of babies who are not growing well, a leading risk factor for stillbirth. Sleep position has also been associated with stillbirth, so we will study fetal heart rate responses during an overnight sleep study to see if breathing events overnight may be an important contributor to stillbirth in growth restricted fetuses.
Environmental Influences In The Establishment Of The Epigenetic Landscape In Children
Funder
National Health and Medical Research Council
Funding Amount
$695,097.00
Summary
The DNA in each of our cells does not exist alone, it is packaged into complex structures called chromosomes, through association with many different proteins. The distribution of these proteins varies along the length of a chromosome depending on the type of cell and this phenomenon is called 'epigenetics', literally meaning 'above the DNA'. Epigenetic analysis is the study of how proteins and other molecules can change the activity of a gene without changing the DNA sequence. All of our cells ....The DNA in each of our cells does not exist alone, it is packaged into complex structures called chromosomes, through association with many different proteins. The distribution of these proteins varies along the length of a chromosome depending on the type of cell and this phenomenon is called 'epigenetics', literally meaning 'above the DNA'. Epigenetic analysis is the study of how proteins and other molecules can change the activity of a gene without changing the DNA sequence. All of our cells use epigenetic changes to help control how they grow and develop. Evidence suggests a direct link between diet and environmental influences on our epigenetic profile. Recent research has traced the origins of many of the health problems of adult life back to the earliest periods of development _ to the time spent in the womb and the first few years of life. If we are born with a low birth weight, we are more likely to get sick later in life. Overwhelming evidence exists that the environment in the womb is critical for a healthy birth weight (and health in later life) and it is thought that epigenetics may be the missing link between this environment, low birth weight, and therefore health in later life. In addition, mounting evidence supports a general link between epigenetic de-regulation and predisposition to disease. However, the timing and the overall contribution of environmental- genetic influences to the establishment of faulty epigenetic markings remain largely unknown. Twins are the best model to study this link as they share similar (but not identical environments) and some share identical genetic makeup. Using twins, Dr Jeffrey Craig and his team will investigate the factors in the prenatal environment that modify specific cells, leading to low birth weight and increase disease risk later in life. They predict that this occurs via specific changes in gene activity caused by epigenetic disruption.Read moreRead less
Epidemiology Of Unexplained Antepartum Fetal Death In Australia
Funder
National Health and Medical Research Council
Funding Amount
$450,350.00
Summary
The death of a baby before birth is a devastating event for the parents and families. In the vast number of these deaths, no cause can be found leaving no clues for parents and care providers struggling with decisions about future pregnancies and how the risk may be reduced for all women in pregnancy. Fetal death before the onset of labour without an apparent cause (Unexplained Antepartum Fetal Death (UAFD) constitutes the most common cause of fetal death. In Australia, the rate of UAFD is appro ....The death of a baby before birth is a devastating event for the parents and families. In the vast number of these deaths, no cause can be found leaving no clues for parents and care providers struggling with decisions about future pregnancies and how the risk may be reduced for all women in pregnancy. Fetal death before the onset of labour without an apparent cause (Unexplained Antepartum Fetal Death (UAFD) constitutes the most common cause of fetal death. In Australia, the rate of UAFD is approximately 2 per 1 000 births, contributing 30% to all fetal deaths. The rate of UAFD is over three times the current rate of Sudden Infant Death Syndrome (SIDS) in Australia. Despite this, little research has been undertaken in this area. The research which has been undertaken suggests that factors which are present during pregnancy may identify women who are at risk. However, the results of these studies are not consistent, largely due to the problems with study design, and therefore the available information is not sufficiently reliable to assist in identification of women at risk. Well designed, large scale studies are urgently needed to determine, from the reported list of risk factors, those factors which truly identify a woman at increased risk in the antenatal period where appropriate care can be provided to decrease the likelihood of fetal death. Recently, a collaborative effort involving clinicians and consumers in Australia has commenced to support and undertake research and related activities and to collaborate with international groups in reducing the risk of UAFD (ANZ Fetal Death Collaborative Group). This study forms the basis for this work within Australia. This study is designed to identify women who are at risk of unexplained antepartum fetal death. The study involves a review of 800 unexplained antepartum fetal deaths in three States of Australia and an analysis of information on all births in Australia which is routinely collected by Health Departments.Read moreRead less
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
Intergenerational Determinants Of Fetal Growth In Aboriginal Western Australians
Funder
National Health and Medical Research Council
Funding Amount
$399,179.00
Summary
We will study birth and disease records over 3 generations of Aboriginal families to investigate how a mother’s birth weight and her diseases in pregnancy influence both her reproductive health and her risk of chronic diseases (eg heart disease and diabetes) later in life. This world-first study will guide effective prevention of chronic disease in Aboriginal Australians; it may suggest that prevention needs to start with grand-mothers rather than in later generations.
Vitamin D In Pregnancy And Growth Of The Offspring.
Funder
National Health and Medical Research Council
Funding Amount
$168,550.00
Summary
Vitamin D is a potent steroid hormone required for bone growth and mineralisation, and there is evidence that it regulates cell proliferation. Insufficiency in pregnant women is a cause for concern. The role of vitamin D in human fetal development has been little investigated. At the severe end of the maternal vitamin D insufficiency spectrum, a very small number of deficient neonates have congenital rickets. Low maternal vitamin D status has also been associated with neonatal hypocalcaemia and ....Vitamin D is a potent steroid hormone required for bone growth and mineralisation, and there is evidence that it regulates cell proliferation. Insufficiency in pregnant women is a cause for concern. The role of vitamin D in human fetal development has been little investigated. At the severe end of the maternal vitamin D insufficiency spectrum, a very small number of deficient neonates have congenital rickets. Low maternal vitamin D status has also been associated with neonatal hypocalcaemia and defective tooth enamel. Randomised trials have shown that giving vitamin D to deficient women significantly improves their offspring's birth size and length at a year of age, in one study even though all infants were given vitamin D supplements post-natally. We do not understand the nature of the relationship between maternal vitamin D status and offspring growth. There could be a continuous association, or a threshold vitamin D level below which offspring growth is impaired. If the latter is the case, that threshold value needs to be known. Furthermore, we do not know whether maternal vitamin D level in early or late gestation is most influential in terms of fetal and infant growth. Raised maternal parathyroid hormone (PTH) level is a marker of disturbed vitamin D metabolism. There is evidence that offspring are shorter with increasing level of maternal PTH. In a study in Geelong, 63% of 20-45 year old women tested in winter, and 32% tested in summer, had vitamin D levels in the range where PTH rises. Thus a significant proportion of women may have insufficient vitamin D, in early or late pregnancy, to sustain optimal fetal growth. These issues are important for the health of mothers and their offspring, and there are public health implications, in terms of maternal health and possibly later health of the offspring. These issues have not been investigated in Australia or elsewhere, and this is a novel and important study.Read moreRead less