The Effect Of Asthma During Pregnancy On Placental Function And Fetal Development
Funder
National Health and Medical Research Council
Funding Amount
$378,600.00
Summary
Asthma affects 12% of the Australian population and is expected to increase to 20% over the next 10 years. This rise will result in an increase in the number of women who suffer from asthma during pregnancy and could emerge as a major public health problem since asthma during pregnancy is associated with low birthweight babies. Lower birthweight itself is an increased risk factor for a number of adult diseases such as diabetes and coronary artery disease and thus the children of asthmatic women ....Asthma affects 12% of the Australian population and is expected to increase to 20% over the next 10 years. This rise will result in an increase in the number of women who suffer from asthma during pregnancy and could emerge as a major public health problem since asthma during pregnancy is associated with low birthweight babies. Lower birthweight itself is an increased risk factor for a number of adult diseases such as diabetes and coronary artery disease and thus the children of asthmatic women are at risk for numerous pathologies throughout life. Nevertheless, the specific mechanisms that cause low birthweight in asthmatic pregnancies are unknown. We currently have a lead in this important area. Our data so far indicates that asthma produces alterations in placental blood flow and glucocorticoid metabolism that are particularly pronounced when the fetus is female. Inhaled glucocorticoid therapy is protective of the effects of asthma on the fetus suggesting the involvement of inflammatory pathways. The long term objectives of our work are to elucidate the effects of asthma on fetal health and to design better ways to manage asthma during pregnancy to improve the outcome for the baby. The short term objective of this grant is to define whether inflammatory factors associated with asthma during pregnancy change placental function to adversely affect fetal development and whether these effects are related to the sex of the fetus. Completion of these studies will provide both scientific and clincial outcomes. Scientifically, a biological basis for understanding alterations in placental physiology observed in women with asthma will be produced. Clinically our work will open avenues to optimize therapy for this group of women to improve their pregnancy and the outcome for their babies.Read moreRead less
The Impact Of Severe Asthma During Pregnancy On Placental Function And Fetal Hypothalamic-pituitary-adrenal Function
Funder
National Health and Medical Research Council
Funding Amount
$209,242.00
Summary
This study will examine whether the glucocorticoids administered for the control of severe asthma during pregnancy affects placental and fetal function. It is known that severe asthma during pregnancy is associated with low birth weight babies but the events that cause reduced growth of the baby are unknown. However in both animal and human pregnancies, increased exposure of the baby to glucocorticoids from the mother causes growth restriction of the baby. Therefore we propose that the increased ....This study will examine whether the glucocorticoids administered for the control of severe asthma during pregnancy affects placental and fetal function. It is known that severe asthma during pregnancy is associated with low birth weight babies but the events that cause reduced growth of the baby are unknown. However in both animal and human pregnancies, increased exposure of the baby to glucocorticoids from the mother causes growth restriction of the baby. Therefore we propose that the increased intake of glucocorticoids for the treatment of asthma during pregnancy changes how the placenta functions and allows the fetus to be exposed to maternal glucocorticoids causing changes in fetal development. We will examine placental blood flow and measure some placental enzymes that may be involved in the control of blood flow in placentas collected from women with mild, moderate and severe asthma and compare them to non-asthmatic women. We will look at placental blood flow in utero using Doppler ultrasound and also in vitro after the placenta is delivered. We want to see if the fetus is affected by increased intake of glucocorticoids by the mother by measuring a hormone estriol, which originates from the fetus. We will measure estriol throughout pregnancy as it can easily be detected in the mothers' urine. These studies will tell us if glucocorticoid intake for the treatment of asthma can exert effects on the placenta and baby during pregnancy. These studies will make a significant contribution both scientifically and clinically. At a scientific level we will be able to examine how increased maternal glucocorticoid intake during pregnancy affects placental mechanisms and whether these changes affect the fetus and clinically the outcome of this study will allow us to optimize asthma therapy during pregnancy so that we can improve the outcome for the baby.Read moreRead less
Pathways Of Neurosteroid-mediated Protection Following Compromised Pregnancy And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$565,785.00
Summary
The hormonal environment of pregnancy is essential for normal development of the fetal brain. Levels of key hormones fall following premature birth and are further suppressed if the fetus is small or subjected to stress. This leads developmental problems in infants from the pregnancies. This project will examine effectiveness of replacement and supplementation treatments with critical neurosteroid hormones in reversing the adverse neurological effects of these complications of pregnancy.
Neuroactive Steroids In The Fetal Brain: Role In The Regulation Of Behaviour And Protection Against Hypoxia
Funder
National Health and Medical Research Council
Funding Amount
$65,685.00
Summary
The major breakdown products of the steroid hormone, progesterone, form a group of hormones termed neuroactive steroids. These steroids have major effects on the activity of the brain and influence behaviour in adult subjects. Changes in the production of steroids by the steroid producing glands influences neurosteroid levels in the adult brain. This in tern may cause behavioural and mood changes in adults, leading to conditions such as premenstrual stress and postnatal depression. In fetal life ....The major breakdown products of the steroid hormone, progesterone, form a group of hormones termed neuroactive steroids. These steroids have major effects on the activity of the brain and influence behaviour in adult subjects. Changes in the production of steroids by the steroid producing glands influences neurosteroid levels in the adult brain. This in tern may cause behavioural and mood changes in adults, leading to conditions such as premenstrual stress and postnatal depression. In fetal life, the placenta releases large amounts of these neuroactive steroids and high concentrations of these steroid are found in the fetal circulation. We have shown that these steroids suppress the activity of the fetal brain, suppress arousal and maintain the fetus in a sleep-like state during pregnancy. In this proposal we investigate the hypothesis that cells in the fetal brain modify the neuroactive steroid environment within the brain so as to suppress fetal brain activity further during times of stress and, therefore, protect the brain from damage caused by excessive excitation. These mechanisms may prevent brain injury due to placental insufficiency during pregnancy and asphyxia during birth. The augmentation of these natural processes may form the bases for treatment strategies to provide additional protection for the fetal brain in high-risk pregnancies.Read moreRead less
Essential Protective Role Of Neuroactive Steroids In The Fetal And Neonatal Brain.
Funder
National Health and Medical Research Council
Funding Amount
$422,036.00
Summary
Brain injury may occur during complicated pregnancies and at birth, as well as in neonates following preterm labour, and is a major problem in neonatal medicine. The consequent nerve cell death leads to ongoing neurological impairment which represents a major cost to the individual and to the community. Neuroactive steroids are hormones related to the steroid hormone progesterone that have been shown to have a major influence on nerve cell activity and nervous transmission. While these hormones ....Brain injury may occur during complicated pregnancies and at birth, as well as in neonates following preterm labour, and is a major problem in neonatal medicine. The consequent nerve cell death leads to ongoing neurological impairment which represents a major cost to the individual and to the community. Neuroactive steroids are hormones related to the steroid hormone progesterone that have been shown to have a major influence on nerve cell activity and nervous transmission. While these hormones influence mood and behaviour in adult subjects, they have an even more important role in the fetus which is exposed to high levels of steroids from the placenta. The fetus is very sensitive to these neuroactive steroids and we have shown that they suppress the activity of the fetal brain so as to maintain the fetus in a sleep-like state during pregnancy. Periods of low oxygen supply (hypoxia) to the fetus may occur during pregnancy, as well as result from asphyxia at birth, and may lead to excessive excitation of nerve cells resulting in nerve cell death. Steroid-induced suppression reduces excitation of nerve cells and results in the fetus being resistant to excessive excitation. In this proposal we investigate the hypothesis that cells in the fetal brain modify the neuroactive steroid environment within the brain so as to suppress fetal brain activity further during times of hypoxic stress and, therefore, further protect the brain from damage caused by excessive excitation. These mechanisms may prevent brain injury due to placental insufficiency during pregnancy, asphyxia during birth and in premature babies. We will investigate whether the supplementation of these processes by administering neuroactive steroids may provide additional nerve protection during high-risk periods during pregnancy. These studies may identify a new as yet unexploited group of natural compounds which may improve infant health without adverse actions on the mother or baby.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