Preclinical Evaluation Of A Novel Allosteric IL-1R Inhibitor (rytvela) For The Prevention Of Perinatal Inflammation-induced Fetal Injury
Funder
National Health and Medical Research Council
Funding Amount
$1,377,827.00
Summary
Interleukin-1 (IL-1) is a potent inflammatory protein involved in many inflammatory disorders, including preterm birth (PTB). Blocking the actions of IL-1 in pregnancies at risk of delivering preterm may protect the fetus from PTB and the long-term harm of exposure to inflammation before birth. Using four different models of antenatal inflammation, we will explore the use of a new IL-1 inhibitor to see if it blocks inflammation ‘in utero’ and improve neonatal health and development.
Fetal Sex: An Important Determinant Of The Placental Transcriptome
Funder
National Health and Medical Research Council
Funding Amount
$553,574.00
Summary
There are fetal sex differences in pregnancy outcomes that place boys at greater risk than girls. These are likely caused by genetic differences in the placenta. We will use 21st century gene sequencing technology to obtain the complete sequence of placental genes in early pregnancy and normal term placenta to determine what the genetic differences are between male and female placentas. This may be important in developing future sex specific therapeutics for babies in the neonatal nursery.
Disrupted Neurosteroid Synthesis Mediates The Adverse Effects Of Prenatal Stress
Funder
National Health and Medical Research Council
Funding Amount
$695,973.00
Summary
Maternal anxiety and related stress in pregnancy influences the fetus causing developmental changes that adversely affect the offspring leading to behavioural problems in childhood. However, mechanisms which transfer maternal changes to the fetus are unclear. We propose that disruption of the fetal-placental neurosteroid system is a major link. We will identify the deficits in this system caused by maternal stress and then examine therapies to reverse these disruptions.
Mitochondrial Damage Following Fetal Hypoxia Or Birth Asphyxia: Using Creatine To Preserve Mitochondrial Function
Funder
National Health and Medical Research Council
Funding Amount
$838,726.00
Summary
There is a need for a therapy that can be given before a mother gives birth to protect the baby should ‘oxygen starvation’ threaten the baby’s brain and other organs such as the heart, kidney, lungs, and the ability to breathe properly. We are suggesting that an increased intake of creatine is a very effective treatment against this threat, and its proven safety and ease of use recommends it for wide application, particularly in countries where the access to medical resources is poor.
Creatine, A Multi-organ Protectant Against Hypoxic Injury In The Neonate
Funder
National Health and Medical Research Council
Funding Amount
$524,802.00
Summary
The WHO estimates that up to 9 million babies suffer birth hypoxia each year, leading to 29% of global neonatal deaths, and significant rates of severe disability. We hypothesise that creatine, given as a supplement to the mothers diet during pregnancy, will protect her babies organs should low oxygen around the time of birth occur. The low cost of creatine is particularly relevant for rural and remote communities and the developing world where, currently, there are no effective therapies.
Creatine Supplementation During Pregnancy As A Means Of Improving Outcomes From Preterm Birth.
Funder
National Health and Medical Research Council
Funding Amount
$479,085.00
Summary
Preterm birth results in significant health problems for babies, especially males who are more likely to die. We have shown that creatine added to the mother’s diet protects the fetus against damage caused by oxygen lack at the end of pregnancy. We will now determine if creatine can benefit babies born prematurely. We have an established model of preterm birth in lambs in which we will address these issues, and expect to show that creatine improves survival and the health of the preterm neonate.
Each year approximately 24,000 Australian children are born too early. A new international study led by Western Australian researchers is studying the role that genetics play in preterm birth. This study will evaluate the genomes of 10,000 women of which 2,000 come from Western Australia. It is anticipated that this study will advance our knowledge about the genetic basis of preterm birth and assist in providing customised clinical care to those at highest risk.
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.
DEVELOPMENT OF FOLDING IN THE FETAL CEREBRAL CORTEX – IDENTIFYING FUNDAMENTAL MECHANISMS AND THEIR SUSCEPTIBILITY TO DISRUPTION IN NORMAL AND ABNORMAL PREGNANCY
Funder
National Health and Medical Research Council
Funding Amount
$607,742.00
Summary
During pregnancy, the surface of the fetal brain gradually develops the ridges, valleys, and folds that are the characteristic feature of our highly developed brain. However, this process can be disturbed if birth occurs prematurely, the unborn baby suffers oxygen starvation in the uterus, or the mother consumes alcohol. In this project we are determining how cell migration results in the development of brain surface folding, and how hypoxia and maternal alcohol consumption affect these importan ....During pregnancy, the surface of the fetal brain gradually develops the ridges, valleys, and folds that are the characteristic feature of our highly developed brain. However, this process can be disturbed if birth occurs prematurely, the unborn baby suffers oxygen starvation in the uterus, or the mother consumes alcohol. In this project we are determining how cell migration results in the development of brain surface folding, and how hypoxia and maternal alcohol consumption affect these important processes.Read moreRead less