Functional And Epigenetic Consequences Of Maternal Folate Deficiency, Supplementation And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$545,183.00
Summary
Growing slowly before birth or being born early and premature are very common. Both conditions greatly increase the risk of illness or death around birth and of the infant developing major conditions such as diabetes and cardiovascular disease in later life. Despite their importance, we understand little of what causes fetal growth failure or prematurity or why they influence an individual's health throughout life. Recent findings suggest that low levels of folate in the mother, due to either di ....Growing slowly before birth or being born early and premature are very common. Both conditions greatly increase the risk of illness or death around birth and of the infant developing major conditions such as diabetes and cardiovascular disease in later life. Despite their importance, we understand little of what causes fetal growth failure or prematurity or why they influence an individual's health throughout life. Recent findings suggest that low levels of folate in the mother, due to either dietary or genetic factors, may be involved in their origins and their long-term outcomes. Folate is a nutrient required regularly in small amounts for growth and maintenance of health. Folate supplementation in women is currently recommended before and in early pregnancy, but may have a role throughout the whole of pregnancy in promoting growth and health of the infant. Using experimental models, this project will determine if too little or too much maternal folate modifies the genetic code of the infant (called epigenetic changes), which leads to later metabolic disease and high blood pressure. These epigenetic changes are mild and subtle chemical modifications of DNA that persist in the cells of the infant altering their function. The efficacy of maternal folate supplementation in improving these outcomes for the small baby will also be tested in the models. Finally, the effect of folate status in the normal and small human infant on the epigenetic state of their placenta, cord blood white blood cells and mucous cells of the mouth will be tested. These outcomes will enable the design and testing of interventions with folate and related nutrients in the mother to improve the health of their babies before birth and subsequently throughout their lives. Because these pregnancy complications of being born small or early are common and account for much of the diabetes that occurs in later life, the health benefits from development of effective interventions may be large.Read moreRead less
Improving The Neonatal Transition In Infants With A Congenital Diaphragmatic Hernia
Funder
National Health and Medical Research Council
Funding Amount
$551,644.00
Summary
Congenital diaphragmatic hernia is a common congenital abnormality and occurs when the diaphragm fails to separate the abdominal and thoracic compartments before birth. This prevents the lung from growing properly and so at birth, the lung is unable to take over the role of gas exchange without considerable assistance. As a result, these infants are at high risk of death or significant disability and this application is focused on improving care and reducing morbidity in these infants.
Creatine Synthesis And Transport In The Fetus - Critical Regulation Of Energy Supply For Fetal Growth & Survival?
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Survival at birth depends on the baby being able to breathe effectively, to maintain adequate blood flow to every organ, and for the brain to coordinate these activities. Failure of any one of these will result in death. In this application we propose that the ability of the fetus and newborn baby to obtain adequate supplies of CREATINE is essential for survival, because this substance is essential for maintaining energy turnover in all cells in the body. In the adult, CREATINE is obtained eithe ....Survival at birth depends on the baby being able to breathe effectively, to maintain adequate blood flow to every organ, and for the brain to coordinate these activities. Failure of any one of these will result in death. In this application we propose that the ability of the fetus and newborn baby to obtain adequate supplies of CREATINE is essential for survival, because this substance is essential for maintaining energy turnover in all cells in the body. In the adult, CREATINE is obtained either from the diet (after absorption from the gut), or after synthesis in, and release from the liver. We do not know how fetal tissues obtain CREATINE, but we do know that when CREATINE is too low the fetus is likely to die, and that if extra CREATINE is supplied in the mother's diet the fetus is more likely to survive profound asphyxia at birth. In this project, in pregnant animals we will determine if fetal tissues can synthesize and take up CREATINE, and if providing extra CREATINE in the maternal diet throughout pregnancy can protect the heart, brain and breathing apparatus from the damaging effects of asphyxia or low oxygen (hypoxia). If successful, we will have developed a new treatment for pregnant women that protects their unborn baby from the dangers of birth asphyxia.Read moreRead less
Asking QUestions About Alcohol In Pregnancy (AQUA): Longitudinal Cohort Study Of The Effects Of Low And Moderate Doses Of Alcohol Exposure On The Fetus
Funder
National Health and Medical Research Council
Funding Amount
$1,368,294.00
Summary
National alcohol guidelines advise women to have no alcohol in pregnancy. However, many find they are unexpectedly pregnant and have been drinking, leading to considerable anxiety. While evidence is clear that heavy drinking is bad for the unborn baby, no-one knows for sure if low or even moderate levels of alcohol in pregnancy are harmful. We will study this important public health problem, following a group of pregnant women through their pregnancy and until their child is two years.
Developmental Programming: Mechanisms And Interventions
Funder
National Health and Medical Research Council
Funding Amount
$705,501.00
Summary
Disturbances during pregnancy can impact on developmental processes and result in increased risk of disease in later life. This project will examine the impact of perturbations such as maternal stress or alcohol consumption on the development of the placenta and fetal kidney. By gaining an understanding of how these organs are affected by prenatal insults, we are likely to be able to develop more effective intervention strategies to ensure all babies receive a healthy start to life.
The Consequences Of Innate Anti-viral Effector Responses On Reproductive Outcomes In Placental Mammals
Funder
National Health and Medical Research Council
Funding Amount
$328,060.00
Summary
The mother's immune system can tolerate the growth of an ostensibly foreign fetus during pregnancy. We will investigate whether exposure to viral infections either just before or during pregnancy can result in reduced fertility and whether it may affect fetal growth and development. These results will contribute in designing effective interventions to limit any potential detrimental outcomes.
Intrauterine Ureaplasma Infection During Pregnancy: Fetal Effects And Characteristics Of Ureaplasma Pathogenicity.
Funder
National Health and Medical Research Council
Funding Amount
$527,097.00
Summary
Ureaplasmas are microorganisms that are commonly found in the urinary tracts of men and women, without any apparent adverse effects; but their presence in amniotic fluid during pregnancy is associated with preterm birth and other adverse pregnancy outcomes. The effects that ureaplasmas in the amniotic fluid have on the developing baby before birth are likely to result in illness after birth, but the range of potential effects is unknown. We also know very little about how ureaplasmas themselves ....Ureaplasmas are microorganisms that are commonly found in the urinary tracts of men and women, without any apparent adverse effects; but their presence in amniotic fluid during pregnancy is associated with preterm birth and other adverse pregnancy outcomes. The effects that ureaplasmas in the amniotic fluid have on the developing baby before birth are likely to result in illness after birth, but the range of potential effects is unknown. We also know very little about how ureaplasmas themselves manage to infect the fetus and other tissues within the pregnant uterus. Our studies are designed to identify the effects that ureaplasmas in amniotic fluid have on the developing fetus and how common treatments during pregnancy impact on those effects. We will also study ureaplasmas to see what it is about them that allows them to affect the fetus and other uterine tissues. We expect that our studies will lead to better diagnosis and treatment of amniotic ureaplasma infection during pregnancy, and will allow us to better care for babies born after exposure to ureaplasmas before birth.Read moreRead less
Treatment Of Cerebral Palsy - An Experimental Approach
Funder
National Health and Medical Research Council
Funding Amount
$589,544.00
Summary
Cerebral palsy is characterised by disordered movement evident early in life leading to lifelong disability. The motor disorder arises from an abnormality within the white-matter of the brain that is non-progressive and is identifiable soon after birth. In humans and experimental models of fetal infection there is an increase in markers of inflammation. We will use induce ovine fetal infection and white matter injury to examine if anti-inflammatory treatments can prevent fetal brain damage.
The Role Of Proteoglycans In Contributing To Placental Thrombosis And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$368,269.00
Summary
Fetal growth restriction (FGR) is a pregnancy complication in which the baby doesn�t grow properly in the womb. Growth restricted babies are much more likely to be stillborn. These babies are also at risk of problems later in life such as obesity, diabetes and heart disease. This study investigates molecules in the placenta that may be responsible for causing FGR. If we can understand how these molecules cause the problem of FGR, we may be able to find better ways of treating or preventing it.
The Role Of Hypoxia In The Developmental Programming Of The Kidney
Funder
National Health and Medical Research Council
Funding Amount
$651,276.00
Summary
We aim to understand how inadequate oxygen supply to the fetus during pregnancy can affect development of the kidney. Many babies do not get enough oxygen whilst developing in the womb. This can be due to a poorly formed placenta or the mother smoking. This can interfere with normal growth and formation of the kidney. Our knowledge may help babies get the best start to life.