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
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
Regulation Of Eicosanoid Production In The Fetal Placenta In Preterm Labour
Funder
National Health and Medical Research Council
Funding Amount
$256,980.00
Summary
Prostaglandins are fatty substances made within the body and they are what causes the pregnant uterus to contract and push out the fetus. At present we can't control preterm birth because we don't understand well enough how prostaglandin synthesis is controlled. New discoveries in our lab have suggested an exciting new possibility- that prostaglandins partially regulate their own synthesis. If we find this is so, there may be far-reaching implications for the ways in which anti-inflammatory drug ....Prostaglandins are fatty substances made within the body and they are what causes the pregnant uterus to contract and push out the fetus. At present we can't control preterm birth because we don't understand well enough how prostaglandin synthesis is controlled. New discoveries in our lab have suggested an exciting new possibility- that prostaglandins partially regulate their own synthesis. If we find this is so, there may be far-reaching implications for the ways in which anti-inflammatory drugs are used, not only in prevention of premature birth, but in inflammatory diseases too. Most research in this area has been directed toward understanding what controls the overall synthesis of prostaglandins, but there are several types of prostaglandins with different functions. we are now in a position to study, for the first time, how the synthesis of the specific prostaglandins is regulated in the pregnant uterus and how this changes during normal and preterm 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.
Identifying And Preventing Inflammation-induced Brain Injury In Preterm Infants
Funder
National Health and Medical Research Council
Funding Amount
$338,652.00
Summary
Exposure to infection/inflammation around the time of birth is one of the most common factors associated with long-term disability. There is no effective treatment. My studies will use world-class techniques for measuring brain structure and function to improve our understanding of how infection/inflammation impacts on development of the preterm brain and determine whether blocking key inflammatory pathways in the brain will help restore normal brain growth and development in preterm infants.
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