Improving The Fetal To Neonatal Transition In Compromised Newborns; Towards Better Outcomes For Babies Born Too Soon Or With Under-developed Lungs
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
The birth of a compromised infant affects 13 million pregnancies worldwide annually and is the greatest cause of neonatal death, disability and chronic disease. I will identify mechanisms to greatly improve the fetal to neonatal transition in premature babies and babies with under-developed lungs. This research is urgently required to provide the necessary evidence to target interventions in the delivery room to reduce the short- and long-term burden of disease in compromised newborns.
Causal Pathways From Maternal Obesity To Pregnancy, Perinatal & Childhood Health Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$775,703.00
Summary
Overweight and obesity affects more than 50% of women entering pregnancy. There are well-documented risks of poor health outcomes associated with obesity during pregnancy. We will evaluate whether an antenatal dietary and lifestyle intervention among pregnant women who are overweight or obese, acts via metabolic, hormonal, and inflammatory pathways, in the contribution of maternal obesity to adverse pregnancy, perinatal and early childhood health outcomes.
Understanding The Contribution Of Sympathetic Overactivity To Maternally Programmed Obesity Related Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$605,083.00
Summary
Obesity and associated diseases are increasing worldwide. Aside from adult risk factors, the environment encountered during development may predispose to later disease. Our data shows that the diet consumed by pregnant mothers can influence the development of obesity and hypertension in her offspring and that the sympathetic nervous system becomes dysregulated. This project will assess how maternal fat intake in pregnancy affects sympathetic nervous system function in the offspring and we invest ....Obesity and associated diseases are increasing worldwide. Aside from adult risk factors, the environment encountered during development may predispose to later disease. Our data shows that the diet consumed by pregnant mothers can influence the development of obesity and hypertension in her offspring and that the sympathetic nervous system becomes dysregulated. This project will assess how maternal fat intake in pregnancy affects sympathetic nervous system function in the offspring and we investigate possible management strategies.Read moreRead less
Intergenerational Transmission Of Gender-specific Metabolic Disease For Offspring Born Small: Maternal, Paternal And Embryonic Roles
Funder
National Health and Medical Research Council
Funding Amount
$689,050.00
Summary
This proposal addresses the underlying metabolic health consequences of poor embryo and growth of the baby across generations. We will define mechanisms by which a poor functioning placenta during a rat mother’s pregnancy programs her offspring born small to transmit gender-specific diseases to the next generation. We will identify mechanistic pathways involved, specifically the relative contributions of maternal and paternal germ lines and adverse maternal adaptations to pregnancy for females b ....This proposal addresses the underlying metabolic health consequences of poor embryo and growth of the baby across generations. We will define mechanisms by which a poor functioning placenta during a rat mother’s pregnancy programs her offspring born small to transmit gender-specific diseases to the next generation. We will identify mechanistic pathways involved, specifically the relative contributions of maternal and paternal germ lines and adverse maternal adaptations to pregnancy for females born small.Read moreRead less
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.
Periconceptional Nutrition And The Programming Of Obesity
Funder
National Health and Medical Research Council
Funding Amount
$468,879.00
Summary
Mothers who enter pregnancy with a high body mass index are at risk of developing diabetes in pregnancy and of having a large baby who will be at increased risk of developing obesity in childhood and later life. Heavy mothers therefore have heavy babies and these babies go on to become heavy adults. This grant will determine the separate contributions of exposure of the embryo to high nutrition and exposure of the fetus in late gestation to high maternal nutrition.
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
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
Vitamin D Deprivation In Early Life: Programming Of Vascular Function In Adulthood
Funder
National Health and Medical Research Council
Funding Amount
$440,250.00
Summary
It is becoming increasing evident that appropriate nutrition in fetal-early life is important in programming the cardiovascular system of the offspring, influencing its function throughout life. Maternal deficiency in vitamin D is a recently-identified concern world-wide, including in Australian women. We have recently found that vitamin D deficiency in pregnant rats results in marked hypertension in the offspring, when only 7 weeks of age. This is associated with impaired endothelium-dependent ....It is becoming increasing evident that appropriate nutrition in fetal-early life is important in programming the cardiovascular system of the offspring, influencing its function throughout life. Maternal deficiency in vitamin D is a recently-identified concern world-wide, including in Australian women. We have recently found that vitamin D deficiency in pregnant rats results in marked hypertension in the offspring, when only 7 weeks of age. This is associated with impaired endothelium-dependent vasodilator function, increased smooth muscle tone and increased constriction to nerve stimulation. A combination of intracellular electrophysiological techniques and tension recordings will be used to investigate detailed mechanisms in arteries isolated from key vascular beds. In vivo studies will probe the role of vitamin D deficiency in the control of regional blood flow control, and its influence on the underlying regulatory mechanisms responsible for the cardiovascular dysfunction that we have observed. We will test whether the cardiovascular dysfunction in the offspring following vitamin D deficiency is reversible upon repletion, or is programmed and thus not reversible with repletion. Our early results suggest that the deleterious effects are not reversible. From this study we aim to be in a position of greater confidence from which to inform women as to the importance for their baby of ensuring adequate vitamin D repletion during pregnancy, to minimise risk of later cardiovascular disease.Read moreRead less
Does Women's Nutrition During Pregnancy Influence Metabolic Health Of Their Children?
Funder
National Health and Medical Research Council
Funding Amount
$255,752.00
Summary
The occurrence of type 2 diabetes is increasing around the world, with the rising incidence among children and adolescents especially worrying. Widespread obesity has clearly contributed to this epidemic, but does not fully explain it. Diabetes develops over many years and obesity appears to exacerbate a pre-existing susceptibility. Our work focuses on understanding and preventing this initial susceptibility. Metabolic changes in the way the body produces and disposes of insulin, and responds to ....The occurrence of type 2 diabetes is increasing around the world, with the rising incidence among children and adolescents especially worrying. Widespread obesity has clearly contributed to this epidemic, but does not fully explain it. Diabetes develops over many years and obesity appears to exacerbate a pre-existing susceptibility. Our work focuses on understanding and preventing this initial susceptibility. Metabolic changes in the way the body produces and disposes of insulin, and responds to glucose, are seen much earlier in individuals who become diabetic. These metabolic defects are thought to be due, in part, to sub-optimal growth and development before birth (affecting the way the pancreas and liver function, for example). Poor nutrition before birth may be an important underlying cause. Animal studies reliably demonstrate that a poor quality diet of the pregnant mother can result in offspring that have impaired glucose tolerance and related metabolic problems. We now need to determine whether this occurs in humans. A limited amount of community-based research suggests this is possible. The balance between carbohydrate and protein in the mother's diet may be a key factor, and possibly the type of carbohydrate (high or low glycaemic). Weight before and during pregnancy could also be influential. We have been following a cohort of 500 children from before birth, through childhood. We collected detailed information on the mothers' diets during pregnancy. In this project, we plan to assess the glucose-insulin metabolism of the children at 8 years of age. We will then investigate whether diet of the mothers during pregnancy affects the metabolism of the children later on. Improving nutrition of pregnant women could lead to life-long improvement in metabolic health of the children. This study will contribute to the evidence-base about whether maternal diet is important, and give specific details about what kinds of changes are needed.Read moreRead less