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
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.
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
Understanding The Biology Of Pregnancy To Prevent Morbidity And Mortality
Funder
National Health and Medical Research Council
Funding Amount
$422,746.00
Summary
Progress in the care of the unborn baby, and thus optimisation of life-long health, will only come with a greater understanding of the fundamental processes that underlie pregnancy. My research is aimed at saving babies lives and reducing the long-term burdens (health, emotional and economic) of major perinatal conditions. I am uniquely placed to carry out this research, using the research tools I have developed to deliver real outcomes that will change clinical practice
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
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.
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
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.
Creatine Supplementation In Pregnancy: Utilising Cells’ “Built-In” Energy Buffering System
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Through pregnancy, the placenta transfers oxygen and nutrients from the mother to the baby. When a placenta doesn’t function properly a baby’s health is compromised. This can lead to morbidity or death. Creatine is the “back-up generator” of all cells and could help the failing placenta increase nutrient and oxygen delivery to the baby. This study will develop creatine as a potential new therapeutic, to improve the survival of babies of complicated pregnancies.
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.