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Identification of pre-eclampsia - eclampsia susceptibility gene[s]

Prof Shaun Brennecke, Prof Eric Moses, Dr Phil Melton, Prof John Blangero

Pre-eclampsia (PE) is the most common serious medical disorder of human pregnancy. Particularly in their first pregnancy, pregnant women can suffer from high blood pressure, kidney dysfunction leading to leakage of protein into the urine, swelling of hands, feet and face, and, in severe cases, dizziness, headaches and difficulties with vision. This condition is called pre-eclampsia. If left untreated, it can lead to convulsions and other life-threatening problems for both mother and baby. Pre-eclampsia only occurs when a woman is pregnant, and currently, the only cure for it is to end the pregnancy, even if the baby is not yet ready for birth.

In Australia, mild pre-eclampsia occurs in 5-10% of pregnancies and severe pre-eclampsia in 1-2% of pregnancies. Pre-eclampsia and complications associated with this condition account for 15% of direct maternal mortality and 10% of perinatal mortality. Pre-eclampsia is the indication for 20% of labour inductions and 15% of Caesarean sections. It also accounts for 5-10% of preterm deliveries. Worlwide, pre-eclampsia and its complications kill many tens of thousands of women and their babies each year.

There is compelling evidence that in many cases pre-eclampsia has a genetic basis, albeit a complex one. With funding support from the National Institutes of Health in the USA, we are undertaking a comprehensive genetic analysis of Australian families affected by PE and have found evidence for a susceptibility' region on chromosome 2. We are now focussing our efforts on this chromosome 2 region to identify the gene(s) responsible.

The potential significance of this project is threefold. Firstly, when the gene is identified, the production of a clinical test both for the early (pre-pregnancy) detection of women at risk and for the actual diagnosis of pre-eclampsia in cases of clinical uncertainty would become feasible. Secondly, such a test, in turn, would facilitate early preventive treatment and thereby improve the outcome for mothers and babies. Thirdly, the knowledge gained would guide further studies on the causes of pre-eclampsia and aid in the development of new treatments for it.

The role of placental factors in the development of pre-eclampsia

Prof Shaun Brennecke, Dr Clare Whitehead, Ms Janet Stevenson, Dr Bill Kalionis

Pre-eclampsia is the most common, serious pregnancy medical disorder of human pregnancy. It has a significant impact on the health and wellbeing of mothers and their babies. It involves pregnancy-induced maternal hypertension and protein in the urine. Its cause is not well understood. The aim of this project is to clarify the cellular and molecular mechanisms that result in this pregnancy disorder. Evidence indicates that during pre-eclampsia the placenta experiences cellular stress and releases factors into the maternal circulation that cause widespread inflammation. This project is investigating the effects of a number of candidate factors on the functions of endothelial cells that line the inside of maternal blood vessels. Placental factors that are at increased concentration in maternal blood with pre-eclampsia, and that cause inflammation of maternal endothelial cells, may be targets for future therapeutic interventions to better manage pre-eclamptic pregnancies.

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