PEARLS
Preeclampsia Research Laboratories
Preeclampsia researchProfessor of Medicine, University of Western Sydney |
 |
Professor Annemarie Hennessy is coordinating an investigation of the pathogenesis of preeclampsia. Our research projects are designed to address the essential goal in preeclampsia; prediction of disease susceptibility by early pregnancy testing.
The project is examining the role of placental pathology in maternal vasoconstriction and the contribution of the maternal tolerance of the feto-placental unit to the development of the placenta. This study involves the use of molecular techniques and protein studies of pathophysiology in humans. This unit has contributed significantly to understanding the mechanisms of normal physiological (particularly cardiovascular) adaptation to pregnancy. Ongoing studies are examining the physiological consequences of alterations at the materno-placental interface.
Further collaborative research with the clinical units at Nepean Hospital, St George Hospital, and Royal North Shore Hospital are designed to examine the relationship between vascular events in pregnancy and later life cardiovascular disease. Coordinated prospective clinical trials with the aim of predicting preeclampsia are currently under-way.
There is ample opportunity to be involved in clinical preeclampsia research at a large multidisciplinary tertiary referral centre. Further, laboratory studies at all levels are available in a large teaching hospital that offers access to a wide range of state-of-the-art techniques.
Project 1: Cytokine abnormalities in Preeclampsia - a loss of maternal tolerance
Investigators - Annemarie Hennessy, Dr Andrew Child, Dr Robert Ogle Dr Angela Makris, Dr Bei Xu.
This study involves the assessment of maternal and placental immune status at the time of delivery. Markers of maternal anti-fetal immunity have been identified in the placental bed and placenta at term delivery. The cellular responses of the uterus to the placental invasive cells is being examined. The active role of the placenta in modifying this uterine response is abnormal in preeclampsia with a decrease in the ability to induce a passive maternal response. The timing and relevance of these changes in the early prediction of the disease will be determined.
Project 2: Prediction of pregnancy outcome by the early maternal immune response to pregnancy
Investigators - Dr Angela Makris, Annemarie Hennessy,Dr Robert Ogle, Dr Alec Welsh, Charlene Thornton, Dr Janet Vaughan, Dr Andrew Child
Tissue study: using chorionic villous sampling the placenta is scored for cytokine activity reflecting tolerance of the placental unit. The findings are being correlated with pregnancy outcome. It is envisaged that alterations of the early placental responses may well determine the depth and sophistication of placental development, allowing a normal pregnancy outcome if fully realized. Dr Robert Ogle is also examining the importance of Free fetal DNA in this context.
Project 3: Inhibition of Placental invasion
Investigators - Angela Makris , Annemarie Hennessy, Phillipa Ramsey.
The hemodynamic implications of altering placental blood flow and protein synthesis is studied in early pregnancy. Monoclonal agents are used to inhibit important placental proteins at a critical time in pregnancy and the local and systemic responses are examined. The fetal growth characteristics and blood flow studies are serially performed using non-invasive techniques. Other studies involve the reduction of placental blood flow and are examining the responses elicited in the placental bed.
Project 4. Placental angiogenesis in preeclampsia
Investigators: Alec Welsh, Angela Makris Annemarie Hennessy, Bei Xu
Although poor blood flow to the uteroplacental unit has been postulated to be the cause of "preeclampsia" there is little direct evidence of a hypoxic response by the placental or maternal tissues at this locations. This study aims to determine the presence of hypoxic responses at the time of delivery in preeclampsia compared to normal pregnancy.
Project 5: Intravenous anti-hypertensive therapy in preeclampsia
Investigators: Dr Angela Makris. Annemarie Hennessy, Adrian Gillin, Andrew Child.
Randomized clinical trials are underway to ascertain the benefit of one IV treatment over another. Data on patients with severe preeclampsia (hypertension and proteinuria in pregnancy) are routinely treated with either hydralazine or diazoxide, both peripheral vasodilators to good effect. However, the treatment outcomes of maternal illness and fetal well-being as well as the caesarean section rate on these drugs has not been determined in our unit. This study aims to define the best treatment for patients with preeclampsia.
Project 6. Antihypertensives and their effect on placental and vascular functions
Investigators: Dr Bei Xu, Annemarie Hennessy, Andrew Child.
The effects of agents used to treat maternal hypertension are being examined for their effects on placental protein production and immunological function. There are no current studies which have investigated the direct effects of these drugs on placental function. There are some clinical studies which suggest that certain agents are more important in causing growth restriction in the babies than other drugs. We are investigating where these effects are mediated by the placental changes.
Project 7. Non-steroidal antiinflammatory agents and post-partum hypertension
Investigators: Dr Laura Baines, Dr Stephen Lord, Dr Brenden Orr, Dr Bill Lewis, Dr Robert Ogle, Dr Alec Welsh, Dr Ian Douglas, Angela Makris, Charlene Thornton, Annemarie Hennessy, Adrian Gillin, Andrew Child.
A randomized clinical trial has recently been approved by Canberra to investigate whether non-steroidal pain killers used after routine caesarean section delivery are implicated in causing high blood pressure after pregnancy. This unit has recently identified a potentially deadly increase in blood pressure in women who already have elevated blood pressure. These events run the risk of damaging the blood vessels and causing longterm damage to the mother. This study will compare an old fashioned non-steroidal treatment with a more modern form of the drug and compare that with placebo. Women will be given adequate pain relief in the form of other medication thought not to be related to increased blood pressure. We are indebted to Welsh Allen for the donation of precious blood pressure monitoring machines and to the Pharmacology Department of the RPA Hospital who have been instrumental in setting up the study. We are also grateful for the guidance of the NHMRC Clinical Trial Centre, at Camperdown for trial design and randomization stratification.
Project 8. The effect of acute preeclampsia on cardiac function
Investigators: Dr Lisa Simmons, Assoc Prof Hennessy
Further investigation of the effects of preeclampsia on regional cardiac blood flow will be undertaken by Lisa Simmons whose landmark work has shown the close relationship between placentas dysfunction and blood supply to the baby.
Project 9. Clinical Outcomes for Preeclampsia and other hypertensive diseases in pregnancy
Investigators: Charlene Thornton, Assoc Prof Annemarie Hennessy, Prof David Henderson Smart, Dr Andrew Child, Dr Robert Ogle.
Our capacity to determine whether women are at long term risk of future cardiovascular disease is only as good as out ability to define the extent of hypertension in their pregnancy. Charlene Thornton has identified the need for accurate data recording to achieve this and has developed clinical indicators where outcomes can be improved for mother and babies by identifying which factors in the management of these ladies which are amenable to change. This study may lead to an improved ability to directly compare outcomes between hospital and states, to determine the best possible care for our mothers and the least risk to their future cardiovascular health.
Copyright Professor Annemarie Hennessy: email for permission to reproduce material on this site
Site under development: email webmaster with suggestions or queries