PEARLS
Preeclampsia Research Laboratories

July 2004 newsletter

PEARLs discovery links pain killer medication with blood pressure

Dr Angela Makris recently appeared at the Science Show in Sydney and presented an important recent discovery of Pearls research. Dr Makris has found that the use of certain types of pain killer medication after caesarean delivery of babies are implicated in the worsening of the mother's blood pressure at that time. This may have contributed to a seizure in some of these women.

This critical discovery is important in the treatment of women affected by preeclampsia because even after the delivery for a short time they are still at risk of having problems related to their blood pressure.

The New South Wales Department of Health has adopted the research in providing its advice about medications which can be used after caesarean delivery. In addition PEARLS is currently designing further studies to determine whether such medications are likely to impact on mothers which might not otherwise be thought to be at risk.

PEARLS Laboratory

We are in our second year in the Heart Research institute and are clearly at home there. The current projects have broadened to include some studies of women and their responses to pain relief medications in pregnancy as well as continuing with our major work following the progress of our mothers who have generously donated their time and blood tests to our projects. We hope the results of these studies will enable us to improve the tests we can use to help define the women who have preeclampsia and find out those at increased risk.

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.

Project 3. 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 4. Intravenous anti-hypertensive therapy in preeclampsia

Investigators: Drs Angela Makris. Annemarie Hennessy, Adrian Gillin, Andrew Child, Robert Ogle

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 5. 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 6. 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

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.

PEARLS Contributes to facts and figures

Charlene Thornton has submitted her Masters thesis this month, but more importantly has had a major publication in the ANZ Journal of Obstetrics and Gynecology showing that we need to improve our systems of reporting the severity of high blood pressure in pregnancy, particularly if we are to decide with mothers and their babies require additional help in their pregnancy. We also think that these definitions are essential to help work out which women are at risk of blood pressure problems in later life.

PEARLS drug testing

Dr Bei XU is examining the effects of routinely used blood pressure medication on placental function. These studies may give us some insights into the potential for some medications to be more beneficial than others used. Bei has also looked at the effects of steroids which are used to help babies lung mature if a premature birth is likely. These medications DO have an effect on some of the functions of the placenta and we may well need to take these into account when we are deciding on safe and effective treatments for mother and their babies. Angela has also looked at some unlikely naturopathic remedies and their effects on placental function - watch for advice on garlic in pregnancy!!

Funding

As always the amazing support of the PEARLS MOTHERS and FRIENDS has kept us going. The contributions of our recent PEARL earring raffle contributed an amazing $4500 to the laboratory and a huge thank you goes to Raphaël Jewellers.

Up coming events include a JAZZ Winter Dinner at the Bambini Trust Cafe, Elizabeth Street Sydney, which is likely to be a annual event - given how quickly the tickets have been snapped up! A big thank you to Michael and Angela Potts for their amazing generosity and to Amanda Davidson for pulling this all together.

We are having our Spring Cocktail party at the Museum of Sydney, on the 10th of September and if you are interested in having a bubbly wine with us we can be contacted on 0418273658 or via our website www.preeclampsia.org.au (Tickets $125 per head)

Tickets are selling for our Beautiful PEARLS Necklace kindly donated by Angela Makris and Charlene Thornton and beautifully handcrafted by Raphaël of Raphaël Jewellers, The Strand Arcade, Sydney

Our Sponsors list grows ever bigger and they can be found on the website.

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