A new and necessary test

COMMERCIAL PROFILE - SCIENCE FOUNDATION IRELAND:A NEW TEST which can accurately predict which pregnant women will develop pre-eclampsia before symptoms arise could be available within the next five years thanks to the work of a Science Foundation Ireland funded research team led by professor Louise Kenny in University College Cork.

Pre-eclampsia is a life-threatening condition characterised by high blood pressure and elevated protein in the urine which usually does not present itself until the second half of pregnancy.

Kenny is professor of obstetrics and gynaecology at the Anu Research Centre at UCC and a consultant obstetrician and gynaecologist at Cork University Maternity Hospital.

“Pre-eclampsia is a common condition,” she explains. “It affects about 2 per cent of pregnant women and is a leading cause of death of both pregnant mothers and their unborn babies – particularly in the developing world. This is a devastating condition, not only because it affects such young people but because we don’t fully understand it and therefore we don’t have an effective treatment.”

Indeed, there is currently no cure other than the delivery of the baby often weeks or months prematurely for this life -threatening condition that affects four million women every year.

Rates vary from two per cent of pregnant women in Europe and Canada to four per cent in the US and up to 10 per cent in the developing world. The World Health Organisation estimates that 100,000 to 200,000 women die each year as a direct cause of pre-eclampsia. Currently there is no predictive test for the condition despite the fact that it is thought to begin in early pregnancy with defective development of the placenta.

This is set to change as a result of the work of Kenny and her international team of scientists and physicians which has identified 14 metabolites – sugars, fats or amino acids – in blood that point to pre-eclampsia risk early in pregnancy. The metabolites have a detection rate of 90 per cent and a false positive rate of around 21 per cent to 24 per cent, making them more accurate than current pregnancy screening for Down’s syndrome.

The researchers are now trying to simplify the technology to develop a single blood test that will be cheap and readily accessible to hospitals everywhere.

“The way we imagine the test working is that in early pregnancy a woman will have the blood test and that will predict if she is at risk or not. It is our ambition that we will have the test available in five years,” says Kenny.

The breakthrough was made possible by the Screening for Pregnancy Endpoints (Scope) trial which is an international trial of approximately 7,000 women with first-time pregnancies and which aims to predict and prevent the major diseases of late pregnancy.

“Everything we know about this condition suggests women do not become sick and present with pre-eclampsia until late in pregnancy, but the condition originates in early pregnancy,” Kenny points out.

“To develop effective treatment and prevention strategies, our ultimate goal, we need to be able to start treatment in early pregnancy. We need to be able tell who is at risk and who is not.”

But that is easier said than done.

Kenny’s team at UCC had already been working on this problem but with limited success before they became involved in the Scope trial.

“Only two per cent of women develop pre-eclampsia and you only find out which ones do in the later stages of pregnancy. This means if you are looking for markers at an early stage you have to study 100 women just to get two cases of pre-eclampsia. The Scope trial gave us access to the number of pregnant women needed for our study.”

Kenny and her team have been engaged in a classic piece of detective work. It has been a case of working backwards from the point where women develop the condition and analysing blood tests taken during the earlier stages of their pregnancies to identify any common markers or metabolites which might be present in their samples but not in those of women who did not go on to develop pre-eclampsia.This naturally requires a study involving a large number of women and Scope facilitated this. The study had two parts.

First, the researchers identified 60 women in the trial who had developed pre-eclampsia. The women were mostly from New Zealand and about 30 years of age. The team then examined the samples which had been taken from the women at 15 weeks gestation – long before there was any indication that they would develop the condition. These samples were compared with those of 60 other women of the same age, ethnicity and body-mass index.

Using a combination of sophisticated emerging technologies and data analysis Kenny and her team detected 14 simple metabolites which have a high accuracy for predicting which women are at risk of developing pre-eclampsia in later pregnancy.

The study’s second phase validated the initial findings in an entirely different group of women in Adelaide, Australia. These women were younger, with an average age of 22 to 23 and were ethnically more diverse compared to the predominantly Caucasian group in New Zealand and 39 women subsequently developed pre-eclampsia later after the early test. There were 40 matched controls.

This breakthrough study was carried out by researchers from University College, Cork, Ireland, University of Manchester UK, University of Auckland, New Zealand, University of Adelaide, Australia and University of Alberta, Canada, which underlines the international dimension of the study.

The Irish team is funded by a combination of Science Foundation Ireland and the Wellcome Trust while the Health Research Board Ireland funds the Irish participation in the Scope study.

The benefits of the new test, when it becomes available, will be profound. In the first instance, it will mean that mothers who are likely to develop pre-eclampsia will be able to avail of much higher quality of care thanks to the resources that will be saved.

“At the moment our whole system of ante-natal care is aimed at detecting pre-eclampsia,” Kenny explains. “Pregnant women go for regular tests where they have their blood pressure taken, their urine tested and their tummies felt all to detect pre-eclampsia. The cost of this is enormous. If we are able to predict accurately who will develop pre-eclampsia, ante-natal can be tailored to meet the needs of those women at most risk.”

There is also the prospect of the development of new treatments for the condition. “There are some really exciting and innovative therapies in the pipeline,” she points out. “But the risk of giving drugs to pregnant women means that you will only be able to use these if you are reasonably sure that they will indeed go on to develop pre-eclampsia.”

This is the nub of the issue. Pre-eclampsia is actually present in early stage pregnancy but does not present itself until later stages when it is too late for any therapeutic intervention bar the delivery of the baby. There is no case for administering drugs to every pregnant woman on the basis that she has a one in 50 chance of developing the condition.

However if there was a 90 per cent or greater chance, the view would probably be a very different. The advent of a test which could give that accuracy of prediction will almost certainly accelerate the development of such new therapies and could eventually lead to far better outcomes for women who develop the condition.