"Breakthrough in detection of pre-eclampsia may save lives of hundreds of babies" is the headline in The Independent, which goes on to say that this test could "save [the] lives of hundreds of babies every year".
Pre-eclampsia is a condition that affects some pregnant women, usually during the second half of pregnancy. It causes high blood pressure and protein in the urine. The only way to cure pre-eclampsia is to deliver the baby. In severe cases a pre-term birth is required, which can place a baby at risk.
Novel research has looked at the effectiveness of a new test for pre-eclampsia. The test measures the blood levels of a protein released by the placenta (placental growth factor, or PGIF) that is found in abnormally low levels in women with the condition.
The test was found to be highly accurate in detecting pre-eclampsia for women who were below 35 weeks of pregnancy. The study found that 96% of the women with pre-eclampsia were correctly identified. The test also reportedly produces results more quickly than existing methods – in as little as 15 minutes.
However, the test was less accurate in detecting pre-eclampsia in women who were over 35 weeks pregnant. It also wasn't as effective at correctly excluding women who didn't have the condition. This is of concern, as it could lead to unnecessary treatment.
The results of the study are encouraging, as improving the accuracy of diagnosis should reduce complications affecting birth and could potentially save lives. However, neither of these outcomes were looked at by the researchers in this study.
What is unknown is whether using this test would give any benefits compared with the standard methods currently used to diagnosis pre-eclampsia. Randomised controlled trials are required in larger groups to look at this.
The study was carried out by researchers from Kings College London and other UK universities and institutions. It was funded by the charity Tommy's, which funds research into pregnancy problems, and Alere, a global diagnostics and medical company that sells the test studied in this piece of research. Some of the researchers have previously worked for Alere as consultants. This potential conflict of interest was made clear.
The study was published in the peer-reviewed journal Circulation.
The story was mostly covered appropriately by the media. However, the headlines are exaggerated and misleading. It is not currently known whether the test could lead to improved outcomes for pregnant women and their babies, and so save lives. Further research is needed to see what impact this new test has on clinical outcomes.
This was a prospective diagnostic study investigating the accuracy of measuring blood levels of placental growth factor (PIGF) among women who presented with suspected pre-eclampsia at 20 to 35 weeks pregnant. PGIF levels increase during pregnancy, peaking at 26 to 30 weeks and reducing nearer to full-term pregnancy.
The researchers say that previous research has shown that PIGF levels are abnormally low in women with pre-eclampsia compared with women who do not have the condition, and is particularly low in women with severe pre-eclampsia.
They wanted to see if the diagnostic test could determine the need for early delivery of the baby as a result of high-risk pre-eclampsia.
This study was carried out across seven maternity units in the UK and Ireland. Women aged 16 years or older were included in the study if they presented with, or were referred for, symptoms or signs of suspected pre-eclampsia when they were between 20 and 40 weeks pregnant.
Symptoms or signs included:
Any women who already met the criteria for confirmed pre-eclampsia at the start of the study were not included.
The researchers wanted to see if a diagnostic test (the Triage PIGF Test) that measures blood levels of placental growth factor (PIGF) was effective. Test results were grouped into values that were considered "normal", "low" or "very low" based on PIGF levels.
The main outcome was correctly predicting pre-eclampsia requiring delivery of the baby within two weeks of the test. Diagnosis was confirmed by two senior clinicians using standard diagnostic methods, including testing for high blood pressure and protein in the urine.
Of 625 women included in the study, 346 (55%) developed confirmed pre-eclampsia.
When the Triage PIGF test measured "low" PIGF concentrations, it had a high level of accuracy in identifying which women presenting with suspected pre-eclampsia prior to 35 weeks were in a high-risk group. This was defined as the women likely to need to deliver their baby within two weeks as a result of the condition.
The sensitivity of the test – that is, the number of women with pre-eclampsia who were accurately diagnosed – was 96% (95% confidence interval [CI] 89-99%).
The test was less accurate among women with a more advanced pregnancy (gestational ages of more than 35 weeks). Seventy per cent of women with pre-eclampsia between 35 and 36 weeks of pregnancy were correctly identified, further reducing to 57% of women with pre-eclampsia at 37 or more weeks of pregnancy.
However, the specificity of the test – the ability of the test to correctly exclude women who did not have pre-eclampsia – wasn't as good. Specificity was 55% below 35 weeks (95% CI 48 to 61%). This means that 45% of women with healthy pregnancies below 35 weeks were wrongly identified by the test. However, there appeared to be an inverse mirroring effect.
While the accuracy of the test for identifying women with pre-eclampsia went down after 35 weeks, the reliability of the test for correctly excluding women without pre-eclampsia actually improved after 35 weeks (specificity increasing to 64% between 35 and 36 weeks, and 77% after 37 weeks).
The Triage PIGF test was found to be more predictive of the need for delivery than other methods commonly used to diagnose pre-eclampsia, either used alone or in combination.
The authors conclude that PIGF testing presents a realistic and innovative addition to the management of women with suspected pre-eclampsia, especially for those that present before their full pregnancy term.
In describing the study findings, Professor Andrew Shennan, who led the study, is reported in The Independent as saying the new test represented "the most important advance" in obstetrics that he had seen in 20 years of working in the specialty.
The researchers say this is the largest and first prospective study to look at PIGF levels in women with suspected pre-eclampsia.
Overall, this study provides early positive findings of a diagnostic test for use in pregnant women with suspected pre-eclampsia. The researchers point out that it is known that plasma PIGF levels normally decline in the latter part of the third trimester (weeks 29 to 40), which reduces the PIGF test performance after 35 weeks gestation.
All new screening and diagnostic tests need to weigh up the benefits against the risks. The benefits of the test could include earlier detection and treatment of pre-eclampsia, which could ultimately lead to the most important outcome – improved pregnancy and birth outcomes for mother and baby.
Possible risks of the test as it currently stands include failure to detect women with pre-eclampsia who are above 35 weeks of pregnancy, and incorrectly flagging a large proportion of women with healthy pregnancies as having possible pre-eclampsia.
This could lead to a lot of unnecessary concern, further testing and monitoring. The cost of unnecessary treatment could offset any savings provided by using the blood test.
Therefore, deciding where the cut-off lies for the protein blood levels and at what stage of pregnancy the test should be used would need to be carefully considered.
A fine balance needs to be established to maximise the correct identification of women with pre-eclampsia, while reducing the number of women with healthy pregnancies who are picked out. This is easier said than done.
The ultimate aim of such a blood test would be to see whether it improves pregnancy and birth outcomes for mother and baby. To look at this, randomised controlled trials are now required to draw further conclusions about how well the test performs, and look at whether it improves outcomes compared with the methods currently used to diagnose pre-eclampsia.