National Institute of Clinical Excellence (NICE) has published new guidelines this month on the diagnosis of preeclampsia. Four new index tests have now been approved to aid in diagnosis, along with clinical judgement and routine testing.
Preeclampsia is a complication of pregnancy which is characterized by high blood pressure, loss of protein in the urine and sometimes swelling of the hands and feet. The condition usually develops after 20 weeks of pregnancy, and it might even occur earlier in rare cases. If untreated, preeclampsia can lead to potentially life-threatening complications including eclampsia, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), disseminated intravascular coagulation, stroke, or organ dysfunction. Preeclampsia is also dangerous for the developing fetus as it can cause growth restriction, pre-mature birth and intra-uterine death.
Up till now, a combination of blood pressure measurements, urinary protein measurements and clinical judgements have been used to diagnose preeclampsia. However, this recent review of research carried out by the NICE in the UK has approved four more blood tests to help diagnose preeclampsia. The tests may also be used in patients of gestational hypertension, to rule out preeclampsia.
All these tests are intended to be used along with clinical judgement and other diagnostic tests to diagnose preeclampsia.
1) The Triage PIGF Test
The first test is called the triage PIGF test and has been developed by Alere International. It measures placental growth factor (PIGF), which is a protein involved in the development of new blood vessels in the placenta. Even though the exact cause of preeclampsia is not known, a viable theory is that new placental blood vessels are formed abnormally and have a narrower lumen which increases resistance to blood flow through them, hence causing an increased blood pressure to overcome this resistance. A normal placenta releases high levels of PIGF, which can be measured in the blood. Low levels of PIGF indicate abnormal placental formation. The test is recommended for use in pregnant women between 20-34 weeks plus six days of gestation.
2) Elecsys Immunoassay sFlt-1/PIGF Ratio
The second test is called the Elecsys immunoassay sFlt-1/PIGF ratio. It uses a ratio between two proteins, PIGF and another substance called FMS‑like tyrosine kinase‑1 (sFlt‑1). sFlt-1 is a protein that is thought to disable other proteins associated with blood vessel formation, such as PlGF. In women who develop preeclampsia, the levels of sFlt‑1 are higher than those seen in a normal pregnancy. The ratio may also be used to help predict pre‑eclampsia, eclampsia and HELLP syndrome in the short term (1 week). This test has been developed by Roche diagnostics.
3) DELFIA Xpress PlGF 1‑2‑3 Test
This test has been developed by Perkin Elmer, a leading biotechnology company. It is a quantitative analysis of PIGF, but measures a wider range of values as compared to the triage PIGF test. The processing time for the test is 30 minutes.
4) BRAHMS sFlt‑1 Kryptor/BRAHMS PlGF Plus Kryptor PE Ratio
Thermo Fisher Scientific has developed their own instrument, the BRAHMS Kryptor compact plus analyser which measures sFlt-1 and PIGF and then uses the sFlt-1/PIGF ratio to arrive at a test result. Reference ranges for each of the assays and the sFlt‑1/PlGF ratio are given in the company instructions, and the company recommends that individual laboratories should validate these ranges or establish their own reference ranges before use.
NICE has approved the above tests after carrying out extensive research of its own, with regard to their efficacy and cost-effectiveness. A total of 12 publications and four research studies were included in the NICE review. According to the review, all the above tests had more than 90% sensitivity in roughly 80% specificity in predicting preeclampsia.
To determine cost effectiveness of these new tests, another review was conducted by NICE. This involved four full studies which specifically analysed these tests for their cost. That is, they focused on potential savings and did not formally evaluate health outcomes of the mother or baby.
Cost reductions per patient compared with standard clinical assessment were £2,896 for the Triage PlGF test and £2,488 for the Elecsys immunoassay sFlt‑1/PlGF ratio. These cost reductions are a significant benefit of these tests, especially when compared to the cost of the tests themselves. The cost of a single Triage PlGF test is £40. The list price for a single Elecsys immunoassay sFlt‑1/PlGF ratio is £57.23.
The BRAHMS sFlt‑1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio and the DELFIA Xpress 1‑2‑3 PlGF test were not included in the cost analysis study, as there was insufficient data on them.
However, as all these tests are relatively new, more clinical studies are needed for validation of their diagnostic accuracy, and to determine the frequency and appropriate intervals for repeat testing if needed. It is hoped in the long term that these tests will help in a faster and more accurate diagnosis of preeclampsia, so that adequate treatment may be started for these patients as soon as possible.