Getting started with pre-eclampsia screening
One of PerkinElmer’s longstanding customers in Belgium answers questions on their experiences in setting up and implementing a pre-eclampsia screening program.
In starting a screening program for pre-eclampsia screening, what were the new laboratory needs?
There was no need for investment in instrument hard- and software or connections to the IT infrastructure; we were already using PerkinElmer tools, so we already had all instruments and connections to achieve useful analyzes to screen for pre-eclampsia. The only thing we had to install was a new app for the calculation of risk estimation.
With regard to the reporting infrastructure, we have always made our results communication as comprehensive as possible in the clinical report. For many years, the results of the three tests (for combined first trimester screening) were presented in the form of a table with the risks of trisomies 21 and 18, biochemical and combined. So we added a second table in which risk of early and late pre-eclampsia (before or after 34 weeks gestation) both anterior and posterior to the biochemical analyses is summarized.
We had absolutely no need for any training in the laboratory, the techniques for estimating the risk of trisomy being identical to those already used for many years! We needed to focus all our efforts on training gynecologic sonographers and obtaining a team of clinicians that can clearly explain the benefits and limitations of the test and perform ultrasound measurements (including Doppler uterine artery) and decision parameters according to international recommendations.
Please describe briefly how the screened patient is told about her screening result. Who talks to her and what advice is given?
It is the gynecologist who informs the patient of the test results. In general, this is at the routine visit after the combined first trimester screening. In case of an abnormal result, the patient is contacted by telephone and invited to an additional appointment during which we explain face to face the results and define additional treatment, for example, with acetylsalicylic acid.
How is your screening service communicated/marketed to other professionals and to the pregnant patients?
After gaining enough internal experience we have presented our data at many gynecological meetings. But we rely mainly on the large experience of our institution relating to pre-eclampsia; many doctoral theses, post doc and clinical research work has already been done on the topic here.
Can you offer any tips or guidance to others who are considering starting pre-eclampsia screening? What was easy? What surprises were there?
The establishment of this new screening really presents no difficulty for a laboratory and gynecology staff well familiar with aneuploidy screening. That said, the complexity lies in building the interest that will make clinicians want to use this new tool at their disposal, so there is certainly a great job of communication needed to demonstrate the usefulness of screening. From our side we look forward to seeing the results of the ASPRE study to confirm and allow extension of our policy of care for patients at risk.
No need for instrument investment when labs already perform combined first trimester screening
A laboratory’s instrumentation requirements for pre-eclampsia screening are basically similar to those for combined first trimester screening. For the biochemistry tests in prenatal screening (PAPP-A and free hCGβ), measurement platforms widely used include PerkinElmer’s AutoDELFIA® high throughput batch analyzer, the semi-automatic DELFIA® system based on the VICTOR™ plate reader and the DELFIA Xpress random access system. Since PlGF is available on all three of the platforms mentioned, for their users it is a simple matter to run this test at the same time and in the same way as the other two. As well as keeping the investment cost low, there is also then a major saving in time and time-related testing costs.
Emmanuel Bujold, Stéphanie Roberge
Aspirin for the prevention of pre-eclampsia
Over the last 30 years, there has been a huge controversy regarding the role of aspirin in the prevention of pre-eclampsia. We are now coming to the end of this journey that will hopefully end this debate.
In 1979, it was observed that women who had been taking aspirin during pregnancy were less likely to develop pre-eclampsia.(1) Following that observation, a French group decided to randomize women at high risk for pre-eclampsia and/or fetal growth restriction (FGR), mainly because of previous history, to receive aspirin 150 mg daily from 12 weeks gestation or no treatment.(2) They observed that aspirin reduced the risk of pre-eclampsia, FGR and perinatal death.
Following that study, more than 60 other randomized trials were performed, on more than 60,000 pregnant women. However, very few of them started the treatment in the first trimester, and they all used lower dosages (<150 mg) of aspirin, with contradictory results. In the meantime, new evidences was published regarding the high rate of aspirin resistance at dosage below 100 mg daily, (3) and that the optimal effect of aspirin, was when it was taken at bedtime.(4)
In 2010, our first meta-analysis provided evidence that aspirin could prevent most cases of pre-eclampsia in high-risk women when started before 16 weeks. (5) In addition, we showed that it was mostly the preterm forms of the disease (early onset before 34 weeks), that are typically associated with deep placentation disorders, that could be prevented.(6)
Sub-sequentially, we demonstrated that most of the large multicenter randomized trials failed to demonstrate any benefits of aspirin because they have been recruiting women too late in pregnancy(> 16 weeks) or because they were using a too small dose of aspirin (60 mg) that could have a decrease in significant benefits. (7)
Last month, we published our last meta-analysis, that included most large randomized trials, and we confirmed the dose-response effect of aspirin initiated in early pregnancy for the prevention of pre-eclampsia and FGR. (8) Based on those results, we believe that a minimum of 100 mg, and ideally 150 mg of aspirin taken at bedtime daily should be used for the prevention of pre-eclampsia and FGR.
"A group in Australia already started to use first-trimester screening combined with 150 mg of aspirin for targeted high-risk women: the rate of early-onset pre-eclampsia decreased by 75% in their population, based on a observational study" with continued results into clinical practice today (9)
It took more than 30 years to have a randomized trial that really aimed to confirm the impressive study of Beaufils et al. The ASPRE trial (10), a double blinded randomized control trial, lead by Leona Poon and Kypros Nicolaides, targeted a group of high-risk women identified in the first-trimester with an accurate screening algorithm; and evaluated the optimal dose of aspirin (150 mg) taken at bedtime for the prevention of the most logical outcome: preterm pre-eclampsia. We are confident that this thoughtfully designed trial will end the controversy and that all women around the world that could benefit from this very accessible prophylactic measure will be now provided the appropriate information and the best treatment in order to minimize risk of this condition in having an adverse outcome for their pregnancy.
References: (1) Crandon, Lancet, 1979 (2) Beaufils, Lancet, 1985 (3) Caron, J Obstet Gynecol Can, 2009 (4) Ayala, Chronobiol. Int. 2013 (5) Bujold, Obstet Gynecol, 2010 (6) Roberge, Fetal. Diagn. Ther. 2012 (7) Roberge, Am J Perinatol, 2016 (8) Roberge, Am J Obstet Gynecol, 2017 (9) Park et al. Ultrasound in Obstetrics and Gynecology Aug 2015 (10) O’Gorman et al. BMJ Open 2016 https://fetalmedicine.org/research/randomized-trials/aspre-1
Emmanuel Bujold, MD, MSc and Stéphanie Roberge, PhD are at Université Laval, Quebec City, Canada.