Academy of Diagnostics & Laboratory Medicine - Scientific Short

Is a single-tube multimarker assay a perspective test in improving the prognoses of preeclampsia?

Kaspar Ratnik and Maris Laan

Pregnancy represents an extra burden for the female organism and sometimes, the body cannot fully cope with it. Preeclampsia (PE) is a pregnancy-specific disorder characterized by a sudden new-onset hypertension with new-onset proteinuria that may rapidly develop any time after 20th gestational week (1). It affects about one in 20 pregnancies worldwide and can be life-threatening for the baby and mother. No corrective treatment is currently available and the only true cure of PE is a delivery. Even in developed countries it is one of the leading causes of maternal mortality and severe morbidities such as failure of liver, renal and cardiovascular systems, fetal prematurity and growth restriction. In long-term, PE is associated with increased maternal risk for cardiovascular disease and type II diabetes.

PE is considered a disease of placenta, caused by defective placental formation and/or its impaired functional capacity towards the end of pregnancy (1). Therefore, signs of placental malfunction have been the prime target to understand the etiology of PE and to identify early biomarkers detectable in maternal circulation before onset of the disease. Early risk alert enables timely consideration of PE preventive measures and upon disease onset, manage its complications under appropriate medical supervision. Therefore, developing screening tests and prediction algorithms for PE has been one of the key areas in maternal-fetal medicine over many years. Classically, the clinical predictive and diagnostic toolset for PE has been based on maternal medical history and routine monitoring of blood pressure and proteinuria. During recent years, prognostic tests based on placental biomarkers detectable in maternal serum have been introduced. Currently, one of the most applied tests is based on estimating the ratio of biomarkers sFlt-1 (soluble fms-like tyrosine kinase 1) and PlGF (placental growth factor), offered by several commercial companies. However, its performance is suboptimal as the PE detection rate is <75% and its accurate prognosis over the period longer than a month has been challenging (2).

Our team has developed an innovative Luminex® xMAP based single-tube multimarker assay for the simultaneous detection of six PE related biomarkers (sFlt-1, PlGF, ADAM12, sENG, PTX3 and leptin) in the sera of pregnant women (3). Combining biomarker measurements with exact gestational day and maternal weight at sampling generated a clinically effective test applicable in the 3rd trimester for accurate PE prediction up to 62 days after sampling. The prognostic yield of the new solution was 96.5% and reached Area Under Curve (AUC) 0.99 with sensitivity 100% and specificity 96.9%. When the same research samples were assessed in parallel using the sFlt-1/PlGF based test (Thermo Fischer Scientific, Hennigsdorf, Germany), correct PE prognosis was reached for only 73.7% of the analyzed pregnancy cases (AUC 0.87).

The developed multiplex test has several advantages for implementation in the clinical routine – well-standardizable performance, low required sample volume, short expected turnover times, maximized capacity and cost-effectiveness as all measurements are run in a single test-tube. The solution can be smoothly applied in any laboratory possessing the Luminex® xMAP or similar technology platform.

REFERENCES

  1. Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: Pathophysiology, Challenges, and Perspectives. Circ. Res. 2019;124:1094-1112
  2. Dragan I, Georgiou T, Prodan N, Akolekar R, Nicolaides KH. Screening for pre-eclampsia using sFlt-1/PlGF ratio cut-off of 38 at 30-37 weeks' gestation. Ultrasound. Obstet. Gynecol. 2017; 49:73-7.
  3. Ratnik K, Rull K, Hanson E, Kisand K, Laan M. Single-Tube Multimarker Assay for Estimating the Risk to Develop Preeclampsia. J Appl Lab Med., 2020; jfaa054, advance article May 15th, 2020.

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Fellows of the Academy use the designation of FADLM. This designation is equivalent to FACB and FAACC, the previous designations used by fellows of the National Academy of Clinical Biochemistry and AACC Academy. Those groups were rebranded as Academy of Diagnostics & Laboratory Medicine in 2023.