Clinical Performance of The sFlt-1/PlGF Test For The Prediction of Preeclampsia Among Asymptomatic and Symptomatic Pregnant Women in Estonia: A Nested Case-Control Study

Abstract

Background: Pre-eclampsia (PE) is a pregnancy complication manifesting as new-onset hypertension and other maternal organ dysfunction after 20th gestational weeks. The study aimed to evaluate the applicability and limitations of the maternal serum soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) test in a clinical setting for the prediction of PE among symptomatic and asymptomatic pregnant women. There is limited knowledge on the performance of this test in asymptomatic women and thus, its value for screening purposes to predict PE is not confidently settled.Methods: The study group comprised of 215 patients developing either PE (n=29) or gestational hypertension/proteinuria (n=22) or representing controls (n=164). Patients had been sampled within 180-291 gestational days in the presence (symptomatic, n=31) or absence (asymptomatic, n=216) of PE-alerting symptoms. Serum samples collected during prospective cohort study ’Happy Pregnancy’ at the Women’s Clinic, Tartu University Hospital, Estonia, and they were analyzed using the BRAHMS sFlt‑1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio test (Thermo Fisher Scientific, Henningdorf, Germany). The results were interpreted using recommendations by Stepan et al 2015 Ultrasound Obstet Gynecol. Results: The assignment of ’Rule-out PE’ (sFlt-1/PlGF ratio <38) had a negative predictive value >99% for four weeks for both asymptomatic and symptomatic women. Among 29 sera assigned to the ‘Rule-in PE’(sFlt-1/PlGF >85/110), only 18 pregnancies (62.1%) eventually developed PE. For four weeks period, the overall PE detection rate was 83% for asymptomatic and 50% for symptomatic pregnancies. Pregnancies receiving false predictions of PE risk based on sFlt-1/PlGF ratio represented either cases with an isolated small-for-gestational age fetus or blood sampling after 34 gestational weeks.Conclusions: The first study in Estonian patients confirmed high reliability of the proposed cut-off value sFlt-1/PlGF <38 as a “Rule-out PE” cut-off value for two weeks in both symptomatic and asymptomatic pregnancies. The test’s limitation in our clinical setting appeared to be high false positive rate in pregnancies with other placental pathologies than PE or due to physiological increase in sFlt-1/PlGF in late gestation. For correct prediction of PE, more specific recommendations are urgently needed for the application and interpretation of the test in routine clinical practice.