Single-Tube Multimarker Assay for Estimating the Risk to Develop Preeclampsia

Ratnik, Kaspar; Rull, Kristiina; Hanson, Ele; Kisand, Kalle; Laan, Maris

doi:10.1093/jalm/jfaa054

Cited by 4 publications

(12 citation statements)

References 34 publications

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“…19 As a solution, inclusion of additional biomarkers has been suggested to improve the prediction accuracy, especially close to term. 20,21 Another scenario behind increased sFlt-1/PlGF ratio in asymptomatic women is fetal growth restriction (FGR) and other placental syndromes, such as premature birth, intrauterine fetal death, abruption of placenta etc. 22,23 Remarkable proportion of adverse maternal and neonatal outcomes among patients with false positive test for PE taken at mid-pregnancy has also been pointed out by Black et al 24 In concordance, more than third of false positive cases in our study suffered from SGA or fetal distress.…”

Section: Discussionmentioning

confidence: 99%

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

Hanson

Rull

Ratnik

et al. 2021

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

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

Hanson

Rull

Ratnik

et al. 2021

Preprint

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“…Late pregnancy serum samples of these 53 cases (28 PE, 206–275 g days; 31 controls, 210–274 g days) have been utilized in our recent study reporting PE prediction models based on 6PLEX assay measurements of late pregnancy serum samples ( 15 ). Two serum samples (one PE and one control, 182 and 180 g days, respectively) from this seminal publication were reallocated in this study to the mid-pregnancy sample set, as more appropriate.…”

Section: Methodsmentioning

confidence: 99%

“…Gestational days are presented as mean ± standard deviation and median (range). The Mann-Whitney U-test for non-categorical variables was applied to compare biomarker levels between groups, * denotes P < 0.05 and ** P < 0.0001. a Data from the study developing PE prognosis models based on 6PLEX assay measurements of late pregnancy serum samples (15). ADAM12, disintegrin and metalloproteinase domain-containing protein 12; PlGF, placental growth factor; PTX3, pentraxin-3; sENG, soluble endoglin; sFlt-1, soluble fms-like tyrosine kinase-1.…”

Section: Statistical Analysis and Pe Prediction Algorithm Developmentmentioning

confidence: 99%

“…Combining 6PLEX measurements of serum samples collected in the second half of pregnancy with gestational age and maternal weight at sampling generated a clinically applicable and effective prediction formula for PE development regardless of gestational age at its clinical manifestation. The new solution exhibited superior prognostic yield compared to the currently used sFlt-1/PlGF ratio in the diagnosis confirmation of symptomatic women in late pregnancy (96.5% vs. 73.7%) (15,16).…”

Section: Introductionmentioning

confidence: 95%

“…We have recently developed an innovative, single-tube multimarker 6PLEX assay for the Luminex ® xMAP platform to measure simultaneously six PE-related biomarkers in the sera of pregnant women, namely, soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), soluble endoglin (sENG), leptin, disintegrin, and metalloproteinase domain-containing protein 12 (ADAM12), and Pentraxin 3 (PTX3) ( 15 ). Combining 6PLEX measurements of serum samples collected in the second half of pregnancy with gestational age and maternal weight at sampling generated a clinically applicable and effective prediction formula for PE development regardless of gestational age at its clinical manifestation.…”

Section: Introductionmentioning

confidence: 99%

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Novel Early Pregnancy Multimarker Screening Test for Preeclampsia Risk Prediction

Ratnik

Rull

Aasmets

et al. 2022

Front. Cardiovasc. Med.

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Preeclampsia (PE) is a common pregnancy-linked disease, causing preterm births, complicated deliveries, and health consequences for mothers and offspring. We have previously developed 6PLEX, a multiplex assay that measures PE-related maternal serum biomarkers ADAM12, sENG, leptin, PlGF, sFlt-1, and PTX3 in a single test tube. This study investigated the potential of 6PLEX to develop novel PE prediction models for early pregnancy. We analyzed 132 serum samples drawn at 70–275 gestational days (g days) from 53 pregnant women (PE, n = 22; controls, n = 31). PE prediction models were developed using a machine learning strategy based on the stepwise selection of the most significant models and incorporating parameters with optimal resampling. Alternative models included also placental FLT1 rs4769613 T/C genotypes, a high-confidence risk factor for PE. The best performing PE prediction model using samples collected at 70–98 g days comprised of PTX3, sFlt-1, and ADAM12, the subject's parity and gestational age at sampling (AUC 0.94 [95%CI 0.84–0.99]). All cases, that developed PE several months later (onset 257.4 ± 15.2 g days), were correctly identified. The model's specificity was 80% [95%CI 65–100] and the overall accuracy was 88% [95%CI 73–95]. Incorporating additionally the placental FLT1 rs4769613 T/C genotype data increased the prediction accuracy to 93.5% [AUC = 0.97 (95%CI 0.89–1.00)]. However, 6PLEX measurements of samples collected at 100–182 g days were insufficiently informative to develop reliable PE prediction models for mid-pregnancy (accuracy <75%). In summary, the developed model opens new horizons for first-trimester PE screening, combining the easily standardizable 6PLEX assay with routinely collected antenatal care data and resulting in high sensitivity and specificity.

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Predictors of preeclampsia. Screening and prophylaxis in the I trimester of pregnancy

2021

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Aim. To examine the current state of the problem of the prediction of preeclampsia in early pregnancy. Materials and methods. The article provides an overview of publications based on search results in electronic resources PubMed, Elibrary, EMBASE and Google Scholar. Results. The currently known predictors of preeclampsia can be divided into biochemical and hemodynamic. A number of markers demonstrate prognostic value already in the early stages of gestation. To predict preeclampsia, algorithms are created. They include various combinations of its predictors and maternal risk factors. Conclusion. Prediction of preeclampsia is gradually moving from theory to practice. The instruments of its early forecasting before the gestational age of 14 weeks 6 days are becoming available. That opens up opportunities for targeted and timely prevention of preeclampsia.

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Single-Tube Multimarker Assay for Estimating the Risk to Develop Preeclampsia

Cited by 4 publications

References 34 publications

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

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

Novel Early Pregnancy Multimarker Screening Test for Preeclampsia Risk Prediction

Predictors of preeclampsia. Screening and prophylaxis in the I trimester of pregnancy

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