Use of the sFlt-1/PlGF ratio to rule out preeclampsia requiring delivery in women with suspected disease. Is the evidence reproducible?

2018 ◽  
Vol 56 (2) ◽  
pp. 303-311 ◽  
Author(s):  
Enric Sabrià ◽  
Paloma Lequerica-Fernández ◽  
Paula Lafuente Ganuza ◽  
Edwin Eguia Ángeles ◽  
Ana I. Escudero ◽  
...  
Keyword(s):  
Early Onset ◽  
Pregnancy Termination ◽  
Positive Likelihood Ratio ◽  
Risk Pregnancy ◽  
Published Evidence ◽  
Ratio Determination ◽  
Early Onset Preeclampsia ◽  
Roche Diagnostics ◽  
Plgf Ratio ◽  
Rule Out

Abstract Background: Soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) ratio has been proven to predict preeclampsia occurrence. Methods: Blood samples from 195 pregnant women with suspected preeclampsia were obtained at obstetric triage admission or from the high-risk pregnancy outpatient office. Serum PlGF and sFlt-1 were measured by an electrochemiluminescence immunoassay (ECLIA) on the immunoanalyser Cobas e601 (Roche Diagnostics) and the corresponding ratio was calculated. Final outcomes were reviewed by an independent obstetrician. Only the first determination was considered. Results: A sFlt-1/PlGF ratio of 38 or lower ruled out the need for pregnancy termination due to preeclampsia in the subsequent week with a negative predictive value (NPV) of 99.1% (sensitivity 97.1% and specificity 67.5%). None of the 76 pregnancies with first determination of an sFlt-1/PlGF ratio of 38 or lower between 24 and 34 weeks of gestation delivered due to early-onset preeclampsia. Positive likelihood ratio (PLR) of an sFlt-1/PlGF ratio above 38 for prediction of pregnancy termination due to preeclampsia within 4 weeks is analogous to published evidence. Conclusions: Between 24 and 34 weeks of gestation, no subsequent determination was needed to completely rule out early-onset preeclampsia when the first sFlt-1/PlGF ratio determination was 38 or lower in singleton pregnancies with signs or symptoms of this syndrome. These findings, if confirmed, will reduce costs and facilitate the implementation of the sFlt-1/PlGF ratio in women with clinical suspicion of preeclampsia in the third trimester.

A more accurate prediction to rule in and rule out pre-eclampsia using the sFlt-1/PlGF ratio and NT-proBNP as biomarkers

2020 ◽  
Vol 58 (3) ◽  
pp. 399-407
Author(s):  
Paula Lafuente-Ganuza ◽  
Paloma Lequerica-Fernandez ◽  
Francisco Carretero ◽  
Ana I. Escudero ◽  
Eduardo Martinez-Morillo ◽  
...  
Keyword(s):  
Predictive Value ◽  
Early Onset ◽  
Retrospective Cohort ◽  
Validation Cohort ◽  
Placental Growth Factor ◽  
Machine Learning Model ◽  
Positive Results ◽  
Plgf Ratio ◽  
Rule Out ◽  
Singleton Pregnancies

AbstractBackgroundThe management of potential pre-eclamptic patients using the soluble FMS-like tyrosine kinase 1 (sFlt-1)/ placental growth factor (PlGF) ratio is characterised by frequent false-positive results.MethodsA retrospective cohort study was conducted to identify and validate cut-off values, obtained using a machine learning model, for the sFlt-1/PlGF ratio and NT-proBNP that would be predictive of the absence or presence of early-onset pre-eclampsia (PE) in singleton pregnancies presenting at 24 to 33 + 6 weeks of gestation.ResultsFor the development cohort, we defined two sFlt-1/PlGF ratio cut-off values of 23 and 45 to rule out and rule in early-onset PE at any time between 24 and 33 + 6 weeks of gestation. Using an sFlt-1/PlGF ratio cut-off value of 23, the negative predictive value (NPV) for the development of early-onset PE was 100% (95% confidence interval [CI]: 99.5–100). The positive predictive value (PPV) of an sFlt-1/PlGF ratio >45 for a diagnosis of early-onset PE was 49.5% (95% CI: 45.8–55.6). When an NT-proBNP value >174 was combined with an sFlt-1/PlGF ratio >45, the PPV was 86% (95% CI: 79.2–92.6). In the validation cohort, the negative and positive values were very similar to those found for the development cohort.ConclusionsAn sFlt-1/PlGF ratio <23 rules out early-onset PE between 24 and 33 + 6 weeks of gestation at any time, with an NPV of 100%. An sFlt-1/PlGF ratio >45 with an NT-proBNP value >174 significantly enhances the probability of developing early-onset PE.

sFlt-1/PlGF ratio as a prognostic marker of adverse outcomes in women with early-onset preeclampsia

2013 ◽  
Vol 3 (3) ◽  
pp. 191-195 ◽  
Author(s):  
Leandro De Oliveira ◽  
José C. Peraçoli ◽  
Maria T. Peraçoli ◽  
Henri Korkes ◽  
Giafranco Zampieri ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Early Onset ◽  
Adverse Outcomes ◽  
Early Onset Preeclampsia ◽  
Plgf Ratio

Circulating Angiogenic Factors and the Risk of Preeclampsia in Systemic Lupus Erythematosus Pregnancies

2015 ◽  
Vol 42 (7) ◽  
pp. 1141-1149 ◽  
Author(s):  
Alfredo Leaños-Miranda ◽  
Inova Campos-Galicia ◽  
María Guadalupe Berumen-Lechuga ◽  
Carlos José Molina-Pérez ◽  
Yolanda García-Paleta ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Early Onset ◽  
Late Onset ◽  
Angiogenic Factors ◽  
Systemic Lupus ◽  
Serum Samples ◽  
Early Onset Preeclampsia ◽  
Nested Case Control ◽  
Plgf Ratio

Objective.To investigate whether angiogenic factors are associated with risk of developing preeclampsia in pregnant women with systemic lupus erythematosus (SLE).Methods.We performed a nested case–control study within a cohort of SLE women with singleton pregnancies. The study included 42 patients with SLE who eventually developed preeclampsia and 75 normal SLE pregnancies. Serum samples were collected at 4-week intervals (from weeks 12 to 36). Serum samples were analyzed for soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng).Results.Women destined to develop preeclampsia had lower PlGF levels and higher sFlt-1 and sEng levels, and a higher sFlt-1/PlGF ratio than normal pregnancies. These changes became significant at 12 weeks in patients destined to develop either early onset (< 34 weeks, p ≤ 0.003) or late-onset preeclampsia (≥ 34 weeks, p ≤ 0.02). The risk to develop preeclampsia was higher among patients with PlGF concentration values in the lowest quartile or with sFlt-1 and sEng levels, and sFlt-1/PlGF ratio, in the highest quartile of the normal SLE pregnancies distribution. The OR were higher and appeared earlier in patients destined to develop early onset preeclampsia (OR ≥ 16.2, from Week 12 onward) than in patients who presented preeclampsia later (OR ≥ 8.9, from Week 24 onward).Conclusion.Changes in circulating concentrations of sFlt-1, PlGF, sEng, and the sFlt-1/PlGF ratio precede the onset of preeclampsia in SLE pregnancies. The risk profile of circulating angiogenic factors for developing preeclampsia distinctly evolves depending on whether this condition is manifested earlier or later.

scholarly journals Elecsys® and Kryptor immunoassays for the measurement of sFlt-1 and PlGF to aid preeclampsia diagnosis: are they comparable?

2019 ◽  
Vol 57 (9) ◽  
pp. 1339-1348 ◽  
Author(s):  
Holger Stepan ◽  
Martin Hund ◽  
Peter Dilba ◽  
Johanna Sillman ◽  
Dietmar Schlembach
Keyword(s):  
Pregnant Women ◽  
Early Onset ◽  
Late Onset ◽  
Correlation Coefficients ◽  
Serum Samples ◽  
Elevated Liver Enzymes ◽  
Low Platelet Count ◽  
Early Onset Preeclampsia ◽  
Plgf Ratio ◽  
Control Study

Abstract Background For pregnant women with suspected preeclampsia, the soluble fms-like tyrosine-kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio is a biomarker to aid diagnosis. We performed method comparisons between Elecsys® and Kryptor sFlt-1 and PlGF immunoassays and assessed the diagnostic performance for preeclampsia. Methods Serum samples from a case-control study involving 113 pregnant women with preeclampsia/elevated liver enzymes and low platelet count (HELLP) and 270 controls were analyzed. sFlt-1 and PlGF were measured using Roche Elecsys® and BRAHMS Kryptor sFlt-1/PlGF immunoassays. The sFlt-1/PlGF ratios were calculated, and Passing-Bablok regression/Bland-Altman plots were performed. Gestation-specific cut-offs, ≤33 and ≥85/≥110, were assessed. Results Mean (±2 standard deviation [SD]) differences between the Elecsys® and Kryptor values were: sFlt-1, 173.13 pg/mL (6237.66, −5891.40); PlGF, −102.71 pg/mL (186.06, −391.48); and sFlt-1/PlGF, 151.74 (1085.11, −781.63). The Elecsys® and Kryptor immunoassays showed high correlation: Pearson’s correlation coefficients were 0.913 (sFlt-1) and 0.945 (PlGF). Slopes were 1.06 (sFlt-1) and 0.79 (PlGF), resulting in ~20% lower values for Kryptor PlGF. Sensitivities and specificities using the sFlt-1/PlGF ≥85 cut-off for early-onset preeclampsia (20 + 0 to 33 + 6 weeks) were 88.1%/100.0% (Elecsys®) and 90.5%/96.2% (Kryptor), respectively, and using the ≥110 cut-off for late-onset preeclampsia (≥34 + 0 weeks) were 51.3%/96.5% (Elecsys®) and 78.9%/90.1% (Kryptor), respectively. Using Elecsys® and Kryptor sFlt-1/PlGF, 0% and 3.8% of women, respectively, were falsely ruled-in for early-onset, and 3.5% and 9.9%, respectively, for late-onset preeclampsia. Conclusions Despite high correlation between the Elecsys® and Kryptor immunoassays, we observed significant differences between sFlt-1/PlGF and PlGF results. Therefore, sFlt-1/PlGF cut-offs validated for Elecsys® immunoassays are not transferable to Kryptor immunoassays.

scholarly journals Decision Threshold for Kryptor sFlt‐1/PlGF Ratio in Women With Suspected Preeclampsia: Retrospective Study in a Routine Clinical Setting

2021 ◽  
Author(s):  
Lise Lotte Torvin Andersen ◽  
Annemarie Helt ◽  
Lene Sperling ◽  
Martin Overgaard
Keyword(s):  
Retrospective Study ◽  
Early Onset ◽  
Operating Characteristic ◽  
Late Onset ◽  
Characteristic Curve ◽  
Predictive Performance ◽  
Decision Threshold ◽  
Operating Characteristic Curve ◽  
Early Onset Preeclampsia ◽  
Plgf Ratio

Background The objective was to evaluate predictive performance and optimal decision threshold of the Kryptor soluble fms‐like tyrosine kinase‐1 (sFlt‐1)/placental growth factor (PlGF) ratio when implemented for routine management of women presenting with symptoms of preeclampsia. Methods and Results Observational retrospective study of a cohort of 501 women with suspected preeclampsia after 20 weeks of gestation. Women referred to maternity ward for observation of preeclampsia had an sFlt‐1/PlGF ratio test included in routine diagnostic workup. Maternal and offspring characteristic data included maternal risk factors, outcomes, delivery mode, and indication for suspected preeclampsia. Biochemical measurements to determine sFlt‐1/PlGF ratio were performed using the BRAHMS/Kryptor sFlt‐1/PlGF ratio immunoassays. Results were analyzed by area under receiver‐operating characteristic curve. Preeclampsia occurred in 150 of 501 (30%) of symptomatic women with an sFlt‐1/PlGF ratio determined before the time of diagnosis. Area under receiver‐operating characteristic curve for diagnosis of early‐onset preeclampsia within 1 and 4 weeks was 0.98 (95% CI, 0.96–1.00) and 0.95 (95% CI, 0.92–0.98), respectively. For late‐onset preeclampsia, predictive performance within 1 and 4 weeks was lower: 0.90 (95% CI, 0.85–0.94) and 0.85 (95% CI, 0.80–0.90), respectively. The optimal single sFlt‐1/PlGF ratio threshold for all preeclampsia and late‐onset preeclampsia within 1 and 4 weeks was 66. The negative and positive predictive values for ruling out and ruling in developing preeclampsia within 1 week were 96% and 70%, respectively. Conclusions The Kryptor sFlt‐1/PlGF ratio is a useful clinical tool ruling out and in preeclampsia within 1 week. Prediction within 4 weeks is superior for early‐onset preeclampsia. A single decision threshold of 66 is indicated for use in clinical routine.

scholarly journals Early Onset Preeclampsia Diagnosis Prior to the 20th Week of Gestation in a Twin Pregnancy Managed via Selective Reduction of an Intrauterine Growth Restriction Fetus: A Case Report and Literature Review

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 531
Author(s):  
Anastasios Konstantopoulos ◽  
Konstantinos Sfakianoudis ◽  
Mara Simopoulou ◽  
Adamantia Kontogeorgi ◽  
Anna Rapani ◽  
...  
Keyword(s):  
Live Birth ◽  
Early Onset ◽  
Intrauterine Growth Restriction ◽  
Twin Pregnancy ◽  
Pregnancy Termination ◽  
Selective Reduction ◽  
Intrauterine Growth ◽  
Protein Levels ◽  
Selective Embryo Reduction ◽  
Early Onset Preeclampsia

A single, healthy, 44-year-old perimenopausal woman pursuing a pregnancy, employed donor embryos, resulting to a dichorionic diamniotic twin pregnancy. In the 18th week of gestation severe symptoms indicated early onset preeclampsia reporting severe hypertension (BP 180/90 mmHg), intense headaches and nausea as well as elevated 24-h urine protein levels (1.5 g/day). Concurrently diagnosis of an IUGR fetus was concluded. Standard pharmaceutical administration for treating preeclampsia was ordered. Persistence of symptoms indicated recommendation for pregnancy termination, however the patient opted against this. Selective embryo reduction was performed as the last resort prior to pregnancy termination. Following selective reduction the headaches and nausea were successfully subdued and the patient’s blood pressure was adjusted (mean BP 130/80 mmHg). This enabled further progression of pregnancy for an impressive 11 week-period, and a live birth on the 30th week. To conclude, only a few rare cases have been reported with diagnosis of early onset preeclampsia prior to the 20th week mark and none report live births. Albeit termination of pregnancy was recommended, the management of selective reduction of the IUGR fetus enabled successful treatment of preeclampsia coupled by a live birth of a healthy infant without any perinatal or postnatal complications reported.

sFlt-1/PlGF ratio for the prediction of delivery within 48 hours and adverse outcomes in expectantly managed early-onset preeclampsia

2020 ◽  
Vol 22 ◽  
pp. 17-23
Author(s):  
Elisa Simón ◽  
Celia Permuy ◽  
Laura Sacristán ◽  
María José Zamoro-Lorenci ◽  
Cecilia Villalaín ◽  
...  
Keyword(s):  
Early Onset ◽  
Adverse Outcomes ◽  
Early Onset Preeclampsia ◽  
Plgf Ratio

Early-Onset Preeclampsia with Pulmonary Edema and Massive Ascites: A Rare Presentation of Severe Preeclampsia or Concomitant Diagnoses?

2020 ◽  
Vol 2020 ◽  
Author(s):  
Elizabeth St. Laurent ◽  
Rebecca Fryer-Gordon ◽  
Tom McNeilis, ◽  
Leonard B. Goldstein
Keyword(s):  
Pulmonary Edema ◽  
Early Onset ◽  
Hellp Syndrome ◽  
Disease Process ◽  
Massive Ascites ◽  
Elevated Liver Enzymes ◽  
Biophysical Profile ◽  
Patient Reported ◽  
Early Onset Preeclampsia ◽  
New Onset

Preeclampsia, eclampsia, and HELLP syndrome, are a continuum of a dangerous disease process that can occur in pregnancy. Preeclampsia is defined by new onset hypertension and proteinuria. In more severe cases, preeclampsia can be associated with pulmonary edema, oliguria, persistent headaches, and impaired liver function. These symptoms reveal maternal end organ damage which may result in danger to the fetus such as oligohydramnios, decreased fetal growth, and placental abruption. The defining difference between preeclampsia and eclampsia is the presence of new onset seizure activity. HELLP syndrome occurs when the mother experiences hemolysis, elevated liver enzymes, and low platelets. This syndrome is seen in about 0.6% of pregnancies. Each of these conditions (preeclampsia, eclampsia, and HELLP) increase both the fetal and maternal morbidity and mortality rates with the most definitive cure being delivery of child and placenta.A 28 year-old Caucasian, G1P0 female at 26w4d presented to OB triage on the recommendation of her physician due to elevated uric acid levels and a recorded blood pressure of 180/110. The patient reported rapid onset of weight gain, facial edema, diminished fetal movements, and frequent headaches. Although the patient denied labor symptoms, she complained of back pain and was admitted to the hospital at 26w4d for observation due to elevated blood pressures. The patient was diagnosed with preeclampsia with severe features. As her presentation progressed, the patient developed massive ascites and pulmonary edema along with decreasing platelet counts and increasing liver enzyme values. Due to decreasing biophysical profile (BPP) scores of the fetus and decompensating lab values of the mother, an emergency cesarean was performed for the safety of mother and baby.This case presentation demonstrates the progression of hypertensive disorders of pregnancy with a rare and severe presentation of early-onset preeclampsia with severe features, pulmonary edema, and massive ascites that ultimately led to class III HELLP syndrome and extreme prematurity of the infant.

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