Short-Term Prediction of Preeclampsia in Chinese Women Using the Soluble fms-Like Tyrosine Kinase 1/Placental Growth Factor Ratio: A Sub-Analysis of the PROGNOSIS Asia Study

The diagnosis of preeclampsia in China currently relies on limited clinical signs and unspecific laboratory findings. These are inadequate predictors of preeclampsia development, limiting early diagnosis and appropriate management. Previously, the Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study (PROGNOSIS) and PROGNOSIS Asia demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio of ≤38 can be used to rule out preeclampsia within 1 week, with negative predictive values of 99.3 and 98.6%, respectively. This is an exploratory sub-analysis of the Chinese cohort (n = 225) of the PROGNOSIS Asia study. The primary objectives were to assess the predictive performance of using the sFlt-1/PlGF ratio to rule out preeclampsia within 1 week and to rule in preeclampsia within 4 weeks. The sFlt-1/PlGF ratio was also examined for short-term prediction of fetal adverse outcomes, maternal adverse outcomes, and time to delivery. The overall prevalence of preeclampsia was 17.3%. With the use of an sFlt-1/PlGF ratio of ≤38, the negative predictive value for ruling out preeclampsia within 1 week was 97.3% [95% confidence interval (CI), 93.8–99.1], with a sensitivity of 64.3% and specificity of 85.3%. With the use of an sFlt-1/PlGF ratio of >38, the positive predictive value for ruling in preeclampsia within 4 weeks was 35.0% (95% CI, 20.6–51.7), with a sensitivity of 50.0% and specificity of 86.8%. In the analyses of the sFlt-1/PlGF ratio and fetal adverse outcomes, the area under the receiver operating characteristic curve was 92.8% (95% CI, 83.5–98.7) for ruling out fetal adverse outcomes within 1 week and 79.9% (95% CI, 68.1–90.3) for ruling in fetal adverse outcomes within 4 weeks. An sFlt-1/PlGF ratio of >38 increased the likelihood of imminent delivery 3.3-fold compared with a ratio of ≤38 [hazard ratio, 3.3 (95% CI, 2.1–5.1)]. This sub-analysis confirms the high predictive performance of the sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia in Chinese women, which may help prevent unnecessary hospitalization of women with low risk of developing preeclampsia.

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Short-Term Prediction of Adverse Outcomes Using the sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor) Ratio in Asian Women With Suspected Preeclampsia

Hypertension ◽

10.1161/hypertensionaha.119.12760 ◽

2019 ◽

Vol 74 (1) ◽

pp. 164-172 ◽

Cited By ~ 13

Author(s):

Xuming Bian ◽

Arijit Biswas ◽

Xianghuang Huang ◽

Kyoung Jin Lee ◽

Thomas Kwok-To Li ◽

...

Keyword(s):

Growth Factor ◽

Tyrosine Kinase ◽

Placental Growth Factor ◽

Adverse Outcomes ◽

Asian Women ◽

Short Term ◽

Term Prediction ◽

Factor Ratio ◽

Short Term Prediction

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Short-term prediction of preeclampsia using the sFlt-1/PlGF ratio: a subanalysis of pregnant Japanese women from the PROGNOSIS Asia study

Hypertension Research ◽

10.1038/s41440-021-00629-x ◽

2021 ◽

Author(s):

Akihide Ohkuchi ◽

Shigeru Saito ◽

Tatsuo Yamamoto ◽

Hisanori Minakami ◽

Hisashi Masuyama ◽

...

Keyword(s):

Predictive Value ◽

Cox Regression ◽

Japanese Women ◽

Adverse Outcomes ◽

Short Term ◽

Multicenter Studies ◽

Term Prediction ◽

Short Term Prediction ◽

Plgf Ratio ◽

Rule Out

AbstractTwo prospective multicenter studies demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio cutoff of ≤38 can rule out preeclampsia within 1 week with a negative predictive value (NPV) of 99.3% (PROGNOSIS) and 98.6% (PROGNOSIS Asia). We report a subanalysis of the Japanese cohort from the PROGNOSIS Asia study. Pregnant women with suspected preeclampsia between gestational weeks 18 + 0 days and 36 + 6 days were enrolled at eight Japanese sites. Primary objectives: Assess the performance of the Elecsys® sFlt-1/PlGF ratio cutoff ≤38 to rule out preeclampsia within 1 week and of the cutoff >38 to rule in preeclampsia within 4 weeks. Key secondary objectives: Prediction of maternal and fetal adverse outcomes (MAOs/FAOs) and their relationship with duration of pregnancy. Of 192 women enrolled, 180 (93.8%)/175 (91.1%) were evaluable for primary/combined endpoint analyses. Overall preeclampsia prevalence was 13.3%. A sFlt-1/PlGF ratio of ≤38 provided an NPV of 100% (95% confidence interval [CI], 97.5–100) for ruling out preeclampsia within 1 week, and a ratio of >38 provided a positive predictive value of 32.4% (95% CI, 18.0–49.8) for ruling in preeclampsia within 4 weeks. The area under the curve for the prediction of preeclampsia/maternal/fetal adverse outcomes within 1 week was 94.2% (95% CI, 89.3–97.8). After adjusting for gestational age and final preeclampsia status, Cox regression indicated a 2.8-fold greater risk of imminent delivery for women with a sFlt-1/PlGF ratio >38 versus ≤38. This subanalysis of Japanese women with suspicion of preeclampsia showed high predictive value for a Elecsys sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia.

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P-017. The Elecsys sFlt-1/PlGF ratio for short-term prediction of preeclampsia in the Japanese cohort of the PROGNOSIS Asia study: Economic evaluation

Pregnancy Hypertension ◽

10.1016/j.preghy.2021.07.052 ◽

2021 ◽

Vol 25 ◽

pp. e34

Author(s):

Akihide Ohkuchi ◽

Hisashi Masuyama ◽

Tatsuo Yamamoto ◽

Takashi Kikuchi ◽

Naoko Taguchi ◽

...

Keyword(s):

Economic Evaluation ◽

Short Term ◽

Japanese Cohort ◽

Term Prediction ◽

Short Term Prediction ◽

Plgf Ratio

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Usefulness of the sFlt-1/PlGF (Soluble fms-Like Tyrosine Kinase-1/Placental Growth Factor) Ratio in Diagnosis or Misdiagnosis in Women With Clinical Diagnosis of Preeclampsia

Hypertension ◽

10.1161/hypertensionaha.120.15552 ◽

2020 ◽

Vol 76 (3) ◽

pp. 892-900 ◽

Cited By ~ 1

Author(s):

Alfredo Leaños-Miranda ◽

Ana Graciela Nolasco-Leaños ◽

Reyes Ismael Carrillo-Juárez ◽

Carlos José Molina-Pérez ◽

Liliana Janet Sillas-Pardo ◽

...

Keyword(s):

Growth Factor ◽

Tyrosine Kinase ◽

Clinical Diagnosis ◽

Correct Diagnosis ◽

Kidney Injury ◽

Placental Growth Factor ◽

Adverse Outcomes ◽

Elevated Liver Enzymes ◽

The Relationship ◽

Plgf Ratio

Preeclampsia is characterized by angiogenic imbalance (AI), sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) is useful for its diagnosis and prediction of adverse outcomes, but the relationship among the degrees of AI as assessed by this ratio with the correct diagnosis, clinical characteristics, and outcomes in women with clinical diagnosis of preeclampsia are unclear. We studied 810 women with clinical diagnosis of preeclampsia. Patients were divided into 3 groups based on their degree of AI, evaluated by the sFlt-1/PlGF ratio: no AI (≤38), mild AI (>38–<85), and severe AI (≥85). Patients with no AI were more likely to have comorbidities and false significant proteinuria compared with patients with mild and severe AI ( P <0.001). The rates of preterm delivery, delivery within 14 days, and small-for-gestational-age infant were higher among patients with severe AI than in patients with no and mild AI ( P <0.001) and in patients with mild AI that in those with no AI ( P ≤0.01). The occurrence of any adverse maternal outcome (HELLP syndrome, elevated liver enzymes, thrombocytopenia, placental abruption, acute kidney injury) was only present in patients with severe AI. Interestingly, the frequency of misdiagnosis of preeclampsia was progressively lower as the degrees of AI increased (no AI: 100%, mild AI: 88.2%, and severe AI: 15.6%). We concluded that in women with clinical diagnosis of preeclampsia, severe AI is characterized by high frequency of true preeclampsia and preeclampsia-related adverse outcomes, in contrast, no and mild AI, are characterized by unnecessary early deliveries, often due to misdiagnosis.

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Prediction of Preeclampsia-Related Adverse Outcomes With the sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor)-Ratio in the Clinical Routine

Hypertension ◽

10.1161/hypertensionaha.120.15146 ◽

2020 ◽

Author(s):

Lisa Antonia Dröge ◽

Frank Holger Perschel ◽

Natalia Stütz ◽

Anna Gafron ◽

Lisa Frank ◽

...

Keyword(s):

Growth Factor ◽

Tyrosine Kinase ◽

Area Under The Curve ◽

Placental Growth Factor ◽

Adverse Outcomes ◽

Low Risk ◽

Cutoff Values ◽

Elevated Liver Enzymes ◽

Factor Ratio ◽

Plgf Ratio

This retrospective real-world study investigated the clinical use of the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio alone or in combination with other clinical tests to predict an adverse maternal (maternal death, kidney failure, hemolysis elevated liver enzymes low platelets-syndrome, pulmonary edema, disseminated intravascular coagulation, cerebral hemorrhage, or eclampsia) or fetal (delivery before 34 weeks because of preeclampsia and/or intrauterine growth restriction, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, placental abruption or intrauterine fetal death or neonatal death within 7 days post natum) pregnancy outcome in patients with signs and symptoms of preeclampsia. We evaluated the sFlt-1/PlGF-ratio cutoff values of 38 and 85 and evaluated its integration into a multimarker model. Of 1117 subjects, 322 (28.8%) developed an adverse fetal or maternal outcome. Patients with an adverse versus no adverse outcome had a median sFlt-1/PlGF-ratio of 177 (interquartile range, 54–362) versus 14 (4–64). Risk-stratification with the sFlt-1/PlGF cutoff values into high- (>85), intermediate- (38–85), and low-risk (<38) showed a significantly shorter time to delivery in high- and intermediate- versus low-risk patients (4 versus 8 versus 29 days). When integrating all available clinical information into a multimarker model, an area under the curve of 88.7% corresponding to a sensitivity, specificity, positive and negative predictive value of 80.0%, 87.3%, 75.0%, and 90.2% was reached. The sFlt-1/PlGF-ratio alone was inferior to the full model with an area under the curve of 85.7%. As expected, blood pressure and proteinuria were significantly less accurate with an area under the curve of 69.0%. Combining biomarker measurements with all available information in a multimarker modeling approach increased detection of adverse outcomes in women with suspected disease.

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