Placental Growth Factor Ratio In Women Research Articles

Predictive value of the sFlt‑1/PlGF ratio in women with suspected preeclampsia: An update (Review).

Preeclampsia (PE) is a major complication of pregnancy with an incidence rate of 2‑8% and is a leading cause of maternal mortality and morbidity. The various consequences of severe preeclampsia for the fetus, neonate and child include intrauterine growth retardation (IUGR), fetal hypoxia, oligohydramnios, intrauterine fetal demise, increased perinatal mortality and morbidity, neurodevelopmental disorders and even irreversible brain damage (cerebral palsy). A number of studies have demonstrated that differences in maternal serum concentrations of angiogenic factors between preeclampsia and normotensive pregnancies can be used as biomarkers, either alone or in combination with other markers, to predict the development of PE. The presence in the maternal circulation of two proteins of placental origin, placental growth factor (PlGF) and soluble fms‑like tyrosine kinase 1 (sFlt‑1), has been shown to be of clinical value, as the sFlt‑1/PlGF ratio appears to be the optimal predictive tool for the development of PE. The measurement of their concentration in maternal serum in screening models, serves as predictive marker for the development of PE or IUGR later in gestation. However, further research is required to improve its clinical applicability and provide guidelines for its use worldwide to achieve more consistent clinical management of women with PE.

To the question of the clinical predictive value of the sFlt-1:PlGF ratio is related to the placental dysfunction

The objective: to evaluate the clinical and prognostic value and meaning of the ratio of the anti-angiogenic factor of soluble fms-like tyrosine kinase-1 (sFlt-1) to the angiogenic factor of the placental growth factor (PlGF) in the dynamics of pregnancy as markers of various variants of placental dysfunction. Materials and methods. A retrospective cohort study of 40 pregnant women, who were distributed by gestation term (up to 34 weeks and after 34 weeks) and the level of sFlt-1:PlGF ratio (<38 is low level, > 110 – high level) was performed. The statistical comparison of the sFlt-1:PlGF ratio with the development of hypertensive disorders during pregnancy and fetal growth retardation (FGR), as well as the duration of the period from research to childbirth was calculated. Results. Preeclampsia (PE) developed in 12 persons out of 40 pregnant women. The sFlt-1:PlGF ratio in the period till 27 weeks of pregnancy in groups of women with PE and without it does not differ with a statistically significant level (p=0.3). In other gestation terms the sFlt-1:PlGF ratio in women with and without placental dysfunction is statistically significant (p<0.05). The sFlt-1:PlGF ratio >38 increases the risk of PE more than 4 times (RR = 4.6) and is statistically significant in a period till 34 weeks [95 % CI: 1.4-14,9]. After 34 weeks of pregnancy the sFlt-1:PlGF ratio >110 has a higher sensitivity (Se=0.75).An analysis of the sFlt-1:PlGF ratio for the purpose of FGR predicting, both in combination with hypertensive disorders during pregnancy or without them, demonstrated its high importance during pregnancy up to 34 weeks (p=0.001). A strong reverse correlation (ƿ= -0.7) was found between the value of the sFlt-1:PlGF ratio and the number of days from the date of research till childbirth at the level of significance of 0.0001 in pregnant women up to 34 weeks. Conclusions. The predictive value of the conventional method of assessing the preeclampsia (PE) risk and the preventive efficiency of acetylsalicylic acid is low. In the absence of clinical manifestation of PE the determination of the sFlt-1:PlGF ratio for a predication till 27 weeks of pregnancy is not informative, so it is not recommended. If the sFlt-1:PlGF ratio is > 38 in the period till 34 weeks, the relative risk is 4.6 [95 % CI: 1.4–14.9]. If the level of the sFlt-1:PlGF ratio is high at first investigation there is no sense to repeat the research in dynamics. In the case of low the sFlt-1:PlGF ratio for a reasonable suspicion of PE development, repeated research can help make an adequate clinical decision. The determination of the sFlt-1:PlGF ratio for a predication or confirmation of fetal growth retardation till 34 weeks is clinically reasonable and informative. There is a strong reverse correlation between the sFlt-1:PlGF ratio and the number of days before the current birth.

Angiogenic factors (sFlt-1, PlGF) in twin pregnancy with placentaassociated complications

Aim : to determine reference values of angiogenic factors dynamics in pregnancy for female patients with twins and different types of placentation for early diagnostics and assessment of preeclampsia (PE) severity. Materials and Methods . There was conducted 2020–2021 prospective study enrolling 93 females with twin pregnancy to examine 68 with dichorionic diamniotic (DCDA) twins and 25 with monochorionic diamniotic (MCDA) twins. All patients were divided into 2 groups: group I consisted of 65 women with twin pregnancy without PE, group II included 28 women with twin pregnancy complicated by PE. In blood serum of pregnant women the level of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and their ratio were studied for diagnosing and predicting PE severity at 4 time points of gestation (20.0–23.6 weeks, 24.0–28.6 weeks, 29.0–33.6 weeks, 34.0–36.6 weeks). Results . No significant difference was found in angiogenic factors level and their ratio in pregnant women with uncomplicated DCDA and MCDA twins. Regardless of placentation type, sFlt-1/PlGF ratio in women with twin pregnancy and PE at 24 weeks of gestation was 103.3, by 20-fold exceeding this level than in uncomplicated twin pregnancy. Cut-off values for sFlt-1/PlGF ratio were determined allowing highly reliable to rule out diagnosis PE (sFlt-1/PlGF < 21.85; sensitivity 100 %, specificity 85 %) and to diagnose PE (sFlt-1/PlGF > 49.4; sensitivity 71.1 %, specificity 100 %). The sFlt-1/PlGF ratio was higher in pregnant women with severe PE compared with the moderate degree of the disease throughout pregnancy (р < 0.05). In pregnant women with early PE, the angiogenic factors ratio exceeded the upper threshold value from 24 weeks of gestation, with late PE – from 34.0–36.6 weeks. Significantly higher sFlt-1 level (18359 ± 8656 pg/ml vs. 5526 ± 2808 pg/ml; р < 0.001) and the sFlt-1/PlGF ratio (118,0 ± 65,2 vs. 32,8 ± 18,6; р < 0.03) as well as severe degree of PE were noted in patients with induced twin pregnancy from 24.0–28.6 weeks of gestation compared with spontaneous multiple pregnancy (42,2 and 22,2 % respectively; p < 0,05). Conclusion . The developed reference values of the sFlt-1/PlGF ratio in pregnant women with twins and different types of placentation can be used not only to diagnose PE, but also to assess the severity and timing of the disease manifestation.

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

BackgroundThe 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 ResultsObservational 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.ConclusionsThe 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.

Preeclampsia for the Nephrologist: Current Understanding in Diagnosis, Management, and Long-term Outcomes.

Preeclampsia is a multisystem progressive disorder of pregnancy that can be potentially catastrophic for the mother and the fetus. It involves complex perturbations of the kidney and systemic physiology, along with long-term effects on vascular and kidney health. Thus, the nephrologist plays a key role in the peripartum and long-term management of preeclampsia. Recent translational research has improved our understanding of its pathophysiology, and there is hope for novel therapies. In this review, we discuss the evolution of diagnostic criteria and dilemmas in the diagnosis of hypertensive disorders in pregnancy. We summarize the advances in the pathogenesis and prediction of preeclampsia. We describe the management and prevention of preeclampsia focusing specially on the forthcoming strategies from the nephrologist's perspective. We address the evidence regarding long-term outcomes for the mother and the child. We end with exploring areas warranting future research.

Effect of Low-Dose Aspirin on Soluble FMS-Like Tyrosine Kinase 1/Placental Growth Factor (sFlt-1/PlGF Ratio) in Pregnancies at High Risk for the Development of Preeclampsia.

Background: Soluble FMS-like Tyrosine Kinase 1 (sFlt-1) and placental growth factor (PlGF) have been reported to be highly predictive several weeks before the onset of preeclampsia. Objective: To investigate longitudinal changes of serum levels sFlt-1 and PlGF in pregnant women at high risk for the development of preeclampsia and to reveal an impact of aspirin on maternal serum concentrations of sFlt-1 and PlGF. Methods: This was a prospective longitudinal study in 394 women with various risk factors for the development of preeclampsia (chronic hypertension, antiphospholipid syndrome/APS or systemic lupus erythematosus/SLE, thrombophilia, women with a history of preeclampsia, pathologic first trimester screening for preeclampsia) and 68 healthy women. Serum levels of sFlt-1 and PlGF were measured prospectively at 4-week intervals (from gestational weeks 12 until postpartum). Results: The sFlt-1/PlGF ratio was significantly higher in women with an adverse obstetric outcome compared to women with a normal pregnancy, starting between 20 and 24 weeks of gestation. There was no effect of aspirin on sFlt-1/PlGF ratio in women with chronic hypertension, APS/SLE, thrombophilia and controls. The use of aspirin showed a trend towards an improvement of the sFlt-1/PlGF ratio in women with preeclampsia in a previous pregnancy and a significant effect on the sFlt-1/PlGF ratio in women with a pathologic first trimester screening for preeclampsia. Conclusions: Our findings reveal an impact of aspirin on sFlt-1/PlGF ratio in women with a pathologic first trimester screening for preeclampsia, strongly supporting its prophylactic use.

Randomized Interventional Study on Prediction of Preeclampsia/Eclampsia in Women With Suspected Preeclampsia

The ratio of maternal serum sFlt-1 (soluble fms-like tyrosine kinase 1) to PlGF (placental growth factor) has been used retrospectively to rule out the occurrence of preeclampsia, a pregnancy hypertensive disorder, within 7 days in women presenting with clinical suspicion of preeclampsia. A prospective, interventional, parallel-group, randomized clinical trial evaluated the use of sFlt-1/PlGF ratio in women presenting with suspected preeclampsia. Women were assigned to reveal (sFlt-1/PlGF result known to clinicians) or nonreveal (result unknown) arms. A ratio cutoff of 38 was used to define low (≤38) and elevated risk (>38) of developing the condition in the subsequent week. The primary end point was hospitalization within 24 hours of the test. Secondary end points were development of preeclampsia and other adverse maternal-fetal outcomes. We recruited 370 women (186 reveal versus 184 nonreveal). Preeclampsia occurred in 85 women (23%). The number of admissions was not significantly different between groups (n=48 nonreveal versus n=60 reveal; P=0.192). The reveal trial arm admitted 100% of the cases that developed preeclampsia within 7 days, whereas the nonreveal admitted 83% (P=0.038). Use of the test yielded a sensitivity of 100% (95% CI, 85.8-100) and a negative predictive value of 100% (95% CI, 97.1-100) compared with a sensitivity of 83.3 (95% CI, 58.6-96.4) and negative predictive value of 97.8 (95% CI, 93.7-99.5) with clinical practice alone. Use of the sFlt-1/PlGF ratio significantly improved clinical precision without changing the admission rate. Clinical Trial Registration- URL: http://www.isrctn.com. Unique identifier: ISRCTN87470468.

A cross sectional study to assess the sFlt-1:PlGF ratio in pregnant women with and without preeclampsia

BackgroundPreeclampsia is a multisystem disorder characterized by vascular endothelial malfunction occurring after 20 weeks of gestation. Placental soluble fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic factor and placental growth factor (PlGF) is a potent angiogenic factor. The imbalance between these factors during placenta and fetal development has been shown to play a role in endothelial damage in preeclampsia.Preeclampsia is the leading cause of maternal mortality in Nepal. This study was designed to compare the sFlt1:PLGF ratio in pregnant women with and without preeclampsia attending Tribhuvan University Teaching Hospital (TUTH).MethodAn observational cross-sectional study was performed in the Gynecology and Obstetrics Department of TUTH involving forty-four subjects with preeclampsia and forty-four age- and gestational-week-matched normal pregnant subjects as controls. Blood pressure, urinary protein levels, serum sFlt-1 levels, serum PlGF levels and the sFlt-1:PlGF ratio was compared in both the cases and control. The concentrations of sFlt-1 and PlGF were measured with commercially available ELISA kits. SPSS ver. 20.0 was used to analyze the data.ResultsThere was no significant difference in age or gestational age in either study group. The ratio of the sFlt-1 and PlGF concentrations was significantly higher in women with preeclampsia (31.6 ± 9.6) than in the controls (3.2 ± 1.3). Likewise, diastolic blood pressure was significantly associated (p-value 0.000), whereas the severity of proteinuria was not associated (p-value 0.773) with the sFlt-1:PlGF ratio in women with preeclampsia. The significantly higher ratio (35.51 ± 8.1 versus 25.4 ± 8.7) was found in women with preeclampsia who developed complications than the group of women with preeclampsia who did not develop complication.ConclusionThe sFlt-1:PlGF ratio is significantly higher in Nepalese women with preeclampsia than in normal controls and this finding can be applied for further planned clinical trials.

Consensus statement on the potential implementation of the sFlt-1/PlGF ratio in women with suspected pre-eclampsia

Pre-eclampsia is one of the leading causes of maternal and perinatal mortality and morbidity worldwide, and places a significant burden on the South African (SA) healthcare system. The soluble fms-like tyrosince kinase (sFlt-1)/placental growth factor (PlGF) ratio can serve as a diagnostic aid for PE, and should be used in combination with clinical judgement and other ancillary tests. The Preeclampsia Advisory Board was convened on 31 March 2017, with experts in the field of PE from various hospitals and universities around the country in attendance. An international expert gave insight into best practices from countries that have implemented the Elecsys immunoassay sFlt-1/PlGF ratio. Others recommend that the sFlt-1/PlGF ratio be implemented in clinical practice when clinical diagnosis is in doubt in patients with suspected PE, in the interests of avoiding unnecessary hospitalisation and interventions. The strength of the test lies in its negative predictive value in ruling out PE. Ruling out PE could drive cost savings, as fewer women would be needlessly admitted to hospital, and there could, in addition, be fewer iatrogenic preterm deliveries, which are associated with considerable morbidity and cost. As most data are derived from high-income countries, multicentre studies are required to assess the clinical performance of this test within the context of SA.

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

Soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) ratio has been proven to predict preeclampsia occurrence. 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. 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. 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.

Association between angiogenic factors and signs of arterial aging in women with pre‐eclampsia

ABSTRACTObjectivePre‐eclampsia (PE) is associated with an increased risk of cardiovascular disease later in life. In cases with PE there is a substantial increase in levels of the antiangiogenic factor soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and decreased levels of the proangiogenic factor placental growth factor (PlGF). Elevated levels of sFlt‐1 are also found in individuals with cardiovascular disease. The aims of this study were to assess levels of sFlt‐1, PlGF and the sFlt‐1/PlGF ratio and their correlation with signs of arterial aging by measuring the common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.MethodsSerum sFlt‐1 and PlGF levels were measured using commercially available enzyme‐linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high‐frequency (22‐MHz) ultrasonography in 55 women at PE diagnosis and in 64 women with normal pregnancy at a similar gestational age, with reassessment at 1 year postpartum.ResultsDuring pregnancy, higher levels of sFlt‐1, lower levels of PlGF, a thicker intima, a thinner media and a higher I/M ratio of the CCA were found in women with PE vs controls (all P < 0.0001). Further, sFlt‐1 and the sFlt‐1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all P < 0.0001). At 1 year postpartum, levels of sFlt‐1 and the sFlt‐1/PlGF ratio had decreased in both groups; however, their levels in the PE group were still higher than in the controls (P = 0.001 and < 0.0001, respectively). Levels of sFlt‐1 and the sFlt‐1/PlGF ratio remained positively correlated with intima thickness and I/M ratio at 1 year postpartum.ConclusionsHigher sFlt‐1 levels and sFlt‐1/PlGF ratio in women with PE were positively associated with signs of arterial aging during pregnancy. At 1 year postpartum, sFlt‐1 levels and the sFlt‐1/PlGF ratio were still higher in the PE group and were associated with the degree of arterial aging. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Predictive Value of the sFlt-1:PlGF Ratio in Women With Suspected Preeclampsia

(N Engl J Med. 2016;374:13–22) Preeclampsia is a serious multisystem disorder affecting up to 5% of pregnancies worldwide. A reliable predictor of preeclampsia would be helpful in allowing health care providers to identify women at risk for developing the disorder. Serum levels of circulating maternal soluble fms-like tyrosine kinase 1 (sFlt-1) are known to be elevated in preeclampsia, while levels of placental growth factor (PlGF) are decreased. A high ratio of sFlt-1 to PlGF indicates an increased risk for preeclampsia and could potentially be a more reliable predictor than either of those factors alone. The authors of this study sought to evaluate the ratio as a predictive tool among women with suspected preeclampsia.

Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia

BackgroundThe ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is elevated in pregnant women before the clinical onset of preeclampsia, but its predictive value in women with suspected preeclampsia is unclear.MethodsWe performed a prospective, multicenter, observational study to derive and validate a ratio of serum sFlt-1 to PlGF that would be predictive of the absence or presence of preeclampsia in the short term in women with singleton pregnancies in whom preeclampsia was suspected (24 weeks 0 days to 36 weeks 6 days of gestation). Primary objectives were to assess whether low sFlt-1:PlGF ratios (at or below a derived cutoff) predict the absence of preeclampsia within 1 week after the first visit and whether high ratios (above the cutoff) predict the presence of preeclampsia within 4 weeks.ResultsIn the development cohort (500 women), we identified an sFlt-1:PlGF ratio cutoff of 38 as having important predictive value. In a subsequent validation study among an additional 550 women, an sFlt-1:PlGF ratio of 38 or lower had a negative predictive value (i.e., no preeclampsia in the subsequent week) of 99.3% (95% confidence interval [CI], 97.9 to 99.9), with 80.0% sensitivity (95% CI, 51.9 to 95.7) and 78.3% specificity (95% CI, 74.6 to 81.7). The positive predictive value of an sFlt-1:PlGF ratio above 38 for a diagnosis of preeclampsia within 4 weeks was 36.7% (95% CI, 28.4 to 45.7), with 66.2% sensitivity (95% CI, 54.0 to 77.0) and 83.1% specificity (95% CI, 79.4 to 86.3).ConclusionsAn sFlt-1:PlGF ratio of 38 or lower can be used to predict the short-term absence of preeclampsia in women in whom the syndrome is suspected clinically. (Funded by Roche Diagnostics.)