Matches in SemOpenAlex for { <https://semopenalex.org/work/W2079661513> ?p ?o ?g. }
- W2079661513 endingPage "246" @default.
- W2079661513 startingPage "241" @default.
- W2079661513 abstract "Pre-eclampsia (PE) is a leading cause of maternal and fetal/neonatal morbidity and mortality worldwide. Clinical diagnosis and definition of PE is commonly based on the measurement of non-specific signs and symptoms, principally hypertension and proteinuria1-3. However, due to the recognition that measurement of proteinuria is prone to inaccuracies and the fact that PE complications often occur before proteinuria becomes significant, most recent guidelines also support the diagnosis of PE on the basis of hypertension and signs of maternal organ dysfunction other than proteinuria3-5. Furthermore, the clinical presentation and course of PE is variable, ranging from severe and rapidly progressing early-onset PE, necessitating preterm delivery, to late-onset PE at term. There may be associated intrauterine growth restriction (IUGR), further increasing neonatal morbidity and mortality. These features suggest that the classical standards for the diagnosis of PE are not sufficient to encompass the complexity of the syndrome. Undoubtedly, proper management of pregnant women at high risk for PE necessitates early and reliable detection and intensified monitoring, with referral to specialized perinatal care centers, to reduce substantially maternal, fetal and neonatal morbidity6, 7. In the decade since Maynard et al.8 reported that excessive placental production of soluble fms-like tyrosine kinase receptor-1 (sFlt-1), an antagonist of vascular endothelial growth factor and placental growth factor (PlGF), contributes to the pathogenesis of PE, extensive research has been published demonstrating the usefulness of angiogenic markers in both diagnosis and the subsequent prediction and management of PE and placenta-related disorders. Various reports have demonstrated that disturbances in angiogenic and antiangiogenic factors are implicated in the pathogenesis of PE and have possible relevance in the diagnosis and prognosis of the disease. Increased serum levels of sFlt-1 and decreased levels of PlGF, thereby resulting in an increased sFlt-1/PlGF ratio, can be detected in the second half of pregnancy in women diagnosed to have not only PE but also IUGR or stillbirth, i.e. placenta-related disorders. These alterations are more pronounced in early-onset rather than late-onset disease and are associated with severity of the clinical disorder. Moreover, the disturbances in angiogenic factors are reported to be detectable prior to the onset of clinical symptoms (disease), thereby allowing discrimination of women with normal pregnancies from those at high risk for developing pregnancy complications, primarily PE9-30. Plasma concentrations of angiogenic/antiangiogenic factors are of prognostic value in obstetric triage: similar to the progressively worsening clinical course observed in women with early-onset PE, changes in the angiogenic profile leading to a more antiangiogenic state can be found. Current definitions of PE are poor in predicting PE-related adverse outcomes. A diagnosis of PE based on blood pressure and proteinuria has a positive predictive value of approximately 30% for predicting PE-related adverse outcomes31. Estimation of the sFlt-1/PlGF ratio allows identification of women at high risk for imminent delivery and adverse maternal and neonatal outcome23, 30, 32-35. Moreover, it has also been shown that the time-dependent slope of the sFlt-1/PlGF ratio between repeated measurements is predictive for pregnancy outcome and the risk of developing PE, and repeated measurements have been suggested36. However, the ‘optimal’ time interval for a follow-up test remains unclear. Finally, high values are closely related to the need to deliver immediately22, 23, 37. Additionally, in normal and complicated pregnancies, angiogenic factors are correlated with Doppler ultrasound parameters, mainly uterine artery (UtA) indices38-42. Combining the sFlt-1/PlGF ratio with UtA Doppler ultrasound, at the time of diagnosis of early-onset PE, has prognostic value mainly for perinatal complications, being limited for the prediction of maternal complications37, 43. The additional measurement of the sFlt-1/PlGF ratio has been shown to improve the sensitivity and specificity of Doppler measurement in predicting PE44-48, supporting its implementation in screening algorithms. Whereas studies on the predictive efficacy of the sFlt-1/PlGF ratio in the first trimester have yielded contradictory results49, reports on the use of this marker as an aid in prediction from the mid trimester onwards have led to its suggested use as a screening tool, especially for identifying all women developing PE and requiring delivery within the subsequent 4 weeks50-52. This short review of the literature highlights that measurement of the sFlt-1/PlGF ratio has the potential to become an additional tool in the management of PE, particularly as automated tests that allow rapid and easy measurement of these markers are now widely available. Nevertheless, although these markers were incorporated recently into the German guidelines53, no formal recommendation regarding how to use sFlt-1, PlGF or the sFlt-1/PlGF ratio has been established in any official protocol. The purpose of this paper is to answer questions that are frequently asked around the use of the sFlt-1/PlGF ratio in the diagnosis and prediction of PE and regarding the implications for clinical practice, in particular, ‘When?’ and ‘In which women?’ should the sFlt-1/PlGF ratio be measured and, ‘What should be done with the results?’, and to provide guidance to educate physicians on the use of the sFlt-1/PlGF ratio in clinical practice. To achieve this, international experts in the use of angiogenic markers have strived to develop a consensus statement on the clinical use of the sFlt-1/PlGF ratio and the consequential management in pregnant women with suspected PE or at a high risk of developing PE. At the outset, it should be emphasized that: 1) the sFlt-1/PlGF ratio has not been evaluated as a screening test and 2) the sFlt-1/PlGF ratio does not replace other techniques to monitor high-risk patients. Furthermore, decisions regarding delivery are not based solely on the sFlt-1/PlGF ratio, but are always made in the context of other established techniques and clinical signs and symptoms. Finally, most of the studies on the sFlt-1/PlGF ratio have been performed using the Elecsys® assay and the cut-off levels described in this guidance have been validated so far only for this assay18, 54. Gestational age-specific sFlt-1/PlGF ratio cut-offs of > 85 (20 + 0 to 33 + 6 weeks) and > 110 (34 + 0 weeks to delivery) have been shown to be highly suggestive of PE55. The same study identified a cut-off of 33 for exclusion of PE (sensitivity, 95%; specificity, 94%). However, no insight was gained regarding the likelihood of these women developing PE over the course of their pregnancy. In the PROGNOSIS study56, 57, a single sFlt-1/PlGF ratio cut-off (<38) was validated to rule out reliably PE within 1 week (negative predictive value >96%) and rule in PE (≥38) within 4 weeks (positive predictive value >25%). The cut-offs for the sFlt-1/PlGF ratio used in this Opinion are based on these studies, adjusted for both early and late gestational age (Table 1). This population includes both women with suspicion of PE (Table 2) and women with PE already confirmed. The criteria contributing to suspicion of PE (adopted from the inclusion criteria in the PROGNOSIS and PreOS study56) are very ‘open’, covering any suspicion of PE, and are in line with usual clinical experience. Statement 1: sFlt-1/PlGF < 38 sFlt-1/PlGF ratio < 38 rules out PE, irrespective of gestational age, for at least 1 week. Further management is according to the clinician's discretion. Statement 2: sFlt-1/PlGF ratio > 85 (early-onset PE) or > 110 (late-onset PE) Diagnosis of PE or placenta-related disorder is highly likely. Management according to local guidelines. Severely elevated sFlt-1/PlGF ratios (> 655 at <34 + 0 weeks; > 201 at ≥ 34 + 0 weeks) are associated closely with the need to deliver within 48 h. Close surveillance and (if < 34 weeks) prompt initiation of antenatal corticoids to accelerate fetal lung maturation are mandatory. Statement 3: sFlt-1/PlGF ratio > 85 (early-onset PE) or > 110 (late-onset PE), repeat measurement Re-measure after 2–4 days to determine trend and follow up according to clinician's discretion depending on severity. The test frequency can be adapted to the clinical situation and trend in sFlt-1/PlGF ratio dynamics. Statement 4: sFlt-1/PlGF ratio 38–85 (early-onset PE) or 38–110 (late-onset PE) The sFlt-1/PlGF ratio provides information about the patient before the onset of overt signs and symptoms. An sFlt-1/PlGF ratio of 38–85 or 38–110 provides extra information as to which women are at moderate risk or at high risk of developing PE within 4 weeks. Current PE or a placenta-related disorder can be ruled out, but women are at (high) risk (especially in the early-onset group). Early onset: Consider a follow-up sFlt-1/PlGF test in 1–2 weeks, according to the individual clinical situation. Results are to be treated accordingly. Late onset: An intermediate result of the sFlt-1/PlGF ratio is suggestive of impending placental dysfunction. Consider lowering the threshold for induction of delivery. Statement 5: The sFlt-1/PlGF ratio has been proven as an aid in diagnosis for PE. In a woman with PE already confirmed (high blood pressure and proteinuria) the sFlt-1/PlGF ratio may be useful to determine the severity of the disorder. Using the sFlt-1/PlGF ratio for clinical management: general considerations The diagnostic and predictive value of the sFlt1/PlGF ratio in patients at risk of placenta-related disorders, i.e. PE, HELLP syndrome, IUGR and stillbirth, has been shown in the recent literature and estimation of the sFlt-1/PlGF ratio has become an additional tool in the management of these disorders, primarily PE. Repeat measurements of the sFlt-1/PlGF ratio are suggested to improve individual risk assessment in these patients, but this has to be proven by further studies. To date, the use of sFlt-1, PlGF or the sFlt-1/PlGF ratio has not been incorporated into official guidelines. In this statement, we have aimed to give good clinical practice guidance for implementation of this method into the management algorithm of pregnant women. Use of the sFlt-1/PlGF ratio may help to optimize care by improving management of women with suspected PE. We would like to thank Julia Heagerty, PhD, of Elements Communications Ltd, Westerham, UK for editorial assistance. Editorial assistance was funded by Roche Diagnostics Ltd. Apart from reimbursement of travel expenses to expert meetings, A.G., D.W., E.K., F.C. and I.H. declare no conflicts of interest. A.R., D.S., E.L., H.S., M.V. and S.B. have also received grant support from Roche Diagnostics for involvement in the PROGNOSIS study (2010−1013) and/or the PreOS study. D.S., H.S. and S.V. have received lecture fees from Roche Diagnostics. O.L. has acted as a consultant for Roche Diagnostics. S.V. has received research support from Roche and acted as an advisor for Roche and has received speaker fees from ThermoFisher." @default.
- W2079661513 created "2016-06-24" @default.
- W2079661513 creator A5014307465 @default.
- W2079661513 creator A5015411385 @default.
- W2079661513 creator A5027048775 @default.
- W2079661513 creator A5034051971 @default.
- W2079661513 creator A5036967843 @default.
- W2079661513 creator A5039597423 @default.
- W2079661513 creator A5045209840 @default.
- W2079661513 creator A5048369508 @default.
- W2079661513 creator A5051045029 @default.
- W2079661513 creator A5052797735 @default.
- W2079661513 creator A5056369229 @default.
- W2079661513 creator A5061267996 @default.
- W2079661513 creator A5072741277 @default.
- W2079661513 date "2015-03-01" @default.
- W2079661513 modified "2023-10-10" @default.
- W2079661513 title "Implementation of the <scp>sFlt</scp>‐1/<scp>PlGF</scp> ratio for prediction and diagnosis of pre‐eclampsia in singleton pregnancy: implications for clinical practice" @default.
- W2079661513 cites W1495350439 @default.
- W2079661513 cites W1501914516 @default.
- W2079661513 cites W1532968976 @default.
- W2079661513 cites W1569789076 @default.
- W2079661513 cites W1913047272 @default.
- W2079661513 cites W1924607308 @default.
- W2079661513 cites W1966757458 @default.
- W2079661513 cites W1967156112 @default.
- W2079661513 cites W1968450351 @default.
- W2079661513 cites W1971346623 @default.
- W2079661513 cites W1972743675 @default.
- W2079661513 cites W1973680815 @default.
- W2079661513 cites W1983328916 @default.
- W2079661513 cites W1989963520 @default.
- W2079661513 cites W1990795537 @default.
- W2079661513 cites W1992740425 @default.
- W2079661513 cites W1992903011 @default.
- W2079661513 cites W2005042579 @default.
- W2079661513 cites W2006522274 @default.
- W2079661513 cites W2014637033 @default.
- W2079661513 cites W2021964897 @default.
- W2079661513 cites W2023214619 @default.
- W2079661513 cites W2026146676 @default.
- W2079661513 cites W2029432061 @default.
- W2079661513 cites W2037814939 @default.
- W2079661513 cites W2038832169 @default.
- W2079661513 cites W2039809433 @default.
- W2079661513 cites W2043606766 @default.
- W2079661513 cites W2044216843 @default.
- W2079661513 cites W2052233024 @default.
- W2079661513 cites W2058315204 @default.
- W2079661513 cites W2059070269 @default.
- W2079661513 cites W2060264217 @default.
- W2079661513 cites W2065594976 @default.
- W2079661513 cites W2069029007 @default.
- W2079661513 cites W2081876722 @default.
- W2079661513 cites W2083348727 @default.
- W2079661513 cites W2086621983 @default.
- W2079661513 cites W2094395765 @default.
- W2079661513 cites W2095868162 @default.
- W2079661513 cites W2096766888 @default.
- W2079661513 cites W2097632192 @default.
- W2079661513 cites W2114279843 @default.
- W2079661513 cites W2134502189 @default.
- W2079661513 cites W2140764146 @default.
- W2079661513 cites W2143180984 @default.
- W2079661513 cites W2149627418 @default.
- W2079661513 cites W2170867031 @default.
- W2079661513 cites W2171250897 @default.
- W2079661513 cites W2260113709 @default.
- W2079661513 cites W2315265341 @default.
- W2079661513 cites W2470467076 @default.
- W2079661513 cites W301622561 @default.
- W2079661513 cites W4236182870 @default.
- W2079661513 cites W4251118184 @default.
- W2079661513 cites W4382916220 @default.
- W2079661513 doi "https://doi.org/10.1002/uog.14799" @default.
- W2079661513 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4369131" @default.
- W2079661513 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25736847" @default.
- W2079661513 hasPublicationYear "2015" @default.
- W2079661513 type Work @default.
- W2079661513 sameAs 2079661513 @default.
- W2079661513 citedByCount "177" @default.
- W2079661513 countsByYear W20796615132014 @default.
- W2079661513 countsByYear W20796615132015 @default.
- W2079661513 countsByYear W20796615132016 @default.
- W2079661513 countsByYear W20796615132017 @default.
- W2079661513 countsByYear W20796615132018 @default.
- W2079661513 countsByYear W20796615132019 @default.
- W2079661513 countsByYear W20796615132020 @default.
- W2079661513 countsByYear W20796615132021 @default.
- W2079661513 countsByYear W20796615132022 @default.
- W2079661513 countsByYear W20796615132023 @default.
- W2079661513 crossrefType "journal-article" @default.
- W2079661513 hasAuthorship W2079661513A5014307465 @default.
- W2079661513 hasAuthorship W2079661513A5015411385 @default.
- W2079661513 hasAuthorship W2079661513A5027048775 @default.
- W2079661513 hasAuthorship W2079661513A5034051971 @default.
- W2079661513 hasAuthorship W2079661513A5036967843 @default.
- W2079661513 hasAuthorship W2079661513A5039597423 @default.