{"id":1863,"date":"2016-12-01T10:02:42","date_gmt":"2016-12-01T10:02:42","guid":{"rendered":"https:\/\/www.lalpathlabs.com\/blog\/?p=1863"},"modified":"2023-10-12T12:49:18","modified_gmt":"2023-10-12T07:19:18","slug":"pre-eclampsia","status":"publish","type":"post","link":"https:\/\/www.lalpathlabs.com\/blog\/pre-eclampsia\/","title":{"rendered":"Pre-eclampsia Prediction Panel"},"content":{"rendered":"

\"Pre-eclampsia<\/p>\n

Pre-eclampsia Prediction Panel<\/span><\/strong><\/span><\/h2>\n

\"introduction<\/p>\n

Hypertensive disorders are the most common medical problems encountered in pregnancy, affecting up\u00a0to15% of pregnancies and accounting for approximately 25% of antenatal admissions. Notably\u00a0Pre-eclampsia (PE) is a major cause of maternal and fetal or neonatal mortality and morbidity. The disorder\u00a0complicates 5%-7% of all pregnancies [1]. Each year, an estimated 50,000 women die from PE worldwide\u00a0[2]. If Pre-eclampsia is not diagnosed and closely monitored, it can lead to potentially life-threatening\u00a0complications including Eclampsia, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets),\u00a0disseminated intravascular coagulation, stroke, or organ dysfunction.<\/p>\n

Diagnostic criteria for PE are new onset of hypertension (systolic BP \u001f140 mmHg, or diastolic BP \u001f90 mmHg\u00a0atleast on 2 determinations) and proteinuria (\u001f300 mg\/day) after 20 weeks of gestation. A diagnosis of PE\u00a0based on blood pressure and proteinuria has positive predictive value of approximately 30% for predicting\u00a0PE related adverse outcomes. However, due to the recognition that measurement of proteinuria is prone to\u00a0inaccuracies and the fact that PE complications often occur before proteinuria becomes significant, most\u00a0recent guidelines also support the diagnosis of PE on the basis of hypertension and signs of maternal organ\u00a0dysfunction other than proteinuria [3]. Furthermore, the clinical presentation and course of PE is variable,\u00a0ranging from severe and rapidly progressing early-onset PE, necessitating preterm delivery, to late-onset PE\u00a0at term. There may be associated Intrauterine Growth Restriction (IUGR), further increasing neonatal
\nmorbidity and mortality. These features suggest that the classical standards for the diagnosis of PE are not\u00a0sufficient to encompass the complexity of the syndrome.<\/p>\n

Till date, no treatment is available to prevent PE or hinder at least progression of the disease. The only causal\u00a0therapy of PE is delivery. Current management is focused on close monitoring of these pregnancies in\u00a0combination with treatment of hypertension<\/a><\/span> and inducing (early) delivery when indicated. Although no\u00a0therapeutic or preventive strategy is available yet, clinical experience suggests that early detection,\u00a0monitoring and supportive care are beneficial to the mother and the fetus. To optimize this, reliable\u00a0prediction of PE would be helpful allowing closer prenatal monitoring, timely diagnosis and timely\u00a0intervention.<\/p>\n

Various clinical studies have reported that routine clinical measurement of soluble Fms-like tyrosine\u00a0kinase-1 (sFlt-1), Placental Growth F-actor (PlGF), and sFlt-1\/PlGF ratio may be particularly beneficial for\u00a0the prediction of PE and in the differential diagnosis of patients with atypical presentation of PE. sFlt-1 and\u00a0PlGF may predict the onset of PE, eclampsia or HELLP some weeks before the actual onset of the disease,\u00a0this would mean that these angiogenic factors may help physicians to diagnose the disease earlier compared\u00a0to the traditional diagnosis of PE [4,5].<\/p>\n

\"pathophysiology\"<\/p>\n

PE appears to progress in two stages: The first, pre-clinical stage is characterized by poor placentation,\u00a0resulting from insufficient endovascular invasion of fetal extravillous cytotrophoblasts into the maternal\u00a0spiral arterioles. The second stage of PE, the clinical manifestation of PE, reflects generalized endothelial\u00a0dysfunction, resulting in vasoconstriction and end organ damage.<\/p>\n

The cause of pre-eclampsia is not fully understood, but there is growing evidence that angiogenic growth\u00a0factors such as PlGF and sFlt-1 play a major role in the development of pre-eclampsia. sFlt-1 is able to bind\u00a0both Vascular Endothelial Growth Factor (VEGF) and PlGF. Being free in serum, it may diminish binding of\u00a0these pro-angiogenic factors to their receptors. In patients with PE increased sFlt-1 is associated with\u00a0decreased free VEGF and PlGF resulting in a net anti-angiogenic state causing endothelial dysfunction. Of\u00a0note, sFlt-1 concentrations are high 5-6 weeks prior to onset of PE. Concentrations of free VEGF and PlGF are\u00a0also found to be low several weeks prior to clinical manifestation. Increased levels of sFlt-1 and reduced\u00a0levels of PlGF herald the onset of PE, whereas the ratio of sFlt-1\/PlGF, an index reflecting changes in both\u00a0biomarkers, is a better predictor of PE than either measure alone [6]. The intra-individual rate of change of\u00a0the sFlt 1\/PlGF ratio is highly predictive of overall PE risk [7]. Severity of disease and time of onset (early\u00a0onset vs late onset PE) seem to correlate with the dimension of change in either sFlt-1 or PlGF serum levels.<\/p>\n

\"increased<\/p>\n

\"PE<\/p>\n

\"figure<\/p>\n

Figure 2: PE is associated with an imbalance of sFlt-1 and PlGF<\/p>\n

\"prognosis<\/p>\n

PROGNOSIS (Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study) was\u00a0designed to investigate the value of using the sFlt-1:PlGF ratio for the short term prediction of the presence\u00a0or absence of preeclampsia in women with clinical suspicion of the syndrome. 1273 patients with suspected\u00a0pre-eclampsia in the gestational age of 20-34 weeks were enrolled in the study. An sFlt-1:PlGF ratio of 38 or\u00a0lower had a negative predictive value (i.e., no preeclampsia in the subsequent week) of 99.3% (95%\u00a0confidence interval [CI], 97.9 to 99.9), with 80.0% sensitivity (95% CI, 51.9 to 95.7) and 78.3% specificity\u00a0(95% CI, 74.6 to 81.7). The positive predictive value of an sFlt-1:PlGF ratio above 38 for a diagnosis of\u00a0preeclampsia within 4 weeks was 36.7% (95% CI, 28.4 to 45.7), with 66.2% sensitivity (95% CI, 54.0 to\u00a077.0) and 83.1% specificity (95% CI, 79.4 to 86.3). The study concluded that sFlt-1:PlGF ratio of 38 or lower\u00a0can be used to predict the short-term absence of preeclampsia in women in whom the syndrome is\u00a0suspected clinically.<\/p>\n

\"use<\/p>\n

At the outset, it is emphasized that:
\n1. The sFlt-1\/PlGF ratio has not been evaluated as a screening test.
\n2. The sFlt-1\/PlGF ratio does not replace other techniques to monitor high-risk patients.
\nFurthermore, decisions regarding delivery are not based solely on the sFlt-1\/PlGF ratio but are always\u00a0made in the context of other established techniques and clinical signs and symptoms.<\/p>\n

\"recommendations\"<\/p>\n

sFlt-1\/PlGF ratio when used with standard clinical assessment and subsequent clinical follow-up, show\u00a0promise in helping to diagnose (rule-in) pre-eclampsia in women<\/a><\/span> presenting with suspected pre-eclampsia\u00a0between 20 weeks and 34 weeks plus 6 days of gestation [8].<\/p>\n

Suspicion of clinical diagnosis of PE may be based on one or more of the following criteria:<\/p>\n

\u2022 New onset of elevated BP
\n\u2022 Aggravation of pre-existing hypertension
\n\u2022 New onset of protein in urine
\n\u2022 Aggravation of preexisting proteinuria
\n\u2022 One or more other reason(s) for clinical suspicion of PE:
\n– PE-related symptoms: epigastric pain, excessive edema, severe swelling (face, hands, feet), headache,\u00a0visual disturbances, sudden weight gain (>1 kg\/week).
\n– PE-related findings: low platelets, elevated liver transaminases, IUGR or abnormal uterine perfusion\u00a0detected by Doppler sonography with mean PI > 95th percentile in second trimester and \/or bilateral\u00a0notch.<\/p>\n

\"interpret\"<\/p>\n

\"result\"<\/p>\n

\u2022 sFlt-1\/PlGF ratio, an sFlt-1\/PlGF ratio < 38 rules out PE for at least one week, irrespective of gestational\u00a0age, providing reassurance to the physician and the patient. With more than 80% of patients belonging\u00a0to this patient group, clinicians are able to exclude the majority of patients, keeping them in routine\u00a0antenatal care, and focus on those who need more attention and care[9]<\/p>\n

\u2022 an sFlt-1\/PlGF ratio above 85 (early onset PE) or above 110 (late onset PE) is highly indicative of PE[9]<\/p>\n

\u2022 sFlt-1\/PlGF ratio, an sFlt-1\/PlGF ratio 38\u201385 (early onset PE) or 38\u2013110 (late onset PE) provides extra\u00a0information as to which women are at moderate risk or at high risk of developing PE within four\u00a0weeks[9]<\/p>\n

\"conclusion\"<\/p>\n

This short review of the literature highlights that measurement of the sFlt-1\/PlGF ratio has the potential to\u00a0become an additional tool in the management of PE. The test should be used in the population in which it is\u00a0most reasonable, i.e., in the high-risk population.<\/p>\n

\"refernces\"<\/p>\n

1. World Health Organization. The World Health Report 2005: make every mother and child count. November 1,\u00a02014 (http:\/\/www .who .int\/ whr\/ 2005\/ en\/ )<\/p>\n

2. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008; 371: 75-84<\/p>\n

3. American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in\u00a0pregnancy. Report of the American College of Obstetricians and Gynecologists\u2019 Task Force on Hypertension in\u00a0Pregnancy. Obstet Gynecol 2013; 122: 1122\u20131131<\/p>\n

4. Hund M, Allegranza D, Schoedl M, Dilba P, Verhagen-Kamerbeek W, Stepan H. Multicenter prospective clinical\u00a0study to evaluate the prediction of short-term outcome in pregnant women with suspected preeclampsia\u00a0(PROGNOSIS): study protocol. BMC Pregnancy Childbirth 2014; 14: 324<\/p>\n

5. Harald Z, Elisa L, Frederic C, Manu V, Anne C, Maria S, Matts O, Shaun P.B. et al. Predictive Value of the sFlt-1:PlGF\u00a0Ratio in Women with Suspected Preeclampsia. N Engl J Med 2016;374:13-22<\/p>\n

6. Verlohren S, Herraiz I, Lapaire O, et al. The sFlt-1\/PlGF ratio in different types of hypertensive pregnancy disorders\u00a0and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol 2012; 206(1):e1-8.<\/p>\n

7. Verlohren S, Herraiz I, Lapaire O, et al. New gestational phase-specific cutoff values for the use of the soluble\u00a0fms-like tyrosine kinase-1\/placental growth factor ratio as a diagnostic test for preeclampsia. Hypertension 2014;\u00a063: 346-52<\/p>\n

8. NICE Guidance, 2016 PlGF-based testing to help diagnose suspected pre-eclampsia Diagnostics guidance Published:\u00a011 May 2016 nice.org.uk\/guidance\/dg23<\/p>\n

9. H. Stepan, I. Herraiz, D. Schlembach, S. Verlohren, S. Brennecke, F. Chantraine, E. Klein, O. Lapaire, E. Llurba, A.\u00a0Ramoni, M. Vatish, D. Wertaschnigg and A. Galindo Implementation of the sFlt 1\/PlGF ratio for prediction and\u00a0diagnosis of pre-eclampsia in singleton pregnancy: implications for clinical practice. Ultrasound Obstet Gynecol
\n2015; 45: 241\u2013246<\/p>\n

Download PDF<\/strong><\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Pre-eclampsia Prediction Panel Hypertensive disorders are the most common medical problems encountered in pregnancy, affecting up\u00a0to15% of pregnancies and accounting for approximately 25% of antenatal admissions. Notably\u00a0Pre-eclampsia (PE) is a major cause of maternal and fetal or neonatal mortality and morbidity. The disorder\u00a0complicates 5%-7% of all pregnancies [1]. Each year, an estimated 50,000 women die […]<\/p>\n","protected":false},"author":6,"featured_media":9809,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[773,774,775,776,777],"acf":[],"_links":{"self":[{"href":"https:\/\/www.lalpathlabs.com\/blog\/wp-json\/wp\/v2\/posts\/1863"}],"collection":[{"href":"https:\/\/www.lalpathlabs.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.lalpathlabs.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.lalpathlabs.com\/blog\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/www.lalpathlabs.com\/blog\/wp-json\/wp\/v2\/comments?post=1863"}],"version-history":[{"count":1,"href":"https:\/\/www.lalpathlabs.com\/blog\/wp-json\/wp\/v2\/posts\/1863\/revisions"}],"predecessor-version":[{"id":9808,"href":"https:\/\/www.lalpathlabs.com\/blog\/wp-json\/wp\/v2\/posts\/1863\/revisions\/9808"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.lalpathlabs.com\/blog\/wp-json\/wp\/v2\/media\/9809"}],"wp:attachment":[{"href":"https:\/\/www.lalpathlabs.com\/blog\/wp-json\/wp\/v2\/media?parent=1863"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.lalpathlabs.com\/blog\/wp-json\/wp\/v2\/categories?post=1863"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.lalpathlabs.com\/blog\/wp-json\/wp\/v2\/tags?post=1863"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}