Preeclampsia: Diagnosis, prevention and treatment SGAR Satellite Meeting – SAOA, November 15, 2012 Olav Lapaire Department of Obstetrics/ Laboratory for Prenatal Medicine, University Hospital Basel, Basel , Switzerland Overview •Diagnosis and definition of preeclampsia •Pathogenesis of preeclampsia •Markers for preeclampsia •Prevention of preeclampsia •Therapy options •Key points Major goal of all interventions during pregnancy: – a healthy mother and a healthy child Public Garden Make Way for Ducklings Shennan A et al. Lancet 2011 Preeclampsia (PE) • Incidence: up to 8% of all pregnancies1 • PE responsible for 1/3 of all obstetrical related morbidities2 – 22 women died between 2006-2008 in Great Britain after PE/eclampsia3 • Arterial hypertension and/or proteinuria are leading risk factors in case of intrauterine fetal death (1/5 of all intrauterine deaths)2 1.WHO international collaborative study of hypertensive disorders of pregnancy. Am J Obstet Gynecol 1988;158:80-83 2. Pre-eclampsia community guideline (PRECOG), Milne F et al.BMJ 2005;330:576-580 3. The Eighth Report of the Confi dential Enquiries into Maternal Deaths in the United Kingdom. BJOG 2011; 118 (suppl 1): 1–203 Definition of PE: Arterial hypertension (> 140/90 mm Hg) plus Proteinuria (≥ 300 mg/24 h / ≥ 2+ [U-Stick]) Preeclampsia- key points • Significant Variance of the clinical pattern! • Onset ≥ 20. weeks of gestation – Early onset disease (20−32 [34] weeks) high fetal/maternal morbidity/mortality – Late onset PE >32-[34].weeks: lower fetal/maternal morbidity/mortality Wikstrom AK, et al. Early postpartum changes in circulating pro- and anti-angiogenic factors in early-onset and late-onset pre-eclampsia. Acta Obstet Gynecol Scand 2008; 87:146-153 Lapaire O et al, Lapaire 2010 O et al. 2010 Significant variance of the clinical pattern Lapaire O et al. 2010 Lapaire O et al. 2010 Steegers EA et al., Lancet 2010 Pathogenesis of preeclampsia (PE) a) early onset PE Pathogenesis of early onset Preeclampsia-IUGR: Failure of the physiological conversion of the arterial wall: Fetal Maternal Physiological: Cytotrophoblast cells degrade tunica media of the spiral arteries Vasodilatation Preeclampsia-IUGR: Impaired invasion of cytotrophoblast cells into the tunica media Absent vasodilatation Reduced placental perfusion Compensation: art. hypertension Karumanchi A 2006 Clinical manifestation of preeclampsia can be explained by a maternal response to A generalized endothelial dysfunction UpToDate 20010 Pathogenesis of preeclampsia (PE) b) late onset PE Huppertz B et al. 2008 STBM: Syncytiotrophoblast microparticles Huppertz B et al. 2008 Predicting which women are at an increased risk of developing preeclampsia remains problematic. Identifying “at-risk” women is an important aim; A marker / marker combination would allow for -closer supervision -accurate diagnosis -timely intervention (e.g. lung maturation) -facilitate recruitment for trials of potential therapeutic agents and markers Eric First trimester screening for Down Syndrome as an exellent example for a non-invasive approach Nuchal translucency and serum markers and maternal age Nuchal translucency and maternal age Triple Test Maternal age 10 20 20 30 80 80 90 100 0 0 10 30 40 40 505060 6070 70 90 100 Detection rate (%) Lapaire O et al. Ther Umsch. 2006;63:683-91 Role of angiogenic proteins Vascular Endothelial Growth Factor (VEGF), Placental Growth Factor (PlGF), soluble fms-like tyrosine kinase (sFlt-1) A variety of proangiogenic (VEGF, PlGF) and antiangiogenic factors (sFlt-1) are elaborated by the developing placenta, the balance among these factors is important for adequate placental development. sFlt-1 and PlGF levels in preeclamptic patients vs controls Biomarker-algorithm LapaireOOetetal.al2010 2010 Lapaire Doppler ultrasound of the uterine arteries as a marker of an impaired placental perfusion Doppler ultrasound reflects the resistance in the peripheral vessels Reflexion of the pulse wave leads to a postsystolic notch Sens. 37 % (95% CI 14-60), Spez. 89% (95% CI 83-95) in the 2. trimester as marker for preeclampsia Cnossen JS. Use of uterine artery Doppler sonography to predict pre-eclampsia A sytematic review and bivariable meta-analysis CMAJ. 2008;178(6):701-11 Timepoint to screen for preeclampsia PE marker in the first trimester www.fetalmedicine.com/fmf/online-education/08-pyramid-of-care https://courses.fetalmedicine.com/calculator/pe?locale=en Early-onset pre-eclampsia screening in the 1st trimester DR% at 5% FPR History MAP ↑ uA Doppler abnormal PAPP-A ↓ PlGF ↓ PP13 ↓ Inhibin-A 33 38 40 44 63 75* 93 Yu et al ., Am J Obstet Gynecol. 2005 Poon et al, Ultrasound Obs Gyn, 2008 Poon et al, Ultrasound Obs Gyn, 2008 Poon et al, Hypertension 2008 Audibert et al. Abstract at SMFM 2010 Poon et al, Hypertension May 2009 Prevention of early-onset preeclampsia Bujold E et al. Early administration of low-dose aspirin for the prevention of preterm and term preeclampsia: a systematic review and meta-analysis. Fetal Diagn Ther. 2012;31(3):141-6 Prevention of late-onset preeclampsia Bujold E et al. Early administration of low-dose aspirin for the prevention of preterm and term preeclampsia: a systematic review and meta-analysis. Fetal Diagn Ther. 2012;31(3):141-6 All new interventions to prevent pre-eclampsia should be properly evaluated in large randomised trials before being introduced into clinical practice. (Grade A) RCOG Pre-eclampsia - study group consensus statement Treatment of preeclampsia risk reduction for women with pre-eclampsia needs a series of strategies: -standardised assessment and surveillance -avoidance and management of severe systolic and diastolic hypertension, -prevention and treatment of seizures of eclampsia, -avoidance of use of aggressive rehydration in case of severe pre-eclampsia. Thierry Girard stabilization and afterwards delivery, which is the sole cure for pre-eclampsia Always a cesarean section in case of preeclampsia? Thierry Girard Antepartum management of patients with preeclampsia Steegers EA et al., Lancet 2010 Think about an early epidural analgesia: insert before Tc-penia or coagulation disorder positive interaction with maternal blood pressure prepared for CS Thierry Girard 14.11.2012 Thierry Girard Magnesiumsulphate to all preeclamptic patients? Consider giving intravenous magnesium sulphate to women with severe pre-eclampsia. Thierry Girard • severe hypertension and proteinuria or • mild or moderate hypertension and proteinuria with one or more of the following: – symptoms of severe headache – problems with vision, such as blurring or flashing before the eyes – severe pain just below the ribs or vomiting – papilloedema – signs of clonus ( 3 beats) – liver tenderness – HELLP syndrome – platelet count falling to below 100 × 109 per litre – abnormal liver enzymes (ALT or AST rising to above 70 IU/litre). Thierry Girard NICE Clinical Guidelines 2011 loading dose of 4 g should be given intravenously over 5 minutes, followed by an infusion of 1 g/hour maintained for 24 hours recurrent seizures should be treated with a further dose of 2–4 g given over 5 minutes. NICE Clinical Guidelines 2011 BD Senkung Key Points • Differentiate early onset and late onset PE • Angiogenic/antiangiogenic marker /doppler ultrasound for risk stratification • Low dose aspirin < 16 weeks of gestation in patients at risk for PE • Delivery mode dependent on severity and gestational age • Consider an early epidural in case of a vaginal delivery • Magnesium sulphate in severe preeclampsia Eric at the gas station Thank you for your attention! Olav Lapaire [email protected]