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Hypertensive Disorders in Pregnancy Aleksandra Rajewska PhD Chair and Department of Obstetrics and Gynecology Hypertensive disorders (HD) in pregnancy Affects 7 – 10% pregnancies Increased perinatal morbidity & mortality Mild hypertension in pregnancy: 33% preterm delivery; 11% SGA neonates Severe hypertension in pregnancy: 62 – 70% preterm delivery; 40% SGA neonates Hypertensive disorders in pregnancy: classification 1. 2. 3. 4. 5. Pregnancy Induced Hypertension (PIH) or Gestational Hypertension (GH) or Transient Hypertension Preeclampsia Eclampsia Chronic hypertension Preeclampsia superimposed on chronic hypertension Maternal & fetal consequences of HD Maternal DIC Cerebral hemorrhage Retinal hemorrhage Liver insufficiency Acute renal failure Cardiac insufficiency Pulmonary edema Placental abruption Fetal IUGR Low birth weight Oligohydramnios Preterm delivery Neonatal prematurity Intrauterine hypoxia Intrauterine fetal death Placental abruption Ethiology Incomplete trophoblastic invasion of uterine vessels: Uteroplacental blood flow impairment Diminished placental perfusion Immunological factors: Microscopic changes: acute graft rejection Impairment of blocking antibodies formation Th1/Th2 imbalance Anticardiolipin antibodies Spiral arteries modification Ethiology Vasculopathy & inflammatory changes Placental ischemia: released factors provoke endothelial injury Oxidative stress: formation of self-propagating lipid peroxides Nutritional factors Antioxidants deficiency Obesity & atherosclerosis Genetic factors: primipaternity? Pathogenesis Vasospasm Endothelial cell activation Increase pressor response Coagulation promotion Pregnancy Induced Hypertension (PIH) 6 – 17% of primiparas 2 – 4% of multiparas Blood pressure ≥ 140/90 mmHg occurring for first time during pregnancy Blood pressure returns to normal < 12 weeks postpartum No proteinuria Edema is not a PIH criterion any more! Final diagnosis – postpartum Preeclampsia (PE) 2 – 7% of primiparas 14% of twin pregnancies 18% with PE in previous pregnancy Minimum criteria BP ≥ 140/90 mmHg after 20 weeks’ gestation Proteinuria ≥ 300 mg/24 hours or ≥ 1+ dipstick Increased certainty BP ≥ 160/110 mmHg Proteinuria ≥ 2.0 g/24 hours or ≥ 2+ dipstick Serum creatinine >1,2 mg/dL Persistent headache or other cerebral or visual disturbances Persistent epigastric pain Preeclampsia (PE) Pregnancy-specific syndrome of reduced organ perfusion secondary to placental hypoperfusion, vasospasm and endothelial activation Risk factors: nulliparity, multifetal gestation, maternal age >35 years, obesity, ethnicity Preeclampsia (PE) Preventive factors: placenta previa, smoking Histopathology: glomerular lesion In severe cases proteinuria may fluctuate over any 24-hours period Eclampsia Generalized tonic-clonic convulsions (beginning about facial muscles) with subsequent coma in a woman with preeclampsia Eclampsia Typically in the third trimester Prognosis always serious Preventable! Fatal coma without convulsions – dgn. controversial Eclampsia Antepartum 38 – 53% Intrapartum 18 – 36% Postpartum 11 – 44% Life threatening for mother & fetus! Maternal mortality: 1,8 – 14% Fetal/neonatal mortality: the earlier in pregnancy E occurs the higher Eclampsia: sequels Transient diaphragm fixation: respiratory arrest Continuous convulsions: „status epilepticus” Placental abruption DIC Massive cerebral hemorrhage Neurological deficits Eclampsia: sequels Aspiration pneumonia Pulmonary edema Cardiopulmonary arrest Acute renal failure Maternal death Eclampsia: differential diagnosis Exclude: Epilepsy Encephalitis Meningitis Cerebral tumor Cysticercosis Ruptured cerebral aneurysm Eclampsia: treatment 1. 2. 3. 4. 5. Loading dose of magnesium sulfate i.v.* Continuous infusion of magnesium sulfate i.v. or periodic i.m. injections Antihypertensive medication (i.v. or oral) if diastolic pressure > 100 mmHg Avoid diuretics and limitations of fluid administration! DELIVERY * Magnesium sulfate in eclampsia is given as anticonvulsant, not as hypertension treatment! Chronic hypertension Blood pressure ≥ 140/90 mmHg before pregnancy or diagnosed before 20 weeks’ gestation or Hypertension first diagnosed after 20 weeks’ gestation or Hypertension persistent after 12 weeks’ postpartum Superimposed preeclampsia New-onset proteinuria ≥ 300 mg/24 hours in hypertensive woman A sudden increase in proteinuria or blood pressure in woman with hypertension and proteinuria before 20 weeks’ gestation Superimposed preeclampsia Often develops earlier in pregnancy and gets more severe than „pure” preeclampsia All chronic hypertensive disorders predispose to development of superimposed preeclampsia and eclampsia! Pathophysiology: cardiovascular system Increased cardiac afterload caused by hypertension Cardiac preload affected by hypovolemia Hemoconcentration: a consequence of general vasoconstriction and vascular permeability Excessive reaction to even normal blood loss at delivery Patophysiology: blood & coagulation Acute thrombocytopenia < 100 000/µL Fragmentation hemolysis (microangiopathic h.): elevated serum lactate dehydrogenase levels HELLP syndrome: Hemolysis, ELevated liver transaminase enzymes, Low Platelets 0,2 – 0,6% of all pregnancies 4 – 12% of pregnancies complicated by PE or E But 15% of pregnancy without hypertension or proteinuria! Patophysiology: volume homeostasis Decrease in renin, angiotensin II & aldosterone activity Paradoxical sodium retention Expanded volume of extracellular fluid: Endothelial injury Reduced plasma oncotic pressure (proteinuria) Pathophysiology: kidney Reduced renal perfusion Reduced glomerular filtration Elevated plasma uric acid concentration Proteinuria: albumins, globulins, hemoglobin & transferrin Pathophysiology: kidney In mild to moderate PE: elevated plasma creatinine values Severe PE: intrarenal vasospasm & oliguria Intensive intravenous fluid therapy contraindicated! Intravenous dopamine infusion recommended! Patophysiology: liver Most common in HELLP syndrome Periportal hemorrhage described by Virchow in 1856 Focal hemorrhages can cause hepatic rupture or subcapsular hematoma Patophysiology: brain Gross hemorrhage due to ruptured arteries caused by severe hypertension: most common in women with underlying chronic hypertension; PE is not necessary! Hyperemia, ischemias, thrombosis & hemorrhage: common in PE, universal with eclampsia Patophysiology: brain Doppler findings in eclampsia: cerebral hyperperfusion similar to hypertensive encephalopathy Cerebral edema Pathophysiology: placenta Uteroplacental perfusion compromised from vasospasm Most common in HELLP syndrome Doppler velocimetry! Prediction Uric acid Fibronectin Coagulation activation Oxidative stress Cytokines Placental peptides Fetal DNA Uterine artery Doppler velocimetry Management: prevention? Low-dose Aspirin Antioixdants No salt intake restrictions No slimming diet! Management: antepartum hospitalization Detailed examination and daily scrutiny for: headache, visual disturbances, epigastric pain and rapid weight gain Everyday weight admittance Analysis for proteinuria (every 2 days) Management: antepartum hospitalization Blood pressure readings (every 4 hours) Measurements of plasma creatinine, hematocrit, platelets, serum liver enzymes Frequent evaluation of fetal size and amniotic fluid volume Management: conservative antihypertensive therapy Aim: to prolong pregnancy and/or modify perinatal outcomes α – metyldopa: central & peripheral action; no compromise of fetal hemodynamics Labetalol: αβ – blocker Management: conservative antihypertensive therapy Nifedipine, werapamil: Ca channel blockers Contraindicated in I trimester! Contraindicated if high risk of eclampsia (magnesium sulfur administration causes hypotony) Dihydralazin: in severe hypertension Management: termination of pregnancy Delivery is the cure for preeclampsia! Mild PE + fetal prematurity: temporizing Moderate to severe PE: labor preinduction & induction Severe PE or unfavorable cervix: elective caesarian section Subarachnoid analgesia recommended Hypertensive disorders in puerperium PIH: recovery in few days Hypotensive agents: 3 – 4 weeks postpartum PE/E: continue magnesium sulfate administration 24 hours postpartum and hypotensive agents Hypertensive disorders in puerperium Eclampsia in puerperium – most common in first 48 hours postpartum; incidentally up to 4 weeks postpartum Chronic hypertension – risk of cardiac failure, pulmonary edema, renal failure, encephalopathy Thank you