Hypertensi ve Disorders in Pregnancy

1. Hypertensive Disorders in Pregnancy Aleksandra Rajewska PhD Chair and Department of Obstetrics and Gynecology

2. 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

3. Hypertensive disorders in pregnancy: classification • Pregnancy Induced Hypertension (PIH) or Gestational Hypertension (GH) or Transient Hypertension • Preeclampsia • Eclampsia • Chronic hypertension • Preeclampsia superimposed on chronic hypertension

4. 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 Maternal & fetal consequences of HD

5. 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

6. Spiral arteries modification

7. 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?

8. Pathogenesis • Vasospasm • Endothelial cell activation • Increase pressor response • Coagulation promotion

9. 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

10. 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)

11. 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

12. Preeclampsia (PE) • Preventive factors: placenta previa, smoking • Histopathology: glomerular lesion • In severe cases proteinuria may fluctuate over any 24-hours period

13. Eclampsia Generalized tonic-clonic convulsions (beginning about facial muscles) with subsequent coma in a woman with preeclampsia

14. Eclampsia • Typically in the third trimester • Prognosis always serious • Preventable! • Fatal coma without convulsions – dgn. controversial

15. 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

16. Eclampsia: sequels • Transient diaphragm fixation: respiratory arrest • Continuous convulsions: „status epilepticus” • Placental abruption • DIC • Massive cerebral hemorrhage • Neurological deficits

17. Eclampsia: sequels • Aspiration pneumonia • Pulmonary edema • Cardiopulmonary arrest • Acute renal failure • Maternal death

18. Eclampsia: differential diagnosis • Exclude: • Epilepsy • Encephalitis • Meningitis • Cerebral tumor • Cysticercosis • Ruptured cerebral aneurysm

19. Eclampsia: treatment • 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!

20. 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

21. 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

22. 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!

23. 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

24. 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!

25. 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)

26. Pathophysiology: kidney • Reduced renal perfusion • Reduced glomerular filtration • Elevated plasma uric acid concentration • Proteinuria: albumins, globulins, hemoglobin & transferrin

27. 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!

28. Patophysiology: liver • Most common in HELLP syndrome • Periportal hemorrhage described by Virchow in 1856 • Focal hemorrhages can cause hepatic rupture or subcapsular hematoma

29. 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

30. Patophysiology: brain • Doppler findings in eclampsia: cerebral hyperperfusion similar to hypertensive encephalopathy • Cerebral edema

31. Pathophysiology: placenta • Uteroplacental perfusion compromised from vasospasm • Most common in HELLP syndrome • Doppler velocimetry!

32. Prediction • Uric acid • Fibronectin • Coagulation activation • Oxidative stress • Cytokines • Placental peptides • Fetal DNA • Uterine artery Doppler velocimetry

33. Management: prevention? • Low-dose Aspirin • Antioixdants • No salt intake restrictions • No slimming diet!

34. 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)

35. 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

36. 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

37. 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

38. 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

39. Hypertensive disordersin puerperium • PIH: recovery in few days • Hypotensive agents: 3 – 4 weeks postpartum • PE/E: continue magnesium sulfate administration24 hours postpartum and hypotensive agents

40. Hypertensive disordersin puerperium • Eclampsia in puerperium – most common in first48 hours postpartum; incidentally up to 4 weeks postpartum • Chronic hypertension – risk of cardiac failure, pulmonary edema, renal failure, encephalopathy

41. Thank you