ΕΓΚΥΜΟΣΥΝΗ ΚΑΙ ΥΠΕΡΤΑΣΗ Ανδρέας Πιτταράς Καρδιολόγος Hypertension specialist ESH

1. ΕΓΚΥΜΟΣΥΝΗ ΚΑΙ ΥΠΕΡΤΑΣΗ Ανδρέας Πιτταράς Καρδιολόγος Hypertension specialist ESH Υπερτασικό Ιατρείου Τζάνειο νοσοκομείο Υπερηχοκαρδιογραφικό εργαστήριο ΝΜΥΑ ΙΚΑ

2. Hypertensive disorders in pregnancy: a major causeof • maternal • fetal • neonatal morbidity and mortality

3. Pregnant women with hypertension at higher risk for • abruptio placentae • cerebrovascular events • organ failure • DIC

4. Fetus at higher risk for • intrauterine growth retardation • prematurity • intrauterine death

5. WHO definition of hypertension in pregnancy 1. SBP > 140 mmHg or DBP > 90 mmHg 2. Rise in SBP > 25 mmHg or rise in DBP > 15 mmHg compared to pre-pregnancy values or those in the first trimester

6. Definition of hypertension in pregnancy SBP > 140 mmHg or DBP > 90 mmHg

7. Cardiovascular changes in pregnancy Parameter Timing All bottom at 20-24 wks, then rise gradually to pre-pregnancy values at term Early 2nd trimester, then stable Early 2nd trimester, then stable Peaks in early 2nd trimester, then until term 4-6 mmHg 8-15 mmHg 6-10 mmHg 12-18 BPM 10-30% 33-45% SBP DBP MAP HR SV CO Main DM, Main EK: Obstetrics and Gynecology, 1984

8. Definition CHS NHBPEPWG WHO DBP > 90 DP > 110 BP > 140/90 or rise SP > 25 and/or DP > 15 mmHg DP > 110 SP > 160 Hypertension, mmHg Severe hypertension BP > 140/90 DP > 110 or SP > 160 CHS = Canadian Hypertension Society NHBEPWG = National High Blood Pressure Education Program Working Group (US) WHO = World Health Organization

9. Definition ISSH ASSH ACOG DP > 90 DP > 110 DP > 90 or SP > 140 DP > 110 SP > 160-180 Hypertension, mmHg Severe hypertension DP > 90 and/or SP > 140, or rise in SP of > 25 and in DP of > 15 DP > 110 and/or SP > 170 ISSH = International Society for Study of Hypertension ASSH = Australian Society for Study of Hypertension ACOG = American College of Obstetricians and Gynecologists

10. Criterion CHS NHBPEPWG WHO IV > 3 IV - Korotkoff sound Severe proteinuria (24-h urine collection, g/d) V > 2 CHS = Canadian Hypertension Society NHBEPWG = National High Blood Pressure Education Program Working Group (US) WHO = World Health Organization

11. Criterion ISSH ASSH ACOG Korotkoff sound Severe proteinuria (24-hr urine collection, g/d) IV > 0.3 or positive dipstick result of > 2+ - > 5 IV > 3 ISSH = International Society for Study of Hypertension ASSH = Australian Society for Study of Hypertension ACOG = American College of Obstetricians and Gynecologists

12. Measurement of BP • Mercury sphygmomanometer • Both Phases IV and V to be recorded • Phase IV should be used for initiating clinical investigation and management

13. Classification of hypertension in pregnancy • pre-existing hypertension • gestational hypertension • pre-existing hypertension plus superimposed gestational hypertension with proteinuria • antenatally unclassifiable hypertension

14. Pre-existing hypertension • 1-5% of pregnancies • BP > 140/90 mmHg predates pregnancy or develops before20 weeks of gestation • In most cases, hypertension persists more than 42 days post partum, it may be associated with proteinuria

15. Gestational hypertension Pregnancy-induced hypertension with or without proteinuria Hypertension develops after 20 weeks´ gestation, in most cases, it resolves within 42 days post partum Poor organ perfusion

16. Pre-existing hypertension plus superimposed gestational hypertension with proteinuria Further worsening of BP and protein excretion > 3 g/day in 24-hour urine collection after 20 weeks´ gestation Previous terminology “chronic hypertension with superimposed pre-eclampsia“

17. Antenatally unclassifiable hypertension Hypertension with or without systemic manifestation BP first recorded after 20 weeks´ gestation, re-assessment necessary at or after 42 days post partum

18. Pre-eclampsia • Gestational hypertension associated • with significant proteinuria • 300 mg/l or • 500 mg/24 h or • dipstick 2+ or more • Poor organ perfusion

19. Basic laboratory tests for monitoring hypertension in pregnancy • Hemoglobin and hematocrit • Platelet count • Serum AST, ALT, LDH • Proteinuria (24-h urine collection) • Urinalysis • Serum uric acid • Serum creatinine

20. Basic laboratory tests for monitoring hypertension in pregnancy Hemoconcentration supports diagnosis of gestational hypertension with or without proteinuria. It indicates severity. Levels may be low in very severe cases because of hemolysis. Low levels < 100,000 x 109/L may suggest consumption in the microvasculature. Levels correspond to severity and are predictive of recovery rate in post-partum period, especially for women with HELLP syndrome.* Hemoglobin and hematocrit Platelet count * HELLP – Hemolysis, Elevated Liver enzyme levels and Low Platelet count

21. Basic laboratory tests for monitoring hypertension in pregnancy Elevated levels aid in differential diagnosis of gestational hypertension and may reflect severity. Levels drop in pregnancy. Elevated levels suggest increasing severity of hypertension;assessment of 24-h creatinine clearance may be necessary. Serum uric acid Serum creatinine

22. Basic laboratory tests for monitoring hypertension in pregnancy Elevated levels suggest hepatic involvement. Increasing levels suggest worsening severity. Elevated levels are associated with hemolysis and hepatic involvement. May reflect severity and may predict potential for recovery post partum, especially for women with HELLP* syndrome. Serum AST, ALT Serum LDH * HELLP – Hemolysis, Elevated Liver enzyme levels and Low Platelet count

23. Basic laboratory tests for monitoring hypertension in pregnancy Urinalysis Proteinuria (24-h urine collection) Dipstick test for proteinuria has significant false-positive and false-negative rates. If dipstick results are positive (> 1), 24-h urine collection is needed to confirm proteinuria. Negative dipstick results do not rule out proteinuria, especially if DBP > 90 mmHg. Standard to quantify proteinuria. If in excess of 2g/day, very close monitoring is warranted. If in excess of 3g/day, delivery should be considered.

24. Management of hypertension in pregnancy • depends on • BP levels • gestational age • associated maternal and fetal risk factors

25. Non-pharmacologic management • SBP 140-149 mmHg or DBP 90-99 mmHg • activity, bed rest (left lateral position) AVOID : weight reduction and salt restriction

26. Emergency management of hypertension • in pregnancy • SBP ≥ 170 or DBP ≥ 110 mmHg • hydralazine, labetalol, methyldopa or nifedipine

27. Thresholds for drug treatment initiation • BP > 140/90 mmHg in women • with gestational hypertension without proteinuria or • pre-existing hypertension before 28 weeks' gestation or • gestational hypertension and proteinuria or symptoms at any time or • pre-existing hypertension and TOD or • pre-existing hypertension and superimposed gestational hypertension • BP > 150/95 mmHg • In all other circumstances • methyldopa, labetalol, calcium antagonists, and beta-blockers • AVOID: ACE inhibitors, AIIA, diuretics • magnesium sulfate: eclampsia, treatment and prevention of seizures

28. Br J Obstet Gynaecol 1998;105:718-22

29. Antihypertensive drugs used in pregnancy Women with pre-existing hypertension are advised to continue their current medication except for ACE inhibitors and AIIA

30. Antihypertensive drugs used in pregnancy Central alfa agonists Beta-blockers Alfa-/beta- blockers Methyldopais the drug of choice. Atenolol and metoprolol appear to be safe and effective in late pregnancy. Labetalol has comparable efficacy with methyldopa, in case of severe hypertension, it could be given intravenously.

31. Antihypertensive drugs used in pregnancy Calcium- channel blockers ACE inhibitors, angiotensin II antagonists Oral nifedipine or i.v. isradipine could be given in hypertensive emergencies. Potential synergism with magnesium sulfate may induce hypotension. Fetal abnormalities including death can be caused and these drugs should not be used in pregnancy.

32. Antihypertensive drugs used in pregnancy Diuretics Direct vasodilators Diuretics are recommended for chronic hypertension if prescribed before gestation or if patients appear to be salt-sensitive. They are not recommended in pre-eclampsia. Hydralazine is no longer the parenteral drug of choice; perinatal adverse effects.

33. Breast-feeding • Does not increase BP in nursing mothers • All antihypertensive agents taken by the nursing mother are excreted into breast milk; however, most of them are present at very low concentrations, except for propranolol and nifedipine concentrations, which are similar to maternal plasma

34. Implications of hypertension in pregnancy

35. Pathophysiologic factors involved in preeclampsia

36. Classification of hypertensive disorders of pregnancy Chronic hypertension BP 140/90 mm Hg before the 20th week of gestation Preeclampsia Elevated BP ( 140/90 mm Hg) in a patient who was normotensive before 20 weeks of gestation, accompanied by      Urinary excretion of 0.3 g of protein in a 24-h collection Other features that increase the certainty of the diagnosis of preeclampsia      BP 160/110 mm Hg      Proteinuria 2.0 g/24 h that appears initially during pregnancy and regresses postpartum      Newly-elevated serum creatinine concentration ( 1.2 mg/dL)      Platelet count 100,000/mm3 and/or evidence of microangiopathic hemolytic anemia      Elevated hepatic enzymes (ALT or AST)

37. Classification of hypertensive disorders of pregnancy Preeclampsia superimposed upon chronic hypertension (which carries a worse prognosis than either condition alone) is more likely with one or more of the following: New onset proteinuria ( 0.3 g/24 h)      Hypertension and proteinuria before 20 weeks of gestation      Sudden increase in proteinuria      Sudden increase in BP, despite previous good control      Thrombocytopenia (platelets 100,000 mm3)      Increase in ALT or AST to abnormal levels

38. Classification of hypertensive disorders of pregnancy Eclampsia  Occurrence of seizures that cannot be attributed to other causes in a patient with preeclampsia Gestational hypertension Transient hypertension of pregnancy (if preeclampsia is not present at time of delivery and BP returns to normal by 12 weeks postpartum)      Chronic hypertension (if the elevated BP seen during pregnancy persists longer than 12 weeks postpartum)

39. Management of hypertension in pregnancy

40. Drug therapy for hypertension in pregnancy Recommended Methyldopa initial drug of choice against which all other antihypertensive agents must be tested; used for the longest time in the treatment of hypertension in pregnancy, so it has the best long-term follow-up data supporting its lack of toxicity; also lowers the number of midtrimester abortions in hypertensive women compared with placebo Hydralazine used extensively, usually with methyldopa, and considered safe for mother and fetus by most obstetricians -blockers (typically atenolol or labetalol) used with caution and concern about growth retardation, fetal bradycardia, and the ability of the fetus to withstand hypoxic stress Nifedipine teratogenic in rats (at 30 the recommended dose in humans); sometimes acutely used in preterm labor, but without FDA approval

41. Drug therapy for hypertension in pregnancy Not recommended Diuretics cause volume depletion, which has been associated with poor fetal outcomes Contraindicated ACE inhibitors or angiotensin II receptor antagonists associated with lethal acute renal failure in neonates of women treated in the third trimester

42. Relative risk of preeclampsia: calcium supplementation vs placebo

43. Preeclampsia: efficacy of anti-platelet agents vs placebo INCIDENCEOUTCOMEANTIPLT. AGENTS VS PLCB RR(95% CI) Pregnancy-induced hypertension 795/8464 (9.4%)810/8450 (9.6%)0.96 (0.88 1.05) Proteinuric preeclampsia 951/13,991 (6.8%)1110/13,973 (7.9%) 0.85 (0.79 0.93) Preterm delivery 1772/13,473 (13.1%)1928/13,534 (14.2%)0.92 (0.87 0.97) Fetal, neonatal, or infant death 361/14,325 (2.5%)407/14,353 (2.8%)0.88 (0.77 1.01) Small for gestational age 668/9439 (7.1%)701/9448 (7.4%)0.94 (0.85 1.04)