Hypertensive Disorders in Pregnancy

1. Hypertensive Disorders in Pregnancy Professor Hassan Chairman Department of Obstetrics and Gynecology Faculty of Medicine King Abdulaziz University

2. Mrs F is a 30-year-old woman with a history of chronic hypertension and possible preeclampsia during her first pregnancy. She is currently trying to conceive and wants to know how her hypertension will affect a future pregnancy and how it should best be managed, both now and during a pregnancy.

3. Hypertension Disorders in Pregnancy Preeclampsia- eclampsia: Pre-existing hypertension: Preeclampsia superimposed upon preexisting hypertension: Gestational hypertension:

4. Definitions • Preeclampsia : • Systolic BP ≥ 140 Mm Hg Or Diastolic BP ≥ 90 Mm Hg • Occurring ≥ 20 Weeks' Gestation • Proteinuria ≥ 300 Mg In A 24 Hour Urine Collection. • Eclampsia: The Development Of Grand Mal Seizures In A Woman With Preeclampsia. • Chronic Hypertension: • Systolic Pressure > Or =140 mmHg, Diastolic Pressure > Or =90 mmHg, Or Both, That Is Present Before The 20th Week Of Pregnancy. • Gestational Hypertension (Transient Hypertension Of Pregnancy): • Systolic Pressure ≥ Or =140 mmHg, Diastolic Pressure ≥ Or =90 mmHg, Or Both, That Develop ≥ 20th Week Of Pregnancy In A Previously Normotensive Woman, But With Out Proteinuria.

5. Preeclampsia superimposed upon chronic hypertension: • New onset proteinuria or greatly increases proteinuria after 20 weeks of gestation. • Sudden exacerbation of BP to the severe range (systolic > or =160 mmHg or diastolic > or =110 mmHg) in the last half of pregnancy. • or other signs of multisystem involvement such as thrombocytopenia or transaminitis in a woman with prior hypertension. Report of the National High Blood pressor Education program Working group on high blood pressure in pregnancy. Am J Obs gyn 2000;183:S1-22

6. (Special conditions)

7. Preeclampsia and other Hypertensive Disorders in Pregnancy • INCIDENCE: • Hypertensive disorders complicate 12 to 22 percent of pregnancies • Preeclampsia occurs in approximately 3 to 14 percent of all pregnancies worldwide • 3 and 7 percent in nulliparas • 0.8 and 5.0 percent in multiparas

8. Pre-eclampsia Diagnosis: Systolic Blood Pressure Of 140 MMHg Or Diastolic Blood Pressure 90 MMHg And Proteinuria Of 0.3 Grams Or Greater In A 24-hour Urine Specimen. On Two Occasions At Least 6 Hours Apart. • Severe • Mild Eclampsia Refers To The Development Of Grand Mal Seizures In A Woman With Gestational Hypertension Or Preeclampsia.

9. Criteria for Severe Pre-eclampsia

10. Pathogenesis

11. The Pathophysiology of preeclampsia PET begins early in pregnancy. It develop over three distinct phases. First Phase: Incomplete invasion of the trophoblast into the endometrium. Second Phase: placental under-perfusion, hypoxia, and ischemia, which then leads to release of stress factors Third Phase: Maternal pre-eclamptic systemic syndrome and endothelial adverse response.

13. Thromboxane: has a vaso-occlusive effect and increases platelets aggregation. Prostacylin:has a vaso-relaxing effect and diminishes platelets aggregation. In normal pregnancy there is a positive balance in favor of Prostacyclin.

14. Pathogenesis of Preeclampsia IMPAIRED TROPHOBLAST INVASION ABNORMAL TROPHOBLAST DIFFERENTIATION PLACENTAL ISCHEMIA IMMUNOLOGIC FACTORS GENETIC FACTORS SYSTEMIC ENDOTHELIAL DYSFUNCTION

16. Abnormal remodeling of spiral arteries 

17. Representation of Myometrial arteries and endometrial arteries

18. In normal pregnancy Invasive CTB invade maternal decidua and vasculature (zone v).

21. Clinical Manifestation of Preeclampsia Preeclampsia is a systemic disease characterized by generalized endothelial dysfunction, vasospasm and and abnormal endothelial expression of procoagulants leads to coagulopathy.

23. Impaired Trophoblast invasion Medical conditions that predispose to vascular insufficiency Obstetrical conditions that increase placental mass with a relative decrease in placental blood flow Placental hyperfusion/ischemia Fetal Growth retardation Oligohydramnios Imbalance of prostacyclin/Thromboxane Systemic endothelial damage Systemic Clinical Manifestations CNS Renal Hematological Hepatic

24. Prevention of PET

25. Preventive Strategies High-protein and low-salt dietNutritional supplementation CalciumMagnesiumZincFish and evening primrose oilAntihypertensive drugs including diureticsAntithrombotic agentsLow-dose aspirinDipyridamoleHeparinVitamins E and C None of these interventions have proven to be effective.

26. Cochrane database meta-analysis of 41randomized controlled trials In more than 36 500 women aspirin use was associated with • 19% decrease in the risk of preeclampsia (RR, 0.81; 95% CI, 0.75-0.88; number needed to treat [NNT], 69; 95% CI, 51-109), • 7% decrease in the risk of preterm delivery (RR, 0.93; 95% CI, 0.89-0.98; NNT,83; 95% CI, 50-238), • 16% decrease in the risk of fetal and neonatal death (RR, 0.84; 95% CI, 0.74-0.96; NNT, 227; 95%CI, 128-909 8% reduction in small for gestation age infants (RR 0.92; 95% CI 0.85-1.00) • No significant effects on the need for CS delivery or induction of labor

27. Risk Factors of PE • Previous history of PET (RR 7.19, 95% CI 5.85 to 8.83) • Antiphospholipids antibodies (9.72, 4.34 to 21.75), • Pre-existing diabetes (3.56, 2.54 to 4.99), • Multiple (twin) pregnancy (2.93, 2.04 to 4.21), • Nulliparity (2.91, 1.28 to 6.61), • family history (2.90, 1.70 to 4.93), • Raised BP (diastolic > or = 80 mm Hg) at booking (1.38, 1.01 to 1.87), • Raised BMI before pregnancy (2.47, 1.66 to 3.67) or at booking (1.55, 1.28 to 1.88), or • Maternal age > or = 40 (1.96, 1.34 to 2.87, for multiparous women). • Interval of >10 years since a previous pregnancy, Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. Duckitt K; Harrington D BMJ 2005 12;330 .

28. Clinical Manifestations and Complications

29. Clinical Manifestation of Preeclampsia Maternal: Hypertension: Renal: Hepatic: Hematologic: Neurologic: Fetal/Neonatal: IUGR:

30. Clinical Manifestation of Preeclampsia Hypertension: Systolic BP ≥ 40 mmHg or Diastolic ≥ BP 90 mmHg in a woman who was normotensive prior to 20 weeks of gestation. • Renal: • Proteinuria: • ≥ 0.3 g protein in a 24-hour urine specimen (or 2+ on dipstick). • Proteinuria is due, in part, to impaired integrity of the glomerular barrier and altered tubular handling of filtered proteins (hypo filtration) leading to increased protein excretion. • Creatinine clearance: Decline • Uric acid: Reduced urinary excretion of uric acid (increase serum level of uric acid)

31. Edemaand Intravascular volume: edema is no longer part of the diagnostic criteria. However, sudden and rapid weight gain and facial edema often occur in women who develop preeclampsia. Hematologic changes: Thrombocytopenia: Is the most common coagulation abnormality is due to formation of microthrombi. The prothrombin time, partial thromboplastin time, and fibrinogen concentration: are affected with complications such as abruptio placentae or with severe liver involvement. Microangiopathic hemolysis: Is detected by examination of a blood smear or elevation in the lactic dehydrogenase concentration.

32. Liver: Affected due to periportal hemorrhage, ischemic lesions, and microvesicular fat deposition. Clinically: right upper quadrant or epigastric pain, elevated liver enzymes and, in severe cases, subcapsular hemorrhage or hepatic rupture. Neurologic: Eclampsia is the most severe complications. Early signs may include headache, blurred vision, photophobia or mental state. Note: Only 50% of eclampsia cases have severe hypertension (> 160/110 mmHg) No Reliable prediction for development of eclampsia in women with preeclampsia.

33. Pulmonaryedema: The etiology is multifactorial. Excessive elevations in pulmonary vascular hydrostatic pressure (PCWP). Capillary leak, left heart failure, and iatrogenic volume overload

34. Fetus and placenta: IUGR: The fetal consequences of chronic placental hypoperfusion are fetal growth restriction and oligohydramnios. Severe or early onset preeclampsia results in the greatest decrements in birth weight compared to normotensive pregnancies. Abruptio placenta: Is infrequent (< 1 percent) in women with mild preeclampsia, but occurs in 3 percent of those with severe disease.

35. The HELLP Syndrome

36. The HELLP Syndrome • HELLP syndrome is a group of symptoms that occur in pregnant women who have: • H – Hemolytic anemia H • EL -- elevated liver enzymes • LP -- lowPlatelet count

37. The HELLP Syndrome Incidence: ranged from 2 to 12 percent. Classification: Class I: platelet nadir below 50,000/mm Class 2: platelet nadirs between 50,000 and 100,000/mm Class 3: a platelet nadir between 100,000 and 150,000/mm • Severe hypertension is not a constant or even a frequent finding in HELLP syndrome. Of 112 patients 66 percent had a diastolic BP of at least 110 mm Hg, 14.5 percent had a diastolic BP of less than 90 mm Hg. • The reported PNM has ranged from 7.7 to 60 percent. • Maternal mortality from 0 to 24 percent. Maternal morbidity is common.

38. Peripheral blood smear of normal case (Left) and patient with microangiopathic hemolytic anemia (right) note marked red cell fragmentation. The smear shows multiple helmet cells (small black arrows), other fragmented red cells (large black arrow); microspherocytes are also seen (blue arrows). The platelet number is reduced; the large platelet in the center (red arrow) suggests that the thrombocytopenia is due to enhanced destruction. In the normal (left) smear note the red cells are of relatively uniform size and shape, several platelets (black arrows) and a normal lymphocyte (blue arrow) can also be seen.

39. Criteria to Establish the Diagnosis of HELLP Syndrome • HemolysisAbnormal peripheral blood smearIncreased bilirubin <1.2 mg/dlIncreased lactic dehydrogenase >600 IU/LElevated liver enzymesIncreased SGOT ≥72 IU/LIncreased lactic dehydrogenase >600 IU/LThrombocytopeniaPlatelet count <100,000/mm

40. It is important to emphasize that these patients may have a variety of unusual signs and symptoms, none of which are diagnostic of severe preeclampsia. Pregnant women with probable preeclampsia presenting with atypical symptoms should have a complete blood count, a platelet count, and liver enzyme determinations irrespective of maternal blood pressure.

41. Clinical Manifestation and Diagnosis • The condition usually develops in the third trimester. It is more common if there are symptoms and sings of severe PET. However the final diagnosis is based on the result of the investigations. • Symptoms and signs:. The most common clinical presentation is abdominal pain and tenderness in the midepigastrium, right upper quadrant, or below the sternum. • Investigation: • Microangiopathic hemolytic anemia: with characteristic schistocytes (also called helmet cells) on blood smear. • Other signs suggestive of hemolysis include: • Elevated LDH (≥600 IU/L) or indirect bilirubin (≥1.2 mg/dL). • Low serum haptoglobin concentration (≤25 mg/dL). • Platelet count ≤100,000 cells/microL. • Serum AST ≥70 IU/L.

42. Hypertension (blood pressure ≥140/90) and proteinuria are present in approximately 85 percent of cases, but it is important to remember that either or both may be absent in women with otherwise severe HELLP syndrome.

43. Medical and Surgical Disorders Confused with the HELLP Syndrome • Acute fatty liver of pregnancyAppendicitisDiabetes mellitusGallbladder diseaseGastroenteritisGlomerulonephritisHemolytic uremic syndromeHepatic encephalopathyHyperemesis gravidarumIdiopathic thrombocytopeniaKidney stonesPeptic ulcerPyelonephritisSystemic lupus erythematosusThrombotic thrombocytopenic purpuraViral hepatitis

45. Complications of PET Long-term maternal risks

46. Long-term maternal risks • Compared with women with no history of the disease, women with PET are at increased risk of : • hypertension(RR 3.70, 95% CI 2.70-5.05 at mean follow-up of 14 years), • IHD (RR 2.16, 95% CI 1.86-2.52 at mean follow-up of 11.7 years) • Stroke (RR 1.81, 95% CI 1.45-2.27 at mean follow-up of 10.4 years • VTE (RR 1.79, 95% CI 1.37-2.33 at mean follow-up of 4.7 years). The absolute risk that a woman with or without a history of preeclampsia would develop one of these cardiovascular events at age 50 to 59 years was estimated to be 17.8 and 8.3 percent, respectively

47. DIAGNOSIS AND INITIAL EVALUATION

49. Management of PET • Confirm the diagnosis: by excluding other disorders characterized by hypertension and proteinuria. • Assess the severity of disease: whether mild or severe. • Fetal Assessment: by a non-stress test or biophysical profile, ultrasound to evaluate growth and amniotic fluid volume.

50. Quick Office Screen for Secondary Causes of Hypertension in Young Women Powrie, R. O. JAMA 2007;298:1548-1558.