Update on Prediction & prevention of Preeclampsia

1. Assist. Prof. S. Rouholamin Update on Prediction & prevention of Preeclampsia

2. Hypertension in Pregnancy

3. Etiology & Definition • Complicates 10-20% of pregnancies • Elevation of BP ≥140 mmHg systolic and/or ≥90 mmHg diastolic, on two occasions at least 6 hours apart.

4. Categories • Chronic Hypertension • Gestational Hypertension • Preeclampsia • Preeclampsia superimposed on Chronic Hypertension

5. Chronic Hypertension • “Preexisting Hypertension” • Definition • Systolic pressure ≥ 140 mmHg, diastolic pressure ≥90 mmHg, or both. • Presents before 20th week of pregnancy or persists longer then 12 weeks postpartum. • Causes • Primary = “Essential Hypertension” • Secondary = Result of other medical condition (ie: renal disease)

6. Prenatal Care for Chronic Hypertensives • Electrocardiogram should be obtained in women with long-standing hypertension. • Baseline laboratory tests • Urinalysis, urine culture, and serum creatinine, glucose, and electrolytes • Tests will rule out renal disease, and identify comorbidities such as diabetes mellitus. • Women with proteinuria on a urine dipstick should have a quantitative test for urine protein.

7. Treatment for Chronic Hypertension • Avoid treatment in women with uncomplicated mild essential HTN as blood pressure may decrease as pregnancy progresses. • May taper or discontinue meds for women with blood pressures less than 120/80 in 1st trimester. • Reinstitute or initiate therapy for persistent diastolic pressures >95 mmHg, systolic pressures >150 mmHg, or signs of hypertensive end-organ damage. • Medication choices = Oral methyldopa and labetalol.

8. Preeclampsia • Definition = New onset of hypertension and proteinuria after 20 weeks gestation. • Systolic blood pressure ≥140 mmHg OR diastolic blood pressure ≥90 mmHg • Proteinuria of 0.3 g or greater in a 24-hour urine specimen • Preeclampsia before 20 weeks, think MOLAR PREGNANCY! • Categories • Mild Preeclampsia • Severe Preeclampsia • Eclampsia • Occurrence of generalized convulsion and/or coma in the setting of preeclampsia, with no other neurological condition.

9. Preeclampsia • Severe Preeclampsia must have one of the following: • Symptoms of central nervous system dysfunction = Blurred vision, scotomata, altered mental status, severe headache • Symptoms of liver capsule distention = Right upper quadrant or epigastric pain • Nausea, vomiting • Hepatocellular injury = Serum transaminase concentration at least twice normal • Systolic blood pressure ≥160 mm Hg or diastolic ≥110 mm Hg on two occasions at least six hours apart • Thrombocytopenia = <100,000 platelets per cubic milimeter • Proteinuria = 5 or more grams in 24 hours • Oliguria = <500 mL in 24 hours • Severe fetal growth restriction • Pulmonary edema or cyanosis • Cerebrovascular accident

10. Preeclampsia superimposed on Chronic Hypertension • Affects 10-25% of patients with chronic HTN • Preexisting Hypertension with the following additional signs/symptoms: • New onset proteinuria • Hypertension and proteinuria beginning prior to 20 weeks of gestation. • A sudden increase in blood pressure. • Thrombocytopenia. • Elevated aminotransferases.

11. Treatment of Preeclampsia • Definitive Treatment = Delivery • Major indication for antihypertensive therapy is prevention of stroke. • Diastolic pressure ≥105-110 mmHg or systolic pressure ≥160 mmHg • Choice of drug therapy: • Acute – IV labetalol, IV hydralazine, SR Nifedipine • Long-term – Oral methyldopa or labetalol

12. Gestational Hypertension • Mild hypertension without proteinuria or other signs of preeclampsia. • Develops in late pregnancy, after 20 weeks gestation. • Resolves by 12 weeks postpartum. • Can progress onto preeclampsia. • Often when hypertension develops <30 weeks gestation. • Indications for and choice of antihypertensive therapy are the same as for women with preeclampsia.

13. Risk Factors for Hypertension in Pregnancy • Nulliparity • Preeclampsia in a previous pregnancy • Age >40 years or <18 years • Family history of pregnancy-induced hypertension • Chronic hypertension • Chronic renal disease • Antiphospholipid antibody syndrome or inherited thrombophilia • Vascular or connective tissue disease • Diabetes mellitus (pregestational and gestational) • Multifetal gestation • High body mass index • Male partner whose previous partner had preeclampsia • Hydropsfetalis • Unexplained fetal growth restriction

14. Evaluation of Hypertension in Pregnancy • History • ID and Complaint • HPI (S/S of Preeclampsia) • Past Medical Hx, Past Family Hx • Past Obstetrical Hx, Past GyneHx • Social Hx • Medications, Allergies • Prenatal serology, blood work • Assess for Hypertension in Pregnancy risk factors • Physical • Vitals • HEENT = Vision • Cardiovascular • Respiratory • Abdominal = Epigastricpain, RUQ pain • Neuromuscular and Extremities = Reflex, Clonus, Edema • Fetus = Leopold’s, FM, NST

15. Evaluation of Hypertension in Pregnancy • Laboratory Tests • CBC (Hgb, Plts) • Renal Function (Cr, UA, Albumin) • Liver Function (AST, ALT, ALP, LD) • Coagulation (PT, PTT, INR, Fibrinogen) • Urine Protein (Dipstick, 24 hour)

16. Management of Hypertension in Pregnancy • Depends on severity of hypertension and gestational age!!!! • Observational Management • Restricted activity • Close Maternal and Fetal Monitoring • BP Monitoring • S/S of preeclampsia • Fetal growth and well being (NST, and U/S) • Routine weekly or biweekly blood work

17. Management of Hypertension in Pregnancy • Medical Management • Acute Therapy = IV Labetalol, IV Hydralazine, SR Nifedipine • Expectant Therapy = Oral Labetalol, Methyldopa, Nifedipine • Eclampsia prevention = MgSO4 • Contraindicated antihypertensive drugs • ACE inhibitors • Angiotensin receptor antagonists

18. Management of Hypertension in Pregnancy • Proceed with Delivery • Vaginal Delivery VS Cesarean Section • Depends on severity of hypertension! • May need to administer antenatal corticosteroids depending on gestation! • Only cure is DELIVERY!!!

19. Prediction: • Routine urine analysis • Prevention: • Chocolate

20. Outline • Introduction • Prediction • Prevention

21. Cochrane Systematic Review Gold Standard' for high-quality systematic reviews

22. Preeclampsia: • Hypertension associated with proteinuria.

23. Pathogenesis: • unknown (Barton& Sibai, 2008). • Impaired trophoblast differentiation& invasion • Placental & endothelial dysfunction • Immune maladaptation to paternal Ags • Exaggerated systemic inflam response.

24. Pathogenesis: • Differs with various risk factors: • PG Vs MG with previous PE • preexisting vas dis • preexisting DM or • multifetal gestation.

25. In PE: Impaired trophoblast differentiation & invasion

26. Placental and endothelial dysfunction

27. PREDICTION OF PE • Why prediction is important? • The ideal screening test • Methods I. Preconception factors II. Pregnancy-Related Factors 1. Risk factors 2. Markers

28. Why prediction is important: • The risk for recurrent PE can be as high as 65%(Barton& Sibai, 2008). • PE is associated with substantial maternal& perinatal complications

29. The ideal Screening test: Simple Noninvasive Rapid Inexpensive Easy to perform early in pregnancy Highly sensitivity & predictive.

30. I. Preconception factors 1st step in the management of a woman with a history of PE is to conduct a detailed evaluation of potential risk factors(Barton& Sibai, 2008).

31. Preconceptional Risk Factors Rates of preeclampsia depend on: severity of underlying complications& combinations of risk factors.

32. II. Pregnancy-Related Factors • Regular antenatal care is mandatory for the prevention & early detection of PE. • Risk factors:Magnitude of risk depends on the number of factors • Hydrops/hydropic degeneration of the placenta • Multifetal gestation • Unexplained FGR • Gestational hypertension • UTI • Periodontal infection • Markers • Biophysical • Biochemical

33. Markers • Many • Based on: pathophysiological abnormalities

34. SCREENING TESTS FOR PE (WHO, 2004) • I. Placental perfusion & vascular resistance dysfunction • Mean arterial blood pressure • Roll over test • Doppler ultrasound • Isometric exercise test • Intravenous infusion of angiotensin II • Platelet angiotensin II binding • Platelet calcium response to arginine vasopressin • Renin • 24-hour ambulatory blood pressure monitoring • II. Fetoplacental unit dysfunction • Human chorionic gonadotropin • Alpha fetoprotein • Estriol • Inhibin A • Pregnancy-associated plasma protein A • Activin A • Corticotropin release hormone

35. III. Renal dysfunction Serum uric acid Microalbuminuria Urinary calcium excretion Urinary kallikrein Microtransferrinuria N-acetyl- glucosarninidase IV. Endothelial& oxidant stress dysfunction Platelet count Platelet activation and endothelial cell adhesion molecules Prostacyclin Cytokines Isoprostanes, Antiphospholipid antibodies, Placenta growth factor Hematocrit Antithrombin Ill Calcium Transferrin Atrial natriuretic peptide Fibronectin Endothelin Thromboxane Homocysteine Serum lipids Insulin resistance Plasminogen activator inhibitor Leptin Total proteins Magnesium Ferritin Haptoglobin microglobulin Genetic markers

36. I. Biophysical • Mean arterial pressure • (2D BP+S BP)/3 • Better predictor of PE than S& D BP(BMJ 200817;336:111; Meta-analysis of 34 RCT) • 2nd trimester MA BP ≥ 90 mm Hg had +ve LR 3.5 and –ve LR 0.46 • BP remains the cornerstone of early diagnosis although it has limitations: • measurement errors associated with sphygmomanometer • effect of maternal posture on BP in pregnant women}.

37. Repeated routine urinalysis throughout pregnancy NOT useful for predicting PE • (JAMA 2003: 12;289(10):1220)

38. Uterine artery Doppler ultrasound • }impaired trophoblastic invasion of the spiral arteries: reduction in uteroplacental blood flow} • High pulsatility index and/or Notch in 1st & 2nd trimesters: poor predictor of PE(Papgeorghiou & Leslie, 2007) • Uterine artery Doppler plus biochemical markers • Promising results • Current data do not support this combination for routine screening for PE (Barton& Sibai, 2008).

39. Diastolic Notch in uterine artery waveform

40. The Roll over test Not of value in predicting PE

41. II. Biochemical Markers Angiogenic factors before& after the onset of PE (Barton& Sibai, 2008). Serum placental growth factor: reduced Soluble fms-like tyrosine kinase: elevated Endoglin: elevated

42. Conclusion • BP remains the cornerstone of early diagnosis • Markers • Reliability is inconsistent • Many suffer from poor specificity & predictive values. • None provided a cutoff value that could be clinically useful for the prediction of PE • (Widmer et al, 2007).

43. Currently: • There is no clinically useful screening test to predict PE(WHO, 2004)

44. Prevention of PE Primary Secondary

45. Primary prevention • Avoiding occurrence of the disease • Obese: • achieve an ideal b wt before conception (Villamor& Cnattingius, 2006) • No RCT • Ch hypertension: • Control BP before conception. • No RCT

46. Pregestational DM: • -Complete her family as early as possible & before vascular complications develop • -Control DM before conception & throughout pregnancy

47. Secondary • Breaking off the disease process before emergence of obvious clinical disease • {Etiology of the disease is unknown} • To correct theoretical pathophysiology • I. Non pharmacological • II. Nutritional • III. Pharmacological

48. I. Non pharmacological • Daily Bed rest • Rest for 4-6 h/d • May reduce risk of • PE for women with normal BP • (level 2 evidence) • (Cochrane Library 2006 Issue 2:CD005939)

49. 2. Life-style changes • High job stress: greater risk of PE(Sharma& Mittal, 2006) • Reducing job stress may be beneficial in the prevention of PE

50. 3. Regular prenatal exercise • May prevent or oppose progression (Weissgerber et al, 2004) • {Stimulation of placental growth • Reduction of oxidative stress • Reversal of maternal endothelial dysfunction}. • Insufficient evidence • Moderate intensity regular aerobic exercise • (Cochrane Library 2006 Issue 2:CD005942) • Aerobic exercise =cardiovascular exercise=any sustained rhythmic activity that involves large muscle groups: makes the lungs work harder as the body's need for oxygen is increased.