Preeclampsia - Eclampsia

1. Preeclampsia - Eclampsia Jack Ludmir, M.D. 2010

2. Maternal Mortality in the World 600,000 per year due to pregnancy-related causes

3. Maternal Mortality • USA: 15/100,000 live births • Mali: 800/100,000 live births • Hemorrhage • Embolism • Preeclampsia • Infection

4. Autopsy Specimen from a 40-Year-Old Woman with Severe Preeclampsia and Subarachnoid Hemorrhage Greene M. N Engl J Med 2003;348:275-276

5. 2200 BC Egypt: pregnant women with fists 400 BC Hippocrates: pregnant women with convulsions Eclampsia: Greek word: suddenly, flash 1619: Varardus: first use of word eclampsia 1843: Lever. Proteinuria. Swelling and convulsions: Nephritic toxemia 1897: Vaquez. Hypertension 1899: Strogonov: treatment, sedation 1900s: prenatal care, preeclampsia New concept in the 20th century 1902: Ballantyne. Pro-maternity clinic. 1910: USA. Nursing visits at home. 1920: Prenatal visits: check for hypertension, swelling, proteinuria to detect : Preeclampsia Maternal mortality reduced in UK from 319/100,000 in 1936 to 15/100,000 in 1985 PRE: History Eclampsia - Preeclampsia Prenatal Care

6. Hypertensive Disorders of Pregnancy Sibai B. N Engl J Med 1996;335:257-265

7. Conditions Sometimes Confused with Preeclampsia or Eclampsia Sibai B. N Engl J Med 1996;335:257-265

8. Preeclampsia - Eclampsia • Hypertension after 20 weeks gestation • Proteinuria > than 300 mg/dl or +1 dipstick • Convulsions: eclampsia

9. Preeclampsia • Incidence: 5 - 8% of all pregnancies. • Etiology remains elusive. • Major cause for maternal and perinatal mortality and morbidity. • To date no treatment for prevention (baby ASA or calcium) or cure, except delivery. • However, the maternal benefits must be weighed against the neonatal risks of preterm delivery.

10. Etiology • Multiple theories: toxins, nephritis, parasites, malnutrition, vitamin deficiency, immunologic, inflammation, oxidation, prostaglandin imbalance, angiogenic factors,……..

11. Pathophysiology • Endothelial cell injury • Generalized vasoconstriction

12. Implantation Rogers et al: Obst Gynecol Survey 54:189,1999

13. Atherosis in placental bed Rogers et al: Obst Gynecol Survey 54:189,1999

14. Renal-Biopsy Specimen Showing Glomerulus with Reactive Endothelial Cells That Narrow Capillary Lumens (Arrowheads) and Duplicated Glomerular Basement Membrane (Arrows) (Periodic Acid-Schiff, x450) Ludmir J and Smith R. N Engl J Med 1998;339:906-913

15. Possible mechanisms in Preeclampsia Friedman and Lindheimer,1999

16. Preeclampsia - Pathophysiology • May be initiated by placental factors that enter the maternal circulation and cause endothelial dysfunction resulting in hypertension and proteinuria. • Recently, soluble fms-like tyrosine kinase 1 (sFlt-1) an antiangiogenic protein has been found to be increased in preeclampsia (Maynard et al.J Clin Invest 2003)

17. + VEGF + PIGF - sFlt1 Angiogenic Factors Endothelium

18. Preeclampsia - Pathophysiology • sFlt-1 acts by binding to placental growth factor(PGF) and vascular endothelial growth factor (VEGF), preventing the interaction with endothelial receptors on the cell surface and inducing endothelial dysfuntion. • Exogenous administration of sFlt-1 in pregnant rats induces hypertension, proteinuria, and glomerular endotheliosis.

19. Circulating Angiogenic Factors and the Risk of Preeclampsia Levine et al. NEJM 2004

20. Circulating angiogenic factors Increased levels of sFlt-1 and reduced levels of PIGF predict the subsequent development of preeclampsia Levine et al. NEJM 2004

21. Preeclampsia - Pathophysiology • Soluble Endoglin (CD105), a cell receptor for transforming growth factor-beta (TGF-β), has been localized to both placental syncytiotrophoblasts and endothelial cells. • The primary role include angiogenesis, endothelial cell differentiation and regulation of vascular tone through endothelial nitric oxide synthetase (enos)

22. Preeclampsia - Pathophysiology • Soluble endoglin as a second trimester marker for preeclampsia • Soluble endoglin elevated in patients destined to develop severe early-onset preeclampsia Robinson JC, Johnson D. AJOG 2007:197

23. Circulating angiogenic factors Increase sFlt-1 Increase Endoglin Decrease PGIF in patients that will develop clinical preeclampsia Levine et al, NEJM; 2004 Robinson CJ, Johnson DD. AJOG 2007

24. Preeclampsia: Management • Mild: 140/90, +1 proteinuria. Management: conservative, bedrest, deliver if close to term • Severe: Significant HTN, proteinuria (>5g/24hrs) or any systemic manifestation of the disease. Management: Consider delivery • Eclampsia: Delivery

25. Severe Preeclampsia Criteria In order to make the diagnosis, one of the following should be present: • Blood pressure of 160 mm Hg systolic or higher or 110 mm Hg diastolic or higher on two occasions at least 6 hours apart while the patient is on bed rest • Proteinuria of 5 g or higher in a 24-hour urine specimen or 3+ or greater on two random urine samples collected at least 4 hours apart • Oliguria of less than 500 mL in 24 hours • Cerebral or visual disturbances • Pulmonary edema or cyanosis • Epigastric or right upper-quadrant pain • Impaired liver function • Thrombocytopenia • Fetal growth restriction ACOG,Practice Bull.2002

26. Hauth (2000) Buchbinder (2002) Hnat (2002) Mild (n=217) Severe (n=109) Mild (n=62) Severe (n=45) Mild (n=86) Severe (n=70) <35wks (%) 1.9 18.5 4.8 11.4 2.3 18.6 SGA (%) 10.2 18.5 4.8 11.4 NR NR Abruption (%) 0.5 3.7 3.2 6.7 0 1.4 Perinatal mortality (%) 1.0 1.8 0 8.9 0 1.4 Severe Preeclampsia: Mild v. Severe

27. Severe PIH Remote from Term - Concerns • Prompt delivery is curative and avoids possible bad consequences to mom and baby. (abruption, seizures…) • Prompt delivery may cause significant morbidity or mortality to baby due to prematurity

28. Severe preeclampsia remote from term: concerns Maternal risks Fetal risks