Preeclampsia - Eclampsia

Jack Ludmir, M.D. 2010

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

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

Autopsy Specimen from a 40-Year-Old Woman with Severe Preeclampsia and Subarachnoid Hemorrhage

Greene M. N Engl J Med 2003;348:275-276

PRE: History
Eclampsia - Preeclampsia

Prenatal Care
New concept in the 20th century 1902: Ballantyne. Promaternity 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

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

Hypertensive Disorders of Pregnancy

Sibai B. N Engl J Med 1996;335:257-265

Conditions Sometimes Confused with Preeclampsia or Eclampsia

Sibai B. N Engl J Med 1996;335:257-265

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

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.

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

Pathophysiology

Endothelial cell injury Generalized vasoconstriction

Implantation

Rogers et al: Obst Gynecol Survey 54:189,1999

Atherosis in placental bed

Rogers et al: Obst Gynecol Survey 54:189,1999

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

Possible mechanisms in Preeclampsia

Friedman and Lindheimer,1999

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)

Angiogenic Factors
Endothelium
+ VEGF + PIGF

- sFlt1

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.

Circulating Angiogenic Factors and the Risk of Preeclampsia

Levine et al. NEJM 2004

Circulating angiogenic factors

Increased levels of sFlt-1 and reduced levels of PIGF predict the subsequent development of preeclampsia

Levine et al. NEJM 2004

Preeclampsia - Pathophysiology
Soluble Endoglin (CD105), a cell receptor for transforming growth factor-beta (TGF-), 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)

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

Circulating angiogenic factors

Increase Increase
Decrease
sFlt-1

Endoglin
PGIF

in patients that will develop clinical preeclampsia

Levine et al, NEJM; 2004 Robinson CJ, Johnson DD. AJOG 2007

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

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

Severe Preeclampsia: Mild v. Severe

Hauth (2000)
Mild (n=217) Severe (n=109)

Buchbinder (2002)
Mild (n=62) Severe (n=45)

Hnat (2002)
Mild (n=86) Severe (n=70)

<35wks (%)
SGA (%) Abruption (%) Perinatal mortality (%)

1.9
10.2 0.5 1.0

18.5
18.5 3.7 1.8

4.8
4.8 3.2 0

11.4
11.4 6.7 8.9

2.3
NR 0 0

18.6
NR 1.4 1.4

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

Severe preeclampsia remote from term: concerns

Maternal risks

Fetal risks