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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.

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preeclampsia eclampsia

Preeclampsia - Eclampsia

Jack Ludmir, M.D. 2010

maternal mortality in the world
Maternal Mortality in the World

600,000 per year due to pregnancy-related causes

maternal mortality
Maternal Mortality
  • USA: 15/100,000 live births
  • Mali: 800/100,000 live births
  • Hemorrhage
  • Embolism
  • Preeclampsia
  • Infection
slide4

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
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

slide6

Hypertensive Disorders of Pregnancy

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

preeclampsia eclampsia8
Preeclampsia - Eclampsia
  • Hypertension after 20 weeks gestation
  • Proteinuria > than 300 mg/dl or +1 dipstick
  • Convulsions: eclampsia
preeclampsia
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
Etiology
  • Multiple theories: toxins, nephritis, parasites, malnutrition, vitamin deficiency, immunologic, inflammation, oxidation, prostaglandin imbalance, angiogenic factors,……..
pathophysiology
Pathophysiology
  • Endothelial cell injury
  • Generalized vasoconstriction
slide12

Implantation

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

slide13

Atherosis in placental bed

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

slide14

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

slide15

Possible mechanisms in Preeclampsia

Friedman and Lindheimer,1999

preeclampsia pathophysiology
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

+ VEGF

+ PIGF

- sFlt1

Angiogenic Factors

Endothelium

preeclampsia pathophysiology18
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

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 pathophysiology21
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)
preeclampsia pathophysiology22
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 factors23
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

preeclampsia management
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
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)

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
severe pih remote from term concerns
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