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  Disease summary:

  
  
  
  
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    Pre-eclampsia is a multisystem disorder unique to pregnancy and occurs in 4% to 7% of women.

    
    
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    This condition is clinically characterized by elevated blood pressure and proteinuria.

    
    
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    The manifestations of pre-eclampsia are thought to occur following an interrelated cascade of abnormal placental implantation, hypoxia, release of antiangiogenic factors, placental/fetal/maternal immunologic dysfunction, and dysfunction/destruction of maternal vascular endothelial cells.

    
    
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    The constellation of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome) represents a variant of pre-eclampsia that may present without significant proteinuria.

    
    
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    Eclampsia is the progression to grand mal seizures in a woman with pre-eclampsia.

  
  
  
  
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  Differential diagnosis:

  
  
  
  
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    Chronic hypertension, gestational hypertension

  
  
  
  
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  Monogenic forms:

  
  
  
  
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    None identified.

  
  
  
  
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  Family history:

  
  
  
  
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    A mother with pre-eclampsia confers a 20% to 40% risk to her daughter for pre-eclampsia; sisters of pre-eclamptic woman face an 11% to 37% risk of pre-eclampsia. Risks for eclampsia appear to be similar if not slightly higher.

  
  
  
  
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  Twin studies:

  
  
  
  
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    60% concordance in monozygotic twins.

  
  
  
  
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  Environmental factors:

  
  
  
  
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    Dietary deficiencies of calcium and antioxidant vitamins C and E have been suspected to play a role in pre-eclampsia on an epidemiologic basis. However, numerous trials of repletion have not shown a benefit.

  
  
  
  
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  Genome-wide associations:

  
  
  
  
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    Genome-wide association studies (GWAS) in Iceland, Australia, New Zealand, and Finland have indicated a possible susceptibility locus on chromosome 2 although complete agreement does not exist as to the specific location. Further refinement with transcription-targeted candidate genes initially derived from androgenic (fetus-free) placentas and applied to whole genome screening successfully further refined a pre-eclampsia-linked site to 2q22. Upregulated in decidua from pre-eclamptic women, a candidate gene within this region, activin (ACVR2) was given the highest priority as a possible gene for pre-eclampsia. However, other loci have been reported from GWAS of populations including 10q21.3, 2p25.1, 9p21, 2p11.2, and 4q34 reflecting the multifactorial nature of pre-eclampsia and limitations of GWAS applications.

  
  
  
  
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  Pharmacogenomics:

  
  
  
  
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    None applicable.

  
  

Diagnostic Criteria for Pre-eclampsia

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  Greater than 20 weeks of gestation

  
  
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  Blood pressure elevation greater than 140 mm Hg systolic or greater than 90 mm Hg diastolic obtained 6 hours apart

  
  
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  Proteinuria defined as urinary excretion of greater than or equal to 0.3 g protein in a 24-hour collection

And the absence of

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  Previously elevated blood pressure (>140/90) before 20 weeks of gestation

Diagnostic Criteria for Severe Pre-eclampsia

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  Greater than 20 weeks of gestation

  
  
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  Blood pressure elevation greater than 160 mm Hg systolic or greater than 100 mm Hg diastolic obtained 6 hours apart

  
  
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  Oliguria less than 500 cc in 24 hours

  
  
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  Cerebral or visual disturbances

  
  
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  Pulmonary edema or cyanosis

  
  
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  Epigastric or right upper quadrant pain

  
  
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  Impaired liver function

  
  
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  Thrombocytopenia

  
  
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  Fetal growth restriction

Diagnostic evaluation should include at least one of the following

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  Blood pressure obtained 6 hours apart, taken sitting or in left lateral position

  
  
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  24-hour collection of urine

  
  
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  Hematocrit, platelet count

  
  
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  Liver function analysis for transaminases

  
  
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  Laboratory assessment of renal function

  
  
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  Laboratory assessment of coagulopathy

  
  
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  Assessment of oxygenation

Clinical Characteristics

This condition is clinically characterized by elevated blood pressure and proteinuria. While not considered essential for the diagnosis, women often have increased hand, ankle, and facial edema. Progression from mild-to-severe pre-eclampsia represents a continuum of the disease although timing and rate of progression is unpredictable. Some women will present initially with severe pre-eclampsia that is characterized by central nervous system (CNS) changes (headache, blurred vision), liver involvement (right upper quadrant pain, elevated transaminases), renal involvement (marked proteinuria, oliguria), and/or fetal growth restriction. Additional laboratory manifestations can include elevation of the hematocrit reflecting an underlying hemoconcentration, lowered platelet count, and evidence of hemolysis. The constellation of HELLP syndrome represents a variant of pre-eclampsia that may present without significant proteinuria. Progression to seizures is a hallmark of eclampsia with increased deep tendon reflexes and clonus being early signs of CNS irritation. Pre-eclampsia may present initially in the postpartum period in a small number of patients.

Clinically, two broad categories of pre-eclampsia exist—early onset (<34 weeks) and late onset (>34 weeks). Early-onset disease is characterized broadly as a disorder of aberrant placentation with a normal maternal response and late-onset disease is described as a condition of normal placentation in the setting of a maternal system with aberrant endothelial responses. Early-onset pre-eclampsia is notable for a higher rate of familial cases, a higher risk of recurrence in subsequent pregnancies, identification of placental vascular abnormalities, and associated fetal growth restriction. Late-onset pre-eclampsia is more common (80%) and is characterized by maternal risk factors such as diabetes, increased blood pressure (but not hypertension) early in pregnancy, cardiovascular disease, increased body mass index (BMI), and older maternal age.

The maternal vascular changes of pre-eclampsia are characterized by hemoconcentration mediated by intense vasospasm. Women with pre-eclampsia tend to be intravascularly depleted and hemoconcentrated yet with endothelial damage which renders their vascular system throughout their bodies more permeable to capillary leak. This may manifest clinically as peripheral or total body edema, pulmonary edema, and CNS edema. Renal consequences of the vasospasm lead to decreased renal flow, lack of the normal expected increase in glomerular filtration rate with pregnancy, and ultimately a decreased urine output. Uteroplacental blood flow is similarly affected with uteroplacental insufficiency resulting from placental infarct with resultant fetal growth restriction, decreased amniotic fluid, placental abruption, and nonreassuring fetal surveillance.