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Key Points

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  • Disease summary:

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

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

    • 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.

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

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

  • Differential diagnosis:

    • Chronic hypertension, gestational hypertension

  • Monogenic forms:

    • None identified.

  • Family history:

    • 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.

  • Twin studies:

    • 60% concordance in monozygotic twins.

  • Environmental factors:

    • 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.

  • Genome-wide associations:

    • 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.

  • Pharmacogenomics:

    • None applicable.

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Diagnostic Criteria and Clinical Characteristics

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Diagnostic Criteria for Pre-eclampsia

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  • Greater than 20 weeks of gestation

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

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

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And the absence of

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

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Diagnostic Criteria for Severe Pre-eclampsia

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  • Greater than 20 weeks of gestation

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

  • Oliguria less than 500 cc in 24 hours

  • Cerebral or visual disturbances

  • Pulmonary edema or cyanosis

  • Epigastric or right upper quadrant pain

  • Impaired liver function

  • Thrombocytopenia

  • Fetal growth restriction

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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

  • 24-hour collection of urine

  • Hematocrit, platelet count

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