102: Pre-eclampsia

Key Points

• 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.

Diagnostic Criteria and Clinical Characteristics

Diagnostic Criteria for Pre-eclampsia

• 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

And the absence of

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

Diagnostic Criteria for Severe Pre-eclampsia

• 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

Diagnostic evaluation should include at least one of the following

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

• 24-hour collection of ...