II. Definitions

III. Epidemiology

  1. Incidence
    1. All pregnancies with Preeclampsia or Eclampsia: 4-5%
    2. Preterm births: 20%
  2. Mortality: 100,000 maternal deaths per year worldwide
    1. Accounts for 10-30% of all maternal deaths yearly

IV. Pathophysiology

  1. Increased Vascular Resistance
    1. Appears to result from endothelial cell dysfunction
    2. Increased resistance to placental Blood Flow with placenta hypoperfusion and chronic placenta ischemia
  2. Endothelial Cell dysfunction
    1. Very active organ system (not just vessel lining)
    2. Surface Area >6300 square meters over 100g of tissue
    3. Associated findings
      1. Edema
      2. Proteinuria
  3. Imbalance of vasoactive substances
    1. Imbalance between Thromboxane and prostacyclin (may be mechanism for Aspirin activity in PIH)
  4. Cardiovascular Effects
    1. Hypertension
    2. Arterial thickening
    3. Left ventricular wall thickening and Diastolic Dysfunction
  5. Decreased Intravascular volume
    1. Hemoconcentrated
    2. Increased Hemoglobin
  6. Coagulation abnormalities
    1. See HELLP Syndrome
  7. Multiple system effects by oxygen free radicals
    1. Perfusion and re-perfusion injury
    2. Lipid peroxidation
    3. Antioxidant mechanisms are protective
  8. Trophoblastic Invasion
    1. Two phases
      1. First: Decidua (abnormal placental implantation)
      2. Second: 12-18 weeks gestation
    2. Effects of PIH are reversed with Trophoblast delivery
  9. Model System
    1. Pregnant ewes
    2. Used to study Prostaglandin synthesis inhibitor
  10. Hypertension is a major mental roadblock
    1. Prevents understanding and treatment of toxemia
    2. Hypertension is an effect of PIH, not a cause

V. Classification

  1. Pregnancy Induced Hypertension (PIH)
    1. Hypertension without Proteinuria or pathologic edema (Gestational Hypertension)
      1. Up to 50% will develop Preeclampsia
    2. Preeclampsia with Proteinuria or pathologic edema
      1. Mild Preeclampsia
      2. Severe Preeclampsia
    3. Eclampsia
      1. Convulsions
      2. Proteinuria
      3. Edema
    4. HELLP Syndrome (complicates 15% of Preeclampsia cases, associated with 30% mortality)
      1. Hemolysis
      2. Elevated Liver Function Tests
      3. Low Platelets
  2. Coincidental Hypertension
    1. Chronic Hypertension
      1. See Chronic Hypertension in Pregnancy
      2. Hypertension onset before 20 weeks gestation, or persisting >12 weeks after delivery
    2. Pregnancy Aggravated Chronic Hypertension
      1. Superimposed Preeclampsia
      2. Superimposed Eclampsia

VI. Risk Factors

  1. Antiphospholipid Antibody Syndrome (RR 10)
  2. Prior history of Preeclampsia in prior pregnancy, esp. if prior to 32 weeks (RR 7)
  3. Diabetes Mellitus (RR 3)
  4. Family History of Preeclampsia in first degree relative (25% of cases, RR 3)
  5. Multiple Gestation (RR 3)
  6. Primigravid (nulliparity) or new paternity (RR 3)
  7. Obesity (RR 2)
  8. Maternal age >40 years (RR 1.6)
  9. Preexisting Chronic Hypertension
  10. Angiotensin gene T235
  11. Hydatiform mole
  12. Fetal hydrops
  13. Duckitt (2005) BMJ 330(7491): 565 [PubMed]

VII. Symptoms: Onset after 20 weeks gestation (and up to 6 weeks postpartum)

  1. Malaise
  2. Hand and face edema
    1. Least reliable PIH indicator
    2. Absent in 33% of PIH cases
    3. Often present in healthy third trimester pregnancies
  3. Headache
  4. Visual disturbance
  5. Epigastric Pain

VIII. Signs: General

  1. Excessive weight gain
  2. Hyperreflexia and Clonus
  3. Blood Pressure
    1. Assumes normal Blood Pressure before pregnancy
    2. Based on two supine Blood Pressures, 4-6 hours apart
    3. Mild Preeclampsia
      1. Blood Pressure greater than or equal to 140/90
      2. Prior guideline: Relative BP increase 30/15
        1. NHLBI Working Group does not recommend using due to high False Positive Rate
        2. Use 140/90 cutoff for all pregnant patients
    4. Severe Preeclampsia
      1. Blood Pressure exceeds 160/110
      2. Start Antihypertensives if systolic Blood Pressure >160 or diastolic Blood Pressure >110 for >15 minutes
      3. See Severe Hypertension Management in Pregnancy

IX. Signs: Severe Preeclampsia (End Organ Injury)

  1. Blood Pressure exceeds 160/110
  2. Proteinuria >5 grams per 24 hours (see labs below)
  3. Urine Output decreased
    1. Urine Output less than 500 ml in 24 hours
  4. Increased Serum Creatinine >1.1 (or >2x baseline)
  5. Thrombocytopenia (Platelet Count <100k)
  6. Pulmonary Edema
  7. Increased hepatic transaminases (>2 fold over baseline)
  8. New Headache or Vision change
  9. Altered Mental Status

X. Labs: Urine

  1. Proteinuria is not a useful screening measure and is NOT required for Severe Preeclampsia diagnosis
    1. Proteinuria is a late finding
    2. Rely on BP and other measures for screening
    3. Proteinuria assesses degree of Pre-Eclampsia
  2. Urine Protein and 24 Hour Urine Protein
    1. Non-Proteinuric Hypertension in Pregnancy
      1. Trace or no Urine Protein present
    2. Mild Preeclampsia
      1. Urine chemstrip 2+ Protein or greater (>=0.3 g/liter)
        1. Based on 2 random urines >6 hours apart
      2. Urine Protein exceeds 300 mg in 24 hours (or Urine Protein to Creatinine Ratio >0.3)
    3. Severe Preeclampsia
      1. Urine chemstrip exceeds 3+ Protein
        1. Based on 2 random urines >6 hours apart
      2. Urine Protein exceeds 5 grams in 24 hours
  3. Urine for single Specimen Protein to Creatinine ratio
    1. Correlates with 24 Hour Urine Protein
    2. Positive if Urine Protein to Creatinine Ratio >0.3
    3. PIH unlikely if Protein to Creatinine ratio < 0.19
      1. Negative Predictive Value: 83%
    4. Confirm abnormal tests with 24 hour urine
    5. References
      1. Wheeler (2007) Am J Obstet Gynecol 196(5): 465 [PubMed]
      2. Young (1996) J Fam Pract 42:385-9 [PubMed]

XIII. Diagnosis: ACOG Criteria

  1. Gestation >=20 weeks (or postpartum up to 6 weeks)
  2. Hypertension (and previously normal Blood Pressure)
    1. Systolic Blood Pressure >=140 or Diastolic Blood Pressure >= 90 (on 2 occasions at least 4 hours apart) OR
    2. Systolic Blood Pressure >=160 or Diastolic Blood Pressure >= 110 (confirmed on at least one recheck)
  3. Proteinuria
    1. Urine Dipstick Protein 1+ or greater OR
    2. Protein to Creatinine ratio >= 0.3 mg/dl
    3. 24 Hour Urine Protein > 300 mg/day
  4. Alternative diagnostic criteria if Proteinuria absent (at least one present)
    1. Thrombocytopenia (Platelet Count <100k)
    2. Serum Creatinine >1.1 mg/dl (or doubling of Serum Creatinine)
    3. Elevated Liver Function Tests with right upper quadrant pain or refractory Epigastric Pain
      1. Elevated Liver Function Tests typically with serum transaminases at least double normal level
    4. Pulmonary Edema
    5. Cerebral or visual symptoms
  5. Resources
    1. ACOG Hypertension in Pregnancy
      1. http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancy

XVI. Prevention

XVIII. Complications: Fetus

XIX. Course: Postpartum

  1. Observe postpartum for 72 hours inpatient or with close home monitoring
  2. PIH may have onset up to 6 weeks postpartum (even without antepartum PIH)
    1. More than 90% of cases present within 7 days of delivery
    2. Consider retained products of conception in postpartum Hypertension differential diagnosis
  3. Most PIH cases improve in first 1-2 days after delivery
    1. Blood Pressure decreases
    2. Diuresis
  4. Eclampsia may occur after delivery (usually <24-48 hours)
    1. Continue Magnesium Sulfate for 12-24 hours after delivery
    2. Continue to follow Blood Pressure and Urine Output
    3. Observe for signs of HELLP Syndrome
  5. Hypertension
    1. See Blood Pressure Management in Pregnancy for protocol and Antihypertensive indications
    2. Anticipate increased Blood Pressure in the first few days after delivery (due to fluid redistribution)
    3. Hypertension remits by 6-12 weeks postpartum

XX. Prognosis

  1. Isolated Preeclampsia risks outside of pregnancy
    1. Confers future risk of Hypertension, vascular disease
    2. Wilson (2003) BMJ 326:845-9 [PubMed]
  2. Increased risk of Preeclampsia in future pregnancies
    1. All women with history of Preeclampsia
    2. Onset before 30 weeks gestation (40% recurrence risk)
    3. Black race
    4. Different father than prior gestation
    5. Preeclampsia previously in Multiparous patient

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