Hypertensive Disorders of Pregnancy

Aka: Hypertensive Disorders of Pregnancy, Hypertension in Pregnancy, Pregnancy Related Hypertension, Pregnancy Induced Hypertension, Hypertension Induced by Pregnancy, Gestational Hypertension-Preeclampsia, Preeclampsia, PIH, EPH gestosis, Pre-Eclampsia

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II. Definitions

  1. Chronic Hypertension
    1. Consistently elevated Blood Pressures presenting at any time, but does not resolve after pregnancy
  2. Gestational Hypertension
    1. New onset Hypertension after 20 weeks gestation, WITHOUT Proteinuria or end-organ dysfunction
  3. Preeclampsia
    1. New onset Hypertension onset after 20 weeks gestation, WITH Proteinuria or end-organ dysfunction
    2. Previously known as EPH gestosis (edema, Proteinuria, Hypertension) or Toxemia of Pregnancy
  4. Preeclampsia With Severe Features
    1. Gestational Hypertension or Preeclampsia AND
    2. End organ injury OR severe range Hypertension (SBP>160 or DBP>110 mmHg on two readings)
      1. See signs below regarding end organ injury criteria
  5. Superimposed Preeclampsia
    1. Chronic Hypertension AND
    2. Proteinuria OR severe features
  6. HELLP Syndrome
    1. Severe Preeclampsia AND
    2. Hemolysis, Elevated Liver enzymes and Low Platelets
  7. Eclampsia
    1. New onset Generalized Tonic Clonic Seizure, multifocal or Focal Seizure AND
    2. Pregnant or postpartum (within 6 weeks) AND
    3. Hypertensive Disorder in Pregnancy AND
    4. No alternative diagnosis for Seizure

III. Epidemiology

  1. Incidence
    1. All pregnancies with Preeclampsia or Eclampsia: 4-5%
    2. Hypertensive Disorders of Pregnancy overall (including chronic Hypertension): 14%
    3. 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. Gestational Hypertension with Severe Features risks the same complications as 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. Non-hispanic black women (RR 5, compared with non-hispanic white women)
  4. Diabetes Mellitus (RR 3)
  5. Family History of Preeclampsia in first degree relative (25% of cases, RR 3)
  6. Multiple Gestation (RR 3)
  7. Primigravid (nulliparity) or new paternity (RR 3)
  8. Obesity (RR 2)
  9. Maternal age >40 years (RR 1.6)
  10. Preexisting Chronic Hypertension
  11. Angiotensin gene T235
  12. Hydatiform mole
  13. Fetal hydrops
  14. Chronic Kidney Disease
  15. 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: Preeclampsia With Severe Features (End Organ Injury)

  1. Blood Pressure > 160/110 mmHg
    1. Based on two values >=4 hours apart (with either SBP or DBP elevated above criteria)
  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. Right upper quadrant or Epigastric Pain (seen in HELLP Syndrome)
  7. Pulmonary Edema
  8. Increased hepatic transaminases (>2 fold over baseline)
  9. New Headache or Vision change
  10. 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 (2 random urine samples >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. Consider confirmation of 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]

XI. Labs: Blood

  1. Complete Blood Count with Platelets
    1. Thrombocytopenia seen in Severe Preeclampsia
  2. Serum Electrolytes
  3. Serum Creatinine (>1.1 in Severe Preeclampsia)
    1. Reduced GFR may progress to Acute Renal Failure
  4. Uric Acid
  5. Liver Function Tests (elevated transaminases)
    1. Aspartate Aminotransferase
    2. Alanine Aminotransferase
    3. Serum Bilirubin
    4. Serum Albumin
    5. Lactic Acid dehydrogenase
  6. Coagulation Studies for Severe Preeclampsia or HELLP
    1. ProTime (PT)
    2. Partial Thromboplastin Time (aPTT)
    3. Fibrin split products (Fibrin Degradation Products)
    4. Fibrinogen

XII. Diagnostics: Fetus

  1. Fetal Nonstress Test
  2. Obstetric Ultrasound
    1. Biophysical Profile
    2. Amniocentesis for Fetal Lung Maturity when indicated

XIII. Diagnosis: Preeclampsia 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 BP 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. Tests that NOT recommended for diagnosis (per ACOG)
    1. sFIT-1/PIGF Ratio
      1. Low accuracy for Preeclampsia (Test Sensitivity 78%, Test Specificity 84%) in 2024
      2. Placental growth factor (PIGF) triggers Vasoconstriction, endothelial damage and may contribute to Preeclampsia
      3. Soluble FMS-Like Tyrosine Kinase-1 (sFIT-1) is a Vascular Endothelial Growth Factor, that inhibits PIGF
      4. Lala (2024) Am Fam Physician 109(5): 470-1 [PubMed]
  6. Resources
    1. ACOG Hypertension in Pregnancy
      1. http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancy

XIV. Monitoring

  1. See Gestational Hypertension (chronic Hypertension)
  2. See Mild Preeclampsia
  3. See Severe Preeclampsia
  4. See HELLP Syndrome

XV. Management

  1. See Delivery Indications in PIH
  2. See Gestational Hypertension Management
  3. See Mild PIH Management
  4. See Severe PIH Management
  5. See Eclampsia
  6. See HELLP Syndrome
  7. See PIH Blood Pressure Management
  8. See PIH Seizure Prophylaxis

XVI. Prevention

  1. See PIH Prophylaxis

XVII. Complications: Maternal

  1. Eclampsia
  2. Left Ventricular Dysfunction
  3. Placental Abruption
  4. Coronary Artery Disease
  5. Chronic Hypertension
  6. Cerebrovascular Accident
  7. Cerebrovascular Accident in Women
    1. See Cerebrovascular Accident Risk in Women

XVIII. Complications: Fetus and Infant

  1. Neonatal Asphyxia
  2. Neonatal Hypoglycemia
  3. Intrauterine Growth Retardation (low birth weight)
  4. Perinatal mortality
  5. Congenital Malformations
  6. Cognitive deficits and Developmental Disability
  7. Increased Cardiovascular Risk longterm (chronic Hypertension, Obesity, cardiovascular disease)

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 (esp. first 48 hours)
    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. Up to 20% of Eclamptic Seizures present postpartum (15% of these cases were without prior PIH diagnosis)
    2. Continue Magnesium Sulfate for 12-24 hours after delivery
    3. Continue to follow Blood Pressure and Urine Output
    4. 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
  6. Other measures
    1. Counsel women on prevention of cardiovascular disease (e.g. Tobacco Cessation, Hyperlipidemia, Exercise)

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

XXI. Prevention

  1. See Pregnancy Induced Hypertension Prophylaxis

XXII. References

  1. Marlow (2021) Crit Dec Emerg Med 35(2): 19-23
  2. (2000) Am J Obstet Gynecol 183(1):S1-22 [PubMed]
  3. Farahi (2024) Am Fam Physician 109(3): 251-60 [PubMed]
  4. Leeman (2008) Am Fam Physician 78:93-100 [PubMed]
  5. Leeman (2016) Am Fam Physician 93(2):121-7 [PubMed]
  6. Sibai (2003) Obstet Gynecol 102:181-92 [PubMed]
  7. Zamorski (2001) Am Fam Physician 64(2): 263-70 [PubMed]

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