Hypertensive Pregnancy Disorders

Hypertensive disorders of pregnancy include chronic hypertension, preeclampsia/eclampsia, gestational hypertension, and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. These syndromes pose a significant risk to the pregnant woman and her fetus. Hypertension is defined as a BP > 140/90 mm Hg and can be diagnosed before (chronic) or after (gestational) the 20th week of gestation. Preeclampsia is gestational hypertension with proteinuria or end-organ damage. Eclampsia is preeclampsia with seizures. HELLP syndrome is a severe manifestation of preeclampsia leading to hemolysis, low platelets, and liver injury. Management is with antihypertensives and magnesium sulfate for seizure prophylaxis. The definitive treatment for all hypertensive disorders of pregnancy is delivery.

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Epidemiology and Etiology

Epidemiology

  • Hypertensive disorders complicate 5%–10% of pregnancies.
  • Preeclampsia:
    • Occurs in 2%–8% of all pregnancies
    • Incidence is 1.5–2 times higher in 1st pregnancies.
  • 20%–25% of women with chronic hypertension develop preeclampsia during pregnancy.
  • 1% of pregnancies are complicated by chronic hypertension.
  • 5%–6% of pregnancies are complicated by gestational hypertension.
  • 70% of women having an eclamptic seizure will suffer from maternal complications, with morbidity reaching up to 14%.

Etiology

  • High-risk factors: 
    • History of preeclampsia
    • History of chronic hypertension
    • Diabetes
    • Renal disease
    • Autoimmune disease
    • Multiple gestation
  • Moderate-risk factors: 
    • Nulliparity
    • > 10 years between pregnancies
    • BMI > 30
    • Low socioeconomic status
    • African American race
    • Family history of preeclampsia in 1st-degree relative
    • Advanced maternal age (≥ 35 years at time of delivery)
    • Intrauterine growth restriction (IUGR)
  • Risk factors in progression to preeclampsia:
    • History of preeclampsia
    • History of HELLP (hemolysis, elevated liver enzymes, low platelets in pregnancy) syndrome
    • Twin and multiple gestations
    • BMI > 30
    • Women > 35 years of age
    • 1st-time mothers
    • Family history

Pathophysiology

Hypertension in pregnancy

The complete pathophysiology of hypertensive disorders in pregnancy is not completely understood, but most theories involve a problem with cytotrophoblastic endothelial invasion.

Hypertension in pregnancy

Hypertension in pregnancy

Image by Lecturio. License: CC BY-NC-SA 4.0

Preeclampsia and HELPP syndrome

  • Defective spiral artery remodeling → placental hypoperfusion → systemic vasoconstriction and endothelial dysfunction → hypertension → proteinuria and/or end-organ damage
  • HELLP is an extension of preeclampsia
    • May be closely related to atypical hemolytic uremic syndrome
    • Endothelial injury with fibrin deposits → thrombotic microangiopathy →  microangiopathic hemolytic anemia (MAHA) + liver damage + platelet-activation and consumption → thrombocytopenia + elevated liver enzymes

Eclampsia

  • Poorly understood, but commonly thought to be multifactorial
  • Seizures are thought to be caused by cerebral vasospasm and cerebral edema. 
  • Hypertensive encephalopathy may also play a role.

Clinical Presentation

Chronic hypertension

  • Asymptomatic
  • Systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg 
  • Begins before the 20th week of gestation
  • Often preexisting 
  • No proteinuria
  • No end-organ damage

Gestational hypertension

  • Asymptomatic
  • Systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg 
  • Begins after the 20th week of gestation
  • No history of preexisting hypertension
  • No proteinuria
  • No end-organ damage

Preeclampsia

  • Occurs between 20 weeks of gestation and up to 6 weeks postpartum.
  • Gestational hypertension with either proteinuria or end-organ damage
  • Very common among critically ill pregnant women
  • Cerebral symptoms
    • Severe headache
    • Altered mental status
  • Visual symptoms 
    • Scotomata
    • Photophobia
    • Blurred vision
    • Temporary blindness
  • Pulmonary edema 
    • Dyspnea
    • Rales
  • Renal impairment with peripheral edema
  • Hepatic impairment with RUQ pain
Timing of onset of preeclampsia

Timing of onset of preeclampsia

Image by Lecturio. License: CC BY-NC-SA 4.0

Eclampsia

  • Preeclampsia with the presence of seizures
  • Other symptoms:
    • Persistent occipital or frontal headaches
    • Blurred vision
    • Photophobia
    • Epigastric or RUQ pain
    • Altered mental status

HELLP syndrome

  • Manifestation of preeclampsia (not a separate disorder).
  • Preeclampsia symptoms (proteinuria and/or end-organ damage) plus:
    • Hemolysis
      • Pallor
      • Malaise
    • Elevated Liver enzymes
      • RUQ pain
      • Nausea and vomiting
    • Low Platelets
  • May cause hepatic hematoma that ruptures → hemoperitoneum

Diagnosis

  • Hypertension is a BP measurement on 2 separate occasions, at least 4 hours apart of:
    • Systolic BP ≥ 140 mm Hg and/or
    • Diastolic BP ≥ 90 mm Hg
  • Chronic hypertension is hypertension diagnosed at < 20 weeks of gestation.
  • Gestational hypertension is hypertension diagnosed at ≥ 20 weeks of gestation when BP was previously normal.
  • Preeclampsia is gestational hypertension with proteinuria or end-organ damage.
    • Proteinuria criteria: 
      • 24-hour urine collection ≥ 300 mg protein or
      • Single voided urine protein/creatinine ratio ≥ 0.3
      • Dipstick reading of 2+ (use only if other quantitative methods not available)
    • If presenting without proteinuria must meet 1 of the following criteria:
      • Thrombocytopenia (platelets < 100,000) 
      • Renal insufficiency (baseline creatinine is doubled or serum creatinine > 1.1 mg/dL) 
      • Pulmonary edema 
      • Impaired liver function (AST/ALT > 2 times the upper limit of normal)
      • New-onset headache that is unresponsive to medications and has no alternative cause.
  • Eclampsia consists of preeclampsia criteria plus seizures:
    • Generalized tonic–clonic seizures 
    • From intrapartum up to 72 hours postpartum
    • Secondary to untreated and/or undertreated preeclampsia
  • HELLP syndrome is a severe form of preeclampsia with:
    • Hemolysis, with:
      • LDH > 600 IU/L
      • ↑ Bilirubin
      • Schistocytes on blood smear
      • Anemia
    • ↑ Liver enzymes, with AST and/or AST > 2 times upper limit of normal
    • ↓ Platelet count, with thrombocytopenia (< 100,000)

Management

Prevention

  • Used when 1 high-risk factor or ≥ 2 moderate-risk factors are present
  • Prophylaxis with 81 mg aspirin between 12 and 28 weeks and continued until delivery.

Management

Definitive treatment of gestational hypertension, preeclampsia, eclampsia, and HELLP is delivery.

  • 1st-line therapies for BP control include:
    • Labetalol
    • Hydralazine
    • Nifedipine
  • Nitroglycerin can be used in pulmonary edema.
  • Teratogenic BP medications (contraindicated in pregnancy):
    • ACEis
    • ARBs
    • Mineralocorticoid receptor antagonists
  • Abnormal findings on any of the following evaluations may require early delivery:
    • Ultrasonography for fetal monitoring:
      • IUGR
      • Placental abruption 
      • Poor placental/umbilical blood flow 
    • Other testing:
    • Fetal nonstress test
    • Amniotic fluid index evaluation
  • In patients with preeclampsia:
    • Magnesium seizure prophylaxis is not indicated until after delivery. 
      • Load with 6 g of IV magnesium sulfate and infuse at 1–2 g/hour. 
      • Monitor carefully and hold the infusion for signs of magnesium toxicity or renal failure.
      • Signs of magnesium toxicity: loss of patellar reflexes, tachypnea due to respiratory muscle weakness
    • Between 24 and 33 weeks, steroid therapy is indicated to promote fetal lung maturity.

Complications

  • Intracranial hemorrhage
  • Pulmonary edema
  • Renal failure
  • Coagulopathy
  • Hemolysis
  • Liver injury
  • Thrombocytopenia
  • IUGR
  • Oligohydramnios
  • Placental abruption
  • Nonreassuring fetal status

Differential Diagnosis

  • Antiphospholipid syndrome: acquired hypercoagulable state created from an underlying autoimmune disorder that causes a patient’s state to be procoagulant. A majority of patients have recurrent miscarriages. Diagnosis is made by laboratory findings of the respective antibodies, and mainstay of management is anticoagulation.
  • Aortic coarctation: defined as a narrowing of the aorta between the aortic arch and the iliac bifurcation. Children and adults present with symptoms of hypoperfusion and/or hypertension. The classic findings include a radiofemoral/brachiofemoral delay and lower BP in the lower limbs. Diagnosis is confirmed by echocardiography. Management is surgery as early as possible to avoid complications of hypertension.
  • Cushing syndrome: hypercortisolism resulting from chronic exposure to excess glucocorticoids. Typical clinical features of Cushing syndrome include central obesity, thin, bruisable skin, abdominal striae, secondary hypertension, hyperglycemia, and proximal muscle weakness. Diagnosis is by elevated cortisol levels. Management options depend on the cause and may include surgery or medical therapy.
  • Hydatidiform mole: due to cystic swelling of the chorionic villi and proliferation of the chorionic epithelium. Hydatidiform mole is a gestational trophoblastic disease resulting from abnormal placental trophoblastic growth. Diagnosis is confirmed by elevated serum beta-hCG and ultrasound findings, which are dependent on the disorder. Management is primarily through dilation and curettage and/or methotrexate. 
  • Hyperthyroidism: caused by sustained overproduction and release of the thyroid hormone T3 and/or T4. Clinical features of thyrotoxicosis are mostly due to an increase in the metabolic rate and overactivity of the sympathetic nervous system. Hyperthyroidism is diagnosed by low levels of TSH and elevated levels of T4 and T3. Depending on the etiology and clinical presentation, it may be treated pharmacologically, surgically, or with radioiodine.

References

  1. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. (2019). ACOG Practice Bulletin no. 203: Chronic hypertension in Pregnancy. Obstet Gynecol 133:e26–e50.
  2. Colussi G, Catena C, Driul L, et al. (2020). Secondary hyperparathyroidism is associated with postpartum blood pressure in preeclamptic women and normal pregnancies. J Hypertens.
  3. Dymara-Konopka W, Laskowska M, Oleszczuk J. (2018). Preeclampsia—current management and future approach. Curr Pharm Biotechnol 19:786–796.
  4. (2020). Gestational hypertension and oreeclampsia: ACOG Practice Bulletin Summary, Number 222. Obstet Gynecol 135:1492–1495. 
  5. Hauspurg A, Sutton EF, Catov JM, Caritis SN. (2018). Aspirin effect on adverse pregnancy outcomes associated with stage 1 hypertension in a high-risk cohort. Hypertension 72:202–207. 
  6. Luger RK, Kight BP. (2020). Hypertension in pregnancy. StatPearls. Retrieved July 1, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK430839/ 
  7. Timpka S, Markovitz A, Schyman T, Mogren I, Fraser A, Franks PW, Rich-Edwards JW. (2018). Midlife development of type 2 diabetes and hypertension in women by history of hypertensive disorders of pregnancy. Cardiovasc Diabetol. 17(1):124
  8. Carson, M. (2018). Hypertension and Pregnancy. Emedicine. Retrieved July 1, 2021, from https://emedicine.medscape.com/article/261435-overview#a4

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