Hypertensive disorders of pregnancy represent a spectrum of disease ranging from gestational hypertension to severe preeclampsia. Preeclampsia is defined as new-onset hypertension (systolic blood pressure ≥140 or diastolic ≥90) after 20 wk gestation or up to 6 wk postpartum in the presence of proteinuria or evidence of end-organ injury.¹ In the absence of proteinuria, other criteria, including thrombocytopenia, acute kidney injury, impaired liver function, pulmonary edema, and new-onset neurologic symptoms, can be used for diagnosis. In 2013, the American College of Obstetricians and Gynecologists (ACOG) Task Force on Hypertension in Pregnancy revised the criteria, making the presence of proteinuria unnecessary to make the diagnosis.² The task force reinforced the importance of hypertension as a necessary condition and deemphasized proteinuria.

Hypertensive disorders of pregnancy can be categorized as follows:¹

• Gestational hypertension: Hypertension in pregnancy after 20 wk without proteinuria or evidence of end-organ injury
• Preeclampsia: Hypertension in pregnancy after 20 wk, with proteinuria but without evidence of end-organ injury
• Preeclampsia with severe features (Table 1)
• Chronic hypertension: Hypertension pre-dating pregnancy or present at <20 wk gestation
• Chronic hypertension with superimposed preeclampsia: The presence of chronic hypertension with elevation in blood pressure from baseline often requiring increasing antihypertensives or with development of new onset of signs or symptoms meeting criteria for severe preeclampsia (Table 1)
• Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome: A severe form of preeclampsia defined by lactate dehydrogenase (LDH) greater than 600 IU/L, liver enzymes (aspartate aminotransferase [AST], alanine transaminase [ALT]) greater than twice the upper limit of normal, and a platelet count less than 100 × 10⁹/L

• Pregnancy-induced hypertension (PIH)
• Hypertensive disorders of pregnancy (HDP)
• Severe gestational hypertension

The underlying causes of preeclampsia have been studied extensively for over a century; however, many uncertainties remain.¹¹

Headache that persists despite treatment with acetaminophen is one of the classic neurologic symptoms of preeclampsia. Visual changes associated with preeclampsia, including scotoma, blurred vision, or aura.^1,12 Classic neurologic exam findings of preeclampsia include hyperreflexia, clonus, or cranial nerve VI palsy.¹³

Endothelial dysfunction and elevated perfusion pressure accompanied by cerebral edema are considered the underlying cause of cerebral injury, including posterior reversible encephalopathy syndrome (PRES), in patients with preeclampsia. PRES is characterized by cerebral edema classically affecting the occipital and parietal lobes. Patients with PRES may manifest headache, visual loss or disturbance, altered sensorium, or altered consciousness.¹³ Severe cases of PRES may result in seizure or coma. PRES is also associated with increased risk of hemorrhagic and ischemic cerebrovascular accident. Importantly, patients with hypertensive disorders of pregnancy have a fivefold increased risk for occurrence of hemorrhagic or ischemic stroke.¹³

Patients with persistent neurologic symptoms are at highest risk for developing PRES. Management of PRES includes controlling hypertension, possible antiepileptic therapy, and indicated follow-up care.

Shortness of breath is often an indicator of underlying pulmonary edema from elevated pulmonary perfusion pressure accompanied by endothelial dysfunction. Rales may be auscultated, and a chest x-ray examination may be useful in confirming the presence of edema. Management includes fluid restriction and use of diuretics as clinically indicated.¹

Dependent edema, which may affect the lower extremities, vulva, or back, is also frequently seen. It occurs due to increased vascular permeability and sodium retention related to renal injury and abnormal RAAS activation. It can be managed with compression and diuretics. Physiologic edema of pregnancy can sometimes be distinguished from pathologic edema by timing of onset. Rapidly progressing edema >4 to 5 lbs of weight gain per wk and facial edema are not typical of healthy pregnancy.¹

The right upper quadrant or epigastric pain classically associated with preeclampsia is thought to be the result of periportal and parenchymal necrosis, with hepatocellular edema sometimes resulting in distension of the Glisson capsule. However, no strong correlation between symptoms and laboratory abnormalities exists.¹⁴

Oliguria in preeclampsia is due to decreased intravascular volume as a result of vascular endothelial dysfunction and RAAS activation.^1,12

1% of patients with preeclampsia and 3% of patients with severe preeclampsia will develop placental abruption. Vaginal bleeding in a preeclamptic patient should prompt a workup for abruption.¹

It is important to remember that patients can be asymptomatic with elevated blood pressures and high risk. Rarely, HELLP or eclampsia may present in a normotensive patient. It is important to maintain a high level of suspicion for preeclampsia in patients at increased risk.

• Acute fatty liver of pregnancy
• Appendicitis
• Autoimmune hepatitis
• Chronic hypertension
• Chronic kidney disease
• Diabetic ketoacidosis
• Gallbladder disease
• Gastroenteritis
• Glomerulonephritis
• Hemolytic-uremic syndrome
• Idiopathic thrombocytopenia
• Thrombotic thrombocytopenic purpura
• Pancreatitis
• Peptic ulcer disease
• Secondary hypertension
• Systemic lupus erythematosus
• Viral hepatitis
• Medications or medication withdrawal
• Migraine headache

Hypertension:

• Two blood pressure measurements at least 4 h apart, with a systolic BP of 140 mm Hg or more or a diastolic blood pressure of 90 mm Hg or more.
• Severe hypertension with systolic BP of 160 mm Hg or more or a diastolic blood pressure of 110 mm Hg or more.
• Severe hypertension can be confirmed in a brief period to allow for immediate treatment of severe range blood pressure.

Proteinuria:

• ≥300 mg per 24-h urine collection
• Protein/creatinine ratio ≥0.3
• 2+ on dipstick (only if other methods not available)

Other diagnostic labs:

• See Table 1

• Generally, the recommended laboratory testing is consistent with labs that can be used to identify end-organ dysfunction.
• CBC to assess for anemia or thrombocytopenia.
• Liver function tests (aspartate aminotransferase, alanine aminotransferase) are useful in determining the presence of hepatic injury and are also useful in excluding HELLP syndrome.
• Serum creatinine (and uric acid).
• Prothrombin time, partial thromboplastin time, and fibrinogen can be checked to rule out disseminated intravascular coagulation, if clinically appropriate.

• Computed tomography or MRI scan of head if persistent headache or neurologic symptoms raising concern for PRES or stroke
• Chest x-ray examination if there is concern for pulmonary edema
• Sonogram of fetus to evaluate for intrauterine growth restriction, amniotic fluid level, placental location
• Sonogram of maternal liver if subcapsular hematoma suspected

Delivery is the treatment of choice and the only cure for the disease. This must be taken in the context of the gestational age of the fetus and severity of the preeclampsia.

• For preeclampsia with severe features, administer magnesium sulfate 4 to 6 g intravenous (IV) loading dose, with 2 g/h maintenance (adjust dosage for renal insufficiency). If there is a contraindication to magnesium sulfate, such as myasthenia gravis, then use phenytoin at 10 to 15 mg/kg loading dose, then 200 mg IV q8h starting 12 h after loading dose.
• Treat blood pressure (BP) >160 mm Hg systolic or >110 mm Hg diastolic either with hydralazine 5 to 10 mg IV, then 10 mg, every 20 min to a max dose of 20 mg; or with labetalol hydrochloride 20, 40, 60, 80 mg IV, escalating dosage every 10 min to a max dose of 300 mg IV; or with nifedipine 10 to 20 mg orally every 20 min to a max dose of 180 mg/day for acute blood pressure control. If maximum dose of one medication is reached, add an additional medication to reach goal of BP 140 to 150/90 to 100 mm Hg.
• Continuous fetal monitoring.
• Epidural is anesthesia of choice for pain management in labor or cesarean delivery.
• All patients undergoing induction of labor or cesarean delivery should receive antiseizure medications (magnesium sulfate) if disease with severe features, for delivery and 12 to 24 h postpartum.

Preeclampsia without severe features: If <37 wk, close observation for worsening maternal or fetal condition with delivery at 37 wk. If 24 to 36 wk, consider antenatal corticosteroids. If severe features develop or there is evidence of fetal compromise, earlier delivery is appropriate.

Preeclampsia with severe features: Delivery in the presence of maternal or fetal compromise, labor, or 34 wk. From 24 to 34 wk consider steroids with close monitoring, and at <24 wk offer termination of pregnancy (Fig. 1). Risks of expectant management include severe worsening of disease, eclampsia, abruptio placenta, stillbirth, HELLP syndrome, and intensive care unit (ICU) admission. Contraindications to expectant management include eclampsia, HELLP syndrome, pulmonary edema, disseminated intravascular coagulation, abruptio placenta, uncontrollable severe hypertension, fetal demise, and nonreassuring fetal status. Labetalol, hydralazine, and nifedipine are the drugs of choice for long-term blood-pressure control during pregnancy.

• Preeclampsia is a progressive and unpredictable disease process; a course of expectancy should be managed with caution. Up to 20% of patients who have seizures are normotensive.
• The reoccurrence rate for preeclampsia in a subsequent pregnancy is approximately 20%, and higher in cases with a second trimester presentation or complications. This risk may be decreased with the use of daily low-dose aspirin.
• For high-risk patients, baseline assessment of renal function (24-h urine collection for total protein and creatinine clearance or protein:creatinine ratio), CBC, serum creatinine, liver function tests (LFTs), and uric acid should be obtained at the first prenatal visit.

Obstetric management with input from maternal-fetal subspecialists in severe cases. Transfer of care to facilities with appropriate level of care for all cases <34 wk.

• Low-dose aspirin exposure during the early stages of placentation decreases the risk of preeclampsia, preterm birth, and intrauterine growth restriction in women who are at high risk of preeclampsia. The ACOG and the U.S. Preventive Services Task Force (USPSTF) recommend the use of low-dose aspirin as preventive medication starting after 12 wk of gestation (ideally before 16 wk) in women who are at high risk for preeclampsia.^16,17
• The development of preeclampsia may be one of the earliest identifiable risk markers for potential future cardiovascular disease in women. Women with a history of preeclampsia are at increased risk for cardiovascular disease, and appropriate follow-up should be encouraged.

• Preeclampsia (Patient Information)
• Eclampsia (Related Key Topic)
• Hypertension (Related Key Topic)