Preeclampsia is a hypertensive disorder in pregnancy-related to 2% to 8% of pregnancy-related complications worldwide. It results in 9% to 26% of maternal deaths in low-income countries and 16% in high-income countries. Preeclampsia is defined as new-onset hypertension. The parameters for initial identification of preeclampsia are specifically defined as a systolic blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm Hg or more on two occasions at least 4 hours apart; or shorter interval timing of systolic blood pressure of 160 mm Hg or more or diastolic blood pressure of 110 mm Hg or more, all of which must be identified after 20 weeks of gestation.

The initial presentation of preeclampsia typically arises in near-term pregnancies. Other significant findings that may or may not be a part of the clinical presentation include proteinuria,  signs of end-organ damage, such as thrombocytopenia, impaired liver function, severe persistent right upper quadrant or epigastric pain, excluding all other alternative diagnoses, new-onset headache unresponsive to all forms of management, pulmonary edema, or renal insufficiency with abnormal lab values. Further distinguishing subcategories of preeclampsia include classification into mild or severe, which are deemed so based upon presentation and clinical criteria, to be described further.

Etiology

Although there is an extensive understanding of clinical presentation, diagnostic criteria, and management of preeclampsia currently utilized routinely, the underlying etiology of preeclampsia is not well-understood. A widely accepted cause of preeclampsia stems from the theory of abnormal placentation leading to significant maternal physiologic dysfunction. Despite these obstacles, the well-supported etiologic origin of preeclampsia has been shown to arise to abnormal placentation, leading to aberrant spiral arteries remodeling, placental ischemia, hypoxia, and oxidative stress.

Epidemiology

Preeclampsia and eclampsia account for greater than 50,000 maternal deaths yearly worldwide. Like hypertensive disorders, the incidence of preeclampsia is correlated to ethnicity and race, most prevalent among African-American and Hispanic patients, making up around 26% of maternal death among this population.

There are several risk factors and predeterminants of preeclampsia. These include nulliparity, multi-gestation pregnancy, advanced maternal age greater than 35 years old, in-vitro fertilization or other forms of assisted reproductive technology, maternal comorbidities (chronic hypertension, chronic kidney disease, diabetes mellitus, thrombophilia, obstructive sleep apnea, obesity with pre-pregnancy BMI greater than 30), family history, history of placental abruption or preeclampsia in a previous pregnancy, or intrauterine fetal growth restriction.

Pathophysiology

As described in the etiology of preeclampsia, abnormal placentation leading to vast abnormal remodeling of placental vessels plays a crucial role in the development of preeclampsia and the perpetuating effects of its pathophysiology. Preeclampsia is a multisystem condition, potentiating possible severe hypertension and end-organ dysfunction or failure. 

As vascular sclerosis and abnormal arteriole remodeling of the placenta lead to progressive placental ischemia, the release of distress markers, like antiangiogenic and pro-inflammatory factors, facilitates an imbalance of increased competition with binding sites for angiogenic and essential growth factors. This causes downstream effects of abnormal vessel formation and inadequate vascular accommodation for multiple organ systems, most notably cardiovascular, renal, and hepatic.

History and Physical

Although preeclampsia typically presents with hallmark history and physical signs and symptoms, several atypical presentations exist. This section will review the most common presentations of preeclampsia and those that should prompt further investigation and diagnostic testing when present. 

The most common history findings in patients with preeclampsia are patient complaints of a new-onset headache not accountable by any other alternative diagnosis (i.e., history of headaches or migraines) that is unresponsive to medication. This complaint may or may not be accompanied by additional complaints of visual disturbance. Patients may also endorse right upper quadrant or epigastric pain, with associated nausea or vomiting. Shortness of breath and a perceived increase in swelling, both worsening from baseline pregnancy-related symptoms, may also be reported. 

Patients who present with any single feature or combination of these history findings should undergo a thorough physical exam. This begins with an evaluation of vital signs, more specifically, blood pressure. Patients with a systolic blood pressure of 140 mmHg or greater, or a diastolic pressure of 90 mmHg or greater, should increase suspicion for preeclampsia. In patients at greater than 20 weeks gestation, blood pressure readings on two measurements at least 4 hours apart should be evaluated with further diagnostic workup.

Recent reevaluation of diagnostic blood pressure readings had expanded to include sustained severe hypertensive readings within minutes of repeat readings to allow for timely intervention with antihypertensive therapy. These blood pressure readings include systolic pressure of 160 mmHg or greater or diastolic of 110 mmHg or more. As per the American College of Obstetrics and Gynecology (ACOG), patients previously diagnosed with gestational hypertension presenting with these severe range blood pressures should be diagnosed with preeclampsia with severe features, regardless of the presence of other diagnostic criteria. Suppose patients present with shortness of breath, auscultation, and percussion of lungs should be undertaken to examine for pulmonary disturbances. Palpation of the right upper quadrant and epigastric areas should also be done to evaluate for tenderness. Overall evaluation for edema should also be completed, specifically evaluating areas of dependent (gravity-related) edema like the lower extremities or independent edema, such as in the face or hands.

Evaluation

Following a detailed history and physical exam, patients who present with signs and symptoms of preeclampsia should undergo timely diagnostic testing. This includes pregnancy-induced hypertension laboratory testing, consisting of a urinalysis to evaluate the presence of proteinuria (either with a urine dipstick result of 2+ or greater if other methods are not readily available, a 24-hour urine collection sample significant for 300mg or greater, or a urine protein to creatinine ratio significant for 0.3 or greater), complete blood count to evaluation for thrombocytopenia (defined as a platelet count of less than 100 K/mm), a complete metabolic panel to assess for impaired liver function (with liver enzymes greater than two times the upper limit of normal), and renal insufficiency (defined as a serum concentration of 1.1 mg/dL or greater, or levels two times greater than baseline). All abnormal laboratory findings must exclude any preexisting aberrations or secondary causes for abnormalities in order to be significant for diagnosis.

Although elevated blood pressure with companying proteinuria is typically thought to be required for the diagnosis of preeclampsia, it may not be present in several cases. In such cases, where the absence of proteinuria and new-onset hypertension is discovered, other new-onset symptoms such as thrombocytopenia, renal insufficiency, pulmonary edema, impaired liver function, or new-onset headache with or without visual disturbance may be used for diagnosis. This typically is referred to as preeclampsia without severe features, including new-onset severe range blood pressures (systolic pressure of 160 mmHg or greater, diastolic pressure of 110 mmHg or greater on two readings at least 4 hours apart), with or without the findings previously mentioned.

Treatment / Management

Management of preeclampsia begins with early diagnosis and intervention, focusing on adequate blood pressure control and seizure prevention. Blood pressure control can be accomplished utilizing beta-blockade, such as labetalol, or calcium-channel blockade, such as nifedipine. 

Fetal evaluation should also include ultrasonography of amniotic fluid index, estimated fetal weight, and antenatal testing, such as non-stress tests and biophysical profiles. Fetal status may also play a major role in determining delivery versus expectant management in preeclamptic patients. 

Ultimately, the definitive treatment of preeclampsia is the delivery of the fetus. While continued observation is permissible for preterm gestations in patients with either well-controlled gestational hypertension or preeclampsia without severe features in the setting of normal antepartum testing, risks of expectant management exist (see “Complications” section). If expectant management is undertaken in stable patients, serial ultrasonography, weekly antepartum testing, and close observation of symptoms and blood pressure and laboratory values should be employed. As per ACOG, it is recommended that patients at 37 weeks gestation diagnosed with gestational hypertension or preeclampsia without severe features should undergo delivery rather than expectant management.

It is also recommended that patients diagnosed with preeclampsia with severe features at or beyond 34 weeks gestation undergo delivery after maternal stabilization and should not be delayed to accommodate steroid administration. In cases where patients less than 34 weeks gestation are diagnosed with preeclampsia with severe features, proper stabilization of both maternal and fetal well-being should be initiated and may be followed with expectant management.

While neonatal and maternal outcomes may benefit from delivery or expectant management, informed decision-making regarding benefits and risks must be discussed with the patient. Antepartum admission with close monitoring of maternal and fetal conditions may be employed with a low threshold for delivery if maternal or fetal deterioration is suspected. Findings that indicate expeditious delivery after stabilization regardless of gestational age can be described as fetal and maternal factors.

Fetal factors include abnormal antepartum testing, sustained reversed end-diastolic flow of the umbilical artery. Maternal factors are uncontrolled blood pressure, continued headaches/visual disturbance or right upper quadrant/epigastric pain despite repeated medical management, myocardial infarction, stroke, pulmonary edema, HELLP syndrome, eclampsia, or suspicion of placental abruption or bleeding with no other diagnosis. Delivery before 34 weeks gestation if indicated should prompt the administration of antenatal steroids for fetal lung maturation, but this should not delay delivery. 

Medications utilized to stabilize severe range blood pressures include intravenous labetalol, hydralazine, and oral immediate-release nifedipine. The first choice for seizure prophylaxis in patients with preeclampsia with severe features is initiated in intravenous magnesium sulfate therapy.

Differential Diagnosis

The differential diagnosis for preeclampsia may coincidently be a risk factor for developing preeclampsia. These include chronic hypertension, gestational hypertension, antiphospholipid antibody syndrome, thrombotic microangiopathies, lupus, epilepsy or seizure disorder, chronic renal disease,  chronic liver disease, or other significant medical conditions (i.e., pheochromocytoma or other endocrinopathies).

Prognosis

Early diagnosis, timely medical intervention, and appropriate maternal and fetal surveillance significantly improve maternal and fetal outcomes. As preeclampsia continues to be responsible for up to a quarter of maternal deaths in certain ethnic backgrounds (the Caribbean and Latin American population, followed by Asian and African populations), prompt care and routine monitoring decrease morbidity and mortality.

Complications

Delayed delivery of the fetus in preeclamptic patients in the late preterm period increases the risk of severe hypertension, with severe consequences such as eclampsia, HELLP syndrome, pulmonary edema, myocardial infarction, acute respiratory distress syndrome, stroke, renal and retinal injury, and fetal complications including fetal growth restrictions, placental abruption, or fetal or maternal death.

Common complications exist with the initiation of medical management for adequate blood pressure control. These include tachycardia, hypotension, headaches, fetal heart tracing abnormalities using labetalol, hydralazine, or nifedipine. The use of magnesium sulfate for seizure prophylaxis also carries additional side effects and complication risks such as respiratory depression and cardiac arrest. Thus, frequent laboratory testing of serum magnesium levels and physical examinations every 4 to 6 hours for magnesium sulfate therapy patients is recommended.