Preeclampsia affects 3 to 7% of pregnant women. Preeclampsia and eclampsia develop after 20 weeks gestation; up to 25% of cases develop postpartum, most often within the first 4 days but sometimes up to 6 weeks postpartum.
Untreated preeclampsia usually smolders for a variable time, then suddenly progresses to eclampsia, which occurs in 1/200 patients with preeclampsia. Untreated eclampsia is usually fatal.
Etiology of Preeclampsia and Eclampsia
Etiology of preeclampsia is unknown.
However, risk factors include the following:
Vascular disorders (eg, renal disorders Renal Insufficiency in Pregnancy Pregnancy often does not worsen renal disorders; it seems to exacerbate noninfectious renal disorders only when uncontrolled hypertension coexists. However, significant renal insufficiency ... read more , diabetic vasculopathy)
Older (> 35) or very young (eg, < 17) maternal age
Family history of preeclampsia
Preeclampsia or poor outcome in previous pregnancies
Thrombotic disorders Thromboembolic Disorders in Pregnancy In the US, thromboembolic disorders—deep venous thrombosis (DVT) or pulmonary embolism (PE)—are a leading cause of maternal mortality. During pregnancy, risk is increased because Venous capacitance... read more (eg, antiphospholipid antibody syndrome Antiphospholipid Antibody Syndrome (APS) Antiphospholipid antibody syndrome is an autoimmune disorder in which patients have autoantibodies to phospholipid-bound proteins. Venous or arterial thrombi may occur. The pathophysiology is... read more )
Pathophysiology of Preeclampsia and Eclampsia
Pathophysiology of preeclampsia and eclampsia is poorly understood. Factors may include poorly developed uterine placental spiral arterioles (which decrease uteroplacental blood flow during late pregnancy), a genetic abnormality on chromosome 13, immunologic abnormalities, and placental ischemia or infarction. Lipid peroxidation of cell membranes induced by free radicals may contribute to preeclampsia.
Fetal growth restriction Small-for-Gestational-Age (SGA) Infant Infants whose weight is the 10th percentile for gestational age are classified as small for gestational age. Complications include perinatal asphyxia, meconium aspiration, polycythemia, and... read more or fetal death Stillbirth Stillbirth is delivery of a dead fetus at > 20 weeks gestation. Maternal and fetal testing is done to determine the cause. Management is as for routine care after live delivery. Stillbirth,... read more may result. Diffuse or multifocal vasospasm can result in maternal ischemia, eventually damaging multiple organs, particularly the brain, kidneys, and liver. Factors that may contribute to vasospasm include decreased prostacyclin (an endothelium-derived vasodilator), increased endothelin (an endothelium-derived vasoconstrictor), and increased soluble Flt-1 (a circulating receptor for vascular endothelial growth factor). Women who have preeclampsia are at risk of abruptio placentae Abruptio Placentae Abruptio placentae is premature separation of a normally implanted placenta from the uterus, usually after 20 weeks gestation. It can be an obstetric emergency. Manifestations may include vaginal... read more in the current and in future pregnancies, possibly because both disorders are related to uteroplacental insufficiency.
The coagulation system is activated, possibly secondary to endothelial cell dysfunction, leading to platelet activation. The HELLP syndrome (hemolysis, elevated liver function tests, and low platelet count) develops in 10 to 20% of women with severe preeclampsia or eclampsia; this incidence is about 100 times that for all pregnancies (1 to 2/1000). Most pregnant women with HELLP syndrome have hypertension and proteinuria, but some have neither.
Symptoms and Signs of Preeclampsia and Eclampsia
Preeclampsia may be asymptomatic or may cause edema or excessive weight gain. Nondependent edema, such as facial or hand swelling (the patient’s ring may no longer fit her finger), is more specific than dependent edema.
Reflex reactivity may be increased, indicating neuromuscular irritability, which can progress to seizures (eclampsia).
Petechiae may develop, as may other signs of coagulopathy.
Pearls & Pitfalls
Preeclampsia with severe features may cause organ damage; these features may include
Epigastric or right upper quadrant abdominal pain (reflecting hepatic ischemia or capsular distention)
Nausea and/or vomiting
Dyspnea (reflecting pulmonary edema, acute respiratory distress syndrome [ARDS], or cardiac dysfunction secondary to increased afterload)
Oliguria (reflecting decreased plasma volume or ischemic acute tubular necrosis)
Diagnosis of Preeclampsia and Eclampsia
New-onset hypertension (blood pressure [BP] > 140/90 mm Hg) plus new unexplained proteinuria (> 300 mg/24 hours after 20 weeks or a urine protein/creatinine ratio of ≥ 0.3)
Diagnosis of preeclampsia is suggested by symptoms or presence of hypertension, defined as systolic BP > 140 mm Hg, diastolic BP > 90 mm Hg, or both. Except in emergencies, hypertension should be documented in > 2 measurements taken at least 4 hours apart. Urine protein excretion is measured in a 24-hour collection.
Proteinuria is defined as > 300 mg/24 hours. Alternatively, proteinuria is diagnosed based on a protein/creatinine ratio ≥ 0.3 or a dipstick reading of 1+; the dipstick test is used only if other quantitative methods are not available. Absence of proteinuria on less accurate tests (eg, urine dipstick testing, routine urinalysis) does not rule out preeclampsia.
In the absence of proteinuria, preeclampsia is also diagnosed if pregnant women have new-onset hypertension plus new onset of any of the following:
Thrombocytopenia (platelets < 100,000/mcL)
Renal insufficiency (serum creatinine > 1.1 mg/dL or doubling of serum creatinine in women without renal disease)
Impaired liver function (aminotransferases > 2 times normal)
Cerebral or visual symptoms
The following points help differentiate among hypertensive disorders in pregnant women:
Chronic hypertension is identified if hypertension precedes pregnancy, is present at < 20 weeks gestation, or persists for > 6 weeks (usually > 12 weeks) postpartum (even if hypertension is first documented at > 20 weeks gestation). Chronic hypertension may be masked during early pregnancy by the physiologic decrease in BP.
Gestational hypertension is hypertension without proteinuria or other findings of preeclampsia; it first occurs at > 20 weeks gestation in women known not to have hypertension before pregnancy and resolves by 12 weeks (usually by 6 weeks) postpartum.
Preeclampsia is new-onset hypertension (BP > 140/90 mm Hg) plus new unexplained proteinuria (> 300 mg/24 hours or urine protein/creatinine ratio ≥ 0.3) after 20 weeks or other criteria (see above).
Preeclampsia superimposed on chronic hypertension is diagnosed when new unexplained proteinuria develops or proteinuria worsens after 20 weeks in a woman known to have hypertension with BP elevations above baseline or when preeclampsia with severe features develops after 20 weeks in a woman known to have hypertension and proteinuria.
If preeclampsia is diagnosed, tests include complete blood count (CBC), platelet count, uric acid, liver tests, blood urea nitrogen (BUN), creatinine, and, if creatinine is abnormal, creatine clearance. The fetus is assessed using a nonstress test or biophysical profile (including assessment of amniotic fluid volume) and tests that estimate fetal weight.
HELLP syndrome is suggested by microangiopathic findings (eg, schistocytes, helmet cells) on peripheral blood smears, elevated liver enzymes, and a low platelet count.
Preeclampsia with severe features is differentiated from mild forms by one or more of the following:
Central nervous system (CNS) dysfunction (eg, blurred vision, scotomata, altered mental status, severe headache unrelieved by acetaminophen)
Symptoms of liver capsule distention (eg, right upper quadrant or epigastric pain)
Nausea and vomiting
Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times normal
Systolic BP > 160 mm Hg or diastolic BP > 110 mm Hg on 2 occasions ≥ 4 hours apart
Platelet count < 100,000/mcL
Urine output < 500 mL/24 hours
Pulmonary edema or cyanosis
Progressive renal insufficiency (serum creatinine > 1.1 mg/dL or doubling of serum creatinine in women without renal disease)
Treatment of Preeclampsia and Eclampsia
Usually hospitalization and sometimes antihypertensive treatment
Delivery, depending on factors such as gestational age and severity of preeclampsia
Sometimes magnesium sulfate to prevent or treat new seizures or to prevent seizures from recurring
Definitive treatment for preeclampsia is delivery. However, risk of early delivery is balanced against gestational age, severity of preeclampsia, and response to other treatments.
Usually, immediate delivery after maternal stabilization (eg, controlling seizures, beginning to control blood pressure [BP]) is indicated for the following:
Pregnancy of ≥ 37 weeks
Preeclampsia with severe features if pregnancy is ≥ 34 weeks
Deteriorating renal, pulmonary, cardiac, or hepatic function (eg, HELLP syndrome)
Nonreassuring results of fetal monitoring or testing
Other treatments aim to optimize maternal health, which usually optimizes fetal health. If delivery can be safely delayed in pregnancies of < 34 weeks, corticosteroids are given for 48 hours to accelerate fetal lung maturity. Some stable patients can be given corticosteroids after 34 weeks and before 36 weeks (late preterm period) if they have not required corticosteroids earlier in the pregnancy.
Most patients are hospitalized. Patients with eclampsia or preeclampsia with severe features are often admitted to a maternal special care unit or an intensive care unit (ICU).
Preeclampsia without severe features
If preeclampsia does not have severe features and occurs before 37 weeks, outpatient treatment is possible; it includes modified activity (modified rest), BP measurements, laboratory monitoring, fetal nonstress testing, and physician visits at least once a week.
However, most patients who have preeclampsia without severe features require hospitalization, at least initially. As long as no criteria for preeclampsia with severe features are met, delivery can occur (eg, by induction) at 37 weeks.
Outpatients are usually evaluated at least once a week for evidence of seizures, preeclampsia with severe features, and vaginal bleeding; BP, reflexes, and fetal heart status (with nonstress testing or a biophysical profile) are also checked. Platelet count, serum creatinine, and serum liver enzymes are measured frequently until stable, then at least once a week.
All hospitalized patients are followed by an obstetrician or a maternal-fetal medicine specialist and evaluated as for outpatients (described above); evaluation is more frequent if preeclampsia with severe features is diagnosed or if gestational age is < 34 weeks.
As soon as eclampsia is diagnosed, magnesium sulfate must be given to prevent seizures from recurring. If patients have preeclampsia with severe features, magnesium sulfate can be given to prevent seizures. Magnesium sulfate is given for 24 hours postpartum. Whether patients who have preeclampsia without severe features always require magnesium sulfate before delivery is controversial.
Magnesium sulfate 4 g IV over 20 minutes is given, followed by a constant IV infusion of about 1 to 3 g/hour, with supplemental doses as necessary. Dose is adjusted based on the patient’s reflexes. Patients with abnormally high magnesium levels (eg, with magnesium levels > 10 mEq/L or a sudden decrease in reflex reactivity), cardiac dysfunction (eg, with dyspnea or chest pain), or hypoventilation after treatment with magnesium sulfate can be treated with calcium gluconate 1 g IV.
IV magnesium sulfate may cause lethargy, hypotonia, and transient respiratory depression in neonates. However, serious neonatal complications are uncommon.
If oral intake is prohibited, hospitalized patients are given IV Ringer lactate or 0.9% normal saline solution, beginning at about 125 mL/hour (to increase urine output). Persistent oliguria is treated with a carefully monitored fluid challenge. Diuretics are usually not used. Monitoring with a pulmonary artery catheter is rarely necessary and, if needed, is done in consultation with a critical care specialist and in an intensive care unit (ICU). Anuric patients with normovolemia may require renal vasodilators or dialysis.
If seizures occur despite magnesium therapy, diazepam or lorazepam can be given IV to stop seizures, and IV hydralazine or labetalol is given in a dose titrated to lower systolic BP to 140 to 155 mm Hg and diastolic BP to 90 to 105 mm Hg.
The most efficient method of delivery should be used. If the cervix is favorable and rapid vaginal delivery seems feasible, a dilute IV infusion of oxytocin is given to accelerate labor; if labor is active, the membranes are ruptured. If the cervix is unfavorable and prompt vaginal delivery is unlikely, cesarean delivery can be considered. Preeclampsia and eclampsia, if not resolved before delivery, usually resolve rapidly afterward, beginning within 6 to 12 hours.
Patients should be evaluated every 1 to 2 weeks postpartum with periodic BP measurement. If BP remains high after 6 weeks postpartum, patients may have chronic hypertension and should be referred to their primary care physician for management.
Low-dose aspirin (81 mg/day) is recommended for patients at high risk of preeclampsia; it should be started at 12 to 28 weeks of gestation (ideally before 16 weeks) and continued until delivery. This treatment can reduce the risk of preeclampsia in subsequent pregnancies. Low-dose aspirin prophylaxis should be considered if patients have more than one moderate risk factors for preeclampsia (1 Treatment reference Preeclampsia is new-onset or worsening of existing hypertension with proteinuria after 20 weeks gestation. Eclampsia is unexplained generalized seizures in patients with preeclampsia. Diagnosis... read more ).
1. American College of Obstetricians and Gynecologists (ACOG): ACOG Committee Opinion No. 743: Low-dose aspirin use during pregnancy. Obstet Gynecol 132 (1):e44-e52, 2018. doi: 10.1097/AOG.0000000000002708
Preeclampsia develops after 20 weeks gestation; it develops postpartum in 25% of cases.
Swelling of the face or hands and hyperreflexia are relatively specific findings for preeclampsia.
Preeclampsia is severe if it causes significant organ dysfunction (detected clinically or by testing).
HELLP syndrome occurs in 10 to 20% of women who have preeclampsia with severe features or eclampsia.
Monitor the mother and fetus closely, usually in a hospital maternal special care unit or ICU.
As soon as eclampsia is diagnosed, treat with magnesium sulfate to prevent seizures from recurring.
If preeclampsia with severe features is diagnosed, consider treatment with magnesium sulfate for seizure prophylaxis; treat with magnesium sulfate for 24 hours after delivery.
For mild preeclampsia, use of magnesium sulfate is less clear.
Delivery is usually indicated when the pregnancy is ≥ 37 weeks, but if preeclampsia with severe features is diagnosed, deliver by 34 weeks; if HELLP syndrome is diagnosed, deliver immediately.