Eclampsia

Etiology

Eclampsia, a severe complication of preeclampsia, has multiple underlying causes, with uteroplacental ischemia being the primary mechanism. Please see StatPearls' companion resource, "Preeclampsia," for more information on preeclampsia. Uteroplacental ischemia involves an inadequate blood supply to the placenta, leading to its infarction and the release of toxic substances into the maternal bloodstream. These substances may trigger seizures, the hallmark of eclampsia. The role of uteroplacental ischemia is supported by various animal models that replicate preeclampsia-like symptoms, including hypertension and proteinuria, through induced reductions in uteroplacental blood flow.[2][4]

Other factors contributing to the development of eclampsia include maternal infections and inflammation, such as periodontal disease and urinary tract infections, which have been linked to an increased risk of preeclampsia. Moreover, maternal obesity, gestational diabetes, and metabolic disorders are significant contributors to the development of eclampsia, likely due to the associated systemic inflammation and endothelial dysfunction.[4]

Additionally, fetal conditions such as trisomy 13 and mirror syndrome (formerly Ballentyne syndrome), as well as complications from multiple gestations, can precipitate preeclampsia, which may progress to eclampsia if not managed effectively. The premature aging of the placenta and breakdowns in maternal-fetal immune tolerance further exacerbate the risk, indicating a complex interplay of genetic, immunological, and environmental factors in the pathogenesis of eclampsia.[2][4]

Epidemiology

Hypertensive disorders during pregnancy are reported to affect approximately 10% to 20% of pregnancies in the United States (US).[1] However, the incidence of new-onset hypertensive disorders of pregnancy has increased by almost 50% in the last 15 years, primarily in rural and urban areas.[5] Moreover, the prevalence of postpartum preeclampsia ranges from 0.3% to 27.5% in the US, with the variability in reported incidence likely arising from the underreporting of patients with milder conditions.[1] 

While preeclampsia is estimated to occur in 3% to 8% of pregnancies, the mortality rate is significantly higher in younger patients, ranging between 5% and 20%.[3] Results from a recent cross-sectional study of nearly 28 million live births between 2009 and 2017 showed that 0.3% were linked to eclampsia.[6] Another study's results, cited by the American Heart Association, reported an adjusted odds ratio for eclampsia in women with hypertensive disorders during pregnancy of 65.9 (43.6–99.6).[7]

Globally, hypertensive disorders of pregnancy are the most common cause of morbidity and mortality in gravidas and infants.[8] The prevalence of preeclampsia is approximately 4.6% worldwide, while eclampsia is estimated at 0.3%, according to the World Health Organization.[9] The incidence of eclampsia varies regionally, with low- and middle-resource countries reporting a higher incidence of 0.5%.[9]

Eclampsia Risk Factors

Eclampsia and other hypertensive disorders of pregnancy have many of the same risk factors: chronic hypertension, younger age, those with lower education levels, and first-time mothers.[10] According to the results from a recent eclampsia study, approximately one-third of eclampsia cases occurred in women younger than 20.[9] Other risk factors include:

• Personal history of pregnancy hypertensive disorder
• Family history of preeclampsia
• Prepregnancy chronic hypertension
• Comorbid conditions such as diabetes, renal disease, and autoimmune disorders
• Maternal obesity (body mass index >30 kg/m²)
• History of preterm birth less than 32 weeks of gestation [11]
• Low socioeconomic status
• Insufficient prenatal care [11]
• Maternal age older than 35
• Multifetal gestation
• Interval since previous birth of 10 or more years
• African American ethnicity
• In vitro fertilization [12][13]

Pathophysiology

Eclampsia and preeclampsia were once thought to be caused by "toxins" or "poisons" entering the gravida's bloodstream, leading to the term "toxemia of pregnancy."[14] Despite multiple studies that have posited several underlying mechanisms, the precise pathophysiology of eclampsia remains unclear.[11]

Theories that have gained more support involve dysfunction of the blood-brain barrier (BBB) and cerebral blood flow autoregulation. The proposed BBB pathophysiologic mechanism suggests that eclampsia may result from disrupted cerebral blood flow autoregulation, similar to hypertensive encephalopathy. This disruption could cause BBB dysfunction, allowing fluids and proteins to enter brain tissue and potentially leading to seizures. The BBB, formed by endothelial cells in the capillaries, regulates the passage of molecules between the blood and the brain. Typically, the BBB maintains a stable environment for neural function by selectively allowing substances to cross and using specific ion channels and transporters to optimize conditions for synaptic signaling. Autoregulation in the cerebral circulation adjusts blood flow in response to changes in blood pressure, with vasoconstriction occurring at high pressures and vasodilation at low pressures.[11]

Another proposed hypothesis is that elevated blood pressure from preeclampsia causes dysfunction of autoregulation of the cerebral vasculature, which causes hypoperfusion, endothelial damage, or edema.[15] During pregnancy, the body adapts to increased plasma volume, requiring adjustments in cerebral circulation to maintain consistent blood flow. Failure in these adaptations may increase BBB permeability, resulting in vasogenic edema, neuroinflammation, and neuronal injury. Autoregulation dysfunction may lead to acute hypertension, increasing hydrostatic pressure, reducing cerebral vascular resistance, and potentially damaging microvessels, ultimately resulting in cerebral edema and eclampsia.[3] However, the observance of eclampsia in women without severe hypertension before seizures indicates that this is not the only underlying mechanism.

Other proposed mechanisms include the impact of circulating factors in preeclampsia, such as vascular endothelial growth factor and oxidized low-density lipoprotein, which may exacerbate BBB dysfunction through oxidative stress and inflammation. Additionally, theories involving cerebral vasospasm and overregulation have been proposed, though studies indicate that overperfusion, rather than vasospasm, might be more relevant to the onset of eclamptic seizures.[11]

Histopathology

Autopsy findings in eclampsia often reveal significant gross cerebral pathology, including extensive brain swelling, white matter hemorrhages, and tissue necrosis. Histologic findings observed in patients with eclampsia include perivascular edema, hemorrhage, hemosiderin deposits, small vessel thrombosis, and parenchymal necrosis. However, these histopathologic characteristics are not diagnostic of eclampsia, as they are also associated with other conditions involving systemic endothelial damage, such as atypical hemolytic-uremic syndrome, hypertensive urgency or emergency, and antiphospholipid antibody syndrome.[11]

History and Physical

The classic presentation of eclampsia is generalized tonic-clonic seizures with no other underlying cause in a patient with a hypertensive pregnancy disorder. Generally, most professional societies use a blood pressure of 140/90 mm Hg or higher as the threshold for hypertension during pregnancy.[7] Additionally, eclampsia may be preceded by various symptoms, including visual disturbances, severe headaches, and epigastric pain, though these symptoms do not reliably predict its occurrence. Common visual changes include blurred vision, double vision, scotomata, flashes of light, and transient cortical blindness. Several studies have reported the most frequent symptoms associated with eclampsia were headaches, visual disturbances, and upper abdominal or epigastric pain.[2][11] 

While hypertension often accompanies eclampsia and is considered a distinguishing feature of the condition, it is not always present; some patients may develop eclampsia without severe blood pressure elevation. Conversely, not all patients with preeclampsia with severe features develop eclampsia.[10][11] Moreover, proteinuria, a standard marker of preeclampsia, may also be absent in some cases of eclampsia. Therefore, the clinical characteristics of eclampsia are not dependable indicators. Additionally, the absence of severe preeclampsia features in some patients with eclampsia challenges the common belief that preeclampsia will always worsen over time, eventually progressing to eclampsia.[2] Clinicians should be careful to consider differential diagnoses, including posterior reversible encephalopathy syndrome, that present similarly to eclampsia and require careful management, including blood pressure control and long-term follow-up.[2][11] Please see StatPearls' companion resource, "Posterior Reversible Encephalopathy Syndrome," for more information on this condition.

Eclamptic seizures can occur before, during, or after delivery, with a significant number occurring during the antepartum period. Postpartum eclampsia, particularly late-onset eclampsia, defined as seizures occurring more than 48 hours after delivery, can still pose a significant risk. A large portion of these seizures occurs in the first 7 to 10 days postpartum, often presenting with neurological symptoms, including headache. Postpartum headaches should be carefully evaluated, especially if accompanied by altered mental status, seizures, or visual disturbances, to rule out other severe conditions such as cerebral venous thrombosis or reversible cerebral vasoconstriction syndrome.[11]

Evaluation

Eclampsia is typically the condition initially suspected in patients presenting with generalized tonic-clonic seizures, especially those individuals with a history of hypertensive pregnancy disorder. Evaluating eclampsia primarily involves assessing various aspects of maternal and fetal health due to the condition’s potential impact on multiple organs and the exclusion of differential diagnoses. Because of the urgent nature of eclampsia, this evaluation is conducted alongside emergent therapeutic interventions.[10][11][16]

The evaluation for eclampsia is centered around the diagnosis of preeclampsia as it is a known life-threatening complication of this disease process. In addition to serial maternal blood pressure measurements and continuous fetal monitoring, diagnostic studies should be performed to assess for indications of end-organ dysfunction, including proteinuria, renal dysfunction, liver dysfunction, central nervous system symptoms, pulmonary edema, and thrombocytopenia.[10][11][16]

Laboratory Studies

Key laboratory studies include liver function panels, platelet counts, and complete metabolic profiles to assess kidney function as performed for preeclampsia and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Please see StatPearls' companion resource, "HELLP syndrome," for more information on diagnostic laboratory studies. Proteinuria, defined as 300 mg or more of protein in a 24-hour urine sample or a urinary protein/creatinine ratio of 0.3 or greater, is no longer essential for diagnosing preeclampsia and may be absent before the onset of seizure activity; this laboratory test is still included during evaluation.[2][17]

Other essential laboratory studies include a hepatic panel to assess liver function, a complete blood count to quantify platelet counts, and a basic metabolic profile to assess kidney function. Platelet levels of 100,000/μL or less and liver transaminase levels more than 2 times the upper limit of normal with or without right upper quadrant or epigastric pain are also associated with preeclampsia with severe features. Laboratory tests to exclude differential diagnoses for seizures should also be considered, including urine drug screens, complete metabolic panels, or toxicology screens. Brain natriuretic peptide testing can help confirm the diagnosis and guide management, as it correlates well with heart function and fluid levels in cases where fluid overload is suspected.[1][11]

Additional Diagnostic Studies

Imaging studies, including chest x-rays and obstetric ultrasounds, can also be utilized to assess maternal pulmonary edema and fetal well-being, respectively. For patients with neurological symptoms, such as persistent headaches or vision changes despite treatment for hypertension, neuroimaging is recommended to rule out conditions like stroke or posterior reversible encephalopathy syndrome.[11][16][10] Neurologic studies, including electroencephalography (EEG), computed tomography (CT), magnetic resonance imaging (MRI), and cerebral angiography may be conducted following seizures. EEGs in women with eclampsia frequently show abnormalities such as slow waves or spikes, typically in the occipital region.

These abnormal EEG findings typically persist even with seizure prophylaxis using magnesium sulfate.[11] Abnormal neuroimaging findings, including cerebral edema, infarction, and hemorrhage, may also be demonstrated. Routine neuroimaging is not recommended for all patients with eclampsia, but it is advised in cases involving focal neurological signs, recurrent seizures, or prolonged coma. Imaging is also warranted for atypical cases, such as seizures occurring before 20 weeks of pregnancy or more than 48 hours postpartum, as these may indicate other underlying neurological conditions that require intervention.[11]

Treatment / Management

Management of Eclampsia

Eclamptic seizures are a medical emergency and require immediate treatment to prevent mortality for the patient and fetus. The management approach for eclampsia should balance immediate supportive measures, seizure control, and the prevention of recurrent convulsions while ensuring a safe and optimally timed delivery and closely monitored postpartum care.[3][10] The management of eclampsia should include the following components:

• Initial supportive measures
  • Call for assistance: Immediate help should be summoned as other trained clinicians are essential to stabilize the patient, evaluate underlying maternal-fetal conditions, and prepare for delivery simultaneously.[10]
  • Maternal positioning: Patients should be placed in the lateral decubitus position to improve blood flow and reduce the risk of aspiration.[2]
  • Preventing injury: Clinicians should ensure the patient's safety by elevating and padding the bed rails. However, restraining the patient during seizures is not advised.[11]
  • Airway and oxygenation: Maintaining a patent airway and preventing aspiration by suctioning secretions are critical. During the seizure, supplemental oxygen administered at 8 to 10 L/min via a face mask is recommended to ensure optimal maternal-fetal oxygenation. Oxygen saturation should continue to be monitored following the seizure to assess for the development of complications, including aspiration and pulmonary edema, which may result in maternal hypoxia and, therefore, necessitate treatment.[2][11]
  • Vital signs and laboratory studies: During and after the seizure, the healthcare team should monitor oxygen saturation, vital signs, urine output, and fluid status closely for at least 72 hours. Following the seizure, laboratory assessments should be performed, including complete blood count, liver function tests, and creatinine levels.[2][11]

• Seizure management
  • Magnesium sulfate: Magnesium sulfate is preferred over other antiseizure treatments for eclamptic seizure prevention. While most seizures are self-limiting, magnesium sulfate is administered primarily to prevent further seizure activity, not to halt the current seizure.[2] The recommended standard loading dose is 6 g intravenous (IV) over 15 to 20 min, followed by a 2 g/hour maintenance dose. In patients without IV access, a loading dose of magnesium sulfate 10 g intramuscularly, followed by a maintenance dose of 5 g intramuscularly every 4 hours, may be used as an alternative regimen.[11][2]
  • In patients with contraindications to magnesium sulfate (eg, myasthenia gravis, hypocalcemia, renal failure, cardiac ischemia, heart block, or myocarditis), alternative antiseizure therapies (eg, phenytoin and diazepam) may be considered.[2] Levetiracetam may be preferable in patients with myasthenia gravis, a condition that may be exacerbated by phenytoin.[18]
  • Recurrent seizures: If convulsions recur, clinicians may consider administering an additional 2 to 4 g of magnesium sulfate over 5 min.[2] If seizures persist after 20 minues, or more than 2 seizures have occurred despite magnesium therapy, lorazepam 4 mg IV over 3 to 5 minutes is recommended.[11] Other alternative seizure interventions that may be utilized include:
    • Sodium amobarbital: 250 mg IV in 3 minutes [2]
    • Diazepam: Loading dose of 10 mg IV over 2 min, then maintenance dose of 40 mg in 500 mL normal saline for 24 hours, followed by 20 mg in 500 mL for the next 24 hours [19]
    • Phenytoin: Loading dose of 10 mg/kg initially in 30 minutes, then 2 hours later administer 5 mg/kg over 10 minutes, followed by a maintenance dose of 300 mg IV over 10 minutes for 24 hours from the last seizure [19]
  • Fetal monitoring: During seizures, fetal heart rate decelerations, bradycardia, or tachycardia may occur secondary to maternal hypoxia and hypercapnia. Uterine contractions can increase but usually resolve once the maternal condition stabilizes.[2][11]
  • Postpartum management: Magnesium sulfate is recommended to prevent eclamptic seizures in postpartum patients with new-onset hypertension and neurologic symptoms (eg, headaches and blurred vision) or preeclampsia with severe features.[1]
(B3)

• Magnesium sulfate monitoring
  • Therapeutic levels: Elevated levels of magnesium sulfate can cause adverse events, including respiratory depression and cardiac arrest. Therefore, clinicians should monitor for clinical signs of toxicity, including decreased urine output, absent deep tendon reflexes, and respiratory depression. Clinicians should assess magnesium serum levels every 4 to 6 hours in patients with renal impairment due to the increased risk of toxicity.[2][11]
  • Toxicity management: In patients demonstrating signs of magnesium toxicity (eg, respiratory depression) or the serum level is >9.6 mg/dL, the magnesium sulfate infusion should be discontinued, and calcium gluconate 10% solution (10 mL IV) can be administered over 3 min as an antidote.[11]
  • Magnesium sulfate duration: Continuing magnesium sulfate administration is recommended for 24 hours after delivery or the last seizure.[11]

• Antihypertensive management
  • Blood pressure control: Treatment of severe hypertension is associated with decreased maternal-fetal morbidity. Experts recommend gradually reducing and maintaining blood pressure between a systolic of 140 and 160 mm Hg and a diastolic blood pressure of 90 and 110 mm Hg without causing a sudden drop that may compromise placental perfusion. Management of a hypertensive crisis usually involves rapid-acting IV first-line medications, such as hydralazine, labetalol, or nifedipine.[3][11]
  • Hydralazine: Hydralazine is typically administered with a dosage of 5 to 10 mg IV, with repeat doses every 20 minutes as needed to a maximum total of 20 mg.[11] Hydralazine works by dilating blood vessels, reducing vascular resistance, and relaxing the smooth muscles of precapillary arterioles, which helps lower blood pressure. Additionally, hydralazine is associated with improved placental circulation. Common adverse events include reflex tachycardia and increased cardiac output, while rarer adverse effects include dizziness, chest pain, fluid retention, and severe hypotension. Clinicians should be especially aware of potential hypotension when using hydralazine as patients with preeclampsia typically have decreased intravascular volume already, and hypotension may result in further uteroplacental insufficiency.[3] Therefore, hydralazine requires careful fluid balance and intravascular volume monitoring to avoid complications, including pulmonary edema.[3] 
  • Labetalol: Labetalol is a beta blocker that dilates blood vessels and reduces vascular resistance, heart rate, and blood pressure while maintaining normal peripheral and uteroplacental circulation. In many institutions, labetalol is preferred over other first-line antihypertensives. The recommended regimen for emergent blood pressure control is 10 to 20 mg IV initially, followed by 20 to 80 mg every 10 to 30 min up to a maximum dosage of 300 mg. Alternatively, an infusion of 1 to 2 mg/min IV may be administered. Labetalol reduces BP while maintaining peripheral circulation, including uteroplacental blood flow. Labetalol is effective with relatively mild adverse effects and is suitable for patients with heart failure or after a heart attack. However, it can cause bradycardia in both mother and fetus and should not be used with calcium channel blockers or in patients with certain conditions, including asthma or heart block.[2][11]
  • Nifedipine: Oral nifedipine may also be used for severe hypertension with a recommended dosage of 10 to 20 mg, repeated in 20 minutes if needed. A subsequent 10 to 20 mg dose may be administered every 2 to 6 hours up to a maximum daily dose of 180 mg. The protective renal effect and rapid onset are benefits of nifedipine.[20] Adverse effects include reflex tachycardia and headache.[2][11]

• Delivery Considerations
  • Delivery timing: Eclampsia is an indication for delivery; cesarean delivery is not necessarily required. The mode of delivery should be based on various clinical features, including gestational age, fetal presentation, and cervical favorability. Please see StatPearls' companion resource, "Bishop Score," for more information on cervical favorability. Due to the increased risk for labor induction failure, in pregnancies under 30 weeks gestation with an unfavorable cervix, cesarean delivery is recommended.[2][11]
  • Maternal resuscitation: The maternal-fetal condition should be stabilized before proceeding with delivery. Following stabilization, fetal heart rate and uterine activity typically normalize.[2][11]
  • Antenatal steroids: A full course of corticosteroids should be administered in pregnancies less than 34 weeks gestation for fetal lung maturation; delivery should not be delayed to complete the steroid course if the maternal-fetal condition begins to deteriorate.[2]
  • Postpartum monitoring: In the postpartum period, seizures most commonly occur in the first 48 hours following delivery, and the seizure risk remains elevated during the first postpartum week. Due to this and the increased risk of seizure in patients with uncontrolled hypertension, clinicians should continue monitoring patients frequently during the postpartum period.[1] Clinical features of pulmonary edema should be especially looked for in patients with renal dysfunction due to the increased risk of this complication. Adjust antihypertensive treatment accordingly to prevent further complications.[2][11]

• Transfer and Tertiary Care
  • Transfer to appropriate facilities: Patients with severe eclampsia should be managed in a facility with intensive and neonatal care units, particularly for those remote from term. Blood pressure and seizures should be controlled before transfer.[10]
  • Ambulance Transfer: Transfer should be done with appropriate medical personnel and fetal monitoring to manage any recurrent seizures during transit.[11]

Differential Diagnosis

Differential diagnoses should be considered when evaluating patients who have had a seizure, particularly in those with atypical presentations (eg, normal blood pressure without proteinuria, focal neurological symptoms, onset occurring before 20 weeks of pregnancy or more than 48 hours postpartum, or extended period of unconsciousness).[11] Alternative potential diagnoses should be based on the patient’s history and physical exam findings. Differential diagnoses to consider include:

• Seizure disorders
• Metabolic abnormalities (eg, hypoglycemia and hyponatremia)
• Cerebral venous thrombosis
• Space-occupying brain lesions
• Posterior reversible encephalopathy syndrome
• Infectious meningitis or encephalitis
• Chronic renal or hepatic disease
• Psychogenic nonepileptic seizures
• Antiphospholipid syndrome
• Hemolytic-uremic syndrome
• Amniotic fluid emboli
• Immune thrombocytopenic purpura
• Thrombotic thrombocytopenic purpura
• Toxins
• Ruptured aneurysm
• Intracranial hemorrhage [11]

Prognosis

Patients who have experienced eclampsia are at a higher risk of developing preeclampsia in future pregnancies, with a recurrence rate of approximately 25% for preeclampsia and 2% for eclampsia, especially if eclampsia occurred in the second trimester. Patients with eclampsia are associated with a 12-fold increased risk of cardiovascular complications, including heart attacks, strokes, and heart failure during the same hospitalization.[11]

Patients with preeclampsia have also been found to have an increased risk of several long-term conditions, including metabolic disorders, renal disease, and cardiovascular disease. Furthermore, the increased cardiovascular risk has also been demonstrated in the children of these patients.[10] Additionally, individuals with a history of eclampsia are more likely to develop seizure disorders later in life, though the absolute risk is low. Moreover, patients with eclampsia tend to report more daily cognitive challenges, memory loss, concentration difficulties, anxiety, depression, persistent headaches, vertigo, and visual disturbances compared to patients who had normotensive pregnancies.[11]

Complications

Eclampsia increases the risk of complications, including:

• Placental abruption
• HELLP syndrome
• Disseminated intravascular coagulation 
• Pulmonary edema
• Aspiration pneumonia
• Cardiopulmonary arrest
• Acute renal failure
• Blood transfusion
• Venous thromboembolism [11]