Eclampsia

Quick Reference Card

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Overview

Eclampsia is defined as the new onset of generalized tonic-clonic seizures in a woman with preeclampsia, or the occurrence of seizures in association with signs and symptoms of preeclampsia, that cannot be attributed to any other cause. [1] This definition emphasizes that eclampsia represents a severe manifestation of the preeclampsia-eclampsia spectrum rather than a separate disease entity.

The condition remains a leading cause of maternal mortality worldwide, particularly in low- and middle-income countries where access to antenatal care and emergency obstetric services is limited. [2] Despite advances in diagnosis and management, eclampsia accounts for approximately 50,000 maternal deaths annually, representing 12% of all maternal mortality globally. [3]

The pathogenesis involves complex interactions between abnormal placentation, systemic endothelial dysfunction, and cerebrovascular changes leading to seizure activity. The central role of cerebral vasogenic edema and posterior reversible encephalopathy syndrome (PRES) has been increasingly recognized, providing insight into why magnesium sulfate is superior to conventional anticonvulsants. [4]

Early recognition, prompt treatment with magnesium sulfate, blood pressure control, and timely delivery remain the cornerstones of management. The Magpie Trial definitively established that magnesium sulfate reduces the risk of eclampsia by more than half and reduces maternal mortality. [5]

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Epidemiology

Global Burden

The incidence of eclampsia varies dramatically between developed and developing nations, reflecting differences in antenatal care access and quality. [2,3]

United Kingdom and Developed Countries

In the UK, the incidence is approximately 2.7 per 10,000 maternities based on the UKOSS surveillance data. [6] The maternal case fatality rate has declined to less than 1% with modern management, though significant morbidity persists.

Temporal Patterns

Late postpartum eclampsia (occurring > 48 hours after delivery) accounts for an increasing proportion of cases and poses diagnostic challenges as patients may present to non-obstetric settings. [7]

Risk Factors

Exam Detail: High-Risk Factors (RR > 2)

Moderate-Risk Factors (RR 1.5-2)

Protective Factors

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Pathophysiology

Two-Stage Model of Preeclampsia-Eclampsia

The underlying pathophysiology follows a two-stage disease model established through decades of research. [8,9]

Stage 1: Abnormal Placentation (Weeks 8-18)

Defective trophoblast invasion of the spiral arteries results in:

• Failure of spiral artery remodeling
• Retention of musculoelastic vessel walls
• Reduced uteroplacental blood flow
• Chronic placental hypoxia and oxidative stress

Stage 2: Maternal Systemic Response

The hypoxic placenta releases factors causing systemic endothelial dysfunction:

• Increased soluble fms-like tyrosine kinase-1 (sFlt-1)
• Decreased placental growth factor (PlGF)
• Elevated soluble endoglin
• Systemic inflammation and oxidative stress

Cerebral Pathophysiology in Eclampsia

Exam Detail: The seizures in eclampsia result from complex cerebrovascular changes that differ from other seizure disorders. [4,10]

Mechanism 1: Cerebral Vasogenic Edema (PRES)

Posterior Reversible Encephalopathy Syndrome (PRES) is the predominant mechanism in most eclampsia cases:

MRI Findings in Eclampsia-Related PRES:

• T2/FLAIR hyperintensities in parieto-occipital white matter
• May involve frontal lobes, basal ganglia, brainstem
• Typically bilateral but may be asymmetric
• Usually reversible within 2-4 weeks with appropriate treatment

Mechanism 2: Cerebral Vasospasm

In a subset of patients, vasospasm contributes to cerebral ischemia:

• Segmental arterial narrowing on angiography
• May result in ischemic infarction
• Responds to magnesium sulfate (vasodilatory effect)

Mechanism 3: Cytotoxic Edema and Hemorrhage

Severe or prolonged cases may develop:

• Cytotoxic edema (irreversible neuronal injury)
• Intracerebral hemorrhage (hypertensive)
• Subarachnoid hemorrhage
• Cerebral infarction

Why Magnesium Works

Magnesium sulfate's superiority over conventional anticonvulsants is explained by its multiple mechanisms addressing eclampsia-specific pathophysiology:

Systemic Manifestations

Eclampsia represents the cerebral manifestation of systemic disease affecting multiple organs:

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Clinical Presentation

Prodromal Symptoms

Most women experience warning symptoms before seizures, though 20-38% have no prodrome. [1,11]

Clinical Pearl: Warning Sign Recognition

The classic triad of severe headache, visual disturbances, and hyperreflexia should prompt immediate assessment for impending eclampsia. However, clinicians must remember that:

• 20-38% of eclamptic seizures occur without prodromal symptoms
• 10-15% occur without significant hypertension
• 15-20% occur without proteinuria

The absence of "classic" preeclampsia features does not exclude eclampsia risk.

Seizure Characteristics

Typical Eclamptic Seizure:

Atypical Features Suggesting Alternative Diagnosis:

• Focal seizures
• Prolonged post-ictal period (> 1-2 hours)
• Seizures before 20 weeks gestation (unless molar pregnancy)
• No improvement with magnesium sulfate
• Onset > 4 weeks postpartum

Physical Examination Findings

Vital Signs:

Neurological Examination:

Systemic Examination:

Fetal Assessment

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Red Flags and Emergencies

Life-Threatening Complications

⚠️ Red Flag: | Emergency | Clinical Features | Immediate Action | |-----------|-------------------|------------------| | Status eclamptic | Seizures lasting > 5 min or recurrent without recovery | Repeat Mg 2g bolus, add benzodiazepine, prepare for intubation | | Intracranial hemorrhage | Sudden severe headache, focal signs, progressive coma | Urgent CT head, neurosurgical consultation | | Acute stroke | Sudden focal deficit, unilateral weakness | CT head, consider thrombectomy if ischemic | | Pulmonary edema | Severe dyspnea, hypoxia, bilateral crackles | Oxygen, diuretics, consider CPAP/intubation | | DIC with hemorrhage | Uncontrolled bleeding, oozing from puncture sites | Blood products, correct coagulopathy | | Placental abruption | Abdominal pain, vaginal bleeding, woody uterus | Urgent delivery, prepare for massive transfusion | | Magnesium toxicity | Absent reflexes, RR less than 12, cardiac depression | Stop Mg, calcium gluconate 1g IV | | HELLP with hepatic rupture | Shock, severe RUQ pain, dropping hemoglobin | Massive transfusion, hepatobiliary surgery |

Atypical Presentations Requiring Alternative Diagnosis

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Differential Diagnosis

Causes of Seizures in Pregnancy

Exam Detail: Key Differentiating Points for Exams:

Cerebral Venous Thrombosis vs Eclampsia:

• Both occur in pregnancy/postpartum
• CVT: may have focal signs, papilledema, no proteinuria
• CVT: MR venography shows absent flow in sinuses
• CVT: anticoagulation is treatment

TTP vs HELLP:

• Both have hemolysis and thrombocytopenia
• TTP: fever, more severe thrombocytopenia (less than 20,000), AKI, neurological features
• TTP: ADAMTS13 less than 10% is diagnostic
• HELLP: usually elevated liver enzymes, responds to delivery

Epilepsy vs Eclampsia:

• Prior seizure history in epilepsy
• AED levels may be subtherapeutic in pregnancy
• Eclampsia: usually has hypertension, proteinuria, headache

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Investigations

Immediate Investigations

Secondary Investigations

Neuroimaging

CT Head Indications:

• Atypical features (focal seizures, prolonged altered consciousness)
• Focal neurological deficits
• No improvement with magnesium sulfate
• Consider before lumbar puncture

MRI Brain:

• More sensitive for PRES changes
• Shows T2/FLAIR hyperintensities in parieto-occipital regions
• Can distinguish vasogenic from cytotoxic edema
• Not urgently required for typical presentation

Fetal Monitoring

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Management

Principles of Management

The management of eclampsia follows a structured approach prioritizing maternal stabilization before delivery. [1,5,12]

Core Principles:

1. Airway protection and supportive care during seizure
2. Magnesium sulfate for seizure control and prevention
3. Blood pressure control to prevent cerebrovascular complications
4. Maternal stabilization before delivery
5. Delivery as definitive treatment
6. Continued monitoring and seizure prophylaxis postpartum

Immediate Seizure Management (First 5 Minutes)

During Active Seizure:

Magnesium Sulfate Protocols

Exam Detail: Zuspan Regimen (IV Only) [13]

Preferred in well-resourced settings with IV pump availability.

Pritchard Regimen (IM/IV Combined) [14]

Developed for resource-limited settings where IV pumps unavailable.

Collaborative Eclampsia Trial Regimen [12]

Evidence Comparison:

The Collaborative Eclampsia Trial (1995) compared magnesium sulfate to diazepam and phenytoin in over 1,600 women with eclampsia. [12]

Magnesium sulfate reduced recurrent seizures by 52% compared to diazepam and 67% compared to phenytoin.

Magnesium Sulfate Monitoring

Magnesium Toxicity:

Management of Magnesium Toxicity:

1. Stop magnesium infusion immediately
2. Administer calcium gluconate 1g (10mL of 10%) IV over 3 minutes
3. Support ventilation (bag-mask, intubation if needed)
4. If cardiac arrest: standard ACLS with calcium
5. Consider hemodialysis if severe/renal failure

Management of Recurrent Seizures

Blood Pressure Management

Exam Detail: Target: SBP less than 160 mmHg, DBP less than 110 mmHg [15]

The goal is to prevent hypertensive cerebrovascular complications (hemorrhagic stroke), NOT to normalize blood pressure.

First-Line Agents:

Second-Line Agents:

Contraindicated Agents:

• ACE inhibitors: Teratogenic, fetotoxic
• ARBs: Teratogenic, fetotoxic
• Nitroprusside: Cyanide toxicity risk (use only if refractory)

Blood Pressure Management Algorithm:

BP ≥160/110 confirmed on 2 readings 15 min apart
                    ↓
        Labetalol 20mg IV OR
        Hydralazine 5mg IV OR
        Nifedipine 10mg PO
                    ↓
    Recheck BP every 10-15 minutes
                    ↓
        If still ≥160/110:
                    ↓
        Repeat agent with escalating doses
                    ↓
        If no response after 3 doses:
                    ↓
        Switch agent or add second agent
        Consider nicardipine infusion

Fluid Management

Oliguria Management:

• Oliguria (less than 25 mL/hr) is common in eclampsia
• Do NOT give aggressive fluid boluses (risk of pulmonary edema)
• Reduce magnesium dose if oliguric (accumulation risk)
• Consider furosemide only if fluid overloaded

Delivery: The Definitive Treatment

Exam Detail: Delivery is the only definitive treatment for eclampsia as it removes the source of pathology (the placenta). [1,16]

Timing of Delivery:

Key Principle: Do not delay delivery for fetal lung maturity when maternal condition is unstable.

Mode of Delivery:

Induction of Labor:

• Prostaglandin (dinoprostone or misoprostol) for cervical ripening
• Amniotomy when safe
• Oxytocin augmentation as needed
• Continuous CTG monitoring throughout
• Assisted second stage may be appropriate

Cesarean Section Considerations:

• Eclampsia itself is NOT an absolute indication for cesarean
• Regional anesthesia (spinal/epidural) generally safe if no coagulopathy
• Platelet count > 75,000 generally acceptable for regional
• General anesthesia if urgent, coagulopathy, or airway concerns
• Avoid ergometrine for uterine atony (hypertensive effect)

Corticosteroids for Fetal Lung Maturity:

Only administer if maternal condition allows safe delay of delivery.

Postpartum Management

Immediate Postpartum (First 24-48 hours):

Antihypertensive Choice Postpartum:

Postpartum Eclampsia

Up to 25-34% of eclampsia cases occur postpartum, with late postpartum cases (> 48 hours) representing a diagnostic challenge. [7]

Risk Period:

• Early postpartum: less than 48 hours (most common)
• Late postpartum: 48 hours to 4-6 weeks
• Very late cases reported up to 8 weeks

Management:

• Same as antepartum/intrapartum eclampsia
• Magnesium sulfate is first-line
• Continue for 24-48 hours after last seizure
• Investigate for alternative causes more readily

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Complications

Maternal Complications

Fetal/Neonatal Complications

Long-Term Maternal Outcomes

Exam Detail: Eclampsia and preeclampsia are associated with significantly increased long-term cardiovascular morbidity. [17]

Counseling Points:

• Preeclampsia/eclampsia is a cardiovascular risk factor
• Lifestyle modification (diet, exercise, weight) is important
• Regular blood pressure monitoring recommended
• Annual cardiovascular risk assessment
• May need cardiology/nephrology follow-up

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Prognosis

Maternal Outcomes

Favorable Prognostic Factors:

• Rapid initiation of magnesium sulfate
• Blood pressure control less than 160/110
• Delivery within 24 hours
• Access to ICU/HDU care
• No intracranial hemorrhage

Poor Prognostic Factors:

• Status epilepticus
• Intracranial hemorrhage
• HELLP syndrome with DIC
• Pulmonary edema
• Delay in receiving care
• Multiple organ dysfunction

Recurrence Risk in Future Pregnancies

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Prevention

Primary Prevention (In High-Risk Patients)

Secondary Prevention (In Women with Preeclampsia)

Exam Detail: Magpie Trial Evidence [5]

The Magpie Trial (2002) was a landmark RCT of over 10,000 women with preeclampsia randomized to magnesium sulfate vs placebo.

NNT to prevent one case of eclampsia:

• Severe preeclampsia: NNT = 50
• Moderate preeclampsia: NNT = 100

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Special Populations

HELLP Syndrome Co-existing with Eclampsia

HELLP syndrome occurs in 10-20% of eclampsia cases and significantly increases maternal morbidity and mortality. [18]

Diagnostic Criteria (Tennessee Classification):

Management Considerations:

• Same principles as eclampsia
• Higher risk of DIC, hepatic hemorrhage
• Platelet transfusion if less than 20,000 or less than 50,000 with bleeding/surgery
• Fresh frozen plasma if coagulopathy
• Monitor for hepatic subcapsular hematoma/rupture
• Consider dexamethasone for platelet recovery (controversial)

Antiphospholipid Syndrome

Chronic Hypertension with Superimposed Preeclampsia

Multiple Gestation

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Disposition

Admission Criteria

All eclampsia patients require hospital admission.

ICU Admission Criteria

• Status epilepticus or recurrent seizures despite magnesium
• Respiratory failure requiring intubation
• Hemodynamic instability requiring vasopressors
• Severe HELLP with DIC
• Intracranial hemorrhage
• Multi-organ dysfunction
• Glasgow Coma Scale less than 8

Postpartum Monitoring Duration

Follow-Up

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Exam Focus: Viva Points

Viva Point: ### Opening Statement

"Eclampsia is defined as the new onset of generalized tonic-clonic seizures in a woman with preeclampsia, or signs of preeclampsia, that cannot be attributed to other causes. It is a life-threatening obstetric emergency with maternal mortality of 1-2% in developed countries and up to 15% in resource-limited settings. The definitive treatment is delivery, but maternal stabilization with magnesium sulfate and blood pressure control must occur first."

Key Examiner Questions

Q1: "What is your immediate management of an eclamptic seizure?"

"I would follow a structured approach:

1. Call for help - obstetric emergency team
2. Protect the airway - left lateral position, suction, high-flow oxygen
3. Protect from injury - lower bed, side rails
4. Do not attempt to restrain or insert airway during seizure
5. Once seizure stops, secure IV access
6. Give magnesium sulfate 4g IV over 5-15 minutes
7. Monitor BP and give antihypertensive if ≥160/110
8. Continuous fetal monitoring
9. Plan for delivery after stabilization"

Q2: "Why is magnesium sulfate superior to benzodiazepines and phenytoin?"

"The Collaborative Eclampsia Trial (1995) randomized over 1,600 women with eclampsia and showed magnesium sulfate reduced recurrent seizures by 52% compared to diazepam and 67% compared to phenytoin. This superiority is because eclamptic seizures arise from vasogenic edema and endothelial dysfunction, not epileptiform activity. Magnesium's mechanisms include NMDA receptor antagonism, cerebral vasodilation relieving vasospasm, endothelial protection, and calcium channel blockade."

Q3: "What are the signs of magnesium toxicity and how do you manage it?"

"The first sign is loss of deep tendon reflexes at levels around 7-10 mEq/L. This is followed by respiratory depression at 10-12 mEq/L and cardiac arrest above 12 mEq/L. Management involves:

1. Stop the magnesium infusion
2. Give calcium gluconate 1g (10mL of 10% solution) IV over 3 minutes as the antidote
3. Support ventilation - bag-mask or intubation if needed
4. If cardiac arrest, standard resuscitation with calcium
5. Consider hemodialysis if renal failure or severe toxicity"

Q4: "When can eclampsia occur without hypertension or proteinuria?"

"Atypical presentations occur in 15-20% of cases. Up to 10-15% may have blood pressure below 140/90, and 15-20% may have no significant proteinuria. This is why the diagnosis is clinical - new-onset generalized seizures with features of preeclampsia. We should not withhold treatment awaiting 'classic' features."

Q5: "What is the definitive treatment and how do you decide on mode of delivery?"

"Delivery is the definitive treatment as it removes the placenta, the source of pathology. However, eclampsia itself is NOT an indication for cesarean section. The mode depends on:

• Cervical favorability (vaginal if Bishop ≥6)
• Fetal status (cesarean if non-reassuring and not immediately deliverable)
• Maternal stability
• Gestational age and estimated fetal weight
• Other obstetric factors

If the cervix is favorable, induction with continuous monitoring is appropriate. If unfavorable with urgent maternal/fetal indication, cesarean is indicated."

Common Mistakes That Fail Candidates

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Key Clinical Pearls

Clinical Pearl: ### Diagnostic Pearls

• 20-38% have seizures without prodromal symptoms - do not rely on warning signs
• 10-15% are normotensive at presentation - eclampsia can occur without classic hypertension
• 15-20% have no significant proteinuria - do not wait for dipstick results
• Can occur up to 4-6 weeks postpartum - maintain suspicion in postpartum headache presentations
• Focal seizures, prolonged post-ictal state, or seizures less than 20 weeks suggest alternative diagnosis

Treatment Pearls

• Magnesium sulfate, NOT benzodiazepines, is first-line - this is evidence-based
• Therapeutic magnesium level is 4-7 mEq/L, but clinical monitoring (reflexes, RR) is sufficient in most cases
• Calcium gluconate is the antidote for magnesium toxicity - have it at the bedside
• BP target is less than 160/110, not normalization - overly aggressive control risks placental hypoperfusion
• Deliver after maternal stabilization, not emergently during seizure
• Continue magnesium 24-48 hours after last seizure or delivery (whichever is later)
• Avoid ergometrine for postpartum hemorrhage - use oxytocin, carboprost, or misoprostol

Disposition Pearls

• All eclampsia patients require admission - no outpatient management
• ICU for status epilepticus, respiratory failure, HELLP with DIC, or neurological concerns
• Postpartum monitoring is essential - late postpartum seizures can occur
• Long-term cardiovascular counseling is mandatory - increased lifetime CV risk
• Plan for future pregnancies includes low-dose aspirin prophylaxis from 12 weeks

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Quality Metrics

Performance Indicators

Documentation Requirements

• Seizure description (timing, duration, witnesses)
• Gestational age and fetal status
• Vital signs trend pre- and post-seizure
• Laboratory results (FBC, LFTs, coagulation, Mg level)
• Magnesium dosing, timing, and route
• Blood pressure management and agents used
• Fetal heart rate monitoring interpretation
• Mode, timing, and indication for delivery
• Postpartum care plan and Mg continuation
• Consultation notes (MFM, ICU, neurology if applicable)
• Counseling regarding future pregnancy and CV risk

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Zuspan regimen? A: 4g IV over 15-20 minutes, followed by 1g/hr maintenance.

4. Q: What is the antidote for magnesium toxicity? A: Calcium gluconate 1g (10mL of 10%) IV over 3 minutes.

5. Q: What proportion of eclampsia occurs postpartum? A: 25-34%, with some occurring up to 4-6 weeks after delivery.

Cloze Cards

1. Magnesium sulfate reduced recurrent seizures by 52% compared to diazepam in the Collaborative Eclampsia Trial.

2. The target blood pressure in eclampsia is SBP less than 160 mmHg and DBP less than 110 mmHg.

3. The therapeutic serum magnesium level is 4-7 mEq/L (2-3.5 mmol/L).

4. Loss of deep tendon reflexes is the first sign of magnesium toxicity.

5. The Magpie Trial showed magnesium sulfate reduced eclampsia by 58% (NNT 50-100) in women with preeclampsia.

Scenario Cards

1. Scenario: A 28-year-old primigravida at 36 weeks has a witnessed generalized tonic-clonic seizure. BP is 172/114 mmHg. What is your immediate management? Answer: Call for help, left lateral position, protect airway with oxygen and suction, give magnesium sulfate 4g IV over 5-15 minutes, then 1g/hr maintenance. Give labetalol 20mg IV for BP control. Continuous CTG. Plan delivery after stabilization.

2. Scenario: During magnesium infusion, the patient's reflexes are absent and RR is 10/min. What do you do? Answer: Stop magnesium infusion immediately. Give calcium gluconate 1g IV over 3 minutes. Support ventilation. Check magnesium level. Resume at lower rate once reflexes return and RR normalizes.

3. Scenario: A woman presents 10 days postpartum with severe headache and a generalized seizure. BP is 168/108, proteinuria 3+. Diagnosis and management? Answer: Late postpartum eclampsia. Manage as eclampsia: magnesium sulfate 4g IV loading, 1g/hr maintenance. Labetalol for BP control. Continue magnesium for 24-48 hours. Investigate for alternative causes if atypical features.

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References

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2. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130-137. doi:10.1053/j.semperi.2009.02.010

3. Say L, Chou D, Gemmill A, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2(6):e323-e333. doi:10.1016/S2214-109X(14)70227-X

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6. Knight M, Nair M, Tuffnell D, et al. Saving Lives, Improving Mothers' Care - Surveillance of maternal deaths in the UK 2012-14. MBRRACE-UK. 2016. Available at: https://www.npeu.ox.ac.uk/mbrrace-uk

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8. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005;308(5728):1592-1594. doi:10.1126/science.1111726

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12. The Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet. 1995;345(8963):1455-1463. doi:10.1016/S0140-6736(95)91034-4

13. Zuspan FP. Treatment of severe preeclampsia and eclampsia. Clin Obstet Gynecol. 1966;9(4):954-972. doi:10.1097/00003081-196612000-00012

14. Pritchard JA, Cunningham FG, Pritchard SA. The Parkland Memorial Hospital protocol for treatment of eclampsia: evaluation of 245 cases. Am J Obstet Gynecol. 1984;148(7):951-963. doi:10.1016/0002-9378(84)90538-6

15. ACOG Committee Opinion No. 767. Emergent therapy for acute-onset, severe hypertension during pregnancy and the postpartum period. Obstet Gynecol. 2019;133(2):e174-e180. doi:10.1097/AOG.0000000000003075

16. Brown MA, Magee LA, Kenny LC, et al. Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice. Hypertension. 2018;72(1):24-43. doi:10.1161/HYPERTENSIONAHA.117.10803

17. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007;335(7627):974. doi:10.1136/bmj.39335.385301.BE

18. Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): much ado about nothing? Am J Obstet Gynecol. 1990;162(2):311-316. doi:10.1016/0002-9378(90)90376-I

19. Rolnik DL, Wright D, Poon LC, et al. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017;377(7):613-622. doi:10.1056/NEJMoa1704559

20. National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. NICE guideline [NG133]. 2019. Available at: https://www.nice.org.uk/guidance/ng133