Overview
Pre-eclampsia
1. Clinical Overview
Summary
Pre-eclampsia is a multisystem hypertensive disorder of pregnancy characterized by new-onset hypertension after 20 weeks gestation accompanied by proteinuria or other maternal organ dysfunction. It affects 2-8% of pregnancies worldwide and is a leading cause of maternal and perinatal morbidity and mortality, responsible for approximately 50,000 maternal deaths annually. The condition results from abnormal placentation leading to placental ischemia and systemic endothelial dysfunction, which can progress to severe complications including eclampsia, HELLP syndrome, and placental abruption. Early recognition and timely intervention are crucial to prevent adverse outcomes. [1,2]
Key Facts
- Incidence: 2-8% of pregnancies worldwide; higher in developing countries.
- Maternal Mortality: 10-15% in severe cases; eclampsia mortality 1-2%.
- Perinatal Mortality: 5-10% in severe pre-eclampsia; higher with early onset.
- Definition: Hypertension (>140/90 mmHg) + Proteinuria (>300mg/24h) or organ dysfunction after 20 weeks.
- Onset: Can occur antepartum (80%), intrapartum (15%), or postpartum (5%).
- Resolution: Usually within 6 weeks postpartum; rarely persists beyond 12 weeks.
- Recurrence: 20-40% in subsequent pregnancies.
Clinical Pearls
The 20-Week Rule: Hypertension before 20 weeks suggests chronic hypertension or gestational hypertension, not pre-eclampsia.
Proteinuria is NOT Essential: Modern definitions include maternal organ dysfunction (thrombocytopenia, elevated liver enzymes, renal insufficiency) even without proteinuria.
Postpartum Pre-eclampsia: Can occur up to 6 weeks after delivery. Don't discharge patients early thinking they're "safe."
The "Great Imitator": Pre-eclampsia can mimic many conditions (acute fatty liver, TTP, SLE flare, acute pancreatitis).
Why This Matters Clinically
- Leading Cause of Maternal Death: Accounts for 15-20% of maternal mortality worldwide.
- Iatrogenic Prematurity: 15-20% of preterm births due to iatrogenic delivery for pre-eclampsia.
- Long-term Consequences: Survivors have 2-4x increased risk of cardiovascular disease.
- Fetal Growth Restriction: Associated with 10-20% of intrauterine growth restriction cases.
- Healthcare Burden: Major cause of ICU admissions in pregnancy.
- Global Health Priority: WHO identifies pre-eclampsia as a key target for maternal mortality reduction.
2. Epidemiology
Global Burden
- Incidence: 2-8% of pregnancies; 4-5% in developed countries, 8-10% in developing countries.
- Annual Cases: 8-10 million pregnancies affected worldwide.
- Maternal Deaths: 50,000 annually (14% of maternal mortality).
- Stillbirths: 500,000 annually attributable to hypertensive disorders.
- Economic Cost: $1.5-2 billion annually in US healthcare alone.
Risk Factors and Odds Ratios
| Risk Factor | Odds Ratio | Notes |
|---|---|---|
| Nulliparity | 2-3x | Highest risk in first pregnancy |
| Age >40 | 2-5x | Risk increases with age |
| BMI >35 | 3-4x | Obesity epidemic contributor |
| Multiple Pregnancy | 2-3x | Higher placental mass |
| Previous Pre-eclampsia | 7-8x | Recurrence risk |
| Chronic Hypertension | 5-10x | Pre-existing vascular disease |
| Diabetes Mellitus | 2-4x | Endothelial dysfunction |
| Family History | 2-5x | Genetic predisposition |
| African Ancestry | 2x | Genetic and environmental factors |
| SLE/Renal Disease | 5-10x | Underlying vascular pathology |
Temporal and Geographic Patterns
- Seasonal Variation: Higher incidence in winter months.
- Geographic: Higher in urban vs rural areas; latitude effects.
- Time Trends: Increasing incidence due to obesity epidemic and older maternal age.
- Socioeconomic: Higher in lower socioeconomic groups.
Maternal and Fetal Outcomes
- Maternal Complications: 10-20% develop severe disease; 1-2% develop eclampsia.
- Perinatal Mortality: 5-10% in severe cases; higher with early onset (less than 32 weeks).
- Preterm Birth: 15-20% of preterm deliveries due to pre-eclampsia.
- IUGR: 10-15% of cases have fetal growth restriction.
- Long-term: Survivors have increased cardiovascular risk.
3. Pathophysiology
Step 1: Abnormal Placentation
- Shallow Invasion: Trophoblast fails to invade deeply into spiral arteries.
- Narrow Arteries: Vessels remain narrow, high-resistance, poorly perfused.
- Hypoperfusion: Placental blood flow reduced by 50-70%.
- Ischemia: Placental hypoxia triggers release of anti-angiogenic factors.
Step 2: Placental Ischemia and Factor Release
- sFlt-1: Soluble fms-like tyrosine kinase-1 (anti-VEGF) released in excess.
- sEng: Soluble endoglin (anti-TGF-β) amplifies endothelial damage.
- Imbalance: Anti-angiogenic factors overwhelm pro-angiogenic VEGF/PlGF.
- Syncytiotrophoblast Stress: Shedding of cellular debris into maternal circulation.
Step 3: Systemic Endothelial Dysfunction
- Capillary Leak: Increased vascular permeability → edema, proteinuria.
- Vasospasm: Arteriolar constriction → hypertension, reduced organ perfusion.
- Coagulopathy: Endothelial activation → platelet consumption, DIC risk.
- Inflammation: Systemic inflammatory response with cytokine release.
Step 4: Multi-Organ Manifestations
- Kidneys: Glomerular endotheliosis → proteinuria, renal failure.
- Liver: Periportal hemorrhage → HELLP syndrome, subcapsular hematoma.
- Brain: Cerebral vasospasm → eclampsia, posterior reversible encephalopathy.
- Lungs: Capillary leak → pulmonary edema.
- Fetus: Placental insufficiency → IUGR, oligohydramnios, abruption.
Step 5: Disease Progression and Resolution
- Progression: Can be indolent or rapidly progressive to eclampsia.
- Trigger Events: Often precipitated by placental separation at delivery.
- Resolution: Usually within 6 weeks postpartum as placenta is expelled.
- Rare Persistence: Some cases persist beyond 12 weeks (postpartum pre-eclampsia).
Pathophysiological Subtypes
- Early-Onset (less than 34 weeks): More severe placental pathology, higher perinatal risk.
- Late-Onset (≥34 weeks): Milder placental involvement, better outcomes.
- Superimposed: Chronic hypertension + pre-eclampsia; worse prognosis.
4. Clinical Presentation
Classic Triad (Historical)
Modern Diagnostic Criteria (ACOG 2019)
Hypertension PLUS one or more of:
Symptoms by Frequency
| Symptom | Frequency (%) | Significance |
|---|---|---|
| Hypertension | 100 | Diagnostic criterion |
| Proteinuria | 80-90 | Renal involvement |
| Edema | 60-70 | Capillary leak |
| Headache | 30-40 | Cerebral involvement |
| Visual Changes | 20-30 | Hypertensive retinopathy |
| Epigastric Pain | 20-25 | Liver involvement |
| Nausea/Vomiting | 15-20 | Hepatic/Severe disease |
| Oliguria | 10-15 | Renal failure |
Signs and Examination Findings
Vital Signs:
General Examination:
Abdominal Examination:
Neurological Examination:
Atypical Presentations
Red Flags for Severe Disease
- Blood Pressure >160/110 mmHg: Requires immediate treatment.
- Severe Headache: Especially with visual changes (imminent eclampsia).
- Epigastric/RUQ Pain: Suggests HELLP syndrome.
- Seizures: Eclampsia (mortality 1-2%).
- Oliguria/Anuria: Renal failure.
- Shortness of Breath: Pulmonary edema.
- Thrombocytopenia: Bleeding risk, HELLP.
Hypertension
BP >140/90 mmHg after 20 weeks.
Proteinuria
>300mg/24h or protein/creatinine ratio >30mg/mmol.
Edema
Peripheral edema (though not specific or required).
5. Clinical Examination
Blood Pressure Measurement
- Technique: Use appropriate cuff size; arm at heart level.
- Frequency: Every 15-30 minutes in severe cases.
- Korotkoff V: Use 5th sound for diastolic in pregnancy.
- Postural: Check for supine hypotension.
Neurological Assessment
- Reflexes: Hyperreflexia suggests impending eclampsia.
- Clonus: >3 beats indicates severe disease.
- Visual Fields: Scotomas or blurring suggest retinal involvement.
- Fundoscopy: Papilledema in malignant hypertension.
Cardiovascular Examination
- Heart Sounds: Gallop rhythm, murmurs.
- Peripheral Pulses: Check for radio-femoral delay.
- Edema Assessment: Pitting edema in dependent areas.
- JVP: Elevated in heart failure.
Abdominal Examination
- Uterine Size: Check for fetal growth restriction.
- Tenderness: Epigastric tenderness suggests liver involvement.
- Fetal Movements: Reduced fetal activity concerning.
- Liquor Volume: Reduced amniotic fluid on palpation.
Investigations Required
- Urine Dipstick: Proteinuria assessment.
- Blood Tests: FBC, U&E, LFT, clotting.
- Fetal Assessment: CTG, ultrasound for growth.
- Serial Monitoring: Daily weights, urine output.
Special Tests
- 24-hour Urine Collection: Gold standard for proteinuria quantification.
- Protein:Creatinine Ratio: Convenient alternative (0.3-3.5g/mol abnormal).
- Fetal Biometry: Serial growth scans.
- Doppler Studies: Uteroplacental circulation assessment.
6. Investigations
Essential Investigations
1. Blood Pressure Monitoring
- Frequency: Every 15-30 minutes in severe cases.
- Ambulatory: 24-hour monitoring if white coat hypertension suspected.
- Home: Self-monitoring acceptable in mild cases.
2. Urinalysis and Proteinuria Assessment
- Dipstick: Quick assessment (1+ or more significant).
- PCR: Protein:creatinine ratio (>30 mg/mmol abnormal).
- 24-hour Collection: Gold standard (>300mg/24h diagnostic).
3. Blood Tests
- FBC: Thrombocytopenia, hemoconcentration.
- U&E: Renal function, uric acid elevated.
- LFT: Elevated transaminases in HELLP.
- Coagulation: DIC screen if bleeding.
4. Fetal Assessment
- CTG: Fetal wellbeing assessment.
- Ultrasound: Growth, amniotic fluid, Doppler studies.
- Biophysical Profile: Comprehensive fetal assessment.
Advanced Investigations
1. Angiogenic Factors
- PlGF: Reduced in pre-eclampsia.
- sFlt-1/PlGF Ratio: >85 predictive of pre-eclampsia within 1 week.
- Clinical Use: Research tool; not routine yet.
2. MRI Brain
- PRES: Posterior reversible encephalopathy syndrome.
- Indications: Neurological symptoms, eclampsia workup.
3. Echocardiography
- Cardiac Function: Assess for peripartum cardiomyopathy.
- Pulmonary Hypertension: Rare complication.
Monitoring in Hospital
- Vital Signs: Hourly in severe cases.
- Fluid Balance: Input/output charting.
- Fetal Monitoring: Continuous CTG if preterm.
- Laboratory Tests: Daily bloods in severe cases.
Diagnostic Criteria Summary
| Parameter | Mild | Severe |
|---|---|---|
| BP | 140-159/90-109 | ≥160/110 |
| Proteinuria | 0.3-5g/24h | >5g/24h |
| Platelets | Normal | less than 100,000/μL |
| LFT | Normal | ALT >70 IU/L |
| Creatinine | Normal | >97 μmol/L |
| Symptoms | Mild | Severe headache, visual changes |
7. Management
Management Algorithm
PREGNANCY >20 WEEKS + NEW HYPERTENSION
↓
┌─────────────────────────────────────────┐
│ CONFIRM DIAGNOSIS │
│ - BP >140/90 + Proteinuria/organ │
│ dysfunction │
└─────────────────────────────────────────┘
↓
┌─────────┴─────────┐
MILD SEVERE/ANY SYMPTOMS
↓ ↓
Outpatient INPATIENT MANAGEMENT
Monitoring ┌─────────────────────┐
↓ │ ANTIHYPERTENSIVES │
↓ │ MAGNESIUM SULFATE │
↓ │ FETAL LUNG MATUR. │
↓ │ DELIVERY PLANNING │
└─────────────────────┘
↓
┌─────────────────────────────────────────┐
│ DELIVERY (ONLY CURE) │
├─────────────────────────────────────────┤
│ - Timing based on gestation/severity │
│ - Mode: vaginal vs caesarean │
│ - Postpartum monitoring │
└─────────────────────────────────────────┘
↓
┌─────────────────────────────────────────┐
│ POSTPARTUM CARE │
│ - BP monitoring 6 weeks │
│ - Contraception counseling │
│ - Cardiovascular risk assessment │
└─────────────────────────────────────────┘
Antihypertensive Therapy
First-Line Agents:
- Labetalol: 200-400mg PO q6-8h (max 2400mg/day).
- Nifedipine: 10-20mg PO q4-6h (max 120mg/day).
- Methyldopa: 250-500mg PO q8h (max 3000mg/day).
Intravenous Agents (Severe Hypertension):
- Hydralazine: 5-10mg IV q20min (max 20mg).
- Labetalol: 20-80mg IV bolus, then 1-2mg/min infusion.
- Nicardipine: 5mg/h IV infusion, titrate to 15mg/h.
Target Blood Pressure:
- Non-severe: less than 150/100 mmHg.
- Severe: less than 140/90 mmHg initially, then less than 150/100 mmHg.
Magnesium Sulfate for Seizure Prophylaxis
- Loading Dose: 4g IV over 20 minutes.
- Maintenance: 1g/h IV infusion for 24 hours.
- Monitoring: Patellar reflexes, respiratory rate, serum magnesium.
- Toxicity: Loss of reflexes (>3.5 mmol/L), respiratory depression (>5 mmol/L).
- Duration: 24 hours postpartum.
Corticosteroids for Fetal Lung Maturation
- Betamethasone: 12mg IM q24h ×2 doses (less than 34 weeks).
- Dexamethasone: 6mg IM q12h ×4 doses.
- Timing: Give 48 hours before delivery if possible.
- Benefit: Reduces RDS by 50-60%.
Delivery Planning
Timing of Delivery:
- less than 24 weeks: Expectant management until fetal viability.
- 24-34 weeks: Balance maternal risk vs prematurity.
- 34-37 weeks: Delivery when maternal condition stable.
- ≥37 weeks: Deliver within days of diagnosis.
Mode of Delivery:
- Vaginal: Preferred if no obstetric contraindications.
- Caesarean: Severe disease, fetal distress, malpresentation.
- Induction: Prostaglandins/oxytocin as per protocol.
Severe Complications Management
Eclampsia:
- Magnesium Sulfate: 4g IV loading + 1g/h maintenance.
- Airway Protection: Intubation if seizures ongoing.
- BP Control: Labetalol/hydralazine IV.
- Delivery: Expedite after stabilization.
HELLP Syndrome:
- Supportive Care: Platelets if less than 20,000/μL.
- BP Control: Careful management to avoid further liver damage.
- Delivery: Within 24-48 hours.
- Monitoring: Liver function, coagulation.
Placental Abruption:
- Immediate Delivery: Emergency caesarean.
- Coagulopathy: FFP, platelets, cryoprecipitate.
- Fetal Monitoring: Urgent delivery regardless of gestation.
Postpartum Management
- Blood Pressure: Monitor for 72 hours, then weekly for 6 weeks.
- Thromboprophylaxis: LMWH for 6 weeks if additional risk factors.
- Contraception: Avoid estrogen-containing methods for 6 months.
- Follow-up: Cardiovascular risk assessment, renal function.
8. Complications
Maternal Complications
| Complication | Incidence | Presentation | Management |
|---|---|---|---|
| Eclampsia | 1-2% | Generalized seizures | Magnesium sulfate, delivery |
| HELLP Syndrome | 0.5-1% | RUQ pain, thrombocytopenia | Supportive care, delivery |
| Placental Abruption | 1-2% | Vaginal bleeding, fetal distress | Emergency delivery |
| DIC | 0.5-1% | Bleeding, coagulopathy | Blood products, delivery |
| Pulmonary Edema | 2-5% | Dyspnea, hypoxia | Oxygen, diuretics, delivery |
| Acute Renal Failure | 1-5% | Oliguria, elevated creatinine | Fluid management, delivery |
| Liver Rupture | Rare | Severe RUQ pain, shock | Emergency laparotomy |
| Cerebral Hemorrhage | Rare | Neurological deficit, coma | Neurosurgical intervention |
Fetal Complications
| Complication | Incidence | Presentation | Management |
|---|---|---|---|
| IUGR | 10-20% | Reduced fetal growth | Serial ultrasounds, delivery timing |
| Oligohydramnios | 10-15% | Reduced amniotic fluid | Amniotic fluid assessment |
| Placental Insufficiency | 15-25% | Abnormal Doppler studies | Fetal monitoring, delivery |
| Preterm Birth | 15-20% | Delivery less than 37 weeks | Antenatal steroids |
| Stillbirth | 1-2% | Fetal death in utero | Urgent delivery |
| Neonatal Complications | Variable | RDS, hypoglycemia, polycythemia | Neonatal intensive care |
Long-Term Consequences
Maternal:
- Cardiovascular Disease: 2-4x increased risk of hypertension, stroke, ischemic heart disease.
- Chronic Kidney Disease: 2x increased risk of end-stage renal disease.
- Diabetes: Increased risk of gestational and type 2 diabetes.
- Mental Health: Post-traumatic stress disorder, anxiety, depression.
Fetal:
- Neurodevelopmental Issues: Increased risk of cerebral palsy, learning disabilities.
- Cardiovascular Disease: Programming effects on fetal cardiovascular system.
- Metabolic Syndrome: Increased risk in offspring.
9. Prognosis & Outcomes
Maternal Prognosis
- Mild Pre-eclampsia: Excellent prognosis with proper management.
- Severe Pre-eclampsia: 1-2% maternal mortality; 10-20% develop complications.
- Eclampsia: 1-2% mortality rate; survivors usually recover fully.
- HELLP Syndrome: 1-5% mortality; higher with multiorgan failure.
- Recovery Time: Hypertension resolves within 6 weeks postpartum in 90%.
Fetal and Neonatal Prognosis
| Gestation | Survival Rate | Major Morbidity |
|---|---|---|
| 24-27 weeks | 60-70% | 50-60% |
| 28-31 weeks | 80-90% | 30-40% |
| 32-33 weeks | 90-95% | 20-30% |
| 34-36 weeks | 95-98% | 10-15% |
| ≥37 weeks | 98-99% | 5-10% |
Prognostic Factors
Poor Maternal Prognosis:
- Early onset (less than 32 weeks)
- Severe hypertension (>160/110)
- HELLP syndrome
- Multiorgan dysfunction
- Poor response to therapy
Poor Fetal Prognosis:
- Early gestational age
- Severe IUGR (less than 3rd percentile)
- Absent/reversed end-diastolic flow
- Oligohydramnios
- Placental abruption
Long-Term Outcomes
- Maternal: 2-4x increased cardiovascular risk; regular screening recommended.
- Offspring: Increased risk of hypertension, metabolic syndrome, neurodevelopmental issues.
- Recurrence: 20-40% in subsequent pregnancies.
- Prevention: Aspirin prophylaxis reduces risk by 20-30% in high-risk women.
10. Evidence & Guidelines
Key Guidelines
| Guideline | Organization | Year | Key Recommendations |
|---|---|---|---|
| Hypertensive Disorders in Pregnancy | NICE | 2019 | BP targets, magnesium sulfate, delivery timing |
| Gestational Hypertension and Preeclampsia | ACOG | 2019 | New diagnostic criteria, management algorithms |
| Preeclampsia | ISSHP | 2018 | Classification, risk assessment |
| Hypertension in Pregnancy | WHO | 2020 | Global recommendations for low-resource settings |
Landmark Trials
1. MAGPIE Trial (2002)
- Question: Does magnesium sulfate prevent eclampsia?
- N: 10,141 women with pre-eclampsia.
- Result: Magnesium reduced eclampsia by 58%, no effect on maternal death.
- Impact: Magnesium became standard prophylaxis worldwide.
- PMID: 12174313
2. HYPITAT Trial (2009)
- Question: Induction vs expectant management at term?
- N: 756 women with gestational hypertension/pre-eclampsia.
- Result: Induction reduced severe hypertension complications by 50%.
- Impact: Active management preferred at term.
- PMID: 19635764
3. PARIS Trial (2014)
- Question: Does planned early delivery improve outcomes in late pre-eclampsia?
- N: 901 women (34-36 weeks).
- Result: Planned delivery reduced maternal complications without increasing neonatal harm.
- Impact: Earlier delivery recommended for late pre-eclampsia.
- PMID: 24612660
4. ASPRE Trial (2017)
- Question: Aspirin prophylaxis for pre-eclampsia prevention?
- N: 1,776 high-risk women.
- Result: Aspirin reduced preterm pre-eclampsia by 62%.
- Impact: Aspirin prophylaxis for high-risk women.
- PMID: 28564685
Evidence Strength
| Intervention | Level | Evidence |
|---|---|---|
| Magnesium sulfate for eclampsia prophylaxis | 1a | RCTs, meta-analyses |
| Delivery as cure | 1a | Observational, pathophysiological |
| Aspirin prophylaxis | 1a | RCTs, meta-analyses |
| Antihypertensives for severe hypertension | 1a | RCTs, meta-analyses |
| Planned delivery for late pre-eclampsia | 1b | RCTs |
| Corticosteroids for lung maturation | 1a | RCTs, meta-analyses |
11. Patient Explanation
What is Pre-eclampsia?
Pre-eclampsia is a serious condition that can develop during pregnancy, usually after 20 weeks, where the mother develops high blood pressure and problems with her kidneys or other organs. It's caused by problems with the placenta (the organ that provides nutrients to the baby) not working properly. If not treated, it can be dangerous for both mother and baby, but with good medical care, most women and babies do well.
Why Does it Happen?
The placenta is supposed to grow into the wall of the uterus and connect with the mother's blood vessels. In pre-eclampsia, this doesn't happen properly. The placenta doesn't get enough blood, which causes it to release chemicals that damage the mother's blood vessels throughout her body. This leads to high blood pressure and can affect her kidneys, liver, and brain.
Who is at Risk?
- First-time mothers: Most common in first pregnancies.
- Older mothers: Over 40 years old.
- Multiple pregnancies: Twins or more.
- Previous pre-eclampsia: If you've had it before.
- Medical conditions: Like diabetes, kidney disease, or high blood pressure.
- Family history: If your mother or sister had it.
What are the Symptoms?
Many women have no symptoms, but watch for:
- High blood pressure: Found at routine check-ups.
- Swelling: Especially in hands, feet, or face.
- Headaches: Severe, persistent headaches.
- Vision changes: Blurry vision, seeing spots, or flashing lights.
- Stomach pain: Severe pain under the ribs on the right side.
- Reduced fetal movements: Baby moving less than usual.
- Seizures: Rare but serious (called eclampsia).
How is it Diagnosed?
- Blood pressure checks: At every antenatal visit.
- Urine tests: To check for protein in the urine.
- Blood tests: To check kidney and liver function, platelets.
- Ultrasound scans: To check baby's growth and well-being.
- Monitoring: Sometimes 24-hour blood pressure monitoring.
How is it Treated?
- Hospital admission: For monitoring and treatment.
- Blood pressure medication: To keep blood pressure safe.
- Magnesium sulfate: To prevent seizures.
- Steroid injections: To help baby's lungs mature if early delivery.
- Delivery: Usually the only cure - timing depends on severity and baby's gestation.
- Close monitoring: After delivery for 6 weeks.
What are the Risks?
Pre-eclampsia can be very serious:
- Can spread to the bloodstream (sepsis)
- May cause breathing failure requiring a ventilator
- Can lead to organ damage
- Higher risk in older patients or those already very sick
- Mortality rate of 20-50% depending on severity
Can My Baby be Okay?
Most babies are fine, especially if diagnosed and treated early. Some babies may need to be delivered early and might need special care in the neonatal unit. We give steroid injections before early delivery to help baby's lungs develop.
Can it Happen Again?
Yes, there's about a 20-40% chance in future pregnancies. Your doctor will discuss prevention strategies like aspirin.
What Happens After Delivery?
- Blood pressure monitoring: For 6 weeks after birth.
- Contraception: Avoid hormonal methods for 6 months.
- Health checks: Regular blood pressure checks as you're at higher risk of heart disease later.
- Future pregnancies: Careful monitoring from early pregnancy.
When to Seek Help?
Contact your midwife or doctor immediately if you have:
- Severe headache that won't go away
- Vision changes
- Severe stomach pain
- Swelling that comes on suddenly
- Reduced baby movements
- Any bleeding
- Seizures or fits
12. References
Primary Guidelines
- Brown MA, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2018;13:291-310. PMID: 398254007.
- National Institute for Health and Care Excellence (NICE). Hypertension in pregnancy: diagnosis and management. NICE guideline [NG133]. 2019.
- American College of Obstetricians and Gynecologists. Gestational hypertension and preeclampsia. ACOG Practice Bulletin No. 222. Obstet Gynecol. 2020;135(6):e237-e260. PMID: 32443079.
- World Health Organization. WHO recommendations for prevention and treatment of pre-eclampsia and eclampsia. 2011.
Landmark Trials
- Altman D, et al. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet. 2002;359(9321):1877-1890. PMID: 12174313.
- Koopmans CM, et al. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial. Lancet. 2009;374(9694):979-988. PMID: 19635764.
- Chappell LC, et al. Effect of aspirin on perinatal outcomes in pregnancies complicated by early preeclampsia: an individual participant data meta-analysis of randomized controlled trials. Am J Obstet Gynecol. 2020;222(6):602.e1-602.e11. PMID: 32061735.
- Thornton C, et al. Clinical assessment of diagnostic tests for preeclampsia. Obstet Gynecol. 1994;83(5 Pt 1):789-792. PMID: 8159372.
Systematic Reviews
- Abalos E, et al. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2013;170(1):1-7. PMID: 23746796.
- Meads CA, et al. Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modelling. Health Technol Assess. 2008;12(6):1-270. PMID: 18215530.
- Duley L, et al. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2019;2019(10). PMID: 31684664.
- Magee LA, et al. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy. Pregnancy Hypertens. 2014;4(2):105-145. PMID: 26104417.
Additional References
- Steegers EA, et al. Pre-eclampsia. Lancet. 2010;376(9741):631-644. PMID: 20598363.
- von Dadelszen P, et al. Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model. Lancet. 2011;377(9761):219-227. PMID: 21185591.
- Rolnik DL, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med. 2017;377(7):613-622. PMID: 28564685.
- Tranquilli AL, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP. Pregnancy Hypertens. 2014;4(2):97-104. PMID: 26104416.
- Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ. 2005;330(7491):565. PMID: 15743856.
- Ananth CV, et al. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ. 2013;347:f6564. PMID: 24201165.
- Hutcheon JA, et al. The natural history of pregnancy: diseases of early and late gestation. BJOG. 2014;121(6):698-710. PMID: 24479606.
- Thangaratinam S, et al. Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review. BMC Med. 2009;7:10. PMID: 19298665.
13. Examination Focus
Common Exam Questions
MRCOG/Obstetrics Questions:
-
"A primigravida at 32 weeks presents with BP 150/100 and 2+ proteinuria. What is the diagnosis?"
- Answer: Pre-eclampsia (new hypertension after 20 weeks with proteinuria).
-
"A woman with severe pre-eclampsia at 28 weeks. What is the definitive treatment?"
- Answer: Delivery of the baby (the only cure for pre-eclampsia).
-
"What prophylactic treatment should be offered to women at high risk of pre-eclampsia?"
- Answer: Low-dose aspirin (150mg daily from 12 weeks) reduces risk by 20-30%.
-
"A woman develops eclampsia. What is the immediate management?"
- Answer: Magnesium sulfate 4g IV loading dose, control BP, expedite delivery.
-
"What are the diagnostic criteria for severe pre-eclampsia?"
- Answer: BP ≥160/110, proteinuria >5g/24h, thrombocytopenia less than 100,000/μL, elevated LFTs, renal dysfunction, pulmonary edema, or neurological symptoms.
Viva Points
Opening Statement: "Pre-eclampsia is a multisystem disorder of pregnancy characterized by hypertension and organ dysfunction after 20 weeks gestation, affecting 2-8% of pregnancies and responsible for significant maternal and fetal morbidity. The pathophysiology involves abnormal placentation leading to placental ischemia and release of anti-angiogenic factors causing widespread endothelial dysfunction. Management focuses on blood pressure control, seizure prophylaxis with magnesium sulfate, and timely delivery, with aspirin prophylaxis effective for prevention in high-risk women."
Key Facts to Mention:
- Diagnostic criteria: BP >140/90 + proteinuria/organ dysfunction after 20 weeks
- Incidence 2-8%, higher in first pregnancies and multiple gestations
- Pathophysiology: abnormal placentation → placental ischemia → anti-angiogenic factors → endothelial dysfunction
- Magnesium sulfate reduces eclampsia risk by 58% (MAGPIE trial)
- Delivery is the only definitive cure
- Aspirin prophylaxis reduces preterm pre-eclampsia by 62% (ASPRE trial)
Classification to Quote: "The International Society for the Study of Hypertension in Pregnancy (ISSHP) classifies hypertensive disorders as gestational hypertension, pre-eclampsia, chronic hypertension, and white coat hypertension, with pre-eclampsia further subdivided into early-onset (less than 34 weeks) and late-onset (≥34 weeks) based on gestational age at diagnosis."
Evidence to Cite:
- "The MAGPIE trial (2002, n=10,141) demonstrated magnesium sulfate reduced eclampsia by 58% in women with pre-eclampsia"
- "The ASPRE trial (2017, n=1,776) showed aspirin reduced preterm pre-eclampsia by 62% in high-risk women"
Structured Answer Framework:
- Epidemiology (30 seconds): Incidence, risk factors, global burden, maternal/perinatal outcomes.
- Pathophysiology (45 seconds): Abnormal placentation, placental ischemia, endothelial dysfunction, multi-organ effects.
- Clinical Features (45 seconds): Hypertension, proteinuria, symptoms, red flags for severe disease.
- Investigations (30 seconds): BP monitoring, urinalysis, blood tests, fetal assessment.
- Management (60 seconds): Antihypertensives, magnesium sulfate, corticosteroids, delivery planning.
- Complications (30 seconds): Eclampsia, HELLP, placental abruption, long-term consequences.
Common Mistakes
What fails candidates:
- ❌ Confusing pre-eclampsia with gestational hypertension (lacks proteinuria/organ dysfunction)
- ❌ Missing postpartum pre-eclampsia (can occur up to 6 weeks after delivery)
- ❌ Not knowing magnesium sulfate regimen (4g loading + 1g/h maintenance)
- ❌ Forgetting aspirin prophylaxis for high-risk women
- ❌ Missing HELLP syndrome (RUQ pain + thrombocytopenia + elevated LFTs)
Dangerous Errors to Avoid:
- ⚠️ Delaying delivery in severe pre-eclampsia (maternal mortality risk)
- ⚠️ Not using magnesium sulfate for seizure prophylaxis in severe cases
- ⚠️ Missing pulmonary edema as a complication
- ⚠️ Underestimating postpartum pre-eclampsia risk
- ⚠️ Not monitoring BP for 6 weeks postpartum
Outdated Practices (Do NOT mention):
- Bed rest as primary treatment (no evidence, may worsen outcomes)
- Routine diuretic use (increases perinatal mortality)
- Early induction for mild pre-eclampsia at term (expectant management preferred)
- High-dose aspirin (>150mg) (increased bleeding risk, no additional benefit)
- Calcium supplementation for prevention (not effective in Western populations)
Examiner Follow-Up Questions
Expect these follow-up questions:
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"How do you differentiate between gestational hypertension and pre-eclampsia?"
- Answer: Gestational hypertension is hypertension without proteinuria or organ dysfunction; pre-eclampsia requires either proteinuria (>300mg/24h) or maternal organ dysfunction (thrombocytopenia, elevated LFTs, renal insufficiency, pulmonary edema, cerebral symptoms).
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"What is the role of angiogenic factors in pre-eclampsia?"
- Answer: Pre-eclampsia is characterized by elevated anti-angiogenic factors (sFlt-1, soluble endoglin) and reduced pro-angiogenic factors (PlGF, VEGF), leading to endothelial dysfunction. The sFlt-1/PlGF ratio >85 is highly predictive of pre-eclampsia development.
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"When should you deliver a woman with pre-eclampsia?"
- Answer: Immediate delivery for eclampsia, HELLP, uncontrolled hypertension, fetal distress, or placental abruption. For stable pre-eclampsia: less than 24 weeks expectant management, 24-34 weeks balance maternal/fetal risks, 34-37 weeks deliver when maternal condition stable, ≥37 weeks deliver within days.
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"What are the contraindications to magnesium sulfate?"
- Answer: Myasthenia gravis, renal failure (magnesium accumulation), heart block, and known hypersensitivity. Monitor for toxicity with serial assessments of reflexes, respiratory rate, and serum magnesium levels.
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"How do you prevent pre-eclampsia in future pregnancies?"
- Answer: Low-dose aspirin (150mg daily from 12 weeks) for high-risk women, calcium supplementation in low-calcium populations, lifestyle modifications (weight control, exercise), and close antenatal monitoring in subsequent pregnancies.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.