Pre-eclampsia

Introduction
Pre-eclampsia is a multisystem hypertensive disorder of pregnancy characterized by new-onset hypertension and proteinuria, or hypertension with end-organ dysfunction, after 20 weeks of gestation in a previously normotensive woman. It is a leading cause of maternal and perinatal morbidity and mortality worldwide. Severe forms can progress rapidly to eclampsia (seizures) or HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count).

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Epidemiology

• Affects 2–8% of pregnancies globally.

• More common in first pregnancies, multifetal gestations, and women with certain risk factors.

• Major cause of preterm birth and fetal growth restriction in low- and middle-income countries.

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Risk Factors

• Maternal:

  • Nulliparity

  • Age <18 or >40 years

  • Obesity

  • Family or personal history of pre-eclampsia

  • Chronic hypertension

  • Diabetes mellitus (type 1 or type 2)

  • Renal disease

  • Autoimmune disorders (e.g., systemic lupus erythematosus, antiphospholipid syndrome)

• Pregnancy-related:

  • Multiple pregnancy

  • Molar pregnancy

  • Fetal chromosomal abnormalities

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Pathophysiology
The underlying mechanism involves abnormal placentation with inadequate trophoblastic invasion of the spiral arteries, leading to:

• High-resistance, low-flow uteroplacental circulation.

• Placental ischemia and hypoxia.

• Release of anti-angiogenic factors (e.g., soluble fms-like tyrosine kinase-1, soluble endoglin) into maternal circulation.

• Widespread endothelial dysfunction, vasoconstriction, increased vascular permeability, and pro-thrombotic state.

This cascade produces hypertension, proteinuria, and damage to organs such as the liver, kidneys, brain, and coagulation system.

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Diagnostic Criteria
Diagnosis after 20 weeks of gestation in a previously normotensive woman:

1. Hypertension

• Systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg on two occasions at least 4 hours apart.

2. Plus one of the following:

• Proteinuria: ≥300 mg/24 hours or protein/creatinine ratio ≥0.3, or dipstick ≥1+ (if other tests unavailable).

• In the absence of proteinuria, new-onset:

  • Thrombocytopenia (<100,000/µL)

  • Renal insufficiency (serum creatinine >1.1 mg/dL or doubling)

  • Elevated liver transaminases (twice normal) with right upper quadrant pain

  • Pulmonary edema

  • New-onset cerebral or visual disturbances

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Classification

1. Pre-eclampsia without severe features:

   • BP ≥140/90 but <160/110 mmHg

   • Proteinuria present

   • No end-organ damage

2. Pre-eclampsia with severe features:

   • BP ≥160/110 mmHg

   • Severe proteinuria or signs of end-organ dysfunction

   • Risk of rapid deterioration and progression to eclampsia

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Clinical Features

• Mild disease: Often asymptomatic, detected on routine prenatal checks.

• Severe disease:

  • Persistent severe headache

  • Visual disturbances (scotomata, blurred vision)

  • Epigastric or right upper quadrant pain

  • Dyspnea (pulmonary edema)

  • Oliguria

  • Rapidly increasing edema (not diagnostic but supportive)

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Investigations

• Blood pressure measurement (repeated).

• Urine analysis: Dipstick, protein/creatinine ratio, 24-hour protein excretion.

• Blood tests: CBC with platelets, liver function tests, renal function tests, coagulation profile if indicated.

• Fetal assessment: Ultrasound for growth and amniotic fluid, Doppler velocimetry of umbilical artery, non-stress test or biophysical profile.

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Management

1. General Principles

• Only definitive cure is delivery of the placenta.

• Balance maternal stabilization with fetal maturity.

• Close monitoring of maternal and fetal status.

2. Mild Pre-eclampsia (without severe features)

• If ≥37 weeks: Delivery is recommended.

• If <37 weeks: Expectant management with close monitoring:

  • BP checks

  • Laboratory tests every 1–2 weeks

  • Fetal surveillance

• Lifestyle: Bed rest not routinely recommended but may limit activity.

3. Severe Pre-eclampsia

• Hospital admission.

• Control severe hypertension:

  • Labetalol:

    • Oral: 100–200 mg twice daily (adjust up to 2,400 mg/day).

    • IV: 20 mg bolus, then 40 mg after 10 min if BP remains high, followed by 80 mg every 10 min (max cumulative 300 mg), or infusion at 1–2 mg/min.

  • Hydralazine: IV 5–10 mg every 20 min as needed, or infusion at 0.5–10 mg/h.

  • Nifedipine: Oral immediate release 10 mg, repeat after 20 min if needed, then 10–20 mg every 4–6 h.

• Seizure prophylaxis:

  • Magnesium sulfate:

    • Loading dose: 4–6 g IV over 15–20 min.

    • Maintenance: 1–2 g/h continuous IV infusion for 24 hours postpartum or after last seizure.

    • Monitor for toxicity (loss of reflexes, respiratory depression); antidote is calcium gluconate 1 g IV.

• Fluid management: Avoid overload (risk of pulmonary edema).

• Delivery:

  • ≥34 weeks or if maternal/fetal condition deteriorates → proceed to delivery.

  • Vaginal delivery preferred unless obstetric indications for cesarean exist.

4. HELLP Syndrome

• Immediate delivery after maternal stabilization, regardless of gestational age.

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Prevention

• Low-dose aspirin: 75–150 mg daily from 12 weeks gestation in high-risk women.

• Calcium supplementation: 1.5–2 g/day in populations with low dietary calcium intake.

• Control of chronic hypertension and optimization of health before pregnancy.

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Complications

• Maternal:

  • Eclampsia

  • HELLP syndrome

  • Stroke

  • Acute kidney injury

  • Pulmonary edema

  • Disseminated intravascular coagulation (DIC)

• Fetal:

  • Intrauterine growth restriction (IUGR)

  • Oligohydramnios

  • Placental abruption

  • Preterm birth

  • Intrauterine fetal demise

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Prognosis

• Most women recover fully after delivery, but increased risk of recurrence in subsequent pregnancies.

• Higher lifetime risk of chronic hypertension, cardiovascular disease, and chronic kidney disease.