Pre-eclampsia is a pregnancy-specific multisystem hypertensive disorder defined by new-onset hypertension (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg on two occasions at least 4 hours apart) arising after 20 weeks' gestation accompanied by either significant proteinuria or maternal end-organ / uteroplacental dysfunction 1,2. Eclampsia is defined by new-onset generalised tonic-clonic seizures or coma in a patient with pre-eclampsia not attributable to another neurological cause 1,2.

1. Etiology & Risk Factors (NICE NG133 / ACOG)

  • High-Risk Factors (≥1 mandates low-dose Aspirin 75–150 mg OD from 12 weeks) 1,2:
    • Hypertensive disease during a previous pregnancy (previous pre-eclampsia or HELLP syndrome).
    • Chronic kidney disease (CKD), Chronic hypertension, Type 1 or Type 2 diabetes mellitus.
    • Autoimmune disease: Systemic lupus erythematosus (SLE) or Antiphospholipid syndrome (APS).
  • Moderate-Risk Factors (≥2 mandate low-dose Aspirin from 12 weeks):
    • Nulliparity (first pregnancy), maternal age ≥40 years, pregnancy interval >10 years, pre-pregnancy BMI ≥35 kg/m², family history of pre-eclampsia, or multifetal gestation (twins/triplets).
    • Note: Complete hydatidiform molar pregnancy can cause severe pre-eclampsia before 20 weeks' gestation.

2. Pathophysiology

In normal placentation, fetal extravillous cytotrophoblasts invade the maternal decidual and myometrial spiral arteries, replacing the musculoelastic media to create high-capacitance, low-resistance vessels. In pre-eclampsia, incomplete trophoblast invasion leaves the spiral arteries narrow and vasoactive, leading to placental hypoxia and release of anti-angiogenic factors — specifically soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) — which neutralise vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). The result is systemic maternal endothelial dysfunction, vasoconstriction, capillary leak, platelet activation, and glomerular endotheliosis 1,2.

Pathophysiological Mechanism — Pre-eclampsia and eclampsia 1 Stage 1 (8–18 Weeks): Defective Cytotrophoblast Invasion of Spiral Arteries Extravillous trophoblasts fail to remodel maternal myometrial spiral arteries into low-resistance vessels 2 Placental Hypoperfusion, Ischaemia-Reperfusion Injury & Oxidative Stress High-resistance uteroplacental circulation (abnormal uterine artery Doppler notching) & fetal growth restriction 3 Stage 2 (>20 Weeks): Anti-Angiogenic Imbalance (Elevated sFlt-1 & Soluble Endoglin / Low PlGF) sFlt-1 binds and neutralises maternal VEGF & PlGF in systemic circulation 4 Widespread Maternal Systemic Endothelial Dysfunction & Vasospasm Hypertension + Glomerular endotheliosis (proteinuria) + Hepatic subcapsular ischaemia (HELLP) + Cerebral oedema (Eclampsia)

3. Clinical Presentation & Severe Features

  • Mild-to-Moderate Pre-eclampsia: often asymptomatic and detected on routine antenatal BP and urine dipstick screening.
  • Pre-eclampsia with Severe Features (Impending Eclampsia Red Flags) 1,2:
    • Severe hypertension: systolic BP ≥160 mmHg or diastolic BP ≥110 mmHg.
    • Neurological features (cerebral vasospasm/oedema): severe persistent frontal/occipital headache unresponsive to analgesia, visual scotomata / photopsia (flashing lights) / cortical blindness (posterior reversible encephalopathy syndrome [PRES]), hyperreflexia, and ankle clonus (≥3 beats).
    • Hepatic features: severe right upper quadrant (RUQ) or epigastric pain due to Glisson's capsule distension from periportal haemorrhage or subcapsular hepatic haematoma.
    • Cardiorespiratory features: acute pulmonary oedema (due to capillary leak and high afterload — always restrict IV fluids to ≤80 mL/hr!).

4. Diagnostic Workup & Interpretation

Investigation Diagnostic Threshold & Clinical Interpretation
Spot Urine Protein:Creatinine Ratio (PCR) ≥30 mg/mmol (≥0.3 mg/mg) or 24-hour urine protein ≥300 mg/24h confirms significant proteinuria (corresponds to ≥2+ on automated dipstick).
sFlt-1 : PlGF Ratio / PlGF Assay PlGF <100 pg/mL or sFlt-1:PlGF ratio >38 strongly predicts pre-eclampsia requiring delivery within 14 days (ratio <38 has a 99% negative predictive value over 1 week).
Full Blood Count & Blood Film Thrombocytopenia (<100 × 10⁹/L) indicates severe feature / HELLP syndrome; schistocytes and elevated LDH (>600 IU/L) indicate microangiopathic haemolysis.
Liver & Renal Function (AST, ALT, Creatinine, Uric Acid) AST or ALT ≥2× upper limit of normal (>70 IU/L); serum creatinine >90 µmol/L (1.1 mg/dL) or doubling of baseline creatinine.
Fetal Surveillance Ultrasound fetal biometry (asymmetrical IUGR), amniotic fluid volume (oligohydramnios), Umbilical Artery Doppler (absent or reversed end-diastolic flow), and cardiotocography (CTG).

5. Differential Diagnosis (2-Column Comparison Table)

Condition Distinguishing Clinical & Biochemical Features
Chronic Hypertension in Pregnancy Hypertension (BP ≥140/90 mmHg) present before 20 weeks' gestation or persisting >12 weeks postpartum without new-onset proteinuria or end-organ damage.
Gestational Hypertension New-onset hypertension after 20 weeks' gestation without proteinuria (PCR <30 mg/mmol) and without maternal/uteroplacental organ dysfunction.
Acute Fatty Liver of Pregnancy (AFLP) Third-trimester emergency presenting with profound hypoglycaemia, coagulopathy (prolonged PT/INR, low fibrinogen), hyperammonaemia, jaundice, and Swansea criteria (LCHAD deficiency).
Thrombotic Thrombocytopenic Purpura (TTP) / HUS Severe thrombocytopenia and MAHA with neurological/renal dysfunction, normal transaminases, and ADAMTS13 activity <10% (requires plasma exchange rather than immediate delivery).

6. Management & Treatment Protocol (NICE NG133 / ACOG / WHO)

  • 1. Antihypertensive Therapy (Target BP ≤135/85 mmHg) 1,2:
    • Standard Oral Therapy (BP 140/90 to 159/109 mmHg):
      • First-line: Oral Labetalol (100–200 mg BD/TDS; contraindicated in asthma).
      • Second-line: Modified-release Nifedipine (10–20 mg BD) or Methyldopa (250–500 mg TDS).
    • Acute Severe Hypertension Emergency (BP ≥160/110 mmHg — Obstetric Emergency to prevent maternal haemorrhagic stroke):
      • Oral Nifedipine (10–20 mg) OR IV Labetalol (20 mg IV bolus over 2 min, escalating to 40 mg / 80 mg every 10 min or infusion) OR IV Hydralazine (5–10 mg IV bolus after 250–500 mL crystalloid preload).
  • 2. Seizure Prophylaxis & Eclampsia Management — Magnesium Sulfate (Collaborative Eclampsia Trial / Magpie Trial) 1,2:
    • Regimen (Zuspan IV Regimen): 4 g IV loading dose infused slowly over 15–20 minutes, followed by a continuous maintenance infusion of 1 g/hour IV continued for 24 hours after the last seizure or delivery.
    • Recurrent Eclamptic Seizure on MgSO₄: give a further 2 g IV bolus of Magnesium sulfate over 5 minutes.
    • Strict Fluid Restriction: limit total IV + oral fluid intake to 80 mL/hour (or 1 mL/kg/hr) to prevent life-threatening pulmonary oedema.
  • 3. Timing of Delivery (Definitive Cure):
    • Pre-eclampsia without severe features: expectant management with twice-weekly maternal labs and fetal surveillance until 37+0 weeks' gestation, then induction of labour.
    • Pre-eclampsia with severe features / Eclampsia / HELLP syndrome: deliver at ≥34+0 weeks (or immediately at any gestation if maternal eclampsia, pulmonary oedema, placental abruption, DIC, refractory hypertension, or non-reassuring fetal status after initial maternal stabilization). Administer antenatal corticosteroids (Betamethasone 12 mg IM × 2 doses 24h apart) for fetal lung maturation if <34 weeks.