Key Facts

Pre-eclampsia is a pregnancy-specific disorder with potentially devastating consequences for mother and baby. It is a leading cause of maternal and perinatal morbidity and mortality worldwide. The only definitive treatment is delivery, but optimising timing of delivery balances maternal safety against fetal prematurity.

Epidemiology

Pre-eclampsia affects approximately 2-5% of pregnancies worldwide and 2-3% in the UK. It is the leading direct cause of maternal death in the UK. Globally, it causes approximately 50,000-70,000 maternal deaths per year. Eclampsia occurs in approximately 0.5-1 per 1,000 deliveries in the UK. HELLP syndrome occurs in approximately 0.2-0.8% of all pregnancies.

Aetiology

Two-stage model:

• Stage 1 (placental): Defective trophoblast invasion of spiral arteries → inadequate remodelling → placental ischaemia/hypoxia
• Stage 2 (maternal): Ischaemic placenta releases anti-angiogenic factors (sFlt-1) → systemic endothelial dysfunction → clinical syndrome

Risk factors:

• High risk (≥1 = aspirin): Previous pre-eclampsia, CKD, autoimmune disease (SLE, APS), type 1/2 diabetes, chronic hypertension
• Moderate risk (≥2 = aspirin): Nulliparity, age ≥40, BMI ≥35, family history, multiple pregnancy, IVF, pregnancy interval >10 years

Pathophysiology

Defective spiral artery remodelling → reduced uteroplacental perfusion → placental oxidative stress → release of anti-angiogenic factors (sFlt-1) and inflammatory mediators → widespread maternal endothelial dysfunction affecting:

• Vascular: Vasoconstriction, hypertension
• Renal: Glomerular endotheliosis → proteinuria; reduced GFR → AKI
• Hepatic: Periportal necrosis, subcapsular haemorrhage → HELLP syndrome, hepatic rupture
• CNS: Cerebral oedema, vasospasm → eclampsia (seizures), PRES (posterior reversible encephalopathy syndrome)
• Haematological: Microangiopathic haemolysis, thrombocytopenia, DIC
• Placental: Growth restriction, abruption, stillbirth

Hypertension

• Systolic ≥140 or diastolic ≥90 mmHg (on 2 occasions at least 4h apart)
• Severe: ≥160/110 mmHg

Proteinuria

• Urine PCR ≥30 mg/mmol (equivalent to ≥300mg/24h)
• Dipstick ≥1+ (must confirm with PCR)

Symptoms of Severe Pre-eclampsia

• Severe headache (frontal, throbbing, not relieved by simple analgesia)
• Visual disturbance (blurred vision, flashing lights, scotomata)
• Epigastric/right upper quadrant pain (hepatic capsule distension)
• Sudden facial/hand oedema
• Nausea and vomiting
• Brisk reflexes, clonus (≥3 beats)

Eclampsia

• Tonic-clonic seizures in the context of pre-eclampsia
• Can occur antepartum (38%), intrapartum (18%), or postpartum (44%)

HELLP Syndrome

• Haemolysis (raised LDH, fragmented red cells, raised unconjugated bilirubin)
• Elevated liver enzymes (AST/ALT >70 IU/L)
• Low platelets (<100 × 10⁹/L)

Red Flags

• BP ≥160/110 — urgent antihypertensive treatment needed
• Symptoms of severe pre-eclampsia — admit, investigate, consider delivery
• Eclamptic seizure — magnesium sulfate, stabilise, plan delivery
• Platelets <50 or rapidly falling — HELLP, risk of DIC
• Pulmonary oedema, oliguria (<0.5ml/kg/h) — ICU involvement

Bedside

• Blood pressure: Validated automated device; manual if automated reading abnormal
• Urine dipstick: Proteinuria screening; confirm with uPCR if ≥1+
• Urine protein:creatinine ratio (uPCR): ≥30 mg/mmol = significant proteinuria
• Reflexes: Brisk reflexes, clonus (≥3 beats) — CNS hyperexcitability
• Fetal assessment: CTG, fetal movements

Bloods

• FBC: Thrombocytopenia (HELLP), haemoconcentration
• U&Es, creatinine, uric acid: AKI (creatinine >90 μmol/L), raised urate
• LFTs: AST/ALT elevation (HELLP, hepatic involvement)
• LDH: Elevated in haemolysis/HELLP
• Coagulation screen: DIC screening (PT, APTT, fibrinogen)
• Blood film: Fragmented red cells (schistocytes) in HELLP
• PlGF-based testing (NICE DG49): Placental growth factor — PlGF <100 pg/mL suggests pre-eclampsia; sFlt-1:PlGF ratio >38 is highly predictive

Imaging

• USS: Fetal growth assessment (SGA common), amniotic fluid volume, umbilical artery Doppler
• Liver USS: If severe RUQ pain — exclude subcapsular haematoma, hepatic rupture

Special Tests

• 24-hour urine protein: Historically used (≥300mg/24h) but uPCR now preferred (faster)
• CT head: If atypical neurological features, to exclude intracranial haemorrhage
• MRI brain: PRES (posterior reversible encephalopathy syndrome) if suspected

Non-pharmacological

• Admission: For severe pre-eclampsia, symptoms, or worsening parameters
• Monitoring: Frequent BP (at least 4-hourly; continuous if severe), daily bloods (FBC, LFTs, U&Es), uPCR, strict fluid balance
• Fetal monitoring: CTG, serial growth scans, umbilical artery Doppler

Pharmacological

• Antihypertensives (NICE NG133):
  • First-line: Labetalol 100mg BD, titrate to max 800mg/day in divided doses (avoid in asthma)
  • Second-line: Nifedipine MR 20mg BD, titrate to max 80mg/day
  • Third-line: Methyldopa 250mg BD-TDS (max 3g/day)
  • IV for severe HTN (≥160/110): IV labetalol 20mg bolus, then 40mg after 10 min, then 80mg (max 200mg total); or IV hydralazine 5mg bolus
• Magnesium sulfate (eclampsia prevention/treatment — MAGPIE trial):
  • Loading: 4g IV over 5-15 minutes
  • Maintenance: 1g/hour for 24 hours
  • Monitor: Respiratory rate (>12/min), urine output (>25ml/h), patellar reflexes (must be present)
  • Toxicity: Calcium gluconate 10ml 10% IV for magnesium toxicity
• Aspirin prophylaxis: 150mg nocte from 12 weeks to 36 weeks for at-risk women (ASPRE trial — 62% reduction in preterm pre-eclampsia)
• Corticosteroids: Betamethasone 12mg IM × 2 doses 24h apart if delivery anticipated <34+6 weeks (fetal lung maturity)

Surgical/Interventional

• Delivery (definitive treatment):
  • ≥37 weeks: Deliver (NICE NG133, supported by HYPITAT trial)
  • 34-37 weeks with severe features: Consider delivery after stabilisation and steroids
  • <34 weeks: Attempt to prolong pregnancy with close monitoring if condition allows; deliver if maternal or fetal deterioration
  • Mode: Vaginal delivery preferred if feasible; caesarean section if deteriorating, failed induction, or fetal compromise
• Postpartum: Continue antihypertensives; monitor BP for at least 6 weeks; review at 6-8 weeks

Referral Criteria

• New hypertension + proteinuria after 20 weeks — urgent obstetric review
• Severe pre-eclampsia or HELLP — consultant-led care, consider HDU/ITU
• Eclampsia — obstetric emergency; senior obstetric and anaesthetic input
• Previous pre-eclampsia — pre-conception counselling for subsequent pregnancies

• Maternal mortality: Pre-eclampsia/eclampsia accounts for ~5% of direct maternal deaths in the UK (MBRRACE-UK)
• HELLP syndrome mortality: ~1-3% (higher if complicated by hepatic rupture or DIC)
• Eclampsia mortality: ~1-2% in developed countries
• Recurrence: ~15-20% risk of pre-eclampsia in subsequent pregnancy (~25% if severe/early-onset)
• Fetal/neonatal: Growth restriction in ~25-30% of pre-eclamptic pregnancies; prematurity if early delivery required
• Long-term maternal risk: Women with pre-eclampsia have 2-4× increased lifetime risk of cardiovascular disease, chronic hypertension, stroke, and CKD
• Aspirin prophylaxis: ASPRE trial showed 62% reduction in preterm pre-eclampsia when aspirin 150mg given from 11-14 weeks
• MAGPIE trial: Magnesium sulfate reduced eclampsia risk by 58% in women with pre-eclampsia

Classification of Hypertensive Disorders in Pregnancy

Key Landmark Trials