Pre-eclampsia and eclampsia
Description
- Placental disorder with systemic maternal endothelial dysfunction - the placenta is the disease, the mother shows the signs
- Proteinuria is NOT required for the diagnosis - a common and important error
Hypertensive disorders of pregnancy - the four categories
| Definition | |
|---|---|
| Chronic hypertension | Pre-dating pregnancy or <20 weeks |
| Gestational hypertension | New hypertension >=20 weeks, no organ dysfunction; ~25% progress to pre-eclampsia |
| Pre-eclampsia | New hypertension >=20 weeks + maternal organ dysfunction OR uteroplacental dysfunction |
| Pre-eclampsia superimposed on chronic hypertension | New organ dysfunction or a step-up in BP/proteinuria |
- Eclampsia - generalised tonic-clonic seizure in pre-eclampsia not attributable to another cause
- ~1/3 occur postpartum, and up to 1/4 occur before hypertension or proteinuria is documented
- HELLP - Haemolysis, Elevated Liver enzymes, Low Platelets; a severe variant, may occur without hypertension
Epidemiology
- Hypertensive disorders complicate ~5-10% of pregnancies; pre-eclampsia ~3-5%
- Leading cause of maternal mortality worldwide; a leading direct cause in Australia
- Nulliparity roughly doubles risk (~4-5% vs 1-2%)
- Recurrence ~15% overall; up to 25-50% if early-onset or severe
- Eclampsia ~1 in 2000-3000 births in Australia
- Higher incidence in Aboriginal and Torres Strait Islander women and in Pacific and South Asian populations
Aetiopathogenesis
Two-stage model
- Stage 1 (asymptomatic, 8-18 weeks) - failure of trophoblast invasion of spiral arteries
- Arteries remain narrow, high-resistance, vasoreactive
- -> placental hypoperfusion, ischaemia-reperfusion, oxidative stress
- Stage 2 (clinical) - release of anti-angiogenic factors into the maternal circulation
- inc sFlt-1 (soluble fms-like tyrosine kinase-1) - scavenges VEGF and PlGF
- inc soluble endoglin, dec PlGF
- -> systemic endothelial dysfunction -> vasoconstriction, inc permeability, activation of coagulation
- Organ consequences:
- Brain - vasogenic oedema (posterior circulation -> PRES), seizure
- Kidney - glomerular endotheliosis -> proteinuria, AKI
- Liver - periportal necrosis, subcapsular haematoma
- Haematological - microangiopathic haemolysis, platelet consumption
- Placenta - infarction, abruption, fetal growth restriction
Risk factors
- High risk (any one -> aspirin): previous pre-eclampsia, chronic hypertension, pre-existing diabetes (T1 or T2), chronic kidney disease, antiphospholipid syndrome or SLE, multiple pregnancy
- Moderate risk (two or more -> aspirin): nulliparity, age >=40, BMI >=30, family history of pre-eclampsia, interpregnancy interval >10 yrs, IVF/assisted reproduction, ethnicity
- Partner-related: new partner, short duration of sexual cohabitation, donor gametes - consistent with an immune-tolerance mechanism
- Smoking is paradoxically protective (not a recommendation)
Diagnosis
Hypertension in pregnancy
- SBP >=140 or DBP >=90 on two occasions (or once if severe)
- Severe: SBP >=160 or DBP >=110 - a treatment emergency
- Correct cuff size; Korotkoff V for diastolic
Pre-eclampsia - hypertension >=20 weeks PLUS at least one of:
Maternal organ dysfunction
- Renal - proteinuria (PCR >=30 mg/mmol or ACR >=8 mg/mmol), creatinine >90 micromol/L or AKI
- Haematological - platelets <150 x10^9/L, DIC, haemolysis
- Hepatic - transaminases >2x upper limit, severe RUQ or epigastric pain
- Neurological - severe headache, visual scotomata, hyperreflexia with clonus, stroke, PRES, eclampsia
- Pulmonary oedema
Uteroplacental dysfunction
- Fetal growth restriction, abnormal umbilical artery Doppler, stillbirth, abnormal angiogenic markers
Angiogenic biomarkers - the meaningful recent addition
- sFlt-1/PlGF ratio
- <=38 effectively rules out pre-eclampsia within the next week (NPV ~99%) - the main value is the negative result, avoiding unnecessary admission and delivery
- High ratio predicts need for delivery within 2 weeks
- First-trimester combined screening (11-13+6 weeks) - maternal factors + MAP + uterine artery PI + PlGF -> identifies high risk for aspirin prophylaxis
Assessment on presentation
- Bloods: FBE (platelets, haemolysis, film for fragments), UEC, LFT, LDH, urate, coagulation, group and hold
- Urine PCR/ACR (spot, not 24 h)
- Fetal: CTG, growth ultrasound, amniotic fluid, umbilical artery Doppler
- Consider CT/MRI brain for atypical or focal neurology
Differentials of the seizing or thrombocytopenic pregnant woman
| Discriminator | |
|---|---|
| Eclampsia | Hypertension, proteinuria, >=20 weeks or postpartum |
| TTP | Fever, marked thrombocytopenia, neurological signs, ADAMTS13 <10%; normal LFTs |
| aHUS | Renal failure dominant; typically postpartum; complement-mediated |
| Acute fatty liver of pregnancy | Hypoglycaemia, high ammonia, coagulopathy, normal/low platelets, Swansea criteria |
| Epilepsy, stroke, CVST, intracranial haemorrhage, hyponatraemia, meningitis | History, imaging |
Management
Delivery of the placenta is the only cure. Everything else buys time safely.
A. Prevention - the highest-yield intervention
- Aspirin 150 mg nocte, started between 12 and 16 weeks (before 16 weeks), continued to 36 weeks, for all at high risk or with >=2 moderate risk factors
- Reduces preterm pre-eclampsia by ~60% (ASPRE); little effect if started after 16 weeks
- Calcium 1.2-2.5 g/day if dietary intake is low
- Optimise weight, BP and glycaemic control pre-pregnancy; switch teratogenic antihypertensives before conception
B. Blood pressure control
- Treat at BP >=140/90 - the threshold lowered in SOMANZ 2023 (CHIPS, CHAP)
- Target ~110-135 systolic and ~85 diastolic
- Tight control reduces severe hypertension without increasing fetal growth restriction
- Oral agents: labetalol, nifedipine (modified-release), methyldopa; second-line hydralazine, prazosin
- Severe hypertension (>=160/110) is an emergency - treat within 30-60 min
- IV labetalol, oral or IV nifedipine, or IV hydralazine
- Avoid precipitous falls - uteroplacental perfusion is pressure-dependent
- *Contraindicated: ACE inhibitors, ARBs, direct renin inhibitors (fetal renal failure, oligohydramnios, skull hypoplasia); avoid diuretics (volume depletion)*
C. Seizure prophylaxis and treatment
- Magnesium sulfate is first-line for BOTH prevention and treatment - superior to phenytoin and to benzodiazepines
- Loading 4 g IV over 20 min, then 1 g/h infusion, continued for 24 h after delivery or the last seizure
- Recurrent seizure: further 2-4 g bolus
- Indications for prophylaxis: eclampsia, and pre-eclampsia with severe features (severe hypertension, neurological symptoms, HELLP, rapidly deteriorating)
- Monitor: deep tendon reflexes (loss = first sign of toxicity), respiratory rate, urine output, conscious state
- Reduce the infusion rate in renal impairment - magnesium is renally cleared
- Antidote: calcium gluconate 1 g IV
- Also neuroprotective for the fetus if delivery <30-32 weeks
D. Fetal considerations
- Corticosteroids for fetal lung maturity if <34-35 weeks (betamethasone)
- Serial growth scans, umbilical artery Doppler, CTG
- Individualised surveillance; inpatient management for severe disease
E. Timing of delivery - the definitive decision
- Pre-eclampsia at >=37 weeks -> deliver (no benefit from expectant management)
- <37 weeks: expectant management with close surveillance in a unit with neonatal capability, provided mother and fetus remain stable
- Deliver regardless of gestation for:
- Eclampsia, uncontrollable severe hypertension, pulmonary oedema
- Deteriorating renal, hepatic or haematological function, HELLP
- Placental abruption, non-reassuring fetal status, reversed end-diastolic flow
- Mode of delivery is obstetric, not dictated by pre-eclampsia; regional anaesthesia acceptable if platelets adequate
F. Postpartum
- *The risk does not end at delivery - BP typically peaks days 3-6 postpartum*; eclampsia can occur up to 4 weeks post
- Continue antihypertensives; labetalol, nifedipine, enalapril and captopril are all breastfeeding-compatible (ACE inhibitors are safe postpartum, unlike antenatally)
- Avoid NSAIDs if hypertension is difficult to control or there is AKI
- VTE prophylaxis
- Review at 6-12 weeks: ensure BP and proteinuria resolve; persistence beyond 3 months -> investigate for underlying renal disease or secondary hypertension
G. Long-term - do not omit
- Pre-eclampsia is a female-specific cardiovascular risk factor
- ~2x ischaemic heart disease, ~2x stroke, ~4x hypertension, increased CKD and T2DM
- Annual BP check, cardiovascular risk assessment, lifestyle counselling; document for future pregnancies
Associations
- Previous pre-eclampsia; family history
- Chronic hypertension, chronic kidney disease
- Pre-existing diabetes, obesity, metabolic syndrome
- Antiphospholipid syndrome, SLE
- Multiple pregnancy, molar pregnancy (pre-eclampsia before 20 weeks is molar until excluded)
- Assisted reproduction, donor oocyte, nulliparity, new partner
- Age >=40, interpregnancy interval >10 years
- Obstructive sleep apnoea
- Thrombophilia (inconsistent)
- Later maternal cardiovascular and renal disease; offspring: preterm birth, low birth weight, later metabolic risk
Natural history & complications
- Progressive while the placenta remains in situ; unpredictable rate of deterioration
- Earlier onset = more severe disease and higher recurrence
- Resolution: BP and proteinuria usually normalise within days to 12 weeks postpartum
- Recurrence 15% overall; 25-50% after early-onset or severe disease
Maternal complications
- Eclampsia, stroke (the leading cause of death - systolic hypertension is the driver), PRES
- HELLP, DIC, hepatic rupture/subcapsular haematoma
- Pulmonary oedema, AKI, retinal detachment, placental abruption
- Postpartum haemorrhage, VTE
Fetal/neonatal complications
- Fetal growth restriction, oligohydramnios, iatrogenic prematurity, stillbirth, perinatal death
Long-term
- Cardiovascular disease ~2x, stroke ~2x, chronic hypertension ~4x, CKD and ESKD increased, T2DM increased
- Treat the pregnancy as a cardiovascular stress test - the result is a lifelong risk marker, and the postpartum review is where that gets acted on
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