Overview
Hypertensive disorders of pregnancy (HDP) affect approximately 10% of pregnancies and remain a leading cause of maternal and perinatal morbidity and mortality. They span a clinical spectrum from pre-existing chronic hypertension to severe pre-eclampsia, HELLP syndrome, and eclampsia. The Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) provides the primary Australian guideline framework; the International Society for the Study of Hypertension in Pregnancy (ISSHP) provides the overarching classification system used internationally.
Classification (ISSHP / SOMANZ)
| Category | Definition | Key Features |
|---|---|---|
| Chronic hypertension | Hypertension pre-dating pregnancy, diagnosed before 20 weeks' gestation, or persisting beyond 12 weeks postpartum | Primary or secondary aetiology; superimposed pre-eclampsia develops in 20-50% of those requiring therapy or with SBP >140 mmHg |
| Gestational hypertension | New-onset BP $\geq 140/90$ mmHg at $\geq 20$ weeks in a previously normotensive woman, without organ dysfunction | Resolves by 12 weeks postpartum; must be distinguished from pre-eclampsia |
| Pre-eclampsia | New hypertension at $\geq 20$ weeks with $\geq 1$ feature of maternal organ dysfunction (see below) | Placenta-derived multisystem disorder; can occur without proteinuria |
| Eclampsia | New-onset generalised seizures superimposed on pre-eclampsia | Occurs antepartum, intrapartum, or up to 4 weeks postpartum; rarely without hypertension or proteinuria |
| Superimposed pre-eclampsia | New or worsening organ dysfunction features in a woman with chronic hypertension at $\geq 20$ weeks | Higher risk with pre-existing renal disease, diabetes, antiphospholipid syndrome |
SOMANZ Diagnostic Thresholds
Blood Pressure Criteria
- Hypertension: sustained BP $\geq 140/90$ mmHg on $\geq 2$ occasions at least 4 hours apart
- Severe hypertension: $\geq 160/110$ mmHg - requires urgent treatment
- Target BP after treatment: $< 135/85$ mmHg
- A change of $> 30/15$ mmHg from preconception baseline warrants close monitoring even if absolute values are below threshold
Pre-eclampsia: Organ Dysfunction Features
| System | Feature |
|---|---|
| Renal | Proteinuria (protein:creatinine ratio $> 30$ mg/mmol or $\geq 300$ mg/24 h), or new/worsening renal impairment |
| Haematological | Thrombocytopenia (platelets $< 150 \times 10^9$/L), haemolysis, DIC |
| Hepatic | Elevated transaminases ($> 2\times$ ULN), severe right upper quadrant or epigastric pain |
| Neurological | Severe persistent headache, visual disturbance, hyperreflexia with sustained clonus, eclampsia |
| Cardiopulmonary | Pulmonary oedema |
| Uteroplacental | Fetal growth restriction, abnormal umbilical artery Doppler |
HELLP Syndrome
A severe variant of pre-eclampsia (can occur without proteinuria):
| Feature | Criterion |
|---|---|
| Haemolytic anaemia | Microangiopathic film, elevated LDH, low haptoglobin |
| Elevated Liver enzymes | $> 2\times$ ULN |
| Low Platelets | $< 100 \times 10^9$/L |
Complications include eclampsia (6%), placental abruption (10%), pulmonary oedema (10%), DIC (8%), acute renal failure (5%), and (rarely) hepatic haemorrhage or rupture. Distinguish from TTP, HUS, and acute fatty liver of pregnancy.
Pathophysiology of Placental Maldevelopment
Normal Placentation
Extravillous cytotrophoblasts (EVTs) invade the decidua and myometrium, replacing smooth muscle and elastic tissue of the spiral arteries. This physiological transformation converts them into wide, low-resistance, high-capacitance conduits, ensuring adequate uteroplacental perfusion throughout gestation.
Abnormal Placentation in Pre-eclampsia
Trophoblast invasion is shallow and incomplete, restricted to the decidual segment of the spiral arteries. The myometrial spiral arteries remain narrow and high-resistance, leading to:
- Placental ischaemia and hypoxia-reperfusion injury
- Release of anti-angiogenic factors into the maternal circulation:
- sFlt-1 (soluble fms-like tyrosine kinase-1): sequesters VEGF and PlGF, reducing free pro-angiogenic signalling
- Soluble endoglin (sEng): inhibits TGF-$\beta$ signalling, augmenting endothelial dysfunction
Angiogenic Imbalance and Endothelial Dysfunction
$$\text{sFlt-1 : PlGF ratio} \uparrow \;\Rightarrow\; \text{endothelial dysfunction} \;\Rightarrow\; \text{multi-organ injury}$$
Systemic maternal endothelial dysfunction produces: - Increased systemic vascular resistance → hypertension - Increased capillary permeability → oedema, proteinuria, pulmonary oedema - Platelet activation and microangiopathy → thrombocytopenia, haemolysis - Vasospasm in cerebral, hepatic, and renal beds
Hypertension is a manifestation of endothelial dysfunction, not its cause; antihypertensive therapy therefore does not alter the underlying disease course.
An immunological mechanism is also proposed: first pregnancy, new paternity, and inter-pregnancy intervals $> 10$ years are associated with increased risk, suggesting reduced maternal immune tolerance to paternal antigens.
Two-Stage Model
| Stage | Timing | Event |
|---|---|---|
| Stage 1 (poor placentation) | First half of pregnancy | Impaired trophoblast invasion; subclinical |
| Stage 2 (maternal syndrome) | Second half of pregnancy | Clinical manifestations from placental factor-driven endothelial damage |
Clinical Features
Symptoms
| Mild-Moderate | Severe / Impending Eclampsia |
|---|---|
| Mild headache | Severe, persistent headache |
| Mild oedema | Visual disturbance (scotomata, blurring, photophobia) |
| Nausea | Right upper quadrant / epigastric pain |
| Rapidly progressive facial and hand oedema | |
| Oliguria ($< 500$ mL/24 h) | |
| Dyspnoea (pulmonary oedema) |
Signs
- BP $\geq 140/90$ mmHg at $\geq 20$ weeks
- Proteinuria confirmed by protein:creatinine ratio
- Hyperreflexia, clonus
- Papilloedema (severe cerebral involvement, rare)
Investigations
| Investigation | Rationale |
|---|---|
| FBC and blood film | Thrombocytopenia, microangiopathic haemolysis |
| Urea, creatinine, electrolytes | Renal impairment (note: eGFR not validated in pregnancy) |
| LFTs, LDH | Hepatic involvement, HELLP |
| Uric acid | Correlated with severity; limited diagnostic utility except possibly in CKD (level $> 5.5$ mg/dL with stable renal function may suggest superimposed pre-eclampsia) |
| Coagulation studies | DIC screen |
| Urinary protein:creatinine ratio | Quantify proteinuria |
| CTG | Fetal wellbeing |
| Ultrasound - growth, liquor, Doppler | Placental function, SGA, FGR |
| PlGF alone or sFlt-1:PlGF ratio | NICE-endorsed biomarker; aids in ruling in or ruling out pre-eclampsia after clinical assessment |
Serial monitoring required at minimum twice weekly in admitted patients; frequency increases with severity. Admit to HDU/ICU if eclampsia or HELLP syndrome develops.
Management
Antihypertensive Therapy
Treatment Thresholds and Targets
| Scenario | Action |
|---|---|
| BP $\geq 140/90$ mmHg sustained | Initiate antihypertensive therapy |
| BP $\geq 160/110$ mmHg | Urgent treatment - risk of cerebral haemorrhage, PRES, eclampsia |
| Target BP after treatment | $< 135/85$ mmHg |
Acute aggressive BP lowering risks fetal distress by reducing already-compromised uteroplacental perfusion; antihypertensive therapy is generally withheld unless BP exceeds 150-160/100-110 mmHg.
Antihypertensive Agents
| Agent | Route | Dose | Mechanism | Notes |
|---|---|---|---|---|
| Labetalol | Oral | 100 mg BD up to 600 mg QDS | $\alpha$- and $\beta$-adrenoceptor antagonist | First-line oral agent; IV acute dosing: 20 mg, then escalating doses (20→40→80→80 mg) every 10 min to max 220 mg total; onset within 5 min; contraindicated in asthma, heart block, decompensated cardiac failure |
| Nifedipine (modified-release) | Oral | 10-30 mg BD | Calcium channel blocker | Second-line oral; causes headache, flushing, reflex tachycardia; do not use sublingual formulation |
| Hydralazine | IV/IM | 5 mg IV; repeat 5-10 mg every 20-30 min; max 20 mg | Direct arteriolar vasodilator | Used for acute severe hypertension; onset ~20 min; associated with maternal hypotension and reflex tachycardia; generally second-line to labetalol IV |
| Methyldopa | Oral | 250 mg BD up to 1 g TDS | Central $\alpha_2$-agonist | Safe antenatally; no longer first-line; convert postpartum - risk of postnatal depression |
Contraindicated agents:
| Agent | Reason |
|---|---|
| ACE inhibitors / ARBs | Fetal renal dysgenesis, oligohydramnios, neonatal renal failure - avoid in all trimesters |
| Spironolactone | Anti-androgenic fetal effects |
Breastfeeding-compatible agents: labetalol, nifedipine (modified-release), enalapril, amlodipine. Avoid methyldopa postpartum.
Magnesium Sulfate - Seizure Prophylaxis and Treatment
Indications
- Seizure prevention in severe pre-eclampsia (reduces eclampsia incidence by ~50%; Magpie trial)
- Treatment of eclampsia (first-line anticonvulsant)
- Fetal neuroprotection for preterm birth at $< 30$ weeks (separate NHMRC indication - reduces risk of cerebral palsy)
- Contraindicated in myasthenia gravis
Dosing Protocol
| Phase | Dose | Route |
|---|---|---|
| Loading dose | 4-6 g over 15-20 min | IV (in 100 mL) |
| Maintenance infusion | 1-2 g/hour | IV infusion |
| Duration | $\geq 24$ hours after delivery or last seizure | - |
| Breakthrough seizure | Additional 2 g IV bolus | IV |
| Renal impairment | Reduce maintenance; monitor serum levels closely | - |
Note: some sources (including SOMANZ-aligned references) use a maintenance dose of 1 g/hour; the Magpie/international protocol uses 2 g/hour. Be familiar with both.
Magnesium Toxicity Monitoring
| Serum Magnesium Level | Effect |
|---|---|
| $3.2-5.0$ mmol/L | Loss of deep tendon reflexes |
| $4.0-6.0$ mmol/L | Slurred speech, respiratory depression |
| $> 12$ mmol/L | Respiratory arrest |
| $> 20$ mmol/L | Cardiac arrest |
Monitor every 1-2 hours: patellar reflex present, RR $> 12$/min, urine output $> 25$ mL/hour, SpO$_2$.
Antidote: Calcium gluconate 1 g IV over 2-5 minutes - reverses respiratory depression.
Additional side effects at sub-toxic levels: flushing, diaphoresis, hypothermia, hypotension. Magnesium also causes uterine atony and may contribute to postpartum haemorrhage.
Fluid Management
- Restrict IV fluids to approximately 80 mL/hour (or 1 mL/kg/hour) - minimise pulmonary oedema risk
- Volume expansion (colloid/albumin) is not routinely recommended and may worsen pulmonary function
- Fluid boluses of 250 mL only for documented hypoperfusion; reassess after each bolus
- Hypotension may not respond to IV fluids; metaraminol and adrenaline are considered safe in pre-eclampsia
- Pulmonary oedema is most common postpartum - treat with furosemide 20-40 mg IV
- Platelet transfusion at delivery or invasive procedures if platelets $< 50 \times 10^9$/L
Antenatal Corticosteroids
Administer if delivery is anticipated before 35 weeks (SOMANZ); some guidelines specify $< 34$ weeks for HELLP:
- Betamethasone 11.4 mg IM, repeated at 24 hours, OR
- Dexamethasone 12 mg IM, repeated at 24 hours
Reduces neonatal death, RDS, and intraventricular haemorrhage.
Timing and Mode of Delivery
Delivery is the only definitive treatment. Balance gestational age, fetal maturity, severity of maternal disease, and fetal wellbeing.
| Gestational Age | Recommendation |
|---|---|
| $< 24$ weeks | Delivery recommended - continued pregnancy carries unacceptable maternal risk; perinatal survival extremely limited |
| 24-34 weeks | Expectant management with close surveillance if stable; administer corticosteroids; MgSO$_4$ for fetal neuroprotection at $< 30$ weeks; deliver for worsening maternal or fetal condition |
| 34-36$^{+6}$ weeks | Individualise; deliver for severe features, HELLP, eclampsia, or FGR with abnormal Doppler; optimal gestation for both maternal and fetal outcome approaches 36 weeks |
| $\geq 37$ weeks | Delivery recommended for all pre-eclampsia |
| Severe features at any gestation | Deliver after maternal stabilisation (usually within 24-48 hours) |
Mode of Delivery
- Vaginal delivery is preferred when maternal and fetal condition are stable - lower morbidity than caesarean section; cervical ripening and induction of labour are appropriate
- Caesarean section: obstetric indications (malpresentation, prior uterine surgery, fetal compromise) or unfavourable cervix requiring rapid delivery
- Eclampsia alone is not an indication for immediate caesarean section - stabilise mother first; fetal heart rate abnormalities typically resolve within minutes of seizure; emergent caesarean is indicated if placental abruption is evident
Postpartum Considerations
- Continue magnesium sulfate for 24 hours postpartum (or 24 hours after last seizure)
- BP may persist or worsen for 3-5 days postpartum; monitor closely; antihypertensives may be required for up to 3 months
- Most pulmonary oedema in pre-eclampsia occurs postpartum - maintain fluid restriction
- Breastfeeding-safe antihypertensives: labetalol, nifedipine, enalapril, amlodipine; avoid methyldopa postpartum
Complications
| Maternal | Fetal/Neonatal |
|---|---|
| Eclampsia | Fetal growth restriction |
| HELLP syndrome | Preterm birth |
| Acute kidney injury | Perinatal asphyxia |
| Pulmonary oedema | Stillbirth |
| Placental abruption | Neonatal RDS |
| PRES | Intraventricular haemorrhage |
| Cerebral haemorrhage | Cerebral palsy |
| Hepatic haemorrhage / rupture (rare) | |
| DIC | |
| Maternal death |
Prevention and Risk Reduction
Low-Dose Aspirin
Women at moderate-high risk (one major or $\geq 2$ moderate risk factors):
- Aspirin 100-150 mg daily, commenced before 16 weeks (ideally by 12 weeks) and continued to 36 weeks
- Reduces preterm pre-eclampsia risk by ~60-70% (ASPRE trial)
Major risk factors: prior pre-eclampsia, chronic hypertension, antiphospholipid syndrome, renal disease, pre-existing diabetes, multiple pregnancy
Calcium Supplementation
- Women with low dietary calcium intake ($< 900$ mg/day): calcium 1-1.5 g/day from 20 weeks
Counselling Points
- Recurrence risk: ~15-25% in subsequent pregnancy; higher with early-onset or severe disease
- Long-term cardiovascular risk: at least double the baseline risk of ischaemic heart disease and stroke - requires lifestyle counselling and primary care surveillance
- Discuss aspirin for the next pregnancy preconception
- Postnatal BP review at 6-8 weeks; antihypertensives may be needed for weeks to months
- Counsel on symptoms requiring urgent return for at least 6 weeks postpartum: headache, visual disturbance, epigastric pain, reduced fetal movement
Medicolegal and Ethical Considerations
- Failure to diagnose and act on BP $\geq 160/110$ mmHg is a common source of preventable maternal mortality and medicolegal claims; document BP measurements and timing of treatment
- Women retain the right to informed refusal of interventions including delivery; document counselling regarding maternal and fetal risks of expectant management at any gestation
- At the threshold of viability ($23^{+0}$-$24^{+6}$ weeks), decisions require multidisciplinary input (obstetrics, neonatology) and ideally documented patient preferences before acute deterioration; the ethical tension between maternal safety and fetal survival must be explicitly addressed
- Multidisciplinary communication (obstetrics, midwifery, anaesthetics, neonatal) is mandatory and must be documented
- All magnesium sulfate orders must include a written monitoring protocol - narrow therapeutic window; administration errors carry significant morbidity