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 ≥140/90 mmHg at ≥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 ≥20 weeks with ≥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 ≥20 weeks | Higher risk with pre-existing renal disease, diabetes, antiphospholipid syndrome |
SOMANZ Diagnostic Thresholds
Blood Pressure Criteria
- Hypertension: sustained BP ≥140/90 mmHg on ≥2 occasions at least 4 hours apart
- Severe hypertension: ≥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 ≥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 ≥140/90 mmHg at ≥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 ≥140/90 mmHg sustained | Initiate antihypertensive therapy |
| BP ≥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 g over 15-20 min | IV (in 100 mL) |
| Maintenance infusion | 1 g/hour | IV infusion |
| Duration | ≥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 |
|---|---|
| 2.0-3.5 mmol/L | Therapeutic range for seizure prophylaxis |
| 3.5-5.0 mmol/L | Loss of deep tendon reflexes |
| 5.0-6.5 mmol/L | Slurred speech, respiratory depression |
| >7.5 mmol/L | Respiratory paralysis; altered cardiac conduction |
| >12.5 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 |
| ≥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 ≥2 moderate risk factors):
- Aspirin 150 mg daily at bedtime, commenced before 16 weeks (ideally by 12 weeks) and ceased between 34 weeks and birth, individualised (SOMANZ 2023)
- 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 (<1 g/day): supplemental calcium is strongly recommended; assess intake first. SOMANZ 2023 does not specify a dose (SOMANZ 2015 advised 1.5 g/day)
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 ≥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