How is pre-eclampsia defined?
Pre-eclampsia is a multisystem disorder of pregnancy defined by NICE NG133 as new-onset hypertension (over 140 mmHg systolic or over 90 mmHg diastolic) after 20 weeks of pregnancy together with one or more new-onset conditions: proteinuria, other maternal organ dysfunction, or uteroplacental dysfunction. The old triad of hypertension, oedema and proteinuria has been replaced by hypertension plus organ dysfunction — oedema is no longer a criterion, and proteinuria is not mandatory.
| Disorder | Definition |
|---|---|
| Chronic hypertension | Hypertension present at booking, before 20 weeks, or already on antihypertensives |
| Gestational hypertension | New hypertension after 20 weeks without significant proteinuria (and no other pre-eclampsia features) |
| Pre-eclampsia | New hypertension after 20 weeks plus proteinuria or maternal organ dysfunction or uteroplacental dysfunction |
| Severe hypertension | Over 160 mmHg systolic or over 110 mmHg diastolic |
| Eclampsia | A convulsive condition associated with pre-eclampsia |
| HELLP syndrome | Haemolysis, Elevated Liver enzymes and Low Platelet count |
| Domain | Criterion |
|---|---|
| Proteinuria | Urine protein:creatinine ratio ≥ 30 mg/mmol, or albumin:creatinine ratio ≥ 8 mg/mmol, or ≥ 1 g/L (2+) on dipstick |
| Renal | Creatinine ≥ 90 µmol/L (≥ 1.02 mg/100 mL) |
| Liver | ALT or AST over 40 IU/L, with or without right upper quadrant or epigastric pain |
| Neurological | Eclampsia, altered mental status, blindness, stroke, clonus, severe headaches or persistent visual scotomata |
| Haematological | Platelets below 150,000/µL, DIC or haemolysis |
| Uteroplacental | Fetal growth restriction, abnormal umbilical artery Doppler, or stillbirth |
What causes pre-eclampsia and who is at risk?
The central mechanism is uteroplacental ischaemia. StatPearls lists the supporting evidence: failure of physiological transformation of the spiral arteries with atherosis, lower uterine blood flow, a raised uterine artery pulsatility index, and frequent ischaemic placental lesions. The ischaemic placenta releases factors that cause a diffuse maternal endothelial dysfunction (vasculopathy) — which explains why almost every organ can be involved.
| Feature | Early-onset ('placental') | Late-onset ('maternal') |
|---|---|---|
| Main driver | Defective placenta — abnormal trophoblast invasion, infarcts, hypoperfusion | Maternal endothelial dysfunction with a relatively healthy placenta |
| Spiral artery conversion | Defective | Little or no change; placental perfusion maintained |
| Fetal impact | Growth restriction more common | Usually milder; can often be managed expectantly to 37 weeks |
Risk factors (StatPearls): nulliparity, advanced maternal age, chronic hypertension, diabetes, renal disease, obesity/high BMI, previous gestational hypertension, autoimmune disease (SLE, antiphospholipid syndrome), hydatidiform mole, multiple pregnancy, fetal macrosomia, assisted reproduction and family history.
What are the severe features of pre-eclampsia?
ACOG-based criteria summarised in StatPearls define pre-eclampsia with severe features by any of the following. A woman with gestational hypertension who reaches severe-range BP is diagnosed with pre-eclampsia with severe features even without other criteria.
- Severe-range BP: systolic ≥ 160 mmHg or diastolic ≥ 110 mmHg (confirmed within minutes so treatment is not delayed)
- Thrombocytopenia: platelets < 100,000/µL
- Impaired liver function: transaminases more than twice the upper limit of normal, or severe right upper quadrant/epigastric pain
- Renal insufficiency: serum creatinine ≥ 1.1 mg/dL or doubling of baseline
- Pulmonary oedema
- New headache unresponsive to medication, or visual disturbance
What is HELLP syndrome and how is it diagnosed?
HELLP syndrome (Haemolysis, Elevated Liver enzymes, Low Platelets) has a prevalence of 0.5–0.9%. About 70% of cases occur in the third trimester and the rest within 48 hours of delivery. Hypertension or proteinuria is absent in 15–20% of patients, so a normotensive woman with epigastric pain and low platelets can still have HELLP.
| Component | Criterion |
|---|---|
| Haemolysis (≥ 2 of) | Schistocytes and burr cells on smear; bilirubin > 1.2 mg/dL; low haptoglobin (< 25 mg/dL) or LDH > 2× upper limit of normal |
| Elevated liver enzymes | AST/ALT raised (more than twice the upper limit of normal) |
| Low platelets | < 100,000/µL |
HELLP is mainly a platelet-activation disorder, so PT, aPTT and fibrinogen are normal unless DIC co-exists — this is how it is distinguished from pre-eclampsia with DIC. Complications include DIC (15–62.5%), placental abruption, PPH, acute kidney injury and subcapsular liver haematoma or rupture (severe RUQ pain needs urgent ultrasound). Management is supportive with stabilisation, BP control, magnesium sulfate and delivery; NICE and WHO advise against corticosteroids to treat HELLP itself, though steroids are still given for fetal lung maturity before 34 weeks.
How is pre-eclampsia prevented — aspirin and calcium?
| Risk group | Factors | Advice |
|---|---|---|
| High risk (any ONE) | Hypertensive disease in a previous pregnancy; chronic kidney disease; SLE or antiphospholipid syndrome; type 1 or type 2 diabetes; chronic hypertension | Aspirin 75–150 mg daily from 12 weeks until birth |
| Moderate risk (MORE THAN ONE) | Nulliparity; age ≥ 40; pregnancy interval > 10 years; BMI ≥ 35 at first visit; family history of pre-eclampsia; multi-fetal pregnancy | Aspirin 75–150 mg daily from 12 weeks until birth |
WHO recommends low-dose aspirin (75 mg/day) for women at high risk, started before 20 weeks. WHO also recommends daily calcium supplementation of 1.5–2.0 g elemental calcium for pregnant women in populations with low dietary calcium intake to reduce the risk of pre-eclampsia. Diuretics (especially thiazides) are not recommended for prevention.
Which antihypertensives are used in pre-eclampsia?
All guidelines agree that severe hypertension must be treated — most maternal deaths from hypertensive disorders come from uncontrolled severe BP (WHO). NICE offers drug treatment to all women with severe hypertension and to those whose BP stays above 140/90 mmHg, aiming for 135/85 mmHg or less. Drug details are in antihypertensive drugs.
| Setting | Drugs | Source |
|---|---|---|
| Acute severe hypertension | IV labetalol, IV hydralazine or oral immediate-release nifedipine (oral nifedipine when IV access is unavailable) | StatPearls |
| Maintenance | Oral labetalol, extended-release nifedipine, clonidine | StatPearls |
| Chronic hypertension | Labetalol first; nifedipine if labetalol unsuitable; methyldopa if both unsuitable | NICE 1.3.10 |
| Avoid | ACE inhibitors, ARBs, sodium nitroprusside (safety concerns); diuretics not for prevention | WHO |
What are the Pritchard and Zuspan magnesium sulfate regimens?
Magnesium sulfate (MgSO4) is recommended by WHO in preference to other anticonvulsants both to prevent eclampsia in severe pre-eclampsia and to treat eclampsia. It is given mainly to prevent further seizures, not to stop the fit in progress. WHO recommends the full IV or IM regimens; where the full regimen cannot be given, a loading dose followed by immediate referral is recommended.
| Regimen | Loading dose | Maintenance | Total in 24 h |
|---|---|---|---|
| Pritchard (mainly IM) | 4 g IV + 10 g IM | 5 g IM every 4 hours | ~44 g |
| Zuspan (IV) | 4 g IV | 1 g/hour IV infusion | ~28 g |
| NICE (Collaborative Eclampsia Trial) | 4 g IV over 5–15 minutes | 1 g/hour for 24 hours (24 h after the last fit) | — |
| US practice (StatPearls) | 6 g IV over 15–20 minutes | 2 g/hour | — |
- Recurrent fits: a further 2–4 g IV over 5–15 minutes (NICE)
- Duration: continue for 24 hours after delivery or after the last seizure, whichever is later
- If MgSO4 fails or is contraindicated (myasthenia gravis, heart block, renal failure, hypocalcaemia): benzodiazepines, phenytoin or levetiracetam (StatPearls)
- Fetal neuroprotection: NICE also offers IV MgSO4 with antenatal corticosteroids when early birth is planned for preterm pre-eclampsia
How is magnesium sulfate toxicity monitored and treated?
| Serum magnesium | Effect |
|---|---|
| 0.7–1.0 mmol/L (1.4–2.0 mEq/L) | Normal |
| 2.0–3.5 mmol/L (4–7 mEq/L) | Therapeutic range in pre-eclampsia/eclampsia |
| 4.0–5.0 mmol/L (8–10 mEq/L) | Loss of patellar reflex — the earliest clinical sign |
| 5.0–7.5 mmol/L (10–15 mEq/L) | Respiratory depression |
| 6.0–7.5 mmol/L (12–15 mEq/L) | Respiratory paralysis |
| 12.5–15.0 mmol/L (25–30 mEq/L) | Cardiac arrest |
Monitoring is clinical: patellar (deep tendon) reflexes, respiratory rate and urine output, with serum levels when needed. Because magnesium is excreted by the kidney, oliguria raises the risk of accumulation. If toxicity is suspected — absent reflexes or respiratory depression — stop the infusion and give 10 mL of 10% calcium gluconate IV over about 3 minutes as the antidote (StatPearls). WHO regards the capacity to give calcium gluconate as an essential part of any MgSO4 service.
How is an eclamptic fit managed?
- Call for help; protect the airway, suction secretions and prevent aspiration
- Oxygen 8–10 L/min by face mask; monitor saturation for aspiration and pulmonary oedema
- Magnesium sulfate loading and maintenance (above) to prevent recurrence
- Control severe hypertension with labetalol, hydralazine or nifedipine
- Monitor vital signs, urine output and fluid balance for at least 72 hours; check CBC, liver tests and creatinine
- Deliver once the mother is stabilised — eclampsia is an indication for delivery regardless of gestation
Eclampsia can occur before, during or after labour. Postpartum fits occur most often in the first 48 hours, and the risk remains raised through the first week; seizures more than 48 hours after delivery or before 20 weeks are atypical and need neuroimaging to exclude posterior reversible encephalopathy syndrome, cerebral venous thrombosis or stroke.
When should a woman with pre-eclampsia be delivered?
Delivery is the only definitive cure. The timing balances maternal risk against fetal prematurity.
| Gestation | NICE NG133 (Table 3) | ACOG via StatPearls |
|---|---|---|
| Before 34 weeks | Continue surveillance unless there are indications for early birth; offer IV MgSO4 and antenatal corticosteroids if birth planned | Severe features: stabilise mother and fetus; expectant management with close inpatient monitoring is usual |
| 34 to 36+6 weeks | Continue surveillance unless indicated; consider corticosteroids | Severe features at ≥ 34 weeks: deliver after stabilisation — do not delay for steroids |
| 37 weeks onwards | Initiate birth within 24–48 hours | Gestational hypertension or pre-eclampsia without severe features: deliver at 37+0 weeks |
Deliver regardless of gestation after stabilisation if there is uncontrolled BP, persistent headache, visual disturbance or epigastric pain despite treatment, eclampsia, HELLP, pulmonary oedema, stroke, myocardial infarction, suspected abruption, abnormal fetal testing or reversed umbilical artery end-diastolic flow (StatPearls). WHO recommends induction of labour for pre-eclampsia at term, and expectant management for severe pre-eclampsia before 34 weeks only when maternal and fetal condition can be monitored.