Definition

New hypertension of 140/90 mmHg or higher after 20 weeks of pregnancy, plus at least one new feature from three groups. Proteinuria, quantified on a urine protein:creatinine or albumin:creatinine ratio. Maternal organ dysfunction: renal or hepatic impairment, low platelets, haemolysis, disseminated intravascular coagulation, or neurological features such as eclampsia, clonus, stroke, blindness or persistent scotomata. Uteroplacental dysfunction: fetal growth restriction, abnormal umbilical artery Doppler or stillbirth. Severe hypertension is over 160 mmHg systolic or over 110 mmHg diastolic. Proteinuria is not required.

Epidemiology

Pre-eclampsia affects between 1 and 5 in every 100 pregnancies; about 1 in 200 become severe. Eclampsia is rare, around 1 in 3000 UK pregnancies. Hypertensive disorders of pregnancy as a whole affect 8% to 10% of pregnant women. The risk factors are those that trigger aspirin prophylaxis. Recurrence after pre-eclampsia is about 1 in 6, rising to about 1 in 3 if the previous birth was at 28 to 34 weeks.

Pathophysiology

Trophoblast invasion of the maternal spiral arteries is incomplete, so those vessels stay narrow and high-resistance and the placenta is underperfused. The stressed placenta releases anti-angiogenic factors that injure maternal endothelium throughout the body. Vasoconstriction raises blood pressure and glomerular injury leaks protein. Hepatic swelling causes upper abdominal pain; cerebral oedema and vasospasm cause headache, scotomata and seizures; capillary leak floods the lungs. Platelet consumption with microangiopathic haemolysis produces HELLP syndrome. The same poor perfusion restricts fetal growth and can cause abruption or stillbirth.

First principles

Proteinuria is one way in, not the only way in

The diagnosis needs new hypertension after 20 weeks plus any one of three things: significant proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. A clean dipstick with a platelet count of 120,000/microlitre and epigastric pain is still pre-eclampsia. Anchoring on the urine is how it gets missed.¹

Drugs treat the complications; only birth treats the disease

Antihypertensives protect the maternal brain from haemorrhagic stroke; magnesium sulfate prevents and stops eclamptic seizures. Neither slows the placental process, so a pressure brought back to 130/80 mmHg does not mean the illness has stopped. Surveillance and a planned date of birth are the treatment.¹

Restrict fluid rather than resuscitate it

Endothelial leak empties the intravascular space while the tissues stay wet. Oliguria is therefore expected, and filling the patient to chase urine output floods the lungs. NICE limits maintenance fluid to 80 mL/hour and forbids a fluid preload before a low-dose epidural.¹

Timing of birth trades maternal risk against prematurity

Before 37 weeks the baby gains from every extra day in utero, so surveillance continues unless a maternal or fetal threshold is crossed. From 37+0 weeks that gain has gone and NICE says initiate birth within 24 to 48 hours. A senior obstetrician makes that call.¹

Presentation

Most cases are found by routine antenatal blood pressure and urine testing in someone who feels well. Symptoms mean late disease: severe headache, visual scotomata (dark or flashing patches in the visual field), epigastric or right upper quadrant pain and vomiting. Breathlessness, sudden facial swelling or reduced fetal movements also count. It can appear for the first time after birth.^1,2

Cardinal features

New hypertension, 140/90 mmHg or higher, after 20 weeks
Proteinuria: protein:creatinine ratio 30 mg/mmol or more, or albumin:creatinine ratio 8 mg/mmol or more
Renal or liver injury: creatinine 90 micromol/litre or more, transaminases over 40 IU/litre
Haematological injury: platelets below 150,000/microlitre, haemolysis or disseminated intravascular coagulation
Neurology: severe headache, persistent visual scotomata, clonus or altered mental state
Fetal clues: growth restriction, abnormal umbilical artery Doppler or reduced movements

Red flags

Severe hypertension: over 160 mmHg systolic or over 110 mmHg diastolic
An eclamptic seizure, or clonus and altered consciousness before one
Breathlessness, crackles or oxygen saturation below 90%: pulmonary oedema
Alanine transaminase over 70 IU/litre, or a new creatinine of 90 micromol/litre or more
Haemolysis, elevated liver enzymes and low platelets: HELLP syndrome
Abruption, reversed end-diastolic flow, a non-reassuring cardiotocograph (CTG) or stillbirth

Investigations

Blood pressure measurement and symptom review

Hypertension is 140/90 mmHg or higher; severe hypertension is over 160/110 mmHg. Ask about headache, visual scotomata and epigastric pain at every reading, and examine for clonus and chest crackles.

Expected finding: Sustained systolic pressure of 160 mmHg or higher is on its own a reason to admit.

¹

Urine protein:creatinine ratio (PCR) or albumin:creatinine ratio (ACR)

Dipstick read by an automated device is the screen; quantify any result of 1+ or more on a random sample. Do not use a first morning void or a 24-hour collection.

Expected finding: PCR 30 mg/mmol or more, or ACR 8 mg/mmol or more, is significant. Repeat on a new sample only if the diagnosis is still uncertain.

¹

FBC, U&E and LFT

Platelets, creatinine and transaminases are both diagnostic criteria and severity markers. Measure them twice weekly in pre-eclampsia, three times weekly if hypertension is severe.

Expected finding: Creatinine 90 micromol/litre or more, transaminases over 40 IU/litre, or platelets below 150,000/microlitre make the diagnosis with no proteinuria at all.

¹

Placental growth factor (PLGF)-based blood test

PLGF is a placental protein that falls when the placenta is failing. NICE recommends one test per episode, alongside standard assessment, when pre-eclampsia is suspected between 20 weeks and 36 weeks plus 6 days.

Expected finding: It helps rule the diagnosis in or out and sets how closely to monitor. It must not be used to decide on early birth.

^3,4

Fetal ultrasound, umbilical artery Doppler and cardiotocography (CTG)

Ultrasound for growth and amniotic fluid with umbilical artery Doppler at diagnosis, repeated every 2 weeks if normal. CTG, a continuous trace of fetal heart rate against uterine activity, at diagnosis and whenever the picture changes.

Expected finding: Growth restriction or abnormal Doppler is uteroplacental dysfunction and is itself diagnostic. Reversed end-diastolic flow or a non-reassuring CTG is a threshold for early birth.

¹

Management

Step	Detail	Source
Assess severity and decide on admission	A clinician trained in hypertensive disorders of pregnancy assesses every case. Admit for any of: sustained systolic 160 mmHg or higher; creatinine 90 micromol/litre or more; alanine transaminase over 70 IU/litre; platelets under 150,000/microlitre. Also admit for impending eclampsia, pulmonary oedema or suspected fetal compromise.¹	NICE NG133 1.5.1, 1.5.2
Treat hypertension to a target of 135/85 mmHg or less	Start treatment above 140/90 mmHg. Labetalol is first line: 100 mg orally twice daily, raised by 100 mg twice daily each week, to a maximum of 2400 mg daily. Continue it through labour.^1,5,6	NICE NG133 table 2, 1.5.6, 1.7.4; labetalol tablets summary of product characteristics (SmPC) 4.2
Use nifedipine, then methyldopa, if labetalol is unsuitable	Modified-release nifedipine 10 mg every 12 hours, titrated to 40 mg every 12 hours (maximum 80 mg daily). Then methyldopa 250 mg two or three times daily (maximum 3 g daily). Check the nifedipine brand: some are contraindicated in pregnancy by the manufacturer.^1,7,8,9,10	NICE NG133 1.5.6; nifedipine and methyldopa SmPCs 4.2
Stop the antihypertensives that damage the fetus	Stop ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin II receptor blockers) within 2 working days of confirming pregnancy. They cause fetal renal dysfunction, oligohydramnios, neonatal anuria and skull ossification defects. Thiazide and thiazide-like diuretics carry a risk of congenital abnormality.^1,11	NICE NG133 1.3.2 to 1.3.4; MHRA (Medicines and Healthcare products Regulatory Agency) Drug Safety Update
Bring severe hypertension down immediately	Above 160/110 mmHg use labetalol, oral nifedipine or intravenous hydralazine. Labetalol 50 mg intravenously over at least 1 minute, repeatable every 5 minutes to 200 mg; or infuse 20 mg/hour, doubled every 30 minutes to 160 mg/hour. Hydralazine 5 to 10 mg slowly intravenously, repeated after 20 to 30 minutes.^1,5,12,13	NICE NG133 1.8.6; labetalol and hydralazine injection SmPCs 4.2
Give magnesium sulfate for eclampsia, consider it in severe disease	Give it intravenously for an eclamptic fit. Consider it in severe pre-eclampsia if birth is planned within 24 hours, or with severe headache, visual scotomata, vomiting, epigastric pain, oliguria plus severe hypertension, or worsening bloods. Diazepam and phenytoin are not alternatives.^1,14	NICE NG133 1.8.1 to 1.8.3, 1.8.5
Prescribe the Collaborative Eclampsia Trial regimen	Loading dose 4 g intravenously over 5 to 15 minutes, then 1 g/hour for 24 hours, or for 24 hours after the last fit. A recurrent fit gets a further 2 to 4 g intravenously over 5 to 15 minutes. Beyond 5 to 7 days it risks neonatal hypocalcaemia and skeletal effects.^1,14,15	NICE NG133 1.8.4; magnesium sulfate SmPC 4.2
Monitor for magnesium toxicity and know the antidote	Record pulse, blood pressure, respiratory rate and patellar reflexes at least every 4 hours. Continue only while the respiratory rate is above 16 per minute, urine output above 25 mL/hour and knee jerks present. Toxicity reverses with calcium gluconate 10%, 10 to 20 mL slowly intravenously over 10 minutes (2.23 to 4.46 mmol calcium).^16,15,17	NICE NG25 1.10.5, 1.10.6; magnesium sulfate SmPC 4.9; calcium gluconate SmPC 4.2
Restrict fluids	Limit maintenance fluid to 80 mL/hour in severe pre-eclampsia unless there are measured losses such as haemorrhage. No volume expansion, and no fluid preload before a low-dose epidural. The exception is up to 500 mL crystalloid with the first intravenous hydralazine dose antenatally.¹	NICE NG133 1.7.6, 1.8.8, 1.8.11, 1.8.12
Set the monitoring intensity	Non-severe: blood pressure at least every 48 hours, with FBC, renal and liver tests twice weekly. Severe: blood pressure every 15 to 30 minutes until below 160/110 mmHg, then four times daily as an inpatient, with bloods three times weekly. Repeat ultrasound and Doppler every 2 weeks.¹	NICE NG133 table 2, 1.6.5 to 1.6.9
Plan the timing of birth	Before 37 weeks continue surveillance unless a threshold is crossed; from 37+0 weeks initiate birth within 24 to 48 hours. Thresholds: uncontrolled pressure on three antihypertensive classes; oxygen saturation below 90%; worsening liver, renal or haematological results; ongoing neurological features or eclampsia; abruption; reversed end-diastolic flow; non-reassuring CTG; stillbirth.¹	NICE NG133 1.5.7, 1.5.12, table 3
Prepare for preterm birth	A senior obstetrician decides timing; tell the anaesthetist, and neonatology if complications are expected. Before 34 weeks give antenatal corticosteroids and magnesium sulfate for fetal neuroprotection: 4 g intravenously over 15 minutes, then 1 g/hour until birth or for 24 hours. Mode of birth is a clinical decision, not automatically caesarean.^1,16	NICE NG133 1.5.8 to 1.5.11, 1.8.13, table 3; NICE NG25 1.9.2, 1.10.4
Manage blood pressure after birth	Measure blood pressure four times daily as an inpatient. Untreated antenatally: check once between days 3 and 5, and start treatment at 150/100 mmHg or higher. Already treated: continue, consider reducing below 140/90 mmHg, reduce below 130/80 mmHg. Stop methyldopa within 2 days of birth.^1,8	NICE NG133 1.5.13, 1.5.14, 1.5.16 to 1.5.18
Choose a postnatal drug that suits breastfeeding	Enalapril is the postnatal first choice, monitoring renal function and potassium. For women of black African or Caribbean family origin use nifedipine, or amlodipine if it has worked before. Where possible do not use diuretics or angiotensin receptor blockers if she is breastfeeding or expressing.¹	NICE NG133 1.9.4 to 1.9.8
Discharge and review	Check platelets, transaminases and creatinine 48 to 72 hours after birth or critical care step-down. Transfer to community care once symptoms have gone, blood pressure is 150/100 mmHg or less and bloods are stable. Review at 2 weeks if still treated, and everyone at 6 to 8 weeks with a urine dipstick.¹	NICE NG133 1.5.19 to 1.5.23, 1.5.25
Offer aspirin prophylaxis from 12 weeks	Aspirin 75 mg to 150 mg once daily from 12 weeks until birth, for one high-risk factor or more than one moderate-risk factor. Bed rest, diuretics, low molecular weight heparin, progesterone, nitric oxide donors and nutritional supplements do not prevent pre-eclampsia.^1,18	NICE NG133 1.1.2 to 1.1.5
Know which risk factors qualify	High risk, any one: hypertensive disease in a previous pregnancy, chronic kidney disease, autoimmune disease such as lupus or antiphospholipid syndrome, type 1 or type 2 diabetes, chronic hypertension. Moderate risk, more than one: nulliparity, age 40 or over, pregnancy interval over 10 years, BMI 35 kg/m2 or more, family history, multi-fetal pregnancy.¹	NICE NG133 1.1.2, 1.1.3

Illustrations

Spiral-artery remodelling in normal pregnancy and pre-eclampsiaComparative diagram of effective trophoblast-associated spiral-artery remodelling in normal pregnancy and shallow, high-resistance remodelling associated with pre-eclampsia.PassFinals · original

Placental signalling and maternal endothelial dysfunctionSchematic showing placental factors contributing to maternal vascular dysfunction, with kidney, liver, brain, lungs and uteroplacental circulation as the clinically important affected systems.PassFinals · original

Placental vasculopathy in pre-eclampsiaHistology showing decidual vasculopathy of uteroplacental vessels in pre-eclampsia; use alongside, not instead of, the current clinical diagnostic criteria.Nephron, Wikimedia Commons · CC-BY-SA-3.0

Differentials

Gestational hypertension

New hypertension after 20 weeks with no proteinuria and no organ or uteroplacental dysfunction.

Chronic hypertension

Hypertension at booking, before 20 weeks, or already treated. New organ dysfunction means superimposed pre-eclampsia.

Eclampsia

A seizure with pre-eclampsia. An emergency even if the blood pressure is unremarkable at the time.

HELLP syndrome

Haemolysis, elevated liver enzymes, low platelets, usually with epigastric pain. Blood pressure may be unimpressive.

Acute fatty liver of pregnancy

Vomiting, hypoglycaemia, coagulopathy and encephalopathy dominate. Needs urgent specialist input.

Lupus nephritis or other renal disease

Proteinuria or renal impairment present before 20 weeks. Compare with the booking bloods.

Complications

Eclamptic seizures and haemorrhagic stroke
HELLP syndrome, haemolysis and disseminated intravascular coagulation
Pulmonary oedema, acute kidney injury and the need for level 2 or 3 critical care
Placental abruption and postpartum haemorrhage
Fetal growth restriction, iatrogenic preterm birth and stillbirth
Persistent postnatal hypertension and raised lifelong cardiovascular risk

Prognosis

Most people recover completely, though blood pressure can take days to weeks to settle and may rise for the first time after birth. Later stroke risk rises about 2 to 3 times and later hypertension 2 to 5 times, so everyone needs cardiovascular risk advice at the 6 to 8 week review.

Guidelines

Hypertension in pregnancy: diagnosis and management (NG133) (NICE, 2019)
PLGF-based testing to help diagnose suspected preterm pre-eclampsia (HTG630) (NICE, 2022)
Preterm labour and birth (NG25) (NICE, 2015)