Hypertension in pregnancy

Hypertension in pregnancy is a blood pressure of 140/90 mmHg or more on two readings at least 4 hours apart (or 160/110 mmHg or more confirmed within 15 minutes), found in pregnancy or the first 6 weeks after birth. Birth is the only cure for pre eclampsia.

The main clinical points are:

• Separate chronic hypertension, gestational hypertension and pre eclampsia.
• Recognise severe disease and organ dysfunction early.
• Control severe hypertension within an hour.
• Prevent eclampsia with magnesium sulphate.
• Time delivery by gestation and severity.

Clinical relevance. Hypertensive disorders cause a large share of maternal deaths (stroke, eclampsia, HELLP syndrome, pulmonary oedema, renal failure, placental abruption), and of stillbirth, growth restriction and preterm birth. The women carry higher lifelong cardiovascular and renal risk.

Physiology. Blood pressure falls in the first half of pregnancy because of vasodilatation, reaches its lowest point at 16 to 20 weeks, and returns toward the pre pregnancy level by term. Postpartum blood pressure peaks on days 3 to 6.

Mechanisms. Pre eclampsia begins with abnormal placentation and reduced spiral artery remodelling. Anti angiogenic factors are then released (soluble fms like tyrosine kinase 1) and placental growth factor falls. This causes widespread endothelial dysfunction, vasospasm, capillary leak and hypercoagulability.

Classification.

• Chronic hypertension: present before pregnancy or diagnosed before 20 weeks.
• Gestational hypertension: new hypertension after 20 weeks without proteinuria or organ dysfunction, resolving by 12 weeks after birth.
• Pre eclampsia: new hypertension after 20 weeks with proteinuria or maternal organ dysfunction or uteroplacental dysfunction.
• Superimposed pre eclampsia: pre eclampsia in a woman with chronic hypertension.
• Eclampsia: seizures from pre eclampsia.
• HELLP syndrome: haemolysis, elevated liver enzymes, low platelets.

Severity and timing.

• Mild to moderate hypertension: 140/90 to 159/109 mmHg.
• Severe hypertension: 160/110 mmHg or more.
• Early onset pre eclampsia: before 34 weeks. Late onset: from 34 weeks.
• Postpartum pre eclampsia: new onset up to 6 weeks after birth.

Key distinctions. Hypertension before 20 weeks suggests chronic hypertension (or molar pregnancy, renal disease, or twins). Proteinuria is not required for the diagnosis of pre eclampsia if organ dysfunction is present. Severe headache, visual disturbance, epigastric pain, hyperreflexia with clonus and pulmonary oedema indicate severe disease whatever the pressure.

History

• Gestation, blood pressure at booking and earlier visits, pre pregnancy blood pressure, urine protein results.
• Symptoms of severe disease: headache (persistent, frontal), visual disturbance (blurring, flashing lights, scotomata), epigastric or right upper quadrant pain, nausea and vomiting, rapid swelling of face, hands and feet, breathlessness, reduced foetal movements, vaginal bleeding, seizures.
• Risk factors for pre eclampsia, high risk: previous pre eclampsia, chronic hypertension, diabetes, chronic kidney disease, autoimmune disease (systemic lupus erythematosus, antiphospholipid syndrome).
• Risk factors for pre eclampsia, moderate risk: first pregnancy, age 40 years or more, interval over 10 years since a previous pregnancy, body mass index 35 or more, family history of pre eclampsia, multiple pregnancy, assisted conception, new partner.
• Medical history: renal disease, endocrine disease (thyroid, aldosteronism, phaeochromocytoma), aortic coarctation, sleep apnoea, migraine.
• Drugs: NSAIDs, decongestants, stimulants, cocaine, corticosteroids, ciclosporin, combined hormonal contraceptives before pregnancy, herbal products containing liquorice, current antihypertensives (ACE inhibitors, angiotensin receptor blockers, atenolol).
• Obstetric: previous pregnancy complications, foetal growth restriction, stillbirth, abruption.
• Social: smoking, alcohol, distance to hospital, ability to monitor blood pressure at home.

Examination

• Blood pressure: seated with the arm at heart level, correct cuff size (a large cuff when the upper arm circumference is over 33 cm). Use a validated automated device or manual measurement, with diastolic read at Korotkoff phase V. Repeat after 15 minutes if raised. Compare both arms once.
• Pulse, respiratory rate, oxygen saturation, temperature, weight, oedema (face, hands, legs), jaundice, pallor.
• Neurological: reflexes, clonus (more than 3 beats), visual fields, fundi, level of consciousness.
• Chest: crackles (pulmonary oedema). Heart: murmurs, displaced apex, radiofemoral delay.
• Abdomen: epigastric and right upper quadrant tenderness, fundal height, uterine tenderness and tone, foetal lie.
• Foetal assessment: heart rate by auscultation, cardiotocography from viability.
• Bedside tests: urine dipstick for protein, capillary glucose, ketones.

Red flags

• Blood pressure 160/110 mmHg or more.
• Severe headache, visual disturbance, epigastric pain, vomiting, clonus, confusion or seizure.
• Breathlessness, hypoxia, crackles (pulmonary oedema).
• Platelets under 100 x 10^9/L, aspartate or alanine aminotransferase over 70 IU/L, creatinine over 90 micromol/L, haemolysis.
• Oliguria (under 0.5 mL/kg/h for 6 hours), or rising creatinine.
• Vaginal bleeding, abdominal pain, tense uterus (abruption).
• Abnormal foetal heart rate, absent end diastolic flow, reduced movements.
• Onset before 20 weeks or after 6 weeks postpartum (suggesting another cause).

Special groups.

• Chronic kidney disease, diabetes, lupus and multiple pregnancy raise the risk of superimposed pre eclampsia.
• Women of African ancestry have higher rates of severe disease.
• Postpartum women: monitor blood pressure on days 3 to 6.
• Region specific: late booking, absent blood pressure checks and delay in reaching hospital contribute to eclampsia deaths.

Organised by diagnosis. Each cause is common unless marked serious or uncommon.

Hypertensive disorders of pregnancy

• Chronic essential hypertension.
• Gestational hypertension.
• Serious: pre eclampsia (early and late onset), superimposed pre eclampsia.
• Serious: eclampsia and HELLP syndrome.
• White coat hypertension and masked hypertension.
• Postpartum hypertension and postpartum pre eclampsia.

Secondary hypertension

• Chronic kidney disease (glomerulonephritis, diabetic nephropathy, reflux nephropathy, polycystic kidney disease, lupus nephritis).
• Renovascular disease (fibromuscular dysplasia).
• Primary aldosteronism.
• Serious: phaeochromocytoma (paroxysmal severe hypertension, headache, sweating, palpitations).
• Cushing syndrome, thyroid disease, hyperparathyroidism.
• Aortic coarctation.
• Obstructive sleep apnoea.

Conditions that mimic or overlap with pre eclampsia

• Serious: acute fatty liver of pregnancy.
• Serious: thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome.
• Systemic lupus erythematosus with nephritis and antiphospholipid syndrome.
• Intrahepatic cholestasis of pregnancy.
• Gestational thrombocytopenia and immune thrombocytopenia.
• Gallbladder disease, pancreatitis, hepatitis.
• Molar pregnancy and twin pregnancy (early hypertension).

Drugs and substances

• NSAIDs, sympathomimetics, decongestants, cocaine, amphetamines, corticosteroids, ciclosporin, tacrolimus, erythropoietin, liquorice, caffeine excess.
• Alcohol withdrawal, pain, anxiety.

Other causes of raised pressure with neurological signs

• Serious: posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome.
• Serious: intracerebral haemorrhage, subarachnoid haemorrhage, cerebral venous thrombosis.

Stepwise reasoning

1. Confirm hypertension with correct technique and repeat readings; exclude white coat effect by home or ambulatory monitoring when readings are borderline.
2. Classify by timing (before or after 20 weeks), proteinuria, and organ dysfunction.
3. Look for severe features and treat severe hypertension at once.
4. Assess the foetus (growth, liquor, Doppler, cardiotocography).
5. Plan monitoring or admission, and delivery.

First line tests

• Urine protein: dipstick (1+ or more), then protein to creatinine ratio (over 30 mg/mmol is abnormal) or 24 hour collection (over 300 mg). Repeat quantification is not needed once proteinuria is confirmed, because the amount does not predict outcome.
• Full blood count (platelets), urea, creatinine (over 90 micromol/L or a doubling is abnormal), electrolytes.
• Liver function tests (aspartate or alanine aminotransferase over 70 IU/L, or twice the upper limit), lactate dehydrogenase (over 600 IU/L), uric acid, glucose.
• Haemolysis screen (film, haptoglobin, bilirubin), coagulation screen with fibrinogen.
• Cardiotocography, ultrasound for growth, liquor volume and umbilical artery Doppler.
• Placental growth factor testing, or soluble fms like tyrosine kinase 1 to placental growth factor ratio where available.
• A ratio of 38 or less rules out pre eclampsia for 1 week. A ratio over 85 before 34 weeks (over 110 from 34 weeks) supports the diagnosis.
• Placental growth factor under 100 pg/mL is abnormal and under 12 pg/mL is severely abnormal.

Diagnostic criteria for pre eclampsia. New hypertension after 20 weeks plus one or more of:

• Proteinuria.
• Creatinine over 90 micromol/L.
• Transaminases over 70 IU/L, or severe right upper quadrant or epigastric pain.
• Platelets under 100 x 10^9/L.
• Haemolysis.
• Pulmonary oedema.
• Neurological features (severe headache, visual disturbance, clonus, seizure, stroke).
• Foetal growth restriction, abnormal umbilical artery Doppler or stillbirth.

Targeted tests

• Chronic hypertension before pregnancy or early: renal ultrasound, urine albumin to creatinine ratio, electrolytes (hypokalaemia suggests aldosteronism), plasma or urinary metanephrines for suspected phaeochromocytoma, thyroid function, electrocardiogram and echocardiography.
• Antiphospholipid antibodies and complement for suspected lupus or antiphospholipid syndrome.
• Fasting bile acids for pruritus.
• ADAMTS13 activity when platelets are low with severe haemolysis and raised creatinine.
• Neuroimaging (MRI with venography) for seizures with atypical features, focal deficit or persistent headache.

Home and ambulatory monitoring. Validated home devices help in mild hypertension; a mean home pressure of 135/85 mmHg or more is abnormal.

Limitations. Dipstick proteinuria is unreliable (false positives with concentrated urine and infection). Pre eclampsia can occur without proteinuria. Blood pressure readings depend heavily on cuff size and technique. Biomarker ratios do not replace clinical assessment.

Immediate steps. Treat blood pressure of 160/110 mmHg or more as an emergency.

• Admit. Position the woman in the left lateral position after 20 weeks.
• Establish intravenous access and send bloods.
• Begin continuous monitoring: blood pressure every 15 minutes, saturation, urine output by catheter.
• Call senior obstetric, anaesthetic and neonatal help.

Severe hypertension: first line drugs (aim for systolic 140 to 150 mmHg and diastolic 90 to 100 mmHg within 30 to 60 minutes)

• Labetalol 200 mg orally, repeated once after 30 minutes if needed.
• Alternatively give intravenous labetalol 20 mg over 2 minutes, then 40 mg, 80 mg and 80 mg at 10 minute intervals to a total of 220 mg. Or give an infusion starting at 20 mg/h and doubling every 30 minutes to a maximum of 160 mg/h.
• Avoid labetalol in asthma, heart block and acute heart failure. Maintenance is 200 mg orally two to three times daily (maximum 2400 mg daily).
• Nifedipine immediate release 10 mg orally, repeated after 30 minutes (maximum 30 mg in the first hour; not sublingual). Then give modified release 10 to 20 mg orally twice daily (maximum 80 mg daily).
• With nifedipine, headache, flushing and tachycardia are common. Severe hypotension can follow with magnesium sulphate, though the interaction is uncommon.
• Hydralazine 5 mg intravenously over 5 to 10 minutes, repeated at 20 minutes (maximum 20 mg). Expect tachycardia and possible foetal heart rate abnormality. Give a crystalloid bolus of 250 to 500 mL beforehand only if hypovolaemic.
• Avoid sodium nitroprusside except in extreme refractory cases (cyanide toxicity to the foetus), and avoid diuretics unless pulmonary oedema develops.

Chronic and mild to moderate hypertension

• Start treatment at 140/90 mmHg or more with a target of about 135/85 mmHg. Avoid falls of diastolic pressure under 80 mmHg that may reduce placental perfusion.
• Labetalol 100 to 200 mg orally two to three times daily (maximum 2400 mg daily).
• Alternatively give nifedipine modified release 10 to 20 mg orally twice daily (maximum 80 mg daily).
• Alternatively give methyldopa 250 mg orally three times daily, increased every 2 days to a maximum of 3 g daily. It causes sedation. Avoid in depression and stop within 2 days of birth because of postnatal depression risk.
• Stop ACE inhibitors, angiotensin receptor blockers, renin inhibitors and mineralocorticoid antagonists (foetal renal damage, oligohydramnios and skull defects). Avoid atenolol (growth restriction).
• Thiazide and other diuretics are continued only if already established and effective, with electrolyte checks.
• Stop statins in pregnancy unless specialist advice.

Prevention.

• Aspirin 75 to 150 mg orally once daily at night from 12 weeks (before 16 weeks if possible) until 36 weeks, for women with one high risk factor or two or more moderate risk factors. Take with food. Avoid with aspirin allergy and peptic ulcer. Some services continue it until birth.
• Calcium 1.5 to 2 g elemental calcium daily from 20 weeks in populations with low dietary intake (evidence limited to such settings).

Magnesium sulphate (prevention and treatment of eclampsia). Give for severe pre eclampsia with neurological features, imminent eclampsia, or eclampsia.

• Give 4 g intravenously over 5 to 15 minutes, then 1 g/h for 24 hours after birth or the last seizure. For a further seizure give 2 g over 5 minutes.
• Monitor respiratory rate (over 12 breaths/min), oxygen saturation, patellar reflexes (loss indicates levels near 3.5 to 5 mmol/L), and urine output (over 0.5 mL/kg/h).
• In renal impairment (creatinine over 100 micromol/L) reduce maintenance to 0.5 g/h and measure levels (therapeutic 2 to 4 mmol/L).
• Antidote: calcium gluconate 10% 10 mL (1 g) intravenously over 10 minutes.
• Where infusion pumps are unavailable, use 4 g intravenously over 5 to 10 minutes plus 10 g intramuscularly (5 g into each buttock). Then give 5 g intramuscularly every 4 hours into alternate buttocks, if reflexes are present, respiratory rate is over 16 breaths/min and urine output is over 100 mL in the preceding 4 hours.

Fluid and haemodynamic care. Restrict total fluids to about 80 mL/h (1 mL/kg/h) to reduce pulmonary oedema. Treat pulmonary oedema with oxygen, furosemide 40 mg intravenously, and glyceryl trinitrate infusion 5 microgram/min titrated every 3 to 5 minutes to a maximum of 100 microgram/min. Avoid fluid loading.

Foetal lung maturity.

• Betamethasone 12 mg intramuscularly, two doses 24 hours apart (or dexamethasone 6 mg intramuscularly every 12 hours for four doses). Give from 24 weeks to 34 weeks and 6 days (and up to 36 weeks and 6 days on specialist advice) when delivery is expected within 7 days.
• Magnesium sulphate for neuroprotection when birth is imminent before 30 weeks: 4 g intravenously over 15 to 30 minutes, then 1 g/h until birth for up to 24 hours. The dose already running for seizure prevention covers this.

Timing of birth

• Gestational hypertension: birth at 37 to 39 weeks (induction at 38 weeks if blood pressure is controlled).
• Chronic hypertension: birth at 38 to 39 weeks if controlled, earlier with complications.
• Pre eclampsia from 37 weeks: induce labour within 24 to 48 hours.
• Pre eclampsia before 34 weeks without severe features: expectant management in a unit with neonatal intensive care. Control blood pressure, check bloods twice weekly, and perform serial growth and Doppler scans. Deliver at 37 weeks, or earlier if the condition worsens.
• Severe features, HELLP syndrome, eclampsia, pulmonary oedema, abruption, refractory hypertension, deteriorating renal or hepatic function, foetal compromise or reversed end diastolic flow: stabilise (blood pressure, magnesium, steroids if time allows) and deliver.
• Vaginal birth is preferred when feasible. Use caesarean section for obstetric indications or if birth is not expected within a reasonable time.
• Platelet count of 75 x 10^9/L or more allows neuraxial anaesthesia. Give platelets to keep a count over 50 x 10^9/L for caesarean section. Avoid ergometrine (use oxytocin) for third stage.

Eclampsia.

• Call for help, protect the airway, use the left lateral position, and give oxygen 10 to 15 L/min.
• Give magnesium sulphate 4 g intravenously over 5 to 15 minutes then 1 g/h. Control blood pressure, check glucose, and begin delivery planning once stable.
• Do not rush delivery during or immediately after a seizure.
• If seizures recur on magnesium, give a further 2 g and consider other causes, imaging and a second anticonvulsant (lorazepam 4 mg intravenously, repeated once after 10 minutes).

HELLP syndrome. Admit to a high dependency unit, control blood pressure, give magnesium sulphate, correct coagulopathy, and deliver. Give corticosteroids for lung maturity if under 34 weeks. Monitor platelets, liver tests and lactate dehydrogenase every 6 to 12 hours. Expect a nadir 24 to 48 hours after birth.

Postpartum care

• Check blood pressure at least four times daily while in hospital, and at least once on days 3 to 5.
• Treat blood pressure of 150/100 mmHg or more. Labetalol, nifedipine modified release, amlodipine 5 to 10 mg orally once daily and enalapril 5 mg orally once daily are acceptable during breastfeeding.
• Enalapril may be increased to 20 mg twice daily. Avoid it in renal artery stenosis and hyperkalaemia.
• Furosemide 20 to 40 mg orally once daily for 3 to 5 days may speed blood pressure control.
• NSAIDs are acceptable for postpartum pain with blood pressure monitoring in hypertensive women without renal impairment. Paracetamol 1 g every 4 to 6 hours (maximum 4 g daily) is first line.
• Reduce treatment gradually when blood pressure is under 130/80 mmHg. Stop methyldopa at birth.
• Give thromboprophylaxis with enoxaparin 40 mg subcutaneously once daily to admitted women with pre eclampsia, caesarean section or other risk factors. Use 20 mg under 50 kg and 60 mg for 91 to 130 kg, and reduce for creatinine clearance under 30 mL/min. Continue for 6 weeks after birth when risk is high.
• Long term: annual blood pressure, lipid and glucose checks, and weight control, because pre eclampsia raises later cardiovascular and renal disease risk.

Special groups.

• Chronic kidney disease: nephrology co care and urine albumin monitoring.
• Twin pregnancy: higher risk and earlier delivery planning.
• Women with diabetes: tighter glucose control.
• Women with HIV: continue antiretroviral therapy and avoid drug interactions with calcium channel blockers.
• Region specific: magnesium sulphate availability and referral systems determine eclampsia mortality. Use the intramuscular regimen and transport at once.

Monitoring. Blood pressure at least four times daily, urine output, fluid balance, reflexes, saturation, cardiotocography daily or more often. Bloods (full blood count, creatinine, liver tests) twice weekly, or daily in severe disease. Ultrasound growth every 2 to 4 weeks.

Referral and escalation. Refer the same day to the obstetric team for blood pressure of 140/90 mmHg or more with symptoms, proteinuria or any severe reading. Refer to critical care or high dependency for eclampsia, HELLP syndrome, pulmonary oedema or refractory hypertension. Refer to the neonatal team early. Refer to nephrology, cardiology or endocrinology for secondary hypertension.

Admission criteria. Blood pressure of 160/110 mmHg or more, any symptom of severe disease, abnormal bloods, confirmed pre eclampsia (at least until stable), abnormal foetal assessment, and inability to monitor safely at home. Women with mild gestational hypertension and normal tests may be monitored as outpatients with twice weekly checks.

Discharge and follow up. Discharge when blood pressure is controlled, bloods are stable and the woman understands the warning symptoms. Postnatal review at 2 weeks and 6 weeks, with plans for the next pregnancy (aspirin from 12 weeks, early booking, pre pregnancy review).

Safety netting. Return at once for headache, visual disturbance, upper abdominal pain, vomiting, swelling, breathlessness, reduced foetal movements, bleeding, seizure or home blood pressure of 160/110 mmHg or more, including up to 6 weeks after birth.