Oedema in pregnancy

Oedema in pregnancy is swelling from excess interstitial fluid, most often in the feet, ankles and legs, but also in the hands and face. Most oedema is physiological and benign, but it can be the first sign of pre eclampsia, deep vein thrombosis, heart failure, nephrotic syndrome or thyroid disease.

The main clinical points are to measure blood pressure and test urine in every woman with oedema, to distinguish symmetrical dependent swelling from unilateral swelling or sudden facial and hand swelling, and to identify cardiac, renal and venous causes early.

Clinical relevance. Oedema is present in most pregnancies, so it has low specificity as a sign. Its absence does not exclude pre eclampsia, and its presence does not diagnose it.

Physiology. Plasma volume rises by 40 to 50%, plasma oncotic pressure falls (albumin falls to 30 to 35 g/L), venous pressure in the legs rises from compression of the inferior vena cava and pelvic veins by the gravid uterus, and sodium and water retention increases. Oedema peaks in the third trimester and is worse in hot weather, after standing, and in the evening.

Mechanisms. Increased capillary hydrostatic pressure (venous obstruction, heart failure, sodium retention), reduced oncotic pressure (nephrotic syndrome, liver disease, malnutrition), increased capillary permeability (pre eclampsia, inflammation, allergy), lymphatic obstruction, and local inflammation.

Classification. By distribution: dependent and bilateral (leg and ankle), unilateral (leg), facial and hand, generalised (anasarca), and localised (hand with carpal tunnel, vulval). By character: pitting or non pitting. By time: gradual or sudden onset.

Key distinctions. Gradual bilateral ankle swelling that improves overnight is usually physiological. Sudden facial, hand or generalised swelling with hypertension suggests pre eclampsia. Unilateral swelling, particularly on the left, suggests deep vein thrombosis. Orthopnoea and a raised jugular venous pressure suggest cardiac failure. Heavy proteinuria with periorbital oedema suggests nephrotic syndrome.

History

• Onset (gradual or sudden), distribution, one or both legs, diurnal pattern, relation to standing, heat and exercise, pitting, pain, redness, skin change.
• Associated: headache, visual disturbance, epigastric pain, reduced foetal movements, rapid weight gain over days, breathlessness, orthopnoea, paroxysmal nocturnal dyspnoea, palpitations, cough, haemoptysis, chest pain, frothy urine, reduced urine output, jaundice, ascites, fatigue, cold intolerance, constipation.
• Risk factors for pre eclampsia (previous pre eclampsia, chronic hypertension, diabetes, kidney disease, autoimmune disease, multiple pregnancy, first pregnancy).
• Risk factors for venous thromboembolism: previous thrombosis, thrombophilia, obesity, immobility, caesarean section, dehydration, hyperemesis, age over 35, smoking, assisted conception, family history.
• Cardiac history: valve disease, congenital heart disease, cardiomyopathy, hypertension; peripartum cardiomyopathy in previous pregnancy.
• Renal, liver and thyroid disease; malnutrition, malabsorption, protein losing states.
• Drugs: nifedipine, amlodipine, corticosteroids, NSAIDs, pioglitazone, labetalol (mild), hormonal therapy, ritodrine and other tocolytics, intravenous fluids.
• Region specific: filariasis, malaria, schistosomiasis, anaemia and hypoproteinaemia from malnutrition.

Examination

• Blood pressure (correct cuff, repeated), pulse, respiratory rate, oxygen saturation, temperature, weight.
• Oedema: site, pitting depth, symmetry, calf circumference (measured 10 cm distal to the tibial tuberosity; a difference of 2 cm or more is significant), skin changes (warmth, redness, venous eczema, varicose veins, lymphoedema), sacral oedema in bed rest.
• Face and hands: periorbital swelling, tight rings, carpal tunnel signs (Tinel and Phalen tests).
• Cardiovascular: jugular venous pressure, heart sounds (murmurs, third sound), basal crackles, pleural effusion.
• Abdomen: ascites, hepatomegaly, uterine size for dates (polyhydramnios, multiple pregnancy), epigastric tenderness.
• Thyroid, skin and hair, delayed relaxation of reflexes (hypothyroidism).
• Neurological: reflexes and clonus.
• Bedside tests: urine dipstick for protein, capillary glucose, point of care ultrasound for deep vein thrombosis compression test where trained.

Red flags

• Blood pressure 140/90 mmHg or more with oedema, headache, visual symptoms, epigastric pain or proteinuria.
• Sudden onset facial and hand swelling, or rapid generalised swelling.
• Unilateral leg swelling, pain, warmth (deep vein thrombosis), especially left sided, with pelvic or back pain.
• Breathlessness at rest or lying flat, chest pain, tachycardia, tachypnoea or hypoxia (pulmonary oedema, pulmonary embolism, peripartum cardiomyopathy).
• Heavy proteinuria (protein to creatinine ratio over 300 mg/mmol) or frothy urine.
• Jaundice, ascites, easy bruising.
• Reduced foetal movements or growth restriction.
• Swollen, red, hot tender leg with fever (cellulitis).

Special groups. Multiple pregnancy and polyhydramnios cause more oedema. Women with heart disease, kidney disease or lupus need early assessment. Postpartum women: oedema from fluids given in labour usually resolves within a week; peripartum cardiomyopathy presents in the last month of pregnancy and up to 5 months after.

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

Physiological

• Dependent oedema of pregnancy (the commonest cause), related to venous compression, heat and standing.
• Pelvic and vulval oedema.
• Carpal tunnel syndrome (hand swelling and paraesthesia).
• Varicose veins and chronic venous insufficiency.

Hypertensive and renal

• Serious: pre eclampsia, eclampsia and HELLP syndrome.
• Serious: nephrotic syndrome (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, lupus nephritis, diabetic nephropathy).
• Acute and chronic kidney disease, acute glomerulonephritis.
• Renal vein thrombosis.

Cardiac and pulmonary

• Serious: peripartum cardiomyopathy and other cardiomyopathies.
• Serious: valvular heart disease (mitral stenosis), congenital heart disease, pulmonary hypertension.
• Arrhythmia, hypertensive heart failure, myocarditis.
• Serious: pulmonary embolism with right heart strain.

Vascular and lymphatic

• Serious: deep vein thrombosis, iliac vein thrombosis (phlegmasia).
• May Thurner syndrome (left iliac vein compression).
• Superficial thrombophlebitis.
• Lymphoedema (filariasis, previous node dissection, tumour obstruction).
• Obstruction by pelvic mass, fibroids or ovarian tumour.
• Inferior vena cava thrombosis or compression.

Hypoproteinaemic and nutritional

• Malnutrition and kwashiorkor, malabsorption, protein losing enteropathy.
• Liver disease and cirrhosis, acute fatty liver of pregnancy.
• Severe anaemia (high output state), thiamine deficiency (wet beriberi).

Endocrine and metabolic

• Hypothyroidism (non pitting myxoedema), hyperthyroidism.
• Hyperaldosteronism, Cushing syndrome.
• Diabetic nephropathy.

Drugs

• Calcium channel blockers (nifedipine, amlodipine), corticosteroids, NSAIDs, pioglitazone, magnesium and other fluids, oestrogen and progestogen therapy, tocolytic beta agonists.

Allergic and inflammatory

• Angioedema (including hereditary angioedema, which may worsen in pregnancy), allergic reaction, contact dermatitis.
• Cellulitis, erysipelas, necrotising infection (serious).
• Pelvic infection, schistosomiasis, onchocerciasis.
• Ovarian hyperstimulation syndrome (early pregnancy after fertility treatment).
• Hydrops, polyhydramnios and multiple pregnancy (disproportionate uterine growth and swelling).

Stepwise reasoning

1. Measure blood pressure with the correct technique and test urine for protein in every woman with oedema.
2. Decide whether the swelling is symmetrical dependent or has features that need investigation (unilateral, sudden, facial, with breathlessness, with heavy proteinuria).
3. Assess for pre eclampsia first, deep vein thrombosis second, and cardiac, renal and thyroid disease when the clinical picture indicates.
4. Order tests directed by findings, and avoid unnecessary imaging when the picture is physiological.

First line tests

• Blood pressure and urine dipstick, with protein to creatinine ratio (over 30 mg/mmol abnormal; over 300 mg/mmol suggests nephrotic range, with 24 hour protein over 3.5 g).
• Full blood count, urea, creatinine (over 90 micromol/L abnormal), electrolytes, liver function tests, albumin (normal in pregnancy 30 to 35 g/L; under 25 g/L suggests nephrotic syndrome or liver disease), uric acid, lactate dehydrogenase, glucose, lipid profile.
• Thyroid stimulating hormone and free thyroxine.
• Coagulation screen.

Targeted tests

• Deep vein thrombosis: compression ultrasound with Doppler of the whole leg including the iliac veins.
• The LEFt rule (left leg, circumference difference of 2 cm or more, first trimester presentation) is a low risk screen. A woman with none of the three criteria has a very low probability of deep vein thrombosis.
• If the ultrasound is negative and suspicion persists, repeat in 3 to 7 days or do MRI venography. D dimer is raised in normal pregnancy and is not useful.
• Pulmonary embolism: CT pulmonary angiography or ventilation perfusion scan after chest radiograph.
• Heart failure: electrocardiogram, chest radiograph, N terminal pro B type natriuretic peptide (a value under 300 ng/L makes heart failure unlikely; levels change little in normal pregnancy), echocardiography (left ventricular ejection fraction under 45% with new heart failure suggests peripartum cardiomyopathy).
• Nephrotic syndrome or glomerular disease: urine microscopy, urine albumin to creatinine ratio, complement, antinuclear antibodies, anti double stranded DNA, antiphospholipid antibodies, hepatitis B and C, HIV, and renal ultrasound. Renal biopsy is considered in selected women with rapid decline.
• Pre eclampsia: placental growth factor testing and soluble fms like tyrosine kinase 1 ratio where available.
• Liver disease: ultrasound, bile acids, hepatitis serology.
• Abdominal and pelvic ultrasound for ascites, pelvic mass or polyhydramnios.
• Region specific: night blood film for filariasis, urine microscopy for schistosomiasis, stool examination, malaria test.

Limitations. Pitting oedema has poor specificity in pregnancy. Calf circumference is imprecise. Compression ultrasound can miss isolated iliac vein thrombosis. Normal albumin in pregnancy is lower than non pregnant ranges, so interpretation needs trimester specific values.

Immediate steps. Treat pre eclampsia with severe features, suspected pulmonary embolism, pulmonary oedema and phlegmasia as emergencies. Give oxygen if saturation is under 94%, establish intravenous access, use the left lateral position after 20 weeks and call senior help.

Physiological oedema

• Reassure and explain that it is common and not harmful.
• Elevate the legs when sitting, rest in the left lateral position, avoid long periods of standing and wear comfortable shoes.
• Use knee length graduated compression stockings (class 1, 14 to 17 mmHg, or class 2, 18 to 24 mmHg for varicose veins) put on in the morning before rising.
• Regular walking and swimming or water immersion reduces swelling. Do not restrict salt or fluids and do not give diuretics, which can reduce placental perfusion and plasma volume.
• Review for carpal tunnel syndrome: night wrist splints in neutral position; hydrocortisone or methylprednisolone local injection for severe symptoms (methylprednisolone acetate 20 mg injected into the carpal tunnel). Surgery is rarely needed in pregnancy.

Pre eclampsia. Admit and follow the pre eclampsia regimen:

• control severe hypertension (160/110 mmHg or more) with labetalol 200 mg orally repeated once after 30 minutes, or nifedipine immediate release 10 mg orally repeated after 30 minutes (maximum 30 mg in the first hour; not sublingual), or hydralazine 5 mg intravenously (maximum 20 mg)
• magnesium sulphate 4 g intravenously over 5 to 15 minutes then 1 g/h for 24 hours
• restrict fluids to about 80 mL/h
• betamethasone 12 mg intramuscularly twice, 24 hours apart, before 34 weeks
• plan birth by gestation and severity

Deep vein thrombosis

• Start therapeutic enoxaparin 1 mg/kg subcutaneously every 12 hours (reduce to 1 mg/kg once daily for creatinine clearance under 30 mL/min) as soon as suspected, before imaging if delay is expected over 4 hours.
• Monitor anti Xa level in extremes of weight or renal impairment (target peak 0.6 to 1.0 IU/mL 4 hours after the dose).
• Continue throughout pregnancy and for at least 6 weeks after birth, with a minimum total of 3 months. Stop the morning dose before planned labour and change to prophylactic dose (24 hours before induction or caesarean section).
• Compression stockings after the acute phase for symptom relief. Mobilise once anticoagulated.
• Vena caval filter only when anticoagulation is contraindicated. Thrombolysis or catheter directed therapy in limb threatening phlegmasia, with specialist teams.
• Warfarin is avoided in pregnancy but may be used after birth, including during breastfeeding. Direct oral anticoagulants are avoided in pregnancy and breastfeeding.

Pulmonary embolism. Give therapeutic enoxaparin 1 mg/kg subcutaneously every 12 hours (once daily for creatinine clearance under 30 mL/min).

For massive embolism or when thrombolysis may be needed, use unfractionated heparin 80 units/kg bolus then 18 units/kg/h infusion, adjusted to anti Xa or activated partial thromboplastin time. Involve the multidisciplinary pulmonary embolism response team for haemodynamic instability.

Heart failure and peripartum cardiomyopathy

• Oxygen, sit upright, furosemide 20 to 40 mg intravenously (repeat after 1 to 2 hours if needed), restricted fluids and daily weights.
• Afterload reduction in pregnancy with hydralazine 25 to 50 mg orally three times daily with isosorbide dinitrate 20 mg orally three times daily. Avoid ACE inhibitors, angiotensin receptor blockers and sacubitril in pregnancy.
• Beta blocker: metoprolol succinate 12.5 to 25 mg orally daily, titrated (avoid atenolol). Postpartum, add enalapril 2.5 mg twice daily and titrate, which is compatible with breastfeeding.
• Anticoagulate with enoxaparin when ejection fraction is under 35% or when thrombus is present.
• Bromocriptine 2.5 mg orally twice daily for 2 weeks, then 2.5 mg daily for 6 weeks, with anticoagulation, may improve recovery in peripartum cardiomyopathy (evidence limited; specialist decision; it suppresses lactation).
• Plan delivery with cardiology and obstetric anaesthesia. Vaginal birth is preferred unless obstetric indications.

Nephrotic syndrome. Specialist nephrology and obstetric care. Control blood pressure, restrict salt, and give furosemide 20 to 40 mg orally once daily for troublesome oedema (watch for hypovolaemia).

Give prophylactic enoxaparin 40 mg subcutaneously once daily when albumin is under 25 g/L (therapeutic dose if thrombosis). Treat the cause: corticosteroids and calcineurin inhibitors for steroid responsive disease, hydroxychloroquine and prednisolone for lupus nephritis. Renal biopsy is deferred until postpartum unless rapidly progressive.

Hypothyroidism. Increase levothyroxine by about 25 to 30% (two additional tablets each week) when pregnancy is confirmed, and titrate to thyroid stimulating hormone under 2.5 mIU/L; check every 4 to 6 weeks in the first half of pregnancy. Start levothyroxine 1.6 microgram/kg daily for new overt disease, taking it 4 hours apart from iron and calcium.

Drug induced oedema. Reduce or change calcium channel blockers (switch nifedipine to labetalol) when oedema is troublesome and blood pressure allows. Avoid NSAIDs after 20 weeks.

Cellulitis. Flucloxacillin 500 mg to 1 g orally four times daily for 5 to 7 days (intravenous 1 to 2 g every 6 hours for severe illness); clarithromycin 500 mg twice daily for penicillin allergy. Admit for necrotising infection with broad spectrum antibiotics and surgery.

Lymphatic filariasis. Diethylcarbamazine and albendazole are avoided during pregnancy. Postpone mass drug treatment, give skin care, leg elevation and treat infection, and treat after birth and weaning.

Hereditary angioedema. C1 esterase inhibitor concentrate 20 units/kg intravenously for attacks (safe in pregnancy); avoid oestrogens and ACE inhibitors. Specialist care.

Special groups. Pre eclampsia and pulmonary embolism can coexist. Postpartum oedema resolving with diuresis; persistent oedema with breathlessness needs echocardiography.

Monitoring. Blood pressure and urine protein at each antenatal visit for all women. For unilateral swelling, repeat compression ultrasound if the first is negative. For heart failure, daily weight, fluid balance and electrolytes. Follow serum albumin and protein excretion in nephrotic syndrome.

Referral and escalation. Refer the same day to the obstetric team for oedema with hypertension, proteinuria or symptoms. Refer urgently to vascular or haematology services for suspected deep vein thrombosis in pregnancy. Refer to cardiology for suspected cardiomyopathy or valve disease, nephrology for nephrotic syndrome, and endocrinology for thyroid disease.

Admission criteria. Hypertension with oedema, symptoms of severe disease, suspected deep vein thrombosis or pulmonary embolism, breathlessness or hypoxia, heavy proteinuria, cellulitis with systemic illness, or rapid generalised swelling.

Discharge and follow up. Discharge physiological oedema with advice and routine antenatal care. Review women with unexplained oedema within 1 week with blood pressure and urine testing.

Safety netting. Return at once for headache, visual change, upper abdominal pain, sudden swelling of the face or hands, breathlessness, chest pain, one swollen painful leg, reduced urine, or reduced foetal movements.