- Pre-eclampsia is defined as pregnancy-induced hypertension in association with proteinuria (>0.3 g in 24 hours) with or without oedema. Virtually any organ system may be affected.
- Pre-eclampsia is a relatively common condition but may become life-threatening for the mother and the fetus. It is characterised by maternal hypertension, proteinuria, oedema, fetal intrauterine growth restriction and premature birth.
- Severe pre-eclampsia is defined as diastolic blood pressure (BP) of at least 110 mm Hg or systolic BP of at least 160 mm Hg, and/or symptoms, and/or biochemical and/or haematological impairment.
- In severe pre-eclampsia, the fetus and/or newborn may have neurological damage induced by hypoxia. Prompt recognition of pre-eclampsia and any signs of clinical deterioration, including a reduction in platelet count, necessitates urgent referral to secondary care to avoid the serious clinical consequences of these conditions.
- Eclampsia is defined as the occurrence of one or more convulsions superimposed on pre-eclampsia.
- Severe pre-eclampsia and eclampsia are relatively rare but serious complications of pregnancy. They are the second leading cause of direct maternal deaths in the UK.
- The incidence of severe pre-eclampsia is about 5/1,000 maternities. The incidence of eclampsia in the UK is around 5/10,000 pregnancies.
- 44% of seizures occur postnatally, the remainder being antepartum (38%) or intrapartum (18%).
- Deaths from eclampsia and pre-eclampsia in the UK and Ireland are now at their lowest ever recorded rate: between 2015-2017 there were three deaths.
- Pre-eclampsia and eclampsia also contribute substantially to the numbers of infants born preterm; half of women with severe pre-eclampsia will deliver before 36 weeks.
The following features put a woman at moderate risk of developing pre-eclampsia:
- 10 years or more since the last pregnancy.
- First pregnancy.
- Age 40 years or more.
- Body mass index (BMI) of 35 or more at presentation.
- Family history of pre-eclampsia (in mother or sister).
- Multiple pregnancy.
Women with the following conditions are at the highest risk of developing pre-eclampsia:
- Pre-eclampsia, eclampsia or hypertension in any previous pregnancy.
- Certain underlying medical conditions:
Women who have changed partner were previously thought to be at increased risk of pre-eclampsia but a large population-based cohort study refutes this. However, it did demonstrate a strong protective effect of a change in partner on the subsequent risk of pre-eclampsia occurring before 37 weeks, in women who had pre-eclampsia in their first pregnancy (OR 0.24; 95% CI, 0.07 to 0.88).
- The aetiology and pathogenesis of pre-eclampsia still remain poorly understood.
- It is characterised by suboptimal uteroplacental perfusion associated with a maternal inflammatory response and maternal vascular endothelial dysfunction. This in turn leads to vascular hyperpermeability, thrombophilia and hypertension, which may compensate for the reduced flow in the uterine arteries.
- Data suggest a protective role of heme oxygenase 1 and its metabolite carbon monoxide; of note, pre-eclampsia is less common in smokers.
- The placenta has a pivotal role in the pathogenesis of pre-eclampsia.
Pre-eclampsia is defined by systolic BP >140 mm Hg or diastolic BP >90 mm Hg in the second half of pregnancy, with ≥1+ proteinuria on reagent stick testing.
- New hypertension.
- New and/or significant proteinuria.
- Features of severe pre-eclampsia include:
- Severe headache - usually frontal.
- Sudden swelling of face, hands and feet.
- Liver tenderness.
- Visual disturbance (eg, blurring or flashing lights in front of the eyes).
- Epigastric pain and/or vomiting.
- Platelet count falling to below 100 x 109/L (a falling platelet count predicts severe disease and these women need urgent referral and further investigation).
- Abnormal liver enzymes (ALT or AST rising to above 70 IU/L).
- HELLP syndrome: Haemolysis, Elevated Liver enzymes, Low Platelets.
- Fetal distress - reduced fetal movements.
- Small for gestational age infant.
Approximately 45% of cases of eclampsia occur after delivery, most by four days postpartum but it can occur up to four weeks later.
- Use a sitting or semi-reclining position so that the arm to be used is at the level of the heart.
- Do not take the BP in the upper arm with the woman on her side, as this will give falsely lower readings.
- Korotkoff phase 5 measurements should be used for taking the diastolic pressure, except in those rare instances when sounds continue to be heard to 0 mm Hg when Korotkoff phase 4 can be used.
Frequency of community monitoring
The National Institute for Health and Care Excellence (NICE) recommends that more frequent BP measurements and urine testing should be considered for pregnant women who have any of the risk factors for pre-eclampsia and that the presence of significant hypertension and/or proteinuria should alert the healthcare professional to the need for increased surveillance.
- No predisposing factors for pre-eclampsia:
- 24 weeks of gestation to delivery - follow local protocols and the NICE antenatal guideline for low-risk multiparous women.
- One predisposing factor listed above but no factor that requires referral in early pregnancy (listed below):
- 24 to 32 weeks of gestation: minimum standard no more than a three-week interval between assessments, adjusted to individual needs and any changes during pregnancy.
- 32 weeks of gestation to delivery: minimum standard no more than two-week interval between assessments, adjusted to individual needs and any changes during pregnancy.
Women should be admitted if they have:
- Raised BP (≥140/90 mm Hg) with proteinuria ≥+1.
- Systolic BP ≥160 mm Hg.
- Diastolic BP ≥100 mm Hg.
- Any clinical symptoms or signs of pre-eclampsia.
These tests should be performed in secondary care:
- Urinalysis: send for microscopy, culture and sensitivities if proteinuria is present.
- Frequent monitoring of FBC, LFTs, renal function, electrolytes and serum urate: to identify rising values to help guide the decision as to when to deliver:
- HELLP syndrome: platelet count falling (below 100 x 109/L), abnormal liver enzymes (ALT or AST >70 IU/L).
- Clotting studies if there is severe pre-eclampsia or thrombocytopenia.
- 24-hour urine collections for protein quantification and creatinine clearance.
- Assessment of fetus - ultrasound assessment of fetal growth and the volume of amniotic fluid, and Doppler velocimetry of umbilical arteries.
- Cerebral imaging (MRI or CT) is not indicated in uncomplicated eclampsia. However, imaging is necessary to exclude haemorrhage and other serious abnormalities in women with focal neurological deficits or prolonged coma.
NB: pre-eclampsia can be difficult to diagnose in women with pre-existing hypertension, especially if there is pre-existing renal disease with proteinuria. Under these circumstances, pre-eclampsia can present in the second half of pregnancy with a surge in BP or proteinuria, or with other features such as thrombocytopenia, a raised level of liver transaminases and reduced fetal growth. Offer placental growth factor (PlGF)-based testing to help rule out pre-eclampsia between 20 weeks and up to 35 weeks of pregnancy, if women with chronic hypertension are suspected of developing pre-eclampsia.
Management in hospital is multidisciplinary with involvement of the obstetric team, anaesthetics and haematology, liaison with paediatrics and appropriate arrangements for in-utero transfer if required and once the woman's condition is stable.
Patients can usually be managed conservatively (ie without delivery of the baby) until at least 34 weeks, as long as they are haemodynamically stable, without coagulation abnormalities and in the absence of HELLP. Delivery of the placenta is the only cure for pre-eclampsia.
- Always ask about headache and epigastric pain each time BP is taken, to be alert for any indication of progression towards eclampsia.
- Assess severity of high BP:
- Mild: 140-149/90-99 mm Hg:
- Monitor BP at least four times per day.
- Twice-weekly blood tests for FBC, electrolytes, renal function and LFTs.
- Moderate: 150-159/100-109 mm Hg:
- Monitor BP at least four times per day.
- Start antihypertensive with labetalol (alternatives are methyldopa or nifedipine) to keep systolic BP <150 mm Hg and diastolic BP between 80-100 mm Hg.
- Blood tests three times per week.
- Severe: ≥160/110 mm Hg:
- Monitor BP more than four times per day, depending on circumstances.
- Start antihypertensive labetalol (alternatives are methyldopa or nifedipine) to keep systolic BP <150 mm Hg and diastolic BP between 80-100 mm Hg.
- Blood tests three times per week.
- Perform ultrasound examination to assess fetal growth and amniotic fluid volume (with umbilical artery Doppler velocimetry) and cardiotocography whenever pre-eclampsia is diagnosed.
- Repeat cardiotocography if there is a change in fetal movements, or vaginal bleeding, abdominal pain or a deterioration in maternal condition.
- Consider using either the fullPIERS or PREP-S validated risk prediction models to help guide decisions about the most appropriate place of care (such as the need for in-utero transfer) and thresholds for intervention.
- When using a risk prediction model, be aware that:
- fullPIERS is intended for use at any time during pregnancy.
- PREP-S is intended for use only up to 34 weeks of pregnancy.
- fullPIERS and PREP‑S models do not predict outcomes for babies.
Management of severe pre-eclampsia
Delivery of the fetus and placenta is the only cure. However, preterm delivery may adversely affect neonatal outcome, with complications resulting from prematurity and low birth weight. The management plan for delivery, including thresholds for early delivery, should be discussed by the consultant and the woman on an individual basis and documented in the notes.
- Antihypertensive treatment should be started in women with a systolic BP over 160 mm Hg or a diastolic BP over 110 mm Hg. In women with other markers of potentially severe disease, treatment can be considered at lower degrees of hypertension:
- Labetalol (given orally or intravenously).
- Nifedipine (oral); or
- Hydralazine (intravenous).
- Atenolol, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists and diuretics should be avoided although may be indicated postpartum.
- Antihypertensive medication should be continued after delivery, as dictated by the BP. It may be necessary to maintain treatment for up to three months, although most women can have treatment stopped before this.
- Prevention of seizures:
- Magnesium sulfate should be considered when there is concern about the risk of eclampsia. Magnesium sulfate reduces the risk of eclampsia by more than half.
- Control of seizures:
- Magnesium sulfate is the therapy of choice to control seizures. Use the Collaborative Eclampsia Trial regimen for administration of magnesium sulfate:
- A loading dose of 4 g should be given intravenously over 5 to 15 minutes, followed by an infusion of 1 g/hour maintained for 24 hours. If the woman has had an eclamptic fit, the infusion should be continued for 24 hours after the last fit.
- Recurrent fits should be treated with a further dose of 2-4 g given intravenously over 5 to 15 minutes.
- Fluid balance:
- Fluid restriction is advisable to reduce the risk of fluid overload in the intrapartum and postpartum periods. Pulmonary oedema has been a significant cause of maternal death in eclampsia/pre-eclampsia, often associated with excess fluid administration. Total fluids should usually be limited to 80 ml/hour or 1 ml/kg/hour.
- The decision to deliver should be made once the woman is stable and with appropriate senior personnel present.
- If the fetus is less than 34 weeks of gestation and delivery can be deferred, corticosteroids should be given, although after 24 hours the benefits of conservative management should be reassessed.
- Conservative management at very early gestations may improve the perinatal outcome but must be carefully balanced with maternal well-being.
- The mode of delivery should be determined after considering the presentation of the fetus and the fetal condition, together with the likelihood of success of induction of labour after assessment of the cervix.
- Measure blood pressure continually.
- The third stage should be managed with 5 units of intramuscular/slow intravenous Syntocinon®. Ergometrine and Syntometrine® should not be given for prevention of haemorrhage, as this can further increase the BP.
- Prophylaxis against thromboembolism should be considered.
Management of eclampsia
- The patient should be placed in the left lateral position and the airway secured.
- Oxygen should be administered.
- Treatment and prophylaxis of seizures:
- Magnesium sulfate is the anticonvulsant drug of choice. See above.
- Intubation may become necessary in women with repeated seizures in order to protect the airway and ensure adequate oxygenation.
- Treatment of hypertension:
- Reduction of severe hypertension (BP >160/110 mm Hg or mean arterial pressure >125 mm Hg) is essential to reduce the risk of cerebrovascular accident. Treatment may also reduce the risk of further seizures.
- Intravenous labetalol or hydralazine are the two most commonly used drugs. Both may precipitate fetal distress and therefore continuous fetal heart rate monitoring is necessary.
- Fluid therapy:
- Close monitoring of fluid intake and urine output is mandatory.
- Do not preload the circulation with colloid prior to regional anaesthesia.
- The definitive treatment of eclampsia is delivery. Attempts to prolong pregnancy in order to improve fetal maturity are unlikely to be of value.
- However, it is unsafe to deliver the baby of an unstable mother even if there is fetal distress. Once seizures are controlled, severe hypertension treated and hypoxia corrected, delivery can be expedited.
- Vaginal delivery should be considered but caesarean section is likely to be required particularly in primigravidae, if well before term or with an unfavourable cervix.
- After delivery, high-dependency care should be continued for a minimum of 24 hours.
- After birth, stop methyldopa (if used) within two days and avoid diuretics if breastfeeding, measuring BP at least four times daily whilst in hospital. Continue to ask about headaches and epigastric pain whenever BP is taken. Measure FBC, LFT and creatinine 72 hours after birth and only repeat after this if abnormal. Step down care (ie to community midwives) when BP is <150/100 mm Hg and blood tests are stable or improving without any pre-eclamptic symptoms.
- Reduce BP treatment if BP falls to <130/80 mm Hg (consider reducing when <140/90 mm Hg).
- Measure BP every 1-2 days for up to two weeks after transfer to community care (or until antihypertensive treatment is stopped). Continue to monitor (ie weekly) and arrange a medical review at two weeks postpartum if still requiring medication. Monitor BP at least until the six-week check where a urine dip should also be performed (and arrange repeat FBC, creatinine and LFTs unless they have previously returned to normal).
- Offer enalapril to treat hypertension in women during the postnatal period, with appropriate monitoring of maternal renal function and maternal serum potassium. For women of black African or Caribbean family origin with hypertension during the postnatal period, consider antihypertensive treatment with nifedipine or amlodipine if the woman has previously used this to successfully control her blood pressure. For women with hypertension in the postnatal period, if blood pressure is not controlled with a single medicine, consider a combination of nifedipine or amlodipine) and enalapril. If this combination is not tolerated or is ineffective, consider either adding atenolol or labetalol to the combination treatment or swapping the medicines already being used for atenolol or labetalol. When treating women with antihypertensive medication during the postnatal period, use medicines that are taken once daily when possible.
All patients need careful follow-up and a formal postnatal review to establish if there is chronic hypertension, proteinuria or liver damage.
- Eclampsia is usually part of a multisystem disorder. Associated complications include haemolysis, HELLP syndrome (3%), disseminated intravascular coagulation (3%), acute kidney injury (4%) and adult respiratory distress syndrome (3%).
- Pre-eclampsia can progress to eclampsia with epileptic fits and sometimes other neurological symptoms, including focal motor deficits and cortical blindness.
- Cerebrovascular haemorrhage is a complicating factor in 1-2%.
- Pre-eclampsia is also associated with intrauterine growth restriction, low birth weight, preterm delivery, small for gestational age infants and infant respiratory distress syndrome.
- The maternal mortality rate of eclampsia is 1.8%.
- Pre-eclampsia recurs in around 15% of women who had pre-eclampsia in their first pregnancy, although this risk may be as high as 25% if the pre-eclampsia led to birth before 34 weeks and as high as 50% if birth was before 28 weeks.
- Women who have had pre-eclampsia are at an increased risk of hypertension and heart disease in later life, although it is not known whether this is due to an effect of pre-eclampsia or a common cause of both cardiovascular disease and pre-eclampsia.
- There is an increased risk of cardiovascular death in women with preterm pre-eclampsia in their first pregnancy and who have no subsequent children.
- Identification and appropriate action for those women with known risk factors at booking.
- Early recognition and appropriate action for those women with symptoms and signs of pre-eclampsia.
- Antiplatelet agents - eg, low-dose aspirin - have moderate benefits when used for prevention of pre-eclampsia. One study has shown that low-dose aspirin has a small effect in the prevention of pre-eclampsia in women considered to be at high risk for the disease but it is not effective in reducing the risk in those at low risk.
- In the UK, NICE recommends 75-100 mg aspirin from 12 weeks of gestation to women at risk of pre-eclampsia. Aspirin is also recommended to women who have two or more of the moderate risk factors (see 'Risk Factors', above).
- High-dose calcium supplementation (≥1 g/day) may reduce the risk of pre-eclampsia and preterm birth, particularly for women with low calcium diets (low-quality evidence). The treatment effect may be overestimated due to small-study effects or publication bias. It reduces the occurrence of the composite outcome 'maternal death or serious morbidity', but not stillbirth or neonatal high care admission. There was an increased risk of HELLP syndrome with calcium supplementation, which was small in absolute numbers. The limited evidence on low-dose calcium supplementation suggests a reduction in pre-eclampsia, hypertension and admission to neonatal high care, but needs to be confirmed by larger, high-quality trials.
Further reading and references
PlGF-based testing to help diagnose suspected pre-eclampsia (Triage PlGF test, Elecsys immunoassay sFlt-1/PlGF ratio, DELFIA Xpress PlGF 1-2-3 test, and BRAHMS sFlt-1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio); NICE Diagnostics guidance, May 2016
Magley M, Hinson MR; Eclampsia
Wikstrom AK, Gunnarsdottir J, Cnattingius S; The paternal role in pre-eclampsia and giving birth to a small for gestational age infant a population-based cohort study. BMJ Open. 2012 Aug 30
Uzan J, Carbonnel M, Piconne O, et al; Pre-eclampsia: pathophysiology, diagnosis, and management. Vasc Health Risk Manag. 20117:467-74. doi: 10.2147/VHRM.S20181. Epub 2011 Jul 19.
Bramham K, Nelson-Piercy C, Brown MJ, et al; Postpartum management of hypertension. BMJ. 2013 Feb 25346:f894. doi: 10.1136/bmj.f894.
Hypertension in pregnancy: diagnosis and management; NICE Guidance (June 2019)
Duley L, Gulmezoglu AM, Henderson-Smart DJ, et al; Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010 Nov 10(11):CD000025. doi: 10.1002/14651858.CD000025.pub2.
Johnson DD; Induced labour for pre-eclampsia and gestational hypertension. Lancet. 2009 Aug 3.
Hernandez-Diaz S, Toh S, Cnattingius S; Risk of pre-eclampsia in first and subsequent pregnancies: prospective cohort study. BMJ. 2009 Jun 18338:b2255. doi: 10.1136/bmj.b2255.
Bellamy L, Casas JP, Hingorani AD, et al; Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007 Nov 10335(7627):974. Epub 2007 Nov 1.
Skjaerven R, Wilcox AJ, Klungsoyr K, et al; Cardiovascular mortality after pre-eclampsia in one child mothers: prospective, population based cohort study. BMJ. 2012 Nov 27345:e7677. doi: 10.1136/bmj.e7677.
Duley L, Henderson-Smart Dj, Meher S, et al; Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2007 Apr 18(2):CD004659.
Trivedi NA; A meta-analysis of low-dose aspirin for prevention of preeclampsia. J Postgrad Med. 2011 Apr-Jun57(2):91-5. doi: 10.4103/0022-3859.81858.
Hofmeyr GJ, Lawrie TA, Atallah AN, et al; Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2018 Oct 110:CD001059. doi: 10.1002/14651858.CD001059.pub5.