Pre-eclampsia and Eclampsia

If you'd like to support us and get something great in return, check out our PDF OSCE Checklist Booklet containing over 100 OSCE checklists in PDF format.


Introduction

Pre-eclampsia is a multisystem syndrome, developing after 20 weeks of pregnancy. It is characterised by de novo hypertension which co-exists with one or more of the following clinical features:

  • Proteinuria
  • Maternal dysfunction
  • Uteroplacental dysfunction

Hypertension may also develop after delivery but typically resolves by 6 weeks postpartum.

Pre-eclampsia is common, occurring in 2-8% of pregnancies.1

Around 0.5% of pregnant women can develop severe pre-eclampsia which can be life-threatening for both the mother and baby.2

Severe pre-eclampsia can progress to eclampsia (1 in 4000 pregnancies), a complication resulting in maternal seizures.2


Aetiology

The underlying pathophysiology of pre-eclampsia is poorly understood. It is thought to be due to abnormal placentation or maternal microvascular disease. Poor perfusion of the placenta results in oxidative stress and the release of pro-inflammatory cytokines, which then cause maternal peripheral endothelial dysfunction. This sequence of events ultimately results in the typical clinical features of pre-eclampsia:

  • Oedema and proteinuria: due to increased capillary permeability and movement of fluid into interstitial spaces.
  • Hypertension and end-organ damage (e.g. kidneys, liver): systemic vasoconstriction occurs secondary to the release of vasoconstrictive factors.

Risk factors

The risk factors for pre-eclampsia are shown in table 1.4

Table 1. Pre-eclampsia risk factors.

High risk Moderate risk

Chronic hypertension

Hypertensive disease in a previous pregnancy

Type I or type II diabetes mellitus

Chronic kidney disease

Autoimmune disease:

  • Anti-phospholipid syndrome
  • Systemic lupus erythematous

Aged 40 years or over

First pregnancy

Pregnancy interval >10 years

Multiple pregnancy

Pre-pregnancy obesity (BMI >35kg/m2)

Family history of pre-eclampsia (first-degree relative)

The risk of adverse maternal and fetal outcomes is increased if pre-eclampsia develops early, before 33 weeks gestation, or at any gestation in those with additional risk factors.


Clinical features

History

Patients with pre-eclampsia often have no symptoms.

However, symptoms of pre-eclampsia may include:

  • Headache
  • Visual disturbance: such as blurring or flashing lights
  • Swelling of the arms, legs and face
  • Nausea and vomiting
  • Abdominal pain
  • Reduced urine output

Clinical examination

Clinical signs of pre-eclampsia may include:

  • Hypertension
  • Oedema: typically in the peripheries and face
  • Epigastric/right upper quadrant tenderness
  • Hyper-reflexia and clonus (indicates an increased risk of eclamptic seizure)
  • Papilloedema

Differential diagnoses

It is important to differentiate between other hypertensive disorders of pregnancy such as:

  • Chronic hypertension: hypertension that occurs before 20 weeks gestation or persists after 12 weeks postpartum.
  • Gestational hypertension: hypertension that occurs after 20 weeks gestation that develops without any co-existing complications.
  • Pre-eclampsia superimposed on chronic hypertension: hypertension that already exists but worsens after 20 weeks gestation alongside the development of co-existing complications.

Investigations

Antenatal screening is used to detect pre-eclampsia at an early stage to allow appropriate management to prevent adverse outcomes. Antenatal appointments include assessment of blood pressure, a urine dipstick test to identify proteinuria (as well as signs of infection) and fetal heart auscultation.

Laboratory investigations

Specific blood tests performed if there is a suspicion of pre-eclampsia include:

  • FBC: low platelet count may suggest HELLP syndrome (see complications).
  • U&Es: raised urea, raised creatinine and low eGFR indicate renal impairment.
  • LFTs: raised ALT or AST indicate liver dysfunction.
  • Clotting profile: clotting may be deranged in the context of disseminated intravascular coagulation (DIC).

Placental growth factor (PIGF) supports trophoblastic growth and therefore has a role in placental angiogenesis. A blood test measuring PIGF levels can be used to aid diagnosis in pre-eclampsia, particularly in patients with chronic or gestational hypertension. Elevated levels of PIGF suggest that pre-eclampsia is unlikely to be present. However, low PIGF levels only indicate, but do not confirm a diagnosis of pre-eclampsia.

Diagnostic criteria

The diagnostic criteria for pre-eclampsia are as follows:

  • Hypertension: blood pressure of ≥140mmHg systolic or ≥90mmHg diastolic.
  • Proteinuria: ≥300 mg protein in a 24-hour urine collection, a urine protein/creatinine ratio ≥30 mg/mmol or two readings of at least ++ protein on urinary dipstick analysis.4
  • Maternal organ dysfunction: liver involvement, renal insufficiency, haematological complications (e.g. thrombocytopenia, DIC) and neurological involvement (e.g. visual disturbance).
  • Uteroplacental dysfunction: intrauterine growth restriction and stillbirth.

Management

Pre-eclampsia typically progresses throughout pregnancy and only resolves after delivery. As a result, management focuses on monitoring progression and managing risk factors until delivery is possible.

Monitoring

Monitoring of the patient’s health involves:

  • Regular blood pressure assessment
  • Regular screening for proteinuria
  • Regular blood tests including FBC, U&Es and LFTs

Regular fetal monitoring is also required for all patients with pre-eclampsia including:4

  • Cardiotocography: assessment of the fetal heartbeat.
  • Ultrasound: assessment of fetal growth and amniotic fluid levels.
  • Umbilical artery Doppler velocimetry: assessment of placental and fetal circulation.

Unless clinically indicated, only the latter two should be repeated regularly throughout pregnancy to monitor fetal development, with monitoring frequency tailored to the severity of pre-eclampsia.

Medical management

All women with pre-eclampsia and a pre-existing chronic medical condition should have a medication review to optimise their treatment.

Aspirin is thought to delay or prevent the onset of pre-eclampsia by inhibiting the inflammatory response in blood vessels. Aspirin (75-150mg once daily) should be prescribed from 12 weeks gestation until delivery for patients with one high-risk factor or two moderate risk factors.4

Antihypertensives are key to reducing cardiovascular risk, particularly stroke risk in patients with pre-eclampsia. They should be started at diagnosis with an aim of reducing blood pressure to 135/85mmHg and should be continued up to 6-12 weeks postpartum. Labetalol is a first-line agent, nifedipine is second-line and methyldopa can be used if the first two are unsuitable. Nifedipine is first-line for Afro-Caribbean patients. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and thiazide diuretics are contraindicated in pregnancy.4

Venous thromboembolism (VTE) prophylaxis is required due to an increased risk of VTE development in pre-eclampsia patients, particularly during hospital admission. Low molecular weight heparin can be used alongside physical measures such as anti-embolism stockings.

Severe pre-eclampsia

Severe pre-eclampsia is defined as a blood pressure of ≥160mmHg systolic or ≥110mmHg diastolic and requires hospital admission.

On admission, the fullPIERS (Preeclampsia Integrated Estimate of Risk) and PREP-S (Prediction model for Risks of complications in Early-onset Preeclampsia – Survival analysis model) risk scores can be used to calculate the risk of adverse maternal outcomes within 48 hours although the PREP-S score should not be used after 34 weeks gestation.4

Both scores take into consideration gestational age and clinical findings.5 6

Management of severe pre-eclampsia should be individualised. Early delivery may be considered, depending on gestational age and other factors such as:

  • Severity of pre-eclampsia
  • Speed of progression
  • Inability to control blood pressure
  • Presence of complications
  • Compromised fetal wellbeing

Complications

Maternal complications of pre-eclampsia include:

  • Multi-organ dysfunction: with progressive worsening to multi-organ failure.
  • Cardiovascular complications: particularly major events such as myocardial infarction and stroke.
  • Placental abruption.
  • Eclampsia
  • HELLP syndrome

Eclampsia

Eclampsia is defined as seizures occurring in pregnancy or within 10 days of delivery in addition to the development of at least two of the following features within 24 hours of the seizure:7

  • Hypertension
  • Proteinuria
  • Thrombocytopenia
  • Raised AST

Eclampsia develops in approximately 1 in 4000 pregnant women and has a high mortality rate (death in 1 in 50 women and 1 in 14 unborn babies).2

If eclampsia develops, it is considered an obstetric emergency requiring hospital admission. Treatment should include early delivery if possible and intravenous magnesium sulphate to treat the mother’s seizures and prevent reoccurrence. If considering early delivery, corticosteroids should be administered to accelerate fetal lung maturation if less than 34 weeks gestation.

HELLP syndrome

HELLP syndrome occurs in 10-20% of women with severe pre-eclampsia.8

HELLP syndrome develops as a result of endothelial damage and consequent thrombi formation, associated with pre-eclampsia. HELLP is an acronym which describes the characteristic features of the syndrome:

  • Haemolysis: red blood cells become damaged by the abnormal endothelium, resulting in microangiopathic haemolytic anaemia.
  • Elevated Liver enzymes: raised ALT and/or AST can occur due to hepatic sinusoid obstruction by fibrin.
  • Low Platelets: platelet levels drop below 150 x109/L due to platelet consumption as a result of thrombi formation.

A blood film from a patient with HELLP syndrome typically reveals schistocytes (fragmented red blood cells).

Early detection and aggressive management with intravenous magnesium sulphate, antihypertensivesblood products and timely delivery reduces disease progression and can help prevent adverse outcomes.


Key points

  • Pre-eclampsia is a hypertensive disorder of pregnancy caused by abnormal placentation leading to a maternal inflammatory response.
  • Most patients with pre-eclampsia are asymptomatic and diagnosed as a result of routine antenatal screening which identifies hypertension and/or proteinuria.
  • Close monitoring of both mother and fetus is key to reducing the risk of adverse outcomes associated with pre-eclampsia.
  • Management of pre-eclampsia typically involves aspirin, antihypertensive therapy and early delivery.
  • Eclampsia is a severe complication of pre-eclampsia involving the development of seizures secondary to hypertension.

Reviewer

Dr Farah Shakeel

Consultant in Obstetrics & Gynaecology


Editor

Dr Chris Jefferies


References

  1. NHS.uk. Pre-eclampsia. Published in 2018. Available from: [LINK]
  2. Royal College of Obstetricians & Gynaecologists. Pre-eclampsia. Published in 2012. Available from: [LINK]
  3. Roberts, J. Pathophysiology of ischemic placental disease. Published in 2014. Available from: [LINK]
  4. NICE. Hypertension in pregnancy: diagnosis and management. Published in 2019. Available from: [LINK]
  5. Evidencio. Prep-S: Risk of complications in early-onset pre-eclampsia. Published in 2015. Available from: [LINK]
  6. Evidencio. fullPIERS: Pre-eclampsia integrated estimate of risk. Published in 2015. Available from: [LINK]
  7. Douglas, KA., Redman CWG. Eclampsia in the United Kingdom. Published in 1994. Available from: [LINK]
  8. Haram, K., Svendsen, Einar., Abildgaard, U. The HELLP syndrome: Clinical issues and management. A Review. Published in 2009. Available from: [LINK]

 

Print Friendly, PDF & Email