Pre-eclampsia and eclampsia

What are pre-eclampsia and eclampsia?

• 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 which 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.

How common is pre-eclampsia and eclampsia? (Epidemiology)

• Severe pre-eclampsia and eclampsia are relatively rare but serious complications of pregnancy. They are the ninth leading cause of direct maternal deaths in the UK.¹

• The incidence of pre-eclampsia varies with parity; it is around 4% in first pregnancies but less than 2% in subsequent pregnancies. The incidence of eclampsia in the UK is around 3/10,000 pregnancies.²

• Approximately (20%) of eclamptic seizures occur postnatally, the remainder being antepartum (60%) or intrapartum (20%).³

• Deaths from eclampsia and pre-eclampsia in the UK and Ireland are now at their lowest ever recorded rate: between 2019-2021 there were nine deaths.¹

• 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.

Risk factors ⁴⁵

The following features put a woman at increased risk of developing pre-eclampsia:

• African ethnicity.

• 10 years or more since the last pregnancy.

• First pregnancy, or first pregnancy with a new partner who has previously fathered a child in a pregnancy complicated by pre-eclampsia.

• Age 40 years or more, or less than 25.

• Body mass index (BMI) of 30 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:

  • Pre-existing hypertension.

  • Pre-existing chronic kidney disease.

  • Pre-existing diabetes mellitus (type 1 and type 2).

  • Certain autoimmune disease (eg, systemic lupus erythematosus (SLE) or antiphospholipid syndrome).

Causes of pre-eclampsia and eclampsia (aetiology)⁶

• 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 - for this reason, hypertension or proteinuria at less than 20 weeks gestation is not usually due to pre-eclampsia; another cause should be sought.

Symptoms of pre-eclampsia and eclampsia (presentation)²

Pre-eclampsia is defined by systolic BP >140 mm Hg or diastolic BP >90 mm Hg in the second half of pregnancy, with new onset of ≥1 of the following conditions:

• ≥1 + proteinuria on reagent stick testing.

• Other maternal organ dysfunction:

  • Renal insufficiency (creatinine 90 micromol/litre or more).

  • Liver involvement (elevated transaminases > 40 IU/L)

  • Neurological complications (eclampsia, altered mental status, blindness, stroke, clonus, severe headaches or persistent visual scotomata).

  • Haematological complications (thrombocytopenia (platelet count below 150,000/microlitre), disseminated intravascular coagulation or haemolysis).

  • Uteroplacental dysfunction (fetal growth restriction, abnormal umbilical artery doppler waveform analysis, or stillbirth).

• 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).

  • Clonus.

  • HELLP syndrome: Haemolysis, Elevated Liver enzymes, Low Platelets.

  • Papilloedema.

  • Fetal distress - reduced fetal movements.

  • Small for gestational age infant.

Assessing the risk of pre-eclampsia²

Women who are at a high-risk of pre-eclampsia should be referred for consultant-led care at booking and given aspirin 75 - 150mg daily from 12 weeks gestation. This is usually arranged in secondary care, but can be started in primary care if women book late and will not be seen in secondary care before 12 weeks.

Pre-eclampsia can be difficult to diagnose in women with pre-existing hypertension, especially if there is pre-existing renal disease with proteinuria. These women will have consultant led care and primary care guidelines are limited - a low threshold for same-day referral for obstetric review would be sensible if there is concern that pre-eclampsia is developing or progressing.

Women are considered to be at a high risk of pre-eclampsia if they have the following:

• One of the following risk factors:

  • A history of hypertensive disease during a previous pregnancy.

  • Chronic kidney disease.

  • Autoimmune disease, such as systemic lupus erythematosus or antiphospholipid syndrome.

  • Type 1 or type 2 diabetes.

  • Chronic hypertension.

• Two of the following risk factors:

  • First pregnancy.

  • Aged 40 years or older.

  • Pregnancy interval of more than 10 years.

  • Body mass index (BMI) of 35 kg/m² or greater at the first visit.

  • Family history of pre-eclampsia.

  • Multiple pregnancy.

Preventing pre-eclampsia and eclampsia²⁷

• 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.

• Use antiplatelet agents - eg, low-dose aspirin - as already discussed.

Referral⁸

Women should be referred to hospital urgently if they have:

• Raised BP - to be seen within 24 hours if ≥ 140/90 and same day if ≥160/110.

• Any clinical symptoms or signs of pre-eclampsia (severe headache, blurred vision or flashing lights in front of the eyes, severe pain below the ribs, vomiting or swelling of the face, hands or feet).

• New proteinuria of 1+ or more after 20 weeks of pregnancy.

Diagnosing pre-eclampsia and eclampsia (investigations)⁹¹⁰

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.

• New tests such as placental growth factor and a fingerprick test to assess pre-eclampsia may be used in some secondary care units.

Managing pre-eclampsia and 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 and management will need to balance the risks of the pre-eclampsia progressing against the risks of prematurity.

Magnesium sulphate is used in secondary care to treat eclampsia.

Postpartum management in primary care

Women with hypertension before pregnancy²¹¹

• Women with hypertension predating the pregnancy should have their blood pressure closely monitored by the community midwives in the days after birth and have a review with their GP or specialist at two weeks postpartum.

• If methyldopa has been used during pregnancy, it should be changed to an alternative agent with two days of delivery, as it carries a risk of depression.

• The National Institute for Health and Care Excellence (NICE) advises enalapril as a first-line anti-hypertensive for breastfeeding women, or nifedipine if the woman is of black African or Caribbean origin. Diuretics and angiotensin receptor blockers should be avoided in women who are breastfeeding.

• All antihypertensives can pass into breastmilk in small quantifies and so women should be advised to monitor their babies for symptoms of hypotension - these include drowsiness, lethargy, pallor, poor feeding or cold peripheries.

Women with pre-eclampsia who did not have hypertension before pregnancy²

• Transfer to primary care should happen only when the woman has no symptoms of pre-eclampsia, her blood pressure off treatment is 150/100 or less, and her blood tests are stable or improving.

• The discharge summary should include an individual care plan with includes the following:

  • Who will provide follow-up care, including medical review if needed.

  • Frequency of blood pressure monitoring.

  • Thresholds for reducing or stopping treatment.

  • Indications for referral to primary care for blood pressure review

  • Advice on self-monitoring for symptoms of pre-eclampsia.

• The target blood pressure is < 140/90 - when this is achieved, treatment reduction can be considered.

• For women who are not breastfeeding, ongoing anti-hypertensives should be chosen as for a member of the general population. For those who are breastfeeding, management should be as discussed in the previous section for women with chronic hypertension.

Complications of pre-eclampsia and eclampsia

• 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%.

Prognosis²

• 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%.

• For women who have had pre-eclampsia, the risk of gestational hypertension in a future pregnancy is around 7%, and the risk of pre-eclampsia is 33% if delivery was between 28 and 34 weeks gestation, 23% if delivery was between 34 and 37 weeks gestation and 16% if delivery was after 37 weeks gestation.

• Women who have had pre-eclampsia are at an increased risk of hypertension and vascular 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.