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Pre-eclampsia is one of several hypertensive disorders that can occur during pregnancy.
It is a placental disease, which affects up to 5% of women in their first pregnancy. In its most severe form, it can result in catastrophic maternal and/or fetal compromise.
In this article, we shall look at the risk factors, clinical features and management of pre-eclampsia.
The exact mechanism of pre-eclampsia is unclear. However, most current theories attribute pre-eclampsia to poor placental perfusion, secondary to abnormal placentation.
In normal placentation, the trophoblast invades the myometrium and the spiral arteries of the uterus, destroying the tunica muscularis media. This renders the spiral arteries dilated and unable to constrict, providing the pregnancy with a high flow, low resistance circulation.
In pre-eclampsia, the remodelling of spiral arteries is incomplete. A high resistance, low-flow uteroplacental circulation develops, as the constrictive muscular walls of the spiral arterioles are maintained.
The resultant increase in blood pressure, combined with hypoxia and oxidative stress from inadequate uteroplacental perfusion, leads to a systemic inflammatory response and endothelial cell dysfunction (resulting in leaky blood vessels).
The risk factors for pre-eclampsia can be divided into moderate risk and high risk:
|Table 1 – Risk Factors for Eclampsia (NICE, Hypertension in Pregnancy)|
|Moderate Risk Factors||High Risk Factors|
Maternal age ≥ 40 years.
Maternal BMI ≥ 35 at initial presentation.
Family history of pre-eclampsia.
Pregnancy interval > 10 years.
HTN, pre-eclampsia or eclampsia in previous pregnancy.
Pre-existing chronic kidney disease
Autoimmune diseases (e.g. SLE, antiphospholipid syndrome)
In the UK, prophylaxis with aspirin 75mg a day is recommended for women with 1 high risk factor or ≥ 2 moderate risk factors. This should be continued from 12 weeks’ gestation until birth.
For a woman to be diagnosed with pre-eclampsia, three criteria should be met:
- Hypertension (systolic BP >140 mmHg or diastolic BP >90 mmHg), on two occasions at least 4 hours apart.
- Significant proteinuria – >300 mg protein in a 24-hour urine sample or >30 mg/mmol urinary protein:creatinine.
- In a woman greater than 20 weeks’ gestation.
The exact clinical presentation of pre-eclampsia varies between individuals. Patients may be asymptomatic – therefore blood pressure and a urine dipstick to check for proteinuria should be performed at each antenatal clinic. In addition to the above, the clinical features of pre-eclampsia include:
- Headaches (usually frontal).
- Visual disturbances e.g. blurred or double vision, halos, flashing lights.
- Epigastric pain (due to hepatic capsule distension/infarction).
- Sudden onset non-dependent oedema.
In the UK, pre-eclampsia is classified as mild, moderate or severe. This is based on the degrees of hypertension, proteinuria and symptoms:
|Mild||BP 140/90-149/99 mmHg|
|Moderate||BP 150/100 – 159/109 mmHg|
|Severe||BP > 160/110 + proteinuria > 0.5 g/ day
BP > 140/90 mmHg + proteinuria + symptoms.
Pre-eclampsia is a multi-system disorder, associated with a number of potentially serious maternal and fetal complications.
Whilst it is not possible to predict which individuals will develop complications, the onset of pre-eclampsia before 34 weeks’ gestation is associated with a poorer prognosis.
The maternal complications of pre-eclampsia include:
- HELLP syndrome – haemolysis, elevated liver enzymes, low platelets.
- Acute Kidney Injury (AKI).
- Disseminated Intravascular Coagulation (DIC).
- Adult Respiratory Distress Syndrome (ARDS).
- Hypertension (4-fold ↑ risk post-partum).
- Cerebrovascular haemorrhage (1-2%)
The major fetal complications are prematurity (iatrogenic and idiopathic), intrauterine growth restriction, placental abruption and intrauterine fetal death.
The main differential diagnoses for hypertension in pregnancy are:
- Essential HTN – HTN prior to 20 weeks’ gestation.
- Pregnancy induced HTN (PIH) – new onset HTN presenting after 20 weeks’ gestation, without significant proteinuria.
- Eclampsia – Pre-eclampsia + seizure(s). This is an obstetric emergency.
Pre-eclampsia is diagnosed by the presence of hypertension and proteinuria. Protein in the urine can be detected by a urine dipstick, and then quantified through a 24-hour urinary collection.
Other investigations are used to monitor for signs of organ dysfunction. The following blood test results may be observed in patients with pre-eclampsia:
- Full blood count: ↓ Hb, ↓ platelets.
- Urea and electrolytes: ↑ urea, ↑ creatinine, ↑ urate, ↓ urine output.
- Liver function tests: ↑ ALT, ↑ AST.
In pre-eclampsia, the two main aims of management are; (i) Prevent development of eclampsia and; (ii) Minimise the risk of complications for mother and fetus.
Therefore, a large part of management is the monitoring of maternal and fetal wellbeing. This can be achieved through regular blood pressure measurements, urinalysis, blood tests, fetal growth scans and cardiotocography. As a general rule, the degree and frequency of monitoring increases with the severity of the disease.
Other aspects of management in pre-eclampsia include:
- Venous thromboembolism prevention – the majority of women are managed on an inpatient-basis, and often require fluid management and VTE prophylaxis. The most common agent used is low molecular weight heparin.
- Antihypertensives – used to reduce the risk of maternal haemorrhagic stroke, but they do not alter the disease course itself.
- Delivery – this is the only definitive cure for pre-eclampsia. The decision regarding when and how to deliver should be made on an individual basis, taking into account the health of both the mother and fetus.
- It should be remembered that prolonging the pregnancy in pre-eclampsia is for the benefit of the fetus alone.
Note: Where a woman is less than 35 weeks’ gestation, and delivery is considered, intramuscular steroids should be administered to aid development of the fetal lungs.
One of the main interventions in the management of pre-eclampsia is to achieve adequate blood pressure control.
The severity of hypertension correlates to the risk of stroke; and thus it is important to maintain the blood pressure at a level that minimises this risk. The main anti-hypertensives are listed below:
|Anti-Hypertensive Medication Used in Pregnancy|
|Medication:||Drug Class:||Common Side-Effects:|
|Labetalol (1st line)||Beta-blocker.||Postural hypotension, fatigue, headache, nausea and vomiting, epigastric pain.|
|Nifedipine||Calcium channel blocker.||Peripheral oedema, dizziness, flushing, headache, constipation.|
|Methyldopa||Alpha-agonist.||Drowsiness, headache, oedema, GI disturbances, dry mouth, postural hypotension, bradycardia, hepatotoxicity.|
|Note: ACE-inhibitors are contra-indicated in pregnancy due to their association with congenital abnormalities.|
Pre-eclampsia resolves following delivery of the placenta. However, it is important to monitor the mother for at least 24 hours post-partum – as they are still at risk of having eclamptic seizures. Generally speaking, by day 5 they can be considered ‘safe’.
Blood pressure should be monitored daily for the first 2 days post-partum, and at least once 3-5 days post-partum. The need for antihypertensives should then be reassessed.
Women should be advised about their risk of developing pregnancy-induced hypertension and pre-eclampsia in subsequent pregnancies.
- Pre-eclampsia is a multi-system disease confined to pregnancy. It is associated with abnormal placentation and inadequate uteroplacental perfusion.
- It is characterised by maternal hypertension after 20 weeks gestation with significant proteinuria +/- oedema.
- There is a variable clinical presentation, and it may be asymptomatic. Screening at antenatal clinics is important.
- The management is based on disease severity and gestational age:
- Labetalol as 1st line anti-hypertensive medication.
- If complications occur, such as fetal distress or maternal deterioration, deliver regardless of gestational age after discussion with an experienced obstetrician.
- Monitor pre-eclamptic patients as an impatient post-partum, as they are still at risk of eclamptic seizures.
- There is an increased risk of developing pre-eclampsia in subsequent pregnancies.