Pre-eclampsia is a multi-system disorder causing widespread vascular endothelial dysfunction, occurring beyond 20 weeks gestation. It affects 2 and 8 per cent of pregnancies.1
Although the prognosis is usually good, pre-eclampsia is a major cause of maternal and fetal morbidity and mortality. It is associated with a raised BP ([s40]140/90mmHg) and proteinuria in a previously normotensive woman.2
The incidence of severe pre-eclampsia and eclampsia is five per 1,000 and five per 10,000 maternities in the UK, respectively.3
The cause of pre-eclampsia is poorly understood, but possible factors include genetics, placental and endothelial dysfunction and abnormal immune response.
Continuous electronic fetal monitoring is required in pre-eclampsia
Involvement of the CNS causes eclampsia or seizures and cerebral haemorrhage. Other features are pulmonary oedema, renal tubular necrosis, jaundice and haemolysis, elevated liver enzymes and lowered platelets (HELLP) syndrome.
Disseminated intravascular coagulation, placental infarction and abruption occur in 10 per cent of women with severe pre-eclampsia.1
Fetal complications include pre-term birth, intra-uterine growth restriction and perinatal mortality.4
Women at risk are identified on the basis of epidemiological and clinical risk factors (see box below). Those with a previous pregnancy complicated by severe pre-eclampsia have a high risk of recurrence in subsequent pregnancies for any type of pre-eclampsia, up to 50 per cent in some studies.
Symptoms that may be associated with pre-eclampsia include persistent headache, epigastric pain, visual disturbances, vomiting, facial swelling and/or peripheral oedema of sudden onset. Hyperreflexia and papilloedema may herald the onset of eclampsia. Clonus and liver edge tenderness may be elicited.1
During pregnancy systolic BP changes little, but diastolic pressure decreases by approximately 10mmHg between 13 and 20 weeks.2 BP rises to pre-pregnancy levels in the third trimester. Women with a BP >140/90 should be referred for further assessment.
Proteinuria is one of the diagnostic criteria. Ideally it should be confirmed over a 24-hour period. Blood investigation may reveal an increased serum creatinine due to decreased intravascular volume and decreased glomerular filtration rate.
There may be a microangiopathic haemolytic anaemia and a reduced platelet count of <100 x 109/l. A falling platelet count is associated with worsening pre-eclampsia and should be a consideration for delivery.
Renal function is generally maintained unless HELLP syndrome develops. Alanine and aspartate aminotransferase may be elevated (>70IU/l) in HELLP syndrome due to hepatocellular injury. Aminotransferases above 150IU/l are linked to an increased maternal morbidity.4
Increased serum uric acid is a poor predictor of maternal and fetal complications.5
Fetal assessment involves consideration of gestation, symphysis-fundal height, presentation, presence of fetal movements and cardiotocography. Patients in labour with severe pre-eclampsia require continuous electronic fetal monitoring.3
The goal of the treatment is to lower BP to prevent cerebrovascular and cardiac complications while maintaining uteroplacental blood flow. Control of mildly increased BP does not appear to improve perinatal morbidity or mortality (although it may reduce birth weight).
Antihypertensive treatment is indicated for systolic BP >160mmHg and diastolic BP >105mmHg (patients with chronic hypertension may tolerate higher values). The aim is to maintain systolic BP at 140-155mmHg and diastolic BP at 90-100mmHg.
Antihypertensives may be used for mild-to-moderate hypertension.2 The use of beta-blockers may cause intra-uterine growth restriction. ACE inhibitors and angiotensin receptor antagonists are contraindicated during pregnancy as they are associated with fetal growth retardation, oligohydramnios, congenital malformations and neonatal renal failure.2
Therefore, women with chronic hypertension taking these medications are given other drugs such as methyldopa and labetalol to control BP.
Antihypertensives are essential for systolic BP [s40]170mmHg or diastolic pressure [s40]110mmHg, although the threshold may be lowered if signs and symptoms of pre-eclampsia are present. Precipitous drops in BP should be avoided.
Traditionally, hydralazine has been used for control of severe hypertension in women with pre-eclampsia.
However, there is conflicting evidence regarding side-effects and maternal/fetal outcomes when compared with labetalol and nifedipine.
Methyldopa is often recommended to manage gestational hypertension and has been proven safe in the long-term follow up of delivered babies.3
Other options include labetalol and calcium-channel blockers to decrease systemic vascular resistance. While reducing BP, diuretics have not been shown to improve other outcome measures and are reserved for pulmonary oedema.6
Magnesium sulphate more than halves the risk of eclampsia, yet this does not have an effect on perinatal mortality.1 If this therapy is commenced, urine output, respiratory rate, maternal reflexes and oxygen saturation should be monitored.
Pre-eclampsia and eclampsia may present after birth (44 per cent of eclampsia has been reported to occur postnatally).3 In the case of severe pre-eclampsia, optimal timing for delivery before 32-34 weeks gestation remains a difficult situation.
Corticosteroids should be given, although after 24 hours the benefits of conservative management should be reassessed in terms of risk to the fetus and to the mother.
Antihypertensives should be continued after delivery, depending on BP. Methyldopa is generally avoided postnatally due to its potential side-effects. In breastfeeding women, labetalol, atenolol, nifedipine and enalapril may be used.6
If there is persistent hypertension and proteinuria at six weeks postpartum, further investigation for renal disease is needed. This may be checked for by the GP at the six-week postnatal check.
Dietary supplementation with 1g of calcium a day appears to reduce the risk of pre-eclampsia,1 but there is no clear relationship of this intervention with perinatal mortality.
Studies show that aspirin reduces the risk of pre-eclampsia by 19 per cent as well as stillbirth and neonatal death.7 One study estimates that this would give an NNT of 69 women to prevent one case of pre-eclampsia.1
Follow up of children up until the age of two has proved reassuring for the intrapartum use of aspirin.
As the diagnostic criteria of pre-eclampsia remain unclear and no known biomarkers are available for screening, prolongation of pregnancy and timely delivery remain the mainstay of treatment.
Dr Kochhar is a GPVTS SHO at Conquest Hospital, Hastings, Dr French is a GPVTS SHO at Royal Sussex County Hospital, Brighton, and Miss Sinha is a consultant in obstetrics and gynaecology at Conquest Hospital, Hastings
- This article was originally published in MIMS Women's Health. To subscribe go to www.lhayreg.co.uk/specials.
- Age below 20 or over 35 years.
- Black race.
- BMI >35.
- Multiple pregnancies.
- Hydatidiform mole.
- Family history of pre-eclampsia.
- More than 10 years between pregnancies.
Severe pre-eclampsia includes at least one of the following:
- Systolic BP >160mmHg or diastolic BP >110mmHg on two occasions six hours apart with the patient at bed rest.
- Proteinuria >5,000mg in a 24-hour period, or >3+ protein on dipstick on two random urine samples collected at least four hours apart.
- Oliguria, with <500ml urine in 24 hours.
- Cerebral or visual disturbance.
- Pulmonary oedema or cyanosis.
- Abdominal pain.
- Impaired liver function.
- Intra-uterine growth retardation.
1. Duley L, Meher S, Abalos E. Management of pre-eclampsia. BMJ 2006; 332: 463-8.
2. Sibai BM. Treatment of hypertension in pregnant women. N Engl J Med 1996; 335: 257-65.
3. RCOG. The management of severe pre-eclampsia/eclampsia (10A). March 2006.
4. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005; 365: 785-99.
5. Thangaratinam S, Ismail KM, Sharp S et al. Accuracy of serum uric acid in predicting complications of pre-eclampsia. BJOG 2006; 113: 369-78.
6. Churchill D, Beevers GD, Meher S, Rhodes C. Diuretics for preventing pre-eclampsia. The Cochrane Library. Issue 1. Wiley, Chichester, 2007.
7. Askie LM, Duley L, Henderson-Smart DJ, Stewart LA. Antiplatelet agents for prevention of pre-eclampsia. Lancet 2007; 369: 1,791-8.