Introduction

Pre-eclampsia is a condition peculiar to pregnancy, characterised by raised blood pressure (BP) and proteinuria. It can be associated with seizures (eclampsia) and multi-organ failure in the mother, while fetal complications include intrauterine growth restriction (IUGR) and placental abruption (Shennan & Chappell, 2001).

Pre-eclampsia leads to increased maternal and fetal mortality and morbidity. In the developed world it is a leading cause of maternal death, and in the UK most deaths have been consistently associated with suboptimal care, particularly by intrapartum care providers (Department of Health (DoH), 1996; CEMACH, 2004).

Underlying pathophysiology of pre-eclampsia

Pre-eclampsia is associated with abnormal implantation of the placenta and concomitant shallow trophoblastic invasion (Pijnenborg, 1994) leading to reduced placental perfusion. The maternal spinal arteries (also known as the uterine arteries) fail to undergo their normal physiological vasodilatation; blood flow may be further impeded by atherotic changes causing obstruction within the vessels.

This pathology causes increased resistance in the uteroplacental circulation with impaired intervillus blood flow resulting in ischaemia and hypoxia, manifested in the second half of pregnancy (Graham et al., 2000).

A similar picture of inadequate trophoblastic invasion exists in pregnancies complicated by IUGR in women with no pre-eclampsia. This suggests that the maternal syndrome of pre-eclampsia must be associated with other features.

Incidence

The incidence of pre-eclampsia varies according to population characteristics and the definitions used to describe it (Davey & MacGillivray, 1988; Chappell et al., 1999; Briley et al., 2006).

UK definition. BP 140/90 or more on two occasions (at least 4 hours apart and within 1 week) with ++ protein or 3.0 g/24 hours or more (International Society for the Study of Hypertension in Pregnancy).

Australasian definition. Hypertension of 140/90 or more with either proteinuria 300 mg/24 hours, protein creatinine ratio ≥30 mg/mmol, dipstick ++ or any other multi-system complication.

Some authors feel that the Australasian definition is more appropriate for the clinical management of a pre-eclamptic woman, since, for example, a hypertensive women with low platelets would meet their definition of pre-eclampsia.

The true incidence is unknown, but is estimated at <5% in most populations. It may be 6–8% in some nations (Lain & Roberts, 2002; Rumbold et al., 2006). Some studies indicate an incidence as low as 2.2%, even in a primigravid population, which is known to have a higher prevalence (Higgins et al., 1997).
Up to 20% of all pregnant women will be hypertensive during pregnancy. Of these fewer than 10% will suffer serious disease.
Pregnancy-induced hypertension (elevated BP with no proteinuria and no pregnancy-related pathology) is approximately three times more common than preeclampsia (Shennan & Chappell, 2001)
In the UK fewer than 10 maternal deaths occur each year, but in the developing countries 50 000 maternal deaths are attributed to eclampsia and a similar number to pre-eclampsia (Duley, 1992).

Facts

All midwives will see women with pre-eclampsia throughout their professional lives.
All pregnant women with a headache, severe enough to seek advice, or with new epigastric pain, should have their BP and urine checked as a minimum (Confidential Enquiry into Maternal and Child Health (CEMACH), 2004).
The International Society for the Study of Hypertension in Pregnancy has adopted the term ‘gestational hypertension’ to describe all hypertensive women, with or without proteinuria, who were normotensive with no proteinuria before pregnancy.
Antenatal women with pre-eclampsia require close monitoring. Placental insufficiency is a common problem with early-onset pre-eclampsia, and this can lead to IUGR in 30% pre-eclamptic pregnancies (Royal College of Obstetricians and Gynaecologists (RCOG), 2006) and sometimes placental abruption and fetal demise.
Late-onset hypertension (>37 weeks gestation) rarely results in serious morbidity for mother or baby. However, hypertension that presents early results developing pre-eclampsia in most women (Shennan & Chappell, 2001).
In severe pre-eclampsia the main causes of maternal death are cerebral haemorrhage and adult or acute respiratory distress syndrome (DoH, 2001). Therefore, management during the intrapartum period concentrates on BP control and fluid balance. Around 50% of UK deaths due to eclampsia involve substandard care, i.e. insufficient involvement of a consultant obstetrician and inadequate treatment leading to intercranial haemorrhage (CEMACH, 2004).

Associated risk factors

There is a well-established genetic link; a family history of a mother or sister with pre-eclampsia increases risk four- to eightfold (Lie et al., 1998).
Paternal influence was first reported in 1983 (Need et al., 1983) with women reported to be at twice the risk of developing pre-eclampsia if their partner has previously fathered a pre-eclamptic pregnancy. Subsequent studies have reported similar associations (Dekker, 2002).
A new partner returns a woman’s risk to that of a primigravida (McCowan et al., 1996).
Assisted conception particularly with donor gametes increases risk (Wang et al., 2002).
Strickland et al. (1986) reported women being ten times more likely to develop preeclampsia in their first pregnancy, with miscarriages and terminations of pregnancy offering some protection. Other authors have also referred to pre-eclampsia as a ‘disease of primiparity’ (Government Office for Science (GOS), 2007).
Multiple pregnancies more than double the risk (Duley et al., 2001).
Maternal age >35 years adds risk. Historically women under 20 have been reported to be at increased risk, although a recent study of women under 19 when they delivered showed a very low pre-eclampsia rate, even though most participants were primigravidae (the ATE study: data publication pending 2008). Obesity (body mass index ≥30) increases the risk fourfold (Shennan et al., 1996; Poston et al., 2006). The UK has the highest levels of obesity in Europe, with recent government reports suggesting that current figures will be increased further by 2050 (GOS, 2007).
Underlying maternal medical conditions increase risk, e.g. chronic hypertension and renal disease (Poston et al., 2006) insulin resistance and glucose intolerance including gestational diabetes (Duley et al., 2001; Ramsay et al., 2006).
The impact of multiple risk factors needs further research; however, a retrospective cohort study in Scotland reported a rate of pre-eclampsia in obese primiparous women as 3.9% compared with 1.6% in multiparous obese women (Smith et al., 2007), suggesting that these two risk factors together increase risk. In the Vitamins in Pre-eclampsia trial (Poston et al., 2006) women with multiple risk factors had a risk ratio of 1.18 (confidence interval 95%, 0.87–1.60) again suggesting a cumulative impact of more than one risk factor.

Ongoing research:

A large multicentre study looking at the genetic components of women with the disease failed to identify a specific gene in women with pre-eclampsia (the GOPEC Consortium, 2005). With technological advances it may be possible to further identify those at risk in the future.
An international screening study is currently underway, looking for biomarkers to predict those at risk of developing pre-eclampsia early in pregnancy to provide a window of opportunity for potential prophylactic measures and stratify antenatal care (www.maps-study.com).

Signs and symptoms

Clinicians cannot rely on BP and proteinuria alone to diagnose pre-eclampsia, as these are only signs of clinical end-organ damage. Just under 50% of all women presenting with pre-eclampsia will have had no previous hypertension or proteinuria (Douglas & Redman, 1994; Milne at al., 2005). The diagnosis must be considered in women with fetal involvement or other signs, such as:

Epigastric pain
Headache/visual disturbances
Intrauterine growth restriction
Note: Oedema is no longer considered a reliable sign of pre-eclampsia, except for rapid-onset facial oedema.

Severe pre-eclampsia is considered in the presence of the following:

Severe hypertension (>160/110 mmHg) or
Hypertension with additional symptoms, such as:

Headache

Visual disturbance

Epigastric pain

Brisk reflexes or clonus

Platelet count below 100 (×10⁹/l)

Aspartate transaminase (AST) or alanine transaminase (ALT) >50 IU/l (there is significantly increased maternal morbidity above 150 IU/l) (RCOG, 2006).

All women presenting in the antenatal period with hypertension and proteinuria will have some or all of the following:

BP and protein urinalysis.
Blood tests (see also ‘Pre-eclampsia’ under the heading ‘Blood tests for specific conditions and blood pictures’ on p. 317, Chapter 23).

Full blood count.

Platelet count. Endothelial dysfunction results in platelet dysfunction. If the platelet count is >50 × 10⁹/l, haemostasis is likely to be normal, but delivery is often considered if the platelet count falls below 100.

Clotting studies if the platelets are <100 × 10⁹/l (RCOG, 2006). Necessary because pre-eclampsia can cause disseminated intravascular coagulation.

Uric acid or urate levels. These are used to assess the severity of the disease and its progression. However, severe disease can occur in the presence of low, normal and high uric acid concentrations (Lie et al., 1998).

Plasma urea and creatinine concentrations. Raised levels of these are generally associated with late renal involvement and serious disease. They are not a useful early indicator of disease severity, but should be obtained longitudinally to assess the progression of renal involvement.

Liver function tests. Pre-eclampsia can cause liver problems, e.g. subcapsular haematoma, rupture and hepatic infarction.

Symphysial fundal height (accurately measured) and/or ultrasound assessment of fetal growth.
Cardiotocograph (CTG). This may give some information about fetal well-being but has no predictive value (RCOG, 2006).
Liquor volume assessment (amniotic fluid index or AFI).
Umbilical artery Doppler analysis.
In some units a uterine artery Doppler waveform assessment may also be carried out, although its value has yet to be clarified (RCOG, 2006). These tests have ±20% positive prediction value (but a 99% negative predictive value), which according to NICE guidelines make it an ineffective test for widespread implementation (National Institute for Health and Clinical Excellence (NICE), 2006). However, in some units it is regularly used either prior to or after the onset of hypertension.

A plan of care will be devised depending on findings. If conservative management is agreed, the woman must be advised to quickly report any pre-eclamptic symptoms. Some women may wish to monitor their own BP at home; any device used should be checked for accuracy.

Many women find it difficult to believe in the potential seriousness of pre-eclampsia, as they often feel quite well unless they are at a significant stage of compromise. It can be difficult to get a balance between clarifying the risks and frightening the woman. Written material may back up explanations, and/or referral to the APEC website, which uses clear language to explain this complex condition.

Box 19.1 summarises BP and urine testing.

Box 19.1 Diagnostic BP and urine criteria for severe pre-eclampsia.

Diastolic/systolic BP (see also ‘Signs and symptoms’).

Diastolic BP ≥90 mm Hg on two or more occasions at least 4 hours (and less than 7 days) apart
Diastolic BP ≥110 mm Hg on one occasion
Systolic >160 mm Hg or diastolic ≥110 mm Hg or a MAP >125 mm Hg (DoH, 2001)
BP ≥140/90 mm Hg with proteinuria (≥0.3 g/day or >2+)

Mean arterial pressure

MAP between 125 and 140 mm Hg for >45 min requires medical referral and treatment
MAP ≥140 mm Hg for >15 min, urgent medical aid and treatment is required
MAP >150 mm Hg represents serious risk of cerebral autoregulatory dysfunction and subsequent risk of cerebral haemorrhage.

Proteinuria

One 24 hours collection with total protein excretion ≥300 mga/24 hours, or
Two ‘clean-catch midstream’ or catheter specimens of urine collected ≥4 hours apart, measuring 2 or more ++ on reagent strip

^a Some units only diagnose pre-eclampsia when proteinuria exceeds 500 mg/24 hours.

BP measurement

Care with BP measurement is essential. There is abundant evidence in the literature to suggest that this is often poorly performed, commonly impacting on practice. Factors to consider include the following:

Equipment. Mercury sphygmomanometry remains the ‘gold standard’ for measuring BP. However due to safety concerns regarding the use of mercury, most units no longer have these machines available in clinical areas. Use a mercury sphygmomanometer for the first reading if possible, and if any uncertainty (CEMACH, 2004; RCOG, 2006). If one is not available cross-check with another validated automated device for increased accuracy (RCOG, 2006). Aneroid machines are commonly used and are reliable when maintained. They require regular calibration to ensure accuracy. There are numerous automated devices available although very few have been validated for use in pregnancy, and even fewer validated as accurate in pre-eclampsia. Most automated devices under-record BP in pre-eclampsia.
Cuff size. Always use the appropriate size cuff. The standard bladder (23 cm × 12 cm) is too small for at least 25% pregnant women. Undercufiing may overestimate BP by >10 mmHg leading to hypertension overdiagnosis. Overcuffing has the opposite (although smaller) effect by underestimating BP by <5 mm Hg (Shennan & Shennan, 1996).
Maternal positioning. Ensure the woman is sitting comfortably and positioned correctly with the mercury scale at heart level. If using an automated device, ensure that she is positioned as per manufacturer’s instructions. Do not talk to the woman and discourage her from speaking during the BP measurement.
Digit preference/digit avoidance. Rounding the final digit of the BP to 0 occurs in >80% BP measurements in antenatal care. Operators also tend to avoid the digits that require action, e.g. they record a diastolic of 88 rather than 90.
Korotkoff sounds. During measurement deflate the cuff at 2–3 mm/second. This prevents overdiagnosis of diastolic hypertension. Korotkoff 4 (the fading or changing of sound) is no longer recommended due to problems with reproducibility. RCOG (2006) now recommends using Korotkoff 5 (the disappearance of sound).
Multiple readings. This may be necessary as there are natural variations in BP (RCOG, 2006).

Urine testing

During urine testing discrepancies can arise with the interpretation of proteinuria. False negatives are common when using dipstick urinalysis. Some of these are being reduced by the use of automated dipstick readers in some units. This is a relatively inexpensive method of limiting operator bias. But in general:

24 hours urine collections should be used to confirm diagnosis if significant proteinuria unless imminent delivery is indicated by other symptoms (RCOG, 2006).
Women with proteinuria >300 mg in 24 hours should be considered at risk.
New innovations in bedside automated devices relating proteinuria to creatinine have not yet been fully evaluated, but may aid clinical practice in the near future (RCOG, 2006).

Care during labour

Most units have a protocol for the management of the severely pre-eclamptic women in labour. All midwives should know where it is. It should be updated as new evidence becomes available.

The decision to deliver will depend on maternal and fetal condition and gestational age. These factors will influence the place and mode of delivery, which ideally will take place in a consultant unit with neonatal facilities (DoH, 1996). Multidisciplinary communication and documentation regarding the management of labour, test results and decisions are essential to ensure a high standard of care. It is important that the midwife caring for the woman should have experience in providing high-risk care and if not should be supported and supervised by a more experienced colleague.

Preterm birth

Pre-eclampsia is a major cause of (usually iatrogenic) prematurity, accounting for 15% of all preterm births, and 25% of all babies born at very low birth weights (<1.5 kg) (Macintosh, 2003). Therefore, many babies born to pre-eclamptic mothers will be admitted to a neonatal unit. If <34 weeks gestation, maternal corticosteroids should be administered to reduce neonatal respiratory problems (Guinn et al., 2001).

If time allows, liaise with the woman and her family and the neonatal unit; this may include a visit or meeting the staff. Some women may require transfer to a specialist neonatal unit: this is likely to be very frightening for the woman and her family. If delivery is imminent and neonatal facilities not available, the baby may require urgent transfer soon after delivery. Take time to explain what is happening and why: this may offer some reassurance.

Psychological support

Due to the intense surveillance and increased intervention during labour and birth, the midwife may easily focus on the woman’s physical condition and forget about her emotional needs.

A relaxed environment may have a physiological as well as psychological effect, as stress will not help the woman’s condition. Providing appropriate lighting and minimising noise can promote an atmosphere of calmness. There may still be choices that women can make if they are well enough.

Women with pre-eclampsia can become seriously ill very quickly, and this can be very frightening for them and those around them. They will need reassurance and a clear calm explanation of what is happening and what interventions are being offered. Whilst informed choice is not always possible, in emergency situations emotional support is essential.

Monitoring the maternal and fetal condition in moderate/severe pre-eclampsia

Blood pressure

BP every 15 min (see Box 19.1).
Be aware that the devices used, cuff size, positioning and technique aresubjectto inaccuracies (see ‘BP measurement’ on p. 269).

Many labour wards (and high dependency units) use mean arterial pressure (MAP) to guide management.

Fluid balance

Women who are severely ill are unlikely to want to eat in labour, but most will require oral fluids.
All women with moderate to severe pre-eclampsia should have an intravenous cannula sited for administration of fluids and medication.
Maintain a strict fluid balance chart. Fluid management is critical:localprotocols may advise restricting fluids in labour to a predefined volume.

Antacids are usually recommended in labour in women with pre-eclampsia due to the increased risk of caesarean section.

Monitoring the fetal heart. Continuous CTG is recommended (NICE, 2007) for monitoring the fetal heart rate and any abnormalities in the trace reported and action taken including fetal blood sampling, where appropriate (see Chapters 3 and 23).

Analgesia. General comfort measures include verbal reassurance, touch, massage and comfortable positions (within the restrictions of monitoring equipment). These simple non-invasive measures may promote a feeling of being supported and cared for which should help the woman cope with a medicalised labour and delivery. Epidural may be recommended because it causes vasodilatation which can lead to a reduction in BP and attenuate surges. An established effective epidural is also advantageous should an operative delivery be indicated. The ultimate choice is the woman, and if she makes an informed decision to decline epidural/spinal anaesthesia the midwife must support her in that decision. Policies vary between units, but if the woman’s platelet count is considered low (≤80), an epidural may be inadvisable.

Intubation (general anaesthetic) should be avoided because it causes hypertension and laryngeal oedema.

Second stage

Management will be determined by maternal and fetal condition. If both allow, a spontaneous vaginal delivery is the mode of choice. In moderate to severe preeclampsia there is a low threshold for intervention leading to instrumental delivery.
Ensure that appropriate medical aid is available and that there are two midwives caring for this woman throughout the delivery.
Monitor the BP closely: it may be unrealistic to check after each contraction, but in severe pre-eclampsia every 5–10 minutes is sensible.
Involuntary pushing, whilst not discouraged, is not actively encouraged until the presenting part is visible on the perineum.
Active pushing is contraindicated as it involves directed, prolonged breath holding and bearing down which alters heart rate and increase stroke volume.
Avoid the supine position: it compresses the distal aorta and reduces blood flow to the uterus and lower extremities (Sleep et al., 2000). It also prolongs the second stage, causes a reduction in circulating oxytocin, reducing the frequency and strength of contractions and can lead to fetal heart rate abnormalities (Gupta et al., 2004). Left lateral and other alternative positions are preferable.

Drugs used in the treatment of severe hypertension

If the woman has not delivered, colloids are usually infused before treatment is started to maintain uteroplacental circulation preventing hypotension and fetal distress.

Antihypertensive treatment should be started in women with a systolic blood pressure over 160 mm Hg or a diastolic blood pressure over 110 mm Hg, but may be introduced at lower BP measurements in women with other symptoms of the disease. Drugs used in the acute management of severe hypertension include oral or intravenous (IV) labetalol, oral nifedipine or IV hydralazine.

In moderate hypertension, effective treatment may enable the continuation of the pregnancy – reducing some of the neonatal complications of prematurity.

Note: Atenolol, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor-blocking (ARB) drugs should be avoided because they have adverse fetal side effects. Similarly, diuretics are contraindicated in hypertension and should only be used in cases of pulmonary oedema.

Nifedipine

Local guidelines may vary, but recommended dosage is 10–20 mg orally (not sublingually as this can cause precipitous hypotension) repeated every 30 minutes to a maximum dose of 50 mg (Sibai, 2003).

Hydralazine

Hydralazine is widely used in the acute management of women with hypertension and is titrated against BP. A recent review for the RCOG (2006) guidelines suggests that other drugs may be preferable to hydralazine, but the currently available evidence is not strong enough to preclude its use. It is given:

5 mg IV in fluid
Repeated every 20 min (at 5 mg IV)
Maximum cumulative dose of 20 mg (four doses of 5 mg IV over 80 min) (DoH, 2001)

Labetalol

Labetalol has the advantage that it can be given initially by mouth in severe hypertension and then, if needed, intravenously. Dosage is as follows:

100 mg BD orally
20 mg IV at 10 min intervals
Increasing to 40, 80 and 80 mg
Maximum cumulative dose of 300 mg (four doses of 20, 40, 80, 80 mg over 40 min) (DoH, 2001)
Avoid in asthmatic women (RCOG, 2006)

Magnesium sulphate

Magnesium sulphate should be considered if it is felt that there is a real risk of fitting (eclampsia); often when a decision to deliver has been made, or in the immediate postnatal period (RCOG, 2006). It has been demonstrated to reduce the risk of seizures in pre-eclampsia (Duley et al., 2002). It is also advisable after any seizure (see later on p. 274)

Care of a woman receiving drug treatment for severe hypertension

Monitor closely ensuring BP falls gradually. Rapid reduction will adversely affect the uteroplacental circulation and lead to fetal distress.
Monitor the fetal heart for signs of fetal compromise.
Low threshold for central venous pressure (CVP) line.

Fluid balance management

Women with pre-eclampsia have leaky capillary membranes and a predisposition to low albumin levels; therefore if fluid administration is excessive or unmonitored they are prone to developing pulmonary oedema. General guidelines include the following:

Maintenance of strict fluid balance charts.
These women are strongly advised to have a urinary catheter inserted.
A urometer should be used to accurately record output per hour. 100 ml urine excreted over 4 hours is commonly said to be sufficient to maintain renal function, although RCOG (2006) states that there is no evidence that maintaining a specific urine output prevents renal failure: oliguria is common in pre-eclampsia and should resolve as the condition improves (RCOG, 2006).
Most protocols limit colloid fluid intake to 85 ml/hour unless the woman haemorrhages in which case fluid restriction is inappropriate (RCOG, 2006).

Management of eclampsia

When pregnant women fit due to pre-eclampsia it is known as eclampsia. This suggests that it is different from other sorts of convulsions, such as those due to epilepsy, but this is not the case. In the event of a fit it is important to stabilise the mother before delivering the baby. Remember that eclampsia is an absolute indication for an urgent delivery once the maternal condition is stabilised. It is extremely important that the midwife explains everything that is happening to the woman and her partner/relatives.

Note: If a pregnant woman presents as semi-conscious or drowsy, non-eclamptic convulsions should be considered: conditions such as epilepsy are more likely to be the cause than eclampsia. However if there is no history of previous convulsions always assume a fit in pregnancy is due to eclampsia.

Incidence

Fewer than 1% of women with pre-eclampsia will have an eclamptic fit (Shennan & Chappell, 2001).
1.6% of women who have an eclamptic fit will die, and 35% will have a major complication (RCOG, 2006).

Facts

Prophylactic use of anticonvulsants (other than magnesium sulphate therapy for severe pre-eclampsia where a fit is predicted (RCOG, 2006)) is controversial and local policies vary (Duley et al., 2002; Poston et al., 2006).
The Collaborative Eclampsia Study (Duley et al., 1995) showed that magnesium sulphate administration following a convulsion, when compared with diazepam and phenytoin, resulted in significantly less maternal ventilation, pneumonia and fewer ITU admissions.