- Fiona Milne, guideline coordinator ()1,
- Chris Redman, professor of obstetric medicine2,
- James Walker, obstetrician3,
- Philip Baker, director4,
- Julian Bradley, general practitioner5,
- Carol Cooper, general practitioner6,
- Michael de Swiet, professor of obstetric medicine7,
- Gillian Fletcher, president8,
- Mervi Jokinen, practice and standards development adviser9,
- Deirdre Murphy, professor of obstetrics and gynaecology10,
- Catherine Nelson-Piercy, obstetric physician11,
- Vicky Osgood, consultant in obstetrics12,
- Stephen Robson, obstetrician13,
- Andrew Shennan, professor of obstetrics11,
- Angela Tuffnell, midwifery sister3,
- Sara Twaddle, health economist1,
- Jason Waugh, consultant obstetrician14
- 1 Action on Pre-eclampsia, Harrow, Middlesex HA1 4HZ
- 2 Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford OX3 9DU
- 3 St James's University Hospital, Leeds LS9 7TF
- 4 Maternal and Fetal Health Research, St Mary's Hospital, Manchester M13 0JH
- 5 Stonedean Practice, Stony Stratford Health Centre, Milton Keynes MK11 1YA
- 6 Cuckoo Lane Practice, London W7 3EY
- 7 Imperial College London, Queen Charlotte's Hospital, London W12 0NN
- 8 National Childbirth Trust, London W3 6NH
- 9 Royal College of Midwives, London W1G 9NH
- 10 Ninewells Hospital and Medical School, Dundee DD1 9SY
- 11 St Thomas' Hospital, King's College, London SE1 7EH
- 12 St Mary's Hospital, Portsmouth, Hampshire PO3 6AD
- 13 School of Surgical and Reproductive Sciences, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP
- 14 Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester LE1 5WW
- Correspondence to: F Milne
- Accepted 5 January 2005
Why is a guideline needed?
Pre-eclampsia is a major cause of poor outcome in pregnancy: the category “hypertensive diseases of pregnancy” remains a leading cause of direct maternal deaths in the United Kingdom1; pre-eclamptic conditions represent one in three cases of severe obstetric morbidity2; hypertension and/or proteinuria is the leading single identifiable risk factor in pregnancy associated with stillbirth (one in five stillbirths in otherwise viable babies)3; and pre-eclampsia is strongly associated with fetal growth restriction, low birth weight, preterm delivery, respiratory distress syndrome, and admission to neonatal intensive care.4
In 46% of maternal deaths1 and 65% of fetal deaths5 due to pre-eclampsia reported through the Confidential Enquiries into Maternal Deaths and the Confidential Enquiry into Stillbirths and Deaths in Infancy, different management would reasonably have expected to alter the outcome. There was a failure to identify and act on known risk factors at booking and to recognise and respond to signs and symptoms from 20 weeks' gestation.6
No guidelines exist for the screening and early detection of pre-eclampsia in the community, and there is no uniformity in referral thresholds and assessment procedures.
What can be done?
We developed the pre-eclampsia community guideline (PRECOG) under the auspices of the charity Action on Pre-eclampsia, following the National Institute for Clinical Excellence's recommendations for the development of guidelines.7 Our guideline is supported by the Royal College of Obstetricians and Gynaecologists, the Royal College of Midwives, the Royal College of General Practitioners, and the National Childbirth Trust. Box 1 lists the definitions used in the guideline; pre-eclampsia is defined as new hypertension and proteinuria (see bmj.com for definition of levels of evidence).
The pre-eclampsia community guideline provides an evidence based risk assessment, with criteria for early referral for specialist input, a two tiered schedule for monitoring women in the community after 20 weeks' gestation, and referral criteria for step-up care. The guideline provides a framework by which pregnant women with pre-eclampsia are offered specialist care at the appropriate time for the best outcome for them and their baby. We recognise that women's emotional, cultural, and midwifery needs should be taken into account when developing individual care plans and we recognise the benefit of continuity of care.
Box 1: Definitions of terms used in pre-eclampsia community guideline
Reduced fetal movements
Small for gestational age infant
Diastolic blood pressure of ≥ 90 mm Hg
Hypertension at or after 20 weeks' gestation in women with a diastolic blood pressure < 90 mm Hg before 20 weeks
Diastolic blood pressure ≥ 90 mm Hg before pregnancy or at booking (before 20 weeks)
Presence of proteinuria as shown by ≥+ (300 mg/l) on dipstick testing, a protein to creatinine ratio of ≥ 30 mg/mmol on a random sample, or a urine protein excretion of ≥ 300 mg in 24 hours
Urine protein excretion ≥ 300 mg in 24 hours
New hypertension and quantified proteinuria at or after 20 weeks of pregnancy, confirmed if it resolves after delivery
Development of features of pre-eclampsia in context of pre-existing hypertension or pre-existing proteinuria, or both
Complementing existing recommendations
Our guideline complements NICE's antenatal guidelines for the routine care of healthy women. Our guideline also provides advice for women excluded from the NICE remit because of risk factors or concurrent medical conditions and recommends test result thresholds and actions for step-up assessment for all women who have antenatal care in the community. Our guideline applies to midwife led or general practitioner led care in the community and is applicable from first contact with a health professional until delivery.
The evidence behind our guideline can be used to adapt other antenatal guidelines, both within the United Kingdom and worldwide, as local circumstances and needs dictate.
Risk assessment early in pregnancy
Before developing an antenatal care plan, women should be assessed for the factors listed in box 2. From meta-analysis and systematic review,8 the unadjusted relative risks of developing pre-eclampsia were: presence of antiphospholipid antibodies (9.72, 95% confidence interval 4.34 to 21.75), history of pre-eclampsia (7.19, 5.85 to 8.83), pre-existing diabetes (3.56, 2.54 to 4.99), multiple pregnancy (2.93, 2.04 to 4.21), nulliparity (2.91, 1.28 to 6.61), family history of pre-eclampsia (2.90, 1.70 to 4.93), women aged ≥ 40 (nulliparous women, 1.68, 1.23 to 2.29; multiparous women, 1.96, 1.34 to 2.87), and a raised body mass index at booking (1.55, 1.28 to 1.88). The risk of pre-eclampsia is also increased with pre-existing hypertension and renal disease, a pregnancy interval of ≥ 10 years, a raised diastolic blood pressure at booking, and confirmed proteinuria.9 The data did not show an increased risk for young women of ≥ 19, ≥ 17, or ≥ 16.
Box 2: What to do before developing an antenatal care plan
Action: identify the presence of any one of the following factors that predispose women in a given pregnancy to pre-eclampsia (grade B/C):
≥ 10 years since last baby
Age ≥ 40 years
Body mass index ≥ 35
Family history of pre-eclampsia (mother or sister)
Booking diastolic blood pressure ≥ 80 mm Hg
Proteinuria at booking (≥+ on more than one occasion or ≥ 300 mg/24 h)
Underlying medical conditions:
Pre-existing renal disease
Presence of antiphospholipid antibodies
Box 3: What to do after the risk assessment
Action: offer women referral before 20 weeks for specialist input to their antenatal care plan if they have one of the following (grade D/good practice point):
Underlying medical conditions:
Pre-existing hypertension or booking diastolic blood pressure ≥ 90 mm Hg
Pre-existing renal disease or booking proteinuria (≥+ on more than one occasion or ≥ 300 mg/24 h)
Presence of antiphospholipid antibodies
Any two other factors from box 2
For the continuous variables, such as age and body mass index, we selected conservative thresholds for action available from the data. Below these cut-off points there is still an increased risk of pre-eclampsia. Data were insufficient to calculate absolute risk for each factor, to see how two factors interact, or to comment on migraine or change of partner. We did not consider donor egg and donor insemination.
Referral in early pregnancy for specialist input
Women should be offered specialist input before 20 weeks if they have one of the criteria listed in box 3. Input may concern further specialist investigation, clarification of risk, or advice on early intervention or pharmacological treatment. We do not prescribe subsequent obstetric care, which will be determined on an individual basis and may be led by specialists, general practitioners, or midwives, or by shared care.
Previous pre-eclampsia is associated with higher rates of moderate, severe, and early onset pre-eclampsia and adverse perinatal outcomes associated with preterm delivery.10 Recurrent pre-eclampsia occurs, on average, between zero and four weeks later than in the first pregnancy. We recommend that women who have asymptomatic proteinuria at booking, if persistent or confirmed by a 24 hour sample, be investigated for possible underlying renal disease (itself a risk factor for pre-eclampsia) or other conditions to accurately determine risk.
Box 4: What to do after 20 weeks (content of assessment)
Action: at every assessment identify the presence of any of the following signs and symptoms of the onset of pre-eclampsia and act according to table 2 (grade B and C):
Symptoms of headache or visual disturbance, or both
Epigastric pain or vomiting, or both
Reduced fetal movements, small for gestational age infant
See box 1 for definitions
Data were lacking on the effect of two predisposing factors on the overall likelihood of developing pre-eclampsia. We recommend that women with two such factors be referred for early specialist input, individual assessment, and discussion of obstetric risk.
Community monitoring after 20 weeks' gestation
A Cochrane review comparing schedules of antenatal care does not provide evidence to recommend a particular schedule for women who do not qualify for early referral:11 no study was powered to identify differences in mortality, or serious outcomes associated with pre-eclampsia. We found absence of antenatal care to be strongly associated with eclampsia and fetal death.12 A UK study showed that reducing the frequency of antenatal care shifts costs to neonatal care, resulting in higher overall costs.13
Serious morbidity associated with pre-eclampsia can occur from 20 weeks' gestation to after delivery: placental abruption; haemolysis, elevated liver enzymes, and low platelet count syndrome; and renal failure are more common before 32 weeks, whereas eclampsia is most common at term.14 15 Onset before 32 weeks has the most serious outcome and the interval between diagnosis and delivery is on average 14 days (range 0-62 days), with a substantial number of women requiring delivery within 72 hours.16 We therefore recommend (see table 1) that before 32 weeks, women with one risk factor (and none from box 3) are seen at least once every three weeks, and then at least once every two weeks, until delivery.
Women with no risk factors for pre-eclampsia may still develop the condition. NICE recommends assessments for pre-eclampsia at weeks 16, 28, 34, 36, 38, 40, and 41 for healthy parous women with a single fetus. Given that pre-eclampsia can progress to a life threatening situation in, on average, two weeks from diagnosis, we recommend that these women are told that pre-eclampsia can develop between antenatal assessments, are made aware of symptoms, and know how to contact their healthcare professionals at all times.
Content of the assessment
After 20 weeks' gestation, women should be assessed for the signs and symptoms of pre-eclampsia (see box 4). Any one of these may be the first indication of pre-eclampsia. The method of measuring blood pressure is critical: errors have been implicated in maternal deaths.1 6 Our recommendations concur with NICE's guideline. In the community, fetal compromise is usually assessed by asking women about reduced fetal movements or by estimating a small for gestational age fetus. The guideline of the Royal College of Obstetricians and Gynaecologists provides evidence based recommendations. Thresholds for step-up assessment (see table 2) are based on the association with poor outcome and rates of progression. Oedema is not predictive, and weight change does not reliably precede other signs.
Women with new hypertension before 32 weeks have a 50% chance of developing pre-eclampsia:17 at 24-28 weeks, new hypertension is predictive of severe pre-eclampsia.18 On average a rise in diastolic blood pressure that does not reach 90 mm Hg at any time during pregnancy is associated with an uncomplicated pregnancy.19 Eclampsia is not always associated with severe hypertension; in a UK population study, 34% of eclamptic women had a maximum diastolic blood pressure of ≤ 100 mm Hg.15
New proteinuria with new hypertension is strongly associated with poor fetal and maternal outcome.20 21 Women may progress rapidly: 25-55% of women with hypertension of ≥ 160 mm Hg systolic or ≥ 110 mm Hg diastolic with new proteinuria (≥+) required delivery within 48 hours of admission.16
Quantified protein excretion is independently associated with undiagnosed underlying medical conditions and a poor obstetric outcome.9 The most reliable method for quantifying protein excretion is urine collection over 24 hours. Although NICE's guideline allows the use of protein creatinine ratios to quantify protein, more recent data22 suggest that although the test is useful for screening (≥ 30 mg/mmol on a random sample) local confirmation of performance is required for quantification, as the results may be modified by the method used to measure the proteinuria.
While + proteinuria with new hypertension is associated with poor outcome and should be considered as pre-eclampsia until otherwise confirmed, a + result on dipstick testing on its own is prone to false positives. Factors affecting the result include reader error (which can be minimised by training, or the use of automated readers) and concentration errors (avoided by the use of the protein creatinine ratio test). Accuracy is not increased by repeating the test on a new sample. A + result on dipstick testing is unlikely to be due to infection, unless the woman has symptoms.
In the presence of pre-eclampsia, headache is an independent risk factor for eclampsia, and epigastric pain and vomiting are independent risk factors for serious morbidity in women with severe pre-eclampsia.23 24 These symptoms should always be followed up immediately, by an assessment of blood pressure and proteinuria as a minimum.
Fetal compromise can be the first clinical indication of pre-eclampsia1 6 and should always be followed up by an assessment of blood pressure and proteinuria as well as following local management protocols.
Day assessment units
Women should be referred to a hospital day assessment unit (available in 75% of hospitals) or similar (see table 2) that have facilities necessary for step-up assessment. Test results should be obtainable within 24 hours.
Many maternal and fetal deaths from pre-eclampsia are associated with substandard care
Poor management includes failure to assess or act on risk at booking or to act on signs and symptoms after 20 weeks' gestation
Our community guideline provides an evidence based risk assessment, a list of factors suitable for early referral, and a two tiered schedule of assessment and step-up referral for signs and symptoms of pre-eclampsia
This is a practical extension of NICE's antenatal guideline
We are developing a guideline for day assessment units that will provide a single, comprehensive step-up assessment to confirm pre-eclampsia and predict outcomes. The predictive value of the tests would provide a woman's usual carer with valuable information that may avoid unnecessary referral at a later date.
We have produced an audit tool for managers to assess the resource implications of implementing our guideline. We anticipate limited impact, depending on the degree to which NICE's guideline on antenatal care has already been implemented and on local circumstances and facilities. In most local circumstances the guideline is most effectively and efficiently introduced at trust level.
Further details concerning the guideline are on bmj.com
Editorial by Greer and Papers p 565
We thank the contributors, who gave their time and expertise without payment. Travel expenses, accommodation, and ad hoc expenses were paid, when appropriate. An adoption, training, and implementation package is available through Action on Pre-eclampsia (http://www.apec.org.uk/).
Contributors The Pre-eclampsia Community Guideline Development Group, chaired by CR and JW, conceived the article. The design of the recommendations and analysis of data were a consensus from that group. References were based on literature searches conducted by FM, CR, JW, PB, SR, Kirsten Duckitt, AS, and JW for sections of the paper, with additional studies from Robyn North (independent reviewer). All studies were independently graded by Kirsten Duckitt and DM. FM wrote the paper; she is guarantor. All authors critically reviewed the paper for intellectual content.
Funding Action on Pre-eclampsia received funding from GlaxoSmithKline and funding in kind by Bayer.
Competing interests None declared.
Ethical approval Not required.