The pre-eclampsia community guideline(PRECOG): how to screen for and detect onset of pre-eclampsia in the community
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
, http://www.100md.com
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
, 百拇医药
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.
, 百拇医药
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).
, 百拇医药
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.
, 百拇医药
Box 1: Definitions of terms used in pre-eclampsia community guideline
Fetal compromise
Reduced fetal movements
Small for gestational age infant
Hypertension
Diastolic blood pressure of 90 mm Hg
New hypertension
Hypertension at or after 20 weeks' gestation in women with a diastolic blood pressure < 90 mm Hg before 20 weeks
, 百拇医药
Pre-existing hypertension
Diastolic blood pressure 90 mm Hg before pregnancy or at booking (before 20 weeks)
New proteinuria
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
Quantified proteinuria
, 百拇医药
Urine protein excretion 300 mg in 24 hours
Pre-eclampsia
New hypertension and quantified proteinuria at or after 20 weeks of pregnancy, confirmed if it resolves after delivery
Superimposed pre-eclampsia
Development of features of pre-eclampsia in context of pre-existing hypertension or pre-existing proteinuria, or both
Complementing existing recommendations
, 百拇医药
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.
, http://www.100md.com
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.
The recommendations
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.
, 百拇医药
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):
First pregnancy
Previous pre-eclampsia
10 years since last baby
Age 40 years
Body mass index 35
, 百拇医药
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)
Multiple pregnancy
Underlying medical conditions:
Pre-existing hypertension
Pre-existing renal disease
, http://www.100md.com
Pre-existing diabetes
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):
Previous pre-eclampsia
Multiple pregnancy:
, http://www.100md.com
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)
Pre-existing diabetes
Presence of antiphospholipid antibodies
Any two other factors from box 2
, 百拇医药 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
, 百拇医药
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.
, 百拇医药
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):
New hypertension
New proteinuria
Symptoms of headache or visual disturbance, or both
Epigastric pain or vomiting, or both
, 百拇医药
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
, 百拇医药
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
, 百拇医药
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.
, 百拇医药
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.
, http://www.100md.com
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.
, http://www.100md.com
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
, http://www.100md.com
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.
, 百拇医药
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.
, http://www.100md.com
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.
, 百拇医药
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.
Summary points
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
, 百拇医药
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.
, http://www.100md.com
Resource implications
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
, http://www.100md.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 (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.
, 百拇医药
Funding: Action on Pre-eclampsia received funding from GlaxoSmithKline and funding in kind by Bayer.
Competing interests: None declared.
Ethical approval: Not required.
References
National Institute for Clinical Excellence, Scottish Executive Health Department, Department of Health, Social Services and Public Safety, Northern Ireland. Why mothers die 2000-2002. The sixth report of the confidential enquiries into maternal deaths in the United Kingdom. London: RCOG Press, 2004.
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Waterstone M, Bewley S, Wolfe C. Incidence and predictors of severe obstetric morbidity: case-control study. BMJ 2001;322: 1089-94.
Maternal and Child Health Research Consortium. Confidential enquiry into stillbirths and deaths in infancy: 6th annual report, 1 January-31 December 1997. London: Maternal and Child Health Research Consortium, 1999.
The Magpie Trial Collaborative Group. Do women with pre-eclampsia and their babies benefit from magnesium sulphate The magpie trial: a randomised placebo-controlled trial. Lancet 2002:359: 1877-90.
, 百拇医药
Maternal and Child Health Research Consortium. Confidential enquiry into stillbirths and deaths in infancy: 8th annual report, 1 January-31 December 1999. London: Maternal and Child Health Research Consortium, 2001.
National Institute for Clinical Excellence, Scottish Executive Health Department, Department of Health, Social Services and Public Safety, Northern Ireland. Why mothers die 1997-1999. The fifth report of the confidential enquiries into maternal deaths in the United Kingdom. London: RCOG Press, 2001.
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NHS National Institute for Clinical Excellence. The guideline development process—information for national collaborating centres and guideline development groups. Issue Dec 2001. www.nice.org.uk
Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: a systematic review of controlled studies. BMJ 2005;330: 565-7.
Stettler RW, Cunningham FG. Natural history of chronic proteinuria complicating pregnancy. Am J Obstet Gynecol 1992;167: 1219-24.
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Koike T, Minakami H, Izumi A, Watanabe T, Matsubara S, Sato I. Recurrence risk of preterm birth due to preeclampsia. Gynecol Obstet Invest 2002;53: 22-7.
Carroli G, Villar J, Piaggio G, Khan-Neelofur D, Gulmezoglu M, Mugford M, et al. WHO systematic review of randomised controlled trials of routine antenatal care. Lancet 2001;357: 1565-70.
Abi Said D, Annegers JF, Combs Cantrell D, Frankowski RF, Willmore LJ. Case-control study of the risk factors for eclampsia. Am J Epidemiol 1995;142: 437-41.
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Henderson J, Roberts T, Sikorski J, Wilson J, Clement S. An economic evaluation comparing two schedules of antenatal visits. J Health Serv Res Policy 2000:5: 69-75.
Banias BB, Devoe LD, Nolan TE. Severe pre-eclampsia in preterm pregnancy between 26 and 32 weeks' gestation. Am J Perinatol 1992;9: 357-60.
Douglas KA, Redman CW. Eclampsia in the United Kingdom. BMJ 1994;309: 1395-1400.
Sibai BM, Mercer BM, Schiff E, Friedman SA. Aggressive versus expectant management of severe pre-eclampsia 28 to 32 weeks gestation: a randomised controlled trial. Am J Obstet Gynecol 1994;171: 818-22.
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Barton JR, O'Brien JM, Bergauer NK, Jacques DL, Sibai BM. Mild gestational hypertension remote from term: progression and outcome. Am J Obstet Gynecol 2001;184: 979-83.
Stamilio DM, Sehdev HM, Morgan MA, Propert K, Macones GA. Can antenatal clinical and biochemical markers predict the development of severe pre-eclampsia Am J Obstet Gynecol 2000;182: 589-94.
North RA, Taylor RS, Schellenberg JC. Evaluation of a definition of preeclampsia. Br J Obstet Gynaecol 1999;106: 767-74.
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Seshadri L, Venkataraman I. Hypertension in pregnancy. Outcomes, proteinuric vs. nonproteinuric. J Reprod Med 1997;42: 88-90.
Ferrazzani S, Caruso A, De Carolis S, Martino IV, Mancuso S. Proteinuria and outcome of 444 pregnancies complicated by hypertension. Am J Obstet Gynecol 1990;162: 366-71.
Durnwald C, Mercer B. A prospective comparison of total protein/creatinine ratio versus 24-hour urine protein in women with suspected pre-eclampsia. Am J Obstet Gynecol 2003;189: 848-52.
, 百拇医药
Martin JN Jr, May WL, Magann EF, Terrone DA, Rinehart BK, Blake PG. Early risk assessment of severe pre-eclampsia: admission battery of symptoms and laboratory tests to predict likelihood of subsequent significant maternal morbidity. Am J Obstet Gynecol 1999;180: 1407-14.
Witlin AG, Saade GR, Mattar F, Sibai BM. Risk factors for abruptio placentae and eclampsia: analysis of 445 consecutively managed women with severe pre-eclampsia and eclampsia. Am J Obstet Gynecol 1999;180: 1322-9., 百拇医药(Fiona Milne, Chris Redman)
, http://www.100md.com
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
, 百拇医药
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.
, 百拇医药
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).
, 百拇医药
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.
, 百拇医药
Box 1: Definitions of terms used in pre-eclampsia community guideline
Fetal compromise
Reduced fetal movements
Small for gestational age infant
Hypertension
Diastolic blood pressure of 90 mm Hg
New hypertension
Hypertension at or after 20 weeks' gestation in women with a diastolic blood pressure < 90 mm Hg before 20 weeks
, 百拇医药
Pre-existing hypertension
Diastolic blood pressure 90 mm Hg before pregnancy or at booking (before 20 weeks)
New proteinuria
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
Quantified proteinuria
, 百拇医药
Urine protein excretion 300 mg in 24 hours
Pre-eclampsia
New hypertension and quantified proteinuria at or after 20 weeks of pregnancy, confirmed if it resolves after delivery
Superimposed pre-eclampsia
Development of features of pre-eclampsia in context of pre-existing hypertension or pre-existing proteinuria, or both
Complementing existing recommendations
, 百拇医药
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.
, http://www.100md.com
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.
The recommendations
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.
, 百拇医药
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):
First pregnancy
Previous pre-eclampsia
10 years since last baby
Age 40 years
Body mass index 35
, 百拇医药
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)
Multiple pregnancy
Underlying medical conditions:
Pre-existing hypertension
Pre-existing renal disease
, http://www.100md.com
Pre-existing diabetes
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):
Previous pre-eclampsia
Multiple pregnancy:
, http://www.100md.com
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)
Pre-existing diabetes
Presence of antiphospholipid antibodies
Any two other factors from box 2
, 百拇医药 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
, 百拇医药
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.
, 百拇医药
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):
New hypertension
New proteinuria
Symptoms of headache or visual disturbance, or both
Epigastric pain or vomiting, or both
, 百拇医药
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
, 百拇医药
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
, 百拇医药
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.
, 百拇医药
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.
, http://www.100md.com
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.
, http://www.100md.com
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
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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.
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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.
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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.
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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.
Summary points
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
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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.
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Resource implications
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
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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 (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.
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Funding: Action on Pre-eclampsia received funding from GlaxoSmithKline and funding in kind by Bayer.
Competing interests: None declared.
Ethical approval: Not required.
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