5Assessment, surveillance

Beth Payne, BSc, PIERS ResearcLaura A. Magee, MD, FRCPC, MPeter von Dadelszen, MBChB, DaDepartment of Obstetrics and Gynaecology, Universb School of Population and Public Health, UniversitycDepartment of Medicine, University of British Columd The CFRI Reproduction and Healthy Pregnancy Clus

Keywords:

* Corresponding author. Department of Obstetrics and Gynaecology, University of British Columbia, 2H30-4500 Oak Street,BC V6H 3NI, Canada Tel.: 1 604 875 3054; Fax: 1 604 875 2725.

E-mail address: bpayne@cw.bc.ca (B. Payne).

Contents lists available at ScienceDirect

Best Practice & Research ClinicalObstetrics and Gynaecology

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Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462Although standardised assessment and surveillance has been shownto improve outcomes, the application of these monitoring strategiesinmanyareas of theworld is not possible owing to the cost associatedwith them. Not all of the tests recommended for surveillance ofwomenwith pre-eclampsia are independently predictive of adverseoutcomes, andmanyunnecessary tests could be avoided if those teststhat are most informative where identied. The Pre-eclampsia Inte-gratedEstimateofRiSk studyhas identiedagroupof tests that canbeused to predict risk of outcomes accurately up to 7 days afteradmission to a tertiaryhospitalwith pre-eclampsia. Thismodelneedsto be validated in new populations and in different clinical settingsbefore it canbe implemented into clinical practice.Until this happens,clinicians should consider the whole clinical picture when assessingwomenwith pre-eclampsia and making decisions around expectantmanagement compared with stabilisation and delivery. FutureprognosisassessmentPIERSpre-eclampsia1521-6934/$ see front matter 2011 Elsevier Ltdoi:10.1016/j.bpobgyn.2011.02.003and prognosis in pre-eclampsia

h Manager a,d,*,Sc, Clinical Associate Professor a,b,c,Phil, FRCSC, Associate Professor a,b,d

ity of British Columbia, 2H30-4500 Oak Street, BC V6H 3NI, Canadaof British Columbia, 2H30-4500 Oak Street, BC V6H 3NI, Canadabia, 2H30-4500 Oak Street, BC V6H 3NI, Canada

ter, University of British Columbia, 2H30-4500 Oak Street, BC V6H 3NI, Canada

The hypertensive disorders of pregnancy (HDP) remain one of themajor causes of maternal mortality and morbidity worldwide. Manyinternational guidelines exist for the classication and assessment ofwomenwith hypertension in pregnancy, but denitions and recom-mendations within these documents are variable. Many recom-mended investigations donot actually correlatewith increased risk ofadverse outcomes, making it difcult to determine true prognosis.d. All rights reserved.

ewedand risk stratication, and effective mareduce adverse outcomes. Unfortunately,and management strategies is lacking, an

elinclassfor severity stipulated in these guidprognostic value. An overview of the

denitions for HDP are presented from tnagement strategies in order to guide care and ultimatelyconsensus amongst these documents relating to denitionsd is confusing for clinicians.25 In addition, many of the criteriaes have not been properly evaluated on the basis of theirication systems is presented in Table 1. Severity criteria andThe international guidelines revi here were intended to provide useful criteria for diagnosisresearch in theareaofprognosisshould focusonwomenwithvariabledenitions of pre-eclampsia and the other HDP. All studies reviewedwere limited to cases of severe pre-eclampsia, and resultsmay not begeneralisable across the spectrum of the disorder.

2011 Elsevier Ltd. All rights reserved.

Introduction

The hypertensive disorders of pregnancy (HDP), including chronic hypertension, gestationalhypertension and pre-eclampsia, are of great concern to clinicians because of the associated adversematernal and fetal outcomes. The HDP, specically pre-eclampsia, remain one of the top four causes ofmaternal mortality and morbidity in high-, middle-, and low-income countries.14 Most deaths asso-ciated with these disorders occur in low- and middle-income countries.

In high-income countries, where maternal mortality is rare, severe morbidities resulting from HDPare of greater concern. Adverse maternal outcomes associated with HDP are a result of excessiveinammation and endothelial damage, and include eclampsia, stroke, retinal detatchment, acute renalfailure, placental abruption, pulmonary oedema, liver haematoma, disseminated intravascular coag-ulation and cerebrovascular bleeding.5,6 Fetal complicationss include stillbirth, intracranial haemor-rhage, oligohydramnios and fetal growth restriction.5 Both maternal and fetal outcomes tend to clusteraround the diagnosis of pre-eclampsia (gestational hypertension and proteinuria), but gestationalhypertension alone and other atypical forms of the disorder are not benign.710 Studies have found that1556% of women who initially present with gestational hypertension will progress to a diagnosis ofpre-eclampsia.7,9,11 It is estimated that 15% of cases of severe pre-eclampsia, however dened, willresult in signicant maternal morbidity.12 This variability in presentation and progression presentsa signicant challenge for effective management of the HDP.

Despite recent advances in our understanding of the pathophysiology of pre-eclampsia5,13 deliveryof the placenta remains the only cure. When presenting early in gestation, delivery is not always thebest option for the fetus. Iatrogenic preterm delivery is associated with increased risks, whether itoccurs in the early or late preterm period.14 Evidence from cohort studies and randomised-controlledtrials show that, remote from term, prolongation of pregnancy by expectant management decreasesserious perinatal morbidity without signicant increases in maternal risk.1518 Uncertainty, however,remains around the magnitude of maternal risk associated with expectant management, as rando-mised-controlled trials were limited towomenwith severe pre-eclampsia and underpowered to detecta difference in outcomes between groups.19,20 An accurate method of predicting maternal outcomes(prognosticating) is required so that perinatal benets can be weighed against maternal risk.

Strategies for the assessment and surveillance of women with HDP should focus on predicting andavoiding associated adverse maternal and fetal outcomes. Several international guidelines for themanagement of women with hypertension in pregnancy exist. In this chapter we will review theclassication systems provided in four of the more recently published guidelines, as well as theirrecommendations for assessment and surveillance.2124 The evidence to support these recommen-dations, based on each suggested investigations ability to predict adverse maternal outcomes, will bereviewed, primarily focusing on the recommendations for maternal assessment. In addition, resultsfrom studies on multivariate prognostic models for the assessment of women with pre-eclampsia willbe reviewed.

International guidelines for classifying and monitoring hypertensive disorders of pregnancy

B. Payne et al. / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462450he UKs National Institute for Health and Clinical Excellence

Table 1Denitions: an international comparison between recent classication systems.

NICE (2010) SOMANZ (2008) SOGC (2008) ASH (2008)

Pre-existing or chronichypertension (bloodpressure 140/90before 200 weeksgestation)

Chronic hypertension:before 20 weeksgestation or being treatedat time of referralprimary or secondaryaetiology

Chronic hypertension:essentialsecondarywhite coatwith or withoutsuperimposed pre-eclampsia

Pre-existing hypertension:with or withoutco-morbid conditionswith or withoutsuperimposed pre-eclampsia

Chronic hypertension:with or withoutsuperimposedpreeclampsia

Gestationalhypertension (bloodpressure 140/90after 196 weeksgestation)

Gestational hypertension:without signicantproteinuria

Gestational hypertension:without signicant proteinuriareturning to normal within12 weeks postpartum

Gestational hypertension:with or withoutco-morbid conditionswith or withoutsuperimposed pre-eclampsia

Gestational hypertensionor transient hypertension:blood pressure returning tonormal within 6 weekspostpartum; Late postpartumhypertension: blood pressurerise developing up to 6 monthspostpartum and normalisedby 1 year postpartum.

Pre-eclampsia(clinical denition)

New hypertension (bloodpressure 140/90) presentingafter 20 weeks gestation withclinically relevant proteinuria(see signicantproteinuria, below)

Gestational hypertension plusone or more of the following:dipstick proteinuria conrmedby either randomproteincreatinine ratio>30 mg/mmol or 0.3 g every 24 hserum or plasmacreatinine >90 mMoliguriathrombocytopoaeniahaemolysisdisseminatedintravascular coagulationraised serum transaminasessevere epigastric or right upperquadrant paineclampsiaHypereexia with sustained clonussevere headachepersistent visual disturbancesstrokepulmonary oedemafetal growth restrictionplacental abruption

Pre-existing hypertension andresistant hypertension, newproteinuria, or adverse condition(see severity criteria, below)Gestational hypertension plusproteinuria (spot proteincreatinineratio >30 mg/mmol or 0.3 gevery 24 h), or adverse condition

Gestational hypertension orChronic hypertensionwith proteinuria(dipstick 1, spotproteincreatinineratio 30 mg/mmolor 0.3 g every 24 h).

(continued on next page)

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Table 1 (continued )

NICE (2010) SOMANZ (2008) SOGC (2008 ASH (2008)

Pre-eclampsia(research denition)

Not dened Denovo hypertension >200 weeks,returning to normal postpartum withproperly documented proteinuria

Not dened Not dened

Severe hypertension 160/110 mmHg 170/110 mmHg 160/110 mm g 160/110 mmHg

Signicant proteinuria >300 mg/dor >30 mg/mmolon spotproteincreatinine ratio

Not dened >300 mg/d >30 mg/mmol onspot protein reatinine ratio

>300 mg/dor >30 mg/mmol onspot proteincreatinine

Severity criteria Severe hypertensionMaternal symptoms (visionproblems, severe headache,epigastric pain, vomiting,papiloedema)Biochemical abnormalities orhaematological impairment(platelet count 70 U/L, elevatedserum creatinine)

Not dened Gestational e at onset

(NICE),24 the Society of Obstetricians and Gynaecologists of Canada (SOGC),21 the American Society ofHypertension (ASH)23 and the Society of Obstetric Medicine of Australia and NewZealand (SOMANZ).22

Denitions of HDP are subdivided into chronic hypertension, gestational hypertension, and pre-eclampsia. Pre-eclampsia is then further dened as severe or non-severe, based on the presence orabsence of a variety of additional signs, symptoms and laboratory ndings. For all classicationsystems, hypertension is dened as systolic blood pressure greater than or equal to 140 mmHg, dia-stolic blood pressure greater than or equal to 90 mmHg, or both. In both the NICE24 and SOGC21

guidelines, denitions are based on real-time diagnosis and do not require retrospective knowledge.This is an improvement on past guidelines, in which diagnosis could not be conrmed until severalweeks postpartum, making decisions around care based on that diagnosis difcult.

For both the NICE24 and SOMANZ22 guidelines, recommendations for maternal assessment andsurveillance differ on the basis of the diagnosis, as outlined in Table 2. In the NICE24 guidelines, thesemonitoring strategies also depend on severity of hypertension, where more intense and regularsurveillance is recommended for women with severe hypertension greater than 160/110 mmHg. Incontrast, the SOGC21 recommends that the same monitoring strategy is used for all cases, regardless ofdiagnosis. Increased monitoring for women with severe pre-eclampsia, and consequently less moni-toring for with what is felt to be milder disorder, reects an attempt to reduce unnecessary inter-ventions and testing in women felt to have less severe disease (better prognosis), therefore reducingcosts. This is carried out with a goal of reducing unnecessary iatrogenic preterm birth.26

Prognosis in medicine, and in the context of this review, refers to the probability of developing anadverse health outcome during the course of that persons care. Having the ability to predict thelikelihood of an individual developing a poor outcome based on that individuals clinical picture iscritical for decision making by both the healthcare provider and patient.27 Any classication systemand monitoring strategy is only useful if it discriminates groups accurately on the basis of prognosis,and can identify those women for whom interventions or treatments are most appropriate.

In the following section, results from studies on the prognostic value of several clinical and labo-ratory investigations in women with pre-eclampsia are reviewed. Guidelines used for reviewingprognostic studies are presented in Table 3.2830 Studies were included if they reported on the asso-ciated risk, or prognostic value of the predictor, with adverse maternal, fetal outcomes, or both. It isimportant to distinguish the identication of a risk factor and a prognostic factor. These concepts areoften used interchangeably in the published studies, but are actually very different. Risk factors havea causal association with the adverse outcome, with the strength of this association generallyexpressed as an odds ratio or relative risk. Prognostic factors, on the other hand, give information onthe absolute probability of an outcome, independent of causation.27,31,32 Prognostic value is generallyexpressed in terms of likelihood ratios, sensitivity, specicity, positive predictive value or negativepredictive value or the area under the curve of the receiver operating characteristic (AUC ROC).

Predicting adverse outcomes by individual investigations

Blood pressure

Severe hypertension greater than 160170/110 mmHg is given on all guidelines reviewed asa severity criterion for pre-eclampsia. Most of the studies found reported only the association betweenhigh blood pressure and adverse outcomes, not its prognostic value. In one case study, which included28 women diagnosed with pre-eclampsia, systolic blood pressure greater than160 mmHg was shownto be an independent risk factor for stroke.33 In another study, which included 216 women diagnosedwith HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome or severe pre-eclampsiausing the ASH criteria,23 diastolic blood pressure at inclusion greater than 105 mmHg was shown to beassociated with a reduced risk of adverse maternal outcomes (OR 0.66; 95% CI 0.45 to 0.96).18 In otherstudies, no association between blood pressure and adverse outcomes was found.34,35

The predictive value of blood pressure was reported in only one study identied. This studyincluded 1259women diagnosed with pre-eclampsia, as dened by the SOGC,21 and found that neitherdiastolic blood pressure nor systolic blood pressure adequately predicted a combined adversematernal

B. Payne et al. / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462 453outcome alone (AUC ROC diastolic blood pressure: 0.664; 95% CI 0.579 to 0.748; systolic blood

Table 2Investigations for assessment and surveillance of maternal and fetal well-being in suspected or conrmed pre-eclampsia: a comparison of International guidelines.

NICE (2010) SOMANZ (2008) SOGC (2008)

Investigations at initialpresentation

For gestational hypertensionand mild hypertension:routine antenatal surveillance

For gestational hypertension andmoderate or severe hypertensionor pre-eclampsia:blood pressure, kidney function,

electrolytes, full blood count,transaminases, and bilirubin

Assessment of symptoms, bloodpressure, urine dipstick andproteinuria by spot or 24 h ifdipstick 1, full blood count,urea, creatinine, electrolytesand liver function

Blood pressure, haemoglobin, WBC anddifferential, platelet count, blood lm, INRand aPTT, brinogen, serum creatinine,serum uric acid, glucose, AST, ALT, LDH,albumin, billirubin, urinalysis (routine andmicroscopy), proteinuria (assessed byurinary protein dipstick, spotproteincreatinine ratio, or 24 h urinalysis)

Investigations forongoing monitoring

For gestational hypertensionand mild hypertension:routine antenatal surveillance

For gestational hypertension andmoderate or severe hypertensionor pre-eclampsia:blood pressure, kidney function,

electrolytes, full blood count,transaminases, and bilirubin

Assessment of symptoms, bloodpressure, urine dipstick andproteinuria by spot or 24 h ifdipstick 1, full blood count,urea, creatinine, electrolytesand liver function

Blood pressure, haemoglobin, WBC anddifferential, platelet count, INR and aPTT,a

brinogen,a serum creatinine, serum uricacid, AST, ALT, LDH, albumin, billirubin,proteinuria (assessed by urinary proteindipstick, spot proteincreatinine ratio,or 24 h urinalysis)

Timing of investigations Blood pressure four times a dayunless 160/110 mmHg then bloodpressure more than four times perday depending on clinical circumstances

Urinalysis assessed at each visit untildiagnosis of pre-eclampsia made, then dailyLaboratory blood investigationstwice weekly or more if unstable

Serial surveillance of bloodpressure and proteinuria:laboratory investigations

carried out at least once perweek antenatally and at leastonce in the rst 3 days postpartum

Proteinuria at each visit untilpre-eclampsia diagnosis madethen repeat measurementnot recommended.Blood tests two to three times aweek depending on severity ofhypertension and presence ofproteinuria

a Tests of coagulation are recommended if there is thrombocytopoenia or placental abruption. INR, international normalised ratio; aPTT, activated partial thromboplastin time; AST,aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase; NICE, National Institute for Health and Clinical Excellence; SOGC, Society of Obstericians andGynaecologists of Canada; SOMANZ, Society of Obstetric Medicine of Australia and New Zealand; WBC, white blood cells.

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pressure: 0.690; 95% CI 0.606 to 0.775).36 No blood pressure cut-off that denes risk can be identiedon the basis of these results. The poor prognostic value of blood pressure is probably due to a highlymodiable variable within this population.

No evidence exists on the optimal timing of blood pressure monitoring, and the optimal level ofblood pressure in women with HDP remains controversial. Some evidence exists that there may beadverse fetal growth effects owing to the drop in mean arterial pressure associated with controlof hypertension in pregnancies complicated by any form of hypertension in pregnancy.11,37,38 The goalof monitoring blood pressure should be to balance blood pressure control for the avoidance of maternalcerebrovascular morbidities and optimisation of fetal growth. Repeat and regular blood pressuremonitoring is recommended but no blood pressure cut-off has been identied that can be used todene risk.

Proteinuria

New onset of proteinuria in pregnancies complicated by hypertension has formed the basis of theclinical diagnosis of pre-eclampsia for many years, and is included in all international guidelines.Signicant proteinuria, however dened, has also been used as criteria for severity of disease in theSOGC21and ASH23 guidelines. More recently, the role of proteinuria measurement in the classicationof pre-eclampsia has been called into question.39 Inaccuracies have been identied with the gold-standard 24-h urine collection method,40 prompting investigation into the utility of other methods ofmeasuring proteinuria in hypertensive pregnancies. The spot proteincreatinine ratio test has beenrecommended by both NICE24 and SOMANZ22 as an acceptable method of testing proteinuria in thispopulation. Results from a systematic review have suggested that using 30 mg/mmol as a threshold forthe spot proteincreatinine ratio is a reasonable alternative to 0.3 g/day to rule-out proteinuria inhypertensive pregnancies (sensitivity 83.6%; 95% CI 77.5 to 89.7% and specicity 77.5%; 95% CI 72.6 to

Table 3Guidelines for the assessment of studies of prognostic factors.

Test Denition Criteria for use in prognosis

Likelihood ratio (LR) Likelihood ratios give a measure of the effectof a positive test (LR) or negative test (LR)on the post-test probability of outcome. Thefurther from 1, in both cases, the greaterthe effect of the test.30

LR >5.0 and LR

A systematic review of proteinuria measured by 24-h urinalysis as a predictor of complications inwomenwith severe pre-eclampsia, variably dened, found that proteinuria is a poor predictor of eithermaternal or fetal complications. Because of the heterogeneity of cut-off values used to deneproteinuria, pooling of data was not possible. The adverse maternal outcomes investigated wereeclampsia and placental abruption and resulted in likelihood ratios for a positive and negative test thatwere below the level required for usefulness in prognosis. For studies included, positive likelihood ratio(LR) ranged from 2.7 to 1.7 and negative likelihood ratio (LR) ranged from 0.41 to 0.62 for predictionof eclampsia. For the prediction of placental abruption, pooled LR was 0.88 (95% CI 0.42 to 1.86) andLRwas 1.1 (95% CI 0.75 to 1.6). No signicant results were found for the prediction of fetal outcomes,including stillbirth, neonatal or infant death or neonatal intensive care unit admission.43

These cohort study and systematic review results were supported by data from the Pre-eclampsiaIntegrated Estimate of RiSk (PIERS) study, a prospective study of 2023 women with pre-eclampsia, inwhich none of dipstick, spot proteincreatinine ratio, or the 24-h urine test predicted maternal or fetaloutcomes accurately (AUC ROC

eclampsia (pooled LR 2.1; 95% CI 1.4 to 3.5; LR0.38; 95% CI 0.18 to 0.81). No other adverse maternaloutcomes were investigated.54 In another study, which included 258 women diagnosed with severepre-eclampsia using criteria similar to those endorsed by the ASH,23 investigators found a moderatelyincreased likelihood of a combined adverse maternal outcome with a positive test using a thresholdvalue of 475.8 mmol/L (LR 3.50; 95% CI 1.27 to 9.64; LR 0.85; 95% CI 0.71to 1.03).55 owing to theheterogeneity of denitions and thresholds used in studies, the clinical utility of uric acidmeasurementremains unclear.

Despite being risk factors for adverse outcomes, none of the laboratory parameters discussed canbe used to predict adverse maternal outcomes accurately. Routine surveillance of these variablesseems appropriate but more studies are required to identify proper thresholds for severity thatwould be clinically informative based on their ability to predict adverse maternal outcomes. Clini-cians should recognise the poor prognostic value of these parameters and use caution when makingdecisions around care of women with pre-eclampsia based solely on the presence of these riskfactors.

Oxygen saturation

No recommendations for the use of pulse oximetry in the assessment and surveillance of womenwith pre-eclampsia exist. Oxygen saturation measured by pulse oximetry (SpO2) is widely used inpediatric and adult populations to predict risk of respiratory complications and for perioperativemonitoring56,57 but its clinical utility in pregnancy has not been widely investigated. In one study,which included 952 healthy pregnant women, SaO2 greater than 96% was suggested as a normaloxygen saturation value during pregnancy.58

The predictive value of SpO2 in pregnancies complicated by pre-eclampsia was investigated in onestudy. In this study, using a prospective cohort of 1534women in the PIERS database, oxygen saturationwas found to be a reasonable predictor of a combined adverse maternal outcome within 48 h ofadmission to hospital with pre-eclampsia (AUC ROC 0.71; 95% CI 0.65 to 0.77). Threshold levels for low,medium and high risk were identied as 9697%, 9495% and 9093%, respectively.59 Further studiesare required to validate these thresholds and investigate their utility in clinical practice.

Symptoms

Clinical symptoms of headache, nausea and vomiting, right upper quadrant or epigastric pain,chest pain or dyspnoea and visual disturbances have all been found to be associated with the HDPand are used to dene severity of disease by all international guidelines reviewed. The use of clinicalsymptoms in pre-eclampsia is controversial, as many of these symptoms are non-specic andcommon to normal pregnancy. In a small cohort of 61 women diagnosed with HELLP syndrome, thepresence of headache (OR 3.6; 95% CI 1.2 to 10.4), visual disturbances (OR 5.2; 95% CI 1.7to 15.9), andepigastric pain (OR 3.75; 95% CI 1.04 to 13.4) were all shown to be associated with increased inci-dence of maternal adverse outcomes.50 In a retrospective cohort of 970 women with severe pre-eclampsia, with or without HELLP syndrome, one study found that nausea and vomiting andepigastric pain where associated with increased incidence of adverse maternal outcomes (P< 0.01),particularly when combined with abnormal laboratory test results for platelet count, liver enzymes(AST, ALT or LDH), uric acid and creatinine.48 Data from 1259 women included in the PIERS databaseshowed that only the symptom complex chest pain and dyspnoea was predictive of adverse maternaloutcomes, although poorly (AUC ROC 0.64; 95% CI 0.54 to to 0.74).36 These data suggest thatsymptoms are of limited utility for determining risk and should not be used alone to guide clinicaldecisions.

Multivariate prognostic models

Given the multi-system nature of pre-eclampsia, and the variability in presentation, it is notsurprising that no individual variable can be identied to predict adverse outcomes alone. Multivariate

B. Payne et al. / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462 457prognostic models have been developed and successfully implemented in several other areas of

medicine.6062 These models, when properly developed and validated, can be used to identify thosepatients for whom intervention would be most benecial and can aid in decision making for both thepatient and healthcare provider.31 Two studies were identied that attempted to develop multivariateprognostic models in women with pre-eclampsia.

In one study, using a prospective cohort of 216 women admitted as part of the Pre-Eclampsia TrialAmsterdam (PETRA) study with HELLP, severe pre-eclampsia (dened by the International Society forthe Study of Hypertension in Pregnancy24), eclampsia or fetal growth restriction with gestationalhypertension, variables were evaluated on the basis of their ability to predict adverse maternaloutcomes at any time after eligibility. Variables found to be associated with the adverse outcome wereas follows: estimated fetal weight below 1100 g (RR 1.49; 95% CI 1.02 to 2.18); diastolic blood pressure

B. Payne et al. / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462458greater than 105 mmHg (RR 0.66; 95% CI 0.45 to 0.96); thrombophillic disorders (RR 1.51 95% CI 1.05 to2.18); maternal age above 30 years (RR 0.62; 95% CI 0.42 to 0.92), and; nulliparity (RR 2.19; 95% CI 1.27to 3.78).When these variables were included in amultivariate logistic regression analysis, the resultantprediction model included only estimated fetal weight and nulliparity, and had poor discriminativepower (AUC ROC 0.65; no condence interval reported).18 No further analysis on the application of thismodel in clinical care was justied.

The PIERS study, a prospective, multicentre observational study, was designed specically todevelop and validate a maternal outcome prediction model for women admitted to hospital with pre-eclampsia.63 Unlike previous studies, inclusion criteria were not limited to women with HELLP orsevere pre-eclampsia. The study included all women admitted with hypertension and proteinuria,hypertension and hyperuricaemia, HELLP, or superimposed pre-eclampsia (as dened by the SOGC21).Using a cohort of 2023 women admitted to tertiary academic centres in the UK, Canada, New Zealandand Australia, variables including demographics, symptoms, signs and laboratory ndings were eval-uated on the basis of their ability to predict adverse maternal outcomes within 48 h of eligibility or upto 7 days after eligibility.64 This time point for outcome prediction differs from that used in the PETRAstudy,18 and was chosen because it is the time frame around which decisions on corticosteroidadministration and maternal transport are made. The PIERS combined adverse maternal outcome isgiven in Table 4 and was developed by international Delphi consensus.65,66

The nal fullPIERS model includes gestational age at onset of disease or delivery (if onset waspostpartum) (OR 0.91; 95% CI 0.88 to 0.95); creatinine (OR 1.02; 95% CI 1.02 to 1.02); platelet count (OR0.99; 95% CI 0.98 to 0.99); AST (OR 1.005; 95% CI 1.00 to 1.001); SpO2 (OR 0.63; 95% CI 0.58 to 0.70);and chest pain or dyspnoea (OR 6.13; 95% CI 3.56 to 10.54). This model predicts adverse maternaloutcomes accurately within 48 h of eligibility (AUC ROC 0.88; 95% CI 0.84 to 0.92) and up to 7 days(AUC ROC 0.76; 95% CI 0.72 to 0.80).64 A secondary and simplied PIERS model, called miniPIERS, isbeing developed for use in low- and middle-income country settings. Results of this study have notbeen reported.

Currently, the fullPIERS model is available online as a calculator tool for use by clinicians.67

However, this model requires external validation in a new dataset before rm recommendations tochange monitoring strategies can be made on the basis of these results. If validated, application of thePIERSmodel into clinical care could improve outcomes by assisting decisions around timing of delivery.In rural and remote areas, it can assist with safety of transport. Therefore, a research priority is tovalidate externally, and then implement, the fullPIERS model into care in new populations and clinicalsettings.

Table 4The The Pre-eclampsia Integrated Estimate of RiSk combined adverse maternal outcome.

Organ System Outcome

Hepatic Dysfunction, failure, haematoma or ruptureCentral nervous system Eclampsia, Glasgow Coma Score 50% Fi02 for >1 h, intubation (not for caesarean)Renal Acute renal insufciency, acute renal failure (if pre-existing renal disease), dialysisHaematological Transfusion

Standardisation of assessment and surveillance through clinical guidelines

Standardisation of care through the use of assessment and surveillance guidelines has beenshown to be effective for reducing adverse outcomes. Instituting surveillance guidelines at BritishColumbia Womens Hospital and Health Centre for all women with any HDP was associated witha drop in the incidence of adverse maternal outcomes (5.1% pre-intervention to 0.7% post-inter-vention; P< 0.001) but with no change in perinatal outcomes.68 When the same surveillanceguideline was actively introduced across the province of British Columbia, a reduction in incidence ofmaternal (3.1% to 1.9%; P< 0.001) and perinatal (1.9% to 1.3%; P 0.006) outcomes was seen.69 Thisreduction in maternal adverse outcomes was signicantly greater than that for non-hypertensivepregnant women in the same time period, suggesting the guideline implementation itself isresponsible for the improvement. These guidelines formed the basis of recommendations made by

21

Conclusion

Conict of interest

B. Payne et al. / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462 459None declared.

Practice points

Current classication systems are limited in their ability to stratify women on the basis of riskof adverse maternal outcomes.

Individual clinical and laboratory variables suggested as severity criteria by internationalguidelines are of limited prognostic value.

The PIERS model is a multivariate prognostic model that correctly identies women at risk ofadverse outcome but requires further validation.

Standardisation of assessment and surveillance for all womenwith a hypertensive disorder ofpregnancy has been shown to improve outcomes.HDP remain one of the major causes of maternal mortality and morbidity worldwide. Manyinternational guidelines exist for the classication and assessment of women with hypertension inpregnancy, but denitions and recommendations within these documents are variable. Many rec-ommended investigations do not actually correlate with increased risk of adverse outcomes, makingit difcult to determine true prognosis. Although standardised assessment and surveillance has beenshown to improve outcomes, the application of these monitoring strategies in many areas of theworld is not possible owing to the cost associated with them. Not all of the tests recommended forsurveillance of women with pre-eclampsia are independently predictive of adverse outcomes, andmany unnecessary tests could be avoided if those tests that are most informative where identied.The PIERS study has identied a group of tests that can be used to predict risk of outcomes accuratelyup to 7 days after admission to a tertiary hospital with pre-eclampsia. This model needs to bevalidated in new populations and in different clinical settings before it can be implemented intoclinical practice.70 In the interim, clinicians should consider the whole clinical picture whenassessing women with pre-eclampsia and making decisions around expectant managementcompared with aggressive intervention. Future research in the area of prognosis should focus onwomen with variable denitions of pre-eclampsia and other HDP. All studies reviewed were limitedto cases of severe pre-eclampsia, and results may not be generalisable across the spectrum of thedisorder.the SOGC in 2008. Similar results were seen when an active guideline implementation strategy wasused in Yorkshire.12

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Research agenda

Identication of proper threshold for severity for common laboratory and clinical variablesused in the assessment and surveillance of women with the HDP based on their ability topredict adverse outcomes.

Validation of thresholds of proteinuria and uric acid that should be used for the diagnosis ofpre-eclampsia for all methods of assessment of these tests.

External validation of the PIERS model in new populations and clinical settings. Updating international guidelines for use in low- and middle-income countries.19. Bombrys AE, Barton JR, Habli M et al. Expectant management of severe preeclampsia at 27(0/7) to 33(6/7) weeksgestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management. AmJ Perinatol 2009; 26: 441446.

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B. Payne et al. / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 449462462

Assessment, surveillance and prognosis in pre-eclampsia Introduction International guidelines for classifying and monitoring hypertensive disorders of pregnancy Predicting adverse outcomes by individual investigations Blood pressure

Proteinuria Laboratory testing Oxygen saturation Symptoms Multivariate prognostic models Standardisation of assessment and surveillance through clinical guidelines Conclusion Conflict of interest References